The search for periodic signals from blazars has become an actively pursued field of research in recent years. This is because periodic signals bring us information about the processes occurring near the innermost regions of blazars, which are mostly inaccessible to our direct view. Such signals provide insights into some of the extreme conditions that take place in the vicinity of supermassive black holes that lead to the launch of the relativistic jets. In addition, studies of characteristic timescales in blazar light curves shed light on some of the challenging issues in blazar physics that includes disk-jet connection, strong gravity near fast rotating supermassive black holes and release of gravitational waves from binary supermassive black hole systems. However, a number of issues associated with the search for quasi-periodic oscillations (QPOs) in blazars e.g., red-noise dominance, modest significance of the detection, periodic modulation lasting for only a couple of cycles and their transient nature, make it difficult to estimate the true significance of the detection. Consequently, it also becomes difficult to make meaningful inferences about the nature of the on-going processes. In this proceedings, results of study focused on searching for QPOs in a number of blazar multi-frequency light curves are summarized. The time series analyses of long term observations of the blazars revealed the presence of year-timescale QPOs in the sources including OJ 287 (optical), Mrk 501 (gamma-ray), J1043+2408 (radio) and PKS 0219 -164 (radio). As likely explanations, we discuss a number of scenarios including binary supermassive black hole systems, Lense–Thirring precession, and jet precession.

Enterovirus 71 (EV71) infection hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby representing a serious public health hazard. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially reveal that the interleukin enhancer binding factor 2 (ILF2) down-regulates EV71 50% tissue culture infective dose (TCID50), attenuates EV71 plaque formation unit (PFU), thereby repressing EV71 infection. Moreover, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects. Chip data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) differentiated macrophages and in human rhabdomyosarcoma (RD) cells. Additionally, EV71 non-structural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm and co-localizes with 2B in the cytoplasm. Therefore, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to cytoplasm through its 2B protein.

In this paper, we study a three step iterative scheme to approximate fixed points of Suzuki's generalized non-expansive mappings. We establish some weak and strong convergence results for such mappings in uniformly convex Banach spaces. Further, we show numerically that iterative scheme (1.8) converges faster than some other known iterations for Suzuki's generalized non-expansive mappings. To support our claim, we give an illustrative example and approximate fixed points of such mappings using Matlab program. Our results are new and generalize several relevant results in the literature.

Fluctuation theorems are a class of equalities each of which links a thermodynamic path functional such as heat and work to a state function such as entropy and free energy. Jinwoo and Tanaka [L. Jinwoo and H. Tanaka, Sci. Rep. 5, 7832 (2015)] have shown that each microstate of a fluctuating system can be regarded as an ensemble (or a 'macrostate') if we consider trajectories that reach each microstate. They have revealed that local forms of entropy and free energy are true thermodynamic potentials of each microstate, encoding heat, and work, respectively, within an ensemble of paths that reach each state. Here we show that information that is characterized by the local form of mutual information between two subsystems in a heat bath is also a true thermodynamic potential of each coupled state and encodes the entropy production of the subsystems and heat bath during a coupling process. To this end, we extend the fluctuation theorem of information exchange [T. Sagawa and M. Ueda, Phys. Rev. Lett. 109, 180602 (2012)] by showing that the fluctuation theorem holds even within an ensemble of paths that reach a coupled state during dynamic co-evolution of two subsystems.

The present reality about the Nigerian economy calls for investment and development in the non-oil sector. This becomes necessary as a result of fall in the oil price in the global market. This paper examined the Bayesian Vector Autoregression (BVAR) modeling and forecasting of the dynamic interrelationship between Economic growth and revenue from the oil and non-oil sectors in Nigeria. To achieve this, annual data on Gross Domestic Product (GDP), revenue from oil and non-oil sectors were collected from Central Bank of Nigeria (CBN) bulletin, the sample from 1981 to 2008 was used for analysis, while sample from 2009 to 2014 was used for model validation. Six (6) versions of Sims-Zha BVAR models were compared for out-of-sample forecast, the result revealed the superiority of the BVAR6 model over the other BVAR models. Lastly, evidence from the decomposition forecast errors revealed that revenue of oil sector contributed 7.69% to GDP while revenue from non-oil sector contributed 0.12% to GDP in Nigeria. This paper therefore recommended that the present government should encourage investment that is geared toward development in the non-oil sector, of which it has the capacity to improve the Economic growth of the Nigerian economy.

Numerical modeling of sedimentation and erosion in reservoirs is an active field of reservoir research. However, simulation of bed-load transport phenomena has rarely been applied to other water bodies, in particular, the fluctuating backwater area. This is because the complex morphological processes between hydrodynamics and sediment transport are generally challenging to accurately predict. In this study, the refinement and application of a two-dimensional shallow-water and bed-load transport model to the fluctuating backwater area is described. The model employs the finite volume method of the Godunov scheme and saturated sediment transport equations. The model was verified against experimental data of a scaled physical model. It was then applied to actual reservoir operation, including reservoir storage, reservoir drawdown and continuous flood process, to predict the morphology of reservoir sedimentation and sediment transport rates and bed level changes in the fluctuating backwater area. It was found that the location and morphology of sedimentation effected by the downstream water level results in random evolution of the river bed, and bed-load sedimentation is transported from upstream to downstream with the slope of the longitudinal section of the river bed generally reduced. Moreover, the sediment is mainly deposited in the main channel and the elevation difference between the riverbank and channel decreases gradually.

In Nature, it is common for living plants and non-living plant tissues to consist of materials with anisotropic multilayer and non-homogenous structure. The structure of tissues determines their self-shaping and self-folding capabilities in response to a stimulus in order to activate different functionalities. Predetermined movements are realized according to changes in environmental conditions, which trigger the fibrous anisotropic structure of the plants’ material. In this study, we present the fabrication process of low-cost anisotropic multilayer materials that are capable of realizing complex movements caused by small temperature changes (<40 ^oC). The mismatch in the thermo-mechanical properties between three or more anisotropic thin layers creates responsive materials that alter their shape owing to the developed internal stresses. Isotropic layers can perform only bending movements, whereas anisotropic multilayer materials can perform bending, twisting or complex combined modes. The movements of the material can be controlled by forming anisotropic homogenous metallic strips over an anisotropic polymer. As a result, inexpensive responsive materials can be developed to passively react to a very broad range of thermal requirements. We studied the major parameters that affect the sensitivity of the developed materials, as well as their failure modes and crack formation under thermal fatigue conditions.

Reconfigurable Intelligent Surface (RIS), as an emerging radio technology, is widely used to expand transmission distance and structure cascade channels to improve the performance of communication systems. However, although RIS-NOMA assisted Internet of Vehicles (IoV) communication system can improve the overall transmission and rate performance with continuous development of wireless communication technology, the physical layer security (PLS) issue has gradually attracted attention and becomes more and more important in the application of the system. The aim of this paper is to investigate the potential threaten for PLS, when RIS is utilized in order to improve the security performance of wireless communications. In particular, this work considers the non-fixed of RIS location and wiretapping behavior of eavesdroppers on the data, and further analyzes the maximum safe-rate for above location assumptions. The results show that RIS demonstrates significant advantages on security performance and provides a useful reference for the security design of future wireless communication systems.

MGMT promotor hypermethylation is the most important biomarker for predicting temozolomide sensitivity in aggressive glioblastoma (GBM), a disease with a poor prognosis. An MGMT status prediction without biopsy is mandatory for tailored therapy because methylated MGMT patients have better prognosis. To this end, this paper proposes the radiogenomic model for predicting the status of MGMT Promoter methylation in glioblastoma patients based on the multi-modal MRI data and the EfficientNet deep learning architecture. Perhaps using sophisticated machine learning-based non-invasive methods of genetic prognosis may decrease risky biopsies. The Magnetic Resonance Imaging (MRI) sequences in the BraTS21 competition dataset include T1-weighted and contrast-enhanced images, T2-weighted images, and Fluid Attenuated Inversion Recovery (FLAIR) images. Image preprocessing consisted of normalization, scaling, and data augmentation Fourier transformations for cross-modal alignment. The EfficientNet-b0 model was initially pre-trained on ImageNet and then fine-tuned to the binary classification of methylation and unmethylated MGMT. The models were evaluated based on AUC-ROC, accuracy, and the F1 score. The model’s capability of accurately identifying MGMT methylation status was moderate, with an AUC-ROC score of 0.62393 at its best. These differences influenced validation findings: overfit and resulted in accuracy variations for the small or unbalanced datasets. Applying multimodal MRI data elevated feature extraction, proving that deep learning models have radiogenic predictive power. Therefore, this study demonstrates that ALC and DL models can noninvasively estimate MGMT promoter methylation status. They also suffer from problems of overfitting or generalization, which will require some optimization. It might be safer than biopsies and can enhance approaches to glioblastoma treatment.

In this study, we successfully reproduced the PSB with laddered patterning, showcasing the predictive capability of the framework of Field Theory of Multiscale Plasticity (FTMP), without relying on ad hoc models, intricate mathematical models, or elaborate finite element discretization. The FTMP-incorporated CP-FEM simulation not only reasonably replicates the experimentally observed laddered morphology and PSB but also effectively simulates surface roughening and grooving, independent of vacancy formation and diffusion. These results highlight the significance of laddered morphology and set the stage for further investigations into the effects of vacancy formation in future studies in Part II. Leveraging incompatibility tensor-based degrees of freedom, the FTMP framework offers exceptional capabilities for natural modeling dislocation substructures typically overlooked in conventional approaches, positioning it as a transformative tool for advancing our understanding of the mechanism that dictate slip band-fatigue crack transitions.

