Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity which occur across the tumor microenvironment (TME). The goal of this study is to get insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis Lung Carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains - capillary and extracellular space. Anisotropy in tumor structure causes nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

In mountain communities like Sebei, Uganda, that are highly vulnerable to emerging and reemerging infectious diseases, community-based surveillance plays an important role in the monitoring of public health hazards. In this survey, we explored capacities of Village Health Teams (VHTs) in Sebei communities of Mount Elgon in undertaking surveillance tasks for emerging and reemerging infectious diseases in the context of a changing climate. We used participatory epidemiology techniques to elucidate VHTs’ perceptions on climate change and public health and assess their capacities in conducting surveillance for emerging and reemerging infectious diseases. Overall, VHTs perceived climate change to be occurring with wider impacts on public health. However, they have inadequate capacities in collecting sur-veillance data. The VHTs lack transport to navigate through their communities and have in-sufficient capacities in using mobile phones for sending alerts. They do not engage in reporting other hazards related with the environment, wildlife and domestic livestock that would ac-celerate infectious disease outbreaks. Records are not maintained for disease surveillance ac-tivities and the abilities of VHTs to analyze data are also limited. However, VHTs have access to platforms that can enable them to disseminate public health information. The VHTs thus need to be retooled to conduct their work effectively and efficiently through equipping them with adequate logistics and knowledge on collecting, storing, analyzing, and relaying data, which will improve infectious disease response and mitigation efforts.

The French-Swiss Professor in inductive philosophy Richard Avenarius (1843-1896), the father of empirio-criticism together with Ernst Mach, is one of the most underrated and misunderstood philosophers ever. It mostly depends upon his terminology, which displays an insurmountable difficulty. However, influenced by the most innovative proposals of his times of transition between the idealistic/rationalist legacies and the new Materialism/scientific interpretation of reality – i.e, by cultural evolutionism, linguistics, biomechanics, entropy/energy and, above all, by the newborn experimental psychology-, he produced a complete system of philosophy and innovative methods of investigation of the laws of knowledge. Hints (chunk, scrap, fragments) of his original ideas can be found not only in philosophers of mind after him - such as Gestalt, phenomenalism, behaviourism, functionalism and cybernetics, autopoiesis, dynamical systems theory, embedded/embodied mind, free-energy principle of the brain – but also in recent neuroscientific theories – nervous transduction, electric spikes, cracking of neural code, multisensory integration -. Our aim is to provide the first chronological English summary of his masterpiece, the “Kritik”, to give the possibility to the (almost) totally unaware English speakers to appreciate such a neglected and innovative thinker.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30-hour Hand Arm Bimanual Intensive Therapy (HABIT) and bimanual performance (activities and participation) in real-world using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30-hour HABIT program. Data was collected from bilateral wrist-worn accelerometers during 30-hours HABIT to quantify the movement intensity, and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in the hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situation in children with UCP.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

During mechanical ventilation, a disparity between flow, pressure or volume demands of the patient and the assistance delivered by the mechanical ventilator often occurs. Asynchrony effect and ventilator performance are frequently studied from ICU datasets or using commercially available lung simulators and test lungs. This paper introduces an alternative approach of simulating and evaluating patient-ventilator interactions with high fidelity using the electro-mechanical lung simulator xPULM™ under selected conditions. The xPULM™ approximates respiratory activities of a patient during alternating phases of spontaneous breathing and apnoea intervals while connected to a mechanical ventilator. Focusing on different triggering events, volume assist-controlled (V/A-C) and pressure support ventilation (PSV) modes were chosen to test patient-ventilator interactions. In V/A-C mode a double-triggering was detected every third breathing cycle leading to an asynchrony index of 16.67%, being classified as severe. This asynchrony causes a major increase of Peak Inspiratory Pressure PIP = 12.80 ± 1.39 cmH2O and Peak Expiratory Flow PEF = -18.33 ± 1.13 L/min when compared to synchronous phases of the breathing simulation. Additionally, events of premature cycling were observed during PSV mode. In this mode, the peak delivered volume during simulated spontaneous breathing phases almost doubles compared to apnoea phases. The presented approach demonstrates the possibility of simulating and evaluating disparities in fundamental ventilation characteristics caused by double-triggering and premature cycling under V/A-C and PSV ventilation modes. Various dynamic clinical situations can be approximated and could help to identify undesired patient-ventilation interactions in the future. Rapidly manufactured ventilator systems could also be tested using this approach.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 minute-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with 2 control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed.Reduced BRS in FM at baseline increased by 41% during two, ≈8 minute-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps<0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (P<0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic pain modulation. These processes seem to be linked by classical and operant conditioning.

The catalytically inactive caspase-8-homologous protein, c-FLIP, is a potent antiapoptotic protein highly expressed in various types of cancers. c-FLIP competes with caspase-8 for binding to the adaptor protein FADD (Fas-Associated Death Domain) following Death Receptors (DRs) activation by the ligands of the TNF-R family. As a consequence, the extrinsic apoptotic signaling pathway involving DRs is inhibited. Inhibition of c-FLIP activity in tumor cells might enhance DR-mediated apoptosis and overcome immune and anticancer drug resistance. Based on an in silico approach, the aim of this work was to identify, new small inhibitory molecules able to bind selectively to c-FLIP and block its anti-apoptotic activity. Using a homology 3D model of c-FLIP, an in silico screening of 1880 compounds from the NCI database (National Cancer Institute) was performed. Nine molecules were selected for in vitro assays, based on their binding affinity to c-FLIP and their high selectivity compared to caspase-8. These compounds selectively bind to the Death Effector Domain 2 (DED2) of c-FLIP. We have tested in vitro the inhibitory effect of these 9 molecules using the human lung cancer cell line H1703 overexpressing c-FLIP. Our results showed that 6 of these newly identified compounds efficiently prevent FADD/c-FLIP interactions in a molecular pull-down assay, as well as in a DISC Immunoprecipitation assay. Overexpression of c-FLIP in H1703 prevents TRAIL-mediated apoptosis, however, combination of TRAIL with these selected molecules signifi-cantly restored TRAIL-induced cell death by rescuing caspase cleavage and activation. Altogether, our findings indicate that new inhibitory chemical compounds efficiently prevent c-FLIP recruit-ment into the DISC complex, thus restoring caspase-8 dependent apoptotic cascade. These results pave the way to design new c-FLIP inhibitory compounds that may serve as anticancer agents in tumors overexpressing c-FLIP.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Catamaran hulls have always been associated with smaller vessels in naval engineering and construction. However, recent research results have shown that by considering specific criteria based on materiality, structure and functionality, they can be designed for a more complex industry, such as hydrofoil design. Among the challenges in this type of vessel, one of the most difficult variables is estimating the resistance to the advance in the function of the degree of uncertainty generated. This research focuses on optimising the drag of a sport sailing catamaran by implementing hydrofoils, through the application of computational fluid dynamics (CFD), at different speeds to demonstrate that it is possible to modify and improve the current appendages of this vessel.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a newly described condition. It has a spectrum of presentations related to hyperinflammation and cytokine storm. We report the first case of PIMS-TS in a child on established anti-Tumor Necrosis Factor-alpha (anti-TNF-α) therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6-weeks of daily fever with mucocutaneous, gastrointestinal, renal and hematologic involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia (up to 691 µ/L; normal 15-80 µg/L), C-reactive protein (CRP) (>100mg/L for >10 days, normal 0-5 mg/L), erythrocyte sedimentation rate (ESR) consistently >100mm/hr (normal 0-15 mm/hr), raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase (LDH), anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin (PUO) were negative. The condition was refractory to treatment with intravenous immunoglobulin (IVIG) but improved within 24hrs of high dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow up. Polymerase chain reaction (PCR) and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock or organ failure. It is postulated that prior anti-TNF-α therapy attenuated the disease course. Infliximab therapy may interfere with serology testing and produce false negative results. This case supports the need for investigation into infliximab as primary therapy for PIMS-TS.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Tidal stream energy is a renewable energy resource that might be developed to offset carbon emissions. A tidal energy demonstration (TED) area has been designated in Minas Passage, Bay of Fundy, for testing and installing marine hydrokinetic (MHK) turbines. Regulations require quantification of the potential for MHK turbine installations to harm local populations of marine animals. Here we use acoustic telemetry to quantify probability that post smolt Inner Bay of Fundy salmon encounter a turbine installation at the TED area. Previous work has quantified detection efficiency of Innovasea HR acoustic tags as a function of current speed and range from a moored HR2 receiver and also demonstrated that drifters carrying HR tags will be effectively detected when the drifter track crosses the array of HR2 receivers in Minas Passage. Salmon smolts were tagged and released in Gaspereau and Stewiacke Rivers, Nova Scotia, in order that the HR2 receiver array could monitor seaward migration of the post smolts through Minas Passage and particularly through the TED area. Presently we demonstrate methods by which tag signals detected by the HR2 array can be used to estimate the expected number of times that a post smolt would encounter a single near-surface MHK turbine installation during its seaward migration.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

