Iron (Fe), the main component of non-exhaust particulates, is known to have variable health effects that depend on the chemical species of iron. This study characterized the possible contribution of iron oxides and hydroxides to airborne brake-wear particles under realistic vehicle driving and braking conditions with different brake-pad friction materials. We found significant differences in wear coefficients and PM₁₀ emissions between non-asbestos organics (NAO) and European performance (ECE) brake pads. Iron was the dominant contributor to PM₁₀ and PM_2.5 brake-wear particles for both NAO and ECE. The iron concentration ratio in the particle mass were comparable to the disc to pads ratio measured by wear mass. The fact that magnetite, which is of interest with respect to health effects, was less abundant in NAO than in ECE suggested that tribo-oxidations occurred in NAO. Metallic iron is generated not only from abrasive wear but also from tribo-chemical reduction with magnetite as the starting material. We found differences not only in PM emissions between brake friction materials but also that the phase transformations of iron differed between friction materials. These differences were apparent in the distribution of iron oxides and hydroxides. Heat, tribo-oxidation, and tribo-reduction are intricately involved in these reactions.

Against the backdrop of the current carbon peaking and carbon neutrality policies, higher requirements have been put forward for the upgrading and construction of smart grids. Non-intrusive load monitoring (NILM) technology is a key technology for advanced measurement systems at the end of the power grid. It obtains detailed power information of the load, without the need for traditional hardware deployment. The key step to solve this problem is load decomposition and identification. This paper first utilized Long Short Term Memory-Denoising Autoencoder(LSTM-DAE) to decompose the mixed current signal on the household busbar and obtain the current signals of multiple independent loads that constituted the mixed current. Then, the obtained independent current signals were combined with voltage signals to generate multi-cycle colored Voltage-Current(VI) trajectories, which were color-coded according to the background. These colored VI trajectories with background colors formed a feature library. When the CNN network was used for load recognition, considering the influence of hyperparameters on recognition results, the BOA algorithm was used for optimization, and the optimized CNN network was employed for VI trajectory recognition. Finally, the proposed method was validated using the PLAID dataset. Experimental results showed that the proposed method exhibited better performance in load decomposition and identification.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

An increasing need for better agricultural practices that are sustainable to provide increased yields of crops for the ever increasing food demand to be met for the growing world population is a current necessity. It is estimated by the UN that in 2050 the world’s populace may be as much as 9.8 billion global, yet, farmers still face several obstacles, which includes soil degradation, extreme temperatures, and drought which as increasingly becoming more severe with climate changes. Plant health monitoring is a method that will help to increase awareness about plant enhancing by studying how to increase crop yields while decreasing the environmental impacts. The use of low-cost, controlled environments, soil quality, water levels, and pathogenic and pests attacks can be regularly monitored. Currently, several diagnostic technologies and portable point-of-use methods and technologies are employed for detection of diseases, although, the current available lab-based methods used for plant’s diagnostics test are inadequate for plant point-of-use monitoring. The promotion of use of these point of use methods will enable pathogen detection, poor plant growth, unsuitable environmental conditions and nutrient use efficiency allowing for immediate and timely corrective actions to ensure minimal damage to the plants with maximal yield. Increase in the use of sustainable agri practices are required for ensuring higher yields with minimal inputs and that are non-destructive to the land and the use of improved methodologies and technologies will be useful tools for achieving sustainable agriculture.

From experimental studies of protein folding, it is now clear that there are two types of folding behavior, i.e., two-state folding and non-two-state folding, and understanding the relationships between these apparently different folding behaviors is essential for fully elucidating the molecular mechanisms of protein folding. This article describes how the presence of the two types of folding behavior has been confirmed experimentally, and discusses the relationships between the two-state and the non-two-state folding reactions, on the basis of available data on the correlations of the folding rate constant with various structure-based properties, which are determined primarily by the backbone topology of proteins. Finally, a two-stage hierarchical model is proposed as a general mechanism of protein folding. In this model, protein folding occurs in a hierarchical manner, reflecting the hierarchy of the native three-dimensional structure, as embodied in the case of non-two-state folding with an accumulation of the molten globule state as a folding intermediate. The two-state folding is thus merely a simplified version of the hierarchical folding caused either by an alteration in the rate-limiting step of folding or by destabilization of the intermediate.

MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.

The overwhelming evidence supports the assertion that the climate is undergoing change. Understanding the perception of locals of the magnitude of climate change and its influence on non-timber forest products (NTFPs) challenge at a global scale. Although studies on climate change, value addition, and the multiple uses of NTFPs and their impact on local livelihoods have been conducted, locals' perceptions of these factors have not been fully explored. This study aims to assess various social factors, including education, gender, and religion, and their influence on locals' perceptions of the abovementioned factors. The research focused on five regions where NTFPs are prevalent in Ghana (Western North, Bono, Ahafo, Ashanti, and Eastern regions). To investigate the impact of social factors on local perceptions of climate change, value addition, and the multiple values of NTFPs within rural communities, a total of 732 interviews with a team of interviewers across these five regions in Ghana were carried out. We applied a logistic regression model to assess the social factors and their influencing locals’ perceptions of the mentioned variables. It was revealed that age, gender, education, and occupation did not significantly influence locals' perceptions of climate change. However, religion was found to influence locals' perceptions of climate change. Furthermore, the results demonstrated that gender (P<0.000328) and education (P<0.00426) strongly influenced locals' perceptions of value addition to NTFPs. In contrast, religion and constraints (related to time, finance, and skills) did not significantly influence locals' perceptions. Additionally, it was observed that gender (0.00132), education (0.00692), and religion (8.12e-05) significantly influenced how locals perceive and use NTFPs. In conclusion, this study provides valuable insights into the intricate interplay among local perceptions, climate change, value addition, multiple uses of NTFPs, and the capacity of NTFPs to enhance the well-being of forest fringe communities. These findings underscore the importance of comprehensive, tailor-made interventions that consider local perspectives and adhere to sustainable approaches, with the aim of optimising the positive impacts of NTFPs in poverty alleviation and overall community development.

Poverty alleviation must be carried out in a planned and sustainable manner by the central government and regional governments, the private sector, and the entire community to achieve a prosperous society by getting special attention from the government. This study aims to analyze the impact of the non-cash food assistance program on poverty alleviation, stunting and economic problems using a public private partnership (PPP) approach that involves the role of the government, the private sector and the community. This study uses a qualitative-explorative research method to examine Indonesia's non-cash food assistance program as a national initiative to fight poverty in the form of food. Data were collected from interviews, field observations, and relevant literature, then Nvivo 12 Pro was used to analyze the results. The location of this research is in Indonesia, namely Takalar Regency. The results of the study show that the implementation of the non-cash basic food assistance program has been effective. The involvement of the government, the private sector, and the community shows this. The success factors for the basic food assistance program are alleviating poverty in Indonesia, reducing stunting rates, and increasing economic growth because people are given a place to be part of small businesses. From the results of this analysis it was concluded that the non-cash basic food assistance program is a special program that can overcome various social problems in society. So that poverty alleviation programs are expected to be sustainable and improved to provide benefits for people's welfare. The implementation of the food aid program also involved several cross-sectoral efforts to channel government assistance.

Simultaneous extraction of trypsin inhibitors and soy isoflavones from soybean meal was investigated using the non-destructive phytochemical extraction process, namely aqueous micellar system. The ethoxylated aliphatic alcohols Genapol X-080, Tergitol 15-S-7, and Tergitol 15-S-9, all non-toxic and biodegradable surfactants, were assessed as potential extractants. A Box-Behnken multifactorial design with the application of the Derringer desirability was used to determine the conditions that maximized the trypsin inhibitors and isoflavone extraction while minimizing the protein extraction. The optimum condition of 5% m/m of surfactant in 50 mM aqueous sodium citrate solution pH 4.5, at 45 °C for 45 min, was established for the three surfactants. The novel methodology would allow the extraction of the main soybean antinutritional factors, trypsin inhibitors, and the valuable isoflavones, preserving the nutritional quality of the treated material. This represents a sustainable alternative methodology for industrial purposes due to its low cost, biodegradability, non-toxicity, and easy scaling up.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the province of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. We performed genomic analysis to identify the changes in genetic diversity of SARS-CoV-2 between December 2019 and November 2020, and through molecular surveillance, we monitored the mutations that could be involved in viral fitness. We analyzed 2,213 complete genomes from 6 geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified 7 frequent mutations that resulted in non-synonymous substitutions (dN). Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein emerged recently and have spread in Oceania and Europe. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

Laws and regulations make powerful contribution in addressing multitudes of public health concerns. We examined the Public Health Act (PHA) in Malawi to understand its relevance to the ever-growing and changing threats posed by infectious and non-infectious diseases. The current Public Health Act of Malawi came into effect in 1948 to protect and preserve public health. The Act has undergone several amendments, the last one being in 1975. It draws much of its inspiration and standards from the 19th century British laws on insanitary housing, poor ventilation, and drainage. Such laws are silent on emerging major public health concerns including non-communicable diseases (NCDs) such as cardiovascular diseases and diabetes as well as road traffic injuries. This makes the Act outdated and ill equipped to address the 21st century public health concerns. Although supplementary legislation such as the HIV/AIDS Act and Mental Treatment Act have recently been enacted, they are yet to be consolidated into the Public Health Act. Consequently, existing policies and strategic plans that are meant to address gaps in public health and ensure coordinated effort lack support of laws and regulations. The Act also places great emphasis on mandatory vaccinations, quarantine and isolation against smallpox, a disease that has long been eradicated. Furthermore, although the Public Health Act outlines powers, duties and penalties, it fails to reinforce acceptable behaviour due to the insignificant penalties for noncompliance. There is a need for immediate and prompt revision and restructuring of the Public Health Act based on scientific evidence. Such laws require adequate consultation and interaction with key experts and stakeholders from a wide range of disciplines.

