Papain-like lysosomal cysteine proteases include 11 human cysteine cathepsins which act as endopeptidases and/or exopeptidases. They are involved in numerous physiological and pathological processes. Among them, only cathepsins B, H, C, and X/Z exhibit exopeptidase activity. Their activities are tightly regulated in various ways to prevent potentially hazardous effects on the cell. In this review, we focus on the structural and functional aspects of these four cysteine cathepsins and their role in neurodegeneration and cancer. Neurodegenerative disorders of aging share an endolysosomal dysfunction and accumulation and spread of oligomeric forms of neurotoxic proteins. The accumulation of various protein aggregates activates the microglia, thus inducing the activation and release of cysteine cathepsins and proinflammatory cytokines, leading to neurodegeneration. In cancer, cysteine cathepsins participate in tumor progression and metastasis. Tumor–stromal crosstalk leads to activation of the stroma and overexpression and secretion of proteolytic enzymes, triggering extracellular matrix degradation and the release of soluble factors. Activated stromal cells (i.e., macrophages, fibroblasts, mast cells) secrete additional growth factors, cytokines, and chemokines that are responsible for the regulation of processes leading to tumor progression and metastasis. Therefore, a better understanding of the role of cysteine cathepsins in neurodegeneration and cancer could lead to novel targeted therapeutic approaches.

UV-A (ca. 365 nm wavelength, a.k.a. 'black light') photocatalysis has been investigated to comprehensively mitigate odor and selected air pollutants in the livestock environment. This study was conducted to confirm the performance of UV-A photocatalysis on the swine farm. The objectives of this research were to (1) scale-up of the UV-A photocatalysis treatment, (2) evaluate the mitigation of odorous gases from swine slurry pit, and (3) test different UV sources, (4) evaluate the effect of suspended particulate matter (PM), and (5) conduct preliminary economic analyses. We tested UV-A photocatalysis at a mobile laboratory-scale capable of treating ~0.2 - 0.8 m3·s-1 of barn exhaust air. The targeted gaseous emissions of barn exhaust air were significantly mitigated (p < 0.05) up to 40% reduction of measured odor; 63%, 44%, 32%, 40%, 66%, and 49% reduction of dimethyl disulfide, isobutyric acid, butanoic acid, p-cresol, indole, and skatole, respectively; 40% reduction of H2S; 100% reduction of O3; and 13% reduction of N2O. The PM mitigation effect was not significant. Formaldehyde levels did not change, and a 21% generation of CO2 was observed. The percent reduction of targeted gases decreased as the airborne PM increased. Simultaneous chemical and sensory analysis confirmed that UV-A treatment changed the overall nuisance odor character of swine barn emissions into weaker manure odor with 'toothpaste and 'mint' notes. The smell of benzoic acid generated in UV-A treatment was likely one of the compounds responsible for the less-offensive overall odor character of the UV-treated emissions. Results are needed to inform the design of a farm-scale trial, where the interior barn walls can be treated with the photocatalyst, and foul air will be passively treated as it moves through the barn.

The critical systems, which the failure and malfunction may result in human, environment and financial severe damages, are essential components in various sectors and particularly in energy domains. Although unwished, integration error problems in supervision of critical systems occurs, incurring significant expenses because of operator’s subjective analysis and on hardware topology failures. In this work, a malleable model design approach is proposed to formulate and solve the integration error problem in the critical systems supervision in terms of reliability. A real Hybrid Power Plant (HPP) case is considered as a requirement for a study case with simulated data. A method framework with informal approach (C4 diagram) and formal approach (Hierarchical Coloured Petri Nets) in radial spectrum is applied to the HPP supervision design. Using formal methods, a formulation and solution to this problem through structured, scalable and compact mathematical representations are possible. This malleable model intends to guarantee functional correctness and then reliability of the plant supervision system based on system software architecture. Outcomes suggest corroboration that the malleable model is appropriate for energy domain, and can be used for other types of critical systems, bringing all the benefits of this methodology to the context in which it will be applied.

The dairy industry relies heavily on milk pasteurization to ensure the safety and quality of milk products. Pasteurization is a process that involves heating milk to a specific temperature for a set period of time to kill harmful bacteria and other pathogens while preserving its nutritional value. recent years, newer techniques such as High Temperature Short Time (HTST) pasteurization have gained popularity due to their efficiency and effectiveness. HTST pasteurization involves rapidly heating milk to a high temperature for a short duration of time, followed by rapid cooling. This process helps to minimize the loss of flavor and nutrients in milk while ensuring its safety. However, there is still a need in the market for a compact and remotely controlled process plant for milk pasteurization. The proposed work aims to address this need by designing a process plant that is not only compact but also remotely controlled, allowing for efficient and convenient operation. can control the process plant remotely, allowing for flexibility and convenience in monitoring and managing the pasteurization process from anywhere with an internet connection

Nanomaterials have shown significant promise for enhancing the performance of composite materials and increasing their functionality for various industrial applications. This review explores the unique properties of nanomaterials, particularly carbon-based nanomaterials, and provides key findings in utilizing them to enhance composite performance. It highlights specific nano-based composite materials and their significant potential in advancing the field of nanocomposites. Challenges associated with nanocomposite production and utilization are also discussed, along with possible solutions to address them. Finally, the study provides recommendations for continued research and innovation in nanocomposites to fully unlock the benefits of these advanced materials for broader future applications.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

The objective of this paper is to present a mathematical formalism that states a bridge between Physics and Psychology, concretely between analytical dynamics and personality theory in order to open new insights in this theory. In this formalism energy plays a central role. First, the short-term personality dynamics can be measured by the General Factor of Personality (GFP) response to an arbitrary stimulus. This GFP dynamical response is modelled by a stimulus-response model: an integro-differential equation. The bridge between Physics and Psychology is provided when the stimulus-response model can be formulated as a linear second order differential equation and, subsequently, reformulated as a Newtonian equation. This bridge is strengthened when the Newtonian equation is derived from a minimum action principle, obtaining the current Lagrangian and Hamiltonian functions. However, the Hamiltonian is a non-conserved energy. Then, some changes provide a conserved Hamiltonian function: the Ermakov-Lewis energy. This energy is presented, as well as the GFP dynamical response that can be derived from it. An application case is presented: an experimental design in which 28 individuals consumed 26.51 g of alcohol. This experiment provides an ordinal scale for the Ermakov-Lewis energies that predicts the effect of a single dose of alcohol.

Transport systems are essential in the path towards sustainable urbanisation and the transition to more sustainable living. Recently, European cities have undergone substantial changes, owing to which suburbanisation is posing new challenges. Suburban areas are often more affordable in terms of housing, but their neighbourhoods tend to be car-oriented. This leads to higher commuter costs, immobility, transport and time poverty, pollution, and accident rates and a lack of social interaction. To offer sustainable mobility options to citizens, we must comprehensively understand their specific mobility practices, together with their personal characteristics, and the built environment. This study centred on the Barcelona Metropolitan Region, which has a public transport network that covers the entire area. The aim of this study was to examine the relationship between travel behaviour, transport mode use, individual characteristics, and place of residence, using detailed information sources. Herein, we used data from the annual travel survey conducted in the Barcelona region from 2018 to 2021, together with land-use and other information sources. Our findings suggest that transport policies have encouraged sustainable mobility practices, particularly in the centre of Barcelona. Despite the positive results, considerable disparities exist between the inner and outer city, with notably decreased sustainable mobility practices in the latter. Our results indicate that promoting sustainable mobility policies requires further changes in transport, city, and land-use planning that consider equity, the socioeconomic profile of citizens, and mixed urban planning.

Noise induces oxidative stress in the cochlea followed by sensory cell death and hearing loss. The proof of principle that injections of antioxidant vitamins and Mg²⁺ prevent noise-induced hearing loss (NIHL) has been established. However, effectiveness of oral administration remains controversial and otoprotection mechanisms unclear. Using auditory evoked potentials, quantitative PCR and immunocytochemistry, we explored effects of oral administration of vitamins A, C, E and Mg²⁺ (ACEMg) on auditory function and sensory cell survival following NIHL in rats. Oral ACEMg reduced auditory thresholds shifts after NIHL. Improved auditory function correlated with increased survival of sensory outer hair cells. In parallel, oral ACEMg modulated the expression timeline of antioxidant enzymes in the cochlea after NIHL. There was increased expression of Glutathione peroxidase-1 and Catalase at 1 and 10 days, respectively. Also, pro-apoptotic Caspase-3 and Bax levels were diminished in ACEMg-treated rats, at 10 and 30 days, respectively, following noise overstimulation, whereas, at day 10 after noise exposure, the levels of anti-apoptotic Bcl-2, were significantly increased. Therefore, oral ACEMg improves auditory function by limiting sensory hair cell death in the auditory receptor following NIHL. Regulation of the expression of antioxidant enzymes and apoptosis-related proteins in cochlear structures is involved in such otoprotective mechanism.