The atomic structures of Zn and Na borophosphate glasses were studied by X-ray and neutron diffraction. Peaks assigned to the B−O, P−O, and O−O distances confirm that only BO4 units co-exist with the PO4 tetrahedra. The Zn−O and Na−O coordination numbers are found to be a little larger than four. The narrowest peaks of the Zn−O first-neighbor distances exist for the glasses along a line connecting the Zn(PO3)2 and BPO4 compositions (50 mol% P2O5) which is explained by networks of ZnO4, BO4, and PO4 tetrahedra with twofold coordinated oxygens. Calculated amounts of the available oxygen support this interpretation. Broadened peaks occur for glasses with lower P2O5 contents, consistent with the presence of threefold coordinated oxygens. The two distinct P−O peak components of the Zn and Na borophosphate glasses differ in their relative abundances which is interpreted by Na+ cations that coordinate oxygens in some P−O−B bridges, something not seen for the Zn2+ ions.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

Matter grows and self-assembles to produce complex structures such as virus capsids, carbon fullerenes, proteins, glasses, etc. Due to its complexity, performing pen-and-paper calculations to explain and describe such assemblies is cumbersome. Many years ago, Richard Kerner presented a pen-and-paper path integral approach to understand self-organized matter. Although successfully addressed many important problems including the yield of fullerene formation, the glass transition temperature of doped chalcogenide glasses, the fraction of boroxol rings in B2O3 glasses, the first theoretical explanation for the empirical recipe of window and Pyrex glass and the understanding of virus capsid self-assembly, still is not the primary choice when tackling similar problems. The reason lies in the fact that it diverges from mainstream approaches based on the energy landscape paradigm and non-equilibrium thermodynamics. In this context, a critical review is presented, demonstrating that the Richard Kerner method is, in fact, a clever way to identify relevant configurations. Its equations are simplified, common physical sense versions to those found in the energy landscape kinetic equations. Subsequently, the utilization of equilibrium Boltzmann factors in the transition Markov chain probabilities is analyzed within the context of local two-level energy landscape models kinetics. This analysis demonstrates that their use remains valid when the local energy barrier between reaction coordinate states is small compared to the thermal energy. This finding places the Richard Kerner model on par with other more sophisticated methods and, hopefully, will promote its adoption as an initial and useful choice for describing the self-agglomeration of matter.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n=148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Se-rum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤ 16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β= -0.018, 95% CI -0.033 to -0.003, P=0.022) and 0.048 SD (standardized β= -0.048, 95% CI -0.083 to -0.014, P=0.006), respectively. Additionally, the high serum 25OHD groups (> 95.9 nmol/L) had 0.038 SD (standardized β= -0.038, 95% CI -0.072 to -0.004, P=0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusion: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

Biological neural network (BNN) is the core brain for creature to accomplish its intelligent behaviors through unique network structure and mechanisms. It also inspires controlling human-designed autonomous agents including robots to generate more advanced intelligent behaviors by mimicking the neural control mechanism of creatures at a deeper and more interactive level. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of cellular synapse. The neural network simulation integrates computational programming and visualization of neurons and synapse connections of C. elegans, containing the specific controllable circuits summarization with their dynamic characteristics within the whole network. To illustrate its particular intelligent control capability in terms of robotics, we introduce the first innovative methodology for applying the BNN model to a 12-legged robot’s movement control based on the established numerical simulation platforms. We accomplished and designed two methods and corresponding encoding processes, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of BNN. Both simulation and experiment results indicate that the robot exhibits stronger autonomy and more intelligent moving performance under the control of BNN. We then summarized the contributions for digitalizing the C. elegans’ whole-brain neural network in real-time and utilizing it to control robot in a closed loop to validate its advanced intelligence control ability in terms of a scientific robot.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

The existences of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative bonds in the complexes formed by fullerene C60 with 1,2,5-chalcogenadiazoles, 2,1,3-benzochalcogenadiazoles and 1,2,4,5-chalcogenatriazoles, respectively. It was found that the N→C dative bonds are formed along with the formation of the N–Ch···C (Ch = S, Se, Te) chalcogen bonds. In the gas phase, from S-containing complexes through Se-containing complexes to Te-containing complexes, the intrinsic interaction energies become more and more negative, which indicates that the N–Ch···C chalcogen bonds can facilitate the formation of the N→C dative bonds. The intrinsic interaction energies are compensated by the large deformation energy of fullerene C60. The total interaction energies of Te-containing complexes are negative, while both of the total interaction energies of S-containing complexes and Se-containing complexes are positive. This means that the N→C dative bonds in the Te-containing complexes are more easily observed in experiments in comparison with those in the S-containing complexes and Se-containing complexes. This study provides a new theoretical perspective on the experimental observation of the N→C dative bonds in the complexes involving fullerenes. Further, the formation of stable N→C dative bonds in the complexes involving fullerenes can significantly change the properties of fullerenes, which will greatly simulate and expand the application range of fullerenes.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

Salmonella Typhimurium is a typical Gram-Negative bacterium associated with food-borne illness threatening public health. This pathogen is reported to have caused millions of infections and thousands of hospitalizations yearly in the United States alone. Salmonella Typhimurium has a sophisticated array of virulent factors, including its flagella, which contributes significantly to its pathogenicity. Cannabidiol (CBD), the non-psychoactive component of the cannabis plant, has attracted the interest of many researchers recently because of its antimicrobial properties. With the growing interest in exploring CBD’s antimicrobial properties, we, in this study, have delved into unravelling how prolonged exposure of Salmonella Typhimurium to CBD influences the expression of the flgA gene. We hypothesized that the exposure of Salmonella Typhimurium to CBD may result in flgA upregulation, causing the bacteria to withstand various stresses and potentially enhance its survival rates and pathogenicity. We have employed several assays, such as mRNA expression, motility assays, pH induction assays, nutrient starvation interventions, and biofilm analysis, to explore the influence of CBD on the pathophysiology of Salmonella Typhimurium. Our findings reveal that CBD-resistant strains exhibit enhanced resilience to extreme pH levels and motility and survive poorly under nutrient starvation, with more robust biofilm formation compared to the susceptible strains. The results contribute to the broader comprehension of CBD resistance mechanisms in bacteria. This work provides insight into the potential therapeutic interventions for controlling CBD-resistant bacterial infections. This study also underscores the essence of exploring novel alternative antimicrobial agents to tackle the ever-persistence of bacterial antibiotic resistance.

