Saponite is a trioctahedral 2:1 smectite with the ideal composition MxMg3AlxSi4-xO10(OH,F)2.nH2O (M = interlayer cation). Both the success of the saponite synthesis and the determination of its applications depends on robust knowledge of the structure and composition of saponite. Among the routine characterization techniques spectroscopic methods are the most common. This review, thus, provides an overview of various spectroscopic methods to characterize natural and synthetic saponite with focus on the extensive work by one of the authors (JTK). The IR and Raman spectra of natural and synthetic saponites are discussed in detail including the assignment of the observed bands. The crystallization of saponite is discussed based on the changes in the IR and Raman spectra and a possible crystallization model is provided. Infrared emission spectroscopy has been used to study the thermal changes of saponite in-situ including the dehydration and (partial) dehydroxylation up to 750˚C. 27Al and 29Si Magic-Angle-Spinning Nuclear Magnetic Resonance Spectroscopy is discussed (as well as 11B and 71Ga for B- and Ga-Si substitution) with respect to, in particular, Al(IV)/Al(VI) and Si/Al(IV) ratios. X-ray Photoelectron Spectroscopy provides besides chemical information also some information related to the local environments of the different elements in the saponite structure as reflected by their binding energies.

Corona virus disease (COVID-19) has infected over more than 10 million people around the globe and killed at least 500K worldwide by the end of June 2020. As this disease continues to evolve and scientists and researchers around the world now trying to find out the way to combat this disease in most effective way. Chest X-rays are widely available modality for immediate care in diagnosing COVID-19. Precise detection and diagnosis of COVID-19 from these chest X-rays would be practical for the current situation. This paper proposes one shot cluster based approach for the accurate detection of COVID-19 chest x-rays. The main objective of one shot learning (OSL) is to mimic the way humans learn in order to make classification or prediction on a wide range of similar but novel problems. The core constraint of this type of task is that the algorithm should decide on the class of a test instance after seeing just one test example. For this purpose we have experimented with widely known Generalized Regression and Probabilistic Neural Networks. Experiments conducted with publicly available chest x-ray images demonstrate that the method can detect COVID-19 accurately with high precision. The obtained results have outperformed many of the convolutional neural network based existing methods proposed in the literature.

Synthetic chalcomenite-type cupric selenite CuSeO₃∙2H₂O has been studied at room temperature under compression up to pressures of 8 GPa by means of single-crystal X-ray diffraction, Raman spectroscopy, and density-functional theory. According to X-ray diffraction, the orthorhombic phase undergoes an isostructural phase transition at 4.0(5) GPa with the thermodynamic character being first-order. This conclusion is supported by Raman spectroscopy studies which have detected the phase transition at 4.5(2) GPa and by the first-principles computing simulations. The structure solution at different pressures has provided information on the change with pressure of unit-cell parameters as well as on the bond and polyhedral compressibility. A Birch-Murnaghan equation of state has been fitted to the unit-cell volume data. We found that chalcomenite is highly compressible with a bulk modulus of 42 – 49 GPa. The possible mechanism driving changes in the crystal structure is discussed, being the behavior of CuSeO₃∙2H₂O mainly dominated by the large compressibility of the coordination polyhedron of Cu. On top of that, an assignation of Raman modes is proposed based upon density-functional theory and the pressure dependence of Raman modes discussed. Finally, the pressure dependence of phonon frequencies is also reported.

JBIR-99 is a secondary metabolite of marine fungi that has been shown to possess strong antibiotic activity. An efficient approach using a combination of size exclusion chromatography with a Sephadex LH-20 and high-speed counter-current chromatography (HSCCC) has been successfully developed for the isolation and purification of a polyketide from the solid-state fermentation of Meyerozyma guilliermondii. The active compound was isolated with purity >95% by HSCCC using an optimized solvent system composed of petroleum ether–ethyl acetate– 95% ethanol–water (5:3:5:3, v/v/v/v) after size exclusion chromatography. This compound was successfully purified in the quantity of 68 mg from 120 mg of the crude extract. The structure of JBIR-99 was elucidated and assigned by 1D, 2D NMR spectroscopic, and positive HRESITOFMS. Moreover, the relative configuration of compound JBIR-99, displaying a quite complex multi-ring structure, is determined by X-ray crystallography for the first time. The purification method developed for JBIR-99 will facilitate the further investigation and development of this antibiotic agent as a lead compound. Furthermore, it is suggested that the combination of size exclusion chromatography and HSCCC could be more widely applied for the isolation and purification of polyketides from marine fungi.

X-ray fluorescence is largely employed in the measurement of the thickness of coatings. Despite of its diffusion, the task is not straightforward because of the complex physics involved that results in high dependence on matrix effects. Thickness quantification is in practice accomplished using the Fundamental Parameters approach, adjusted with empirical measurements of standards with known composition and thickness. This approach has two major drawbacks: i) there are no standards for any possible coating and coating architecture and ii) even relying on standards, the quantification of unknown samples requires the precise knowledge of the matrix nature (e.g., in case of multilayer coatings the thickness and the composition of each underlayer). In this work, we describe a semiquantitative approach to coatings thickness measurement based on the construction of calibration curves through simulated XRF spectra built with Monte Carlo simulations. Simulations have been performed with the freeware software XMI-MSIM. We have assessed the accuracy of the methods by comparing the results with those obtained by i) XRF thickness determination with standards and ii) FIB-SEM cross-sectioning. Then we evaluated which parameters are critical in this kind of indirect thickness measurements.

Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.

In this paper, we present a comprehensive 4D study of the early stage of plastic deformation in a polycrystalline binary AlLi alloy. The entire microstructure is mapped with X-ray diffraction contrast tomography and a set of bulk grains is further studied via X-ray topotomography during mechanical loading. The observed contrast is analyzed with respect to the slip system activation and the evolution of the orientation spread is measured as a function of applied strain. The experimental observations are augmented by the mechanical response predicted by crystal plasticity finite element simulations to analyze the onset of plasticity in details. Simulation results show a general agreement of the individual slip system activation during loading and that comparison with experiments at the length scale of the grains may be used to fine tune the constitutive model parameters.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Abstract: We have filled a 24 mm diameter glass sphere with a transparent polymer-gel that is radio-fluorogenic, i.e. it becomes (permanently) fluorescent when irradiated, with an intensity proportional to the local dose deposited. The gel consists of >99.9% tertiary-butyl acrylate (TBA) pre-polymerized to ~15% conversion, and ~100 ppm maleimido-pyrene (MPy). Its dimensions and physical properties are close to those of the vitreous body of the human eye. We have irradiated the gel with a 3 mm diameter, 200 kVp X-ray beam with a dose rate of ~1 Gy/min. A 3D (video) view of the beam within the gel has been constructed from tomographic images obtained by scanning the sample through a thin sheet of UV light. To minimize optical artifacts, the cell was immersed in a square tank containing a refractive-index-matching medium. The 20%-80% penumbra of the beam was determined to be ~0.4 mm. The research was a preparatory investigation of the possibility of using the method to monitor the millimetre diameter proton pencil beams used in ocular radiotherapy.

Friction and wear take place on two solid surfaces in sliding contact as a result of the mechanical, thermal and chemical interactions with the participation of environmental species. Electron microscopy and the associated spectroscopic analyses are powerful in probing these mechanisms in spatial resolutions from micro to atomic scale. This article provides a review of the author’s work in the wear and friction mechanisms of PVD hard coatings in which various SEM- and TEM-based microscopic and spectroscopic techniques were employed. Understanding on the failure mechanisms and the origin of self-adaptive friction has been improved to nano-scale. Other related issues are also discussed, such as sample preparation techniques for cross-sectional electron microscopy, energy dispersive X-ray spectroscopy and electron energy loss spectroscopy.

Background/Objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma, often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma; Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils and asthma mouse model; Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues; Conclusions: These results suggest that CBD-X extract could offer a novel, complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

In this research paper an algorithm for the derivation of methods based on theorems and axioms of fuzzy logic is presented, analyzed and applied. This new proposed procedure generates fuzzy methods and evaluates the value of fuzzy propositions through fuzzy implication. The new implications of the family should satisfy a number of axioms. Also, we denote the conditions in order to satisfy the maximum number of axioms. Moreover, authors state and prove theorems focusing on fuzzy implication, observing the rule: the fuzzy function of fuzzy implication is strong and that lead to fuzzy negation. In addition, the optimal number of repetitions is calculated according to the expected truth value. The formulas produced are verified through the use of temperature and humidity values over a certain period of time and in a certain geographical area in Greece. The basic steps of the methodology are the fuzzification of the data given ​​using four membership degree functions and the application of the membership degrees of temperature and humidity values on a new type of fuzzy implication. Finally, we observed that the isosceles trapezium gave the best results and the type of fuzzy implication can be effectively applied.