Drag reduction by laminarization, an innovative technology in aerodynamics design, provides the possibility to improve significantly the aerodynamic performance of aircraft and remains to be one of the most promising and effective technologies. In this paper, the design method for transonic natural laminar flow (NLF) wing at high Reynolds number is investigated in details and a new optimization model is established to solve conflicts between the increase of a laminar flow region and the shock wave strength at the trailing edge. In order to numerically handle this competitive situation efficiently, a two-objective hierarchical variable fidelity Pareto evolutionary optimization model based on search space contraction is proposed and implemented. Numerical experiments show that it can capture simultaneously a Pareto front of the two-objectives: a wave drag minimization and a laminar flow region maximization. The results also show that both wave drag and skin friction drag performances of non-dominated Pareto members can be significantly improved via the optimal laminar wing shape and shock wave control device. Nearly 40% of the laminar flow area on the wing surface is achieved at the Reynolds number of 107. It is concluded that the present hierarchical variable-fidelity multi-objective evolutionary optimization method is computationally efficient, and illustrate its potential for solving complex engineering design problems.

In this paper we report the possibility of using the X-ray powder diffraction (XRPD) technique to detect the gamma-hydroxybutyric acid (GHB) as its sodium salt in different beverages but because it is not possible to freely buy them, beta-hydroxybutyric acid (BHB) and its sodium salt (NaBHB) were used as a model to fine tune an X-ray diffraction method for the qualitative analysis of the sodium salt of GHB. The method requires a small quantity of beverage, and an easy sample preparation, that consists only in the NaOH addition to the drink and a subsequent drying step. The dry residue obtained can be easily analyzed with XRPD using a single crystal X-ray diffractometer to exploit its high sensitivity that allows very fast patterns collection. Several beverages with different NaBHB:NaOH molar ratios were tested and the results show that NaBHB is detected in all drinks analyzed when NaBHB:NaOH molar ratio is 1:50 using characteristic peak at very low 2θ values that permits to detect its presence also in complex beverage matrices. Moreover, depending on the NaOH amount added, shifting and/or splitting of the characteristic peak of the NaBHB salt was observed, and the origin of this behavior was investigated.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen progression–free survival (PSA-PFS) from ARSI initiation were assessed using Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA-PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥3.67 ng/ml at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS.

Although the spanwise periodicity within the gap between two tandem circular cylinders has been observed by some researchers, there is a lack of systematic study on the properties of this pe-riodicity. For the spanwise periodicity within the gap, this study aims to ascertain its characteris-tics, its influences on the flow field, and its variation trend with increasing spacing ratio. By nu-merically simulating the flow around two tandem circular cylinders with a diameter ratio of d/D=0.6 and seventeen spacing ratios (L/D=1.00~6.00) at Re=3900, this study shows four flow re-gimes: Reattachment Flow (L/D=1.00~3.15), Bi-stable Flow (L/D=3.24), Intermittent Lock-in Co-shedding (L/D= 3.30~3.50) and Subharmonic Lock-in Co-shedding (L/D=4.00~6.00). Further, de-pending on the spanwise periodicity length of the time-averaged flow structures (i.e. Pz) within the gap, Reattachment Flow is, for the first time, subdivided into three new sub-flow regimes: Small-scale Periodic Reattachment (L/D=1.00~1.50, Pz/D=(0, 4]), Large-scale Periodic Reattachment (L/D=2.00~2.25, Pz/D>4) and Non-periodic Reattachment (L/D=2.50~3.15, no spanwise periodicity). The formation mechanisms are elaborated by analyzing the combined effect of both the L/D value and the spanwise-averaged time-averaged reattachment angle of the downstream cylinder. Moreover, this study proves that the newly-defined Small-scale Periodic Reattachment and Large-scale Periodic Reattachment are responsible for the pronounced asymmetry of the flow along the transverse direction within the gap. In addition, detailed flow properties and statistical pa-rameters are provided for each flow regime, such as velocity, vorticity, force coefficient, separa-tion/reattachment angle, Strouhal number and Q-criterion.

In this article the problem of detection and isolation (FDI) in wheeled mobile robot is 1 treated. first of all we consider a master-slave robot system in which the master robot has to follow a 2 desired trajectory given by a well-determined control law, then the slave is controlled by the master. 3 However in real environment there is no ideality because faults can appear in the master or slave 4 or even the both and affect the system and may lead to unacceptable results so to ensure a well 5 functioning an extended kalman filter is tuned to diagnosis eventual faults and to generate residuals 6 in order to detect and isolate them. The performance of an estimator based on an EKF is simulated 7 based MATLAB Simulink simulations.

The response of building elements during earthquakes has been an area of concern for different researchers around the world. The NSEs are the first elements to attain failure, the buildings after damages in safety priority are classified as in “Life Safety” mode, but in reality, they are in “Collapse Safety” mode and the occupants inside the buildings are in a state of “Non-Life Safety” as a result of falling of the hazardous NSE’s like cladding's, partitions, hanging objects. In addition to the Life Cycle Cost Assessment (LCCA), the Social Life Cycle Assessment (SLCA) is overlooked by the majority of the researchers, the community must be prepared to respond to an event more efficiently without any major casualties or loss of life. It is expected that by the end of 2050, almost double the construction will take place, the embodied energy during the pre-construction, post-construction and demolition generates a lot of CO2s into the environment, hence sustainability should be given due importance, helping in the achievement of Sustainable Developmental Goals (SDGs).

Respiratory viral infections (RVI) are common reasons for healthcare consultations. The inpatient management of RVI consumes significant resources. From 2009-2014, we assessed the costs of RVI management in 4776 hospitalized chil-dren aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by de-tailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU (“non-ICU”) versus management requiring ICU-care (“ICU”) added up to 2,767.14€ (non-ICU) vs. 29,941.71€ (ICU) for Influenza, 2,713.14€ (non-ICU) vs. 16,951.06€ (ICU) for RSV infections, and 2,767.33€ (non-ICU) vs. 14,394.02€ (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all 8 RVI studied: Influenza, RSV, hRV, ade-novirus (hAdV), metapneumovirus (hMPV), parainfluenzavirus (hPIV), bocavirus (hBoV) and seasonal coronavirus (hCoV) infections. ICU-costs for Influenza however, ex-ceeded all other RVI. At the time of the study, Influenza was the only RVI with antivi-ral treatment options available for children, but only 9.8% of Influenza patients (non-ICU) and 1.5% of ICU-patients with Influenza received antivirals; only 2.9% were vac-cinated. Future studies should investigate the economic impact of treatment and pre-vention of Influenza-, COVID-19-, and RSV post vaccine introduction.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

Objetives: Adequate donor-recipient matching is necessary to achieve the best renal function after transplantation. The nephron load received from the donor, which can be reflected in variables such as age, sex and body mass index, may influence the evolution of the graft. Our objetive was develop a combined score according to the donor-recipient pairing in age, sex and body mass index, and assess its influence on the evolution of the renal graft. Materials and methods: Transplant patients between 2013 and 2020 who had at least 1 year of post-transplant follow-up. A ranking of 0 to 2 points was awarded according to the match between donor and recipient for sex, age and body mass index individually, with higher rank to greater mismatch. Subsequently, a Score with value of 0 to 6 points was created with the combined ranking of the indivudual variables, analyzing its influence on the evolution of the graft by multivariate linear regression. Results: 280 patients followed for 4.3 years of median. Worse renal function was observed at the end of follow-up as the range of each variable increased separately, and the Score created, with a worsening of renal function as the combined Score increased in the multivariate analysis: Coefficient B= -2.4 ml/min, p=0.018. Conclusions: An adequate match between donor and recipient in age, sex and body mass index using this combined Score can help achieve better kidney function after transplantation.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

For many years, energy monitoring at the most disaggregate level has been mainly sought through the idea of Non-Intrusive Load Monitoring (NILM). Nevertheless, a practical application of this concept in the residential sector should address the underlying concerns raised by the technical specifications of case studies. From one side, such an operation must handle common matters related to the essence of any NILM system. Although this aspect has been thoroughly investigated by basic research, it is limited to the properties of public datasets. On the other side, it must deal with specific concerns corresponding to uncommon situations. These circumstances impose further restrictions on existent NILM schemes, however, they have been overlooked due to the lack of pertinent databases to scrutinize. Accordingly, this paper presents applied research on a potential solution to NILM for Quebec residences. It carries out a relevant investigation into the multi-faceted nature of this problem in order to reveal barriers to feasible implementations in the context of Quebec. This work commences with a concise discussion about the NILM idea to highlight its essential requirements for a fruitful practice. Afterward, it provides a comparative statistical analysis to represent the specificity and potential challenges of the case study in accordance with NILM necessities. For this purpose, the examination exploits data from real-world measurement systems in the same and European regions. Subsequently, this study focuses on a load identification exercise by proposing a combinatory approach that utilizes the promise of sub-meter smart technologies to integrate the intrusive aspect of load monitoring with the non-intrusive one. The former is aimed at extracting overall heating demand from the aggregate one by a supervised procedure based on Deep Learning (DL) models while the latter is designed for disaggregating the residual load through an unsupervised process on the basis of clustering techniques. The results demonstrate that geographically-dependent cases create electricity consumption scenarios under which existing NILM methods can be questioned. From a realistic standpoint, this research elaborates on critical remarks to realize viable NILM systems, particularly, in Quebec houses.

The approach based on molecular modeling was developed to study dNTP derivatives characterized by new polymerase-specific properties. For this purpose, the relative efficiency of PCR amplification with modified dUTPs was studied using Taq, Tth, Pfu, Vent, Deep Vent, Vent (exo-), and Deep Vent (exo-) DNA polymerases. The efficiency of PCR amplification with modified dUTPs was compared with the results of molecular modeling using the known 3D structures of KlenTaq polymerase–DNA–dNTP complexes. The dUTPs were C5-modified with bulky functional groups (the Cy5 dye analogs) or lighter aromatic groups. Comparing the experimental data and the results of molecular modeling revealed the decrease of PCR efficiency in the presence of modified dUTPs with an increase in the number of non-covalent bonds between the substituents and the DNA polymerase (about 15% decrease per one extra non-covalent bond). Generalization of the revealed patterns to all the studied polymerases of the A and B families is discussed herein. The number of non-covalent bonds between the substituents and polymerase amino acid residues is proposed to be a potentially variable parameter for regulating enzyme activity.