The work and life routine of long-haul truck drivers involves the use of truck stops and rest areas to meet their basic human needs. These extensions of their workspaces while on the road, do not always offer adequate physical structures and services that drivers need for optimal health. Aim: To evaluate long-haul truck drivers’ perceptions about the services of food, safety, physical activity, rest and personal hygiene offered at truck stops and rest areas in Brazil. Method: Quantitative study conducted with long-haul truck drivers from the Southern region of Brazil. For data collection, a sociodemographic questionnaire and a Likert scale on food, rest, personal hygiene, safety and physical activity services were used, offered in general at the truck stops and rest areas along Brazilian roads, from March to August 2023. The data were analyzed with simple frequency descriptive statistics. Results: 175 long-haul truck drivers participated, 70.29% declared that the services of the truck stop and rest areas were charged; more than half (53.59%) of the professionals evaluated the rest service as “good” or “excellent”; the food services, was “good” or “excellent” for 42.24% of the drivers. The spaces for physical activities were the worst evaluated as “bad” or “terrible”, by 41.61%, followed by bathroom service (28.42%) and safety (34.24%), evaluated as “bad” or “terrible”. Conclusions: In the perception of long-haul truck drivers, the rest and feeding services had better evaluations, on the other hand, the services of bathroom, safety and physical activity presented worse evaluations. The perception of drivers demonstrates the lack of investments to improve basic services such as personal hygiene, safe environment and physical exercises, fundamental to the health of the worker, aiming to reduce vulnerability, sedentary lifestyle, and meeting the basic human needs of long-haul truck drivers.

Ferns and lycophytes, now known as monilophytes, have received scant molecular attention in comparison to angiosperms. The advent of high-throughput technologies allowed an advance towards a greater knowledge of their elusive genomes. In this work, proteomic analyses of heart-shaped gametophytes of two ferns were performed: the apomictic species Dryopteris affinis ssp. affinis and its sexual relative Dryopteris oreades. In total, a set of 218 proteins shared by these two gametophytes were analyzed using the STRING database, and the proteome associated with metabolism, genetic information processing, and responses to abiotic stress is discussed. Specifi-cally, we report proteins involved in the metabolism of carbohydrates, lipids, and nucleotides, the biosynthesis of amino acids, and secondary compounds, energy, oxido-reduction, transcrip-tion, translation, protein folding, sorting and degradation, and responses to abiotic stress. Look-ing at the interactome of this set of proteins, it represents a total network composed of 218 nodes and 1,792 interactions, obtained mostly from databases and textmining. The interactions among the identified proteins of the ferns D. affinis and D. oreades, together with the description of their biological functions, might contribute to a better understanding of the function and develop-ment of ferns as well as to fill knowledge gaps in plant evolution.

Preconception lifestyle modification and reducing several known risk factors may have an influence on the future pregnancy outcome. The aim of the study was to analyse health behaviour and personal values, as well as to assess the relationship of these factors in women without children, in pregnant ones and in women who had already delivered babies. The questionnaire survey included Health Behaviour Inventory (HBI), Personal Value List (PVL) and the sociodemographic data and was conducted in 538 women. These women were divided into 3 groups: women who recently delivered (n = 235), pregnant women (n = 121) and childless women (n = 182). Pregnant women demonstrated a significantly higher level of declared health behaviours and also they rated higher subscales values "positive mental attitude" and "health practices" in comparison to women who recently delivered and to childless women. In all tested groups the highest rated personal value was "a successful family life", while the most appreciated symbol of happiness was "love and friendship". Our results suggest that the system of values and the perception of happiness symbols may influence women's health behaviours. Positioning “health” in the hierarchy of personal values as the most important one may facilitate introduction of healthy behaviours. This in turn could reduce several adverse pregnancy outcomes that are potentially modifiable with changing preconception health attitudes. Our results also identify several unanswered questions and highlights areas where new research is needed.

Acute myeloid leukemia (AML) is a hematological malignancy that is the culmination of genetic and epigenetic alterations in the hematopoietic progenitor cells, leading to uncontrolled proliferation at the expense of normal hematopoiesis and bone marrow exhaustion. Although the outcomes for pediatric AML have improved in recent decades, at least one third of children still have relapses. Recent studies have notably highlighted the important role of dysregulated epi-genetic mechanisms in myeloid leukemogenesis. Epigenetic modifications are frequently reversible compared to genetic alterations, thus providing opportunities for targeted epigenetic therapy. In this review, we summarize the landscape of epigenetic alterations and the progress to date in epigenetic targeted therapy, and focus on the future role of epigenetic abnormalities in predicting relapse and the precision therapy in pediatric AML.

The Um Ara granites are a suite of granitoid rocks located in the south Eastern Desert of Egypt. The combination of Back Scattered Electron imaging (BSE), X-ray compositional mapping, and the data of the Electron Probe Micro Analyzer (EPMA) has provided valuable insights into the alteration process of zircon in the Um Ara granite. The investigated zircon grains have measurable amount of non-formula elements such as U, Th, Hf, REEs, P, Al, Ca, Fe, and Ti, along with extensive structural features indicative of radiation damage. These characteristics point to significant hydrothermal alteration of the zircon following its initial crystallization. The textural and geochemical evidence suggests the alteration of the Um Ara zircons was driven by coupled dissolution-reprecipitation processes influenced by aqueous fluids. The breakdown of accessory minerals like xenotime, thorite, monazite, and apatite during a major hydrothermal event around 1.8 Ga released the non-formula elements (U, Th, P, Ca, Al, Fe, REEs) that were then incorporated into the zircon structures. Subsequent pluvial periods around 50,000-159,000 years ago may have allowed further uptake of these elements during low-temperature alteration. The shear zones within the Um Ara granites facilitated the mobilization and transport of the non-formula element-bearing fluids, likely as carbonate and fluoride complexes. The temperature regime, with fluids remaining below 300°C, was crucial in preserving the radiation damage features in the zircons despite the extensive chemical changes.

Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and its co-morbidities, like fatty liver disease, insulin resistance/diabetes and cardiovascular events. Among several factors, dietary patterns, probiotics, prebiotics, synbiotics, antimicrobials and non-dietary factors, such as stress, age, exercise and climatic conditions, can dramatically impact the human gut microbiota diversity and equilibrium. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.

The emergence of non-canonical amino acids (ncAAs) has enriched the functional pool inherent in canonical amino acids (cAAs). ncAAs are important building blocks in the production of various pharmaceuticals. The biosynthesis of ncAAs has emerged as an alternative to traditional chemical synthesis because of its environmental friendliness and high efficiency. The breakthrough genetic code expansion (GCE) technique developed in recent years has allowed for the incorporation of ncAAs into target proteins, giving them special functions and biological activities. Biosynthesis of ncAAs and their incorporation into target proteins within a single microbe has become an enticing application of such molecules. Based on that, in this study we first review the biosynthesis methods for ncAAs and analyze the difficulties in biosynthesis. We then summarize the GCE methods and analyze their advantages and disadvantages. Further, we review the application progress of ncAAs and anticipate the challenges and future development directions of ncAAs.

There must exist a reformulation of quantum field theory, even at low energies, which does not depend on classical time. The octonionic theory proposes such a reformulation, leading to a pre-quantum pre-spacetime theory. The ingredients for constructing such a theory, which is also a unification of the standard model with gravitation, are : (i) the pre-quantum theory of trace dynamics – a matrix-valued Lagrangian dynamics, (ii) the spectral action principle of non-commutative geometry, (iii) the number system known as the octonions, for constructing a non-commutative manifold and for defining elementary particles via Clifford algebras, (iv) a Lagrangian with $E_8 \times E_8$ symmetry. The split bioctonions define a sixteen dimensional space (with left-right symmetry) whose geometry (evolving in Connes time) relates to the four known fundamental forces, while predicting two new forces, $SU(3)_{grav}$ and $U(1)_{grav}$. This latter interaction is possibly the theoretical origin of MOND. Coupling constants of the standard model result from left-right symmetry breaking, and their values are theoretically determined by the characteristic equation of the exceptional Jordan algebra of the octonions. The quantum-to-classical transition, precipitated by the entanglement of a critical number of fermions, is responsible for the emergence of classical spacetime, and also for the familiar formulation of quantum theory on a spacetime background.

Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, while new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.