This study presents an in–depth analysis and strategic planning techniques for approaching a situation or achieving progress related to information technology services of Nueva Ecija University of Science and Technology, particularly the San Isidro Campus. As an educational organization and one in the region excellence providers in education, the University has so much vital information to manage and services to offer to provide the student's needs through the Management Information System department, application of IT services as a competing instrument to combat tedious tasks such as online admission, grade release, enrollment information, and online learning, university announcement, and possible students’ internship. The objective of this study is to determine the influence of information technology in day–to–day activities of the organization and strategy applied to streamline processes more conveniently. The researchers develop a conceptual model that would analyze the IT services' impact by identifying its strengths, weaknesses, opportunities, and threats and cleverly act on it using the TOWS Matrix in generating strategic decisions. The overall results were beneficial to the University and MIS as a basis for formulating competitive strategies and integrating it in an extended development plan.

The El Niño-Southern Oscillation (ENSO) stands as the paramount tropical phenomenon of climatic magnitude resulting from ocean-atmosphere interaction. Due to its atmospheric teleconnection mechanism, ENSO wields influence over diverse environmental variables spanning distinct atmospheric scales, thereby potentially impacting the spatiotemporal distribution of atmospheric aerosols. Within this framework, this study aims to appraise the relationship between ENSO and atmospheric aerosols across the Legal Amazon during the period between 2006 and 2011. Over this quinquennium, four ENSO events were identified. Concurrently, an analysis was conducted on the spatiotemporal variability of aerosol optical depth (AOD) and AOD extinction for Black Carbon (EAOD-BC), concomitant with said ENSO events, utilizing data derived from the Aerosol Robotic Network (AERONET), MERRA-2 model, and ERSSTV5. Through the Windowed Cross Correlation (WCC) approach, statistically significant phase lags of up to 4 to 6 months were observed between ENSO indicators and atmospheric aerosols. Moreover, conspicuous increases of over 100% in atmospheric aerosol concentration were evidenced subsequent to El Niño periods, especially during the intervals encompassing the La Niña phase, particularly within the La Niña CP (Central Pacific)/Modoki category. By analyzing specific humidity anomalies (QA), exceptional scenarios in the region were detectable. This observation suggests a notable singularity when juxtaposed with antecedent investigations and typical average patterns characterizing the impacts on the Amazonian region.

We follow the PRISMA extension for scoping reviews to review the emerging international body of empirical evidence on consumers’ attitudes and willingness to pay (WTP) for novel foods produced with New Plant Engineering Techniques (NPETs). NPETs include genome/gene editing, cisgenesis, intragenesis, RNA interference and others. These novel foods are often beneficial for the environment and human health and more sustainable under increasingly prevalent climate extremes. These techniques can also improve animal welfare and disease resistance when applied to animals. Despite these promising attributes, evidence suggests that many, but not all, consumers discount these novel foods relative to conventional ones. Our review sorts out findings to identify conditioning factors that can increase the acceptance of and WTP for these novel foods in a significant segment of consumers. International patterns of acceptance are identified. We also analyze how information and knowledge interact with consumer acceptance of these novel foods and technologies. Heterogeneity of consumers—across cultures and borders and in attitudes towards science and innovation—emerges as a key determinant of acceptance and WTP. Acceptance and WTP tend to increase when socially beneficial attributes—as opposed to producer-oriented cost-saving attributes—are generated by NPETs. NPET-improved foods are systematically less discounted than transgenic foods. Most of the valuation estimates are based on hypothetical experiments and surveys and await validation through revealed preferences in actual purchases in food retailing environments.

Ensuring access to water, sanitation, and hygiene (WASH) facilities, coupled with behavior change education in schools, is fundamental for fostering a conducive learning environment and promoting principles of inclusion, dignity, and equality. This study focuses on 12 primary schools in Anápolis, Brazil, encompassing 4,394 students and 248 teachers. WASH assessments were conducted through a questionnaire, observation of water and sanitation facilities and structures, and microbiological analysis. Over the period 2018 to 2020, the proportion of schools with safely managed drinking water surged from 42% to 92%. However, sanitation conditions in the schools were categorized as a basic level, with hygiene services rated as limited in 92% of the schools due to the absence of soap. While this study reveals that Anápolis schools generally align with WASH guidelines for basic/advanced drinking water services, there is a crucial need for enhancements in both hardware and software facilities to address sanitation and hygiene challenges.

Mangoes have a unique nutrient profile (carotenoids, polyphenols, sugars, vitamins) that we hypothesized would mitigate post-exercise inflammation. This study examined the effects of mango ingestion in moderating exercise-induced inflammation in a randomized crossover trial with 22 cyclists. In random order with trials separated by a 2-week washout period, the cyclists ingested 330 g/day mangoes with 0.5 liters water or 0.5 liters water alone for 2 weeks, followed by a 2.25-h cycling bout challenge. Blood and urine samples were collected pre- and post-2 weeks supplementation, with additional blood samples collected immediately post-exercise, and then 1.5-h, 3-h, and 24-h post-exercise. Urine samples were analyzed for targeted mango-related metabolites. The blood samples were analyzed for 67 oxylipins that are upstream regulators of inflammation and other physiological processes. After 2-weeks mango ingestion, three targeted urine mango-related phenolic metabolites were significantly elevated compared to water alone (interaction effects, p≤0.003). Significant post-exercise increases were measured for 49 oxylipins, but various subgroup analyses showed no differences in the pattern of change between trials (all interaction effects, p&gt;0.150). The 2.25-h cycling bouts induced significant inflammation but no countermeasure effect was found after 2-weeks mango ingestion despite the elevation of mango gut-derived phenolic metabolites.

During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca2+) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLCζ). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLCζ are incapable of generating Ca2+oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLCζ and to diagnose patients with reduced/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLCζ recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLCζ, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLCζ dysfunction ability.

Recent years have experienced an increase in construction and demolition waste (C&amp;DW), which is the most significant solid waste stream. C&amp;DW is contributing to exceeding all planetary boundaries and presents a range of other issues. In order to better understand the existing research on C&amp;DW, a global bibliographic analysis was undertaken through seven groups of keyword searches and the results visualised using VOCviewer. The results show that C&amp;DW receives only a modest research attention compared to other areas of waste, and this is despite an exponential increase in C&amp;DW research since 2016. The analyses also show that concrete is the most researched material in terms of C&amp;DW, and that reuse, recycling, and circular economy are so far attracting only proportionally modest research attention. This signals a need for further acceleration of the C&amp;DW research, and specifically for more research on reuse, recycling, and circular economy for materials other than concrete.

Hepatitis C virus (HCV) is diffused worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of host’s immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct acting antivirals (DAA) has shed hopes for progressive elimination of chronic HCV infection; however, this approach requires a global monumental effort. Moreover, DAA treatment does not completely restore the normal immunologic homeostasis. Here we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind.

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras expressing or transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Oncogenes induce replication stress, re-sulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment cause toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overex-pressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but interestingly not by nucleoside supplementation. This suggest that cancer selectivity is unrelated oncogene-induced replication stress. We conclude that the molecular toxi-cological mechanisms how TH588 and TH1579 kill c-Myc overexpressing cells have several com-ponents and involves MTH1-independent proteosomal degradation of c-Myc itself, c-Myc driven transcription and CDK activation, and is likely unrelated to oncogene-induced replication stress.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

The influence of pore size on the toughness of Fe-Mo-Cu-C sintered and carburized components was investigated. The charpy impact value of the component made from Fe-0.4%Mo diffusion-alloyed steel powder mixed with 2%Cu powder and 0.3% graphite powder significantly increased with a decrease in pore size. The highest impact value of 17 J/cm2 was obtained at the average pore size of 12 µm. This value was 25% higher than that of the sintered and carburized component made from conventional Fe- 4%Ni-1.5%Cu-0.5%Mo alloyed steel powder called 4Ni even though the component was made from a Ni-free alloyed steel powder. The mechanism of the improvement of the impact value by pore size refinement and the influence of microstructural difference between the components made from Fe- 0.4%Mo diffusion-alloyed steel powder and 4Ni on toughness is discussed based on optical microstructural observation and crystal orientation analysis data.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Nickel based superalloys finds extensive usage in manufacturing of intricate part shapes in gas turbine, aircraft, submarine, and chemical industries owing their excellent mechanical property and heat resistant abilities. However, machining of such difficult-to-machine alloys up to the desired accuracy and preciseness is a complex task owing to a rapid tool wear and failure. In view of this, present work proposes an experimental investigation and optimization of process parameters of the cryogenic assisted turning process during machining of Nimonic C-263 super alloy with a multilayer CVD insert. Taguchi’s L-27 orthogonal array is used plan the experiments. Effect of input parameters viz. cutting speed (N), cutting feed (f), depth of cut (d) are studied on responses viz. surface roughness (SR), nose wear (NW) and cutting forces (F) under hybrid cryogenic (direct+indirect) machining environment. A scanning electron microscope (SEM) analysis is carried out to explore the post-machining outcomes on the performance measures. The multiple responses are converted in to single response and ranked according to Taguchi based gray relational grade (TGRG). Feed rate (f) is found to be the most influential parameter from the analysis of variance of GRG. The means of GRG for each level of process parameters are used to improve the optimal process parameters further. Finally, the confirmative experiment is performed with these optimal set of process parameters which showed an improvement of 9.34% in the value of GRG. The proposed work can be beneficial to choose ideal process conditions to enhance the performance of turning operation.