Electrochemical Promotion was used to modify the activity and selectivity of a Rh catalyst-electrode in the CO2 hydrogenation reaction. The experiments were carried out in a temperature range of 350-430οC at ambient pressure and at different CO2 to H2 gas feeding ratios (1:2 to 4:1). The only reaction products observed were CO and CH4, both under open and closed-circuit conditions. The CH4 formation rate was found to increase with both positive and negative potential or current application. The CO formation rate followed the opposite trend. The selectivity to CH4 increased under high values of hydrogen partial pressure and decreased at high pressures of CO2. The results demonstrate how Electrochemical Promotion can be used to finely tune activity and selectivity for a reaction of high technical and environmental importance.

In the context of autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) plays a key role as biomarker of disease progression and response to therapy and has been recently recognized as enrichment biomarker and possible surrogate endpoint. Several imaging modalities and methods are available to calculate TKV, and the choice depends on the purpose of use. Technological advancements have made it possible to accurately assess cyst burden, that can be crucial to assess the disease state and help identifying rapid progressors. Moreover, the development of automated algorithms has increased the efficiency of total kidney and cyst volume measurements. Beyond total kidney and cyst volume, the quantification and characterization of non-cystic kidney tissue show potential to early stratify ADPKD patients, monitor disease progression, and possibly predict renal function loss. A broad spectrum of kid-ney MRI techniques are available to characterize kidney tissue, showing promise to non-invasively pick up early signs of ADPKD progression. Radiomics has been used to extract tex-tural features from ADPKD images, providing valuable information about the heterogeneity of the cystic and non-cystic components. This review provides an overview of ADPKD imaging bi-omarkers, focusing on quantification methods, potential, and necessary steps towards successful translation to clinical practice.

Laser energy per unit surface, necessary to trigger the material removal, decreases with the pulse shortening becoming the pulse-time independent in the sub-picosecond range. These pulses are shorter the electron-to-ion energy transfer time and electronic heat conduction time minimizing the energy losses. The electrons receiving the energy larger than the threshold, drag the ions off the surface in the mode of electrostatic ablation. We show that the pulse shorter than the ion period (Shorter-the-Limit (StL)) ejects conduction electrons with the energy larger than the work function (from a metal) leaving the bare ions immobile in a few atomic layers. The electrons emission is followed by the bare ion’s explosion, ablation, and THz radiation from expanding plasma. We compare this phenomenon to the classic photo effect, nanocluster Coulomb explosions, show differences and consider possibilities for detecting the new mode of ablation experimentally by emitted THz radiation and consider applications of high-precision nano-machining with this low intensity irradiation.

We find at least 4 quantum properties that are indeed universal in some number systems; and we can use them for quantum consciousness. Using the sets B={0,1}, N, Z, or Q has the +4 quantum properties that one can trust, as archetypes of easy communication to friends and foes, to ignoranti or cognoscenti, and for quantum computing. This paper proposes the use of Bayesian geometry to reduce the space of possible results, reducing or increasing initial beliefs by successive experimentation. This is exemplified in biology and mathematics, and can be applied to physics and other sciences. The conclusion is that an experimental fact can be absolutely verified. Any mathematical choice (as verified by computers) militating against R=Q, is under an absolutely low chance to succeed. Infinitesimals are denied based on 3^16 independent factors. This is not a probabilistic result, but based on reduction of the Bayes geometry for updating beliefs. This work applies to non-probabilistic and unknown phenomena, such as those found in oscillations (neutrino, health), evolution, and quantum computing, denies Gödel's uncertainty, and solves the liar's paradox by reflection. This connects different scientific fields with one another, in an internet, i.e., in a network of connections of multiple open networks, using the set Q, resembling a hologram, and includes entanglement.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute toxic events and, in the long term, by associations between cyanobacteria and neurodegenerative diseases. One of the implicated mechanisms includes a misincorporation of cyanobacterial non-proteogenic amino acids leading to mistranslation and protein misfolding. A better understanding of the interaction between the cyanopeptide metabolism and the nervous system will be crucial to target or to prevent pathogenic response.

Lung cancer is a common malignant tumor of the lung and the leading cause of cancer mortality worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80%–85% of lung cancer, 40% of NSCLCs will have spread beyond the lungs by the time it is diagnosed. Long non-coding RNA (LncRNA) prostate androgen-regulated transcript 1 (PART-1) was reported that promote the development of several cancers. In the current study, we conducted experiments to investigate the role of PART-1 in the proliferation, invasion, and migration of NSCLC. The expression level of the PART-1 gene increased significantly in the NSCLC cell lines, including A549, H1229, H1650, H1975, and PC9. Knocking down of PART-1 inhibited the proliferation, invasion, and migration of A549 cells, moreover, decreased the tumor proliferation in nude mice. We confirmed that PART-1 targeted miR-204-3p directly, and miR-204-3p targeted the insulin-like growth factor binding protein 2 (IGFBP-2) directly. Furthermore, we discovered that PART-1 involved the NSCLC progression by regulating the miR-204-3p-targeted IGFBP-2 pathway. LncRNA PART-1 might be a target for treating NSCLC, and a warning sign of diagnosis of early lung cancer.

This paper presents an approach to the vibration analysis of axially functionally graded (AFG) non-prismatic Euler-Bernoulli beams using the finite difference method (FDM). The characteristics (cross-sectional area, moment of inertia, elastic moduli, and mass density) of AFG beams vary along the longitudinal axis. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, differential equations were formulated with finite differences, and additional points were introduced at the beam’s ends and at positions of discontinuity (supports, hinges, springs, concentrated mass, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. Vibration analysis of AFG non-prismatic Euler-Bernoulli beams was conducted with this model, and natural frequencies were determined. Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of AFG non-prismatic Euler-Bernoulli beams, considering the damping. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was always increased through a grid refinement.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Among non-conventional yeasts of industrial interest, the dimorphic oleaginous yeast Yarrowia lipolytica appears as one of the most attractive for a large range of white biotechnology applications, from heterologous proteins secretion to cell factories process development. The past, present and potential applications of wild type, traditionally improved or genetically modified Yarrowia lipolytica strains will be resumed, together with the wide array of molecular tools now available to genetically engineer and metabolically remodel this yeast. The present review will also provide a detailed description of Yarrowia lipolytica strains and highlight the natural biodiversity of this yeast, a subject little touched upon in most previous reviews. This work intends to fill this gap by retracing the genealogy of the main Yarrowia lipolytica strains of industrial interest, by illustrating the search for new genetic backgrounds and by providing data about the main publicly available strains in yeast collections worldwide. At last, it will focus on exemplifying how advances in engineering tools can leverage a better biotechnological exploitation of the natural biodiversity of Yarrowia lipolytica and of other yeasts from the Yarrowia clade.

In this work the existence and nonexistence of stationary radial solutions to the elliptic partial differential equation arising in the molecular beam epitaxy are studied. Since we are interested in radial solutions we arrive at the following fourth-order differential equation

The preservation of the authenticity of a building artefact is a responsible practice. On the other side, the need to save the building artefact from the natural and anthropic degradation, to ensure the structural reliability to the different actions, to define an efficient maintenance program are big challenges, that involves the cooperation of several professionals, responsible use of innovative techniques and materials that are nowadays available. This paper focuses on a specific design approach for the rehabilitation works of ancient constructions in archaeological sites. The proposed conceptual design approach implies different steps that allow the optimization of the design at an increasing level of knowledge on the existing structures and their materials. The design procedure on historical constructions generally includes the following steps: the collection of data, the structural identification, hazard, and vulnerability analysis, damage and risk analysis, a cost-benefit analysis, so only at the end of the process, the final design is achieved. In the archaeological area, some important design aspects cannot be defined before the execution work phase, since some elements could be revealed and identified during work execution, as a consequence, the final design has been often optimized after all this information has been acquired. A studied case in the archaeological site of Pompeii is herein presented to prove the efficiency of the proposed approach.

This paper deals with a non-standard finite difference scheme defined on a quasi-uniform mesh for approximate solutions of the Magneto-Hydro Dynamics (MHD) boundary layer flow of an incompressible fluid past a flat plate for a wide range of the magnetic parameter. We show how to improve the obtained numerical results via a mesh refinement and a Richardson extrapolation. The obtained numerical results are favourably compared with those available in the literature.

Background: Objectives. The objective of this study was to compare the efficacy of direct current stimulation (DCS) applied at the transcranial, suboccipital and spinal level on experimental sensory modalities and pain outcome measures in healthy subjects. The hypothesis of this study was that systematic analysis of the efficacy of DCS on modulating evoked thermal and mechanical pain modalities and mechanisms such as endogenous pain modulation in healthy individuals would reveal sensitive outcome measures help develop this technique for the control of chronic pain. Materials and Methods. Database searches were conducted up to December 2019 for randomized controlled trials that performed sham-controlled DCS of experimental sensory modalities and pain outcomes following transcranial, suboccipital and spinal locations in healthy participants. Standardized mean differences with 95% confidence intervals were calculated for sensory modalities, including random-effect metanalysis. Results: Thirty-one studies were included for analysis (647 participants). A significant decrease in pain intensity for active vs sham transcranial stimulation was identified for pain intensity (n=158; SMD=0.79; 95% CI=0.56 to 1.02), a significant increase in heat pain threshold (n=222; SMD=1.16; 95% CI=0.95 to 1.37), and a significant increase in cold pain threshold (n = 155; SMD = 0.77, 95% CI 0.53 to 1.01). No significant modulation of pressure pain threshold was identified with DCS and only a limited number of studies focused on experimental pain modulation following neuromodulation at the suboccipital or spinal level. Conclusions: These results show significant transcranial DCS neuromodulation of pain intensity and on thermal pain modalities. Future studies should focus on endogenous pain and sensory modality modulation with sham-controlled DCS applied at transcranial, suboccipital and spinal locations.

Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential for sustenance of life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context, to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were tested and implemented for mostly cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more complex systems (for instance, multi-protein complexes, oligomeric assemblies, membrane proteins and post-translationally modified proteins), the initial axioms defined by Michaelis-Menten (MM) kinetics are rendered inadequate and the development of a new kind of kinetic analysis to study these systems is required. The current review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug-discovery for such systems, to enable effective screening and characterisation of small-molecule inhibitors with desirable physiological outcomes.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

Crop type and field boundary mapping enable cost-efficient crop management on the field scale and serve as the basis for yield forecasts. Our study uses a data set with crop types and corresponding field borders from the federal state of Bavaria, Germany, as documented by farmers from 2016 to 2018. The study classified corn, winter wheat, barley, sugar beet, potato, and rapeseed as the main crops grown in Upper Bavaria. Corresponding Sentinel-2 data sets include the normalised difference vegetation index (NDVI) and raw band data from 2016 to 2018 for each selected field. The influences of clouds, raw bands, and NDVI on crop type classification are analysed, and the classification algorithms, i.e., support vector machine (SVM) and random forest (RF), are compared. Field boundary detection and extraction are based on non-iterative clustering and a newly developed procedure based on Canny edge detection. The results emphasise the application of Sentinel’s raw bands (B1–B12) and RF, which outperforms SVM with an accuracy of up to 94%. Furthermore, we forecast data for an unknown year, which slightly reduces the classification accuracy. The results demonstrate the usefulness of the proof-of-concept and its readiness for use in real applications.

Phylogenomics, the use of large datasets to examine phylogeny, has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life; this could reflect, at least in part, the poor-fit of the models used to analyze heterogeneous datasets. Some of the heterogeneity may reflect the different patterns of selection on proteins based on their structures. To test that hypothesis, we developed a pipeline to divide phylogenomic protein datasets into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had distinct signals for the topology of the deepest branches in the metazoan tree. The most striking difference in phylogenetic signal reflected relative solvent accessibility; analyses of exposed sites (on the surface of proteins) yielded a tree that placed ctenophores sister to all other animals whereas sites buried inside proteins yielded a tree with a sponge-ctenophore clade. These differences in phylogenetic signal were not ameliorated when we repeated our analyses using the CAT model, a mixture model that is often used for analyses of protein datasets. In fact, the heterogeneous CAT model resulted in several rearrangements that are unlikely to represent evolutionary history. However, analyses conducted after recoding amino acids to limit the impact of deviations from compositional stationarity increased the congruence in the estimates of phylogeny for exposed and buried sites; after recoding amino acids both trees supported placement of ctenophores sister to all other animals. These results provide striking evidence that it is necessary to achieve a better understanding of the constraints due to protein structure to improve phylogenetic estimation.

Paenibacillus sp. tmac-D7 was isolated from coastline growing Trifolium macraei (double-head clover) root nodules from Bodega Bay, California. The draft genome is 5,567,337 bp with a G+C% of 52.4%, an N50 of 114,261 bp, and 5,282 predicted protein-coding genes. Paenibacillus, while found in many other environments, is frequently isolated from root nodules, with many acting as plant pathogen antagonists. Paenibacillus sp. tmac-D7 is the first genome of a non-rhizobial endophyte isolate from wild Trifolium macraei (double-head clover).

This paper discusses a cross-disciplinary, international collaboration aimed at researching a series of 15th century choir books at the abbey of San Giorgio Maggiore on the homonymous island in Venice. Produced for the abbey itself, the books have never left the island during their 500-years history, thereby allowing a unique opportunity to analyse historic artefacts, which have undergone little modification over time. Prompted by ongoing cataloguing work on the manuscripts, a week-long analytical campaign using a combination of non-invasive analytical methods used in portable configuration allowed the comprehensive characterisation of ten volumes. The manuscripts’ palette and painting techniques were analysed using near-infrared imaging, reflectance spectroscopy in the UV-vis-NIR range, Raman spectroscopy, X-ray fluorescence mapping and digital microscopy. The paper will discuss the challenges linked to the fragility and the large dimensions of the volumes as well as the most interesting results of the investigation. These include the detection of unusual painting materials such as bismuth ink, as well as the discovery of a less homogeneous palette than originally expected, which prompted a partial revision of the attribution of the decoration in one of the volumes to a single artist.

Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents.

External quantum efficiency of industrial-grade green InGaN light-emitting diodes (LEDs) has been measured in a wide range of operating currents at various temperatures from 13 K to 300 K. Unlike blue LEDs, the efficiency as a function of current is found to have a multi-peak character, which could not be fitted by a simple ABC-model. This observation correlated with splitting of LED emission spectra into two peaks at certain currents. The characterization data are interpreted in terms of non-uniformity of the LED active region, which is tentatively attributed to extended defects like V-pits. We suggest a new approach to evaluation of temperature-dependent light extraction and internal quantum efficiencies taking into account the active region non-uniformity. As a result, the temperature dependence of light extraction and internal quantum efficiencies have been evaluated in the temperature range mentioned above and compared with those of blue LEDs.

A conventional electrical grid mostly depends on the electrical power generated from fossil fuels. However, the pollutants from fossil fuels are the key factors for adverse climate change. Most of the developed countries of the world have already recognized the fact that the energy mix requires to be diversified by incorporating renewable energy. This is especially relevant for many of the member countries of the Organization of Islamic Cooperation (OIC), consisting of 57 countries, whose abundance of fossil fuel reserve indicates that much of their electric power is still generated from fossil fuels. In order to integrate renewable energy sources into the hybrid energy mix, an existing conventional grid needs to undergo drastic changes. Alongside this, the population boom in the OIC member countries has caused higher demand for a steady supply of electricity that the conventional grids have long been struggling to cope with. With a view to solving this multifaceted problem, incorporation of the smart power management schemes is indispensable using a smart electrical grid, where information and communications technology is integrated into its major building blocks. This allows advanced applications of a grid, such as the formation of micro-grids, demand-side management, energy storage, high-tech power electronic converters, etc. As the smart grids are being adopted by many developed countries, it is high time for the OIC member countries to pay due attention to this development, if they have not already done so. This paper explains, with special focus on the OIC member countries, the various smart power management technologies, their operations and applications, and the benefits and challenges. Then it goes on to carry out the Strength-Weakness-Opportunity-Threat with Analytical-Heuristic-Procedure (SWOT-AHP) analysis to evaluate its feasibility of incorporation and the underlying strategies appropriate for its implementation. Furthermore, a Hybrid Multi-Criteria-Decision-Making (MCDM) analysis is performed to evaluate the sequence of the emphasis that should be given on each of the technologies from those available for the smart power management initiative. Finally, the study reinforces the stance by drawing parallels from the UN Sustainable Development Goals (SDG) and highlights the importance of the smart grid in line with the global vision of SDG. This paper aims at assisting the decision-makers in implementing smart power management schemes in the OIC member countries, in particular, and other countries of the world, in general.

Citizens Advice on Prescription (CAP), a Liverpool (UK) based service, provides welfare advice and link worker social prescribing support to people experiencing and at risk of financial or social hardship. CAP, which receives referrals from healthcare and third sector services, aims to improve service users’ financial security, health, and wellbeing. A mixed-method Social Return on Investment (SROI) analysis was used to evaluate the service. Between May 2022 and November 2023, a subset of service users (n=538) completed the Short Warwick-Edinburgh Mental Wellbeing Survey (SWEMWBS) at baseline and 2-month follow-up. Supporting quantitative and qualitative economic data was also collected (Feb 2023 - Feb 2024) through semi-structured interviews (n=16). Social value changes were generated using the change in SWEMWBS scores and social valuations from the Mental Health Social Value Bank (MHSVB). SROI ratios were calculated from change of social value against service provision costs. The mean service provision cost was £148.66 per person. The overall study reported a positive SROI return of £1: £3.40-£4.69. Results indicate that non-clinical support services, like CAP, can be an effective intervention to address the wider determinants of health and wellbeing.

Non-orthogonal multiple access (NOMA) enables the parallel offloading of multiuser tasks, effectively enhancing throughput and reducing latency. Backscatter communication, which passively reflects radio frequency (RF) signals, improves energy efficiency and extends the operational lifespan of terminal devices. Both technologies are pivotal for the next generation of wireless networks. However, there is little research focusing on optimizing the transmit power in backscatter-assisted NOMA-MEC systems from a green IoT perspective. In this paper, we aim to minimize the transmit energy consumption of a Hybrid Access Point (HAP) while ensuring task deadlines are met. We consider the integration of Backscatter Communication (BackCom) and Active Transmission (AT), and leverage NOMA technology and user cooperation to mitigate the double near-far effect. Specifically, we formulate a transmit energy consumption minimization problem, accounting for task deadline constraints, task offloading decisions, transmit power allocation, and energy constraints. To tackle the non-convex optimization problem, we employ variable substitution and convex optimization theory to transform the original non-convex problem into a convex one, which is then efficiently solved. We deduce the semi-closed form expression of the optimal solution and propose an energy-efficient algorithm to minimize the transmit power of the entire wireless powered MEC. Simulation results demonstrate that our proposed scheme significantly reduces the transmit power of the HAP compared to existing schemes, validating the effectiveness of our approach.This study provides valuable insights for the design of green IoT systems by optimizing the transmit power in NOMA-MEC networks.