The present analysis deals with the study of the $f(Q, T )$ theory of gravity which was recently considered by many cosmologists. In this theory of gravity, the action is taken as an arbitrary function $f(Q, T )$ where $Q$ is non-metricity and $T$ is the trace of energy-momentum tensor for matter fluid. In this study, we have taken three different forms of the function $f(Q, T )$ as $f(Q,T)=a_1Q+a_2 T$ and $f(Q,T)=a_3 Q^2+a_4 T$ and discussed some physical properties of the same. Also, we have obtained the various cosmological parameters towards Friedmann-Lemaitre-Robertson-walker (FLRW) Universe by defining the transit form of scale factor which yields the Hubble parameter in redshift form as $H(z)=\frac{H_{0}}{(\lambda+1)} \left(\lambda+ (1+z)^{\delta}\right)$. %We have obtained the approx best-fit values of model parameters using the least square method for observational constraints on available datasets like Hubble dataset $H(z)$, Supernova dataset SNe-Ia, etc., by applying the Root Mean Squared Error formula (RMSE). By applying the Root Mean Squared Error formula (RMSE), we were able to determine the approximate best-fit values of model parameters using the least square approach for observational constraints on the datasets Hubble dataset $H(z)$, Supernova dataset SNe-Ia, etc. We have observed that the deceleration parameter $q(z)$ exhibits a signature-flipping (transition) point within the range $0.623 \le z_{0} \le 1.668$ through which it changes its phase from the decelerated to the accelerated expanding universe with $\omega = -1$ at $z=-1$ for the approximate best-fit values of the model parameters. %For obtained approx best-fit values of model parameters we have observed that the deceleration parameter $q(z)$ shows a signature-flipping (transition) point within the range $0.623 \le z_{0} \le 1.668$ through which it changes its phase from decelerated to the accelerated expanding universe with $\omega = -1$ at $z=-1$.

We employ hierarchy of models (HoM) with 2, 3 and 4 parameters to reanalyze the nucleation kinetics in the electrodeposition as quantified by n(t) - “the number of nuclei vs. time” data obtained at different overvoltages from precise experiments on electrodeposition of Hg on two different types of Pt-cathodes by Ivan V. Markov and Evgenia Stoycheva [1]. The obtained two scales, nmax and , are used to rescale the original data mapping it on a master curve in coordinates . Our main result is obtained by studying further the dependence of these two scales on the overvoltage (analogue of supersaturation). Surprisingly, for one of the two cathode types - the “hemispherical single-crystal electrode” (as defined by the authors), there is discontinuity in the “ vs. overvoltage” dependence – an almost horizontal jump from 85 to 86 mV accompanied by a change in the slope of the dependence - it is ~ -1 and ~ -0.5 after. For the other cathode - “plane structureless platinum electrode”,  decreases smoothly. Combined, these two behaviors point at the so called “cusp catastrophe”. We compare our findings with published results on protein nucleation.

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Although many small molecules have been proposed as inhibitors of amyloid formation, few have been successful in clinical trials. Amyloid formation is complex and several individual steps could be targeted by small molecules. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules. Furthermore, commonly used assays are prone to artifacts that must be controlled for. Here, potential mechanisms by which small molecules could inhibit aggregation of immunoglobulin light chain dimers, the precursor proteins for AL amyloidosis are studied in assays that recapitulate different aspects of amyloidogenesis in vitro. One molecule reduced unfolding-coupled proteolysis of light chains, but no molecules inhibited aggregation of light chains or disrupted pre-formed amyloid fibrils. This work demonstrates the challenges associated with drug development for amyloidosis, but also highlights the potential to combine therapies that target different aspects of amyloidogenesis.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

One of the biggest challenges for European industry is to introduce sustainability principles into business models. This is particularly important in raw material and energy intensive manufacturing sectors such as the ceramic industry. The present state of knowledge lacks a comprehensive operational tool for industry to support decision-making processes geared towards sustainability. In the ceramic sector, the economic and social dimensions of the product and processes have not yet been given sufficient importance. Moreover, the traditional research on industrial districts lacks an analysis of the relations between firms and the territory with a view to sustainability. Finally, the attention of scholars in the field of economic and social sustainability, has not yet turned to the analysis of the Sassuolo district. Therefore, in this paper we define the Territorial Life Cycle Sustainability Assessment (T-LCSA), a method that can be a suitable tool to fill this gap, because through a mathematical model it is possible to obtain the information useful for decision makers to integrate the principles of sustainability both at the microeconomic level in enterprises, and at the meso-economic level for the definition of economic policies and territorial governance. Environmental and socio-economic analysis was performed from the extraction of raw materials to the packaging of the product on different product categories manufactured by the Italian ceramic industries of the Sassuolo district (northern Italy). For the first time the T-LCSA model, usually applied to unitary processes, is extended to the economic and industrial activities of the entire district, extending the prospect of investigation from the enterprise and its value chain to the integrated network of district enterprises.

Gaia-X, a European initiative, aims to create a digital sovereignty framework for service ecosystems in the future internet. Its applicability to the health domain has been explored in the Gaia-X-Med project, which aimed to establish a common dataspace for various medical use cases based on Gaia-X principles. This paper presents the approach to secure authentication and digital contract negotiation central to this endeavour and discusses the challenges that arose during adoption of the Gaia-X framework, in particular relating to the strict requirements of the European healthcare domain with regards to privacy and consent regulations. By exploring the practical implications of Gaia-X in the healthcare context, this paper aims to contribute to the ongoing discussions surrounding digital sovereignty of both citizens and corporations, as well as its realization via future internet technologies.

Geochemical mapping of river sands in the Manufahi area of Timor-Leste revealed potential areas for future mineral exploration. River sand samples from the study area were collected and geochemically analyzed to identify anomalous concentration distributions of several valuable elements and locate potential target areas and geological formations that may host mineral deposits. The 26 major and minor elements were identified using wavelength-dispersive X-ray fluorescence. The river sands exhibited varying elemental concentrations, with Cr, Cu, Zn, and Ba showing deviations from the normal distribution patterns. Identification of geochemical anomalies is an important task in mineral exploration geochemistry. The mean + 2 standard deviations (mean+2STD), median + 2 median absolute deviations (median+2MAD), and Tukeyâs inner fence (TIF) methods were used to determine the geochemical thresholds. This study shows that TIF and principal component analysis (PCA) methods are highly effective in calculating appropriate threshold values and identifying relevant elemental associations. These approaches have proven useful for delineating target areas for mineral deposits, resulting in reliable outcomes. Four predicted target areas with high potential for deposits and mineralization anomalies of Cr, Cu, Ni, and Ba were delineated in the study area.

This paper presents a demonstration of a linearly-polarized transmit-arrays antenna with high-efficiency and wideband operating in X-band. The topology of the unit cell consists of two identical patch antennas loaded by C-loop slot and interconnected by a metalized via through a ground plane sandwiched between two identical substrates [18]. A waveguide measurement system WGMS has been used for single cell characterization (reflection/transmission coefficients). Good results have been demonstrated in terms of matching performances; the reflection coefficient S11 is under 10-dB in the 9.4-10.4 GHz band (i.e. 10.1% around 9.9 GHz) and with only 0.35 dB-insertion loss at 10 GHz. The transmit-arrays prototype permitted to achieve 22.4 dBi of directivity and 20.1 dBi of gain. The aperture and radiation efficiencies are about 28.2% and 58.3%, respectively. With a focal ratio (F/D) of 1/2 the spill-over loss is less than 2 dB. Beam-scanning up to ± 35° has been achieved with the same phase quantization (passive) and less than 3 dB of gain losses.

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

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth from a particular context. The feature of mathematics from the article title is not quite new. Church's thesis, which is known from the beginning of computability theory, is based on the observation that the currently known computable functions are recursive, where the notion of a computable function is informal. It proves that the predicate of the current mathematical knowledge slightly increases the intuitive mathematics. For a set X⊆N whose infiniteness is false or unproven, we define which elements of X are classified as known. No known set X⊆N satisfies Conditions (1)-(4) and is widely known in number theory or naturally defined, where this term has only informal meaning. (1) A known algorithm with no input returns an integer n satisfying card(X)<ω ⇒ X⊆(-∞,n]. (2) A known algorithm for every k∈N decides whether or not k∈X. (3) No known algorithm with no input returns the logical value of the statement card(X)=ω. (4) There are many elements of X and it is conjectured, though so far unproven, that X is infinite. (5) X is naturally defined. The infiniteness of X is false or unproven. X has the simplest definition among known sets Y⊆N with the same set of known elements. We prove that the set X={n∈N: the interval [-1,n] contains more than 29.5+(11!/(3n+1))∙sin(n) primes of the form k!+1} satisfies Conditions (1)-(5) except the requirement that X is naturally defined. 501893∈X. Condition (1) holds with n=501893. card(X∩[0,501893])=159827. X∩[501894,∞)={n∈N: the interval [-1,n] contains at least 30 primes of the form k!+1}. If we add to X some set W satisfying 14≤card(W)≤23, then the following statements hold: X does not satisfy Condition (1), 159827+14≤card(X), the above lower bound is currently the best known, card(X)<ω ⇒ card(X)≤159827+23, the above upper bound is currently the best known, X satisfies Conditions (2)-(5) except the requirement that X is naturally defined. Analogical statements hold, if we add to X the set ⋃_{x∈N, x divides 99!} {k∈N: k-501894 is the x-th element of P(n^2+1)}, where P(n^2+1) denote the set of primes of the form n^2+1. For a non-negative integer n, let θ(n) denote the largest integer divisor of 10^{10^{10}} smaller than n. Let κ:N→N be defined by setting κ(n) to be the exponent of 2 in the prime factorization of n+1. The set X={n∈N: (θ(n)+κ(n))^2+1 is prime} satisfies Conditions (1)-(5) except the requirement that X is naturally defined. Condition (1) holds with n=0^{10^{10}}. We present a table that shows satisfiable conjunctions of the form #(Condition1)∧ (Condition 2)∧#(Condition 3)∧(Condition 4)∧#(Condition 5), where # denotes the negation ¬ or the absence of any symbol. No set X⊆N will satisfy Conditions (1)-(4) forever, if for every algorithm with no input, at some future day, a computer will be able to execute this algorithm in 1 second or less. The physical limits of computation disprove this assumption.