Anthropogenic activities have increased the amount of urban wastewater discharged into natural aquatic reservoirs confining in them a high amount of nutrients and organics contaminants. Several studies have reported that an alternative to reduce those contaminants is using consortiums of microalgae and endogenous bacteria. In this research, a genome-scale biochemical reaction network is reconstructed for the co-culture between the microalga Chlorella vulgaris and the bacterium Pesudomonas aeruginosa. Metabolic Pathway Analysis (MPA), is applied to understand the metabolic capabilities of the co-culture and to elucidate the best conditions in removing nutrients such as Phosphorus (inorganic phosphorous and phosphate) and Nitrogen (nitrates and ammonia). Theoretical yields for Phosphorus removal under photoheterotrophic conditions are calculated, determining their values as 0.042 mmol of PO₄/ g DW of C. vulgaris, 19.53 mmol of inorganic Phosphorus /g DW of C. vulgaris and 4.90 mmol of inorganic Phosphorus/ g DW of P. aeruginosa. Similarly, according to the genome-scale biochemical reaction network the theoretical yields for Nitrogen removal are 10.3 mmol of NH₃/g DW of P. aeruginosa and 7.19 mmol of NO₃ /g DW of C. vulgaris. Thus, this research proves the metabolic capacity of these microorganisms in removing nutrients and their theoretical yields are calculated.

Acute myeloid leukemia (AML) is a rare subtype of acute leukemia in the pediatric and adolescent population but causes disproportionate morbidity and mortality in this age group. Standard chemotherapeutic regimens for AML have changed very little in the past 3-4 decades, but addition of targeted agents in recent years have led to improved survival in select subsets of patients as well as a better biologic understanding of the disease. One key paradigm of bench-to-bedside practice in the context of adult AML currently is the focus on leukemia stem cell (LSC)-targeted therapies. Here we review current and emerging immunotherapies and other targeted agents that are in clinical use for pediatric AML, through the lens of what is known (and not known) about their LSC-targeting capability. Based on a growing understanding of pediatric LSC biology, we also briefly discuss potential future agents on the horizon.

With the evolution of toxic chemicals continuing to progress, developing methods for the destruction of chemical warfare agents (CWAs) has become an increasingly important research topic. Metal-organic frameworks (MOFs) are a class of porous crystalline solids that have sparked interest in this area. Due to their exceptional porosities and large surface areas, MOFs possess superior adsorption, reactivity, and catalytic abilities, making them structurally ideal candidates for the capture and decomposition of target species. Additionally, the tunable networks of MOFs allow their chemical functionalities to be customized for various applications and operating conditions, making them practicable in personal protective equipment and adjustable to dynamic environments. This paper reviews experimental and computational studies on CWA removal by MOFs, with a special emphasis on nerve agent (GB, GD, and VX) removal via hydrolysis and sulfur mustard (HD) removal via selective photooxidation. With extraordinary structural stability and reusability, zirconium-based MOFs are the most promising materials for hydrolytic and photooxidative degradation of CWAs and are thus the primary focus of this work. First-principles approximations of the intrinsic catalytic reaction mechanisms towards different agents in Zr-MOFs are summarized, and developments in the structure-property relationships governing Zr-MOF design rules for efficient degradation in the aqueous and solid phases are discussed. We also examine recent progress in tuning and functionalizing MOFs to promote practical CWA removal under realistic battlefield conditions.

NASA’s ICESat-2space-borne photon-counting lidar mission is providing global elevation measurements that will provide significant benefits to a variety of bio-geoscience research applications. Given the novelty of elevation and the derived data products from the ICESat-2 mission, the research community needs software tools that can facilitate photon-level analyses to support product validation and development new analysis methods. Here, we describe PhotonLabeler, a free graphic user interface (GUI) for manual labeling and visualization of ICESat-2 Geolocated Photon data (ATL03). Developed in MATLAB, the GUI facilitates the reading and display of ATL03 Hierarchical Data Format (HDF) files, the manual labeling of individual photons into target classes of choice using a number of point selections tools and enables eventual saving of labeled data in ASCII format. Other capabilities include saving and loading of labeling sessions to manage labeling tasks over time. We expect labeled data generated using the application to serve two main purposes. First, serve as ground truth for validating various products from ICESat-2 mission, especially for study sites around the world that do not have existing reference datasets such as airborne lidar. Second, serve as training and validation data in the development of new algorithms for generating various ICESat-2 data products. We demonstrate the first use case through a validation case study for the land and vegetation product (ATL08), which provides canopy and terrain height estimates, over two sites. For the first site, located in northwestern Zambia, we used ICESat-2 ATL03 data acquired at night and for our second site in Texas, US, we used ATL03 data acquired during the day. The PhotonLabeler application is freely available as a compiled MATLAB binary to enable free access and utilization by interested researchers.

This paper gives both a general canonical quantum gravity theory and the general canonical quantum gravity theories of the Universe and general black hole, and discovers the relations reflecting symmetric properties of the standard nonlinear gravitational Lagrangian, which are not relevant to any concrete metric models. This paper concretely shows the general commutation relations of the general gravitational field operators and their zeroth, first, second and third style, respectively, of high order canonical momentum operators for the general nonlinear system of the standard gravitational Lagrangian, and then has finished all the four styles of the canonical quantization of the standard gravity.

This article addresses the trajectory tracking between two non-identical systems with chaotic properties. We employ the Rossler chaotic and RCL-shunted Josephson junctions model in similar phase space to study trajectory tracking. In order to achieve the goal tracking, we afford two stages to approximate the target tracking. The first stage utilizes the active control technique to transfer the output signal from the RCLs-J system into the quasi-Rossler system. Then next, the RCLs-J system employs the proposed the iterative learning control scheme and the control signal from the drive system to trace the trajectory of Rossler system. The numerical results demonstrate the proposed method and the tracking system is asymptotically stable.

(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.

Food-grade titanium dioxide (E171) contains variable percentages of TiO2 nanoparticles (NPs) posing awareness about its potential effects on human and animal health. Despite many studies, the actual relationship between the physicochemical properties of E171 NPs and their interaction with biological targets is still far from clear. We evaluated the acute toxicity of E171 in invertebrate and vertebrate animals. In the nematode C. elegans, E171 up to 1.0 mg/mL did not affect worm’s viability and lifespan but significantly impaired pharyngeal function, reproduction, and development. We also focused our attention on the fate of E171 after its penetration inside the circulatory tree, investigating whether its intravenous administration to mice could result in an acute over-absorption to filter organs. A significant increase of hepatic Ti concentration and the formation of microgranulomas were observed. Interstitial inflammation and parenchymal modification were found in lung coupled with Ti accumulation, probably due to the propensity of TiO2 NPs to agglomerate, as demonstrated by transmission electron microscopy experiments showing that the incubation of E171 with serum promoted the formation of compact clusters. Overall, these data emphasize, once again, the actual risk for human and animal exposure to E171.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

Unmanned aerial vehicles (UAVs), commonly known as drones, present a cost-effective solution for the swift collection of data from vast and remote areas that are otherwise difficult to access. The Mediterranean Basin, known for being a hot spot for plant biodiversity, hosts several habitats and taxa of significant naturalistic value. However, many of these areas are often inaccessible to botanists, making exploration and research challenging. The aim of this paper is to involve the utilization of drone surveys and open-source software for botanical research. Our primary goal is to show the effectiveness of these tools in the field and demonstrate their practical application in Natura 2000 sites. The protected area chosen for this research is Rocca di Novara, situated in northeastern Sicily. Thanks to our drone investigations, we were able to capture images of the mountain’s side that is inaccessible to humans. This allowed us to observe the habitat of some species in detail. One of the most fascinating discoveries was the reappearance of Saxifraga callosa subsp. australis, which had not been confirmed in this area for over 140 years. Using drones for botanical research can boost field research, making monitoring easier and more cost-effective over time, especially in Natura 2000 sites.

