The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

The carbonized elastomer-based composites (CECs) possess a number of attractive features in terms of thermomechanical and electromechanical performance, durability in aggressive media and facile net-shape formability, but their relatively low ductility and strength limit their suitability for structural engineering applications. Prospective applications such as structural elements of MEMS can be envisaged, since smaller principal dimensions reduce the susceptibility of components to residual stress accumulation during carbonization, and to brittle fracture in general. We report the results of operando in-SEM study of micro-deformation and fracture behavior of CECs based on NBR elastomeric matrices filled with carbon and silicon carbide. Nanostructured carbon composite materials were manufactured via compounding of elastomeric substance with carbon and SiC fillers using mixing rolling mill, vulcanization, and low-temperature carbonization. Double Edge Notched Tensile (DENT) specimens of vulcanized and carbonized elastomeric composites were subjected to in situ tensile testing in the chamber of the scanning electron microscope (SEM) Tescan Vega 3 using Deben Microtest 1 kN Tensile Stage. The series of acquired SEM images were analyzed by means of Digital Image Correlation (DIC) using Ncorr open source software to map the spatial distribution of strain. These maps were correlated with Finite Element Modelling (FEM) simulations to refine the values of elastic moduli. Besides, the elastic moduli were derived from unloading curve nanoindentation hardness measurements carried out using NanoScan-4D tester and interpreted using the Oliver-Pharr method. Carbonization causes significant increase of elastic moduli from 0.86 ± 0.07 to 14.12 ± 1.20 GPa for the composite with graphite and carbon black fillers. Nanoindentation measurements yield somewhat lower values, namely, 0.25 ± 0.02 GPa and 9.83 ± 1.10 GPa before and after carbonization respectively. The analysis of fractography images suggests that crack initiation, growth and propagation may occur both at the notch stress concentrator and relatively far from the notch. Possible causes of such response are discussed, namely, (1) residual stresses introduced by processing; (2) shape and size of fillers; and (3) the emanation and accumulation of gases in composites during carbonization.

Abstract: In order to accelerate deployment of distributed recycling by providing low-cost feed stocks of granulated post-consumer waste plastic, this study analyzes an open source waste plastic granulator system. It is designed, built and tested for its ability to convert post-consumer waste, 3-D printed products and waste into polymer feedstock for recyclebots of fused particle/granule printers. The technical specifications of the device are quantified in terms of power consumption (380 to 404W for PET and PLA, respectively) and particle size distribution. The open source device can be fabricated for less than USD$2000 in materials. The experimentally-measured power use is only a minor contribution to the overall embodied energy of distributed recycling of waste plastic. The resultant plastic particle size distributions were found to be appropriate for use in both recyclebots and direct material extrusion 3-D printers. Simple retrofits are shown to reduce sound levels during operation by 4dB-5dB for the vacuum. These results indicate that the open source waste plastic granulator is an appropriate technology for community, library, makespace, fab lab or small business-based distributed recycling.

In our previous published papers, considering 3 large atomic gravitational constants assumed to be associated with weak, strong and electromagnetic interactions, we have proposed the existence of a nuclear charge of magnitude, e_n=2.95e and developed a nuclear mass formula associated with strong and weak interactions having 4 simple terms and only one energy coefficient. Two important assumptions are, there exists a weak fermion of rest energy 585 GeV and strong coupling constant is the squared ratio of electromagnetic charge and nuclear charge. The aim of this paper is associated with understanding the mystery of quantum of magnetic flux, Planck’s quantum radiation constant and Reduced Planck’s constant. Proceeding further, quark charges, strong coupling constant, nuclear stability, nuclear binding energy, medium and heavy atomic X-ray levels and celestial magnetic moments can be understood in a unified approach. It may also be noted that, by considering integral nature of elementary particle masses, it seems possible to understand the discreteness of angular momentum. Considering our proposed e_n=2.95e=3e as a characteristic nuclear charge, it seems possible to understand the integral nature of quarks electromagnetic charge. With this idea, neutron, proton and pions decay can be understood very easily. In all the cases, up quark of charge (±2e) seems to play a crucial role with the internal transformation of down quark of charge (±e) and external observable elementary basic elementary particles. It needs further study at fundamental level.

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

In this paper, we present the interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles and cytisine and salsoline alkaloids. It has been shown that the reaction results in the one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction is affected by the presence of a base and the order in which the reagents are added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity has been carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking shows that the compounds have insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increases the affinity of these substrates for target proteins selected.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-concerted [2n+2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the more favourable regioisomeric transition state structure (TS) is located 8.5 kcal•mol⁻¹ below the reagents, in complete agreement with the high polar character of the TS. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pra-type of reactivity.