In this note, I analyze the data generated by M. Fodje's (2013) simulation programs "epr-simple" and "epr-clocked". They were written in Python and published on Github. Inspection of the program descriptions shows that they make use of the detection-loophole and the coincidence-loophole respectively. I evaluate them with appropriate modified Bell-CHSH type inequalities: the Larsson detection-loophole adjusted CHSH, and the Larsson-Gill coincidence-loophole adjusted CHSH (NB: its correctness is conjecture, we do not have proof). The experimental efficiencies turn out to be approximately eta = 81% (close to optimal) and gamma = 55% (far from optimal). The observed values of CHSH are, as they should be, within the appropriately adjusted bounds. Fodjes' detection-loophole model turns out to be very, very close to Pearle's famous 1970 model, so the efficiency is close to optimal. The model has the same defect as Pearle's: the joint detection rates exhibit signaling. Fodje's coincidence-loophole model is actually a clever modification of his detection-loophole model. Because of this, however, it cannot lead to optimal efficiency.

This article reevaluates the Woesean concept of crossing a ‘Darwinian threshold’ from pre-genomic communality, as prevailing in an ancestral ‘progenote’ state, to vertically stable lineages of autonomous and self-similar cells. This transition from collective trunk-line evolution to Darwinian speciation is dependent on the generation of modular organismal genomes. The same general principle should be valid at subcellular levels, allowing the emergence of semi-autonomous genomic agents, such as viruses and plasmid-carrying endogenous vesicles with organelle-like properties. As compartmentalized agents of endogenous nature could start with smaller genomes than those required for fully autonomous cells, it is conjectured that stable subcellular lineages emerged earlier than their cellular counterparts. Referring to the recent ‘pre-endosymbiont hypothesis’, it is proposed that free-living bacteria (the first ‘prokaryote’ cells) arose by ‘lineage escape’ from plasmid-bearing organelle-like compartments, evolving inside the internally complexifying ‘paracells’ of the progenote community. The double-membrane envelopes of diderm bacteria may have resulted from cell-biological processes facilitating cellular lineage escape. The later emergence of archaeal cells (resembling bacteria in ‘prokaryote’ appearance with unichromosomal genomes) and eukaryotic organisms (with compartmented cells and multichromosal genomes) can also be interpreted in terms of this modified progenote hypothesis. Conceivably, the multichromosomal genomes of eukaryotes were bundled in endogenous nuclear compartments to organize a ‘nuclear-cytoplasmic lineage’, which became vertically stable by perfecting mitosis/meiosis-like divisions and yet retained some intra-species population confluence by sexual division-fusion cycles.

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

Fe[C5H5N]2[N(CN)2]2 (1) was synthesized from a reaction of stoichiometric amounts of NaN(CN)2 and FeCl2·4 H2O in a methanol/pyridine solution. Single-crystal and powder diffraction show that 1 crystallizes in the monoclinic space group I2/m (no. 12), different from Mn[C5H5N]2[N(CN)2]2 (P21/c, no. 14) due to tilted pyridine rings, with a = 7.453(7) Å, b = 13.167(13) Å, c = 8.522(6) Å, β = 114.98(6)° and Z = 2. ATR-IR, AAS, and CHN measurements confirm the presence of dicyanamide and pyridine. Thermogravimetric analysis shows that π-stacking interactions of the pyridine rings play an important role in structural stabilization. Based on DFT-optimized structures, a chemical bonding analysis was performed using a local-orbital framework by projection from a plane-wave basis. The resulting bond orders and atomic charges are in good agreement with the expectations based on the structure analysis. SQUID magnetic susceptibility measurements show a high-spin state FeII compound with predominantly antiferromagnetic exchange interactions at lower temperatures.

The Great Reset has been presented by the World Economic Forum (WEF) in response to the COVID-19 pandemic in 2022 as a model through which a “stakeholder economy” would achieve “resilient, equitable and sustainable” economic, social and environmental goals. A more equitable distribution of resources, better working conditions, and ecological transitions are included in a social, economic and environmental reform agenda. This article raises the question of whether the Great Reset project should be interpreted as a “realistic utopia” and what is its reform potential. In an attempt to answer the question of whether the Great Reset as a realist utopia is consistent with the current state of science and philosophy, the article re-examines the idea of utopia in the light of recent philosophical and scientific approaches, such as critical realism in philosophy, so-cial systems theory in sociology and complexity theory in science. A comparative conceptual analysis is carried out and discussed introducing the idea of a realist utopia in Rawls' theory of justice as fairness. In the final discussion, some doubts are raised about the logical coherence, rigor of scientific theorizing, policy prescriptions, and predictive potential of the Great Reset emerging paradigm. It is concluded that utopian projects of radical reform can become realistic when they offer explanations of the deep structural changes that underlie social and economic evolution, drawing from these explanations the policy implications and prescription that can support struc-tural changes, rather than from assumed long-term effects of exogenous shocks or “black swan” events such as the COVID-19 pandemic.

The endocannabinoid system (ECS) is a complex neuromodulatory network in the human body that have enormous impact in developing the central nervous system, as well as modulates various physiological processes. The ECS is made up of anandamide, 2-arachidonoylglycerol (2-AG), which are responsible for the synthesis and degradation of endocannabinoids, and enzymes such as FAAH and MAGL ensures the precise control over endocannabinoid levels. The ECS relies on CB1 receptors found in the central nervous system (CNS), and CB2 receptors found in the peripheral nervous system and immune cells. Dysregulation of the ECS has been associated with several health conditions, prompting investigations into its association with phytocannabinoids to harness their therapeutic potential. The ECS is intricately linked with the nervous system, and it is known to modulate neuronal activities in the CNS, influencing pain and mood modulation. The ECS is also associated with neuropathies-peripheral nerve damage leading to symptoms such as weakness, numbness and pain as evidenced in diabetic neuropathy, Guillain-Barré Syndrome, carpal tunnel syndrome, peripheral neuropathy, and postherpetic neuralgia. The focus of this review is on the interplay between 2-arachidonoylglycerol and anandamide amidohydrolase in neuropathy, elucidating their roles in pain regulation, inflammation, and specific neuropathies. The knowledge generated is expected to have broad implications, providing comprehensive insights into neuropathic conditions and how to improve on them. Ultimately, this understanding may lead to more effective treatments and improved quality of life for individuals affected by these conditions.

The environment is seldom optimal for plant growth and changes in abiotic and biotic signals, including temperature, water availability, radiation and pests, induce plant responses to optimise survival. The New Zealand native plant species and close relative to Arabidopsis thaliana, Pachycladon cheesemanii grows under environmental conditions that are unsustainable for many plant species. Here we compare the responses of both plant species to different stressors (low temperature, salt and UV-B radiation) to help understand how P. cheesemanii can grow in such harsh environments. The stress transcriptomes were then determined and comparative transcriptome and network analyses discovered similar and unique responses within species between different stresses, and between the two plant species. A number of widely studied plant stress processes were highly conserved in A. thaliana and P. cheesemanii. However, in response to cold stress, Gene Ontology terms related to glycosinolate metabolism were only enriched in P. cheesemanii. Salt stress was associated with alteration of the cuticle and proline biosynthesis in A. thaliana and P. cheesemanii, respectively. Anthocyanin production may be a strategy to cope with UV-B radiation stress in P. cheesemanii only. These results allowed us to construct broad stress response pathways in A. thaliana and P. cheesemanii and identify possible novel plant strategies that help mitigate environmental stress.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Low temperature is a common biological abiotic stress in major cotton growing areas. Cold stress significantly affects the growth, yield and yield quality of cotton. Therefore, it is important to develop a more robust and cold stress tolerant cotton germplasms. Climate change and erratic climatic condition, plants have evolved various survival mechanisms, one of which induction of various stress responsive transcriptome factors, such as the C-repeat binding factor GthCBF4, which have been found to enhance cold tolerance in various plants. In this study detailed evaluation of the cotton C-repeat binding factor has been carried out. A total of29, 28, 25, 21, 30, 26 and 15 proteins encoded by the C-repeat binding factor were identified in G. herbaceum, G. arboreum, G. thurberi, G. raimondii, G. turneri, G. longicalyx and G. australe, respectively. Phylogeny evaluation revealed that the proteins were grouped into seven clades, with clade 1 and 6 being the largest. Moreover, majority of the proteins encoded by the genes were predicted to be located within. the nucleus, while some are distributed in other parts of the cell. Based on the transcriptome and RT-qPCR analysis, Gthu17439 (GthCBF4) was highly upregulated and was further validated through forward genetics. The Gthu17439 (GthCBF4) overexpressed plants showed a significantly tolerance to cold stress, with higher growth vigour compared to the wild types. The results showed that the Gthu17439 (GthCBF4) could be playing a significant role in enhancing cold stress tolerance in cotton and can be further exploited in developing a more cold stress tolerance cotton germplasm