Epidermal Growth Factor Receptor (EGFR) expression is an important aspect in the non-small cell lung cancer (NSCLC) diagnosis and treatment. Therefore, it becomes important to identify factors that may influence EGFR level. There are reports suggesting that one of the positive EGFR gene transcription regulators may be Special AT-rich Binding Protein 1 (SATB1), but so far these ob-servations have not been confirmed in NSCLC. The main aim of the present study was to investigate the possible links between the EGFR and SATB1 expression on both protein and mRNA levels in NSCLC clinical samples, and to correlate the obtained results with the clinical-pathological data of the patients. Additionally, we analysed the relationships between the expression levels of EGFR and the known tumour promoters, in-cluding Ki67 proliferative antigen and EMT-promoting transcription factors - SLUG, SNAIL, and Twist1. We demonstrated that EGFR expression in NSCLC was positively correlated both with the SATB1 level and with the expression of EMT-promoting proteins. Moreover, we were the first to analyse EGFR expression exclusively in NSCLC cancer cells without the interference caused by respiratory epithelium and tumour stroma. Our analysis revealed that the prognostic significance of EGFR expression was dependent on tumour histology and differed significantly between the AC and LSCC samples.

Cyclic straining simulations using incompatibility-incorporated crystal plasticity-FEM, which exhibit PSB ladder structure evolutions as detailed in Part I, are coupled with diffusion analyses of produced vacancies. We introduce a new vacancy source model based on the Field Theory of Multiscale Plasticity (FTMP), interpreting the relationship between the incompatibility rate and the flux of dislocation density as edge dipole annihilation processes. Both direct and indirect coupling diffusion analyses, with and without cyclic straining, demonstrate that varying incompatibility rates tend to further promote vacancy diffusion, leading to surface grooving, enhanced extension rates, and eventual transition to cracks. The findings reveal that: (i) the evolved PSB ladder structure serves as a site for vacancy formation, (ii) it provides a diffusion path toward the specimen surface, and (iii) it significantly enhances groove extension rates. These factors effectively facilitate the transition from a "groove" to a "crack," evidenced by the abrupt acceleration of the extension rate, mirroring systematic experimental observations by Nakai et al. These achievements validate the FTMP's capability to simulate complex phenomena and significantly deepen our understanding of slip band-fatigue crack transition mechanisms.

Physics is imagined in the human brain which was formed in Darwin's Evolution by responding to certain threats for the survival of our evolutionary ancestors. The struggle to survive prevented us from wasting resources by paying attention to parts of reality that had no survival impact. These parts are of unknown scope and dimension. Can we negotiate this Darwin's barrier? As to reality within our reach, we suffer from imbalance between information absorption capacity and information analysis capacity which resulted in ignoring the overflow of information to match human capacity to make sense of it. Also James Clerk Maxwell suggested that reality has small scale phenomena beyond our human reach. Since we have no brain other than what Darwin equipped us with, this barrier looked unsurmountable. But lo and behold: much as we have built vehicles to carry us further than our biological legs, so we now build artificial intelligence machines that carry us beyond our Darwinist barrier. Physics may transform to building AI capability to ride on. This capability may require a more universal geometry and material representation to fit AI inference engines. Suggesting Depth Unbound Reality Architecture (DURA). AI connects raw data to its conclusion potential, by-passing a storied theory of nature. The objective of physics ahead may be to build theory-replacement AI machines.

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is a clinical entity characterized by the absence of significant coronary artery obstruction in epicardial arteries (&lt; 50%) on coronary angiography in the setting of acute myocardial infarction (AMI). This article aims to provide a narrative review of the pathophysiological mechanisms, diagnostic challenges, and prognosis associated with MINOCA focusing only on cases associated with myocardial ischemia but of non-atherosclerotic origin. Etiological factors, including thromboembolism, coronary artery spasm, spontaneous coronary artery dissection, coronary microvascular disease, and supply-demand mismatch are addressed. Imaging modalities such as echocardiography, advances in coronary angiography like intravascular ultrasound (IVUS) and optical coherence tomography (OCT), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) are also analyzed. MINOCA patients have a better short-term prognosis compared to those with obstructive coronary artery disease but face significant long-term risks, underscoring the need for precise diagnosis and management strategies. Elevated inflammatory markers and specific genetic predispositions are also associated with adverse outcomes in MINOCA. This review focused on MINOCA from the pathophysiological perspective on ischemic, non-atherosclerotic causes, the diverse underlying mechanisms, the challenges in achieving accurate diagnosis, the importance of a tailored therapeutic approach and the necessity for further investigation of clinical outcomes.

In this work, we analyzed non-Darcy two-component single-phase isothermal flow in naturally fractured tight gas reservoirs for enhanced gas recovery (EGR) and carbon dioxide storage as a possible application. We used the Peng-Robinson equation of state to evaluate the thermodynamic properties of the components, and we performed the discretization of the governing partial differential equations using the Finite Volume Method. This process leads to two subsystems of algebraic equations, which, after linearization and use of an operator splitting method, are solved by the Conjugate Gradient (CG) and Biconjugate Gradient Stabilized (BiCGSTAB) methods for determining the pressure and fraction molar, respectively. We include inertial effects using the Barree and Conway model, gas slippage via a more recent model than Klinkenberg’s and we use a simplified model for the effects of effective stress. We also utilize a mesh refinement technique to represent the discrete fractures. Finally, we implemented simulations to show the influence of inertial, slippage and stress effects on production in fractured tight gas reservoirs.

Protein 53 (P53) shows different functions either to support or to contrast malignant growth. P53 history tells that discoveries of molecular features have contributed to the emergence of P53 functions. Conversely, the shift of paradigms demonstrates that P53 functions coexist even if are in conflict with one another. Since 1979, five paradigms have been assembled then deconstructed by taking into account P53 functions of viral protein, oncogene, tumor suppressor gene, transcription factor, apoptotic factor. By summarizing the past five disassembled P53 paradigms, in this investigation the current paradigm involving P53 in the modulation of a composite bio-morphological entity namely, tumor immune microenvironment (TIME) is analyzed. The aims of this investigation were to provide an overview of solid and validated knowledge occurring in all P53 paradigms and to determine P53 abilities to modify TIME through manipulation of viruses. As a result, definitive P53 evidence concerns its genetic localization, amino acids composition, its isoforms and subcellular expression in organelles. P53 “mutome” assembles all mutations affecting this complex protein. Lastly, both categories of tumor promoting and non-oncogenic viruses related to P53 were scrutinized. In conclusion, paradigms teach that P53 is undruggable because its drugs inevitably target all P53 functions.

Through analysis of the constituent components of the observation data from 12 geoe-lectric field stations located approximately 600 km form the epicenter of the Jishishan Ms6.2 earthquake, this study reveals that during earthquake preparation and occurrence, the geoelec-tric field at each station exhibit non-uniform variations. These variations are characterized by significant decreases or increases in correlation coefficients between different azimuths (δxy) and between long and short polar distances within the same azimuth (δxx). Additionally, there are discrete or extruding changes observed in the dominant azimuth angles of the telluric field at the stations, ranging approximately from 40° to 90°. These anomalies indicate local site effects and exhibit quasi-synchronous temporal characteristics. The study found that stations located in regions with intense tectonic activities, such as Menyuan and Jingtai, experience more significant anomalous changes influenced by the tectonic activities of the Qaidam-Qilian Mountain block. When multiple stations with anomalous changes are used to determine the earthquake epicenter, earthquakes often occur within or near the intersection area of the predicted ranges of these sta-tions. The specific time of earthquake occurrence shows no clear relationship with the locations or tectonic activities of the stations.

Non-destructive testing has many advantages, such as the ability to obtain a large number of data without destroying existing structures. However, the reliability of the estimation accuracy and the limited range of applicable targets remains an issue. This study proposes to a novel pin penetration test method to determine the early age compressive strength of concrete before demolding. The timing of demolding and initial curing are determined according to the strength development of concrete. Therefore, it is important to determine the compressive strength at the early age before demolding at the actual construction site. The applicability of this strength estimation methodology at actual construction is investigated. Small test holes (12 mm in diameter) are prepared on the mold surface in real construction sites and mock-up specimens in advance. The pin is penetrated into these test holes to obtain the relationship between the compressive strength and the penetration depth. As a result, it is confirmed that the pin penetration test method is suitable to measure the early age compressive strength at actual construction site. This allows the benchmark values for compressive strength, necessary to avoid early frost damage, to be directly verified on the concrete structural members at the construction site. For instance, the compressive strengths of greater than 5 MPa and 10 MPa can be confirmed by the penetration depths benchmark values of 8.0 mm and 6.7mm or less, respectively.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Non-Linear Simulation by Harmonic Balance Techniques of Load Modulated Power Amplifier Driven by Random Modulated Signals. Comparison with measured results.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines’ storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, rather than thrombolysis performed, to avoid potential adverse events of the latter in the setting of SCAD.

Non-ulcerated cutaneous leishmaniasis (NUCL) is an atypical and peculiar clinical form of the disease that was first described by Ponce et al. (1988) in Honduras (Central America), where iso-lated or disseminated popular and/or nodular skin lesions are commonly seen in adolescents and young adults. Leishmania (L.) chagasi was then incriminated as the causal agent of the disease, as well as of American visceral leishmaniasis (AVL), although NUCL has been shown to be more prevalent than AVL in the region. Considering, however, the dubious taxonomic character of the causal agent of NUCL, as there is no evidence of this form of disease associated with L. (L.) cha-gasi in South America, this study aimed to carry out a retrospective taxonomic analysis on a se-ries of studies on the diagnostic approach to the Honduran parasite in loco (El Tigre island, Amapala municipality, west coast of Honduras), where taxonomic characters of a biological (in vitro and in vivo), epidemiological (vector and canine reservoir), clinical-immunological (im-munopathological features of in situ skin lesion and systemic infection) and molecular (ge-nomic/phylogenetic analyses) nature were considered. The findings, particularly those of mo-lecular nature, such as: the Honduran parasite showed to be more ancestral (molecular clock analysis of the DNA polymerase alpha subunit gene) than all viscerotropic ones [L. (L.) chagasi, L. (L.) donovani and L. (L.) infantum], as well as presenting an absolutely unprecedented structural variation on chromosome 17 and the highest frequency of genomic SNPs (more than twice the number seen in the Brazilian parasite), in addition to representing a different phylogenetic lin-eage (mainly in the NJ - RNA Pol II tree) from those viscerotropic ones, have pointed to the characterization of a new leishmanine parasite, Leishmania (Leishmania) poncei n. sp. (Kinetoplas-tea: Trypanosomatidae), in honor of Professor Ponce, who was the first researcher to describe NUCL in Honduras.

