A rigorous model for the electron is presented by generalizing the Coulomb's Law or Gauss's Law of electrostatics, using a unified theory of electricity and gravity. The permittivity of the free-space is allowed to be variable, dependent on the energy density associated with the electric field at a given location, employing generalized concepts of gravity and mass/energy density. The electric field becomes a non-linear function of the source charge, where concept of the energy density needs to be properly defined. Stable solutions are derived for a spherically symmetric, surface-charge distribution of an elementary charge. This is implemented by assuming that the gravitational field and its equivalent permittivity function is proportional to the energy density, as a simple first-order approximation, with the constant of proportionality referred to as the Unifield Electro-Gravity (UEG) constant. The stable solution with the lowest mass/energy is assumed to represent a ``static'' electron without any spin. Further, assuming that the mass/energy of a static electron is half of the total mass/energy of an electron including its spin contribution, the required UEG constant is estimated. More fundamentally, the lowest stable mass of a static elementary charged particle, its associated classical radius, and the UEG constant are related to each other by a dimensionless constant, independent of any specific value of the charge or mass of the particle. This dimensionless constant is numerologically found to be closely related to the the fine structure constant. This possible origin of the fine structure constant is further strengthened by applying the proposed theory to successfully model the Casimir effect, from which approximately the same above relationship between the UEG constant, electron's mass and classical radius, and the fine structure constant, emerges.

Dispersed silver nanoparticles (AgNPs) on the surface of titanium alloy (Ti6Al4V) and titanium alloy modified by titania nanotube layer (Ti6Al4V/TNT) substrates were produced by chemical vapor deposition method (CVD) using novel precursor of the formula [Ag₅(O₂CC₂F₅)₅(H₂O)₃]. The structure and volatile properties of this compound were determined using single crystal X-ray diffractometry, variable temperature IR spectrophotometry (VT IR), and electron inducted mass spectrometry (EI MS). The morphology and the structure of the produced Ti6Al4V/AgNPs, and Ti6Al4V/TNT/AgNPs composites were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Moreover, measurements of hardness, Young’s modulus, adhesion, and surface free energy have been carried out. The ability to release silver ions from the surface of produced nanocomposite materials immersed in PBS solution has been estimated using inductively coupled plasma mass spectrometry (ICP MS). The wettability and the surface free energy of samples were estimated on the base of contact angle studies with the use of water and diiodomethane. Among the studied surface-modified titanium alloy implants, the best nano-mechanical properties were noticed for the Ti6Al4V/TNT15/AgNPs composite. The location of silver nanoparticles inside of titania nanotubes caused their lowest release rate, which may indicate on suitable properties above mentioned type of the composite for the construction of implants with a long term of antimicrobial activity.

In the coded pulse scanning light detection and ranging (LIDAR) system, the number of laser pulses used at a given measurement point changes depending on the modulation and the method of spreading used in optical code-division multiple access (OCDMA). The number of laser pulses determines the pulse width, output power, and duration of the pulse transmission of a measurement point. These parameters determine the maximum measurement distance of the laser and the number of measurement points that can be employed per second. In this paper, we evaluate the performance and characteristics of combinations of modulation and spreading technology that can be used for OCDMA, and study optimal combinations according to varying operating environments.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

Age-strengthened aluminum alloys as important structural lightweight materials have much lower fatigue properties than conventional steel. This study focuses on the effect of the precipitation-free zone (PFZ) on the mechanical properties of age-strengthened aluminum alloys. A polycrystalline model containing PFZ was created by secondary development of the traditional polycrystalline model and combined with the crystal plasticity finite element method to simulate the stress-strain response and local plastic deformation behaviors under different microstructures. The presence of PFZ significantly reduces the yield strength of the alloy and concentrates the stresses in the PFZ region, especially under cyclic loading, and the strain energy dissipation in the PFZ region is significantly higher than that in the intracrystalline region, and far exceeds that without the precipitation zone. region and far exceeds the model without PFZ, indicating that PFZ is the main region for fatigue crack initiation. In addition, the introduction of a rotation factor to simulate the inhomogeneous rotation within the grain reveals that the additional stress concentration in the PFZ introduced by the aluminum alloy forming process further increases the fatigue crack initiation driving force.

Here, we consider a closed composite system consisting of a primary system where the chemical reaction occurs and is located in a p, T reservoir. In the ideal isentropic case (thermodynamic process), the change in the internal energy of the composite system (due to a chemical reaction) is wholly converted into useful work - maximum useful work. Irreversibility - a measure for the degradation of useful work - in a closed system generates entropy, i.e., the thermodynamic process is no longer isentropic. Applying the principle of maximum entropy and minimum internal energy to a part of the system's total volume and applying the elements of the system's volume for which the law of local equilibrium applies useful work and irreversibility can be defined. Suppose the primary system is viewed as a set of black box volume elements in which a chemical reaction occurs. In that case, the criterion of an isentropic process or a process with entropy generation becomes the Gibbs-Duham equation. It has been proven that De Donder's equation of entropy production of a chemical reaction is a particular form of Calen's equation –TdST = dUT where dST is the differential change of total entropy and dUT is the differential change of total internal energy of the composite system.

Background/Objectives: Head and neck free flap reconstructions are often required to treat tumors or extensive post-traumatic jaw defects. The facial artery is the standard receiving vessel for intraoral microvascular anastomoses. However, its use is associated with several disadvantages, such as lesions of buccal nerve branches or the parotid duct and variability in course and diameter. This study aims to investigate whether sublingual artery branches can be considered an alternative intraoral supply vessel to the facial artery to avoid these drawbacks. Methods: 12 formalin-fixed cadaveric heads with 24 sides were dissected. The sublingual artery's origin, course, branching pattern, and distribution were examined. In addition, the diameters of the branches of the sublingual artery were assessed to identify potential supply vessels for anastomoses. Results: In ten of the 24 cases (41.7 %), the sublingual artery originated from the lingual artery and nine cases (37.5 %) from the facial artery. The main trunk of the sublingual artery was present in the floor of the mouth in all cases (100 %) with a diameter of ≥ 0.9 mm in vitro (1 mm in vivo). In 15 of the 24 half heads (62.5 %), branches of the sublingual artery with ≥ 0.9 mm were identified in this space. Conclusions: The large diameter of the sublingual artery on the floor of the mandible suggests that this vessel or its branches could be considered alternative pedicles for intraoral anastomoses in mandibular microvascular free flap grafts.

Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC). cHCC-ICC is generally considered to exhibit a more aggressive clinical course compared to ICC; however, its risk factors and outcomes remain largely undefined. A single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC from June 2011 and January 2023, all of whom underwent surgical resection. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 vs. 46; ALT median 165.5 vs. 48; p=0.012 and p=0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 vs. 104; p=0.03). CA 19-9 values (p=0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (p=0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p=0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p=0.007). cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Our study showed that RFS is lower in the cHCC-ICC group as compared to ICC patients alone. Further studies are warranted and possibly suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.

Abstract Precision medicine is essentially based on reliable and non-invasive biomarkers. Aim of this review has been to describe the newest biomarkers in the field of kidney transplantation and the kidney rejection, one of the commonest and severe complications. Standard of care tools to identify acute rejection are largely full of errors and of drawbacks. In recent years new and reliable biomarkers have been found. They are avoid of risks, non-invasive and able to detect rejection even in those frequent cases in which acute rejection are clinically asymptomatic and not otherwise identifiable. In recent years several biomarkers have been identified. Very recently have been found new relevant biomarkers able to diagnose rejection with high positive predictive value and low negative predictive value. These are the donor derived cell free DNA found in the recipient, the gene expression profile of the donor found in the recipient and the urinary cytokines that express modification in the graft tissue. The aim of this study has been to find the most recent findings in the literature on this topic and to describe the utility and possible limitation of such new biomarkers on kidney rejection.

The purpose of this study is to show an automated laser vision correction (LVC) with the transep-ithelial refractive keratectomy (TransPRK) surgery technique. Since more surgical steps have been automated over the years, we have standardized the TransPRK technique. We have been using it since 2010. This paper aims to illustrate the processes that are readily applicable to automation. To meet the patient's expectations and ensure that the patient has uncorrected visual acuity at least equal to the preoperative corrected vision with glasses, patient selection is crucial in refractive surgical procedures. One major benefit of automating the surgery is that it can be performed in a similar way by each surgeon or laser correction centre, so once the standard and results are good, these can be per-formed by different surgeons.

Study design: Technical note. Objectives: To present a new technique of treatment for a patient with thoracolumbar focal kyphosis due to osteoporotic verte-bral fracture (OVFs). Background : OVFs are common among the elderly population. Following a severe wedged fracture, patients often experience low back pain and disruptions in activities of daily living. Reconstruction surgeries, such as corpectomy, are among the treatment options for this condition. However, corpectomy requires longer surgical times and involves a significant amount of blood loss. Materials and Methods : An 80-year-old woman presented to our hospital with severe low back pain and gait disturbance. She had experienced an L2 OVF six years prior. Although she had no neurological deficit, she could not walk more than 200m due to pain. Preoperative spinal radiographs revealed severe sagittal malalignment, with the L2 vertebra collapsed and focal kyphosis of L1-3 measuring 34 degrees. Results: The patient underwent anterior and posterior surgery in the right decubitus position using a C-arm free technique. The surgical time was 133 minutes with an estimated blood loss of 100 ml. Hyperlordotic cages were inserted in the upper and lower disc space via a lateral approach, while percutaneous pedicle screws (PPS) were inserted from a posterior approach. These procedures were performed simultaneously under navigation guidance only. Post-operative images showed excellent spinal alignment, with local kyphosis reduced from 34 to 14 degrees, and no major or severe complications occurred. At one-year follow-up, the patient was able to walk smoothly, with her visual analogue scale for low back pain improving from 73mm to 13mm, and her Oswestry Disability Index improving from 53.3% to 13.3%. Conclusions/Level of Evidence : The simultaneous use of hyperlordotic cages and PPS is an effective and innovative navigation technique that yields promising outcomes for thoracolumbar focal kyphosis resulting from OVFs. This approach not only reduces surgical time but also minimizes intraoperative blood loss. Level V.