Does the choice of proxy for stock market development matter? This paper suggests that the growth effect of stock market development is sensitive to the choice of proxy and using alternative financial development indicators have practically no influence on the results. We found that using either the stock market capitalization to GDP ratio or the stock market returns; have a positive and significant effect on growth. However, we cannot make same conclusion when one uses either the ratio of total value of trades on the major stock exchanges to GDP or stock market turnover ratio to proxy for stock market development as the coefficient on these variables were found to be statistically insignificant. The indexes extracted from principal component analysis confirm the sensitivity of the effect to the choice of proxy. This finding suggest that stock market development is a conceptual terms, thus, representing it with single indicators make it impossible to identify which stock market development indicators have a significant positive growth effects.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

To show that underlying Schmitt's account of fascist politics lies a Gnostic-like metaphysical dualism separating the realms of value and power. Contrary to the normative political tradition of the West, which defends an ethical politics, Schmitt - jurist and theorist of the Nazis - aligns himself with Machiavelli and Hobbes to defend realpolitik: where sovereignty is ultimately a function of the Dictator's will alone. This paper shows the contradiction within such a position, which criticizes values in politics but by its advocacy, and its defense of the Dictator's willing, relies on valuation, choice, and hence the ethical.

Autism spectrum disorder (ASD) is characterized by diverse patterns of social interaction, communication, and behavior. This study explores the application of clustering and stochastic migration models to visualize and understand the social and neural connectivity patterns associated with autism. The clustering model, with its strong internal connections and limited external connections, mirrors the tight-knit social groups and communication barriers often observed in individuals with autism. In contrast, the stochastic model, characterized by more dispersed connections and greater adaptability, represents the variability and flexibility seen in social interactions across typical individuals. By comparing these models, we can gain deeper insights into the unique challenges and strengths of individuals with autism, highlighting the importance of personalized interventions. Additionally, these models provide a visual framework for understanding the differences in brain connectivity patterns observed in autism, with implications for both behavioral and neural correlates. This study underscores the value of computational models in advancing our understanding of autism and guiding effective support strategies.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

Abstract: Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Glioblastoma is a highly aggressive brain tumor characterized by rapid growth, extensive infiltration, and poor prognosis. Understanding the complex interplay of biological processes driving glioblastoma progression is crucial for developing effective therapeutic strategies. In this study, we present a comprehensive mathematical model that incorporates key aspects of glioblastoma growth and dissemination, including tumor cell diffusion, angiogenesis, nutrient availability, molecular signaling pathways, and blood-brain barrier (BBB) interactions. The model is based on a system of coupled partial differential equations (PDEs) and ordinary differential equations (ODEs) that capture the spatiotemporal dynamics of tumor cell density, nutrient concentration, signaling molecule concentrations, and BBB integrity. We employ numerical simulation techniques, such as the finite difference method and the Runge-Kutta method, to solve the model equations and visualize the evolution of tumor growth and its associated biological processes. The model parameters are estimated using experimental data from the literature, and the model is validated against clinical observations. Furthermore, we perform a comprehensive sensitivity analysis to identify the key parameters that significantly influence tumor growth, diffusion, and dissemination. The sensitivity analysis reveals the relative importance of each parameter in driving glioblastoma progression and highlights potential targets for therapeutic interventions. Our computational framework provides a powerful tool for understanding the complex dynamics of glioblastoma growth and offers valuable insights into the underlying biological mechanisms. The model can be used to test hypotheses, predict tumor response to various treatment strategies, and guide the design of targeted therapies. The findings from this study contribute to the ongoing efforts in developing personalized treatment approaches for glioblastoma patients and improving their clinical outcomes.

Solar pasteurization, as a means of treating milk in remote rural areas without electrical power, is based on using solar energy to thermally inactivate pathogenic microorganisms at temperatures below the boiling point to maintain or improve milk quality. A solar milk pasteurizer of flat‐plate water‐heating glass acting as the solar collector, connected to a stainless-steel cylindrical milk vat, was constructed and evaluated in Navrongo, in the tropical savanna zone of Ghana, West Africa. The novel approach taken in this project is to integrate the solar collection and heat exchanger into a single unit using materials and fabrication techniques readily available in the developing world. The vat comprises a 1.5 mm thick stainless steel cylindrical tank, a 2.2 cm wide hot water jacket, and an outer layer of 5.0 mm thick aluminium foil insulation. Hot water produced by the collector was used for pasteurizing milk. The optimum quantity of milk that this device could pasteurize under the study conditions was 8 L. The device could pasteurize raw milk to a maximum temperature of 74 °C at 14:00 h GMT. The ambient temperature during the pasteurization ranged from 30 °C to 43 °C. The microbial analysis before and after the pasteurization was done, and the result shows that the total bacteria count before pasteurization was 6.6x10⁶ log CFU/mL per unit volume, and the total bacteria count after pasteurization was 1.0x10² log CFU/mL. By acceptable standards, the total bacteria count after pasteurization is within a safe range for consumption, and coliform counts were negative. The solar milk pasteurization system is cost-effective. Hence, it is appropriate for milk producers in arid pastoral areas without electricity to adopt the solar pasteurizer as an alternative to firewood as a fuel source for milk pasteurization. This approach can potentially create a cottage industry that may also play a crucial role as a water treatment technology that will improve the health of rural populations.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

This article explores the intricate dynamics of complexity and emergence through the lens of a graphical model representing hippocampal functions. Utilizing a series of overlapping curves that intersect at varying degrees and frequencies, we create a visual metaphor for the sophisticated processes to store information observed in the hippocampus. This model not only depicts the spatial and frequency-related interactions of these curves but also illustrates the emergent patterns that arise from these interactions. These patterns exemplify the principles of complexity and emergence, where the collective behavior of simple elements results in intricate and unexpected outcomes. This graphical representation serves as a bridge between the abstract mathematical concepts of complexity theory and the tangible biological processes observed in neuroscience. By drawing parallels to the hippocampus, known for its role in memory formation and spatial navigation, the article sheds light on how complex systems, such as neural networks, exhibit properties that are more than just the sum of their parts. The model thus offers a unique perspective on understanding complex systems, not only in neuroscience but in broader scientific inquiries where complexity and emergent phenomena are pivotal.

As urban development increases in density, the space to grow urban trees becomes more constrained. In heavily developed areas, small stature trees can be planted to reduce both above- and below-ground conflicts with infrastructure elements. However, even these species have their limits when placed in extremely confining conditions. In this study, we build on past work to determine the minimum planting widths of small stature urban trees. We found that species, stem diameter, and the height at which stem diameter measurements occurred were all strong predictors of trunk flare diameter (adjusted R² of 0.843). Additionally, we modelled the relationship between planting space and the presence or absence of hardscape conflicts – using the predictions derived from this effort to project the potential cost savings in two United States cities. Study results provide a guideline to create sufficient space for urban trees and minimize infrastructure damage and associated cost savings.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by the demyelination of neural fibers in the central nervous system. Understanding the impact of demyelination on neural network efficiency is crucial for elucidating the pathophysiological mechanisms underlying MS. This study aims to model the effects of demyelination on neural network efficiency, specifically focusing on how increased resistance and path lengths due to demyelination correlate with the clinical symptoms of MS. We employed a graph-theoretical approach to simulate neural networks, introducing varying degrees of demyelination. The demyelination was represented by increasing the resistance (weights) of selected edges within the network, affecting both random and clustered distributions of network connections. The primary metric analyzed was the average shortest path length, indicative of network efficiency. The models demonstrated a significant increase in the average shortest path length in demyelinated networks compared to intact ones. Specifically, networks with clustered demyelination exhibited localized inefficiencies, correlating with the focal nature of MS lesions. The increase in path length was associated with reduced signal transmission efficiency, providing insights into a range of MS symptoms including motor and sensory impairments, cognitive dysfunction, visual disturbances, and fatigue. The graph-theoretical model of neural network demyelination offers a novel perspective on how structural changes in the brain's connectivity due to MS can lead to diverse clinical manifestations. While the model simplifies the complexity of neural networks, it underscores the potential of computational approaches in understanding and predicting the course of neurological disorders like MS.