Many studies discuss carbon-based materials because of the versatility of the carbon element. They present different sorts of understandings fairly at convincing and compelling levels. A gas-state carbon atom converts into its various states depending on the conditions of processing. The electron transfer mechanism in the gas-state carbon atom is responsible for its conversion to various states, namely, graphite, nanotube, fullerene, diamond, lonsdaleite and graphene. The shape of energy responsible to transfer electron from the sides (east- and west-poles) of its atom is like parabola. That energy is linked to states (from filled state to nearby unfilled state) where exerted force to relevant poles of transferring electron is remained neutral. So, the mechanism of originating different states from a gaseous carbon atom is under the involvement of energy at first, which is not the case for atoms executing their confined inter-state electron-dynamics where force is involved at first. Structure evolved in graphite-, nanotubes- and fullerene-states have respectively one-dimensional, two-dimensional and four-dimensional atoms. Moreover, the associated energy curve is a parabola, indicating the transfer of electrons under neutral exertion of forces to their relevant poles. The graphite structure under only attained-dynamics of atoms is also developed but in two-dimension. Here, binding energy between graphitic carbon atoms is engaged under the influence of a small difference available between their involved forces along opposite poles. Structural evolution in diamond, lonsdaleite and graphene atoms involve potential energy of electrons required to undertake infinitesimal displacements under orientationally-controlled exerting forces to their relevant poles. In this study, the growth of diamond is found to be south to ground where atoms bound ground to south. Thus, diamond atoms merge for a tetra-electron ground to south topological structure. Lonsdaleite atoms merge for a bi-electron ground to just-south topological structure. The growth of graphene was just-north to ground; however, the binding of atoms was ground to just-north showing tetra-electrons ground to just-north topological structure. Glassy carbon exhibits layered-topological structure which successively binds tri-layers of gas-, graphite- and lonsdaleite-state atoms in repetitive manner. Orientating pair of electrons of each atom of below gas layer and above lonsdaleite layer enter from the rear side and front side respectively to undertake another clamping of unfilled energy knots belonging to each atom of intermediate graphitic layer. Different carbon atoms develop amorphous structures when they bind under frustrating amalgamation. Hardness of carbon-based materials was also sketched in the light of force-energy behaviors of different state carbon atoms. Here, structure evolution in each carbon state atom explores its own science.

The rapid development in industries manufacturing plastic bags is taking serious consideration to save the environment and human health, one way or the other. This study examines the composition of degradable and non-degradable plastic bags collected from the markets of different sectors of Islamabad. Hundred samples of both Degradable and non-degradable plastic bags were collected from the open market. The concentrations, proportion, and patterns of different heavy metals (additives) were used in the production of both degradable and non-degradable plastic bags by using the standard method with the help of Hands Held X-Ray Fluorescent (HHXRF) instrument. Samples results of the study showed Titanium, Calcium and Copper used in massive amounts, some of the toxic metals i.e., Arsenic, Lead, Cadmium, Chromium and Mercury were also detected. This study also reveals that degradable plastic bags might be more hazardous than non-degradable plastic bags because due to the Photolytic properties of additives used in degradable plastic bags when the chains of polymers break, the heavy metals are released in environment and become the part of it. So, concern department like Ministry of climate change and Pakistan Environmental Protection Agency should take serious step to control these serious issues.

Ferns and fern-allies, now known as Monylophytes, have received scant molecular attention, in relation to angiosperm group. The advent of high-throughput technologies allows to advance towards a greater knowledge of their elusive genome. In this work, samples of apogamous and sexual heart-shaped gametophytes from two ferns: the apomictic species Dryopteris affinis ssp. af-finisand its sexual relative Dryopteris oreades were extracted and identified. In total, a set of 218 proteins shared by these gametophytes were analysed by using the STRING database, and the proteome associated to metabolism, genetic information processing and responses to abitotic stress is discussed. Specifically, there are reported proteins involved in metabolism of carbohy-drates and lipids, biosynthesis of amino acids, metabolism of nucleotides, energy, and secondary compounds, oxido-reduction, transcription, translation, folding, sorting, and degradation, and response to abiotic stress. Some homologs of proteins found are MACCI-BOU (MAB1), MOSAIC DEATH 1 (MOD1), MAINTENANCE OF PHOTOSYSTEM II UNDER HIGH LIGHT 2 (MPH2), TRANSPARENT TESTA 5 (TT5), ALBINO OR GLASSY YELLOW 1 (AGY1), LEUCYL AMINOPEP-TIDASE 1 and 3 (LAP1 and LAP3), or LOW EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (LOS1). The interactome of the set of proteins was also studied, being the most common interac-tions database and textmining. All these data about the interactions that exist between the stud-ied proteins of the ferns D. affinis and D. oreades, together with the description of their biological function, might contribute to better understand the functioning and development of ferns as well as to fulfil gaps of knowledge in plant evolution.

Successful strategies that can contribute to poverty reduction and improve the livelihoods of the poor, particularly in Sub-Saharan Africa (SSA), are critically needed to address the technology adoption constraints. The objectives of this study were to assess the adoption rate of improved technologies and management practices and to identify the key factors influencing their adoption in the major wheat-producing areas of Sudan's irrigated, dry, and heat-prone environments. A farm survey was conducted in 2021 using a structured questionnaire that included all recommended technological options for optimum and sustainable wheat production. A total of 300 farmers, 93, 101, and 106 from Northern (NS), Kassala (KS), and Gezira (GS) states, respectively, were selected and interviewed. Besides descriptive statistics, a binary logistic model was used to identify the socioeconomic and production factors affecting farmers' perceptions of improved and recommended technological options. The study found a wide range of adoption rates depending on the specific technology practice and the area surveyed. The lowest adoption rate was observed for land preparation (6.5%) in NS. Adoption rates ranging from 26-100% were observed for technologies such as sowing date, seed rate, seed treatment, awareness of released varieties, nitrogen and phosphorus fertilizers application, and chemical weed control. The difference in the productivity of technological options adopters was significant (P = 0.015) compared to non-adopters. The binary logistic regression results showed that five out of seven explanatory variables hypothesized to influence wheat farmers' perceptions on the decision to adopt improved and recommended technologies significantly influenced farmers' decision to adopt the technologies. In particular, access to quality seed, financial credit, and extension services were found to be the most critical determinants of adopting improved technologies. Approaches that bring together all stakeholders along the crop value chain, including policymakers, to jointly analyze, identify, and prioritize challenges, develop and apply solutions and work plans using feedback and learning mechanisms are expected to increase farmer awareness and adoption of improved technologies, ultimately leading to sustainable wheat production.

For the soil in different regions, the nutrient fertility contained in it is different, and the detection and zoning management of soil nutrients before tillage every year can improve grain yield. In this paper, an integrated learning strategy model based on black soil hyperspectral data is designed for rapid classification of organic matter content classification of black soil. Soil hyperspectral image dataset of Xiangyang Experimental Base was collected; by changing the internal structure of the stacking model, an LSVM-stacking model with (MLP, SVC, DTree, XGBl, kNN) five classifiers as the L1 layer was built, and the simulated annealing algorithm was used for hyperparameter optimization. Compared to other stacking models, the LSVM-stacking metrics are significantly improved. The accuracy rate of hyperparameter optimization is improved by 38.6515%, the accuracy rate of the independent test data set is 0.9488, and the comparison of individual learners can improve the recognition classification accuracy of label"1" to 1.0.

Abstract: This work is part of the interest of solving the problems of water contamination with last generation pollutants, for which a novel and in an aqueous medium FeBTC material incorporated with magnetite nanoparticles was proposed. That material was synthesized by in situ solvothermal method, the Fe3O4 nanoparticles were added during the Fe-BTC MOF synthesis and used in the drug’s adsorption. The materials were characterized by XRD, FTIR and Raman spectroscopy, and N2-physisorption at 77 K. Fe3O4-FeBTC material showed a maximum adsorption capacity of 357.1 mg g−1 for diclofenac sodium, 70.9 mg g−1 for naproxen sodium, and 122.9 mg g−1 for Ibuprofen. A pseudo-second-order kinetic model can describe the adsorption process, and the thermodynamic study revealed that the adsorption of the three drugs was a feasible, spontaneous, and exothermic process. The incorporation of magnetite nanoparticles in the FeBTC considerably increased the adsorption capacity of pristine FeBTC. Also, hybridization of the FeBTC with magnetite nanoparticles reinforced the most vulnerable part of the MOF, increasing its thermal and aqueous media stability. The electrostatic interaction, H-bonding, and interactions in the open-metal sites played a vital role in drug adsorption. The competition of sites in the multicomponent mixture's adsorption showed selective adsorption at diclofenac sodium and naproxen sodium.

Keywords: Chronic Obstructive Pulmonary Disease (COPD), Long Non-Coding RNAs (lncRNAs), Molecular Pathogenesis, Inflammation, Lung Cancer, Diagnostic Biomarkers