The detection and analysis of small molecules, typically defined as molecules under 1000 Da, is of growing interest ranging from the development of small molecule drugs and inhibitors to the sensing of toxins and biomarkers. However, due to challenges such as their small size and low mass, many biosensing technologies struggle to have the sensitivity and selectivity for the detection of small molecules. Notably, their small size limits the usage of labeled techniques that can change the properties of small molecule analytes. Furthermore, the capability of real-time detection is highly desired for small molecule biosensors’ application in diagnostics or screening. This review highlights recent advances in label-free real-time biosensing technologies utilizing different types of transducers to meet the growing demand for small molecule detection.

Modification the biodegradable matrix was carried by graft-copolymerization polylactide with methacrylic acid of various concentrations. Ultraviolet irradiation with different exposure times to the samples was chosen as the initiator of copolymerization. In the experiment the effect of ultraviolet light on polylactide and graft copolymerization was investigated: the resulting samples were studied by viscosimetry, gravimetry, FTIR, static cation- exchange capacity analysis . The conditions for obtaining grafted copolymers and the dependence of the characteristics on the reaction conditions are established.

Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian(EOC) and impact on survival. Methods: In our prospective study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score(NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152. Patients >65 years-old, with ascites of >500 ml, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated by NRS-2002(p-values = 0.014, 0.001, and 0.007, respectively). An NRS-2002<3 was an independent predictive factor for complete tumor resectability (p=0.009). The patients with NRS-2002≥3 had a median overall survival(OS) of seven months (95% CI=0-24 months), as compared to the patients with NRS-2002<3 where median OS was 46 months(p=0,001). Phase angle(PhAα)≤ 4.5 was the strongest predictor of OS. Conclusion: Malnutrition is an independent predictor of incomplete cytoreduction in study population. It is an independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in identification of high-risk groups within EOC characterized by poor clinical outcome.

Considering the aging society and budget constraints, a strategy for reforming public transportation welfare policies is essential for sustainability. Among the various transportation welfare policies, fare discount policies are provided to specific age groups, and most countries offer benefits to several public transportation. South Korea provides a fare-free policy limited to subways, and the need for policy modification is emerging due to sustainability problems caused by an aging society. Hence, the scope of the policy should be expanded to all travel modes, but the discount rate should be reduced, or the target group should be reduced in consideration of the budget. This study proposes a travel mode to focus on by city through the preference of the elderly. The latent class model is employed to classfy stated preference data collected from the survey. The estimation results show a significant preference heterogeneity depending on the level of subway supply by region, and a policy focused on subways would be more reasonable in cities with sufficient subway infrastructure. Hence, regarding sustainability, it may be more appropriate to focus on specific means than to provide the same discount policy for all public transport.

Proteins in biological systems function at the interface of single molecule and bulk chemistry and thus provide novel insights into the basic physical chemistry of scaling and emergent phenomena. For example, a binary mechanical model based on the chemistry of muscle contraction unifies molecular mechanics and thermodynamics and provides an explicit solution to the Gibbs paradox. Using the same model system, here I show that chemical activities of molecular states have no effect on chemical kinetics or energetics. Specifically, while the concentration or number of molecules in a molecular state is widely thought to contribute to reaction free energies, here I show that it is not the physical presence of molecules that pushes a reaction forward but the number of microstates, , accessible in a chemical state that pulls a reaction toward equilibrium with an entropic force down an entropic funnel. With the derivation of an entropic contribution to chemical kinetics, I develop a novel chemical kinetic formulation that fully describes the chemical thermodynamics of both equilibrium and non-equilibrium reactions in terms of an a priori system reaction energy landscape.

In this study, a numerical simulation of fluid flow through railway ballast in the time domain is presented, providing a model for unsteady-state flow. It is demonstrated that the position of the free surface with respect to time can also be used to solve the steady flow case. The effect of ballast fouling is included in the model to capture the realistic behavior of railway ballast, which is critical to understanding the impact of flooding. A thorough comparison with a range of previous studies, including theoretical and experimental approaches, is made and very close agreement is obtained. The significant impact of ballast fouling on fluid flow and its potential consequences for railway infrastructure are highlighted by the simulation. Valuable insights into the behavior of water flow through porous media and its relevance to railway ballast management are offered by this study.

Iron oxide nanozymes are a form of nanomaterial with both superparamagnetic and enzyme-mimicking properties. Given the multifunctional nature of iron oxide nanozymes, it is attractive for creating iron oxide hybrid nanozymes through biomolecular modifications to imbue with auxillary properties. Such iron oxide hybrid nanozymes can be useful for rapid and cost-effective analysis of circulating tumor nucleic acids (ctNAs) in patient liquid biopsies during minimal residual disease (MRD) monitoring of cancer recurrence. Herein, the use of streptavidin-modified iron oxide hybrid nanozymes is reported for magnetic enrichment and bioelectrocatalytic sensing of three prostate cancer (PCa) ctRNA biomarkers with high detection specificity and sensitivity (10 copies) over an ultrabroad dynamic range (five orders of magnitude). Furthermore, the feasibility of ctRNA analysis for pre- and post-cancer treatment MRD monitoring is demonstrated using PCa urinary liquid biopsy samples.

Biosensors have shown great potential in realizing rapid, low cost and portable on-site detection for diseases. This work reports the development of a new bioelectronic sensor called AC electrokinetics-based capacitive (ABC) biosensor, for the detection of genomic DNA (gDNA) of methicillin-resistant Staphylococcus aureus (MRSA). The ABC sensor is based on interdigitated microelectrodes biofunctionalized with oligonucleotide probes. It uses a special AC signal for direct capacitive monitoring of topological change on nanostructured sensor surface, which simultaneously induce dieletrophoretic enrichment of target gDNAs. As a result, rapid and specific detection of gDNA/probe hybridization can be realized with high sensitivity. It requires no signal amplification such as labelling, hybridization chain reaction, or nucleic acid sequence-based amplification. This method involves only simple sample preparation. After optimization of nano-structured sensor surface and signal processing, the ABC sensor demonstrated fast turnaround of results (~10 s detection), excellent sensitivity (a detection limit of 4.7 DNA copies /µL MRSA gDNA) and high specificity, suitable for point of care diagnosis. As a bioelectronic sensor, the developed ABC sensors can be easily adapted for detection of other infectious agents.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

Eddy current based approaches have been investigated for a wide range of inspection applications. Dodd-Deeds model and the truncated region eigenfunction expansion (TREE) method are widely applied in various occasions, mostly for the cases that the sample is relatively larger than the radius of the sensor coil. The TREE method converts the integral expressions to the summation of many terms in the truncated region. In a recent work, the impedance of the co-axial air-cored sensor due to a plate of finite radius was calculated by the modified Dodd-Deeds analytical approach proposed by authors. In this paper, combining the modified analytical solution and the TREE method, a new finite region eigenfunction expansion (FREE) method is proposed. This method involves modifying its initial summation point from the first zero of the Bessel function to a value related to the radius of the plate, therefore makes it suitable for plate with finite dimensions. Experiments and simulations have been carried out and compared for the verification of the proposed method. Further, the planar size measurements of the metallic circular plate can be achieved by utilising the measured peak frequency feature.

As there exist no repulsive forces in strong interaction, in a hypothetical approach, strong interaction can be assumed to be equivalent to a large gravitational coupling. Based on this concept, strong coupling constant can be defined as a ratio of the electromagnetic force and the gravitational force associated with proton, neutron, up quark and down quark. With respect to the product of strong coupling constant and fine structure ratio, we review our recently proposed two semi empirical relations and coefficients 0.00189 and 0.00642 connected with nuclear stability and binding energy. We wish to emphasize that- by classifying nucleons as ‘free nucleons’ and ‘active nucleons’, nuclear binding energy can be fitted with a new class of ‘three term’ formula having one unique energy coefficient. Based on the geometry and quantum nature, currently believed harmonic oscillator and spin orbit magic numbers can be considered as the lower and upper “mass limits” of quark clusters.

Data creation is often the only way for researchers to produce basic geospatial information for the pursuit of more complex tasks and procedures such as those that lead to the production of new data for studies concerning river basins, slope morphodynamics, applied geomorphology and geology, urban and territorial planning, detailed studies, for example, in architecture and civil engineering, among others. This exercise results from a reflection where specific data processing tasks executed in Google Sketchup (Pro version, 2018) can be used in a context of interoperability with Geographical Information Systems (GIS) software. The focus is based on the production of contour lines and Digital Elevation Models (DEM) using an innovative sequence of tasks and procedures in both environments (GS and GIS). It starts in Google Sketchup (GS) graphic interface, with the selection of a satellite image referring to the study area—which can be anywhere on Earth's surface; subsequent processing steps lead to the production of elevation data at the selected scale and equidistance. This new data must be exported to GIS software in vector formats such as Autodesk Design Web format—DWG or Autodesk Drawing Exchange format—DXF. In this essay the option for the use of GIS Open Source Software (gvSIG and QGIS) was made. Correcting the original SHP by removing “data noise” that resulted from DXF file conversion permits the author to create new clean vector data in SHP format and, at a later stage, generate DEM data. This means that new elevation data becomes available, using simple but intuitive and interoperable procedures and techniques which confgures a costless work flow.

Among the most important variables in the design of falling film microreactors (FFMRs) is the liquid film thickness as well as the gas/liquid interfacial area, which dictate the mass and heat transfer rates. In a previous work conducted in our lab the characteristics of a free-falling Newtonian liquid film have been studied and appropriate correlations have been proposed. In this work the geometrical characteristics of a non-Newtonian shear thinning liquid, flowing in an inclined open microchannel, have been experimentally investigated and design correlations that can predict with reasonable accuracy the features of a FFMR have been proposed. The test section used was an open μ-channel with square cross section (Wo=1200 μm) made of brass which can be set to various inclination angles. The liquid film characteristics were measured by a non-intrusive technique that is based on the features of a μ-PIV system. Relevant CFD simulations revealed that the volume average dynamic viscosity over the flow domain is practically the same as the corresponding asymptotic viscosity value, which can thus be used in proposed the design equations. Finally, a generalized algorithm for the design of FFMRs, containing non-Newtonian shear thinning liquids, is suggested.