This study explores the intriguing phenomenon of action potentials reverberating and propagating in high-resistance tissues, such as gliosis, leading to the emergence of short circuits within the brain. Gliosis, characterized by increased tissue resistance, presents a unique environment for electrical signals. My research investigates the possible mechanisms behind these reverberations and their role in the creation of self-empowering short circuits that can potentially affect the entire brain's functionality. Understanding these processes may have significant implications for the treatment and management of neurological disorders associated with gliosis and abnormal electrical activity in the brain.

This project aims to simulate and analyze population dynamics in evolutionary systems, using stochastic differential equations and probabilistic rules for crossbreeding and benefits. The study employs advanced computational techniques to model the evolution of populations over an extended period. Specifically, we explore a scenario with ten distinct groups, each starting with an equal population and evolving under defined genetic and cooperative behaviors. The simulation spans 1000 years, incorporating individual lifespans, stochastic updates, and probabilistic interactions. To ensure robustness and reliability, the study includes detailed statistical analysis, encompassing descriptive statistics, confidence intervals, and ANOVA tests. We further visualize the temporal behavior of populations and subpopulations, providing insights into the evolutionary dynamics and stability of the system. The results demonstrate the effectiveness of balanced cooperation and genetic diversity in maintaining stable population distributions. The project showcases the integration of mathematical modeling, statistical analysis, and computational simulations, contributing valuable insights into evolutionary biology and complex systems. It highlights the importance of interdisciplinary approaches in understanding and predicting population behaviors, with implications for both theoretical research and practical applications in fields such as ecology, genetics, probability and social sciences.

Psychiatric disorders, characterized by complex and fluctuating patterns of thoughts, emotions, and behaviors, can be effectively modeled and visualized using mathematical wave equations. This study explores the representation of three major psychiatric conditions— Psychosis, Bipolar Disorder and Obsessive Compulsive Disorder (OCD)—through the application of differential equations, damping factors, and noise perturbations. Psychosis is modeled using Lissajous figures with high-frequency components, damping, and noise, symbolizing the irregular and erratic thought patterns characteristic of this condition. The inclusion of random perturbations and varying frequencies illustrates the chaotic and unpredictable nature of psychotic episodes, while damping effects reflect the temporary reductions in symptom intensity. For bipolar disorder, a system of partial differential equations simulates the cyclical nature of manic and depressive episodes. The model captures high-energy manic phases with periodic disturbances and the subsequent transition to lower-energy depressive states through damping effects. This representation highlights the oscillatory behavior and recurring episodes inherent to bipolar disorder. OCD is represented with Circumferential Complex Equations in Mult directions. The resulting graphical representations provide intuitive visual insights into the dynamics of these psychiatric disorders. By leveraging wave equations and mathematical modeling, this approach offers a novel perspective on understanding and analyzing the complex behaviors associated with OCD, bipolar disorder and psychosis. This method not only aids in the conceptualization of psychiatric phenomena but also underscores the potential of mathematical tools in the study of mental health conditions.

Attention-Deficit/Hyperactivity Disorder (ADHD) exhibits a notable prevalence across diverse populations, with estimates ranging from 4% to 6%. This wide range prompts an investigation into the evolutionary and genetic underpinnings of ADHD, especially considering the markedly different environments faced by ancestral human populations compared to today's structured societies. This study examines the potential adaptive advantages of ADHD-associated traits in hunter-gatherer contexts, where hyperactivity, impulsivity, and novelty-seeking behaviors may have conferred survival benefits. We employ the principles of population genetics, including Hardy-Weinberg equilibrium, selection coefficients, and genetic drift, to model the dynamics of ADHD allele frequencies over time. Additionally, we discuss balancing selection as a mechanism for maintaining genetic diversity and how gene-environment interactions (GxE) contribute to the expression of ADHD in contemporary settings. Our analysis suggests that traits associated with ADHD, while potentially maladaptive in modern structured environments, could have been preserved through evolutionary processes due to their adaptive value in ancestral contexts. Understanding these dynamics provides a comprehensive view of ADHD's prevalence and highlights the significance of genetic and environmental interplay in shaping human behavior.

A series of dinuclear copper(I) N,C,N- and P,C,P-carbodiphosphorane (CDP) complexes using multidentate ligands CDP(Py)2 (1) and (CDP(CH2PPh2)2 (13) have been isolated and characterized. Detailed structural information was gained by single crystal XRD analyses of nine representative examples. The common structural motive is the central double ylidic carbon atom with its characteristic two lone-pairs involved into binding of two geminal L-Cu(I) fragments at Cu-Cu distances in the range 2.55 – 2.67 Å. In order to enhance conformational rigidity within the characteristic Cu-C-Cu triangle, two types of chelating side arms were symmetrically attached to each phosphorus atom: two 2-pyridyl functions in ligand CDP(Py)2 (1) and its dinuclear copper complexes 2-9 and 11, as well as two diphenylphosphinomethylene functions in ligand CDP(CH2PPh2)2 (13) and its di- and mononuclear complexes 14-18. Neutral complexes were typically obtained via reaction of 1 with Cu(I) species CuCl, CuI, and CuSPh or via salt elimination reaction of [(CuCl)2(CDP(Py)2] (2) with sodium carbazolate. Cationic Cu(I) complexes were prepared upon treating 1 with two equivalents of [Cu(NCMe)4]PF6, followed by the addition of either two equivalent of an aryl phosphine (PPh3, P(C6H4OMe)3) or one equivalent of a bisphosphine ligands DPEPhos, XantPhos or dppf. For the first time carbodiphosphorane CDP(CH2PPh2)2 (13) could be isolated upon treating its precursor [CH(dppm)2]Cl (12) with NaNH2 in liquid NH3. A protonated and a deprotonated derivative of ligand 13 were prepared and their coordination was compared to neutral CDP ligand 13. NMR analysis and DFT calculations reveal, that the most stable tautomer of 13 does not show a CDP (or carbone) structure in its uncoordinated base form. For most of the prepared complexes, photoluminescence upon irradiation with UV light at room temperature was observed. Quantum yields (PL) were determined to 36% for dicationic [(CuPPh3)2(CDP(Py)2)](PF6)2 (4) and to 60% for neutral [(CuSPh)2(CDP(CH2PPh2)2] (16).

In this paper, several two-dimensional clustering scenarios are given. In those scenarios, soft partitioning clustering algorithms (Fuzzy C-means (FCM) and Possibilistic c-means (PCM)) are applied. Afterward, VAT is used to investigate the clustering tendency visually, and then in order of checking cluster validation, three types of indices (e.g., PC, DI, and DBI) were used. After observing the clustering algorithms, it was evident that each of them has its limitations; however, PCM is more robust to noise than FCM as in case of FCM a noise point has to be considered as a member of any of the cluster.