Docosahexaenoate is a cytoprotective ω-3 polyunsaturated lipid which is abundant in the retina and is essential for its function. Due to its six unsaturated double bonds, docosahexaenoate is highly susceptible to oxidation and formation of products with photosensitizing properties. The aim of this study was to test on cultured human retinal pigment epithelial cells ARPE-19 the (photo)cytotoxic potential of partly oxidized docosahexaenoate and its effect on the formation of lipofuscin from phagocytosed photoreceptor outer segments (POS). The results demonstrate that the cytoprotective effects of docosahexaenoate do not counteract the deleterious effects of its oxidation products leading to the concentration-dependent loss of cell metabolic activity, which is exacerbated by concomitant exposure to visible light. Partly oxidized docosahexaenoate does not cause permeability of the cell plasma membrane but does cause apoptosis. While vitamin E can provide partial protection from the (photo)toxicity of partly oxidized docosahexaenoate, zeaxanthin undergoes rapid photodegradation and can exacerbate the (photo)toxicity. Feeding cells with POS enriched in partly oxidized docosahexaenoate results in a greater accumulation of intracellular fluorescent lipofuscin than in cells fed POS without the addition. In conclusion, partly oxidized docosahexaenoate increases the accumulation of lipofuscin-like intracellular deposits, is cytotoxic, and its toxicity increases during exposure to light.

We study Cartan-Schouten metrics, explore invariant dual connections, and propose them as models for Information Geometry. Based on the underlying Riemannian barycenter and the biinvariant mean of Lie groups, we subsequently propose a new parametric mean for data science and machine learning which comes with several advantages compared to traditional tools such as the arithmetic mean, median, mode, expectation, least square method, maximum likelihood, linear regression. We call a metric on a Lie group, a Cartan-Schouten metric, if its Levi-Civita connection is biinvariant, so every 1-parameter subgroup through the unit is a geodesic. Except for not being left or right invariant in general, Cartan-Schouten metrics enjoy the same geometry as biinvariant metrics, since they share the same Levi-Civita connection. To bypass the non-invariance apparent drawback, we show that Cartan-Schouten metrics are completely determined by their value at the unit. We give an explicit formula for recovering them from their value at the unit, thus making them much less computationally demanding, compared to general metrics on manifolds. Furthermore, Lie groups with Cartan-Schouten metrics are complete Riemannian or pseudo-Riemannian manifolds. We give a complete characterization of Lie groups with Riemannian or Lorentzian Cartan-Schouten metrics. Cartan-Schouten metrics are in abundance on 2-nilpotent Lie groups. Namely, on every 2-nilpotent Lie group, there is a 1-1 correspondence between the set of left invariant metrics and that of Cartan-Schouten metrics.

Nutrition, diabetes, and mental disorders are interconnected and significantly impact an individual's overall health and well-being. This comprehensive review aims to explore the complex interplay between nutrition, diabetes, and mental disorders, highlighting the latest research findings in this field. While the influence of nutrition on the development and management of both diabetes and mental disorders is widely recognized, there remains a gap in understanding the intricate interplay between nutrition, mental health, and diabetes. Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Thus, the mechanisms linking nutrition, diabetes, and mental disorders are complex and multi-factorial. Inflammation, oxidative stress, gut microbiota alterations, and neuroendocrine dysregulation have emerged as potential pathways that may mediate the relationship between nutrition, diabetes, and mental disorders. Additionally, deficiencies in essential nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. Our findings indicate that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.

Activation of the NLRP3 inflammasome plays a crucial role in innate immune response. During cell division, the NLRP3 inflammasome activation must be strictly controlled. Here, we discovered the anaphase promoting complex subunit 10 (Anapc10, APC10), a substrate recognition protein of the anaphase promoting complex/cyclosome (APC/C), is a critical mediator of the NLRP3 inflammasome activation. APC10 protein interacts with NLRP3, and co-localizes with NLRP3 protein in the cytoplasm. During interphase, APC10 interacts with NLRP3 to promote the NLRP3 inflammasome activation. During mitosis, APC10 disassociates from the NLRP3 inflammasome to inhibit the inflammatory responses. This study reveals a distinct mechanism by which APC10 serves as a switch of the NLRP3 inflammasome activation during cell cycle.