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

Exosomal microRNAs (miRNAs) from cancer cells play a key role in mediating the oral squamous cell carcinoma (OSCC) microenvironment. The objective aimed to investigate how long non-coding RNA (lncRNA) MEG3 affects OSCC angiogenesis through exosomal miR-421. Global miRNA microarray analysis and quantitative real-time PCR (qRT-PCR) were performed to determine the level of miRNAs in OSCC cells-derived exosomes. Cell migration, invasion, tube formation, immunohistochemistry and hemoglobin concentration were used to study the effects of exosomal miR-421 in angiogenesis. Western blotting was used to determine the expression level of HS2ST1 and VEGFR2-related downstream proteins. MiRNA array and qRT-PCR identified upregulation of miR-421 in OSCC cell-derived exosomes. Furthermore, exosome-miR-421 can be taken up by human umbilical vein endothelial cells (HUVEC) and then targets HS2ST1 through VEGF-mediated ERK and AKT phosphorylation, thereby promoting HUVEC migration, invasion, and tube formation. Additionally, enforced expression of lncRNA MEG3 in OSCC cells reduced exosomal miR-421 levels and then increased HS2ST1 expression, thereby reducing the VEGF/VEGFR2 pathway in HUVEC. Our results demonstrate a novel mechanism by which lncRNA MEG3 can act as a tumor suppressor and regulate endothelial angiogenesis through the exosomal miR-421/HS2ST1 axis, which provides a potential therapeutic strategy for OSCC angiogenesis.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have been linked to changes in amino acid (ΑΑ) levels. The current observational study sought to investigate the relationship between plasma AA concentrations in a NAFLD population and MRI parameters reflecting inflammation and fibrosis, inflammatory and oxidative stress markers, and disease-related anthropometric and biochemical indicators. Approach & Results: Plasma AA levels were quantified with liquid chromatography in 97 NAFLD patients from the MAST4HEALTH study. Medical, anthropometric and lifestyle characteristics were collected and biochemical parameters, as well as inflammatory and oxidative stress biomarkers were measured. In total, males and subjects with higher MRI-proton density fat fraction (MRI-PDFF) exhibited higher plasma AA levels compared to females and subjects with lower PDFF respectively. Several associations of AAs with disease related markers were revealed, with the more prominent ones being those of aromatic amino acids with log-PDFF (beta: 1.190E-02, p-Value: 0.001) and log-ALT (beta: 7.55E-03, p-Value: 0.001), of branched amino acids with log-insulin (beta: 1.97E-03, p-Value: 1.16E-04) and of ethanolamine (beta: 0.036, p-Value: 3.65E-04) and L-ornithine (beta: 5.4E-04, p-Value: 0.021) with log-total antioxidant status (TAS). Conclusions: Plasma AA levels varied according to sex, BMI, and several MRI clinical factors. Furthermore, significant relationships were demonstrated between AA and several disease indicators, such as MRI parameters, biochemical and oxidative stress indices, showing the potential utility of AAs as diagnostic dis-ease-related indicators activity.

Talker variability has been reported to facilitate generalization and retention of speech learning, but is also shown to place demands on cognitive resources. Our recent study provided evidence that phonetically-irrelevant acoustic variability in single-talker (ST) speech is sufficient to induce equivalent amounts of learning to the use of multiple-talker (MT) training. This study is a follow-up contrasting MT versus ST training with varying degrees of temporal exaggeration to examine how cognitive measures of individual learners may influence the role of input variability in immediate learning and long-term retention. Native Chinese-speaking adults were trained on the English /i/-/ɪ/ contrast. We assessed the trainees’ working memory and selective attention before training. Trained participants showed retention of more native-like cue weighting in both perception and production regardless of talker variability condition. The ST training group showed long-term benefit in word identification, whereas the MT training group did not retain the improvement. The results demonstrate the role of phonetically-irrelevant variability in robust speech learning and modulatory functions of nonlinguistic working memory and selective attention, highlighting the necessity to consider the interaction between input characteristics, task difficulty, and individual differences in cognitive abilities in assessing learning outcomes.

Pesticides have a vital contribution to the agricultural industry in Australia. However, pesticide applications may not always selective to its target organism. Exposure to pesticide has been associated with negative impacts to human health. One of the ways to reduce pesticide risk to the population and the environment is through government regulations. To put Australia pesticide regulations into perspective, comparisons were made between Australia and other nation’s pesticides regulations. The EU pesticide regulatory system was chosen for comparison with the Australian’s in the aspect of protecting the population from pesticide exposure. The comparison showed that the assessment to authorize a pesticide in Australia is based on the risk while in the EU, the assessment is based on the hazard of the pesticide. A registered active substance in Australia can be authorized for use indefinitely unless it is nominated for reconsideration while the period of registration of an active substance in the EU lasts for 10 years. In addition, no routine systematic chemical residue surveys are conducted in Australia for food commodities. The results highlight areas for improvement in the Australian pesticide regulatory system from the perspective of controlling undue exposure among the general population.

During the last 150 years, the trout-culture industry focused on enhancing trout populations by stocking, in response to the growing anglers’ demand and the habitat degradation associated to the rapid urbanization and hydropower development. The industrialized north of Italy, home to the Italian Alpine and subalpine trout populations, is the source of most of the revenues of the national trout-culture industry. Its rapid growth and the massive introduction of non-native interfertile trouts eroded the genetic diversity of native lineages, leading to harsh confrontations between scientists, institutions, and sportfishing associations. We review here the state of art of the taxonomy and distribution of the northern Italian native trouts, presenting both scientific results and historical documentation. We think the only native trouts in this region are Salmo marmoratus, widespread in this region, plus small and fragmented populations of S. ghigii, present only in the Southwestern Alps. We strongly recommend the interruption of stocking of domesticated interfertile non-native trouts in this area, and recommend the adoption of Evolutionary Significant Units for salmonid fishery management. We further propose future research directions for a sustainable approach to the conservation and ecosystem management of the fishery resources and inland waters of northern Italy.

The Chebyshev collocation method (ChC) implemented as Chebfun is used in order to solve a class of second order one-dimensional singular and genuinely nonlinear boundary value problems. Efforts to solve these problems with conventional ChC have generally failed, and the outcomes obtained by finite differences or finite elements are seldom satisfactory. We try to fix this situation using the new Chebfun programming environment. However, for toughest problems we have to loosen the default Chebfun tolerance in Newton's solver as the ChC runs into trouble with ill-conditioning of the spectral differentiation matrices. Although in such cases the convergence is not quadratic the Newton updates decrease monotonically. This fact, along with the decreasing behaviour of Chebyshev coefficients of solutions, suggests that the outcomes are trustworthy, i.e., the collocation method has exponential (geometric) rate of convergence or at least an algebraic rate. We consider first a set of problems that have exact solutions or prime integrals and then another set of benchmark problems that do not possess these properties. Actually, for each test problem carried out we have determined how Chebfun solution converges, its length, the accuracy of the Newton method and especially how well the numerical results overlap with the analytical ones (existence and uniqueness).

In this paper, we proposed a new model of non-linear electrodynamics with parameter. Firstly, we study the weak limit approximation and by using the Gauss Bonnet theorem, we obtain the deflection angle of photon from magnetized black hole and effect of bnon-linear electrodynamics. In doing so, we find the corresponding optical metric after that we calculate the Gaussian curvature which is used in Gauss Bonnet theorem. Then we show the deflection angle in the leading order terms. We also analyzed that our results reduces into Maxwell's electrodynamics and RN solution with the reduction of parameters. Moreover, we also investigate the graphical behavior of deflection angle w.r.t correction parameter, black hole charge and impact parameter.

Except for a few species, the outer shape of vertebrates normally is characterized by bilateral symmetry. The inner organs, on the other hand, normally are arranged in bilaterally asymmetric patterns, which are of special importance for the normal function of the cardiovascular system of lung-breathing vertebrates. Deviations from the normal organ asymmetry can occur in the form of mirror imagery of the normal arrangement (situs inversus), or in the form of arrangements that have the tendency for development of bilateral symmetry, either in a pattern of bilateral left-sideness (left isomerism) or bilateral right-sidedness (right isomerism). The latter two forms of visceral situs anomalies are called “heterotaxy syndromes”. During the past 30 years, remarkable progress has been made in uncovering of the genetic etiology of heterotaxy syndromes. However, the pathogenetic mechanisms causing the spectrum of cardiovascular defects found in these syndromes remain poorly understood. In the present report, a spontaneous case of left cardiac isomerism found in a HH-stage 23 chick embryo is described. The observations made in this case suggest that hearts with left cardiac isomerism may have the tendency for development of a non-compaction cardiomyopathy caused by defective development of the proepicardium.

Large scale cropland erosion rates mapping and dynamic monitoring are critical for agricultural planning but extremely challenging. In this study, by using field investigation data collected from 20,155 land parcels in 2,781 sample units in the National Soil Erosion Survey, land use change data for two decades from the National Land Use/Cover Database of China (NLUD-C), we proposed a new point to surface approach to quantitatively assess long-term cropland erosion based on the CSLE model and non-homogeneous voting. The results show that cropland in Yunnan suffers from serious problem with unsustainable mean soil erosion rate of 40.47t/(ha·a) and erosion ratio of 70.11%, which are significantly higher than those of other land types. Engineering control measures (ECMS) have a profound impact on reducing soil erosion, soil erosion rate of cropland with and without ESMs differs by more than five times. Over the past two decades, the cropland area in Yunnan continues to decrease, with a net reduction of 7461.83 km2 and a ratio of −10.55%, which causes corresponding 0.32×108 t (12.12% ) decrease in cropland soil loss. We also quantified the impact of different LUCC scenarios on cropland erosion, and extraordinarily high variability was found in soil loss in different basins and periods. Conversion from cropland to forest contributes the most to cropland erosion reduction, while conversion from grassland to cropland contributes 56.18% of the increase in soil erosion. Considering the current speed of cropland regulation, it is the sharp reduction in land area that leads to cropland erosion reduction rather than treatments. The dilemma between the Grain for Green Policy and Cropland Protecting Strategy in mountainous areas should be treated carefully with shared understanding and collaborations from different roles.

Circular RNAs (circRNAs) served as covalently closed single-stranded RNAs have been proposed to influence plant development and stress resistance. Grapevine is the most economically valuable fruit crops cultivated worldwide and threaten by various abiotic stresses. Herein, we reported that a circRNA (Vv-circPTCD1) processed from the second exon of a pentatricopeptide repeat family gene PTCD1 was preferentially expressed in leaves and responded to salt and drought but not heat stress in grapevine. Additionally, the second exon sequence of PTCD1 was highly conserved but the biogenesis of Vv-circPTCD1 is species-dependent in plants. It was further found that the overexpressed Vv-circPTCD1 can slightly decreased abundance of the cognate host gene and the neighboring genes were barely affected in grapevine callus. Furthermore, we also successfully overexpressed the Vv-circPTCD1, and found that the Vv-circPTCD1 deteriorated the growth during heat, salt, and drought stresses in Arabidopsis. However, the biological effects on grapevine callus were not always consistent with that of Arabidopsis. Interestingly, we found that the transgenic plants of linear counterpart sequence also conferred the same phenotypes as that of circRNA during the three stress conditions, no matter what species. Those results imply that although the sequences are conserved, the biogenesis and functions of Vv-circPTCD1 are species-dependent. Our results indicate that the plant circRNA function investigation should be conducted in homologous species, which support valuable reference for further plant circRNA studies.