This study presents a computational simulation to explore the distinctive patterns of neural connectivity in Autism Spectrum Disorder (ASD), focusing on the concepts of spatial and topological proximities. ASD is characterized by unique cognitive and behavioral profiles, often attributed to atypical neural development and connectivity. Our simulation employs a two-pronged approach: first, by modeling spatial proximity through the generation of clustered 3D node positions, we mimic the observed over-connectivity in localized brain regions in ASD. Second, we construct a topological network to represent the complex interplay of under-connectivity and over-connectivity in functional brain networks, a hallmark of ASD's neural landscape. The spatial model demonstrates pronounced clustering, reflecting the structural brain differences and atypical growth patterns reported in neuroimaging studies of individuals with ASD. In contrast, the topological model reveals a network with a mix of sparse and dense connections, simulating the diverse and often contradictory findings of functional connectivity in ASD, such as reduced long-range connections and increased local connections. Our simulation provides a visual and conceptual framework for understanding the altered neural connectivity in ASD. It underscores the importance of considering both physical (spatial) and functional (topological) aspects of brain connectivity to grasp the full extent of neurodevelopmental deviations in ASD. This approach not only aids in elucidating the neural underpinnings of ASD's core symptoms but also offers a foundation for developing targeted interventions. Future research, integrating more complex and individual-specific data, could further refine this model, enhancing our understanding of ASD's neural dynamics and contributing to personalized therapeutic strategies.

Negative temperature coefficient (NTC) materials are usually based on ceramic semiconductors and electrons are involved in their transport mechanism. A new type of NTC material, adequate for alternating current (AC) applications, is represented by zeolites. Indeed, zeolites are single-charge carrier ionic conductors with a temperature-dependent electrical conductivity. In particular, electrical transport in zeolites is due to the monovalent charge-balancing cations, like K⁺, capable of hopping between negatively charged sites in the aluminosilicate framework. Owing to the highly non-linear electrical behavior of the traditional electronic NTC materials, the possibility to have alternative types of materials, showing linearity in the electrical behavior, is very desirable. Among different zeolites, the natural clinoptilolite has been selected for investigating the NTC behavior since it is characterized by high zeolite content, convenient Si/Al atomic ratio, good mechanical strength, due to its compact microstructure, and low toxicity. Clinoptilolite has shown a rapid and quite reversible impedance change under heating, characterized by a linear dependence on temperature. X-ray diffraction (XRD) has been used to identify the natural zeolite, to establish all types of crystalline phases present in the mineral, and to investigate the thermal stability of these phases up to 150°C. X-ray photoelectron spectroscopy (XPS) analysis has been used for the chemical characterization of the natural clinoptilolite sample, providing important information on the cationic content and framework composition. In addition, since electrical transport takes place in the zeolite free-volume, a Brunauer–Emmett–Teller (BET) analysis of the mineral has been also performed.

Human mesenchymal stem cells (hMSCs) constitute of cells having potential of self-renewal and proliferation and are commonly isolated from bone marrow aspirates of large bones. The osteogenic potential of these stem cells has been extensively exploited by scientists during the last many years for the biological evaluation of synthetic scaffolds with applications in tissue engineering. Current work aimed to synthesize N-arylhydrazone derivatives of orotic acid and their evaluation as stimulators of human mesenchymal stem cells. Some of the analogs show good to moderate proliferation rate.

Using a safe subset of C++ is a promising direction for increasing the safety of the programming language while maintaining its performance and productivity. In this paper, we examine how close existing C/C++ code is to conforming to a safe subset of C++. We examine the rules presented in existing safe C++ standards and safe C++ subsets. We analyze the code characteristics of 5.8 million code samples from the Exebench benchmark suite and 5 modern C++ applications using a static analysis tool. We find that raw pointers, unsafe casts, and unsafe library functions are used in both C++ code at large and modern C++ applications. In general, C++ code at large does not differ much from modern C++ code, and continued work will be required to transition from existing C/C++ code to a safe subset of C++.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Attention-Deficit/Hyperactivity Disorder (ADHD) is traditionally conceptualized within a framework emphasizing deficits in attention regulation and executive function. However, emerging evidence from the fields of predictive coding and active inference offers a novel lens through which to understand ADHD not merely as a disorder of attention but as a distinctive mode of neurodevelopmental variation. This article synthesizes current research and theoretical models to propose a redefined understanding of ADHD. By integrating insights from Ryan Smith, Paul B. Badcock, and Karl J. Friston (2020), we explore the premise that individuals with ADHD exhibit unique differences in how their brains generate and update predictions about the environment, leading to the characteristic behavioral patterns observed in ADHD. We argue that ADHD involves a divergence in the brain's predictive models and its ability to minimize prediction error, impacting sensory processing, attention allocation, and motor control. This perspective illuminates the adaptive aspects of ADHD, suggesting that what are often labeled as deficits could also reflect an adaptive fit to certain environmental contexts, underscoring the role of neurodiversity in human evolution. Furthermore, we discuss the implications of this reconceptualization for clinical practice, including diagnosis, treatment, and support for individuals with ADHD, emphasizing approaches that align with their unique neurocognitive profiles. This article calls for a shift in the narrative surrounding ADHD, advocating for a model that appreciates the complexity and adaptiveness of neurodevelopmental diversity.

Computational neuroscience has undergone a significant transformation in recent years, driven by the exponential growth of neural data and advancements in data science and machine learning. While traditional theoretical models remain valuable, there is a growing emphasis on integrating data-driven approaches to develop more accurate, biologically plausible, and predictive models of neural function. This shift has led to a new equilibrium in the field, where data-driven model development, machine learning techniques, and hybrid approaches that combine data and theory are increasingly prevalent. In this article, we discuss the evolving landscape of computational neuroscience, highlighting the importance of data-driven methods and the emergence of a more integrative approach that leverages both data and theory to unlock the mysteries of the brain. We also explore the implications of this shift for future research and clinical applications, emphasizing the potential for data-driven computational neuroscience to revolutionize our understanding of neural function and pave the way for new treatments for neurological disorders.

The complex dynamics of the neocortex, the outermost layer of the brain, have been a subject of intense research in neuroscience. Recent studies have suggested that magnetic fields generated by neuronal activity may play a significant role in neocortical dynamics. This paper presents a simplified mathematical model that explores the hypothesized interactions between magnetic dynamos, nondissipative systems, Hamiltonian equations, and the Lorenz force in the context of neocortical dynamics. The proposed model is based on a set of coupled Hamiltonian equations inspired by the Lorenz system, a well-known chaotic dynamical system. The generalized coordinates in the model represent the magnetic field components, while the generalized momenta are related to the electric field components or other relevant quantities. The Hamiltonian equations describe the conservative dynamics of the system, and the coupling terms in the equations are interpreted as representing the interactions between the magnetic and electric field components, analogous to the Lorenz force in electromagnetism. The model is implemented using Python, and the Hamiltonian equations are numerically solved using the odeint function from the scipy.integrate module. The resulting dynamics of the magnetic field components are visualized using matplotlib. While the model is highly simplified and does not capture the full complexity of neocortical dynamics, it serves as a starting point for investigating the potential role of magnetic dynamos and Lorenz force interactions in the brain. The paper discusses the limitations of the current model and highlights the need for further refinements, such as incorporating more realistic biological constraints, considering energy dissipation and compensation mechanisms, and validating the model against experimental data. Future work should focus on developing a more comprehensive and biologically plausible model that integrates the latest findings from neuroscience, physics, and computational modeling. By presenting this simplified Hamiltonian model, the paper aims to stimulate further research and discussion on the potential significance of magnetic dynamos and Lorenz force interactions in neocortical dynamics. The model provides a framework for exploring these hypothesized mechanisms and may guide future experimental and theoretical investigations in this emerging field of neuroscience

This paper presents data supporting the IC Regimen for potentiating the effectiveness of lorlatinib in treating ALK positive cancers, and specifically non-small cell lung cancer. Lorlatinib is an effective treatment for ALK driven non-small cell lung cancer and other ALK driven cancers. Lorlatinib inhibits ALK kinase and achieves good brain tissue levels, a common site for metastases in lung cancers. However, resistance to lorlatinib usually supervenes and the cancer awakens and starts growing again, resistant to lorlatinib. This paper analyses data indicating that adding two common generic drugs, itraconazole and cilostazol, to lorlatinib treatment may delay resistance development. Itraconazole is marketed worldwide as a generic antifungal drug that also inhibits Hedgehog signaling, CYP3A4, and the p-gp efflux pump. Cilostazol is a generic anti-thrombosis, phosphodiesterase 3 inhibiting drug that carries minimal bleeding risk. Cilostazol may enhance lorlatinib by deprivation of trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by reducing or stopping a Hedgehog centered amplifying feedback loop with ALK kinase. The combination of metastatic non-small cell lung cancer being a low-survival disease and the general safety itraconazole plus cilostazol augmentation, make a clinical trial of this trio worthwhile.