The novel phosphor Eu3+ doped Na5Zn2Gd(MoO4)6 triple molybdate were prepared by the sol-gel method. The structure, morphology, and luminescent properties have been characterized by X-ray diffraction, thermogravimetry-differential thermal analysis, scanning electron microscopy, FTIR spectroscopy and Luminescence spectroscopy. The results indicated that the synthesized Na5Zn2Gd1-x(MoO4)6: xEu3+phosphor consisted of a pure phase with monoclinic structure. Under excitation at 465 nm, the Na5Zn2Gd1-x(MoO4)6: xEu3+ phosphor exhibits intensive red emission band around 610 nm corresponding to the transition of 5D0→7F2 is much higher than that 5D0→7F1 at 594 nm, which was appropriate for blue LED. According to the influence of the synthesis conditions, the phosphors show the highest emission intensity as the doping concentration of Eu3+ was 25 mol.% and the molar ratio of citric acid to metal ions was 2:1. Na5Zn2Gd0.75(MoO4)6: 0.25 Eu3+ with the color coordinates (x= 0.658, y= 0.341) is a stable red phosphor for blue-based white LEDs due to it is closer to the NTSC standard values (0.670, 0.330) comparing with the color coordinates (0.48, 0.50) of the commercial Y2O2S: Eu3+ red phosphor.

Overhydration (OH) is a common medical problem found in patients with kidney or heart failure, but still a specific marker has not been found. Clinicians today use bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function like NT-pro-BNP, GFR or creatinine levels. New serum markers such as Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are being researched with promising results. The need to discover a more precise marker of overhydration is dire mainly because physical examination is extremely imprecise. Signs and symptoms of fluid overload like edema or gradual increase of body mass are not always present, especially in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation focusing especially on kidney diseases.

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in RGD (arginine-glycine-aspartic acid) sequences, with good processability that is being investigated for regenerative medicine applications. Recently, the biocompatibility and osteogenic ability of β-TCP/RCP (RCP granules combined with β-tricalcium phosphate (TCP) submicron particles) were demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects (three-walled bone defect) created in beagle dogs to investigate tissue responses and subsequent regenerative effects. Micro computed tomography image analysis at 8 weeks postoperatively showed that the amount of new bone after β-TCP/RCP graft was significantly greater (2.2 fold, P<0.05) than that of the control (no graft) group. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including TRAP-positive and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control, and significantly suppressed gingival recession and epithelial downgrowth (P<0.05). These results suggest that β-TCP/RCP is effective as a periodontal tissue regenerative material.

Mitochondrial pyruvate dehydrogenase complex (PDHC) is essential for the brain glucose and neurotransmitter metabolism, dysregulated in many pathologies. Using specific inhibitors of PDHC in vivo, we determine biochemical and physiological responses to PDHC dysfunction. Dose dependence of the responses to membrane-permeable dimethyl acetylphosphonate (Ac-PMe2) is non-monotonous. Primary decreases in glutathione and its redox potential, methionine and ethanolamine are alleviated with increasing PDHC inhibition, the alleviation accompanied by physiological changes. Comparison of 39 brain biochemical parameters after administration of four phosphinate and phosphonate analogs of pyruvate at a fixed dose of 0.1 mmol/kg reveals no primary, but the secondary changes, such as activation of 2-oxoglutarate dehydrogenase complex (OGDHC) and decreased levels of glutamate, isoleucine and leucine. The accompanying decreases in RMSSD of ECG and freezing time are most pronounced after administration of me-thyl acetylphosphinate and dimethyl acetylphosphonate. The levels of PDHA1 expression and phosphorylation, sirtuin 3 and total protein acetylation are not significantly changed by the PDHC inhibitors that affect the brain protein succinylation and glutarylation. Thus, decreased production of the tricarboxylic acid cycle substrate acetyl-CoA by inhibited PDHC is compen-sated by increased degradation of amino acids through the cycle with activated OGDHC, increas-ing total protein succinylation and decreasing anxiety indicators.

Centrifuges are commonly required devices in medical diagnostics facilities as well as scientific laboratories. Although there are commercial and open source centrifuges, costs of the former and required electricity to operate the latter, limit accessibility in resource-constrained settings. There is a need for low-cost, human-powered, verified and reliable lab-scale centrifuge. This study provides the designs for a low-cost 100% 3-D printed centrifuge, which can be fabricated on any low-cost RepRap-class fused filament fabrication (FFF) or fused particle fabrication (FPF)-based 3-D printer. In addition, validation procedures are provided using a web camera and free and open source software. This paper provides the complete open source plans including instructions for fabrication and operation for a hand-powered centrifuge. This study successfully tested and validated the instrument, which can be operated anywhere in the world with no electricity inputs obtaining a radial velocity of over 1750rpm and over 50N of relative centrifugal force. Using commercial filament the instrument costs about US$25, which is less than half of all commercially available systems; however, the costs can be dropped further using recycled plastics on open source systems for over 99% savings. The results are discussed in the contexts of resource-constrained medical and scientific facilities.