Soil CO2 efflux (FCO2) plays a dominant role in the terrestrial carbon (C) cycle but interpreting constraints on local observations is impeded by challenges in disentangling belowground CO2 sources. Trees contribute most C to forest soils, so linking aboveground properties to FCO2 could open new avenues to study plant-soil feedbacks and facilitate scaling; furthermore, FCO2 responds dynamically to meteorological conditions, complicating predictions of total FCO2 and forest C balance. We tested for proximity effects of individual Acer saccharum Marsh. trees on FCO2, comparing FCO2 within 1 m of mature stems to background fluxes before and after an intense rainfall event. Wetting significantly increased background FCO2 (6.4±0.3 vs. 8.6±0.6 s.e. μmol CO2 m-2s-1), with a much larger enhancement near tree stems (6.3±0.3 vs. 10.8±0.4 μmol CO2 m-2s-1). FCO2 varied significantly among individual trees and post-rain values increased with tree diameter (with a slope of 0.058 μmol CO2 m-2s-1 cm-1). Post-wetting amplification of FCO2 (the ‘Birch effect’) in root zones often results from the improved mobility of labile carbohydrates and further metabolization of recalcitrant organic matter, which may both occur at higher densities near larger trees. Our results indicate that plant-soil feedbacks change through tree ontogeny and provide evidence for a novel link between whole-system carbon fluxes and forest structure.

Polymeric drag reducers have been developed over many years due to the great number of practical applications. In all of them, the molecular stability is an essential requirement. Usually, polymers break down under turbulent flows, which causes a decrease in their efficiency as drag reducers. Besides that, some specific applications, in agro and biomedical fields, impose a specific requirement that must be fulfilled, which is the use of non-toxic materials. A suitable stable material that is elected to accomplish this necessity is the mucilage of aloe vera, which is a bio-polymer that can be used as an alternative to the synthetic ones. Here, we investigate the role played by the aging of aloe vera on its capacity to reduce drag. The results obtained by ¹H nuclear magnetic resonance indicate that the compositions of young and mature leaves of aloe vera are different and such a difference plays an important role on their efficiency as drag reducers. Tests were performed to analyse the drag reduction in a rotating apparatus and in a pipeline system and the efficiencies of leaves of different ages were compared to their composition. The main conclusion of these experiments is that the young mucilage samples, which are richer in complex polysaccharides and exhibit lower acid contents, are more efficient drag reducers.

This paper studies long economic series to assess the long-lasting effects of pandemics. We analyze if periods of time that cover pandemics have a change in trend and persistence in growth, and in level and persistence in unemployment. We find that there is an upward trend in the persistence level of growth across the centuries. In particular, shocks originated by pandemics in recent times seem to have permanent effect in growth. Moreover, our results show that the unemployment rate increases and it becomes more persistent after a pandemic. In this regard, our findings support the design and implementation of counter-cyclical policies to soften the shock of the pandemic.

This research not only dedicated a less restrictive method of iteration-varying function for a learning control law to design a controller but also synchronize two nonlinear systems with free time-delay. In addition, the mathematical theory of system synchronization has proved rigorously and the theory verified through an example to demonstrate the behavior of each parameter in the theory. The design of a controller using the iterative learning control law is significant for robotic tracking. The controller in this research generates a feed-forward control input using the error dynamics among the drive-response systems. The error dynamics satisfies the Lyapunov function and the combination of output errors, which respectively represented relative estimated differences of the drive-response systems. The iterative learning control rule serves the function of a filter adding previous control error after the end of each iteration. The numerical example of a synchronous system is given a Lorenz system for driving and another with the iterative learning control law for response under different initial condition. The results verify and demonstrate the proposed mathematical theory. The simulation exhibits consistency in the behavior of each parameter to match mathematical theory.

(1) Background: Grapes and their associated by-products (as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich egg with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A, and gallic acid were determined; (3) Results: In eggs laid by hens fed GP diet, Haugh units and yolk colour score were enhanced, and eggshell became thinner, but without affecting the breaking strength. No dietary effect was observed on vitamin contents in yolk. Higher gallic acid content was observed in yolk of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness and α- and γ-tocopherol concentration in yolks; (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound, but reduced shell thickness.

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B₁₂ (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.

Maize is the staple cereal in Malawi, with a daily per capita consumption of 383g (dry matter basis), primarily consumed as dehulled maize flour used to cook nsima, a thick porridge. However, the extent of mass and nutrient loss during dehulling remains unclear in this food-insecure country, where the household maize harvest typically lasts only 6–7 months. In the current study, a milling experiment to determine yield and micronutrient losses was conducted. Milling batches (30 kg) of four maize grain varieties were dehulled at three abrasive disk dehullers under controlled conditions. Mass losses ranged from 18.8% to 42.7%, with a mean of 28.2±5.7%. Maize variety and dehuller significantly affected mass loss (p&lt;0.05). Initial protein, iron, and zinc concentrations were 8.8 ±1.0 g/100g, 20.5±2.0 µg/g, and 18.2 ±2.6 µg/g, respectively. Post-dehulling nutrient true retention varied for protein (49.7% to 75.6%, mean=64.7±7.0%), iron (18.7% to 71.6%, mean=37.6±12.0 %), and zinc (11.0% to 46.2%, mean=27.9±8.7 %). Maize variety significantly influenced mass and protein loss (p &lt; 0.05), while dehuller influenced mass, iron, and zinc losses. However, no significant difference (p &gt; 0.05) was found in the interaction between dehullers and variety on mass and nutrient losses, respectively. Given Malawi's precarious food insecurity situation, transitioning from dehulled maize flour nsima to whole maize flour or less refined nsima, is imperative. Our study findings can have food and nutritional savings for other southern Africa countries where the dehulling practice is rampant.

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

This study develops a vitamin C controlled-release system trackable via color changes as a function of vitamin C release. The system is composed of coaxial microfibers prepared via coaxial electrospinning, with a core of poly(ethylene oxide) (PEO) incorporating vitamin C, and a shell composed of polycaprolactone (PCL) containing polydiacetylene (PDA) as the color-changing material. The shell thickness was controlled by adjusting the amount of PCL ejected during electrospinning, allowing the regulation of the release rate of vitamin C. When vitamin C added to PEO penetrated the PCL layer, the color of PDA changed from blue to red, indicating a color change. The results of this study can be applied to devices that require immediate detection of vitamin C release levels.

Oxide additive-free α- ⇀ β-Si3N4 phase transformation of a high-purity commercial α-Si3N4 powder was investigated at 1600 to 1900 ℃ under nitrogen pressure of 980 kPa. The XRD analysis revealed that the α- ⇀ β-Si3N4 phase transformation proceeded mainly at 1900 ℃, and was completed by the extensive 1900 ℃-heat treatment for 20 h. This phase transformation temperature was 33 ℃ lower than the theoretical α-Si3N4 dissociation temperature and confirmed as completely different from that often discussed for the liquid phase sintering of α-Si3N4 powder by direct comparison with the phase transformation behavior of a reference powder, α-Si3N4 powder doped with 1 mol% Y2O3. The unique α- ⇀ β-Si3N4 phase transformation was further studied by a set of characterization techniques including elemental analysis, HAADF-STEM and STEM-EDS analyses. The results strongly suggested that the oxide additive-free α- ⇀ β-Si3N4 phase transformation was governed by the for-mation of metastable solid solution between α-Si3N4 and impurity oxygen of approximately 0.6 wt%, which promoted the dissociation below the theoretical α-Si3N4 dissociation temperature to afford thermodynamically favorable β-Si3N4. Along with the β-Si3N4 formation, the impurity oxygen was concentrated at the Si3N4 crystal grain boundaries and subsequently released from the sample via the grain boundary diffusion.

Theories on life’s origin generally acknowledge the advantage of a semi-permeable vesicle (protocell) for enhancing the chemical reaction-diffusion processes involved in abiogenesis. However, more and more evidence indicates that the origin of life concerned the photo-chemical dissipative structuring of the fundamental molecules under UV-C light. In this paper, we analyze the Mie UV scattering properties of such a vesicle made from long chain fatty acids. We find that the vesicle could have provided early life with a shield from the faint, but dangerous, hard UV-C ionizing light (180-210 nm) that probably bathed Earth’s surface from before the origin of life and until perhaps 1,500 million years after, until the formation of a protective ozone layer as a result of the evolution of oxygenic photosynthesis.

Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include interactions between drugs and the nematodes’ bacterial food source, and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, using smaller quantities of compound, and enhanced uptake of three dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, indicating that liposomes cannot ensure uptake of any compound. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT) and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially-mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection, and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also show how nematode-bacteria interactions can determine the effects of compounds on C. elegans lifespan in a variety of ways.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (> 100 mg/L) and signs of respiratory failure were treated with CRP apheresis. 2-12 CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest x-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. All patients had comorbidities. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation require-ments. Our clinical observations regarding the here presented seven patients support the hypoth-esis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

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

Hepatitis C Virus (HCV) is the main causative factor for liver cirrhosis and the development of liver cancer, with a confirmed ~ 180 million infections worldwide. E2 is an HCV structural protein responsible for virus entry to the host cell. Heat Shock Protein A5 (HSPA5), also termed BiP and GRP78, is the master regulator of the unfolded protein response mechanism, where it mainly localizes in the lumen of the Endoplasmic Reticulum (ER) in normal conditions. Under the stress of HCV infection or carcinogenesis, HSPA5 is upregulated. Consequently, HSPA5 escapes the ER retention localization and translocates to the cytoplasm and plasma membrane. Pep42, a cyclic peptide that was reported to target explicitly cell-surface HSPA5 in vivo. Owing to the high sequence and structural conservation between the C554-C566 region of HCV E2 and the Pep42, then we propose that the HCV E2 C554-C566 region could be the recognition site. The motivation of this work is to predict the possible binding mode between HCV E2 and HSPA5 by implementing molecular docking to test such proposed binding. Docking results reveal the high potent binding of the HCV E2 C554-C566 region to HSPA5 substrate-binding domain β (SBDβ). Moreover, the full-length HCV E2 also exhibits high binding potency to HSPA5 SBDβ. Defining the binding mode between HCV E2 and HSPA5 is of significance, so one can interfere with such binding and reducing the viral infection.