Candida boidinii NAD+-dependent formate dehydrogenase (CbFDH) has gained significant attention for its potential applications in the production of biofuels and various industrial chemicals from inorganic carbon dioxide. In this study, we present an atomic X-ray crystal structure of the apo CbFDH to 1.4 Å resolution determined at cryogenic temperature at the Turkish Light Source, “Turkish DeLight”. This structure offers a comprehensive view of the apo enzyme's dynamics, filling the gaps in our understanding from previous studies. Also, comparison of our high-resolution apo and previously available holo enzyme structures reveals major conformational changes of this dynamic enzyme in the absence and presence of the coenzyme and substrate/inhibitor complexes. Collectively all these information may provide invaluable insights into future protein engineering efforts that could enhance enzymatic activity and stability, potentially increasing its efficiency and effectiveness of CbFDH in industrial processes.

The crystals, C11H4BrF5N2S, (I), 1-((4-bromothiophen-2-yl)methylene)-2-(perfluorophenyl)hydrazine and C12H6BrF5N2S, (II), 1-((4-bromo-5-methylthiophen-2-yl)methylene)-2-(perfluorophenyl)hydrazine are molecules with two rings and hydrazone part like a centre of the molecule. The compounds have been synthesized and characterized by elemental, spectroscopic (¹H-NMR) analysis. The crystal structures of the solid phase were determined by single crystal X-ray diffraction method. They crystallize in the monoclinic space group with Z = 4 and Z = 2 molecules per unit-cell. The compound (I) crystallizes as a racemate in the centrosymmetric space group and the compound (II) crystallizes as a non-racemate in the non-centrosymmetric space group. The “absolute configuration and conformation for bond values” were derived from the anomalous dispersion (ad) for (II). The crystal structures are revealed diverse non-covalent interactions such as intra- and interhydrogen bonding, π-ring···π-ring, C-H···π-ring and they were investigated. The expected stereochemistry of hydrazones atoms C7, N2 and N1 were confirmed for (I) and (II). The hole molecule of the (I), and (II) possesses “a boat conformation” like a 6-membered ring. The results of the single crystal studies are reproduced with the help of Hirshfeld surface study and Gaussian software.

The art of observing and describing behaviors has driven diagnosis and informed basic science in Psychiatry. In recent times, studies of mental illness are focused on understanding the brain’s neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In Precision Medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes genes’ expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate genes’ expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing the genes’ expressions on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological ones. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g. Autism, Schizophrenia, Depression) through DSM-observation criteria, have strong convergence with well-known neurological ones (e.g. Ataxias, Parkinson), but less overlap with non-neurological ones. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain-body connection and the contributions of the peripheral nervous systems to mental health.

In the current manuscript we assess to what extent X-ray photoelectron spectroscopy is a suitable tool for probing the dipoles formed at interfaces between self-assembled monolayers and metal substrates. To that aim, we perform dispersion-corrected, slab-type band-structure calculations on a number of biphenyl-based systems bonded to a Au(111) surface via different docking groups. In addition to changing the docking chemistry (and the associated interface dipoles), also the impacts of polar tail-group substituents and varying dipole densities are investigated. We find that for densely-packed monolayers the shifts of the peak positions of the simulated XP-spectra are a direct measure for the interface dipoles. In the absence of polar tail-group substituents they also directly correlate with adsorption-induced work-function changes. At reduced dipole-densities this correlation deteriorates, as work function measurements probe the difference between the Fermi-level of the substrate and the electrostatic energy far above the interface, while core level shifts are determined by the local electrostatic energy in the region of the atom from which the photoelectron is excited.

There are potentially promising mitigation activities for epidemic and pandemic scenarios that are not currently the subject of significant research effort. Large epidemics and pandemics pose risks that are important to mitigate, even if the likelihood of the events is low and uncertain. While some efforts are the subject of extensive funding and consideration, other approaches are neglected. Here, we consider such neglected interventions which could significantly reduce the impact of such an epidemic or large-scale pandemic. These are identified via a narrative literature review of extant literature reviews and overviews of mitigations in epidemic and pandemic situations, followed by consideration of the economic value of information of further study of heretofore neglected interventions and approaches.Based on that analysis, we considered several classes of mitigations, and conducted more exploratory reviews of each. Those discussed include mitigations for (1) reducing transmission, such as personal protective equipment and encouraging improved hygiene, (2) reducing exposure by changing norms and targeted changes for high-risk or critical professions and activities, (3) reducing impact for those infected, and (4) increasing large scale resilience using disaster and infrastructure continuity planning.Some proposed mitigations are found to be of low marginal value. Other mitigations are likely to be valuable, but the concepts or applications are underdeveloped. In those cases, further research, resources, or preparation are valuable for mitigating both routine and extreme disease outbreak events. Still more areas of research are identified as having uncertain value based on specific but resolvable uncertainties. In both of the latter cases, there is no guarantee that mitigations identified as worthy of further consideration will be valuable, but the argument for further research is clear.

To harness light-matter interaction at nano-/micro-scale better control tools have to be developed. Here, it is shown that by applying external electric and/or magnetic field, ablation of Si and glass under ultra-short (sub-1~ps) laser pulse irradiation can be controlled via the Lorentz force $\mathbf{F} = e\mathbf{E} + e[\mathbf{v}\times\mathbf{B}]$, where $\mathbf{v}$ is velocity of charge $e$, $\mathbf{E}$ is the applied electrical bias and $\mathbf{B}$ is the magnetic flux density. The external electric E-field was applied during laser ablation using suspended micro-electrodes above glass substrate with an air gap for the incident laser beam. The counter-facing Al-electrodes on Si surface were used to study debris formation patterns on Si. Debris was deposited preferentially towards the negative electrode in the case of glass and Si ablation. Also, an external magnetic field was applied during laser ablation of Si in different geometries and is shown to affect ripple formation. The vectorial nature of the Lorentz force widens application potential of surface modifications and debris formation in external E-/B-fields with potential applications in mass and charge spectroscopes.

In this article, the effect of substitution of Zr and Ga in Dy2Fe17 prepared by arc melting technique are studied. The substitution of Zr and Ga in Dy2Fe17 was found to have an important effect on their structure and magnetic properties. The Rietveld analysis conformed that the crystalline system wereTh2Ni17 structure. Lattice parameters a (Å) and c (Å), unit cell volume (Å3), bonding distance (Å) were calculated by using Rietveld analysis. The unit cell volume of Dy2Fe17-xZrx and Dy2Fe16Ga1-xZrx increase linearly with the Zr and Ga substitution. The substitution of Zr and Ga are limited up to x=1 in order to avoid the decrease in saturation magnetization. The Curie temperature (Tc) of Dy2Fe17-xZrx and Dy2Fe16Ga1-xZrx are found to be Zr content dependent. The Curie temperature is found to be increasing first and then decrease for higher Zr content. The maximum curie temperature was observed 510K at x = 0.75 for Dy2Fe17-xZrx and 505.1 K at x = 0.5 for Dy2Fe17-xZrx which are102 K and 97 K higher than Dy2Fe17. The room temperature Mössbauer analysis shows the decrease in average hyperfine field and increase in isomer shift with Zr doping.

The acylation of unsymmetrical N-benzylbispidinols in aromatic solvents without external base led to formation of supramolecular gels, which possess different thickness and stability depending on the substituents in para-positions of benzylic group and nature of acylating agent as well as on the nature of the solvent used. Structural features of the native gels as well as of their dried forms were studied by complementary techniques including FT IR- and ATR-spectroscopy, AFM, TEM, SEM, SAXS. Structures of the key crystalline compounds were established by X-ray diffraction. Analysis of obtained data allowed speculating on the crucial structural and condition factors that governed the gel formation. The most important factors were: (i) absence of base, either external or internal; (ii) presence of HCl; (iii) presence of carbonyl and hydroxyl groups to allow hydrogen bonding; (iv) presence of two (hetero)aromatic rings at both sides of the molecule. The hydrogen bonding involving amide carbonyl, hydroxyl at 9th position and, very probably, ammonium N-H+ and Cl- anion appear to be responsible for the formation of infinite molecular chains required for the first step of gel formation. Subsequent lateral cooperation of molecular chains into fibers occured, presumably, due to the aromatic pi-pi-stacking interactions. sc-CO2 drying of the gels gave rise to aerogels morphology different from that of air dried samples.

A graphene-containing LDH was prepared by re-hydration of the oxides produced by the calcination of an organic LDH. While the memory effect is a widely recognized effect on oxides produced by inorganic LDHs, it is unprecedented from the calcination/re-hydration of organic ones. Different temperatures (400, 600 and 1100 °C) were tested, on the basis of thermogravimetric data. Water instead of a carbonate solution was used for the re-hydration, with CO₂ available from water itself and/or air to induce a slower process with an easier and better intercalation of the carbonaceous species within the layers. The samples were characterized by X-ray Powder Diffraction (XRPD), IR and Raman spectroscopy and scanning electron microscopy (SEM). XRPD indicate the presence of carbonate LDH mixed with a layered phase with a larger d-spacing. IR confirmed that the prevailing anion is carbonate, coming from the water used for the re-hydration and/or air. Raman data indicated the presence of low-ordered graphenic species moieties and SEM the absence of separated graphene of graphitic sheets, suggesting an intimate mixing of the carbonaceous phase with reconstructed LDH. Organic LDHs gave better memory effect after calcination at 400 °C. Conversely, the graphenic species are observed after rehydration of the sample calcined at 600 °C with a reduced memory effect, demonstrating the interference of the carbonaceous phase with LDH reconstruction and the bonding with LDH layers to form a graphene-LDH nanocomposite.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

The SARS-CoV-2 virus, which is responsible for the COVID-19 pandemic which emerged and spread, has sparked intense research on its spike protein, which is essential for viral entrance into host cells. Viral reproduction and transmission, host immune response regulation, receptor recognition and host cell entrance mechanisms, as well as structural and functional effects have all been linked to mutations in the spike protein. Spike protein mutations can also result in immune evasion mechanisms that impair vaccine effectiveness and escape, and they are linked to illness severity and clinical consequences. Numerous studies have been conducted to determine the effects of these mutations on the spike protein structure and how it interacts with host factors. These results have important implications for the design and development of medicines and vaccines based on spike proteins as well as for the assessment of those products' efficiency against newly discovered spike protein mutations. The paper gives a general overview of how spike protein mutations are categorized and named, as well as the genomic and phylogenetic techniques that have been used to track their genesis and dissemination. Additionally, it looks at the links between spike protein mutations and clinical outcomes, illness severity, unanswered problems, and future research prospects. Additionally, explored are the effects of these mutations on vaccine effectiveness as well as the possible therapeutic targeting of spike protein mutations.