The article reviews the current status of label-free integrated optical sensors focusing on the evolution over the years of their analytical performance. At first a short introduction to the evanescent wave optics is provided followed by detailed description of the main categories of label-free optical sensors including sensors based on surface plasmon resonance (SPR), grating coupler, photonic crystals, ring resonators and interferometric transducers. After a short reference to SPR techniques, including localized SPR, integrated optical sensors i.e., grating-couplers, interferometers, photonic crystals, microring resonators are reviewed. For each type of sensor, the detection principle is first provided followed by description of the different transducer configurations so far developed and their performance as biosensors. Finally, a short discussion about the current limitations and future perspectives of integrated label-free biosensors optical sensors is provided

Viruses can infect a cell via one or both routes viz. cell-to-cell (c-c) or cell-free (c-f) . Pathogenesis studies of various viruses, including HIV, have shown that c-c transmission yields a significantly higher infection magnitude than the c-f route. Expectedly, potent antibodies inhibited c-f infection more efficiently than with c-cell transmission. To achieve a one-step, synchronous infection cycle that provides amplified infection, we have studied a consistent and efficient c-c HIV infection model since 1992. H9 cells persistently infected with HTLV-IIIB (H3B cells) and uninfected target CD4+ lymphocyte line (HuT78) were mixed in a ratio of 1:4 respectively. We have recently used this model to produce HIV designer antigens that have been shown to elicit monoclonal as well as polyclonal specific antibodies against novel epitopes that are formed post virus-cell engagement, but prior to fusion. The model can be extended for HIV neutralizing antibody assays or drug inhibitors against high multiplicity of infection.

In Europe we can see a change in the social structure in the last period. Average life expectancy has increased dramatically over the last 50 years. Because of the improved life situation and advanced level of health care, older people are slower. With advancing age, the likelihood of experiencing a variety of constraints such as visual impairment, reduced hearing or physical ability increases. In such a life stage tenants are often forced to leave their long-term living space because these homes can not serve "new" individual needs and the resulting personal protection goal. This transition from the privacy of their home to the new environment often appears to be a painful change. They will take their familiar and well-known surroundings, because their homes can not be adapted to serve new needs. It must be the policy’s role to create a new inclusive social space and the requirement for architects and designers to create new goals for the design of an adaptable environment. This is a comprehensive approach to the design of the outer and inner space that could serve people even if there is an unexpected situation and changes in movement and physiological limitations of older people. The contribution shows the results of the survey conducted in Germany and Slovakia. In the survey respondents expressed their opinion on what they considered important in creating an adaptive environment. Results are processed graphically with explanation. The results were mainly for designers and developers of the indoor environment. Based on the results of the questionnaire survey, studies of possible modifications in the interior of the flats were then prepared. The contribution yielded these results in three age groups of respondents; i. people aged 35, 50 and over 50.

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

The relationship of the animal with its environment has been of longstanding interest in philosophy and science. Here I provide a brief introduction to concepts that place an emphasis on mutualism as the basis of organism - environment interaction, in contrast to the long standing view that the environment exerts an instrumental role in shaping the organism. Two influential theories have been von Uexküll’s theory of umwelt and Gibson’s theory of affordances. The former envisioned the animal as immersed in its surroundings (umwelt) to form a functional unit. In a similar manner, the latter theory describes a unity between 1) environmental information that provides the animal with opportunities for action (affordances) and 2) the ability of the animal to perceive and engage with those affordances. These views have influenced more recent ecological models of the organism as the functional unit of biology and have also influenced models of immune function. In ecological models, agency is seen as the ability of the organism to predict and control its engagement with the environment in order to maintain its integrity. The predominant contemporary model of neural function in which perception and action are understood to operate through Bayes-like active inference complements the concept of agency as proposed by the mutualism models. However, it is suggested that rather than a constant mutualism, encounters between organism and environment range over a dynamic spectrum from dualism to mutualism. It is also suggested that along this spectrum, agency emerges when the balance of instrumentality shifts from the environment to the organism, and that the balance of this relationship can further progress towards a felicitous mutualism. Meaning emerges between environmental information and an agent as opportunity for action. Implications for opportunities to foster agency in animals within our care is noted.

This article investigates a proposed new mathematical model that considers the infected individuals using various rate coefficients such as transmission, progression, recovery and vaccination. The fact that the dynamic analysis is completely determined by the basic reproduction number is established. More specifically, local and global stabilities of the disease-free equilibrium and the endemic equilibrium are proved under certain parameter conditions when the basic reproduction number is below or above unity. A realistic computer simulation is performed for better understanding of the variations in trends of different compartments after the outbreak of the disease.

In a Water-Cooled Lithium-Lead (WCLL) Breeding Blanket (BB), the heat generated by the plasma thermal radiation and nuclear reactions is removed mainly by two components; namely, the First Wall (FW) and the Breeding Zone (BZ). The FW faces the neutrons and charged particles fluxes generated by the fusion reactions and the thermal radiation coming from the plasma. The present work takes into account the FW cooling system inspired by the WCLL BB 2018 design of DEMO 2017 baseline. Unlike the baseline where a Pressurized-Water Reactor (PWR) setup is used for the coolant, various setup between the Boiling Water Reactor (BWR) and the High-Pressure (HP) BWR are studied in the present work operating in the Two-Phase Flow (TPF) regime. The 3D model of the FW in the WCLL BB 2018 design is simplified into a 1D model and a steady state analysis is carried out to optimize the mass flow rate of the water and the number of parallel channels at the BB cells at different poloidal locations of the reactor, which helps not only in reducing the used coolant but also in improving the Tritium Breeding Ratio (TBR). The present work takes into account forced convection in the liquid only region, the subcooled boiling region, and the saturated boiling region using suitable empirical or semi-empirical models from the literature. The results are validated against the existing results in the literature. In the end, related conclusions are made regarding the pros and cons of the studied operating conditions.

The requirement for developing tools capable of detecting and monitoring heavy metals (HMs) has recently taken on more significance due to worries about their toxic effect on human health and aquatic habitats. In this study, a simple electrochemical sensing carbon paste electrode (CPE) based on composite of Zinc/Iron layered double hydroxide (LDH) and polyaniline (PANI) was developed for the determination of lead ions in aquatic solutions. For this purpose, Zn-Fe LDH/PANI was prepared and characterized by Fourier transform infrared (FTIR), X ray diffraction (XRD), and scanning electron microscopy (SEM). Modified carbon electrode based Zn-Fe LDH/PANI was electrochemically characterized compared with unmodified electrode in FCN as a redox probe using cyclic voltammetry (CV). Thus, Zn-Fe LDH/PANI was utilized as sensing material for the electrochemical determination of lead ions using differential pulse voltammetry (DPV). Zn-Fe LDH/PANI/CPE show limits of detection (LOD) and quantification (LOQ) of 167.8 nM and 559.4 nM, respectively. Zn/Mg/Fe LDH was prepared using co-precipitation method and characterized by XRD, FTIR, SEM and BET, used for removal of Pb+2 ions. Removal process was investigated at different conditions as pH, metal ion concentrations, starting adsorbent dose at first and contact time. Zn/Mg/Fe LDH was evaluated as an effective adsorbent material for lead ions elimination in aquatic solutions, with capacity of adsorption 700 mg/g. The elimination of lead ions on Zn/Mg/Fe LDH fitted the pseudo first-order kinetics model and the isotherm was matched with Langmuir model. Studies revealed that the ideal removal conditions were pH = 5.0, an adsorbent mass of 0.05 g, and 20 ml of 50 ppm metal ion concentration at 60 min. The Zn-Fe LDH/PANI composite also showed potential anti-cancer properties against lung cancer cells (A549) while maintaining safety for normal lung fibroblast cells (WI-38). Collectively, advancements in electrochemical sensors offer promising solutions for lead ion detection, with wide-reaching applications in wastewater treatment and cytotoxicity assessment. These innovations have the potential to enhance environmental monitoring and public health safety.

Sustainable urban drainage systems (SuDS) such as swales are designed to collect, store and infiltrate a large amount of surface runoff water during heavy rainfall. Stormwater is known to transport pollutants, such as particle-bound Potential Toxic Elements (PTE), which are known to often accumulate in the topsoil. A portable XRF instrument (pXRF) is used to provide in situ spatial characterization of soil pollutants, specifically lead (Pb), zink (Zn) and copper (Cu). The method uses pXRF measurements of PTE along profiles with set intervals (1 meter) to cover the swale with cross-sections, across the inlet, the deepest point and the outlet. Soil samples are collected, and the In-Situ measurements are verified by the results from laboratory analyses. Stormwater is here shown to be the transporting media for the pollutants, so it is of importance to investigate areas most prone to flooding and infiltration. This quick scan method is time and cost-efficient, easy to execute and the results are comparable to any known (inter)national threshold criteria for polluted soils. The results are of great importance for all stakeholders in cities that are involved in climate adaptation and implementing green infrastructure in urban areas. However, too little is still known about the long-term functioning of the soil-based SuDS facilities.

Active inference under the Free Energy Principle has been proposed as an across-scales compatible framework for understanding and modelling behaviour and self-maintenance. Crucially, a collective of active inference agents can, if they maintain a group-level Markov Blanket, constitute a larger group-level active inference agent with a generative model of its own. This potential for computational, scale-free structures speaks to the application of active inference to self-organizing systems across spatiotemporal scales, from cells to human collectives. Due to the difficulty of reconstructing the generative model — that explains the behaviour — of emergent group-level agents, there has been little research on this kind of multi-scale active inference. Here, we propose a data-driven methodology for characterising the relation between the generative model of a group-level agent and the dynamics of its constituent individual agents. We apply methods from computational cognitive modelling and computational psychiatry, applicable for active inference as well as other types of modelling approaches. Using a simple multi-armed bandit task as an example, we employ the new ActiveInference.jl library for Julia to simulate a collective of agents who are equipped with a Markov blanket. We use sampling-based parameter estimation to make inferences about the generative model of the group-level agent and we show that there is a non-trivial relationship between the generative models of individual agents and the group-level agent they constitute, even in this simple setting. Finally, we point to a number of ways in which this methodology might be applied to better understand the relations between nested active inference agents across scales.