Consider a uniquely ergodic $C^*$-dynamical system ba\-sed on a unital $*$-endomorphism $\Phi$ of a $C^*$-algebra. We prove the uniform convergence of Cesaro averages $\frac1{n}\sum_{k=0}^{n-1}\lambda^{-n}\Phi(a)$ for all values $\lambda$ in the unit circle which are not eigenvalues corresponding to "measurable non continuous" eigenfunctions. This result generalises the analogous one in commutative ergodic theory presented in [19], which turns out to be a combination of the Wiener-Wintner Theorem (cf. [22]) and the uniformly convergent ergodic theorem of Krylov and Bogolioubov (cf. [15]).

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes Fusarium head blight (FHB) disease in cereal crops. Ingestion of food contaminated with DON poses serious human health complications. However, the DON cytotoxicity has been mostly deduced from animal studies. In this study, we used the nematode Caenorhabditis elegans (C. elegans) as a tractable animal model to dissect the toxic effect of DON. Our results indicate that DON reduces the fecundity and lifespan of C. elegans. The real-time RT-PCR analysis showed that DON upregulates innate immunity-related genes including C17H12.8 and K08D8.5 encoding PMK-1 (mitogen activated protein kinase-1)-regulated immune effectors, and F35E12.5 encoding a CUB-like domain-containing protein. Furthermore, our RNAseq data demonstrate that out of ~ 17,000 C. elegans genes, 313 are upregulated and 166 were downregulated by DON treatment. Among the DON-upregulated genes, several are ugt genes encoding UDP-glucuronosyl transferase (UGTs) which are known to be involved in chemical detoxification. The three upregulated genes, F52F10.4 (oac-32), C10H11.6 (ugt-26) and C10H11.4 (ugt-28) encoding the O-acyltransferase homolog, UGT26 and UGT 28, respectively, are shown to contribute to DON tolerance by RNAi bacterial feeding experiment. The results of this study provide insights to the targets of DON cytotoxicity and potential mitigation measures.

Background. A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. Methods. A longitudinal study was carried out in rats subjected to incisional myringotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7, 10, 14 and weekly thereafter until perforation closure, for up to 6 months. Results. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated with saline had a mean healing time of 8.5 days. At 8 weeks, 70.5% of these remained perforated and at 6 months this number fell to 21.4%. Conclusion. This technique is able to maintain more than 70% of tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.

Unpaid family caregivers might suffer losses in income as a result of care provision. Here we used data from the baseline survey of the China Health and Retirement Longitudinal Study to assess the relationship between hours of weekly caregiving provided to grandchildren/parents/parents-in-law and individual’s monthly employment income. Our study sample comprised 3,718 middle-aged Chinese adults who were of working age (45-60 years). For women and men separately, we used a likelihood-based method to determine a caregiving threshold in a two-stage Heckman selection procedure. Instrumental variables were used to rule out the endogeneity of caregiving hours. Our analysis revealed a negative association between caregiving and income for women that depended on a caregiving threshold of 63-hours per week. There was an absence of caregiving-income relationship among men. These results offer new insights into the opportunity costs of unpaid caregiving and support tailored policies to protect the financial well-being of female caregivers.

The links between mindfulness, savoring positive experiences, and depressive symptoms have been well-established in the literature. Nevertheless, little has been done to disentangle the prospective relations among these constructs. Clarifying the longitudinal relations is crucial, as it enables researchers and practitioners to discern potential trajectories of mental health interventions. In this study, 180 emerging adults between 18 and 27 years old were recruited twice at 3 months apart to complete self-reported measures including mindfulness, savoring positive experiences, and depressive symptoms. Cross-lagged path analysis indicated that savoring the moment was predictive of mindfulness three months later, whereas depressive symptoms were predictive of both mindfulness and savoring the moment three months later, above and beyond the effects of age, gender, and family income. Additionally, mindfulness, savoring positive experiences, and depressive symptoms were significantly correlated at baseline. The present study evidenced short-term inversed effects of depressive symptoms on mindfulness and savoring the moment, as well as a positive effect of savoring the moment on mindfulness. Hence, interventions gearing towards symptom reduction of depression are likely to carry concurrent and prospective benefits of psychological functioning, namely the ability to be present in the moment and to savor. Taken together, reducing depressive symptoms may be crucial in fostering psychological well-being.

This paper gives solutions to puzzles of double Wheeler’s delayed choice experiments, a photon’s passing two paths simultaneously and wave collapse velocity measure, and shows new quantum control, new quantum oscillation and new controlling photon oscillator (that can be arranged in quantum computer and quantum network as their classical correspondences) in experiments. Furthermore, this paper obtains the measured attractive state and the new useful key technology of altering state’s evolving paths for quantum systems. We discover the reason and the technological way for the present changes the past, further show their feasible experiments of new quantum control, new quantum oscillation and new quantum oscillator. Finally, this paper achieves the collapse response time t of wave, further concretely deduces the measured collapse velocity of quantum system. In the past, the collapse velocity cannot be objectively deduced and experimentally measured.

In the context of Shared Autonomous Vehicles, the need to monitor the environment inside the car will be crucial. This article focuses on the application of deep learning algorithms to detect objects, namely lost/forgotten items to inform the passengers, and aggressive items to monitoring if violent actions may arise between passengers. For object detection algorithms was used public datasets (COCO and TAO) to train state-of-the-art algorithms, such as YOLOv5. For violent action detection was used the MoLa InCar dataset to train on state-of-the-art algorithms such as I3D, R(2+1)D, SlowFast, TSN and TSM. At the end an embedded automotive solution was used to demonstrate both methods running in real-time.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

This research investigates the relationship between the long-term orientation of top managers and their strategic decision-making processes, emphasising the comprehensiveness, speed, and inventiveness of decisions. The study employed structural equation modelling to look into the suggested connections using a sample of CEOs. The findings demonstrated a high and positive correlation between long-term orientation and decision comprehensiveness and speed, but not for decision creativity. The study contributes to the growing body of research on how human variations, such as temporal orientation, affect business outcomes and strategic decision-making. Moreover, the fact that a number of the results differed from those of other studies carried out in other contexts highlights how important it is to consider the industry and cultural environment when assessing these connections.

In practice, a post-extractivist vision for farmer communities in the Amazon demands the study and demonstration, in the field, of alternative economic activities that are not based on resource extraction but on adding value to currently generated residual biomass. Following principles of bioeconomy, this study presents an experimental analysis of a retort burner and a pilot-scale auger-type pyrolysis reactor used to convert coffee husks generated in a post-harvesting facility of a farmer´s cooperative into thermal energy and biochar, respectively. The study shows that use of coffee husks, whether for combustion or pyrolysis processes, can supply the thermal energy required by the post-harvesting processes. The combustion or pyrolysis of coffee husks avoids its accumulation and decomposition while replacing the fossil fuels used in post-harvesting operations, reducing costs and making the farmers independent of fossil fuel subsidies. Unlike combustion, the CO concentration in the flue gas during the pyrolysis process was below the eco-design standard of 500 mg/Nm3. According to the European Biochar Certificate, carbonized coffee husks can be regarded as biochar for soil amendment and carbon sequestration. A study is required to assess the ability of cooperatives to generate and trade carbon credits linked with the application of biochar in their cropping systems.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

Deep learning dominates automated animal activity recognition (AAR) tasks due to the high performance on large-scale datasets. However, constructing centralised data across diverse farms raises data privacy issues. Federated learning (FL) provides a distributed learning solution to train a shared model by coordinating multiple farms (clients) without sharing their private data. Whereas directly applying FL to AAR tasks often faces two challenges: client-drift during local training and gradient conflicts during global aggregation. In this study, we develop a novel FL framework called FedAAR to achieve AAR with sensor data. Specifically, we devise a prototype-guided local update module to alleviate the client-drift issue, which introduces global prototypes as shared knowledge to force clients to learn consistent features. To reduce gradient conflicts between clients, we design a gradient refinement-based aggregation module to eliminate conflicting components between client gradients during global aggregation, thereby improving the agreement between clients. Experiments are conducted on a public dataset to verify FedAAR’s effectiveness, which consists of 87,621 2-s motion data. The results demonstrate that FedAAR outperforms state-of-the-arts, with precision (75.23%), recall (75.17%), F1-score (74.70%), and accuracy (88.88%), respectively. The ablation experiments also show FedAAR’s robustness against various factors (i.e., different data sizes, communication frequency, and client numbers).