An overview of the chemical compounds forming the rare smectic T phases is cited with references to the historical context. Thermodynamics (transition temperatures, enthalpies) along with the factors (stereochemical constraints, electrostatic interactions, aliphatic chain stacking, intermolecular forces) contributing to the adoption of tetragonal scaffolds are also discussed. Characteristic optical microscopy textures and x-rays diffraction patterns are presented. In parallel, a comparison of the geometrical parameters such as distances between atoms, molecular areas, volumes, and lattice parameters with the closest two-dimensional and three-dimensional organizations, is performed.

Though early-stage colorectal cancer has a high 5-year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments. We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair proficient patients to immunotherapy.

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.

Abstract: : 2,3-dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD), molecular formula =C8H4N4O10 is a completely nitrated in aromatic ring 1,4-benzodioxane derivative. The con-venient method of TNBD synthesis was developed (yield=81 %). The detailed structure of this compound has been investigated by X-ray crystallography. The results of differential thermal analysis (DTA) obtained with twice re-crystallized material showed onset at 247 and isoterm at 288 0C, with further total degradation at 300 0C. The experimental density 1,85 g/cm3 of TNBD was determined by X-ray crystallography. The spectral properties of TNBD (NMR, FT-IR, Ra-man) were explored. The detonation properties of TNBD calculated by EXPLO 5 code was slightly superior in comparison to standard high energy material - tetryl (detonation velocity of TNBD - 7727 m/s; detonation pressure - 278 kbar; tetryl – 7570 m/s and 226.4 kbar at 1.614 g/cm3, or 260 kbar at higher density - 1.71 g/cm3. The obtained preliminary results might suggest TNBD can be a potential thermostable high energy and density material (HEDM).

The new diprotic ligand 3,5-di-tert-butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H2(3,5-t-Bu2)-sal4eT, exists as the thio-keto tautomer and adopts the E-configuration with respect to the imine double bond as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc)2·H2O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me2-phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn) concomitantly with tautomerization and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5-t-Bu2)-sal4eT}(2,9-Me2-phen)] (1) and [Cu2{3,5-t-Bu2)-sal4eT}2(phen)] (2). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accord with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence there is a disparity between its two Cu–N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ4 = 0.082) and the other distorted square pyramidal (τ5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.

The average sizes \ {\bar{L}}_{i\ } and their dispersion W_i along the i-th axis of crystallites in powders are used to determine the X-ray diffraction sizes, D_{i\ XRD}, averaged over crystallite columns within the BWA method. Numerical calculations have been carried out for an orthorhombic lattice of crystallites, such as LiFePO4, NMC, having Lamé's g-type superellipsoid shape. For Lognormal distributions, the analytical expression for the normalized coefficient Kn is found and includes two constants. The first K_{g,0} is a constant at W→0, the second K_g is a constant depending on the g -type shape. The dependences of D_{i\ XRD} are also calculated for Normal distribution. A fairly simple equation can be obtained as a result of analytical transformations in the framework of experimentally validated approximations. However, a simpler way is to carry out numerical computer calculations with subsequent approximation of the calculated curves. Using the obtained analytical expressions to control technologies from nuclear fuel to cathode materials will improve the efficiency of flexible energy network especially storage in autonomous and standby power plants.

It is well known that fiber sizing is one of the most important component in the manufacturing of composites, and it does affect the mechanical properties including strength and stiffness. In this work, the influence of fiber sizing levels on the mechanical properties of carbon fibers (CF) is reported at room temperature by using single fiber tensile testing (Favimat+), single fiber pullout testing (SFPO), and interfacial elemental analysis using X-ray photoelectron spectroscopy (XPS). Standard modulus of CF (7±0.2 μm in diameter) were sized using two Michelman commercially available sizing formulations. The average solid content for each sizing formulation is 26.3 ± 0.2% and 34.1 ± 0.2%, respectively. HEXION RIMR 135 with curing agent RIMH 137 was used as a model thermoset epoxy matrix during the SFPO measurements. A predictive engineering fiber sizing methodology is also developed. Sizing amounts of 0.5, 1, and 2 wt. % on the surface of the fiber is achieved for both sizing formulations. For each fiber sizing level, 50 single fiber tensile testing experiments and 20 single fiber pull-out tests were conducted. The ultimate tensile strength (σult) of the carbon fibers and the interfacial shear strength (τ_app) of the single fiber composite were analyzed. it is also investigated the effect of the sizing levels on the interfacial shear stress and the O/C (Oxygen/Carbon) surface composition ratio. As a result, generalized fiber sizing and characterization methods were established. The developed methods can be used to characterize the strength and interfacial shear strength of any man-made fibers with different sizing formulations and solid contents, irrespective of the matrix i.e. thermoset or thermoplastic.

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.

This article has been studied the synthesis of a new derivative of the known alkaloid cytisine contained in the seeds of plants of Cytisus laburnum L. and Thermopsis lanceolata R.Br., both of the Lugiminosae family. The new compound has been obtained from two biologically active compounds such as isoxazole and cytisine. It has been demonstrated that the reaction led to the single-stage method under very mild conditions to obtain some 4-[(3,5-dimethyl-1,2-oxazole-4-yl)sulfonyl]amides. This class of compounds is promising to obtain the new biologically active compounds. This article has examined in detail a structure with using the 1H and 13C NMR and two-dimensional NMR spectroscopy of COSY (1H-1H), HMQC (1H-13C) and NMVS (1H-13C). As a result, the homo- and heteronuclear spin-spin couplings should be established. The X-ray diffraction analysis has determined the spatial structure of a new derivative based on cytisine alkaloid. Thus, its hemorheological activity has been studied.

During the past few decades, hybrid nanoparticles (HNPs) based on a magnetic material and gold have attracted interest for applications in catalysis, diagnostics and nanomedicine. In this paper, magnetic CoFe2O4/Au HNPs with an average particle size of 10–20 nm decorated with 2-nm gold clusters were prepared using methionine as a reducer and an anchor between CoFe2O4 and gold. The obtained nanoparticles were studied by X-Ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectroscopy and X-Ray photoelectron spectroscopy (XPS) and UV-Vis spectroscopy techniques. The TEM images of the HNPs obtained after one, six and ten gold deposition cycles showed that the surface of cobalt ferrite was covered with gold nanoclusters, which slightly increased with an increase in the number of gold deposition cycles (from 2.12 ± 0.15 nm after one cycle to 2.46 ± 0.13 nm after ten cycles) without any change in surface density. The magnetic measurements showed that the obtained HNPs possessed typical ferrimagnetic behaviour, which corresponds to that of CoFe2O4 nanoparticles. The toxicity evaluation of the synthesised HNPs on Chlorella vulgaris indicated that they can be applied to biomedical applications such as magnetic hyperthermia, photothermal therapy, drug delivery, bioimaging and biosensing.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

Lithium titanates are used in various applications, such as anode materials for lithium intercalation (Li4Ti5O12) or breeding materials in fusion reactors (Li2TiO3). Here, we report the formation of nano-crystalline lithium titanates by a mechanochemical approach and present a deeper insight into their structural characteristics by PXRD and solid-state NMR spectroscopy. The compounds were synthesized in a high energy planetary ball mill with varying milling parameters and different grinding tools. NaCl type Li2TiO3 (α-Li2TiO3) was formed by dry milling of lithium hydroxide with titania (rutile or anatase) and by a milling induced structure transformation of monoclinic β Li2TiO3 or spinel type Li4Ti5O12. Heating of mechanochemical prepared α Li2TiO3 induces a phase transformation to the monoclinic phase similar to hydrothermal reaction products, but a higher thermal stability was observed for the mechanochemical formed product. Microstructure and crystallographic structure were characterized by PXRD via Rietveld analysis. Detailed phase analysis shows the formation of the cubic phase from the various educts. A set of two lattice parameters for α Li2TiO3 was refined, depending on the presence of OH- during the milling process. An average crystallite size of less than 15 nm was observed for the mechanochemical generated products. The local Li environment detected by 6Li SPE MAS NMR revealed Li defects in the form of tetrahedral instead of octahedral site occupation. Subsequent adjustment of the structural model for Rietveld refinement leads to better fits, supporting this interpretation.

We proposed a so-called Beta Kumaraswamy Burr Type X distribution which gives the extension of the Kumaraswamy-G class of family distribution. Some properties of this proposed model were provided, like: the expansion of densi- ties and quantile function. We considered the Bayes and maximum likelihood methods to estimate the parameters and also simulate the model parameters to validate the methods based on dierent set of true values. Some real data sets were employed to show the usefulness and exibility of the model which serves as generalization to many sub-models in the elds of engineering, medical, survival and reliability analysis.