Within the fields of English for Academic Purposes (EAP) and English for Research Publication Purposes (ERPP), there is an unquestioned orthodoxy that scholars with English as an Additional Language (EAL) are particularly disadvantaged by the pressure to publish in English (though see Kuteeva 2015 and debate between Hyland 2016a, 2016b and Politzer-Ahlesa et al. 2016). In this paper, I challenge this orthodoxy, raising questions about the evidence upon which it is based. Within a framework of ‘verbal hygiene’ (Cameron 1995, 2012), I will argue that the attention accorded to ‘non-nativeness’ may be disproportionate to its significance for publication success. I conclude by proposing some reorientations for researchers and practitioners in the field that centre on broadening the scope to encompass non-linguistic structures of inequity.

Hydrogen peroxide (H2O2) is an essential analyte for detecting neurodegenerative diseases and in-flammatory processes and plays a crucial role in pharmaceutical, food industry, and environmental monitoring. However, conventional H2O2 detection methods have drawbacks such as lengthy analysis time, high costs, and bulky equipment. Non-enzymatic sensors have emerged as promising alternatives to overcome these limitations. In this study, we introduce a simple, portable, and cost-effective non-enzymatic electrochemical sensor based on carbon black (CB) and silver nano-particle-modified δ-FeOOH (Ag/δ-FeOOH), integrated into a disposable electrochemical cell (DCell). Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and electrochemical impedance spectroscopy (EIS), confirmed successful CB and Ag/δ-FeOOH immo-bilization on the DCell working electrode. Electrochemical investigations revealed that the DCell-CB//Ag/δ-FeOOH sensor exhibited an approximately twofold higher apparent heterogene-ous electron transfer rate constant than the DCell–Ag/δ-FeOOH sensor, capitalizing on CB ad-vantages. Moreover, the sensor displayed excellent electrochemical response for H2O2 reduction, boasting a low detection limit of 22 µM and a high analytical sensitivity of 214 μA mM-1 cm-2. Notably, the DCell-CB//Ag/δ-FeOOH sensor exhibited outstanding selectivity for H2O2 detection, even in potential interferents such as dopamine, uric acid, and ascorbic acid. Furthermore, the sensor demonstrated its suitability for monitoring H2O2 in complex biological samples, as evidenced by H2O2 recoveries ranging from 92% to 103% in 10% fetal bovine serum. These findings underscore the considerable potential of the DCell-CB//Ag/δ-FeOOH sensor for precise and reliable H2O2 monitoring in diverse biomedical and environmental applications.

Aim: This study aimed to evaluate the sociodemographic, behavioral, and biological profile and its relationship with the emergence of chronic non-communicable diseases in riverside populations in the Xingu region, Pará, Brazil. Methods: Characteristics related to health indicators and which risk factors are considered most important were also analyzed. This is a cross-sectional, exploratory, and descriptive study. The sample consisted of riverside people over 18 years of both sexes. The sample size (n.86) was calculated with a confidence level of 95% and a sample error of 5%. To divide the groups, the K-means clustering algorithm was adopted through an unsupervised method and the values were expressed as median. For continuous and categorical data, the Mann-Whitney and Chi-square tests were used, respectively, and the significance level was set at p<5%. To classify the degree of importance of each variable, the multi-layer perceptron algorithm was applied. Results: Based on this information, the sample was divided into two groups: the group with low or no education, with bad habits and worse health conditions, and the group with opposite characteristics. The risk factors considered for cardiovascular diseases and diabetes in the groups were low education (p < 0.001), sedentary lifestyle (p < 0.01), smoking, alcoholism, body mass index (p < 0.05) and the waist-hip ratio, with values above the expected, in both groups. Conclusions: The factors considered important to have a good health condition or not were the educational and social conditions of these communities and a part of the riverside population was considered healthier than the other.

Equine herpesvirus-1 (EHV-1) causes respiratory diseases, abortion, and encephalomyelitis in horses. EHV-1 immediate-early (IE) protein, essential for viral replication, is transactivated by the binding of a multiprotein complex including the open reading frame 12 (ORF12) and some host factors to the IE promoter region. Promoter-associated non-coding RNAs (pancRNAs), which are transcribed from bidirectional promoters, regulate the transcription of neighboring genes in mammals and pathogens. In this study, we identified a novel pancRNA transcribed from across the areas of the 5’-untranslated region and promoter of EHV-1 IE and named it IE pancRNA. IE pancRNA and mRNA were simultaneously expressed in EHV-1-infected RN33B-A68B2M cells. This pancRNA was also transcribed in RK13 and E. Derm cells, which are highly susceptible to EHV-1 infection. Furthermore, IE pancRNA upregulated IE gene expression in the presence of ORF12, and stable expression of IE pancRNA increased the number of EHV-1-infected RN33B-A68B2M cells. These results suggest that IE pancRNAs facilitate EHV-1 proliferation by promoting IE gene expression.

In the last century, statistical process control has been considered a successful methodology for monitoring the variability and stability of a process over time. The analysis of variability using functional data analysis has become widespread during the early years of the 21st century. The present study proposes the implementation of a hybrid methodology called functional process control based on the functional data analysis methodology and combines its advantages with those of statistical process control, in order to provide a tool for detecting functional deviations. The phases are: (1) stabilization of processes through the identification and elimination of special causes of functional variability; (2) improvement of the process to be controlled by minimizing the common causes of functional variability; and (3) monitoring of the processes to ensure the maintenance or addition of further improvements.

Traditional shipping ships abbreviated as Pelra have a different character from conventional ships. Hypothetically, the application of Safety Management System (SMS) on Pelra is influenced by technical and non-technical factors. These factors are control variables and determinants of action priorities if SMS is applied to the safety of traditional shipping, so that it has implications as a basis for formulating and developing safety policies for traditional shipping transportation in an effort to reduce the risk of accidents. This research uses Structural Equation Modeling by analyzing expert opinions. The results of the analysis show that technical and non-technical factors have a direct and interconnected effect on Pelra safety management. The dominant influences are non-technical factors of authority and responsibility of the company and crew as well as the feasibility of ship construction as technical and environmental factors..

Biofilm-associated proteins (BAPs) are important in the development and resilience of biofilms, which are intricate populations of microbes protected by extracellular matrix. All members of the BAP family are known to possess common characteristics such as high molecular weight and a signal sequence for extracellular secretion. It has been shown that BAPs are directly linked to the pathogenicity of many bacteria. This mini review highlights several potential strategies to target BAPs for drug development.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

Influenza virus can cause several complications during pregnancy. Therefore, we aimed to inves-tigate the effects of influenza on the development of congenital abnormalities (CAs) by analyzing the database of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCS-CA). In our multicenter, case-control, population-based study, we processed clinician-reported outcomes and diagnoses collected in the HCCSCA. The case group included newborns with dif-ferent non-chromosomal birth defects, while controls were newborns without CAs. Maternal in-fluenza, as a risk factor for CAs, was analyzed by using a logistic regression model and odds ra-tios with 95% confidence intervals (CIs). Our results showed that maternal influenza in the first trimester was associated with increased odds of developing non-chromosomal CAs (OR: 1.41, CI: 1.28–1.55). There were increased odds of neural tube defects (OR: 2.22, CI: 1.78–2.76), orofacial clefts (OR: 2.28, CI: 1.87–2.78) and congenital heart defects (OR: 1.28, CI: 1.10–1.49) after influenza infection. In all cases, we found a protective effect of folic acid supplementation in the first tri-mester. The odds of non-chromosomal birth defects are higher after maternal influenza in the first -trimester. Folic acid or pregnancy vitamin supplementation and antipyretic therapy may reduce the effect of maternal influenza during the first trimester.

Besides living as a free-ranging primate in the horn of Africa and the Arabian Peninsula, the hamadryas baboon has an important place in zoos and can be found in biomedical research centers worldwide. To be valuable as a non-human primate laboratory model for man, its anatomy should be portrayed in detail allowing for the correct interpretation and translation of obtained research results. Reviewing the literature on the use of the baboon in biomedical research revealed that very limited anatomical works on this species are available. Anatomical atlases are incomplete, use archaic nomenclature and fail to provide high definition color photographs. Therefore, the skeletons of two male hamadryas baboons were prepared by manually removing as much soft tissues as possible followed by maceration in warm water to which enzyme-containing washing powder was added. The bones were bleached with hydrogen peroxide and degreased by means of methylene chloride. Photographs of the various bones were taken, and the anatomical structures were identified using the latest version of the Nomina Anatomica Veterinaria. As such, the present article shows 31 annotated multipanel figures. The skeleton of the hamadryas baboon generally parallels the human skeleton, but some remarkable differences have been noticed. If these are taken into consideration when evaluating the results of experiments using the hamadryas baboon, justified conclusions can be drawn.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

The dissolution of Al2O3 non-metallic inclusions from slag containing FexO was investigated in this study. The slag system used in the experiments was a quaternary system of CaO-SiO2-Al2O3-FexO. The composition of the slag was studied by fixing the basicity (CaO/SiO2 ratio) to 1 and varying the FexO content to 10 and 20wt%. In addition, the experimental temperature was varied as 1550℃, 1575℃, and 1600℃ to study the effect of temperature on the Al2O3 dissolution behavior. The experimental equipment is a single hot thermocouple apparatus. The dissolution rate of Al2O3 particles increased linearly with increasing temperature and FexO content. In addition, the mass transfer activation energy of Al2O3 dissolution in FexO 10wt% and FexO 20wt% was calculated by an Arrhenius type analysis. The obtained mass transfer activation energies were 159 and 189 kJ/mole, respectively.