This article advances the discourse on sustainable and energy-efficient software by examining the performance and energy efficiency of intelligent algorithms within the framework of green and sustainable computing. Building on previous research, it explores the theoretical implications of Bremermann's Limit on efforts to enhance computer performance through more extensive methods. The study presents an empirical investigation into heuristic methods for search and optimisation, demonstrating the energy efficiency of various algorithms in both simple and complex tasks. It also identifies key factors influencing the energy consumption of algorithms and their potential impact on computational processes. Furthermore, the article discusses cognitive concepts and their interplay with computational intelligence, highlighting the role of cognition in the evolution of intelligent algorithms. The conclusion offers insights into the future directions of research in this area, emphasising the need for continued exploration of energy-efficient computing methodologies.

Recent advancements in molecular diagnostics have highlighted the potential of circulating cell-free DNA (ccfDNA) as a biomarker in various diseases. This study aims to explore the role of ccfDNA in the early diagnosis, prognosis, and therapeutic monitoring of diseases, with a focus on oncology. We conducted a comprehensive review and analysis of current literature, combined with experimental approaches involving advanced genomic sequencing and bioinformatics techniques. Our research systematically characterizes the molecular composition of ccfDNA, including its origins, size distribution, and methylation patterns, across different disease states. Furthermore, we investigate the dynamics of ccfDNA release and clearance in the bloodstream, elucidating mechanisms that could influence its diagnostic accuracy. In the context of cancer, we analyze the correlation between tumor-derived ccfDNA and disease progression, response to therapy, and overall survival. Our findings indicate that ccfDNA holds promise as a non-invasive biomarker for early disease detection, real-time monitoring of treatment efficacy, and potentially, predicting relapse. This study contributes to the growing field of liquid biopsies and opens new avenues for personalized medicine, emphasizing the need for standardized protocols in ccfDNA analysis to maximize its clinical utility. The implications of our findings extend beyond oncology, suggesting potential applications of ccfDNA in other pathological conditions.

Photosystem I is a key component of primary energy conversion in oxygenic photosynthesis. Electron transfer reactions in Photosystem I take place across two, parallel, electron transfer chains that converge after a few electron transfer steps, sharing both the terminal electron acceptors, that are a series of three Iron-Sulphur (Fe-S) clusters known as , and , and the terminal donor, . The two electron transfer chains show kinetic differences which are, due to their close geometrical symmetry, mainly attributable to the tuning of the physical-chemical reactivity of the bound cofactors, exerted by the protein surroundings. The factors controlling the rate of electron transfer between the terminal Fe-S clusters are still not fully understood because of the difficulties of monitoring these events directly. Here we present a discussion concerning the driving forces associated to electron transfer between and as well as and , employing a tunnelling-based description of the reaction rates coupled to the kinetic modelling of forward and recombination reactions. It is concluded that the reorganisation energy for oxidation shall be lower than 1 eV. Moreover, it is suggested that the analysis of mutants with altered redox properties can also provide useful information concerning the upstream, phylloquinone, cofactor energetics.

This paper, based on the "Unified Theory of Forces," rigorously proves the formula of de Broglie's wave function. This helps us better understand the following important issues: 1) Theoretically prove and understand the essence of de Broglie's wave function; 2) Prove that when the particle's momentum P is determined, the greater the mass of the particle, the more concentrated its wave function distribution, and the weaker the interference effect; 3) Correct the spatial distribution of the wave function of free particles, proving that the wave function of free particles is strictly constrained within a finite spatial range, which is consistent with the facts we observe.

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of cortical neurodevelopment, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth, explaining the spatial organization and functional significance of neuron response preferences, and compatible with features of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations provide a preliminary anatomically realistic model of cortical information processing.

In Korea, the underground silo structure for low- and intermediate-level radioactive waste disposal facilities has been constructed and operated since 2014. Large-scale earthquakes occurred in 2016 and 2017, respectively, in Gyeongju and Pohang areas near the underground silo structures, and interest in the stability of the underground silo increased significantly. In this paper, one-dimensional free field analyses have been carried out before the three-dimensional silo dynamic analyses subjected to earthquake loadings. As an additional study, a new form of finite element equilibrium equation is derived in terms of relative motions, which is essentially the same equation as that expressed in terms of total motions where the base shear force is applied for earthquake load. The accuracy of conventional finite element solutions is evaluated by directly comparing them with closed-form solutions by frequency domain analysis such as SHAKE91.

Background: The proven efficacy of mTOR inhibitors (mTORI), tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) therapies in metastatic renal cell carcinoma (RCC), suggested that these agents should be investigated as adjuvant therapy with the aim of eliminating any residual undetectable microscopic disease after curative resection. Our study aimed to compare the efficacy of these treatments through the application of an innovative method that reconstructs individual patient data. Methods: Nine phase III studies describing different treatment options for adjuvant RCC were selected. Individual patient data were reconstructed from Kaplan–Meier (KM) curves through the “IPDfromKM method”. Disease-free survival (DFS) were compared among combination treatments and control arm (placebo). Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, this study showed that two ICIs (pembrolizumab and nivolumab plus ipilimumab) and one TKI (sunitinib) showed superiority over placebo, whereas both TKI and mTORI did not. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown.. Conclusion: This novel approach to investigating survival has allowed us to conduct all of the indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted.

This paper introduces new improvements to the modified version of the BIRECT (BI secting RECTangles) algorithm referred to as BIRECTv. We explore various approaches, by first including a grouping strategy for hyper-rectangles having almost the same sizes by categorizing them into different classes. Therefore constraining them not to exceed a certain pre-defined threshold (a small positive value to define the tolerance level). This approach allows for more efficient computation and can be particularly useful when dealing with a large number of hyper-rectangles with varying sizes. To avoid over-sampling, and preventing redundant or excessive sampling, at some shared vertices in descendant subregions, a particular vertex database is used to limit the number of samples taken within each subregion to two. The experimental investigation shows that these improvements have a positive impact on the performance of the BIRECTv(imp.) algorithm and the proposal is a promising global optimization algorithm compared to the original BIRECTv algorithm and its variants. Additionally, the BIRECTv(imp.) algorithm showed particular efficacy in solving high-dimensional problems.

Objectives: This study aimed to assess the impact of a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis from a single center between 2015 to 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features and Gleason score (GS). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. using the Kaplan-Meier survival function and Cox regression model were assessed. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after curative prostatectomy were 5%, 13%, and 21%, respectively. The survival analysis showed that adverse MRI features as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GS≥8, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE- and GS &lt;(4+4)) the presence of adverse MRI features, has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision-making; mECE+, TCCL, capsular disruption, and GS≥8 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who would benefit from closer monitoring.

In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) enables determination of room-temperature structures without causing radiation damage. Using an optical pump-probe or mix-and-injection, SFX enables the intermediate state visualization of a molecular reaction. In SFX experiments, serial and stable microcrystal delivery to the X-ray interaction point is vital for reasonable data collection and efficient beam time. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) facility established SFX instruments at a nanocrystallography and coherent imaging (NCI) experimental station. Various sample delivery methods, including injection, fixed-target scanning, and hybrid methods, have been developed and applied to collect XFEL diffraction data. Herein, we review the currently available sample delivery methods for SFX at the NCI experimental station at the PAL-XFEL. This article will help PAL-XFEL users access the SFX system for their experiments.

Residual stresses in fiber metal laminates (FML) inevitably develop during the manufacturing process. The main contributor to these stresses is the difference in the coefficients of thermal expansion (CTE) between fibers and metal in combination with high process temperatures. To quantify these stresses, the use of specimens with an asymmetric layup is an easily adaptable method. The curvature that develops after the manufacturing of flat laminates with an asymmetrical layer stack is a measure of the level of residual stresses evolving during cure. However, the accuracy of the curvature evaluation is highly dependent on specimen design and other influencing parameters. In this work a large set of FML specimens is investigated to identify relevant influencing parameters and derive conclusions about specimen design and evaluation techniques. For certain layups and process parameters, there is a good correlation between the curvature and the stress-free temperature, which is further covered by analytical solutions for bimetals. This correlation is the basis to transfer curvature into a stress-free temperature that can consequently be used for the quantification of residual stress levels in more complex FMLs. The transfer is validated by in-situ strain measurements during cure using a strain gage technique. Based on the results, the application of asymmetric specimens for residual stress characterization in more complex laminates is presented in the form of a workflow.

Tapping panel dryness (TPD) syndrome is a complex disease of Rubber tree (Hevea brasiliensis L.) which causes cessation of latex drainage upon tapping of rubber tree. Rubber tree virus (RTV1) was identified as a novel pathogen associated with rubber tree and a potential causal agent of TPD. RTV1 is a monopartite RNA virus that is linear, non-enveloped and has a single-stranded (ss) positive RNA genome of approximately 6081 nucleotides and is composed of two major open reading frames (ORFs), ORF1 (polyprotein), and ORF2 (movement protein. This study aimed to investigate the possibility of rubber genome encoded tree microRNAs (miRNAs) as novel therapeutic targets against RTV1 using in silico algorithms. Mature rubber tree miRNAs are retrieved from the miRBase database and are used for hybridization of RTV1 using five different five different computational algorithms including miRanda, RNA22, RNAhybrid and psRNATarget. A total of eleven common rubber tree miRNAs were identified based on consensus genomic positions. The consensus of four algorithms predicted the hybridization sites of hbr-miR396a and hbr-miR398 at common locus positions 6676, 1840 respectively. To validate the prediction, secondary structures of the consensual rubber tree miRNAs and free energy of duplex binding were calculated using the RNAfold and RNAcofold algorithms respectively. We created a plot between rubber tree miRNAs and RTV1 ORFs by using Circos algorithm. In this study, we predicted eleven consensual rubber tree miRNAs. Among these miRNAs, hbr-miR398 was identified as the most effectual miRNA that may target the ORF1 gene of the RTV1 genome. The predicted data will be important in the development of rubber trees resistant to RTV1.