We proposed a so-called Beta Kumaraswamy Burr Type X distribution which gives the extension of the Kumaraswamy-G class of family distribution. Some properties of this proposed model were provided, like: the expansion of densities and quantile function. We considered the Bayes and maximum likelihood methods to estimate the parameters and also simulate the model parameters to validate the methods based on different set of true values. Some real data sets were employed to show the usefulness and flexibility of the model which serves as generalization to many sub-models in the field of engineering, medical, survival and reliability analysis.

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it has been around for centuries. The origin of cancer immunotherapy in modern medicine can be traced back to the initial reports of spontaneous regression of malignant tumors in some patients following an acute febrile infection, at the turn of the twentieth century. This review briefly revisits the historical accounts of immunotherapy, highlighting some of the significant developments in the field of cancer immunobiology, that have been instrumental in bringing back the immunotherapeutic approaches to the forefront of cancer research. Some of the topics covered are: Coley's toxin - the first immunotherapeutic; the genesis of the theory of immune surveillance; discovery of T-lymphocytes and dendritic cells and their roles; the role of tumor antigens; relevance of tumor microenvironment; anti-tumor (therapeutic) ability of Bacillus Calmette Guerin; Melacine - the first therapeutic vaccine engineered; theories of immunoediting and immunophenotyping of cancer; and Provenge – the first FDA approved therapeutic vaccine. In this review, head and neck cancer has been taken as the reference tumor, for narrating the progression of cancer immunobiology, particularly, for highlighting the advent of immunotherapuetic agents.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

PitNETs, although typically benign, comprise a small percentage of therapy-resistant aggressive, occasionally metastatic tumors, underpinning a need to identify novel therapeutic targets. PitNETs carry few mutations but associate with conditions that promote alternative splicing as an oncogenic alternative and express the TrkA neurotrophin receptor, which exhibits oncogenic alternative TrkAIII splicing in other tumors. Alternative TrkAIII splicing was assessed by RT-PCR in 53 PitNETs and compared to HIF1a, HIF2a, SF3B1, SRSF2, U2AF1 and JCPyV large T antigen mRNA expression, unconventional Xbp1 splicing, SF3B1 mutation, and TrkA isoform(s) immunoreactivity by confocal immunofluorescence (IF). Alternative TrkAIII mRNA splicing was detected in all invasive PitNET phenotypes, was significantly elevated in invasive compared to non-invasive PIT1 PitNETs, relatively high in invasive and non-invasive SF1 and TPIT PitNETs, and was associated with IF consistent with intracellular TrkAIII activation but not with hotspot SF3B1 mutations, altered SF3B1, SRSF2 and U2AF1 splice factor mRNA expression, JCPyV large T antigen expression or unconventional Xbp1 splicing. A potential role for hypoxia in TrkAIII mRNA splicing was supported by significant elevation of HIF2a mRNA expression in invasive PIT1 PitNETs. These data demonstrate that alternative TrkAIII splicing, potentially promoted by hypoxia, occurs frequently in PitNETs and may associate with IF consistent with intracellular TrkAIII activation, supporting a potential role for TrkAIII in PitNET pathogenesis and progression, identifying TrkAIII as a novel potential target in refractory PitNETs.

Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional B cells. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death-1 (PD-1) are upregulated in patients with CLL and may correlate with prognostic markers such as beta-2 microglobulin (B2M). The aim of this study was to evaluate the levels of immune checkpoints on B-cell subsets and to further correlate them with B2M levels in patients with CLL. We recruited 21 patients with CLL and 12 controls. B cell subsets and the levels of immune checkpoint expression were determined using conventional multi-color flowcytometry. Basal levels of B2M in patients with CLL were measured using an Enzyme-linked immunosorbent assay. Patients with CLL had increased levels of activated B cells when compared to the control group, p< 0.001. The expression of PD-1 and CTLA-4 were increased on activated B cells and memory B cells, p< 0.05. There were no associations between B2M levels and the measured immune checkpoints on B cell subsets, after adjusting for sex and age. African patients with CLL express elevated levels of PD-1 and CTLA-4 immune checkpoints on activated and memory B cell subsets. However, there is no correlation between these immune checkpoint expressions and B2M levels.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using immunohistochemical analysis of the expression of anti-gens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells, and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET, in general, is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers) able to identify specific immune system targets are under investigation in pre-clinical and clinical settings. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells, and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

By using the method of high-temperature solid-phase reaction, the new piezoceramic SrBi2Nb2-2xWxSnxO9 was obtained, in which partial substitution of niobium (Nb) atoms with Sn4+ and W6+ atoms in the compound SrBi2Nb2O9 took place in the octahedra of the perovskite layer (B-position). X-ray diffraction studies have shown that these compounds are single-phase SrBi2Nb2-2xWxSnxO9 (x = 0.1, 0.2) and two-phase SrBi2Nb2-2xWxSnxO9 (x = 0.3, 0.4), but they all had the structure of Aurivillius – Smolensky phases (ASPs) with similar parameters of orthorhombic elementary cells, corresponding to the spatial group A21am. The dependences on temperature of the relative permittivity ε/ε0 and the tangent of the loss angle tan d at different frequencies were measured.

- Early and accurate detection of pneumonia from chest X-ray images is crucial for timely treatment and patient care. In study presents a robust computational framework leveraging the CheXnet algorithm, a deep learning model, to identify pneumonia from chest X-rays. Developed a neural network architecture trained on a substantial dataset of chest X- ray images labeled as 'Normal' and 'Pneumonia'. The user- friendly interface of the system allows for seamless uploading of images, with the model subsequently providing predictions, a confusion matrix, accuracy metrics, and layer activations visualizations. The algorithm's performance was rigorously evaluated, with a confusion matrix indicating a high number of true positives and true negatives. Specifically, the model detected pneumonia with an accuracy of 92.47%, as shown by the results displayed in the system's interface. The precision, recall, and F1-score for pneumonia detection were 0.90, 0.96, and 0.93 respectively, with the overall system achieving an accuracy of 0.91 across the test set of 624 images. Visualizations of the neural network layers reveal the complex feature mappings the model uses to differentiate between normal and pathological findings. These insights could be vital for enhancing the interpretability of deep learning models in medical diagnostics. The Results indicate that the CheXnet-based neural network is a promising tool for automating pneumonia detection in clinical settings, which can assist radiologists in the diagnostic process and potentially improve patient outcomes through earlier intervention.

Fragile X syndrome (FXS) is an intellectual developmental disorder characterized, inter alia, by deficits in short-term processing of neural information such as sensory processing and working memory. The primary cause of FXS is the loss of fragile X messenger ribonucleoprotein (FMRP), which is profoundly involved in synaptic function and plasticity. Short-term synaptic plasticity (STSP) may play important roles in functions that are affected by FXS. Recent evidence points to a crucial involvement of presynaptic calcium sensor synaptotagmin-7 in STSP. However, how the loss of FMRP affects STSP and synaptotagmin-7 have been insufficiently studied. Further-more, males and females are affected differently by FXS, but the underlying mechanisms remain elusive. The aim of the present study is to investigate possible changes in STSP and the expres-sion of synaptotagmin-7 along the hippocampus of adult males and females in the Fmr1 knock-out (KO) rat model of FXS. We found that paired-pulse ratio and frequency facilita-tion/depression, two forms of STSP, as well as the expression of synaptotagmin-7, are normal in adult KO males, but paired-pulse ratio is increased in the ventral hippocampus of KO females. Furthermore, we found no gender-related but robust region-dependent difference in STSP. AM-PA receptors are similarly expressed in the two hippocampal segments of the two genotypes and in both genders. Also, basal excitatory synaptic transmission is higher in males compared with females. Interestingly, we found more than twofold higher levels of synaptotagmin-7, not syn-aptotagmin-1, in the dorsal compared with the ventral hippocampus in males of both genotypes and in wild type females. These results point to the susceptibility of the female ventral hippo-campus to FMRP loss. Importantly, the different levels of synaptotagmin-7 that parallel the higher score of synaptic facilitation in the dorsal vs ventral hippocampus suggest that synapto-tagmin-7 may play a pivotal role in defining the striking difference in STSP along the long axis of the hippocampus.

Taking into consideration the arising resistance towards the currently available antimycobacterial, there is still an unmet need for the development of new chemotherapeutic agents to combat the infectious agent. This study presents the X-ray single-crystal analysis to verify the structure of leading sulfonyl hydrazone 3b, which have proven their potent antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC value of 0.0716 μM, respectively, low cytotoxicity and very high selectivity indexes (SI=2216) and fully characterized by NMR and HRMS methods. Furthermore, this study assessed the ex vivo antioxidant activity, acute and subacute toxicity, and in vitro inhibition capacity against enoyl-ACP reductase of hydrazones 3a and 3b, as 3a was identified as the second leading compound in our previous research. Compared to isoniazid, compounds 3a and 3b demonstrated lower acute toxicity for intraperitoneal administration, with LD50 values of 866 and 1224.7 mg/kg, respectively. Subacute toxicity tests, involving the repeated administration of a single dose of the test samples per day, revealed no significant deviations in hematological and biochemical parameters or pathomorphological tissues. The compounds exhibited potent antioxidant capabilities, reducing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH). Enzyme inhibition assays of the sulfonyl hydrazones 3a and 3b with IC50 values of 18.2 µM and 10.7 µM, respectively and molecular docking studies revealed enoyl acyl carrier protein reductase (InhA) as the possible target enzyme of the compounds to show their antitubercular activities. In conclusion, the investigated sulfonyl hydrazones display promising antitubercular drug-like properties and warrant further investigation.