This paper presents a non-perturbative method for solving eigenproblems. This method applies to almost all potentials and provides non-perturbative approximations for any energy level. The method converts an eigenproblem into a perturbation problem, obtains perturbation solutions through standard perturbation theory, and then analytically continues the perturbative solution into a non-perturbative solution.

Abstract Background: Parkinson's disease (PD) is a neurodegenerative disorder featured with motor and non-motor deficits. Using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine neuron degeneration has been widely used to produce reliable animal models of the PD. However, most of previous preclinical studies focused on the motor dysfunctions, few non-motor symptoms were evaluated. So far there is a lack of comprehensive investigation of the non-motor symptoms in animal models. Objectives: In this study, we aim to use a battery of behavioral methods to evaluate the non-motor symptoms in MPTP-induced non-human primate PD models. Methods: Cognitive functions, sleep and psychiatric behaviors were evaluated in MPTP-treated cynomolgus monkeys. The tests consisted of delayed matching-to-sample (DMTS), physical activity monitor (PAM), apathy feeding task (AFT), human intruder test (HIT), novel fruit test (NFT) and predator confrontation test (PCT). In addition, we tested whether the dopamine receptor agonist pramipexole (PPX) will improve these non-motor symptoms. Results: The present results show that the MPTP-treated monkeys exhibited cognitive deficits, abnormal sleep, and anxiety-like behaviors as compared to the control monkeys. These symptoms were relieved partially by PPX. Conclusions: These results suggest that MPTP-induced PD monkeys displayed non-motor symptoms that were similar to those found in PD patients. PPX treatment showed moderate therapeutic effects on these non-motor symptoms. This battery of behavioral tests may provide a valuable model for future preclinical research.

Quantum theory predicts a whole class of non-local phenomena, observable via coincident detection of EPR-type systems. An important feature of these observations is their non-signaling character. Technically, non-local phenomena should only be observable for post-selected sub-ensembles, rather than for complete projections. Otherwise, superluminal telegraphy becomes possible. Yet, a couple of recent Bell experiments reported the observation of quantum non-locality for 100% of the detected events. Does it follow that signaling non-locality is possible? If so, was quantum theory falsified? This puzzle is solved by revisiting the interpretation of the spin projection operator, with special focus on its dual nature (combining spectral decomposition with spectral transformation). “Component switching” is not a loophole, but rather a requirement of quantum mechanics in this context, because sharp spin projections are partial (as well as partially overlapping). Surprisingly, it is possible to pre-select incompatible statistical sub-ensembles with heralded detection and to reveal the same behavior as in post-selected observations. Therefore, Bell experiments confirm the predictions of quantum theory without violating the non-signaling principle.

We summarise contributions made to the computational phase-field modelling of alloy solidification from the University of Leeds spoke of the LiME project. We begin with a general introduction to phase-field, and then reference the numerical issues that arise from solution of the model, before detailing each contribution to the modelling itself. These latter contributions range from controlling and developing interface-width independent modelling; controlling morphology in both single and multiphase settings; generalising from single to multi-phase models; and creating a thermodynamic consistent framework for modelling entropy flow and thereby postulate a temperature field consistent with the concepts of, and applicable in, multiphase and density-dependent settings.

All the arguments of a wavefunction are defined at the same instant implying a notion of simultaneity. In a somewhat related matter, certain phenomena in quantum mechanics seem to have non-local causal relations. Both concepts are in contradiction with special relativity. We propose to define the wavefunction with respect to the invariant proper time of special relativity instead of standard time. Moreover, we shall adopt the original idea of Schrodinger suggesting that the wavefunction represents an ontological cloud-like object that we shall call ‘individual fabric’ that has a finite density amplitude vanishing at infinity. Consequently, measurement can be assimilated to a confining potential that triggers an inherent non-local mechanism within the individual fabric. It is formalised by multiplying the wavefunction with a localising gaussian as in the GRW theory but in a deterministic manner.

In recent years, advances in science, technology, and the way in which we view our world have led to anincreasingly broad use of the term “intelligence”. As we learn more about biological systems, we find more and more examples of complex and precise adaptive behavior in animals and plants. Similarly, as we build more complex computational systems, we recognize the emergence of highly sophisticated structures capable of solving increasingly complex problems. These behaviors show characteristics in common with the sort of complex behaviors and learning capabilities we find in humans, and therefore it is common to see them referred to as “intelligent”. These analogies are problematic as the term "intelligence" is inextricably associated with human-like capabilities. While these issues have been discussed by leading researchers of AI and renowned psychologists and biologists highlighting the commonalities and differences between AI and biological intelligence, there have been few rigorous attempts to create an interdisciplinary approach to the modern problem of intelligence. This article proposes a comparative framework to discuss what we call “purposeful behavior”, a characteristic shared by systems capable of gathering and processing information from their surroundings and modifying their actions in order to fulfill a series of implicit or explicit goals. Our aim is twofold: on the one hand, the term purposeful behavior allows us to describe the behavior of these systems without using the term "intelligence", avoiding the comparison with human capabilities. On the other hand, we hope that our framework encourages interdisciplinary discussion to help advance our understanding of the relationships among different systems and their capabilities.

A 40 years old male Nile crocodile (Crocodylus niloticus) was diagnosed with pulmonary mycobacteriosis caused by a member of Mycobacterium chelonae/abscessus group. Post-mortem examination showed a severe systemic visceral granulomatous involvement, with lesions in lungs, heart, liver, spleen and kidneys. Histopathological examination of lung, spleen, heart and liver revealed multifocal to coalescing granulomas showing eterophils in central zone and outer rim of epithelioid histiocytes, multinucleated giant cells and lymphocytes. The Ziehl–Neelsen histological staining revealed rare vacuoles containing numerous alcohol-acid resistant bacteria. Mycobacterial infection was confirmed by culture and PCR targeting rRNA 16S gene. Sequence analysis of the DNA amplicon revealed a 100% homology with the M. chelonae/ abscessus group. Even if the classification of the memebrr of this group is still on updating, to the best of our knowledge, this is the first report of M. chelonae/abscessus member infection in a Nile crocodile species.

With improved measurement and modelling technology, variability has emerged as an essential feature in non-equilibrium processes. While traditionally, mean values and variance have been heavily used, they are not appropriate in describing extreme events where a significant deviation from mean values often occurs. Furthermore, stationary Probability Density Functions (PDFs) miss crucial information about the dynamics associated with variability. It is thus critical to go beyond a traditional approach and deal with time-dependent PDFs. Here, we consider atmospheric data from the Whole Atmosphere Community Climate Model (WACCM) and calculate time-dependent PDFs and the information length from these PDFs, which is the total number of statistically different states that a system passes through in time. Time-dependent PDFs are shown to be non-Gaussian in general, and the information length calculated from these PDFs shed us a new perspective of understanding variabilities, correlation among different variables and regions. Specifically, we calculate time-dependent PDFs and information length and show that the information length tends to increase with the altitude albeit in a complex form. This tendency is more robust for flows/shears than temperature. Also, much similarity among flows and shears in the information length is found in comparison with the temperature. This means a stronger correlation among flows/shears because of a strong coupling through gravity waves in this particular WACCM model. We also find the increase of the information length with the latitude and interesting hemispheric asymmetry for flows/shears/temperature, a stronger anti-correlation (correlation) between flows/shears and temperature at a higher (low) latitude. These results also suggest the importance of high latitude/altitude in the information budge in the Earth's atmosphere, the spatial gradient of the information as a useful proxy for the transport of physical quantities.

The EPR paradox is known as an interpretive problem, as well as a technical discovery in quantum mechanics. It defined the basic features of two-quantum entanglement, as needed to study the relationships between two non-commuting variables. In contrast, four variables are observed in a typical Bell experiment. This is no longer the same problem. The full complexity of this process can only be captured by the analysis of four-quantum entanglement. Indeed, a new paradox emerges in this context, with straightforward consequences. Either quantum behavior is capable of signaling non-locality, or it is local. Both alternatives appear to contradict existing knowledge. Still, one of them has to be true, and the final answer can be obtained conclusively with a four-quantum Bell experiment.

We study a conformation of an albumin protein in the temperature range of 300K-315K, i.e. in the physiological range of temperature. Using simulations we calculate values of two backbone angles, that carry most of information about positioning of the protein chain in a conformational space. Given these, we calculate energy components of such protein. Further, using the Flory theory we determine the temperature in which investigated albumin chain model is closest to the free joined chain model. Near the Flory temperature, we study energy components and the conformational entropy, both derived from two angles that reflect most of the chain dynamics in a conformational space. We show that the conformational entropy is an oscillating function of time in considered range of temperature. Our finding is that, the only regular oscillation pattern appears near the Flory temperature.