A facile and novel synthesis of thirteen 2-amino-3-cyanopyridine derivatives 5(a-m), by a one-pot multicomponent reaction (MCRs), is described for the first time, starting from aromatic aldehydes, malononitrile, methyl ketones, or cyclohexanone and ammonium acetate in the presence of the nanostructured diphosphate Na2CaP2O7 (DIPH) at 80 °C, under solvent-free conditions. These compounds were synthesized in short reaction times with good to excellent yields (84-94%). The diphosphate Na2CaP2O7 is used as an efficient catalyst, environmentally, easy handling, non-toxic, stable, and reusable. Our study was strengthened by the synthesis of five new pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by intramolecular cyclization of 2-amino-3-cyanopyridines 5(b, c, g, h, j), with formamide. The synthesized products were characterized by FT-IR, SEM, XRD, TEM, 1H NMR, 13C NMR, TLC, and BET. The operating conditions were optimized using a model reaction in which the catalyst amount, temperature, time, and solvent effect were evaluated. The antibacterial activity was tested against Gram-positive and Gram-negative strains for the synthesized compounds.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

This article presents, for the first time, the kinetics and the general conversion features of a 3-component system, BT(BC)/iodonium/Amine, based on proposed mechanism of Liu et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using the new multi-functional initiator of benzophenone–triphenylamine (BT). The additives, iodonium and EDB, have the dual function of (i) regeneration BT and (ii) produce of extra radicals for improved FRP and CP. Analytic formulas are developed to explore the new features including: (i) the conversion efficacy (CE) of FRP is an increasing function of the light intensity, the effective absorption coefficient, and the concentration sum of each of the components, BT, Iod, amine, for transient state. However, CE at steady-state is independent to the light intensity; (ii) the trifunctional hybrid structures of BT3 leads to larger light absorption than other types of BT; it also provides more active sites for the H-abstraction in the presence of EDB, leading to high CE; (iii) the efficacy of FRP is an increasing function of the amine (EDB) concentration, in contrast to that of CP having an opposite dependence; (iv) the consumption rate of BT3 in the BT3/ Iod/EDB system is slower than that of the BT3/Iod system due to photoredox catalytic cycle, and the larger initiator regeneration (RGE)
in the three-component system. A comprehensive model is also proposed that the CE (for both FRP and CP) is governed by (N_jK_jbI), whereas more complex formulas are developed; where Kj is an effective rate constant proportional to the electron transfer quantum yield, and the combined effects of other coupling rate constants; b is an effective absorption coefficient given by the light absorption and excited state quantum yield.

This review covers some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, and the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in {\it The Foundations of Statistics} and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called `small worlds' but cannot work in `large worlds'. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions still need to be answered in all three fields in order to make progress on these problems.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

It is of merit to study the appropriate amount of fiber to add to free-range chickens feed to improve the microbial diversity and gut health in times of plant fiber deprivation. OptiCell is a useful source of fiber as a type of eubiotic lignocellulose, and its positive effects on the growth performance and laying performance of chickens has already been proven. However, few researchers have researched the effects of adding OptiCell on the gut microbiota of chickens. In this research we added three different levels of OptiCell (0%, 2% and 4%) to the feed of caged and free-range Bian chickens from September to November, aiming to observe the effects of adding OptiCell and different feeding modes on the gut microbial diversity and gut health of chickens, and aiming to determine an appropriate amount of OptiCell. The results showed that adding OptiCell could increase the thickness of the cecum mucus layer and the abundance of Akkermansia and Faecalibacterium in caged chickens, and 4% OptiCell was optimum. In addition, adding OptiCell increased the microbial diversity and the abundance of the butyrate-producing bacteria Faecalibacterium and Roseburia of fee-range chickens. The α-diversity and the length of the small intestine with 2% OptiCell in free-range chickens were better than with 2% OptiCell in caged chickens. In addition, compared with caged chickens, the free-range chickens had longer small intestine and lower GLP-1. Taken together, an appropriate amount of OptiCell benefitted the microbial diversity and health of chickens; it was necessary to add dietary fiber to the feed of free-range chickens when plant fibers was lacking, and 2% OptiCell was found to be optimum.

The current study aims to study the optimal fermentation conditions for producing microbial bioactive compounds. The microwave parameters consist on 2450 MHz, and 500-watt for 20, 30, and 40 seconds. The solubility of solvents was tested for the extraction of antioxidant compounds from fermented rice (Koji) by A. flavus, Ethyl acetate was the best solvent used for extraction purposes. Antioxidant properties were differentiated by blocking the oxidation of the linoleic acid with an inhibition rate of 73.13% at a concentration of 200 mg/mL, in addition to increasing its effectiveness for free radical extraction and reduction strength by increasing concentrations gradually. The bond ability to irons was lower compared to the EDTA-2Na, in addition to the obtained total content corresponding to phenolic compounds in the ethyl acetate extract of fermented rice (Koji) by A. flavus was 232.11 mg, on the basis of galic acid/mg. The stability of the antioxidant compounds of the ethyl acetate extract of fermented rice (Koji) by A. flavus was also studied; showing stability under neutral conditions, as well as at high temperatures (185 °C during two hours). However, no stability was obtained under acidic and alkaline conditions.

The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.

The processing of cloud free geo-referenced imagery is one of the preliminary processing step of any land application. This letter describe the methodology developed to obtain a seamless cloud free composite of Africa for 2016 using Sentinel-2A data at 10 meters resolution freely available from the European Space Agency. The method is based on an hybrid method resulting from the merging of the two most robust time series methods namely the "darkest pixel" and the "maximum NDVI" previously developed with AVHRR time series.

Background CDK4/6 inhibitors are the standard of care for HR+/HER2-negative metastatic breast cancer in combination with endocrine therapy. However, the real-world efficacy and safety of standard versus reduced doses in elderly patients remain unclear. This study aims to compare the clinical outcomes of standard versus reduced doses of CDK4/6 inhibitors in elderly patients with metastatic breast cancer. Methods This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. PFS and OS were estimated using the Kaplan-Meier method, and comparisons between groups were performed using the log-rank test. Results Of the total population, 108 patients (68.4%) received the standard dose, and 50 patients (31.6%) received a reduced dose. The standard dose group had significantly longer median PFS compared to the reduced dose group (21.3 vs. 15.2 months, p = 0.014), while median OS did not differ significantly (37.2 vs. 37.2 months, p = 0.103). Subgroup analyses revealed no significant differences in PFS or OS between standard and reduced doses for Ademaciclib and Ribociclib, while Palbociclib at standard dose showed superior PFS (21.9 vs. 12.7 months, p = 0.029) and OS (50.5 vs. 28.6 months, p = 0.026). The incidence of Grade 2-4 AEs was higher in the standard dose group (74.2% vs. 56.8%, p = 0.044). Conclusions Dose reduction of CDK4/6 inhibitors, particularly Ademaciclib and Ribociclib, is a viable option in elderly patients, maintaining comparable OS outcomes to standard dosing while reducing the risk of adverse events. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.

There is a strong global demand for sulfate- free personal cleansing products. The objective of sulfate-free personal cleansing technology should not be aimed at the absence of “sulfate” wording in the ingredient listing, but on the true benefits to both people and the planet, including but not limited to safety, mildness, and sensory for the people perspective and renewability, low carbon footprint, low water footprint, biodegradability &amp; sustainability for the planet perspective. In addition, some surfactants or their precursors contain 1,4-dioxane as a by-product in their manufacturing, which is a major safety concern. In this paper, several commonly used sulfate-free surfactants are compared based on a variety of desirable criteria from both the people and the planet perspective. There is also an important trend promoting green manufacturing processes using natural, renewable, safe, biodegradable &amp; sustainable feedstocks to mitigate the challenges presented by climate change. It is concluded that the best options for the sulfate-free personal cleansing products of the future are glutamates for skin cleansing and alaninates for hair cleansing.

Patients with heart failure (HF) with improved LVEF (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. Identification of predictors for HFimpEF may play a crucial role in individual management of HF with reduced EF (HFrEF). Cell-free nuclear (cf-nDNA) DNA are released from damaged cells and contribute to adverse cardiac remodeling, cardiac dysfunction and inflammation. The purpose of the study was to elucidate whether cf-nDNAs are associated with HFimpEF. It has been prescreened 1416 patients with HF using local database. Between October 2021 and August 2022 we included 452 patients chronic HFrEF after prescription of optimal guideline-based therapy and identified HFimpEF in 177 individuals from them according to the criteria of European Society of Cardiology. Measurements of circulating biomarkers were performed at baseline and in 6 months. Detection of cf-nDNA was executed with real time quantitative PCR (qPCR) using NADH dehydrogenase, ND2 and beta-2-microglobulin. We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. Presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; confidence interval [CI] = 0.62 – 0.88; p = 0.044), type 2 diabetes mellitus (OR = 0.77; CI = 0.71 – 0.82; p = 0.042) and digoxin administration (OR = 0.85; CI = 0.72-0.97; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤1940 pmol/mL (OR = 1.42; 95% CI = 1.19-1.98, p = 0.001), relative decrease in NT-proBNP levels (&gt;35% vs. ≤35%) from baseline (OR = 1.52; 95% CI = 1.38-0.69, p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.56; 95% CI = 1.07-2.94, p = 0.001) were positive predictors for HFimpEF. Multivariate logistic regression adjusted to ischemia-induced cardiomyopathy, IV HF NYHA class, and digoxin use yielded that NT-proBNP ≤1940 pmol/mL (OR = 1.43; 95% CI = 1.21-1.88, p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.64; 95% CI = 1.19-2.15, p = 0.001) independently predicted HFimpEF. In conclusions: we established that the levels of cf-nDNA≤7.5 μmol/L independently predicted HFimpEF and improved discriminative ability of as single measured NT-proBNP as well as relative decrease in NT-proBNP levels ≤35% from baseline.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity, and differentiate it from ICI-induced enterocolitis. Methods and Material: We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. Comparative analysis was performed to identify the key differences between the two groups. Results: Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-CD. On pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. Conclusion: ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and discontinuation of antineoplastic immunotherapy.