The structural evolution and phase composition of multi-block thermoplastic polyurethanes, with different nature of the soft segments based on poly(butylene adipate) (PBA), were analyzed during in-situ thermal treatments. A combination of synchrotron small- and wide-angle X-ray scattering, differential scanning calorimetry, thermogravimetric analysis, and FTIR spectroscopy was used to determine the influence of macrodiol nature and crystallization conditions on the polymorphic behavior of PBA. Using a new synthesis scheme, a relatively high degree of crystallinity for urethane blocks was achieved, which depends on the diisocyanate type in the structure of the soft segment. The hard segment domains impose geometrical constraints on PBA, thereby altering its crystallization process compared to the neat oligomer. Thus, crystallization after annealing at a low temperature (80 °C) is fast, predominantly yielding a metastable β-phase. When heated to 180 °C, which is higher than the hard-segment melting temperature, a phase-separated structure is observed. Subsequent crystallization is slower, favoring the formation of the stable α-PBA modification. The phase separation can be observed even after the hard block melting. A notably slow crystallization from an isotropic melt was documented after the disruption of phase separation at 230 °C.

The X-ray induced spin crossover transition of an Fe(II) molecular thin film in the presence and absence of a magnetic field has been investigated. The thermal activation energy barrier in the soft X-ray activation of the spin crossover transition for [Fe{H2B(pz)2}2(bipy)] molecular thin films is reduced in the presence of an applied magnetic field, as measured through X-ray absorption spectroscopy at various temperatures. The influence of a 1.8 T magnetic field is sufficient to cause deviations from the expected exponential spin state transition behavior that is measured in the field free case. We find that orbital moment diminishes with increasing temperature, relative to the spin moment in the vicinity of room temperature.

Planktonic foraminiferal biomineralization intensity, reflected by their shell calcite mass, affects global carbonate deposition and is known to follow the climate cycles by being increased during glacial stages and decreased during interglacial ones. Here we measure the dissolution state and the mass of the shells of the planktonic foraminifera species Globigerina bulloides from a Tropical Eastern North Atlantic site over the last two glacial-interglacial climatic transitions and we report no major changes in plankton calcite production with the atmospheric pCO2 variations. We attribute this consistency in foraminifera calcification to the climatic and hydrological stability of the tropical regions. We however recorded increased shell masses midway through the penultimate deglaciation (Termination II). In order to elucidate the cause of the increased shell weights we performed δ18O, Mg/Ca and μCT measurements on the same shells from a number of samples surrounding this event. We find that shells of increased mass are internally contaminated by sediment infilling and that shell weights are responding to local hydrographic changes.

We put forward a co-axial pump(optical)-probe(X-rays) experimental concept and show performance of the optical component. A Bessel beam generator with a central 100 micrometers-diameter hole (on the optical axis) was fabricated using femtosecond (fs) laser structuring inside a silica plate. This flat-axicon optical element produces a needle-like axial intensity distribution which can be used for the optical pump pulse. The fs-X-ray free electron laser (X-FEL) beam of sub-1 micrometer diameter can be introduced through the central hole along the optical axis onto a target as a probe. Different realisations of optical pump are discussed. Such optical elements facilitate alignment of ultra-short fs-pulses in space and time and can be used in light-matter interaction experiments at extreme energy densities on the surface and in the volume of targets. Full advantage of ultra-short 10 fs X-FEL probe pulses with fs-pump(optical) opens an unexplored temporal dimension of phase transitions and the fastest laser-induced rates of material heating and quenching. A wider field of applications of fs-laser-enabled structuring of materials and design of specific optical elements for astrophotonics is presented.

Jumping side volley has created breathtaking moments and cherished memories for us. Regrettably, a scientific study on the skill has not been found in literature. Relying on talent of athletes to improvise on the fly can hardly be considered a viable learning strategy. This study targets to fill the gap by quantifying factors contributing to develop its coaching method. Using 3D motion capture (12-cameras, 200Hz) and full-body biomechanical modeling, our study aimed to identify elements that govern entrainment of the skill by examining jumping, kicking and falling phases of its execution. Given the rarity of players who have acquired this skill, we found five subjects for the study. Twenty-three trials were captured and quantified. The results unveil the following key elements: 1) the control of trunk rotation during the jumping, 2) the angle between thighs upon take-off, 3) the whip-like control of the kicking leg during airborne, 4) timing between ball motion and limbs’ coordination, and 5) damping mechanism during falling. An accurate kick can only be achieved through repetitive training. This underlines the need for athletes to master a safe landing technique that minimizes risk of injury during practice. Therefore, training should begin with learning a safe falling technique.

In fuel-cell technological development, one of the most important objectives is to minimize the amount of Pt, the most employed material as oxygen reduction and methanol oxidation electro-catalyst. In this paper we report the synthesis and characterization of Te nanotubes (TeNTs) decorated with Pt nanoparticles, readily prepared from stirred aqueous solutions of PtCl2 containing a suspension of TeNTs and ethanol acting as a reducing agent, avoiding the use of any hydrophobic surfactants as capping stabilizing substance. The as obtained TeNTs decorated with Pt nanoparticles (TeNTs/PtNPs) have been fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area diffraction patterns (SAD), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV). We demonstrate that the new material can be successfully employed in fuel cell either as anodic (for methanol oxidation reaction) and cathodic (for oxygen reduction reaction) electrode with high efficiency in terms of related mass activities and on-set improvement. Remarkably, the cell operates in aqueous electrolyte buffered at pH 7.0, thus avoiding acidic or alkaline conditions that may lead e. g. to Pt dissolution (at low pH) and paving the way for the development of biocompatible devices and on chip fuel cells.

2-(Adamantan-1-yl)-2H-isoindole-1-carbonitrile (1) has been identified as a neurobiological fluorescent ligand that may be used to develop receptor and enzyme binding affinity assays. Compound 1 was synthesised using an optimised microwave irradiation reaction and crystallised from ethanol. Crystallization occurred in the orthorhombic space group P212121 with unit cell parameters: a = 6.4487(12) Å, b = 13.648(3) Å, c = 16.571(3) Å, V = 1458(5) Å3, Z = 4. Density functional theory (DFT) (B3LYP/6-311++G (d,p)) calculations of 1 were carried out. Results showed that the optimised geometry is similar to the crystal structure parameters with a root-mean-squared deviation of 0.143 Å. Frontier molecular orbital energies and net atomic charges are discussed with a focus on potential biological interactions. Docking experiments within the active site of the neuronal nitric oxide synthase (nNOS) protein crystal structure were carried out and analysed. Important binding interactions between the DFT optimised structure and amino acids within the nNOS active site were identified that explain the strong NOS binding affinity reported. Fluorescent properties of 1 were studied using aprotic solvents of different polarities. Compound 1 showed the highest fluorescence intensity in polar solvents with excitation and emission values of 336 nm and 380 nm, respectively.

A metastable β-Ti alloy, Ti–10V–3Fe–3Al (wt.%), was subjected to thermos-mechanical processing including the compression test at 725°C, which is below the β transus temperature (780°C), and at strain rate of 10-3s-1. The presence of phases was determined using transmission electron microscopy and X-ray diffraction. Although the dynamic recovery took place together with slip, both deformation-induced α˝ martensite and ω were detected as other operating mechanisms for the first time in metastable-β Ti alloys deformed in α+β region. The volume fraction of stress-induced α˝ was higher than that of the same alloy deformed at room temperature due to higher strain applied. Stress-induced twinning was not operational, which could be related to the priority of slip mechanism at high temperature resulted from thermally-assisted nucleation and lateral migration of kink-pairs.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

Two ferrocene derivatives, namely, 1,2-(tetramethylene)-ferrocene and 1,2,1’,2’-bis(tetramethylene)-ferrocene, were synthesized in a four-step reaction sequence starting from ferrocene. Friedel-Craft acylation of ferrocene with succinic anhydride gave mono- or bis(3-carboxypropinoyl)ferrocene depending on the stoichiometry of succinic anhydride. The reduction of the keto groups to methylene, followed by ring-closing using trifluoroacetic anhydride gave 1,2-(α-ketotetramethylene)-ferrocene or 1,2,1’,2’-bis(α-ketotetramethylene)ferrocene. The diastereomeric mixture of the latter diketones was separated by column chromatography, characterized by single-crystal X-ray analysis, and assigned their stereochemistry. Reduction of the keto groups to methylene under Clemmensen conditions gave homoannular mono- or bis(tetramethylene) ferrocene derivatives. The molecular structure of 1,2-(tetramethylene)-ferrocene revealed that the ipso carbon atoms of the cyclopentadienyl group are 0.023(3) Å farther away from Fe(II) compared to the remaining three carbon atoms. Both complexes exhibit lower half-wave oxidation potentials than ferrocene, possibly due to the electron-releasing effects of the tetramethylene bridges.

Categorical data analysis of 2 x 2 contingency tables is extremely common, not least because they provide odds and risk ratio statistics in medical research. The χ2 test is most often used, although some researchers use the likelihood ratio test (LRT). Does it matter which test is used? This paper argues that the LRT rather than the χ2 test should be used when we are interested in testing whether two variables are independent, as is typically the case. In contrast, the χ2 test should be reserved for where the data appear to match too closely a particular hypothesis (e.g. the null hypothesis), as may occur in the investigation of data integrity. Finally, it is argued that the evidential approach provides a consistent and coherent way in which tests can be made for each of these situations.