Accurate measurement of solid precipitation (S) has a critical importance for proper understanding of the Earth’s hydrological cycle, validation of emerging technologies and weather prediction models, and developing parameterizations of severe weather elements such as visibility (Vis). However, measuring S is still a challenging problem mainly because of wind effects. The wind effects are normally mitigated by using a Double-Fence Automated Reference (DFAR) system to reduce the wind speed (Ug). To contribute towards addressing some of these issues we have analyzed data sets collected at a site located in Southern Ontario, Canada using several instruments. The instruments include two Geonor gauges, one placed inside a DFAR (SDFAR) and the other inside a double Alter shield (DASG), a Pluvio2 gauge inside a single Alter shield (SASP), a HotPlate, a PARSIVEL2 Disdrometer that measures S and fall velocity (V), and a FD12P senor that measures S and type and Vis. The results show that for the Ug observed in this study (Ug &lt; 6 ms-1), both DASG and SASP have similar collection efficiency (CE) of near 70%. The transfer functions (TF) for DASG and SASP as a function of Ug and also Ug, and V have been derived. The TF for the DASG that includes both Ug and V showed better agreement with observation than just Ug alone. The S measured using all the other instruments were correlated well with SDFAR, but the PARSIVEL2 and FD12P overestimated and underestimated the snow amount respectively as compared the SDFAR. However, the HotPlate captured similar amount of S as the SDFAR. According to this study, the SDFAR showed good correlation with Vis.

Considering the controversial benefits of video-assisted thoracoscopic surgery (VATS), we intended to evaluate the impact of surgical approach on cardiac function after lung resection using myocardial work analysis. Echocardiographic data of 45 patients (25 thoracotomy vs. 20 VATS) were retrospectively analyzed. All patients underwent transthoracic echocardiography (TTE) 2 weeks before and after surgery, including two-dimensional speckle tracking and tissue doppler imaging. No notable changes in left ventricular (LV) function, assessed mainly using the LV global longitudinal strain (GLS), global myocardial work index (GMWI), and global work efficiency (GWE), were observed. Right ventricular (RV) TTE values, including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV), and RV free-wall GLS (RVFWGLS), indicated greater RV function impairment in the thoracotomy group than in the VATS group [TAPSE (mm): 17.90 ± 3.80 vs. 20.60 ± 3.50, p &lt; 0.018; TASV (cm/s): 12.40 ± 2.90 vs. 14.60 ± 2.50, p &lt; 0.010; RVFWGLS (%): −11.50 ± 8.50 vs. −17.50 ± 9.70, p &lt; 0.033), respectively]. Unlike RV function, LV function remained preserved after lung resection. The thoracotomy group exhibited greater RV function impairment than did the VATS group. Further studies should evaluate the long-term impact of surgical approach on cardiac function.

The present article describes a one-pot and cascade mode process using biocompatible/biodegradable reagents, for directly and simply obtaining surfactant compositions of mixtures of D-mannuronic acid and L-guluronic acid directly from oligoalginates or semi-refined alginates (mixtures of alginate, cellulose, hemicellulose, laminaran and fucan). Simple treatments of partial purification of the reaction crudes (elimination of the salts and/or the residual fatty alcohols) or isolation of the surfactant compositions result in derived compounds and in compositions having performance levels appropriate to applications in detergency. In addition, the challenging extension of this cascading one-pot synthesis technology to crude milled brown seaweeds was successfully carried out to provide promising surface-active compositions made up of alkyl uronate and alkyl glycoside monosaccharides.

The main aim of this paper is to analyse the performance of different intelligent compaction measurement values (ICMVs) and compare them with spot test measurements for asphalt pavement. To accomplish this, a two-layer asphalt testbed was constructed using an instrumented double-drum roller. All ICMVs [compaction meter value ( ), compaction control value ( ), roller-integrated stiffness ( ), and vibratory modulus ( )] were calculated using the same accelerometer data collected during the construction of the asphalt testbed. A novel method using the cross-correlation technique was developed to estimate the phase lag between the excitation force of the roller drum and the ground reaction, which is required for and calculations. The analysis of ICMV data showed a strong correlation between and , while and demonstrated a strong correlation only when double jump of the roller drum did not occur. Further, none of the ICMVs recorded during the last roller pass of asphalt compaction showed an acceptable correlation with asphalt densities [measured using a non-nuclear density gauge (NNDG)], mainly due to the influences of the underlying support and asphalt temperature on ICMVs. A correction method to decouple the influence of underlying support on was developed and validated using existing data from the literature. The applicability of this method for different field scenarios was demonstrated using numerical modelling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

Indirect imaging methods involve at least two steps, namely optical recording, and computational reconstruction. The optical recording process uses an optical modulator that transforms the light from the object into a typical intensity distribution. This distribution is numerically processed to reconstruct the object’s image corresponding to different spatial and spectral dimensions. There have been numerous optical modulation functions and reconstruction methods developed in the past years for different applications. In most cases, a compatible pair of optical modulation function and reconstruction method gives optimal performance. A new reconstruction method termed non-linear reconstruction (NLR) was developed in 2017 to reconstruct the object image in the case of optical scattering modulators. During the years, it was revealed that the NLR could reconstruct an object’s image modulated by an axicons, bifocal lenses and even exotic spiral diffractive elements, which generate deterministic optical fields. Apparently, NLR seems to be a universal reconstruction method for indirect imaging. In this review, the performance of NLR has been investigated for many deterministic and stochastic optical fields. Simulation and experimental results for different cases are presented and discussed.

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

Since its inception in the late 2000s, blockchain has emerged as a powerful tool for creating trust without intermediaries to incentivize global communities for working for a common goal, such as the improvement of its very ecosystem, its applications and community adoption. While first blockchains were mainly devised for confirming transactions of their innate cryptocurrencies like Bitcoin, smart-contract blockchains like Ethereum can interface with the real-world through so-called “oracles”, which feed trustful off-chain information. This paper introduces digital twins of physical objects and processes as computational oracles to effectively unleash the tremendous opportunity offered by blockchain to the realm of fundamental science, research and technology development (RTD). The crowdsourcing concept is illustrated with the example of centrifugal flow control in microfluidic “Lab-on-a-Disc” (LoaD) systems.

The three-armed cluster-randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%; arm II 9.9%; arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care. Trial registration: ISRCTN, ISRCTN58150046

Rapid search and localization for nuclear sources can be an important aspect in preventing human harm from illicit material in dirty bombs or from contamination. In the case of a single mobile radiation detector, there are numerous challenges to overcome such as weak source intensity, multiple sources, background radiation, and the presence of obstructions, i.e., a non-convex environment. In this work, we investigate the sequential decision making capability of deep reinforcement learning in the nuclear source search context. A novel neural network architecture (RAD-A2C) based on the actor critic (A2C) framework and a particle filter gated recurrent unit for localization is proposed. Performance is studied in a randomized 20 x 20 m convex and non-convex environment across a range of signal-to-noise ratio (SNR)s for a single detector and single source. RAD-A2C performance is compared to both an information-driven controller that uses a bootstrap particle filter and to a gradient search (GS) algorithm. We find that the RAD-A2C has comparable performance to the information-driven controller across SNR in a convex environment and at lower computational complexity per action. The RAD-A2C far outperforms the GS algorithm in the non-convex environment with greater than 95% median completion rate for up to seven obstructions.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Because of the toxicity of cyanides, many are working on the development of cyanide-free baths, which are promising but not satisfactory to replace the classic methods. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized by their morphology, chemical composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structures observed were fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at.% copper and exhibited relatively strong corrosion resistance. High improvement of corrosion properties was found in the case of copper and brass coatings with an olive-like structure.

Ongoing COVID-19 Pandemic has resulted into massive damage to various platforms of global economy which has caused disruption to human livelihood. Natural Language Processing has been extensively used in different organizations to categorize sentiments, perform recommendation, summarizing information and topic modelling. This research aims to understand the non-medical impact of COVID-19 on global economy by leveraging the natural language processing methodology. This methodology comprises of text classification which includes topic modelling on unstructured COVID-19 media articles dataset provided by Anacode. Like other Natural Language Processing algorithms, Latent Dirichlet allocation (LDA) and Non-negative matrix factorization (NMF) has been proposed to classify the media articles dataset in order to analyze COVID-19 pandemic impacts in the different sectors of global economy. Model Accuracy was examined based on the coherence and perplexity score which came out to be 0.51 and -10.90 using LDA algorithm. Both the LDA and NMF algorithm identified similar prevalent topics that was impacted by COVID-19 pandemic in multiple sectors of economy. Through intertopic distance map visualization produced by LDA algorithm, it can be reciprocated that general industries which includes children schooling, parental care, and family gatherings had the major impact followed by business sector and the financial industry.