The intricate architecture of dendritic arborization is fundamental to the formation and functionality of neural networks, serving as the primary site for synaptic integration and signal propagation. This study presents a pioneering computational model that simulates dendritic growth dynamics, employing exponential and logarithmic scaling over an extended developmental period of 720 days. This model offers a valuable tool for investigating the implications of diverse dendritic growth patterns on neural development, synaptic connectivity, and ultimately, cognitive functions. The computational framework incorporates biologically plausible parameters, allowing for the systematic exploration of dendritic branching patterns and their potential impact on neuronal information processing. By simulating exponential and logarithmic growth scales, the model captures the inherent complexity and diversity of dendritic morphologies observed in various neuronal populations across different brain regions. The findings from this study hold significant implications for our understanding of neural circuit assembly, synaptic integration, and the potential functional consequences of aberrant dendritic growth patterns observed in neurodevelopmental disorders. Furthermore, the model's ability to simulate extended developmental trajectories over a prolonged period of 720 days offers insights into the dynamic interplay between dendritic growth and synaptic pruning, which is crucial for the refinement and optimization of neural networks.

Two polyurethanes (PUs) were similarly synthesized by reacting a cycloaliphatic isocyanate with 1,4 butanediol and two polyols of different nature (polyester, polycarbonate diol) with molecular weights of 1000 Da. The PU made with polycarbonate diol polyol (YCD) was the only showing intrinsic self-healing at 20 °C. For assessing the mechanism of intrinsic self-healing of YCD, a structural characterization by molecular weights determination, infrared and X-ray photoelectronic spectroscopies, differential scanning calorimetry, X-ray diffraction, thermal gravimetric analysis and dynamic mechanical thermal analysis was carried out. It was concluded that the self-healing at 20 °C of YCD was due to non-covalent dynamic exchange interactions among the carbonate groups of the soft segments. Therefore, the chemical nature of the polyol played a key role in developing PUs with intrinsic self-healing at 20 °C.

Autism spectrum disorder (ASD) is a common condition with lifelong implications and a strong hereditary component suggesting genetic underpinnings. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes not associated with ASD (P = 0.0002, odds ratio 29), validating that most are indeed disease related. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. Variants that we assigned as PDVs yet not on the report were predominately de novo in genes not yet reported as ASD associated. Many subjects both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

COVID-19 differential spread and impacts across regions is a major focus for researchers and policy makers. Africa has attracted tremendous attention due to predictions of catastrophic impacts that have not yet materialized. Early in the pandemic, the seemingly low African case count was largely attributed to low testing and case reporting. However, there is also reason to consider that many African countries got out ahead of the virus early on. Factors explaining low spread include early government mandated lockdowns, community-wide actions, population distribution, social contacts, and ecology of human habitation. While recent data from seroprevalence studies posit more extensive circulation of the virus, continuing low COVID-19 burden may be explained by the demographic pyramid, prevalence of pre-existing conditions, trained immunity, genetics, and broader sociocultural dynamics. Though all these prongs contribute to the observed profile of COVID-19 in Africa, some provide stronger evidence than others. This review is important to expand what is known about the differential impacts of pandemics enhancing scientific understanding and gearing appropriate public health responses. Also, highlighting potential lessons the world may draw from Africa for global health on assumptions regarding deadly viral pandemics given its long experience with infectious diseases.

The Flack Parameter is now almost universally reported for all chiral materials characterized by X-ray crystallography. It’s elegantly simplicity was an inspired development by Flack, and although the original algorithm for its computation has been strengthened by other workers, it remains an essential outcome for any crystallographic structure determination. As with any one-parameter metric, it needs to be interpreted in the context of its standard uncertainty.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

The role of foods is shifting from focusing on the provision of energy and basic nutrients to also include bioactive compounds that prevent the development of chronic age-related diseases. Mi-croalgae offer a source of nutritional compounds with important health effects, and have the po-tential for production of health-promoting products, without increasing agricultural land use and negatively impacting the environment. Here we investigate the health effects of microalgal ex-tracts with high levels of the colourless carotenoid phytoene. Phytoene is widely available from dietary sources and can be detected across different tissues in the human body. However, it is usually regarded as a precursor for the synthesis of other carotenoids, rather than a bioactive molecule. We utilised the model organism C. elegans to show that phytoene-rich extracts from Chlorella sorokiniana and Dunaliella bardawil have anti-ageing properties. The extracts protect against oxidative damage and amyloid-β42 proteotoxicity (a major pathology of Alzheimer's disease), and extends lifespan. We show that pure phytoene also has these anti-ageing effects, suggesting that phytoene is a bioactive molecule with positive effects on ageing and longevity.

Simulated crime scene investigation is an essential component of forensic science education, but its implementation poses challenges relating to cost, accessibility and breadth of experience. Virtual reality (VR) is an emerging technology which offers exciting prospects for teaching and learning, especially for imparting practical skills. We document here a multidisciplinary experimental study in which a bespoke VR crime scene app was designed and implemented, after which it was tested by both undergraduate student and staff/postgraduate student cohorts. Through both qualitative and quantitative analyses, we demonstrate that VR applications support learning of practical crime scene processing skills. VR-based practical sessions have the potential to add value to forensic science courses through offering cost-effective practical experience and the ability to work in isolation, in a variety of different scenarios. Both user groups reported high levels of satisfaction with the process and reports of adverse effects (motion sickness) were minimal. With reference to user feedback, we proceed to evaluate the scalability and development challenges associated with large-scale implementation of VR as an adjunct to forensic science education.

Visible-light photocatalysis, particularly in its application to organic synthesis, has experienced a big renaissance in the past decade. The rational design of new photocatalysts with designed and improved photocatalytic properties, that at the same time circumvents the necessity of using scarce and toxic transition metals, will predictably play a key role in photocatalysis in the next few years. Although free-base porphyrins were identified some years ago as a promising, easily accessible and easily tunable class of organic photoredox catalysts, a systematic study on the effect of the electronic nature and of the position of the substituents on both the ground-state and the excited-state redox potentials of these compounds is still lacking. We have prepared a set of known functionalized derivatives of meso-tetraphenyl porphyrin containing different substituents either in one of the meso-positions or at a beta-pyrrole carbon and we have determined their ground- and (singlet) excited-state redox potentials. This survey has led us to conclude that the introduction of a carbonyl group at the beta-pyrrolic position strongly increases the facility of the monoelectronic reduction of the porphyrin both in the ground state and in the singlet excited state. We have also prepared a second set of four previously unknown benzoyl derivatives of meso-tetraphenylporphyrin, and we have confirmed the validity of our conclusions.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