β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

Background: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2 has posed unprecedented challenges to healthcare systems worldwide. Here, we have identified proteomic and genetic signatures for improved prognosis which is vital for COVID-19 research. Methods: We investigated the proteomic and genomic profile of COVID-19 positive patients (n=400 for proteomics, n=483 for genomics), focusing on differential regulation between hospitalised and non-hospitalised COVID-19 patients. Signatures had their predictive capabilities tested using independent machine learning models such as Support Vector Machine (SVM), Random Forest (RF) and Logistic Regression (LR). Results: This study has identified 224 differentially expressed proteins in hospitalised COVID-19 patients compared to non-hospitalised COVID-19 patients, involved in various inflammatory and immunological pathways. LGALS9 (p-value < 0.001), LAMP3 (p-value < 0.001), PRSS8 (p-value < 0.001) and AGRN (p-value < 0.001), were identified as the most statistically significant proteins. Several hundred rsIDs were queried across the top 10 significant signatures, identifying three significant SNPs on the FSTL3 gene showing correlation with hospitalisation status. Conclusion: Our study has not only identified key signatures of COVID-19 patients with worsened health but has also demonstrated their predictive capabilities as potential biomarkers, which suggests a staple role in the worsened health effects caused by COVID-19.

Cement production contributes to about 7% of CO2 emissions into the atmosphere. Despite our best efforts, we cannot find a competitive substitute that is both reliable and environmentally friendly. The simplest way to solve the problem is to rationalize the resources and try to minimize its use by substitute them with other materials. A concrete that contains a substantial amount of fly ash is already available, but its use is limited by the current shortage in the market and reduced initial resistance. In this context, ternary mixtures have been used to conduct an experiment. A significant volume of cement has been replaced with fly ash and metakaolin, which serves as a correction factor for the performance. In this work the main advantages and disadvantages of the simultaneous use of these two additions, which may reveal to be very interesting with high volumes of substitution will be presented. The performance of this ternary mixture is very promising. Provide a wide range of possibilities for replacing cement, maintaining or even improving its mechanical and durability properties. A solution for an ecological concrete with enhanced performance for general use in construction as an alternative to conventional concrete.

The upsurge in and havoc being wrecked by antibiotic resistant bacteria makes urgent the need for efficacious alternatives to antibiotics. This study assessed the antibacterial efficacy of two isobutyl-cyanoacrylate nanoparticles (iBCA-NPs), D6O and NP30, against major bacterial pathogens of fish. In vivo tests on rainbow trout were preceded by tests of in vitro minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). NP30 exhibited higher efficacy, but both iBCA-NPs demonstrated dose-dependent and species-specific in vitro antibacterial properties against the bacterial isolates. Generally, Gram-negative bacteria were more resistant to the iBCA-NPs. Streptococcus iniae, Tenacibaculum maritimum, and Photobacterium damselae were particularly sensitive to both iBCA-NPs. Orally administered to rainbow trout, the iBCA-NPs produced relative gain rate and survival rates comparable to the control (P > 0.05). Condition factor, hepatosomatic and viscerosomatic indices of fish were indifferentiable (P > 0.05) between the iBCA-NP groups and the control. The iBCA-NPs caused no alteration in stress, oxidative stress (superoxide dismutase, SOD), plasma complement titre, and lysozyme activity. The results of this study suggest that D60 and NP30 may contribute to reducing the amount of antibiotics and chemotherapeutic agents being used in aquaculture.

Multifunctional landscapes are complex systems that integrate biophysical, cultural-historical and socio-economic components into unique territorial structures and regional ensembles. Facing increasing pressures generated by urbanization, climate change and overexploitation of natural resources, assessing the sustainability of these landscapes has become an urgent priority. The present research is based on the development and parametrization of a new tool for evaluating the sustainability of multifunctional landscapes that aims to measure the level of biocultural resilience of a landscape, integrating biological, cultural and socio-economic indicators in a single analytical framework. This index, called the biocultural resilience index (BRI), provides a holistic perspective on the dynamics of landscapes, allowing the identification of vulnerability areas and the development of conservation and sustainable management strategies. The evaluation of the of multifunctional landscapes sustainability requires a comprehensive approach that has to integrate both biological aspects, such as biodiversity and ecosystem health, as well as identity and cultural aspects, such as cultural value and the relationship of the local communities with the environment. In this context, this study highlights the fact that the development of appropriate tools and methods for assessing and monitoring the sustainability of multifunctional landscapes becomes essential for their sustainable management and for protecting the benefits they offer to society. Our findings show that the biocultural resilience index (BRI) can be used in a variety of contexts and fields, including spatial planning, biodiversity conservation, sustainable rural development and ecotourism. In the meanwhile, this index offers a robust and flexible analytical framework, adaptable to the needs and particularities of different regions and communities.

Colorectal cancer is a major threat to the society causing the death through metastasis to several patients with stage IV. Computational tools provide a relatively quick procedure in order to evaluate several molecules for their drug activity. Prenylated flavonoids are well known for their anticancer properties even in colon cancer. Here, we provided altered structures of chalcones, based on theoretical studies that are showing better binding affinities to several colon cancer related proteins. Using molecular docking and dynamics, alongside with density function theory and ADMET studies we are representing two new derivatives of Xanthohumol prenylated flavonoids having promising results against this disease.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

The Soil Conservation Service - Curve Number (SCS-CN) method is extensively used to calculate the runoff from rainfall over a large catchment over the world. Slope is an important criterion for runoff but a very few attempts have been made to evaluate the effect of slope on the CN with runoff potential. The objective of this paper is to summarise the historical review on the effects of slope on CN and runoff potential in various regions by the hydrologists. This paper also depicts that how the various researchers proved the importance of consideration of slope for CN and runoff estimation. In addition, paper highlights the key features of research in future like to classify the watersheds on slope based CN, accurate Antecedent Moisture Condition (AMC) and proper initial abstraction in the various regions etc. Considering these parameters an accurate runoff estimation can be predicted and managed properly in the urban watersheds.

Although the presence of dark energy is well established from various observations, its true nature is still not well understood. The cosmological constant term seems to be the preferred candidate. In earlier work we had a constant cosmological constant term to limit the sizes of large-scale structures at lower redshifts. In this work, we extend this to large scale structures at higher redshifts. Here we invoke a time varying cosmological constant to set constraints on sizes of galaxies at high redshifts and see that they are consistent with their observed sizes. The time-varying cosmological constant also provides a possible solution to the puzzle of structure formation of large disk galaxies (like the Wolfe disk) observed at very early stages of the Universe. Future observations of galaxies at even higher redshifts could support our approach.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlighting the clinical importance, underlying mechanisms, and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

Background: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coro-nary heart disease. We investigated the relationship of CRP with findings from myocardial per-fusion imaging (MPI). Methods: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) that underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6mg/L) within 1 month from MPI, were included. Patients had no infection or recent acute coronary syndrome. Results: the median CRP level was 4mg/L (2,10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (P = 0.006) and summed rest score (SRS) (P = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, P = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (P = 0.027 and P = 0.005 respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). Conclusion: A high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

This study investigates the effect of Re addition on the microstructure evolution and oxidation resistance of Co-Cr-Ta-Ti-C alloys. The alloys tested in this study consist of a Co-rich matrix with mixed HCP and FCC phases, together with TaTiC2 and Ti-based carbides. The addition of Re promotes the precipitation and growth of a CoCr-rich σ phase. Differential thermal analysis (DTA) showed that the melting temperatures did not change drastically up to 10 at% Re addition, whereas 15 at% Re addition significantly increased the melting temperature of the alloys. Oxidation tests in air at 1200°C showed that excessive Re content could lead to deterioration in oxidation resistance, mainly due to the accelerated formation of volatile Re oxides.

Umbu is a tropical fruit with high content of bioactive compounds. However, maturation causes significant losses on nutrient density reducing the nutritional value of this highly appreciated fruit. Thus, the objective of the present work was to encapsulate the Umbu fruit bioactive compounds using spray drying and identify the variables affecting the biomolecules preservation. A Box-Behnken experimental design with 3 factors was set varying inlet temperature, atomization flow rate, and maltodextrin concentration for process otimization. Then the powder physicochemical and chemical properties were characterized, and results were modeled using a polynomial equation. Results revealed that the droplet size and maltodextrin concentration had a significant influence on the conservation of the biomolecules. Drying kinetics favoring fast formation of a particle crust increases encapsulation efficiency. Bioactive compounds retention was achieved by increasing maltodextrin even at high temperatures, where a matrix is formed hindering chemical degradation. Process optimization was validated and revealed low inlet temperatures (122ºC), high atomization flow rate (5kg/h) and high maltodextrin concentration (20%) to be the most desirable conditions for bioactive compounds retention.