Smart Transformer (ST)-based Meshed Hybrid AC/DC Microgrids (MHM) are a feasible alternative to increase the performance of conventional microgrids (MG) and to increase the penetration of Distributed Energy Resource (DER) at the same time, active and reactive power dispatch on the system. Despite this, MHMs present challenges in managing resources under uncertainties and controlling electronic converters associated with the ST and DER, making it complex to achieve optimal system performance. In this paper, a Data-Driven Distributionally Robust Optimization (DDDRO) for Day-Ahead Operation Planning of an ST-based MHM considering the reactive power dispatch of the DER that minimizes network losses, voltage deviations, and operation cost simultaneously, considering uncertainties of Photovoltaic Generators (PVG) and demand, is proposed. The Column and Constraint Generation (C&amp;CG) algorithm and Duality-Free Decomposition (DFD) method are adopted. Besides, the original mixed-integer non-linear planning problem is converted into a Mixed-Integer (MI) Second-Order Cone Programming (SOCP) problem through second-order cone relaxation and positive octagonal constraint method. Simulation experiments and results with a connected MHM system demonstrate the effectiveness and performance of the proposed model. Finally, we observe the effect of the meshed structure of MG and the positive impact of integrating the ST to form MHM, taking advantage of the degrees of freedom of this multi-stage converter for optimal energy management under uncertain conditions.

Rapidly digestible starch can be obtained by gelatinization (cooking), cooking extrusion, use of small granule starch, breaking down starch granules, or by hydrolysis to maltodextrins. Resistant starch includes five groups: the first group is physically encapsulated starch within a food/polymer matrix, the second one is some native starch, the third one is recrystallized starch, the fourth one is chemically modified starch, and the fifth one is starch-lipid complexes. Starch digestion in the human body is also influenced by the degree of chewing, activity of α-amylase in the intestine, and transit time through the stomach and small intestine. Resistant starch or dietary fiber (DF) enriches specific bacterial groups located in the large intes-tine. They produce short chain fatty acids (SCFAs) and gases, causes the lowering of the pH, and inhibits pathogens. SCFAs are considered endogenous signaling molecules, acting through their free fatty-acid receptors 2 and 3 which can trigger the secretion of glucagon-like peptide-1 and peptide PYY, being released together following a meal to mediate postprandial satiety. A sufficient intake of DF reduces the risk of cardiovascular disease, coronary heart disease, stroke, hyperten-sion, colorectal cancer, and type 2 diabetes. Gluten matrix or phenolic compounds can lead to a low digestion rate of starch.

To date, various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an E. coli cell-free expression method to screen better chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the amount variables between samples without protein purification. We applied it to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin, and determined the rank orders of antibacterial activities on different S. aureus strains in our experimental conditions.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders globally, and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Methods: Using droplet digital polymerase chain reaction (ddPCR) we comprehensively analyzed and distinguished ccfDNA and ccf mtDNA in the serum and CSF of PD and control patients. Results: The quantitative analysis of serum ccf-DNA in PD patients demonstrated significant increase of ccf mtDNA and ccfDNA compared to healthy control patients and significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients compared to healthy controls. These decreases were not statistically significant, but were in agreement with previous data. In-terestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. Limitations: the small sample size of serum and CSF were the main limitations of this study. Conclusion: To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR and indicating the distribution of the copy number of ccf mtDNA, as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater than ccfDNA potential to lead the development of novel treatments for PD patients.

Space–air–ground integrated network (SAGIN) is considered as an enabler for the sixth-generation (6G) networks. By integrating terrestrial and non-terrestrial (satellite, aerial) networks, SAGIN seem to be a quite promising solution to provide reliable connectivity everywhere and all the time. Their availability can be further enhanced if hybrid free space optical (FSO)/radio frequency (RF) links are adopted. In this paper, the performance of a hybrid FSO/RF communication system operating in SAGIN has been analytically evaluated. In the considered system, a high altitude platform station (HAPS) is used to forward the satellite signal to the ground station. Moreover, the FSO channel model assumed takes into account the turbulence, pointing errors and path losses, while for the RF links, a relatively new composite fading model has been considered. In this context, a new link selection scheme has been proposed that is designed to reduced the signaling overhead required for the switching operations between the RF and FSO links. The analytical framework that has been developed is based on the Markov chain theory. Capitalizing on this framework, the performance of the system has been investigated using the criteria of outage probability and the average number of link estimations. The numerical results presented reveal that the new selection scheme offers a good compromise between performance and complexity.

Resveratrol is currently considered an option for chemoprevention and treatment of oral cancer, but the instability and unfavorable pharmacokinetics hinder its use in clinical practice. The present study deals with the preparation of resveratrol liposomes by a method that preserves stability and provides payload high enough for chemoprevention and/or treatment of oral cancer. Different temperatures, RSV concentrations and molar fractions, as well as the presence or absence of vitamin C in the hydration media were assayed. Liposome hydrodynamic diameter, polydispersity and zeta potential were evaluated by dynamic light scattering. In vitro biocompatibility, antioxidant activity and permeability were evaluated using TR146 cells and PermeaPad® membranes. Liposomes were included in hydrogels and films, and their suitability for buccal application was evaluated. According to the results, a temperature of 37ºC was optima to efficiently produce the resveratrol liposomes. Vitamin C was found to influence the liposome size, while resveratrol concentration significantly influenced the entrapment efficiency. High cell biocompatibility and potent intracellular antioxidant activity were observed and the inclusion of vitamin C reinforced the antioxidant effects. High permeation across PermeaPad® membranes and efficient uptake by TR146 cells was proved for resveratrol loaded liposomes. Liposomal hydrogels and films appropriated for buccal application were obtained and the payload of the formulations was high enough to produce mucosa concentrations above resveratrol IC50 values reported for cancer cells.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles: spins interactions with in each sub-ensemble are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors, and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents (, , , ) gives way to the non-classical form (, , , ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions, but only shifts their critical points, allowing for control of the system’s parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau, and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model.

A topical challenge for algorithms in general and for automatic image categorization and generation in particular is presented with the aim of highlighting strengths and deficiencies of current Artificial Intelligence approaches while sketching a way forward. A general lack of encompassing symbol-embedding and (not only) -grounding in some bodily basis is made responsible for current deficiencies. A concomitant dearth of hierarchical organization of concepts follows suite. As a remedy for these shortcomings, it is proposed to take a wide step back and to newly incorporate aspects of cybernetics and analog control processes. It is claimed that a promising overarching perspective is provided by the Ouroboros Model with a valid and versatile algorithmic backbone for general cognition at all accessible levels of abstraction and capabilities.

Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metastases-free survival; overall survival; toxicity.

Variable Angle Tow (VAT) laminates offer a promising alternative to classical straight fiber composites in terms of design and performance. However, analyzing these structures can be more complex due to the introduction of new design variables. Carrera's Unified Formulation (CUF) has been successful in previous works for buckling, vibrational, and stress analysis of VAT plates. Typically, one-dimensional (1D) and two-dimensional (2D) CUF models are used, with a linear law describing the fiber orientation variation in the main plane of the structure. The objective of this article is to expand the CUF 2D plate finite elements family to perform free vibration analysis of composite laminated plate structures with curvilinear fibers. The primary contribution is the application of Reissner's Mixed Variational Theorem (RMVT) to a CUF finite element model. The Principle of Virtual Displacements (PVD) and RMVT are both used as variational statements for the study of monolayer and multilayer VAT plates dynamic behavior. The proposed approach is compared to Abaqus three-dimensional (3D) reference solutions, classical theories and literature results to investigate the effectiveness of the developed models. Results demonstrate that mixed theories provide the best approximation of the reference solution in all cases.

The objective of parsing is to transform a natural language sentence it in to a standard order. and in a same way a sentence is tokenized with an appropriate format. There are certain English grammar evaluation rules and the parsing approach which is to be followed for the proper formation of a particular sentence syntactically and semantically using the parsing approach. A sentence in English language is the main element in the semantic parser, which creates a parse tree with the help of applying semantic dating technique to a number of phrases. A parser divides a token into smaller components by applying sets of guidelines that characterize and a series of the tokens to determine its structure of the language, which specified by grammar. The illustration provides easy records on grammatical connections, which can simply know and put into practice with those who have no prior knowledge of the language, such as those who need to obtain textual family members. The semantic family members represent the relationships of a number of the words in the sentence. We advocate utilizing our parser to acquire the tagged sets as well as a context-free layout grammatical representation for the source form. All pronouns, adverbs, singular, plural, nouns, verbs, people, adjectives, tenses and other words are kept in a database.

Apple replant disease is a severe problem in orchards and tree nurseries. Evidence for the involvement of a nematode-microbe disease complex was reported. To search for this complex, plots with a history of apple replanting, and control plots cultivated for the first time with apple were sampled in two fields in two years. Shoot weight drastically decreased with each replanting. Nematodes were extracted from soil samples by floatation-centrifugation, washed on a 20 µm-sieve, and used for DNA extraction. Nematode communities and co-extracted fungi and bacteria were analyzed by high-throughput sequencing of amplified ribosomal fragments. The nematode community and co-extracted fungal and bacterial communities significantly differed between replanted and control plots. Free-living nematodes of the genera Aphelenchus, Cephalenchus, and an unidentified Dorylaimida were associated with replanted plots, as indicated by linear discriminant analysis effect size. Among the co-extracted fungi and bacteria, Mortierella was most indicative of replanting. Some genera, mostly Rhabditis, indicated healthy control plots. Isolating and investigating the putative disease complexes will help to understand and alleviate stress-induced root damage of apple in replanted soil.