The Boltzmann-Gibbs (BG) entropy has been used in a wide variety of problems for more than a century. It is well known that BG entropy is extensive, but for certain systems such as those dictated by long-range interactions, the entropy must be non-extensive. Tsallis entropy possesses non-extensive characteristics, which is parametrized by a variable q (q = 1 being the classic BG limit), but unless q is determined from microscopic dynamics, the model remains but a phenomenological tool. To this date very few examples have emerged in which q can be computed from first principles. This paper shows that the space plasma environment, which is governed by long-range collective electromagnetic interaction, represents a perfect example for which the q parameter can be computed from micro-physics. By taking the electron velocity distribution function measured in the heliospheric environment into account, and considering them to be in quasi equilibrium state with electrostatic turbulence known as the quasi-thermal noise, it is shown that the value corresponding to q = 9/13 = 0.6923 may be deduced. This prediction is verified against observation made by spacecraft, and it is shown to be in excellent agreement.

Long non-coding RNAs (lncRNAs) have been found to be involved in many biological processes, including the regulation of cell differentiation, but a complete characterization of lncRNA is still lacking. Additionally, there is evidence that lncRNAs interact with ribosomes, raising questions about their functions in cells. Here, we used a developmentally staged protocol to induce cardiogenic commitment of hESCs and then investigated the differential association of lncRNAs with polysomes. Our results identified lncRNAs in both the ribosome-free and polysome-bound fractions during cardiogenesis and showed a very well-defined temporal lncRNA association with polysomes. Clustering of lncRNAs was performed according to the gene expression patterns during the five timepoints analyzed. In addition, differential lncRNA recruitment to polysomes was observed when comparing the differentially expressed lncRNAs in the ribosome-free and polysome-bound fractions or when calculating the polysome-bound vs ribosome-free ratio. The association of lncRNAs with polysomes could represent an additional cytoplasmic role of lncRNAs, e.g., in translational regulation of mRNA expression.

In standard construction of hyperrational numbers using ultra-power we assume that the ultra lter is selective. It makes possible toassign real value to any nite hyperrational number. So, we can consider hyperrational numbers with selective ultra lter as extension of traditional real numbers. Also proved the existence of strictly monotonic or stationary representing sequence for any hyperrational number.

NiFe alloy nanoparticles/graphene oxide hybrid (NiFe/GO) was prepared for electrochemical glucose sensing. The as-prepared NiFe/GO hybrid was characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The results indicated that NiFe alloy nanoparticles can be successfully deposited on GO. The electrochemical glucose sensing performance of the as-prepared NiFe/GO was studied by cyclic voltammetry and amperometric measurement. Results showed that NiFe/GO modified glassy carbon electrode had sensitivity of 173 μA mM⁻¹cm⁻² for glucose sensing with a linear range up to 5 mM, which was superior to commonly used Ni nanoparticles. Furthermore, high selectivity for glucose detection can be achieved by NiFe/GO. All the results demonstrated that NiFe/GO hybrid was promising for using in electrochemical glucose sensing.

According to the operation conditions of time unlimited passive containment heat removal system (TUPAC), a separate effect experiment facility was established to investigate the heat transfer performance of steam condensation in presence of non-condensable gas. The effect of wall subcooling temperature, total pressure and mass fraction of the air on heat transfer process was analyzed. The heat transfer model was also developed. The results showed that the heat transfer coefficient decreased with the rising of subcooling temperature, the decreasing of the total pressure and air mass fraction. It was revealed that Dehbi’s correlation predicted the heat transfer coefficient conservatively, especially in the low pressure and low temperature region. The novel correlation was fitted by the data obtained in the following range: 0.20~0.45 MPa in pressure, 20% ~ 80% in mass fraction, 15°C ~ 45°C in temperature. The discrepancy of the correlation and experiment data was with ±20%.

Objective: It was aimed to investigate the cerebral vascular territories in stroke patients with NVAF as an etiologic factor. Material and Methods: A total of 104 patients who were referred to our hospital between January 2015 and September 2016, who were over 55 years of age, identified or documented as having a standard ECG or Holter ECG record on their medical history, and diagnosed with stroke were included. Our study was designed as a retrospective analysis of prospective data. Detailed history, physical examination and electrocardiography (ECG) evaluations of the patients were performed. Descriptive statistics were used in the detection of findings, and t-test, Pearson-square test and Fisher's exact test were used for differences analysis. Results: 53.8% (N = 56) of the patients were male and 46.2% (N = 48) were female. The mean age was 73.5. MCA was the most common site of vascular involvement in NVAF-dependent strokes. In MCA vascular territory, ischemic infarcts were detected most frequently in the upper and lower divisions. SCA and PCA followed MCA. Approximately 64% of the NVAF-related strokes were anterior circulation infarction (ASE) and 22% were posterior circulation infarct (PSE). There was a significant difference in age and past stroke history factors in favor of ASE (p<0.05). There was no significant difference between ASE and PSE in HT, cardiac history and DM factors (p>0.05). Conclusion: It was emphasized that the area of the vessel that underwent ischemia in the acutely displayed infarcts and the etiological factor for this vessel area could be predicted

Breast cancer is the most common malignancies in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER, PR and HER2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether HDACi would be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enrich breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence based live cell non-invasive apoptosis detection sensor (IADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also be accompanied with chemotherapeutic agent such as doxorubicin to synergic drug sensitivity on TNBC cell (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in clinic.

Bottom-up synthesis of porous NiMo alloy reduced by NiMoO₄ nanofibers was systematically investigated to fabricate non-noble metal porous electrodes for hydrogen production. The different annealing temperatures of NiMoO₄ nanofibers under hydrogen atmosphere reveal that the 950 °C annealing temperature is a key to produce bicontinuous porous NiMo alloy without oxide phases. The porous NiMo alloy as cathodes in electrical water splitting demonstrates not only almost identical catalytic activity with commercial Pt/C in 1.0 M KOH solution, but also superb stability for 12 days at an electrode potential of −200 mV (v.s. RHE).

Human non-conscious reasoning is one of the most successful procedures developed to solve everyday problems in an efficient way. This is why the field of artificial intelligence should analyze, formalize and emulate the multiple ways of non-conscious reasoning with the purpose of applying them in knowledge based systems, neurocomputers and similar devices for aiding people in the problem-solving process. In this paper, a framework for those non-conscious ways of reasoning is presented based on object-oriented representations, fuzzy sets and multivalued logic.

We present an exact expression for the upscaled dynamic dispersion coefficient (D) for one-dimensional transport by Hagen-Poiseuille flow which is the basis for modeling transport in porous media idealized as capillary tubes. The theoretical model is validated by comparing the breakthrough curves (BTCs) from a 1D advection-dispersion model with dynamic D to that from direct numerical solutions utilizing a 2D advection-diffusion model. Both Taylor dispersion theory and our new theory are good predictors of D at lower Peclet Number (Pe) regime, but gradually fail to capture most parts of BTCs as Pe increases. However, our model generally predicts the mixing and spreading of solutes better than Taylor’s theory since it covers all transport regimes from molecular diffusion, through anomalous transport, and to Taylor dispersion. The model accurately predicts D based on the early part of BTCs even at relatively high Pe regime (~62) where the Taylor’s theory fails. Furthermore, the model allows for calculation of the time scale that separates Fickian from non-Fickian transport. Therefore, our model can readily be used to calculate dispersion through short tubes of arbitrary radii such as the pore throats in a pore network model.

This paper presents an upcoming nonvolatile memories (NVM) overview. Non-volatile memory devices are electrically programmable and erasable to store charge in a location within the device and to retain that charge when voltage supply from the device is disconnected. The non-volatile memory is typically a semiconductor memory comprising thousands of individual transistors configured on a substrate to form a matrix of rows and columns of memory cells. Non-volatile memories are used in digital computing devices for the storage of data. In this paper we have given introduction including a brief survey on upcoming NVM's such as FeRAM, MRAM, CBRAM, PRAM, SONOS, RRAM, Racetrack memory and NRAM. In future Non-volatile memory may eliminate the need for comparatively slow forms of secondary storage systems, which include hard disks.

Most of the pore-scale imaging and simulations of non-Newtonian fluid are based on the simplifying geometry of network modeling and overlook the fluid rheology and heat transfer. In the present paper, we developed a non-isothermal and non-Newtonian numerical model of the flow properties at pore-scale by direct simulation of the 3D micro-CT images using a Finite Volume Method (FVM). The numerical model is based on the resolution of the momentum and energy conservation equations. Owing to an adaptive meshing technique and appropriate boundary conditions, rock permeability and mobility are accurately computed. A temperature and concentration-dependent power-law viscosity model in line with the experimental measurement of the fluid rheology is adopted. The model is first applied at isothermal condition to 2 benchmark samples, namely Fontainebleau sandstone and Grosmont carbonate, and is found to be in good agreement with the Lattice Boltzmann method (LBM). Finally, at non-isothermal conditions, an effective mobility is introduced that enables to perform a numerical sensitivity study to fluid rheology, heat transfer, and operating conditions. While the mobility seems to evolve linearly with polymer concentration, the effect of the temperature seems negligible by comparison. However, a sharp contrast is found between carbonate and sandstone under the effect of a constant temperature gradient. Besides concerning the flow index and consistency factor, a good master curve is derived when normalizing the mobility for both the carbonate and the sandstone.