The runoff coefficient (C) represents the relationship between the surface runoff volume and the precipitated volume. It is used in engineering projects for flood estimation methods. Although C values are tabulated and consecrated in hydrological engineering, as if they were constant, they may not correspond to the reality, because in the same catchment, they can vary according to the intensity, temporal and spatial distribution of precipitation events, humidity conditions, and ground cover. This study had the objective of analyzing extreme events of precipitation and the corresponding flows to obtain experimental runoff coefficients (C) and compare them with the tabulated values. The study was conducted in four experimental catchments in the State of São Paulo, Brazil, with different land uses and soils. The runoff coefficients (C) were obtained from the analysis of hydrograms and using a digital filter, which allowed the separation of the direct runoff, of the total flow. When analyzing flow and precipitation data in different seasons of the year, selecting events of the floods of catchments and separating the flows, we observed a variation of the flow coefficient values, different from those obtained from tables.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

This paper uncovers that quantum uncertain principle makes the single particle with global property have no certain path, and then wave of quantum particle can simultaneously do pass the double slits. The two subwaves after passing Young’s double slits are entanglement, they may form interference of subwaves. Consequently, we find a kind of quantum probabilistic entanglements with Wheeler's delayed choice. Quantum particles such as photons, electrons, neutrons, protons etc mean that wave of the quantum particle can simultaneously do pass through Young's double slits, rather than individual quantum particle may pass through Young's double slits at the same time. When considering wave property, we cannot consider particle property (Just as in the photoelectric effect, considering the particle nature of the system, people cannot consider wave property, otherwise the photoelectric effect cannot appear). Therefore, this paper discovers that the ability of single photon to hit electrons out in photoelectric effect is complementarily equivalent to the ability of wave of the single photon to simultaneously pass through Young's double slits in wave-particle duality. Objective criteria for distinguishing classical and quantum particles are discovered and objectively give the applicable realm of quantum mechanics for the first time. The crisis of the single particle’s simultaneously passing through Young's double slits, which has been plaguing physicists in the whole world up to now for decades, is solved, in which the studies are classified as classical and quantum particles, the classical particle and quantum particle wave cannot and can pass the Young’s slits, respectively. This paper discovers both the new physics mechanism of passing the double slits of the wave with the amplitude of 4-dimensional momentum representation wave function reflecting particle nature and the principle of self-adaptive emergence of wave-particle duality, and then using the principle, this paper gives both direct explanations to the current experiments and new predictions of new some experiments for wave-particle duality. All the deduced results here are consistent with all relevant physics experiments.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

One of the biggest challenges in modern physics is how to unify gravity with quantum theory. There is an absence of a complete quantum theory of gravity, and conventionally it is thought that the effects of quantum gravity occur only at high energies (Planck scale). Here we suggest that certain novel quantum effects of gravity can become significant even at lower energies and could be tested at laboratory scales. We also suggest a few indirect effects of dark energy that can show up at laboratory scales. Using these ideas, we set observational constraints on radio recombination lines of the Rydberg atoms. We further suggest that high-precision measurements of Casimir effects for smaller plate separation could also show some manifestations of the presence of dark energy.

Hepatitis B and C are major health issues in developing countries such as Pakistan and Afghan-istan. The aim of this study was to determine the prevalence and effectiveness of a screening program for hepatitis B and C in a region with no existing programs, and to estimate their prev-alence in the general population in Khyber Pakhtunkhwa Province, Pakistan, as well as in Afghan refugees or migrants. A prospective cohort study was done in the general population of Peshawar and its adjacent districts, as well as migrants from neighboring provinces of Afghani-stan, who presented to our tertiary-care health facility. A Microsoft Excel registry was created for data collection, which were analyzed using IBM SPSS via descriptive analysis, normal distribution curve histograms, and chi-squared tests. A total of 9563 individuals were screened for hepatitis (5894 males and 3669 females), including Afghan migrants in Peshawar and surrounding districts. 876 individuals tested positive for hepatitis, with 538 positive for hepatitis B (383 males and 155 females) and 330 positive for hepatitis C (198 males and 134 females). Eight individuals had a hepatitis B and C co-infection. Among the study population, the prevalence rates were 2.2% for hepatitis B and 2.3% for hepatitis C, of which the Afghan migrants accounted for 2.7% and 0.5%, respectively. According to the gender-based distribution, hepatitis B was more prevalent in males, whereas there was no significant gender-based difference for hepatitis C. Our results highlight the need for a comprehensive approach to control hepatitis B and C in Pakistan and Afghanistan. Increased awareness, improved healthcare, and preventive measures such as screening and elimination programs to prevent severe liver diseases and eradicate hepatitis are necessary.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

The study aimed to determine the relationship between glucose, C-peptide, BDNF, and leptin between mother and fetus and neonatal weight. Methods: In the prospective observational cohort study, we included 66 women with T1DM. According to the z-score for neonatal weight, patients were divided into Healthy weight neonates (n=42) and Overweight neonates (n=24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, CRP, leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, FT3, FT4, and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. Results: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Increased odds for Overweight neonates were BMI, BDNF, and TSH in the first trimester of pregnancy. Maternal leptin concentration decreased the odds of Overweight neonates. Conclusions: Maternal glucose concentrations affect the fetus’s glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, its fat body mass is responsible for increased leptin concentrations.

Hepatitis is the eighth highest cause of mortality globally and second-highest in Pakistan. The purpose of this study was to determine frequency of Hepatitis B and C and related lifestyle and socio-demographic risk factors among adults. The data were collected though questionnaire from Hepatitis B and C patients from Mayo and Jinnah hospital Lahore. The data was analyzed using SPSS version 18. There were 5095 patients with Hepatitis B and C out of which 146 patients (67 males and 79 females) filled questionnaire. The frequency of hepatitis C was higher than hepatitis B. The significant risk factors associated with hepatitis B and C were education, marital status, family history, household income, and type of food consumed. Therefore, socio-demographic and lifestyle risk factors related interventions are needed to reduce frequency of Hepatitis B and C.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

The stress imposed by ethanol to Saccharomyces cerevisiae cells are one of the most challenging limiting factors in industrial fuel-ethanol production. Consequently, the toxicity and tolerance to high ethanol concentrations has been the subject of extensive research, allowing the identification of several genes important for increasing the tolerance to this stress factor. However, most studies were performed with well characterized laboratory strains, and how the results obtained with these strains work in industrial strains remains unknown. In the present work we have tested three different strategies known to increase ethanol tolerance by laboratory strains in an industrial fuel-ethanol producing strain: overexpression of the TRP1 or MSN2 genes, or overexpression of a truncated version of the MSN2 gene. Our results show that the industrial CAT-1 strain tolerates up to 14% ethanol, and indeed the three strategies increased its tolerance to ethanol. When these strains were subjected to fermentations with high sugar content and cell-recycle, simulating the industrial conditions used in Brazilian distilleries, only the strain with overexpression of the truncated MSN2 gene showed improved fermentation performance, allowing the production of 16% ethanol from 33% of total reducing sugars present in sugarcane molasses. Our results highlight the importance of testing genetic modifications in industrial yeast strains under industrial conditions in order to improve the production of industrial fuel ethanol by S. cerevisiae.

Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future.

The Bessel function of the first kind J_N(kx) is expanded in a Fourier-Legendre series, as is the modified Bessel functions of the first kind I_N(kx) . Known polynomial approximations for the range −3≤x≤3 (having five-digit accuracy) are compared with those arising from this Legendre series and substitute versions are given with twice the number of terms and range (with five-digit accuracy or having fifteen-digit accuracy over −3≤x≤3). It is shown that infinite series of like-powered contributors (involving _2F_3 hypergeometric functions) extracted from the Fourier-Legendre series may be summed, having values that are inverse powers of the first five primes 1/(2^i 3^j 5^k 7^l 11^mm) for powers of order x24.

Newton’s law of universal gravitation applies between two point-masses. True gravitation of solid Earth is volume integration of gravitation of all point-masses inside the solid Earth on a point-mass in atmosphere. However, in meteorology the Earth “shrinks” into a point-mass located at Earth center with entire Earth mass to identify the Earth gravitation (untrue). Combination of untrue gravitational and centrifugal accelerations gives effective gravity (geff). Combination of true gravitational and centrifugal accelerations leads to true gravity (g). The true gravity g minus the effective gravity geff is the gravity disturbance vector, δg = g – geff. With the true gravity g used in the basic equations, seven non-dimensional numbers are proposed to identify the importance of δg versus traditional forcing terms such as horizontal pressure gradient force and Coriolis force. These non-dimensional numbers are calculated from two publicly available datasets with the geoid undulation (N) from the static gravity field model EIGEN-6C4 and long-term mean geopotential height (Z), wind velocity (u, v), and temperature (Ta) at 12 pressure levels in troposphere from the NCEP/NCAR reanalyzed climatology. The results demonstrate δg nonnegligible in hydrostatic equilibrium, geostrophic wind, geostrophic vorticity, Ekman pumping, Q vector, and Omega equation, but negligible in thermal wind relation.