The synergic features and enhancing strategies for various photopolymerization systems are reviewed by kinetic schemes and the associated measurements. The important topics include: (i) photo crosslinking of corneas for the treatmnet of corneal deseases using UVA-light (365 nm) light and riboflavin as the photosensitizer; (ii) synergic effects by a dual-function enhancer in a 3-initiator system; (iii) synergic effects by a 3-initiator C/B/A system, having an electron-transfer and oxygen-mediated energy-transfer pathways; (iv) copper-complex (G1) photoredox catalyst in G1/Iod/NVK systems for free radiical (FRP) and cationic photopolymeriation (CP); (v) radical-mediated thiol-ene (TE) photopolymerizations; (vi) superbase photogenerator based-catalyzed thiol−acrylate Michael (TM) addition reaction; and the combined system of TE and TM usinghual wavelength; (vii) dual-wavelength (UV and blue) controlled photopolymerization confinement (PC); (viii) dual-wavelength (UV and red) selectively controlled 3D printing; and (ix) 3-wavelength selectively controlled in 3D printing and additive manufacturing (AM). With minimum mathematics, we present ( for the first time), the synergic features and enhancing strategies for various systems of multi-commponents, initiators, monomers, and under one- two- and there-wavelength light. Therefore, this Review provides not only the bridging between modeling and measurements, but also guidances for further experimantal stuides and new applications in 3D printings and additive manufacturing (AM), based on the innovative concepts (kinetics/schemes).

The development of platinum group metal-free (PGM-free) electrocatalysts derived from cheap and environmentally friendly biomasses for oxygen reduction reaction (ORR) is a topic of relevant interest, particularly from the point of view of sustainability. Fe-nitrogen-doped carbon materials (Fe-N-C) have attracted particular interest as alternative to Pt-based materials, due to the high activity and selectivity of Fe-Nx active sites, the high availability and good tolerance to poisoning. Recently, many studies focused on developing synthetic strategies, which could transform N-containing biomasses into N-doped carbons. In this paper chitosan was employed as a suitable N-containing biomass for preparing Fe-N-C catalyst in virtue of its high N content (7.1%) and unique chemical structure. Moreover, the major application of chitosan is based on its ability to strongly coordinate metal ions, a precondition for the formation of Fe-Nx active sites. The synthesis of Fe-N-C consists in a double step thermochemical conversion of a dried chitosan hydrogel. In acidic aqueous solution, the preparation of physical cross-linked hydrogel allows to obtain sophisticated organization, which assure an optimal mesoporosity before and after the pyrolysis. After the second thermal treatment at 900 °C, a highly graphitized material was obtained, which has been fully characterized in term of textural, morphological and chemical properties. RRDE technique was used for understanding the activity and the selectivity of the material versus the ORR in 0.5 M H2SO4 electrolyte. Special attention was put in the determination of the active site density according to nitrite electrochemical reduction measurements. It was clearly established that the catalytic activity expressed as half wave potential linearly scales with the number of Fe-Nx sites. It was also established that the addition of the iron precursor after the first pyrolysis step leads to an increased activity because of both an increased number of active sites and of a hierarchical structure, which improves the access to active sites. At the same time, the increased graphitization degree, and a reduced density of pyrrolic nitrogen groups are helpful to increase the selectivity toward the 4e- ORR pathway.

As reported by us and others previously (1, 2), the D614G mutation appeared in the spike glycoprotein (SPG) of the SARS-CoV-2 (the pathogen behind COVID-19) at the early stages of the pandemic and then G614 containing variant of SARS-CoV-2 became the predominant strain in most human populations across the world. However, one of the most recent reports from India (3) stated the incidence of G614 to be only 26% in the Indian population. This report is contradictory to the information available through the GenBank (4) SARS-CoV-2 sequence deposits made by various laboratories from India. The above stated report currently circulating in the Indian media is likely to create a public perception that the Indian strain is less contagious and such a notion could be harmful to people’s welfare. In view of this concern we have re-evaluated, updated and recalculated the incidence of the G614 variant in the Indian population by analyzing 395 Indian SARS-CoV-2 genomic sequences available in the GenBank as of June 26, 2020. In our analysis we have categorized the samples by the month in which the samples were collected. We have used an alignment-free software tool named Compare (5, 6), and the Basic Local Alignment Search Tool (BLAST) (7) in the present analysis. We finally inspected each of the 395 sequences physically for the presence of aspartic acid (D) or glycine (G) at the 614^th position of the spike glycoprotein. We analyzed an Australian cohort in parallel for comparison. We have found that the prevalence of G614 variant in the Indian samples for the month of June 2020 is 90.6%. The trends are similar with the Australian samples.

Reduced nutrient mineralization rates under minimum tillage are usually compensated by mineral fertilizer application. These cannot be applied in organic farming systems, however. We hypothesized that organic minimum tillage based on frequent cover cropping and application of dead mulch will improve soil fertility and can compensate for the potential negative effects of minimum tillage. Two long-term field experiments were set up in 2010 and 2011 comparing plough versus minimum tillage including application of transferred mulch. As second factor, the application of compost versus mineral potassium and phosphorus was compared. In 2019, soils were analyzed for soil pH, organic carbon, macro-, micronutrients, microbial biomass, microbial activity and total nematode abundance. In addition, performance of pea in the same soils was determined under greenhouse conditions. Across both experiments, macronutrients (+52%), micronutrients (+11%), microbial biomass (+51%), microbial activity (+86%), and bacterivorous nematodes (+112%) increased in minimum tillage compared with the plough-based system. In the greenhouse, pea biomass was 45% higher in the soil that had been subjected to minimum tillage compared to the plough. In conclusion, soil fertility can be improved in organic minimum tillage systems by intensive cover cropping and application of dead mulch to levels higher than in a plough-based system.

In this paper, we study a generalised CIR process with externally-exciting and self-exciting jumps, and focus on the distributional properties and applications of this process and its aggregated process. The first and second moments of this jump-diffusion process are used to calculate the insurance premium based on mean-variance principle. The Laplace transform of the aggregated process is derived, and this leads to an application for pricing default-free bonds which could capture the impacts of both exogenous and endogenous shocks. Illustrative numerical examples and comparisons with other models are also provided.

Background: Video assisted thoracoscopic surgery (VATS) has become the recommended approach for treatment of resectable lung cancer. However, no large randomized clinical trial has been conducted formally comparing surgical resections completed by VATS to those done by open thoracotomy (OT) in low volume centers. The current study sought to assess differences in recurrence-free survival (RFS), overall survival (OS), positive margins and postoperative length of stay (LOS) between VATS and OT lobectomies in our center. Method: A single institution retrospective chart review from May 2005 through May 2015 was conducted. All patients diagnosed with stage I through III lung cancer who underwent surgical resection were selected. Patient and tumor characteristics recorded included age at diagnosis, sex, tobacco use, tumor location (side and lobe), stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographics, tumor characteristics and LOS. Multiple logistic and Cox regression analyses were used to compute relative risk (RR) for positive margins and mortality hazard ratios along with 95 percent confidence intervals (95%CI), respectively. Results: Of the 235 patients, 101 subjects had VATS while OT was performed in 134 patients. Age at diagnosis, sex, tobacco use, tumor location, and size were comparable for VATS and OT. No significant difference was observed in the relative risk of positive margins for VATS versus OT, RR = 0.56 (95%CI = 0.26, 1.05). However, VATS had shorter median LOS compared to OT (4 vs. 6 days, respectively), p = 0.002. A comparison of VATS versus OT showed no significant difference in the risk of recurrence, HR = 1.21 (95%CI = 0.74, 2.00), or death, HR = 1.34 (95%CI = 0.88, 2.06), in the intent-to-treat population. Similarly, no significant differences in recurrence or mortality risk were observed between VATS versus OT for analyses conducted separately for each cancer stage group or those limited to patients with negative margins. Conclusion: Our study indicates that compared to OT, VATS leads to shorter LOS while achieving comparable margins status, recurrence-free and overall survival regardless of tumor stage at diagnosis.

Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.

A new optical steganography scheme is proposed that transmits a stealth optical code-division multiple-access (OCDMA) signal through a public binary phase-shift keying (BPSK) channel. Polarization beam splitters and arrayed waveguide gratings are used to implement a spectral-polarization coding (SPC) system with an incoherent optical source. We employ a Walsh–Hadamard code as the signature code of the user who wants to transmit stealth information using the system. A free space optical link applied to this system maintains the polarization states of light during propagation. The secret data is extracted using correlation detection and balanced subtraction in the OCDMA decoder of the intended receiver, and the other signal from the public channel is reduced by the OCDMA decoder. At the demodulator of the public channel, BPSK demodulation eliminates the stealth signal so that the public channel is not affected by the stealth signal. The two signals cannot interfere with each other. The results of this study show that our proposed optical steganography system is highly secure. The stealth signal can be favorably hidden in the public channel when the average source power of the stealth signal, public noise, and public signal are −5, −3, and 0 dBm, respectively.

The activity and cyclability of Cu-MOF-74 as catalyst was studied for the ligand-free C-O cross-coupling reaction of 4-nitrobenzaldehyde (NB) with phenol (Ph) to form 4-formyldiphenyl ether (FDE). Cu-MOF-74 is characterized by unsaturated copper sites in a highly porous metal-organic framework. The influence of solvent, reaction temperature, NB/Ph ratio, catalyst concentration and basic agent (type and concentration) were evaluated. High conversions were achieved at 120°C, 5 mol% of catalyst, NB/Ph ratio of 1:2, DMF as solvent and 1 equivalent of K2CO3 base. The activity of Cu-MOF-74 material was higher than other ligand-free copper catalytic systems tested in this study. This catalyst was easily separated and reused in five successive runs, achieving a remarkable performance without significant porous framework degradation. The leaching of copper species in the reaction medium was negligible. The O-arylation between NB and Ph took place only in the presence of Cu-MOF-74 material, being negligible without the solid catalyst.