How, if at all, consciousness can be part of the physical universe remains a baffling problem. This article outlines a new, developing philosophical theory of how it could do so, and offers a preliminary mathematical formulation of a physical grounding for key aspects of the theory. Because the philosophical side has radical elements, so does the physical-theory side. The philosophical side is radical, first, in proposing that the productivity or dynamism in the universe that many believe to be responsible for its systematic regularities is actually itself a physical constituent of the universe, along with more familiar entities. Indeed, it proposes that instances of dynamism can themselves take part in physical interactions with other entities, this interaction then being “meta-dynamism” (a type of meta-causation). Secondly, the theory is radical, and unique, in arguing that consciousness is necessarily partly constituted of meta-dynamic auto-sensitivity, in other words it must react via meta-dynamism to its own dynamism, and also in conjecturing that some specific form of this sensitivity is sufficient for and indeed constitutive of consciousness. The article proposes a way for physical laws to be modified to accommodate meta-dynamism, via the radical step of including elements that explicitly refer to dynamism itself. Additionally, laws become, explicitly, temporally non-local in referring directly to quantity values holding at times prior to a given instant of application of the law. The approach therefore implicitly brings in considerations about what information determines states. Because of the temporal non-locality, and also because of the deep connections between dynamism and time-flow, the approach also implicitly connects to the topic of entropy insofar as this is related to time.

RNA polymerase II (RNAPII) frequently transcribes non-protein coding DNA sequences in eukaryotic genomes into long non-coding RNA (lncRNA). Here, we focus on the impact of the act of lncRNA transcription on nearby functional DNA units. Distinct molecular mechanisms linked to the position of lncRNA relative to the coding gene illustrate how non-coding transcription controls gene expression. We review the biological significance of the act of lncRNA transcription on DNA processing, highlighting common themes, such as mediating cellular responses to environmental changes. This review presents the background in chromatin signaling to appreciate examples in different organisms where we can interpret functions of non-coding DNA through the act of RNAPII transcription.

Therapeutically effective treatments of cancer are limited. To calibrate the efficiency of the novel technique we recently discovered to modulate cancer cell viability using tuned electromagnetic fields; H1299 human lung cancer cells were irradiated in a sweeping regime of W-band (75-105 GHz) millimeter waves (MMW) at 0.2 mW/cm² (2 W/m²). Effects on cell morphology, cell death and senescence were examined and compared to that of non-tumorigenic MCF-10A human epithelial cells. MMW irradiation led to alterations of cell and nucleus morphology of H1299 cells, significantly increasing mortality and senescence over 14 days of observation. Extended irradiation of 10 minutes duration resulted in complete death of exposed H1299 cell population within two days, while healthy MCF-10A cells remained unaffected even after 16 minutes of irradiation under the same conditions. Irradiation effects were observed to be specific to MMW treated H1299 cells and absent in the control group of non-irradiated cells. MMW irradiation affected nuclear morphology of H1299 cells only and not of the immortalized MCF-10A cells. Irradiation with low intensity MMW shows an antitumor effect on H1299 lung cancer cells. This method provides a novel treatment modality enabling targeted specificity for various types of cancers.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

We construct a family of two-step optimal fourth order iterative methods for finding single root of non-linear equations. We generalize these methods to simultaneous iterative methods for determining all the distinct as well as multiple roots of single variable non-linear equations. Convergence analysis is present for both cases to show that the order of convergence is four in case of single root finding method and is twelve for simultaneous determination of all roots of non-linear equation. The computational cost, Basin of attraction, efficiency, log of residual and numerical test examples shows, the newly constructed methods are more efficient as compared to the existing methods in literature.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Beer is a fermented beverage with a history as old as human civilization and its productive process has been spread all around the world becoming unique in every country and iconic of entire populations. Ales and lagers are by far the most common beers; however, the combination of raw materials, manufacture techniques and aroma profiles are almost infinite, so it is not surprising to notice that there is a large amount of different beer styles, each of them with unique characteristics. Nowadays, diversification is becoming increasingly important in the brewing market and the brewers are continuously interested in improving and extending the already wide range of products, especially in craft brewery. One of the major components that can have a deep impact on the final product is yeast, since it is able to convert carbohydrates in wort, especially maltose and maltotriose, into ethanol, carbon dioxide and other minor aroma-active compounds. Saccharomyces cerevisiae (top‐fermenting yeasts used to produce ales) and Saccharomyces pastorianus (cryotolerant bottom‐fermenting hybrids between S. cerevisiae and Saccharomyces eubayanus responsible for the fermentation of lagers) are most used in breweries. However, an increasing number of different yeast starter cultures are commercially available, to improve the production efficiency also at relative low temperatures and to obtain desirable and diversified aroma profiles avoiding undesired compounds. Four main genetic engineering-free trends are becoming popular in craft brewing yeast development: 1) the research for novel reservoirs as source of new performant S. cerevisiae yeasts; 2) the creation of synthetic hybrids between S. cerevisiae and Saccharomyces non-cerevisiae in order to mimic lager yeasts by expanding their genetic background; 3) the exploitation of evolutionary engineering approaches; 4) the usage of non-Saccharomyces yeasts either in co-coculture or in sequential fermentation with S. cerevisiae. In the present work we summarized pro and contra of these approaches and provided an overview on the most recent advances on how brewing yeast genome evolved and domestication took place. Finally, we delineated how the correlations maps between genotypes and relevant brewing phenotypes can assist and further improve the search for novel craft beer starter yeasts.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

In recent years, numerous topologies of single phase and three phase Field Excited Flux-Switching Machine (FEFSM) have been developed for several applications. Comparative study of three types of single-phase low-priced Field Excited Flux-Switching Machine (FEFSM) is presented in this paper. Both the conventional 8S/4P sub-part rotor design and 6S/3P salient rotor design have an overlapped winding arrangements between armature coil and field excitation coil that depicts high copper losses as well as results in increased size of motor. Additionally, FEFSM with salient structure of the rotor have high flux strength in the stator-core that has much impact on high iron losses. Copper consumption and iron loss being a crucial proportion in total machine losses. Therefore a novel topology of single phase modular rotor field excited FSM with 8S/6P configuration is proposed, which enable non-overlap arrangement between armature coil and FEC winding that facilitates devaluation in the copper losses. The proposed modular rotor design acquires reduced iron losses as well as reduced active rotor mass comparatively to conventional rotor design. It is very persuasive to analyze the best range of speed for these rotors to avoid cracks and deformation, the maximum tensile strength (can be measured with principal stress in research) of the rotor analysis is conducted using JMAG. A deterministic optimization technique is used to enhance the performance of 8S/6P modular rotor design. The electromagnetic performance of conventional sub-part rotor design, F1-A3-3P design and proposed novel-modular rotor design are analyzed by 3D-Finite Element Analysis (3D-FEA), includes flux linkage, flux distribution, flux strength, back-EMF, cogging torque, torque characteristics, iron losses and efficiency.

Thunderstorm electrification has been studied for hundreds of years. Several mechanisms have been proposed to elucidate the electrification, including convective charging, inductive precipitation charging, and ice crystal-graupel collision charging. Field observations and model studies have demonstrated the vital roles that graupel and ice crystals play in the electrification, but the mechanism of the collision charging is still unclear. The fundamental essence of relative growth rate theory used for explaining the tripole charge structure in thunderclouds also needs a further exploration. We analyze the processes of ice crystal-graupel collision charging from charge migration inside hydrometeors to charge separation between two hydrometeors. The driving effects of temperature gradient and chemical potential gradient in charge migration are clarified, as well as the applicability of the relative growth rate theory, thermoelectric effect and surface tension gradient in different humidities. Based on the understanding from these electrification mechanisms, we propose that the essence of charge separation is driven by non-thermal equilibrium, and future studies on thunderstorm electrification should focus on the dynamical non-thermal equilibrium of cloud particles.

Magnetic nanoparticles are met across many biological species ranging from magnetosensitive bacteria, fishes, bees, bats, rats, birds, to humans. They can be both of biogenetic origin and due to environmental contamination, being either in paramagnetic or ferromagnetic state. The energy of such naturally occurring single-domain magnetic nanoparticles can reach up to 10-20 room k_BT in the magnetic field of the Earth, which naturally led to supposition that they can serve as sensory elements in various animals. This work explores within a stochastic modeling framework a fascinating hypothesis of magnetosensitive ion channels with magnetic nanoparticles serving as sensory elements, especially, how realistic it is given a highly dissipative viscoelastic interior of living cells and typical sizes of nanoparticles possibly involved.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

This study presents a novel lake ecosystem model that captures the intricate dynamics of nutrient cycling through nonlinear interactions. The model incorporates external phosphorus loading and internal recycling rates to explore a range of ecological outcomes, from stable equilibria to chaotic oscillations. We investigate the bifurcation phenomena within this model, revealing how changes in parameters can lead to significant shifts in ecosystem behavior. Our analysis demonstrates that the model can replicate behaviors similar to the Hénon map under specific parameter settings. Through numerical simulations, we examine the system's sensitivity to variations in nutrient parameters, uncovering the potential for unpredictable dynamics and chaos as the recycling rate increases. The emergence of chaotic behavior is further supported by entropy analysis, highlighting the model's complexity and its implications for real-world ecosystems. Notably, our findings resonate with the work of Tay et al., demonstrating that increased nutrient recycling can lead to bistability and abrupt shifts in ecosystem stability, emphasizing the critical importance of effective nutrient management to avert detrimental ecological consequences. This research contributes valuable insights into the dynamics of freshwater ecosystems, underscoring the intricate interplay between nutrient inflow, recycling, and bifurcation in maintaining ecological balance.