The performance of the presurgical test (preSurg) for temporal lobe epilepsy (TLE) was evaluated via video-electroencephalography (VEEG), electroencephalography (EEG), 99mTc-HmPAO single-photon emission tomography (SPECT) and 1.5 T magnetic resonance imaging (MRI) in a group of 112 men (37.0 ± 1.1 years) and 106 women (39.7 ± 1.1 years) operated on for TLE. The epileptic zone (EZ) was adequately identified to determine whether the patient reached an Engel I grade (EI) at least one year postop. Accuracy was evaluated by the coefficient α, ranging from 3 (when result = EZ) to 2 (result in the same hemisphere as the EZ), 1 (noninformative result) or 0 (EZ in the contralateral hemisphere). The simplicity of diagnosis was defined as the number of preSurg surgeries needed to identify the EZ. EI was obtained in 85.8% of patients even though 42.2% of patients had noninformative MRI results. For preSurg α was (mean ± SEM) = VEEG (2.83 ± 0.04) &gt; MRI (2.14 ± 0.08) &gt; EEG (1.87 ± 0.09) &gt; SPECT (1.71 ± 0.09). The accuracy (combination of sensitivity and specificity) was calculated as follows: VEEG (0.797) &gt; MRI (0.518) &gt; EEG (0.446) &gt; SPECT (0.360). The likelihood positive ratio was greater, and the likelihood negative ratio was lower for VEEG. The most relevant factor for the regression model was VEEG (3.106) &gt; MRI (2.558) &gt; EEG (1.905), and the factors were not significantly related to SPECT. EZs in EI patients with low simplicity were identified mainly by VEEG. A very good postoperative outcome can be obtained even in TLE patients with no lesions on MRI. The VEEG is the most reliable preSurg test and may be the only reliable test for patients with very low simplicity (i.e., difficult).single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Cardiovascular diseases (CVDs) are the leading cause of death in the globally. Morbidity and disability related to non-fatal events are increasing exponentially. There are several symptoms that may arise after invasive therapeutic approaches such as coronary artery bypass graft (CABG), including chronic pain in anatomical areas connected to the mediastinum; these pains can be found not only initially after surgery, but also years later. We present a case where non-specific neck pain (NNP), in a patient undergoing CABG five years earlier, was approached with an osteopathic technique, working the pericardial area. To the knowledge of the Authors, it is the first case report where osteopathy is associated with a gentle treatment on the pericardial area to resolve a NNP.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to explore the mechanisms behind the vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactivated protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

At 2.3 megabases in length, the dystrophin gene is enormous: transcription of a single mRNA requires approximately 16 hours. Principally expressed in skeletal muscle, the dystrophin protein product protects the muscle sarcolemma against contraction-induced injury, and dystrophin deficiency results in the fatal muscle-wasting disease, Duchenne muscular dystrophy. This gene is thus of key clinical interest, and therapeutic strategies aimed at eliciting dystrophin restoration require quantitative analysis of its expression. Approaches for quantifying dystrophin at the protein level are well established, however study at the mRNA level warrants closer scrutiny: measured expression values differ in a sequence-dependent fashion, with significant consequences for data interpretation. In this manuscript we discuss these nuances of expression and present evidence to support a transcriptional model whereby the long transcription time is coupled to a short mature mRNA half-life, with dystrophin transcripts being predominantly nascent as consequence. We explore the effects of such a model on cellular transcriptional dynamics, and then discuss key implications for the study of dystrophin gene expression, focussing both on conventional (qPCR) and next-gen (RNAseq) approaches.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

Suzuki cross-coupling reaction has developed one of the furthermost effectual approaches for the synthesis of biaryls or substituted aromatic moieties from aryl halides and arylboronic acids with a palladium-catalyst in the past two era’s. Herein, Pd-free layered double hydroxide containing nickel catalysts were prepared by co-precipitation method under ultrasonic irradiation and N2 atmosphere with different molar ratios of Ni: Mg: Al and coded as (1NiLDHs-Dr), (1.5NiLDHs-Dr) and (2NiLDHs-Dr). A series of reduced catalysts under 5%H2/N2 at different temperatures were coded as 1NiLDHs-R200, 1.5NiLDHs-R200 and 2NiLDHs-R200. As-synthesized 2NiLDHs-Dr was the superlative catalyst when coupling different aryl halides with different boronic acids derivatives. Deep investigation of all catalysts was done using different techniques such as inductively coupled plasma optical emission spectroscopy (ICP-OES), x-ray photoelectron spectroscopy (XPS), powder x-ray diffraction (XRD), thermogravimetric analyses (TGA), Fourier transfer infrared (FTIR), scanning electron microscope (SEM) connected with energy dispersive x-ray (EDX) and N2-physisorption at -196 ℃. The results attained verified that ɑ-Ni(OH)2 was fashioned for 2NiLDHs-Dr catalyst and the enclosure of nickel ions in the cationic sheet of layered structure were responsible for the fascinating catalytic efficacy rather than the basic nature of material. The Ni-containing LDHs catalysts encourage forthcoming studies in Pd-free catalyzed C-C coupling reactions.

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.

Detailed evaluation is provided for the likelihood statistics intrinsic to interlocking Sequential Bayes analysis, which allows estimation of evidential support for dendrograms charting the macroevolution of taxa. It involves complexity functions, such as fractal evolution, to generate well-supported evolutionary trees. Required are data on trait changes from ancestral species to descendant species, which is facilitated by reduction of large genera to monothetic groups (one ancestral species each), most conveniently named as separate genera. Assigning each species one Shannon informational bit per new trait, then adding the traits as sequential Bayesian analysis (each posterior probability used as the prior for the next iteration of Bayes Formula), then interpretation with an odds chart, provides a posterior probability that the ancestor-descendant order is correct, that is, entirely follows evolutionary theory involving adaptation and rarity of total trait reversals. The key fact is that the most recently acquired traits of the ancestral species are selectively inviolate and passed on without change to each descendant species. The details of sequential Bayesian analysis were clarified by calculation of likelihood ratios and Bayes factors that compare optimal models with the next most likely model. Such analysis demonstrated that the optimum arrangement of ancestor and descendant species leads to high support values for fitting evolutionary theory, comparable to statistical support levels reported for molecular evolutionary trees. The fact that phylogenetic analysis does not offer an ancestor-descendant model in is found to be conducive of precision at the expense of accuracy, and leads to wrong ancestor-free models with likelihoods explaining data at high credible levels. The number of advanced traits in the outgroup as a Bayesian prior greatly enhances posterior probability. The method is simple, free of special computer analysis, and well-suited to standard taxonomic practice.

Differences between the quantum mechanical and relativistic concepts of time observed in GPS satellites are accounted for by applying the equivalence principle to the transitioning electron of an atomic clock. It allows a differential equation of motion to be derived for the electron in the Minkowski space between electron shells. Using Hamilton’s principle we transform the differential equation relativistically into an integral equation of motion, the time integral of a Lagrangian. This newly derived equation accounts for the abstract mathematics of the more familiar non-relativistic model by means of a physical interpretation. Abstract rotations in Hilbert space are replaced by the rotations of real particle field geometries in Minkowski space. Because the properties of energy are universal the same equations are then used to describe the field geometry of galaxies despite vast differences in lifetime. They reveal a symmetry between the electromagnetic fields of atoms and the gravitational fields of galaxies due to similarities in the exchange of energy by radial and transverse fields. Our analysis reveals that the conjugate variables energy and time permit differences between atomic and galactic structure to be compared in a more intuitive way than by means of the differential equations of motion which use the conjugate variables position and momentum.

During glioblastoma treatment, the pharmaceutical monoclonal antibody to VEGF, bevacizumab, has improved quality of life and delayed progression for several months but has not, or only marginally prolonged overall survival. In 2017 several dramatic research papers appeared that are crucial to our understanding of glioblastoma vis a vis the mode of action of bevacizumab. As a consequence of these papers, a new, potentially more effective, treatment protocol can be built around bevacizumab. This is the ADZT Regimen where four old drugs are added to bevacizumab. These four are apremilast, marketed to treat psoriasis, dapsone, marketed to treat Hansen’s disease, zonisamide, marketed to treat seizures, and telmisartan, marketed to treat hypertension. The ancillary attributes of each of these drugs has been shown to augment bevacizumab. This paper will detail the research data supporting that contention.