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

The thermoelectric generator (TEG) has much potential as a renewable energy technology that could be used in ocean thermal energy conversion (OTEC). This technique employs TEGs and heat exchangers as substitutes for the intricate elements found in conventional OTEC systems, including pressure valves, evaporators, condensers, and turbine generators. By harnessing the temperature difference between warm surface seawater and cold deep seawater, it facilitates the conversion of this thermal gradient into electrical energy. This study used computer simulations to look at and compare three different types of heat exchangers: a cavity-type heat exchanger, a heat exchanger with flat fins, and a heat exchanger with longitudinal vortex generators (LVGs). The objective was to evaluate the influence of these designs on the thermoelectric conversion performance when implemented in OTEC systems. The study's findings indicate that using heat exchanger configurations featuring flat fins, or LVGs, enhances the efficiency of thermal energy transfer from warm seawater to TEGs, resulting in a notable enhancement in the output power of TEGs. Furthermore, the efficiency of TEG thermoelectric conversion is influenced by varying seawater flow rates in relation to the performance of flat fins and LVGs. In contrast to the cavity-type heat exchanger, the utilization of a heat exchanger equipped with flat fins has been found to yield a notable enhancement in the output power of TEGs by approximately 22.92%. Furthermore, this configuration demonstrates a substantial improvement in thermoelectric conversion efficiency, exhibiting an increase of around 40.01%. These improvements are observed under certain conditions pertaining to flow rates and fin heights. Utilizing heat exchangers equipped with LVGs has been found to enhance the output power of TEGs by 13.02% and improve the overall thermoelectric conversion efficiency by 17.72%. These improvements are observed under certain conditions, including specific flow rates, LVG tilt angles, and locations.

Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. This unique aquatic species has been found to have the capacity to regenerate their spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in the central and peripheral nervous systems upon glial cell injury remains unclear. This review paper focuses on the molecular mechanisms and cellular processes that underlie spinal cord regeneration in four initial phases: proliferation and initial migration; migration and differentiation; glial bridge formation; and remodeling. We propose that within these four phases the cellular mechanisms that underlie spinal cord regeneration each express a terminating signal that aborts one step of the process and initiates the next. Specifically, future studies would be devoted to investigate transmitting signals in the spinal cord injury micro-environment in hope to contribute to the understanding of underlying cellular mechanisms by connecting each process of spinal cord regeneration in zebrafish.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

In this paper, we study the effect of parasitic channel on electrical characteristics and power consumptions of vertically stacked gate-all-around (GAA) silicon nanosheet (NS) MOSFETs of the bulk and silicon-on-insulator (SOI) substrates. Through deliberate control of the bottom parasitic channel coverage, we systematically assess its influence on DC, AC, and RF characteristics including power consumption. The observed findings highlight a significant differentiation among the bottom parasitic channels: GAA (i.e., control sample with 100% coverage), omega-shaped gate NS (70% and 80% coverages), and FinFET (60% coverage). Compared with the device with a 60% coverage channel, the device with a 100% coverage channel possesses 3520% and 8030% normalized leakage current improvement for both NFET and PFET under the bulk substrate, respectively. Compared with bulk-substrate devices, the SOI-substrate devices further significantly improve the leakage current. Due to enhanced off-state current leakages in the 100% covered bulk-substrate device, the static power demonstrates a notable improvement (about 98.1%), compared to 60% covered devices. Hence, the utilization of a 60% covered channel will result in a degradation of both device and circuit performance. The observation of GAA NS MOSFET indicates that an increase in the bottom parasitic channel coverage ratio leads to a positive impact on power consumption and leakage currents. The examination presented here is useful in the fabrication of stacked GAA NS MOSFETs.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

The paper briefly reviews the Clifford algebras of space Cl(3,0) and anti-space Cl(0,3) with a particular focus on the paravector representation, emphasizing the fact that both algebras have an isomorphic center represented just by two coordinates. Since the paravector representation allows assigning the scalar element of grade 0 to the time coordinate, we consider the relativity in such two-dimensional spacetime for a uniformly accelerated frame with the constant acceleration 3Hc. Using the Rindler coordinate transformations in two-dimensional spacetime and then applying it to Minkowski coordinates, we obtain the FLRW metric, which in the case of the Clifford algebra of space Cl(3,0) corresponds to the anti-de Sitter (AdS) flat (k=0) case, the negative cosmological term and an oscillating model of the universe. The approach with anti-Euclidean Clifford algebra Cl(0,3) leads to the de Sitter model with the positive cosmological term and the exact form of the scale factor used in modern cosmology.