Market dynamics is based on classical electrodynamics and uses quantum electrodynamics as a reference model framework. Its construction is always based on Bourbaki structuralism. Market dynamics studies the interaction between price, demand and supply. Quantum electrodynamics studies the interaction between photons, electrons and positrons. Both belong to the category of single charge dynamics and share a symmetry group. Market dynamics introduces market charge and defines demand and supply respectively. By examining the market hesitation phenomenon, spin is introduced as the intrinsic property of demand and supply. Therefore, demand and supply can be defined by Dirac spinors. By introducing the coin cone and valence shell, virtual prices are defined; demand and supply interact by exchanging virtual prices. These interactions can be described by Feynman diagrams. The cognitive field has the function of polarizing decision-making and is described by the magnetic field. Market dynamics believes that the social economy itself is an experiment and every market participant is an observer. We established the non-commutative relationship of market observation and the market version of the uncertainty principle of observation information, and defined the quantum version of the invisible hand. On the basis of classical electrodynamics, the relationship between price field and Maxwell field is discussed, and the concept of gauge potential is introduced. Market fluctuations (including mesoscopic and quantum fluctuations) caused by high-order cognition (including gaming, decision-making and reasoning). The fluctuation phenomena inherent in various markets are the basis for understanding both the cognition of market participants and the phase transition of the market. Six components of the market wave function are defined, namely the global phase factor, global gauge potential and global gauge field strength, as well as the local phase factor, local gauge potential and local gauge field strength. Gauge transformation is a integral part of quantum electrodynamics and market dynamics. The gauge principle is then given to show that global symmetry is a necessary condition for local symmetry. Four operators are introduced, namely the Newton mean operator, the Einstein cone operator, the Schrödinger evolution operator and the Dirac field theory operator. These four operators are applied to the market wave function respectively, presenting four operator phases of the market wave function. The change of operator state is called the phase transition of the market wave function.

Microgrid (MG) control is essential for efficient, reliable, and sustainable energy management in distributed energy systems. Genetic Algorithm-based energy management systems (GA-EMS) can optimally control a MG by finding global optima and handling complex, non-linear, and non-convex problems, but they can be computationally intensive, making real-time control challenging. Model Predictive Control (MPC)-based EMS predicts future behaviour over a defined horizon, ensuring optimal performance and constraint satisfaction but typically relies on linear models. This paper proposes a novel Genetic Predictive Control (GPC) method, combining GA and MPC to enhance resource allocation, balance multiple objectives, and adapt dynamically to changing conditions. Integrating GA with MPC significantly improves the handling of non-linearities and non-convexity in the system model, leading to more accurate and effective control. Comparative analysis shows that GPC significantly reduces excess power production—surplus power generated beyond load demand—improving resource allocation efficiency. For instance, in the Mutation–Random Selection scenario, GPC reduced excess power to 76.0W compared to 87.0W with GA. Additionally, GPC balances cost, emissions, and power efficiency. In the Crossover-Elitism scenario, GPC achieved a daily cost of $113.94 compared to GA's $127.80, and carbon emissions of 52.83 kg CO2e compared to GA's 69.71 kg CO2e, demonstrating GPC's cost efficiency and environmental benefits. While MPC optimizes a weighted sum of objectives, designing appropriate weights can be challenging and may result in non-convex problems. GA handles multiple, conflicting objectives through multi-objective optimization, providing Pareto-optimal solutions. GPC's dynamic adaptability maintains optimal performance by forecasting future load demands and adjusting control actions. GPC consistently achieves lower emissions than GA across various scenarios and, although it sometimes incurs higher costs, such as $113.94 compared to $131.90 in the Crossover–Random Selection scenario, its holistic approach balances these costs with other metrics, making it cost-effective in the long run. By reducing excess power production and emissions, GPC contributes to economic savings and promotes sustainable practices. These findings underscore GPC's potential as a versatile, efficient, and environmentally beneficial optimization tool for power generation systems.

In order to solve the problem of large eddy current loss and high temperature rise caused by large amount of permanent magnet, a new type of combined magnetic pole permanent magnet motor is proposed in this paper. The sinusoidal distribution subdomain model of non-uniform air gap rotor is established by using Laplace equation, and the analytical expression of eddy current loss of rotor in uniform air-gap and non-uniform air-gap is derived. The effect of rotor eccentricity on eddy current loss is obtained. According to the characteristics of distributed winding of non-uniform air gap combined pole permanent magnet motor, equivalent treatment is performed to obtain the equivalent thermal conductivity, so as to establish equivalent thermal network model of motor, calculate the temperature value of each component of the motor, and verify the correctness of the thermal network model through the method of magnetothermal bidirectional coupling. Finally, an experimental platform is set up to carry out temperature rise experiments on the two prototypes respectively. Experimental results show that the non-uniform air-gap rotor structure can effectively reduce the rotor eddy current loss and motor temperature rise, and also verify the accuracy of the analytical model calculation results.

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylal-lyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associ-ated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop pro-tection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interven-tions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear encoded mitochondrial peptidase that has been conserved through evolutionary history as has its target enzyme ‘mitochondrial glycerol phosphate dehydrogenase 2’ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear encoded mitochondrial respiratory related protein cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse and in this study EchoMRI analysis found that many organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p&lt;0.05). Moreover, all of the organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lower in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to wildtype when glutamate was used as substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2 we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together these findings suggest that the respiratory related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues in the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial encoded cytochrome b (Cyb) in Complex III had been altered as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS) which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration comprised of a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration where the latter was consistent with the decreases in substrate specific mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

There were designed and synthesized two new sulfone 2-aminobenzimidazole derivatives. Coordination compounds were obtained with nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) and these novel ligands. There were fully characterized by spectroscopic and analytical techniques. Single crystal X-ray structural analysis was performed on order to study the relevant intra and inter non-covalent interactions, mainly H...π, lone pair·...π, π...π, highlighting the difference between the ethyl and phenyl groups in such interactions. Dimeric and trimeric supramolecular syntons were found for some of these compounds. Their biological activity was investigated, being the copper(II) compounds with the sulfone phenyl derivative the most active.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

Petrochemical plants use on-stream inspection more often to detect and monitor the corrosion on the equipment and piping system. Compared to ultrasonic thickness gauging and pulse-echo A-scan, phased array corrosion mapping has better coverability and can scan a large area to detect general and localized corrosion. This paper's objective is to obtain documentary evidence on the accuracy of corrosion detection from 30°C to 250°C on A36 low-carbon steel by carrying out simulation experiments every 10°C steps. A minimum of three sets of phased array corrosion mapping data in each temperature were collected to study and evaluate the detectability. The data evidence could enhance the confidence level of the plant's end users to use the phased array mapping in the future during an inspection. The experiments were found to be insufficiently thorough despite addressing the initial concerns, leaving more area for discussion in further studies, such as expanding the investigation to thicker carbon steel, stainless steel, and wedge materials.

Seed germination and seedling growth represent two vulnerable stages in a plant life cycle and it is important to determine how they will be affected by environmental changes associated with climate change. This study examines the impact of salinity levels (0, 50, 100, and 150 mM) at each of three temperatures (15, 25, and 35˚C) on seed germination and radicle growth for three dormant and three non-dormant varieties of conventional, glyphosate resistant, or reduced lignin alfalfa. The genetic basis and phenotypic plasticity for seed germination and seedling growth in response to salinity and temperature were determined. Both traits were phenotypically plastic with respect to temperature and salinity. Seed germination was 87.0% ± 1.7 at 25˚C, 0mM (no salinity), but decreased to 33.9% ± 3.9 germination at 35˚C and 150mM. Radicle length went from 36.7 ± 1.5 mm after four days at 25˚C, 0mM, to 10.5 ± 0.7 mm at 35˚C, 150mM. The phenotypic response brought seed germination and radicle length away from their optimum, but we detected standing genetic variation for both seed germination and radicle length. Selection to increase both traits at high temperature and salinity would facilitate alfalfa establishment under climate change.

Since its emergence, COVID-19 has caused a great impact in health and social terms. Governments and health authorities have attempted to minimize this impact by enforcing different mandates. Recent studies have addressed the relationship between various socioeconomic variables and compliance level to these interventions. However, little attention has been paid to what constitutes people's response and whether people behave differently when faced with different interventions. Data collected from different sources show very significant regional differences across the United States. In this paper, we attempted to shed light on the fact that a response may be different depending on the health system capacity and each individuals’ social status. For that, we analyzed the correlation between different societal variables (i.e. education, income levels, population density, etc.) along with healthcare capacity related variables (i.e. hospital occupancy rates, percentage of essential workers, etc.) with regards to people's level of compliance with three main governmental mandates in the United States: mobility restrictions, mask adoption, and vaccine participation. Our aim was to isolate the most influential variables impacting behavior in response to these policies. We found that there was a strong relationship between individuals' educational levels and political preferences with respect to compliance with each of these mandates.

Seniors safety is a compelling need, which necessitates 24/7 real-time monitoring and timely dangerous action recognition. Being able to mirror characteristics of physical objects (PO) to corresponding logical objects (LO) and seamlessly monitor their footprints thus detect anomaly parameters, Digital Twins (DT) has been considered a practical way to provide virtual health services for seniors safety. Meanwhile, widely adopted Internet of Medical Things (IoMT) consisting of wearable sensors and non-contact optical cameras for self and remote health data monitoring also raises concerns on information security and privacy violation. Therefore, security of POs, LOs and reliable data sharing among healthcare professionals are challenging as constructing trust and privacy-preserving virtual health services. Thanks to characteristics of decentralization, traceability and unalterability, Blockchain is promising to enhance security and privacy properties in many areas like data analysis, finance and healthcare. This paper envisions a lightweight authentication framework (LAF) to enable secure and privacy-preserving virtual healthcare services. Leveraging Non-Fungible Token (NFT) technology to tokenize LOs and data streams on blockchain, anyone can certify the authenticity of a digital LO along with its synchronized data between PO without relying on a third-party agency. In addition, the NFT-based tokenization not only allows owners fully control their IoMT devices and data, but it also enables verifiable ownership and traceable transferability during data sharing process. Moreover, NFT only contains references to encrypted raw data that are saved on off-chain storage like local files or distributed databases, such a hybrid storage strategy ensures privacy-preservation for sensitive information. A proof-of-concept prototype is implemented and tests are conducted on a case study of seniors safety. The experimental evaluation shows the feasibility and effectiveness of the proposed LAF solution.