Advanced composite materials have drawn significant interest in the last years as an alternative to traditional materials due to their higher performance. However, industry struggle to provide low-cost, higher occupational safety, lower footprint with composites, making them suitable for holistic analyses. Therefore, the material design becomes an essential element that can impact the competitiveness, particularly in terms of productivity, circularity, safety, sustainability, and quality of the value chain. The Material Design-for-eXcellence is a state-of-art methodology for material performance multi-dimensional assessment along its life cycle phases, either useful to support ma-terial selection for new products or also to new material design support optimizing resource effi-ciency. In this methodology, the material behaviour and its multiple characteristics assessment, and the manufacturing processes efficiency are evaluated. The framework considers the analogy of product design holistic approaches, as Lean Design-for-X, to organize and assess the mul-ti-dimensional performance for each “X” Material Property. In this work, it was possible to observe that the bio-based composites solutions could be a good sustainable alternative for several sectors. Every day researchers are creating more new materials, having a diversity of properties at different scales, Material Design-for-eXcellence must also in the near future consider other factors. Hence, additional studies are thus foreseen to explore and develop this new tool.

Panoramic and periapical radiograph tools help dentists diagnose the most common dental diseases. Generally, dentists identify dental caries manually by inspecting X-ray images. However, due to their heavy workload, or poor image quality, dentists may sometimes overlook some unnoticeable dental caries, which may ultimately hinder the patient treatment. The purpose of this study was to develop an algorithm that classifies the teeth X-Ray images into three categories of “Normal”, “Caries”, and “Filled”. Our study used a dataset of 116 patients and 3712 single teeth images for training, validation and testing. Images were pre-processed using a sharpening filter and an intensity color map. We used a pre-trained transfer learning model, the NASNetMobile, which served as the feature extractor and the Convolutional Neural Network (CNN) model served as the classifier. The training dataset had a “Recall” of 0.92, 0.90 and 0.91 for “Normal”, “Caries” and “Filled” respectively and the test dataset had a “Recall” of 0.86, 0.81 and 0.85 for “Normal”, “Caries” and “Filled” respectively. The classification of the teeth X-Rays was successful and can be valuable for dentist as the artificial intelligence algorithm can serve as a decision support tool to aid dentists when they need to diagnose dental treatment.

With the decline in fossil fuels, hydrogen-based alternatives provide a reliable and clean source for sustainable energy generation. In these endeavors, photochemical splitting for hydrogen production through tandem cells has been the source of much theoretical and experimental research in science. Much focus has been placed on interfacial band gap engineering as one of the most promising routes in the generation of hydrogen.This present work explores sputtering of n-silicon to form the active electrode in a n-Si | n-TiO₂ tandem cell and investigates the effect of variations in sputtering and post sputtering treatment parameters (rapid thermal annealing and long cycle annealing) for successful deposition of crystalline Silicon. The samples were successfully characterized via Raman Spectroscopy, X-ray Diffraction and Optical Transmission Spectroscopy to ascertain prevalent crystalline order and optical band gap, under different sputtering and post-sputtering conditions. Relevant conclusions were drawn to ascertain the best possible deposition parameters of n-Si for photocatalytic water splitting.

It is widely believed that the dramatic transformation of the spherical outflows of AGB stars into the extreme aspherical geometries seen during the planetary nebula (PN) phase is linked to binarity and driven by the associated production of fast jets and central disks/torii. The key to understanding the engines that produce these jets and the jet-shaping mechanisms lies in the study of objects in transition between the AGB and PN phases. I discuss the results of our recent studies with high-angular-resolution (with ALMA & HST) and at high-energies (with GALEX, XMM-Newton & Chandra) of several such objects, which reveal new details of close binary interactions and high-speed outflows. These include two PPNe (the Boomerang Nebula and IRAS16342-3814), and the late carbon star, V Hya. The Boomerang is notable for a massive, high-speed outflow that has cooled below the microwave background temperature, making it the coldest object in the Universe. IRAS16342 is the prime example of the class of water-fountain PPNe (very young PPNe with high-velocity H₂O masers) and shows the signature of a precessing jet. V Hya ejects high-speed bullets every 8.5 years associated with the periastron passage of a companion in an eccentric orbit. I discuss our work on AGB stars with strongly-variable high-energy (FUV, X-ray) emission, suggesting that these objects are in the early stages of binary interactions that result in the formation of accretion disks and jets.

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

The rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., which is known as “Golsebo” in Korea, has been traditionally used to treat various inflammatory conditions, including bone metabolism disorders. It relieves blood extravasation, stops bleeding, repairs broken bone tissue, treats bone fractures, and kills bacteria. Recently, D. fortunei-derived polysaccharides (DFP) have been identified as bioactive compounds that act against numerous human diseases. However, the molecular mechanism underlying the bone metabolism-improving effect of DFP has not been elucidated. In this study, we evaluated the modulatory effects of DFP on the differentiation of bone marrow-derived macrophages into osteoclasts. We performed tartrate-resistant acid phosphatase assays using DFP (different concentrations and molecular weights) to evaluate the degree of bone resorption in the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis of bone marrow-derived macrophages. DFP significantly inhibited RANKL-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP, and cathepsin K) expression. DFP has potential as a nutraceutical candidate for treating bone loss diseases, including osteoporosis in postmenopausal women.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

High temperature Ni-superalloys are limited by reliance on critical elements and complex processing steps. High entropy alloys (HEAs) have demonstrated stable single/dual phase microstructures with strong ordering tendencies. A dual phase (FCC+BCC) Al0.5Co0.5CrFeNi1.5Ti0.25 alloy (developed using CALPHAD) was tested for room and high temperature compression behavior. The microstructure mainly comprises of coarse ordered FCC(L12) surrounding decomposed lamellae of ordered FCC(L12) and BCC(L21) phases, which coarsened upon annealing at high temperature (1100 °C) into a bi-continuous structure of disordered FCC+BCC(B2). Additionally, cold rollability of the cast alloy increased from &lt;5% to ~40% after annealing, with a corresponding softening observed in room temperature compression mainly due to disordering of FCC and BCC phases. Peak flow stresses of 793.45MPa, 535.12MPa, and 324.40MPa were achieved at 800oC, 900oC, and 1000oC respectively for the high temperature annealed alloy.

The inability to delineate a unified physical ontology that accounts simultaneously for the laws of special relativity and the results of quantum experiments has been a defining problem in physics for more than 100 years. This analysis addresses the problem by positing an ontic, mixed ontology composed of a “discrete” 4D spacetime and a physical, ultra-high dimensional (3 x N) “Planck Space.” Together, Planck Space and the three spatial dimensions of 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the “Dual Ontology”). Critically, the Dual Ontology’s structure replaces 1) the continuous, differentiable manifold of 4D spacetime with a discrete 4D spacetime and 2) mathematical 3N configuration spaces with a physical (3 x N) Planck Space. Moreover, the Dual Ontology is structurally and dynamically predicated on the one-to-one mapping and identity between the discrete spatial units that simultaneously form 4D spacetime and Planck Space. The one-to-one mapping and identity of the discrete spatial units support an integrated quantum dynamics based upon the dynamic evolution of single and N-body quantum states in 4D spacetime in full compliance with the laws of special relativity and the instantaneous collapse of all quantum states in an ontic Planck Space, where special and general relativity and more generally, 4D spacetime’s laws of physics, do not apply.

The quest for surgical advancements regarding the enhancement of the submental and cervicofacial regions has witnessed a remarkable upsurge in recent years. Informed patients are actively seeking sophisticated plastic surgery techniques to achieve comprehensive rejuvenation in these specific areas. Common complaints expressed by these patients include sagging of the jawline, the emergence of deep perioral wrinkles, and the formation of "marionette lines" within the lower third of the face. Furthermore, the manifestation of age-related signs, including neck laxity, submental adipose accumulation, "witch's chin" deformity, and weakened platysma musculature, are common within this anatomical region. This literature review aims to summarize the recent technical improvements, historical evolution, indications, postoperative care, and challenges for facial rejuvenation of the lower third of the face and neck. Lastly, the application of minimally invasive procedures as part of a comprehensive approach to an aging face will also be discussed.

The quest for surgical advancements regarding the enhancement of the submental and cervicofacial regions has witnessed a remarkable upsurge in recent years. Informed patients are actively seeking sophisticated plastic surgery techniques to achieve comprehensive rejuvenation in these specific areas. Our clinical practice encounters an annual influx of approximately 400 patients, with 20% of them aged over 60, seeking facial rejuvenation encompassing the details of lower third of the face and neck. Common concerns expressed by these patients include sagging of the jawline, the emergence of deep perioral wrinkles, and the formation of "marionette lines" within the lower third of the face. Furthermore, the manifestation of age-related signs, including neck laxity, submental adipose accumulation, "witch's chin" deformity, and weakened platysma musculature, is frequently encountered within this intricate anatomical domain. This review aims to summarize the recent technical improvements, historical evolution, indications, postoperative care and challenges for facial rejuvenation of the lower third of the face and neck. Lastly, the application of minimally invasive procedures as part of a comprehensive approach to an aging face will also be discussed.

In this work, a novel single crystal (3-(4-chlorophenyl)-4,5-dihydroisoxazol-5-yl)methyl benzenesulfonate has been synthetized via a one-pot sequential strategy under sonication. A single crystal X-ray diffraction analysis was reported. In the crystal, a layer structure is generated by C—H···O and C—H···N hydrogen bonds. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H···H (28.9%), H···O/O···H (26.7%) and H···C/C···H (15.8%) interactions. The optimized structure calculated using density functional theory at the B3LYP/6–311 G+(d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap is 4.6548 eV.