E-commerce businesses employ recommender models to assist in identifying a personalized set of products for each visitor. To accurately assess the recommendations’ influence on customer clicks and buys, three target areas—customer behavior, data collection, user-interface —will be explored for possible sources of erroneous data. Varied customer behavior misrepresents the recommendations’ true influence on a customer due to the presence of B2B interactions and outlier customers. Non-parametric statistical procedures for outlier removal are delineated and other strategies are investigated to account for the effect of a large percentage of new customers or high bounce rates. Subsequently, in data collection we identify probable misleading interactions in the raw data, propose a robust method of tracking unique visitors, and accurately attributing the buy influence for combo products. Lastly, user-interface issues discuss the possible problems caused due to the recommendation widget’s positioning on the e-commerce website and the stringent conditions that should be imposed when utilizing data from the product listing page. This collective methodology results in an exact and valid estimation of the customer’s interactions influenced by the recommendation model in the context of standard industry metrics such as Click-through rates, Buy-through rates, and Conversion revenue.

Air pollution has been a major environmental issue worldwide from the last few decades. It is a man-made issue that has a serious harmful impact on the environment and the health of humans. There are different sources of emission, but industrial processes and motor vehicles contribute to a chief part of air pollution. It has acute as well as chronic effects on the health of humans and affects different organs. It is thought the main environmental risk factor in the incidence and progression of several diseases such as lung cancer, asthma, Alzheimer's and Parkinson's diseases. Long-term exposure to air pollution has different toxicological impacts on humans such as respiratory and cardiovascular diseases, neuropsychiatric complications, eye irritation and skin diseases. As per the study by the World Health Organization (WHO), nitrogen oxides (NOx), carbon monoxide (CO), ozone (O₃), sulfur dioxide (SO₂), volatile organic compounds (VOCs) and heavy metals are the major air contaminants. These pollutants are different in their properties, composition and time of disintegration. The aim of this study is to review the different sources, types, impacts, challenges and mitigation of air pollution in detail.

In an age of unprecedented global complexity, interconnectedness, and urgency, the inadequacy of traditional, reductionist models of knowledge production has become glaringly apparent. This pioneering, landmark article offers a sweeping, paradigm-shifting exploration of the revolutionary emergence of "Mode 4" knowledge production - a fundamental reconceptualization of the epistemological, organizational, and methodological foundations of the research enterprise. Drawing on cutting-edge theoretical frameworks and a vast corpus of rigorous empirical evidence, this work argues that Mode 4 represents a transformative leap towards a more collaborative, transdisciplinary, and adaptive approach to knowledge creation - one that holds the potential to catalyze a profound and lasting transformation in the way we conceive of, organize, and mobilize research to address the complex, interconnected challenges facing our world. At the heart of this paradigm shift lies the groundbreaking "decuple helix" framework, which expands the scope of stakeholder engagement and knowledge co-creation to incorporate a comprehensive range of actors, from academia and industry to marginalized communities, the natural environment, and international organizations. This article delves deeply into the multifaceted roles and invaluable contributions of this diverse array of stakeholders, demonstrating how their active integration can unlock the transformative power of collaborative, values-oriented research and innovation. Furthermore, the paper provides a comprehensive example of how Mode 4 knowledge production concepts could be implemented using cutting edge innovationology research. By drawing on a rich tapestry of theoretical foundations, including complexity theory, quantum physics, humanities, social sciences, spirituality, and the arts, innovationology exemplifies the transdisciplinary ethos at the core of this paradigm shift. The article delves deeply into the collaborative co-creation, iterative and adaptive methodologies, and holistic, values-driven vision that define this groundbreaking transdisciplinary science. However, this work also candidly explores the significant institutional, methodological, equity-related, and scalability challenges that continue to hinder the widespread adoption and implementation of the Mode 4 and decuple helix frameworks. In doing so, it charts a course forward, outlining a comprehensive set of practical implications and recommendations to address these barriers and unlock the transformative potential of these emerging paradigms. Ultimately, this article offers a sweeping, cohesive, and visionary analysis of the revolutionary emergence of Mode 4 knowledge production and the decuple helix framework - positioning itself as a landmark contribution that has the potential to catalyze a profound transformation in the way we conceive of, organize, and mobilize research for a sustainable and equitable future. With its groundbreaking insights, bold vision, and rigorous interdisciplinary foundation, this work stands as a clarion call for a new era of collaborative, transdisciplinary knowledge production that can truly address the complex, interconnected crises facing our world.

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.