This research introduces Genus-Physiognomy-Ecosystem (GPE) mapping at a prefecture level through machine learning of multi-spectral and multi-temporal satellite images at 10m spatial resolution, and later integration of prefecture wise maps into country scale for dealing with 88 GPE types to be classified from a large size of training data involved in the research effectively. This research was made possible by harnessing entire archives of Level-2A product, Bottom of Atmosphere reflectance images collected by MultiSpectral Instruments onboard a constellation of two polar-orbiting Sentinel-2 mission satellites. The satellite images were pre-processed for cloud masking and monthly median composite images consisting of 10 multi-spectral bands and 7 spectral indexes were generated. The ground truth labels were extracted from extant vegetation survey maps by implementing systematic stratified sampling approach and noisy labels were dropped out for preparing a reliable ground truth database. Graphics Processing Unit (GPU) implementation of Gradient Boosting Decision Trees (GBDT) classifier was employed for classification of 88 GPE types from 204 satellite features. The classification accuracy computed with 25% test data varied from 65-81% in terms of F1-score across 48 prefectural regions. This research produced seamless maps of 88 GPE types first time at a country scale with an average 72% F1-score. In addition, mapping of solar panels and vegetation disturbance are added.

Utilization of Bidirectional Reflectance Distribution Function (BRDF) model parameters obtained from the multi-angular remote sensing is one of the approaches for the retrieval of vegetation structural information. In this research, the potential of multi-angular vegetation indices, formulated by the combination of multi-spectral reflectance from different view angles, for the retrieval of forest above ground biomass was assessed. This research was implemented in the New England region with the availability of a high quality forest inventory database. The multi-angular vegetation indices were generated by the simulation of the Moderate Resolution Imaging Spectroradiometer (MODIS) BRDF/Albedo Model Parameters Product (MCD43A1 Version 6) based BRDF parameters. The effects of seasonal (spring, summer, autumn, and winter) composites of the multi-angular vegetation indices on above ground biomass, angular relationship of the spectral reflectance with above ground biomass, and the interrelationships between the multi-angular vegetation indices were analyzed. Among the existing multi-angular vegetation indices, only the Nadir BRDF-adjusted NDVI ( and Hot-spot incorporated NDVI ( showed significant relationship (more than 50%) with the above ground biomass. This research proposed two more sensitive vegetation structural indices, Fore-scattering Back-scattering NDVI and Vegetation Structure Index (VSI). The Fore-scattering Back-scattering NDVI showed higher sensitivity (R² = 0.62, RMSE = 52.46) towards the above ground biomass than existing multi-angular vegetation indices. Furthermore, the VSI performed in the most efficient way explaining 64% variation of the above ground biomass, suggesting that the right choice of the spectral channel and observation geometry should be considered for improving the estimates of the above ground biomass. In addition, the right choice of seasonal data (summer) was found to be important for estimating the forest biomass while other seasonal data were either insensitive or pointless. The promising results shown by the VSI suggest that it could be an appropriate candidate for monitoring vegetation structure from the multi-angular satellite remote sensing.

This paper presents ensemble learning of multi-source satellite sensors dataset to obtain better predictive performance of the forest biomass. Spectral, spectral-indices, and spectral-textural features were generated from two optical satellite sensors, Landsat 8 Operational Land Imager (OLI) and Sentinel-2 Multispectral Instrument (MSI). In addition, two radar satellite sensors, Sentinel-1 C-band Synthetic Aperture Radar (CSAR), and Advanced Land Observing Satellite (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) were utilized to generate backscattering and backscattering-textural features. The plot-wise above ground biomass data available from five forests in New England region were utilized. Ensemble learning of multi-source satellite sensors dataset was carried out by employing four machine learning regressors namely, Support Vector Machines (SVM), Random Forests (RF), Gradient Boosting (GB), and Multilayer Perceptron (MLP). A five-fold cross-validation method was used to evaluate predictive performance of the multi-source satellite sensors. The integration of multi-source satellite features, comprising of spectral, spectral-indices, backscattering, spectral-textural, and backscattering-textural information, through ensemble learning and cross-validation approach implemented in the research showed promising results (R² = 0.81, RMSE = 46.2 Mg/ha) for the estimation of plots-level forest biomass in New England region.

There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer’s disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma parasites. Also, some of the antimicrobial and antiviral agents that are used to treat them have shown promise for AD interventions. I describe this evidence and assert it is now time to accelerate clinical trials of these existing drugs, already federally approved, to determine if such treatments can delay, halt, or reverse AD.

In Newtonian mechanics, time as well as space are perceived as absolute entities. In 2 Einstein’s special relativity, time is frame dependent. Time is also affected by gravitational field 3 and as the field varies in space, time also varies throughout space. In the present article, a 4 thermodynamic-based time is investigated. The entity is called "irreversibility", which is generated 5 when availability (also known as exergy) is destroyed. Since each thermodynamic system may 6 generate different amount of irreversibility, this quantity is system dependent. The time’s arrow is 7 automatically satisfied, since irreversibility generation always proceeds in one direction (toward 8 future). We have demonstrated that, like common time, irreversibility is frame dependent, and 9 affected by gravity in the similar manner as the common time. For this reason, we propose to 10 assign the entity irreversibility of the system as thermodynamic time. A possible application of the 11 thermodynamic time is an interpretation and managing of the aging of biological systems. The 12 metabolic efficiency is related to the irreversibility of the chemical processes and affect the aging of 13 the system. Our sensation of time-flow may be attributed to the flow of availability and destruction 14 of it through the living system. It is shown by other authors that entropy generation (equivalent to 15 irreversibility) is a parameter for the human life span. Since the thermodynamic time is based on a 16 concept of thermodynamics that is universal, further applications to other subjects, such as biological 17 clock, telomere, and cosmology are possible.

Cognitive neuroscience is the study of how the human brain functions on tasks like decision making, language, perception and reasoning. Deep learning is a class of machine learning algorithms that use neural networks. They are designed to model the responses of neurons in the human brain. Learning can be supervised or unsupervised. Ngram token models are used extensively in language prediction. Ngrams are probabilistic models that are used in predicting the next word or token. They are a statistical model of word sequences or tokens and are called Language Models or Lms. Ngrams are essential in creating language prediction models. We are exploring a broader sandbox ecosystems enabling for AI. Specifically, around Deep learning applications on unstructured content form on the web.

The web ecosystem is rapidly evolving with changing business and functional models. Cloud platforms are available in a SaaS, PaaS and IaaS model designed around commoditized Linux based servers. 10 billion users will be online and accessing the web and its various content. The industry has seen a convergence around IP based technology. Additionally, Linux based designs allow for a system wide profiling of application characteristics. The customer is an OEM who provides Linux based servers for telecom solutions. The end customer will develop business applications on the server. Customers are interested in a latency profiling mechanism which helps them to understand how the application behaves at run time. The latency profiler is supposed to find the code path which makes an application block on I/O, and other synchronization primitives. This will allow the customer to understand the performance bottleneck and tune the system and application parameters.

Advancement in physics often results from analyzing numerical data and then creating a theoretical model that can explain and predict those data. In the field of lens design, the reverse is true: longstanding theoretical understanding is being overtaken by more powerful numerical methods.

This paper puts forward an alteration for Tensor Calculus utliized in a coordinate system which is under a dynamic distortion drawing inspiration from similar fields such as the Calculus of Moving Surfaces (CMS). The paper establishes transformation laws for Tensors within these regions and establishes Operators such as the Tensorial Field Derivative which enforce a Tensorial Transformation on Tensors defined within a Dynamically Moving coordinate system. This variation of Tensor Calculus can be utilized to observe how disciplines such as QFT and Continuum Mechanics would change to accomodate for a distorting coordinate system and can be utliized to develop new theoretical models which account for this temporal distortion particularly within Biological Settings.

The life and work of Ignacio Ellacuría, S.J. is of radical vision, and revolutionary change. His dynamic life and works accompanied El Salvador and the Universidad Centroamericana through perhaps the most tumultuous years of the country’s history, yet there has been limited work done to examine his contributions. This paper shows how Ellacuría viewed the role of a Christian intellectual, and a Christian university within his philosophical and theological framework. I argue that Ignacio Ellacuría held, similarly to his soteriological views, that the intellectual must also be willing to sacrifice all for the sake of his/her work in a pattern of discipleship/martyrdom prefigured by his exemplars Christ and Socrates. It was this dedication to praxis and theory that western theology and philosophy had respectfully lost since their foundations which he sought to restore to a central role. In conclusion, the Christian intellectual and institution, according to Ellacuría, must use its voice and life in service of the people even to the point of martyrdom; he would argue, the implicit reason for Christian martyrdom and the crucifixion of Christ himself.