Material identification based on R_value (transparency natural logarithm ratio of low-energy to high-energy) of line-scan dual-energy X-ray transmission (DE-XRT) has a good prospect for industrial application. Unfortunately, the DE-XRT signals before attenuation cannot be directly measured, whereas their precision is very important to R_value. Therefore, a context-based signal synthesis method which takes the filtered signals that remove high-frequency noises and retain low-frequency actual fluctuations as the reference value, and takes into account the vertical (forward/column) direction and horizontal (scanning/row) direction anisotropy of line-scan images was proposed. The vertical is a time series with continuity of signal trend; the horizontal is a spatial characteristic with the fluctuation synchronization within the same row signals. The special synthesis evaluations of curve synthesis difference and surface synthesis difference were also proposed. Experimental results show that the tow evaluations are both only about 0.0007, and it only takes 35 ms to complete the surface synthesis of 119×119 pixels on the CPU with 3.4 GHz main frequency. The presented method can achieve high signal synthesis precision and calculation real-time, so as to facilitate DE-XRT material identification. It can be extended to improve the precision of numerical synthesis in other line-scan uncomplete signals.

The Golgi apparatus (GA) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GA are implicated in a wide range of neurodegenerative diseases. GA defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GA regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GA during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GA? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GA will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GA in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HAADF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GA.

Adult X-linked hypophosphatemia (XLH) patients present with specific symptoms, including enthesopathies (e.g., ossification of the longitudinal ligament (OPLL), osteophytes around the large joint, and enthesopathy in the Achilles tendon), the development of severe secondary and tertiary hyperparathyroidism (SHPT/THPT) and the subsequent progression of chronic kidney disease (CKD). In addition, these patients exhibit the typical phenotypes of osteomalacia, such as pseudofracture and fracture in weight-bearing bones, odontitis, and tooth abscess. The mechanism underlying enthesopathy development is unknown; however, a common underlying mechanism among XLH and autosomal recessive hypophosphatemic rickets, ARHR1.2, due to mutations in PHEX, DMP1, and ENPP1, is assumed. Clarification of the pathogenesis and drug discovery for this complication is an urgent issue to address, as many adult XLH patients suffer subsequent debilitating nervus symptoms or impingement syndrome, and existing treatments are ineffective. Severe SHPT and THPT are associated with conventional therapy, including active vitamin D and phosphate supplementation, and complicated and careful adjustment of the dosage by experienced clinicians is required to avoid SHPT/THPT. Burosumab is a very effective therapy without risk for the development of SHPT/THPT. However, the indication of this drug should be carefully considered along with the cost-effectiveness, guidelines or recommendations and health care system of each country.

This paper extends the application of the ROTASE model for the formation of spiral arms of disc galaxies, questions and confusions from readers about this model are addressed. The optical trail effect behind the spiral arm rotation is the natural consequence of the model. The morphologies of ring-galaxies are classified into four categories: type I: single ring; type II: 8-shaped double ring; type III: 8-shaped double ring wrapped by a larger outer ring; type IV: single ring without spiral and bar. All four types of ring galaxies can be described by the ROTASE model. The ROTASE model predicts that the false impression of spiral arm rotating ahead of the galactic bar in the galaxy MCG+00-04-051 will change with time, it will look like a normal galaxy with about 30° to 40° bar rotation in the future and the galactic bar ends will look like rotating ahead of the spiral arms with further 10 ° to 15 °bar rotation. The formation of one arm galaxies is due to X-matter at one side of supermassive black hole is much stronger than other side. More evidence is found to support the explanation of the formation and the evolution of the Hoag’s object. The possible evolution of spiral pattern of galaxies is illustrated by UGC 6093. The winding of the Milky Way could be tighter in the future based on the ROTASE model.

Synthetic fuels play an important role in the defossilization of future aviation transport. To reduce the ecological impact of remote airports due to long range transportation of kerosene, a decentralized on-site-production of synthetic paraffinic kerosene is applicable, preferably as near-drop-in fuel or alternatively as blend. One possible solution for such a production of synthetic kerosene is the Power-to-Liquid process. The basic development of a simplified plant layout addressing the specific challenges of a decentralized kerosene production which differ from most current approaches for infrastructural well-connected regions is described. The decisive influence of the Fischer-Tropsch synthesis on the PtL process is shown by means of a steady-state reactor model which was developed in Python and serves as basis for further development of a modular environment able to represent entire process chains. The reactor model is based on reaction kinetics according current literature. The effects of adjustments of the main operation parameters on the reactor behavior are evaluated and the impacts on up- and downstream processes are described. The results prove the governing influence of the Fischer-Tropsch reactor on the PtL process and show its flexibility regarding the desired product fraction output, which makes it an appropriate solution for a decentralized kerosene production.

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

A smart city is a futuristic approach that evolves with new technologies. It can start as a simple community and evolve into future cities. In most developing countries, where the population growth is faster, and where the organization and the urbanization are slower, there is a serious need for a framework for progressive change towards sustainable cities. This article discusses the level of intelligence of smart city components and proposes indicators as well as a methodology for measuring intelligence based on the objectives to be achieved as well as a certain number of technical requirements and some cognitive processes implemented.

Biomimicry in additive manufacturing often refers to topology optimization and the use of lattice structures, due to the organic shape of the topology-optimized designs, and the lattices often looking similar to many light-weight structures found in nature such as trabecular bone, wood, sponges, coral, to name a few. Real biomimetic design however involves the use of design principles taken in some way from natural systems. In this work we use a methodology whereby high resolution 3D analysis of a natural material with desirable properties is “reverse-engineered” and the design tested for the purpose. This allows more accurate replication of the desired properties, and adaption of the design parameters to the material used for production (which usually differs from the biological material). One such example is the impact-protective natural design of the glyptodont body armour. In this paper we report on the production of body armour models in metal (Ti4Al4V) and analyze the resulting mechanical properties, assessing their potential for impact protective applications. This is the first biomimetic study using metal additive manufacturing to date.

Scientific knowledge evolves in small steps, with occasional backsteps to correct inaccuracies, all occurring within a competitive environment. This perspective for the first time looks at the history of latency-related RNA (LR-RNA) that was later renamed latency-associated transcript (LAT). At the 1986 International Herpesvirus Workshop (IHW) meeting in Leeds, England, Daniel L Rock and Anthony B Nesburn first reported the discovery of human herpes virus 1 (HSV-1) latency-related (LR)-RNA that is antisense to ICP0. Less than a month after the IHW meeting a paper was submitted to Science magazine and 8 months later appeared in print thanking “D. Rock for suggesting RNA complementary to the ICP0 message may be present in latently infected cells”. This perspective is not a review of LAT literature but intends to clarify the timeline of LAT discovery and subsequent breakthroughs such as reactivation, apoptosis, CD8+ T cell exhaustion, and LAT expression in different cell types detected during latency. While many review articles have been written about LAT since 1987, the most comprehensive and balanced review about LAT was written by Dr. David Bloom’s group (1). In this overview, I will discuss our original collaboration with Dr. Dan Rock and subsequent work that our group performed, which is still ongoing. Finally, I will discuss the controversies associated with LAT from its inception to current times.

The bi- or multi-nucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of EBV-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC) derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: i) to be of germinal center-derived B-cell origin, ii) to be EBV-negative to avoid EBV latency III expression, and iii) to support permanent LMP1 expression upon induction. These conditions are unified in the EBV-, Diffuse Large B-Cell Lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstuctive nanotechnology revealed spatial, quantititive and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, further progression during transition to RS-like cells, including progressive complexity of the karytotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed on diagnostic patient samples and correlate with clincal outcome. Moreover, in vitro signficant disturbance of the lamin AC/telomere interaction progressively occured. In summary, our research over the past three decades identifed cHL as the first lymphoid maligancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.

Since severe acute respiratory syndrome coronavirus (SARS-CoV)-2 emerged in December 2019, significant research has been conducted around the world to understand the virus- and vaccine-generated immune response, and to identify the drivers of severe coronavirus disease 19 (COVID-19). Although viral tropism is largely limited to the respiratory tract, SARS-CoV-2 infection can lead to severe COVID-19 disease, which is characterized by multiorgan failure and permanent cognitive disorders. The combined effects of virus-mediated inhibition of host antiviral mechanisms and the recognition of pathogen-associated molecules by pattern recognition receptors (PRRs) are the main drivers in the pathogenesis of severe disease. The innate immune system constitutes the first line of defense against SARS-CoV-2 by limiting the entry of the virus into the host cell, suppressing viral replication, detecting virus-infected cells, and accelerating the formation of the adaptive immune response. The adaptive immune system is composed of two basic cells, B and T cells, which serve different but complementary functions in viral infections. Although the critical role of adaptive immunity in clearing SARS-CoV-2 infection is well known, its function in the development of virus-induced immunopathogenesis remains poorly understood. The basic characteristic of the humoral immune response is the creation of specific antibodies to each foreign antigen encountered. Antibodies that sense pathogens are classified as neutralizing antibodies (nAbs) and non-neutralizing antibodies (non-nAbs) based on their capacity to neutralize pathogens and inhibit membrane fusion. While nAbs exert their activities by blocking ACE2-dependent viral entry into host cells and neutralizing pathogens, the functions of non-nAbs are often undetectable. The level of anti-SARS-CoV-2 antibodies in serum and mucosal tissues varies with the stage and severity of the COVID-19 infection. Although current COVID-19 vaccines elicit robust antibody responses, this effect decreases over time, due to the weakening of immunity and the emergence of novel variants that evade the antibody response, such as Delta and Omicron. SARS-CoV-2 may evade host innate immune surveillance by minimizing host recognition and interfering with cellular immune signaling. In this review article, the central role of host immune responses in the pathogenesis of COVID-19 and the effectiveness of COVID-19 vaccines, as well as the immune evasion strategies of SARS-CoV-2 are discussed in detail in the light of novel knowledge.