With the advent of Web 3.0, the swift advancement of technology confronts an imminent threat from quantum computing. Security protocols safeguarding the integrity of Web 2.0 and Web 3.0 are growing more susceptible to both quantum attacks and sophisticated classical threats. The article introduces our novel long-distance free-space quantum secure direct communication (LF QSDC) as a method to safeguard against security breaches in both quantum and classical contexts. Differing from techniques like quantum key distribution (QKD), LF QSDC surpasses constraints by facilitating encrypted data transmission sans key exchanges, thus diminishing the inherent weaknesses of key-based systems. The distinctiveness of this attribute, coupled with its quantum mechanics base, protects against quantum computer assaults and advanced non-quantum dangers, harmonizing seamlessly with the untrustworthy tenets of the Web 3.0 age. The focus of our study is the technical design and incorporation of LF QSDC into web 3.0 network infrastructures, highlighting its efficacy for extended-range communication. LF QSDC is based on the memory DL04 protocol and enhanced with our novel Quantum-Aware Low-Density Parity Check (LDPC), Pointing, Acquisition, and Tracking (PAT) technologies, and Atmospheric Quantum Correction Algorithm (AQCA). Utilizing this method not only bolsters the security of worldwide Web 3.0 networks but also guarantees their endurance in a time when quantum and sophisticated classical threats exist simultaneously. Consequently, LF QSDC stands out as a robust security solution, well-suited for Web 3.0 systems amidst the constantly evolving digital environment.

In this study, global response analysis was performed to explore the mechanism of action of Usnic acid and its synergy with Norfloxacin, a well-known quinolone antibiotic to which MRSA clinical isolates showed resistance (MIC, 500 µg/mL). Microdilution assay, growth kinetics, microscopic analysis, and cell-based assays consistently showed that Usnic acid possess strong anti-staphylococcal activity (MIC, 7.8 µg/ml), causes cell leakage, modulates efflux pump activity, and synergizes with Norfloxacin against multi-drug resistant clinical isolate MRSA 2071. Whole cell proteome profiling using gel-free based nano-LC-ESI-QTOF-MS/MS revealed several proteins whose expression was significantly modulated by Usnic acid and Norfloxacin alone or in combination. Usnic acid downregulated the abundance of RNA polymerase subunits (RpoB, RpoC), carbamoyl phosphate synthase large subunit (PyrAB), chaperone (GroEL), and adenylosuccinate synthetase (PurA). Interestingly, proteins found to be upregulated in the presence of Usnic acid and Norfloxacin included oxidative stress-related proteins such as peroxidase (Tpx), alkyl hydroperoxide reductase (AphC), and general stress protein (UspA). This study clearly showed that Usnic acid affects numerous cellular targets and can potentiate the action of Norfloxacin. Furthermore, an in-vivo study emphasized the use of Usnic acid to develop as a safe phytopharmaceutical to repurpose old antibiotics through combination therapy against MRSA infections.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as by elemental analysis and by HR-MS. The structure of a n-hexane monosolvate has been determined by single crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677 and C. tropicalis ATCC 64677) has been tested, using the disk diffusion and the microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

Fast Field-Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry is a powerful non-destructive magnetic resonance technique that enables, among other things, the investigation of slow molecular dynamics at low magnetic field intensities. FFC-NMR relaxometry measurements provide insight into molecular motion across various timescales within a single experiment. This study focuses on a \textit{model-free} approach, representing the NMRD profile $R_1$ as a linear combination of Lorentzian functions, thereby addressing the challenges of fitting data within an ill-conditioned linear least-squares framework. Tackling this problem, we present a comprehensive review and experimental validation of three regularization approaches to implement the model-free approach to analysing NMRD profiles. These include: (1) \nameUpe, utilizing locally adapted $L_2$ regularization; (2) \nameL, based on $L_1$ penalties; and (3) a hybrid approach combining locally adapted $L_2$ and global $L_1$ penalties. Each method's regularization parameters are determined automatically, according to the Balancing and Uniform Penalty principles. % Our contributions include the implementation and experimental validation of the \nameUpe{} and \nameUp{} algorithms, and the development of a "dispersion analysis" technique to assess the existence range of the estimated parameters. The objective of this work is to delineate the variance in fit quality and correlation time distribution yielded by each algorithm, thus broadening the set of software tools for the analysis of sample structures in FFC-NMR studies. The findings underline the efficacy and applicability of these algorithms in the analysis of NMRD profiles from samples representing different potential scenarios. 1

This study evaluates audiogenic epilepsy in Krushinsky-Molodkina rats using a wireless EEG system to overcome the limitations of traditional methods that restrict animal movement. Nine male KM rats, prone to audiogenic seizures, were implanted with electrodes in areas critical for seizure activity (inferior colliculus, ventrolateral periaqueductal gray, dorsal area of the secondary auditory cortex, and motor cortex). This setup allowed for the observation of seizures without movement restriction. Results showed that targeted neural intervention via electrode implantation reduced the intensity of convulsive seizures in half of the subjects, suggesting a potential therapeutic approach. The severity of seizures was influenced by the pre-phonostimulation EEG background activity in specific brain regions, identifying them as key in the genesis and generalization of seizures. Observations of dual generalized seizure waves and induced hyperkinesis challenge conventional epilepsy models and suggest new directions for research and therapy development.

Abstract: The ever-increasing use of motor vehicles causes a number of traffic safety and community issues, which are particularly severe in cities, accompanied with scarcity of parking spaces and challenges encountered in the road layout alteration projects. The commonly applied solutions include designation of through streets and implementation of on-street parking on residential streets and retrofitted traffic calming measures (TCMs). This article presents the results of the study conducted on a two-way street where Metered Parking System MPS was implemented together with diagonal and parallel parking spaces, refuge islands, horizontal deflection and lane narrowing by a single-sided chicane. The aim of this study was to identify those TCMs that effectively helped to reduce the island approach speed. Heuristic method was applied to assess the effect of the respective TCMs on reducing the island approach speed and the key speed reduction determinants were defined using cause and effect diagram and Pareto chart. Comparative analyses were carried out to rate the respective TCMs as effective, moderately effective or ineffective. Section 1 of this article presents the output of the literature review on urban parking analyses and TCM efficacy. Section 2 presents the study site and the applied heuristic method. The study results are presented in Section 3. Section 3 defines the determinants on the cause and effect diagram and analyses the determinants using the Pareto chart. The final conclusions and comments are given in Section 5. Although the study was limited to a single street in Poland, the findings may hold true in other countries where similar TCMs are used.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

Continual learning (CL), a.k.a lifelong learning, is an emerging research topic that has been attracting increasing interest in the field of machine learning. With human activity recognition (HAR) playing a key role in enabling numerous real-world applications, an essential step towards the long-term deployment of such systems is to extend the activity model to dynamically adapt to changes in people’s everyday behavior. Current research in CL applied to HAR domain is still under-explored with researchers exploring existing methods developed for computer vision in HAR. Moreover, analysis has so far focused on task-incremental or class-incremental learning paradigms where task boundaries are known. This impedes the applicability of such methods for real-world systems. To push this field forward, we build on recent advances in the area of continual learning and design a lifelong adaptive learning framework using Prototypical Networks, LAPNet-HAR, that processes sensor-based data streams in a task-free data-incremental fashion and mitigates catastrophic forgetting using experience replay and continual prototype adaptation. Online learning is further facilitated using contrastive loss to enforce inter-class separation. LAPNet-HAR is evaluated on 5 publicly available activity datasets in terms of its ability to acquire new information while preserving previous knowledge. Our extensive empirical results demonstrate the effectiveness of LAPNet-HAR in task-free CL and uncover useful insights for future challenges.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

The Thermodynamic Formalism provides a rigorous mathematical framework to study quantitative and qualitative aspects of dynamical systems. At its core there is a variational principle and corresponding, in its simplest form, to the Maximum Entropy principle, used as a statistical inference procedure to represent, by specific probability measures (Gibbs measures), the collective behaviour of complex systems. This framework has found applications in different domains of scienThe Thermodynamic Formalism provides a rigorous mathematical framework to study quantitative and qualitative aspects of dynamical systems. At its core there is a variational principle and corresponding, in its simplest form, to the Maximum Entropy principle, used as a statistical inference procedure to represent, by specific probability measures (Gibbs measures), the collective behaviour of complex systems. This framework has found applications in different domains of science, in particular, has been fruitful and influential in neurosciences. In this article, we review how the Thermodynamic Formalism can be exploited in the field of theoretical neuroscience, as a conceptual and operational tool, to link the dynamics of interacting neurons and the statistics of action potentials from either experimental data or mathematical models. We comment on perspectives and open problems in theoretical neuroscience that could be addressed within this formalism.ce, in particular, has been fruitful and influential in neurosciences. In this article, we review how the Thermodynamic Formalism can be exploited in the field of theoretical neuroscience, as a conceptual and operational tool, to link the dynamics of interacting neurons and the statistics of action potentials from either experimental data or mathematical models. We comment on perspectives and open problems in theoretical neuroscience that could be addressed within this formalism.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

Perioperative acute pain management in pediatric patients is essential to reduce complications. Adenoidectomy-Tonsillectomy are surgical procedures requiring pain control, and risk minimization for postoperative bleeding, nausea, and vomiting. Despite their known secondary effects, the use of opioid analgesics remains preponderant in pediatric perioperative management. We present an updated review on perioperative pain management in children and describe the development and implementation of a multimodal analgesia protocol aimed to improve patients’ pain management while consistently reducing opioids use. Information from relevant articles was summarized, then compared to our clinical needs. Learnings were used to create and implement a multimodal analgesia protocol to be used in patients 3-9 years-old undergoing adenoidectomy/tonsillectomy. Analgesic strategies have emerged to reduce or avoid the use of opioids. Among these strategies, combining different non-opioid analgesics (Ibuprofen, Paracetamol, Metamizole) has been shown to be an effective and safe pharmacological strategy when implemented as part of postoperative multimodal analgesia protocols. Significant evidence associating the use of NSAIDs with a bigger risk of postoperative bleeding does not exist. Multimodal and preventive analgesia has shown to provide significantly more effective analgesia than some opioid regimens. Ibuprofen offers highly effective analgesia for postoperative pain, particularly when combined with acetaminophen.