Predicting the growth response of seedlings from the environmental responses of photosynthesis and metabolism may be improved by considering the dynamics of non-structural carbohydrate, NSC, over a diurnal cycle. Attenuation of growth metabolism when NSC content is low could explain why some NSC is conserved through the night. A dynamic model, incorporating diurnal variation in NSC, was developed to simulate growth of seedlings hour-by-hour. I compared predictions of this model to published growth and NSC data for seedlings that varied according to temperature, light, day length, or CO₂. Prolonged-darkness experiments showed a temperature dependent upper limit on the respiration capacity. Respiration was attenuated as NSC was depleted. Furthermore, when NSC was high at dawn, inhibition of photosynthesis could attenuate the accumulation of NSC under low temperature, or high light, or high CO₂. These concepts were used to simulate plant metabolism and growth rates and diurnal variation of NSC in tomato seedlings under two light levels and various temperatures. Comparison of other results using the same model parameters showed the dynamic model could predict results for starch and starch-less plants, and when growth was affected by CO₂ enrichment and day length.

Non-coding RNA regions have long been considered the "dark matter" of the genome, with their significance in gene regulation remaining enigmatic. However, recent advances in genomics and molecular biology have illuminated the pivotal role that non-coding RNA regions play in the fine-tuned orchestration of hemoglobin expression. Hemoglobin, the oxygen-carrying protein vital for life, is tightly regulated, and any disruption in its production can lead to severe medical conditions, such as hemoglobinopathies. This review delves into the intricate world of non-coding RNA regions, exploring how they act as master conductors in controlling hemoglobin gene expression. We will discuss various classes of non-coding RNAs, including long non-coding RNAs, microRNAs, and circular RNAs, and their specific mechanisms in fine-tuning hemoglobin levels. Additionally, we will highlight emerging therapeutic approaches that target non-coding RNA regions to ameliorate hemoglobin-related disorders. Understanding the critical role of non-coding RNA regions in hemoglobin regulation opens new avenues for precision medicine and gene therapies, offering hope for those affected by hemoglobinopathies and related conditions. This comprehensive review sheds light on the significance of these non-coding RNA regions, demonstrating that the "silent" players in the genome are, in fact, the conductors of harmony in the symphony of hemoglobin regulation.

This study demonstrates a global, non-parametric, non-iterative optimization of time-mean value of a kind of index vibrated by time-varying forcing. It is based on the fact that the (steady) forced vibration of non-autonomous ordinary differential equation systems is well approximated by an analytical solution when the amplitude of forcing is sufficiently small and its base state without forcing is linearly stable and steady. It is applied to optimize a time-averaged heat-transfer rate on a two-dimensional thermal convection field in a square cavity with horizontal temperature difference, and the globally optimal way of vibrational forcing, i.e. the globally optimal, spatial distribution of vibrational heat and vorticity sources, is first obtained. The maximized vibrational thermal convection corresponds well to the state of internal gravity wave resonance. In contrast, the minimized thermal convection is weak, keeping the boundary layers on both sidewalls thick.

The software design of autonomous vehicles (AVs) incorporates artificial intelligence (AI) characteristics to enhance their safety and overall driving performance. Central to vehicle’s operation is the ability to reason effectively in complex and uncertain environments. However, traditional logical systems, such as monotonic logic, often struggle to handle the inherent uncertainties and exceptions encountered in real-world scenarios. This paper proposes the utilization of non-monotonic logic in order to enhance the reasoning capabilities of autonomous vehicles. By incorporating non-monotonic reasoning, vehicles can navigate intricate traffic scenarios, make plausible inferences, and adapt their decisions when faced with conflicting information. This research aims to provide a comprehensive review of non-monotonic logic's application in autonomous vehicles, highlighting its advantages over traditional logical systems and its potential impact on safety and performance. Additionally, through this research, we seek to contribute to the advancement of autonomous driving technology by enhancing the reasoning capabilities of vehicles in various scenarios, such as car- following related to critical safety events. The personalized cognitive agent is proposed in driving behavior to consider particularly in their assumptions of homogeneous drivers. The personalized cognitive agent is incorporating heterogeneous driving behaviors, based on individual user preferences, characteristics, and needs. Driving behavior is a complex interplay of various factors, encompassing both human and external elements. Human factors, including age, experience, and gender, contribute significantly to how individuals navigate the roads. These factors influence decisions, reactions, and risk-taking tendencies on the part of drivers. Additionally, external factors such as weather conditions further compound this intricate dynamic, requiring drivers to adapt their behavior to the prevailing environment. The goal of a personalized cognitive agent is to provide tailored and customized experiences to cognitive vehicles, taking into account the unique requirements and individual preferences of occupants inside autonomous vehicles.

So that the levels of water stress are not harmful to the development of the crop and affect its productivity, its detection and monitoring are necessary, and it can occur in different ways. One of them is through the Crop Water Stress Index (CWSI). This index quantifies water stress through the normalization of leaf temperature between the maximum and minimum plant temperatures as a function of evaporation conditions. The responses of a low-cost infrared (IR) sensor were crossed with image processing through segmentation by the Excess Green model to develop a water stress detection system using CWSI. A soil/plant temperature map was generated through a point-to-point scan of the IR sensor. And when it overlaid with a segmented image of the experimental area, only points identified as plants had their temperature values maintained. The Non-Water-Stressed Baseline (NWSB) equation was parameterized for the same conditions of the experiment and external environmental. The experimental area was divided into three different treatments, maintained under stable water conditions throughout the experiment and the system was able to identify stably different stress values between treatments. Although the relationship between crop and environment affected the results, this work showed that using an irrigation system based on CWSI is possible.

For the electromagnetic eddy current testing, various methods have been proposed for reducing the lift-off error on the measurement of samples. In this paper, instead of eliminating the measurement error caused by the lift-off effect, an algorithm has been proposed to directly measure the lift-off distance between the sensor and non-magnetic conductive plates. The algorithm is based on a sample-independent inductance (SII) feature. That is, under high working frequencies, the inductance is found sensitive to the lift-off distance and independent of the test piece under an optimal single high working frequency (43.87 kHz). Furthermore, the predicted lift-off distance is used for the thickness prediction of the non-magnetic conductive samples using an iterative method. Considering the eddy current skin depth, the thickness prediction is operated under a single lower frequency (0.20 kHz). As the inductance has different sensitivities to the lift-off and thickness, the prediction error of the sample thickness is different from that of the lift-off distance. From the experiments on three different nonmagnetic samples – aluminium, copper, and brass, the maximum prediction error of the lift-off distance and sample thickness is 1.1 mm and 5.42 % respectively at the lift-off of 12.0 mm.

Through its suggestive name, non-targeted methods (NTMs) do not aim at a predefined "needle in the haystack". Instead, they exploit all the constituents of the haystack. This new form of analytical methods is increasingly finding applications in food and feed testing. However, the concepts, terms, and considerations related to this burgeoning field of analytical testing needs to be propagated for the benefit of ones associated in academic research, commercial development, and official control. This paper addresses the frequently asked questions around notations and terminologies surrounding NTMs. The widespread development and adoption of these methods also necessitates the need to develop approaches to NTM validation, i.e., evaluating the performance characteristics of a method to determine if it is fit-for-purpose. This work aims to provide a roadmap to approaching NTM validation. In doing so, the paper deliberates on the different considerations that influence the approach to validation and provides suggestions thereof.

Artificial Intelligence is increasingly being used by social media platforms to tackle online hate speech. The sheer quantity of content, the speed at which is it developed and the enhanced pressure companies are facing by States to remove hate speech quickly from their platforms have led to a tricky situation. This commentary argues that automated mechanisms, which may have biased datasets and be unable to pick up on the nuances of language, should not be left unattended with hate speech as this can lead to issues of violating freedom of expression and the right to non-discrimination.

Abstract The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication. This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction. This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.

Nitrogen and phosphorous support the ecosystem by supplying nutrients to algae and aquatic plants. Having them in excess results in the eutrophication of waters creating quality problems. In the past, nitrogen has been widely investigated for wells in the context of groundwater flow. However, a national-scale nitrogen assessment in rivers and streams has not received enough attention. In this research, the Wilcoxon rank sum test, as a non-parametric hypothesis testing method, has been applied to nitrogen concentration in the form of nitrate-nitrogen and nitrite-nitrogen in rivers and streams of the Contiguous United States. This approach was particularly selected because of the non-normal and positively skewed nitrogen levels occurring in the surface flow. This method was able to identify the impaired body of waters as well as quantify the confidence, significance, and errors involved. The Northern Appalachians (NAP), Northern Plains (NPL), and Xeric (XER) ecoregions were worsening in the nitrogen-nitrate condition with NAP, and XER needed immediate actions. The nitrite-nitrogen condition did not pose an immediate threat, so mitigation plans should focus more on nitrate-nitrogen remediation. It was shown that the method was superior to the two-sample t-test by yielding lower type II errors.

This study presents a novel technique utilizing high frequency vibration to shorten treatment time and preserve alveolar bone in challenging orthodontic cases treated with Invisalign® clear aligners. Four non-growing orthodontic patients (age range 14-47 years old) with Class II skeletal patterns (convex profiles with retrognathic mandibles) who sought correction of their crowded teeth and non-surgical correction of their convex profiles were included in this study. These patients were treated using Invisalign clear aligners together with high frequency vibration (HFV) devices (120 Hz) (VPro5™) that were used by all patients for five minutes per day during active orthodontic treatment. Vertical control and forward rotation of the mandible for each patient was achieved through pre-programming the Invisalign to produce posterior teeth intrusion. Successful forward rotation of the mandibles achieved in all patients led to improvement of their facial convex profiles (ANB improved 2.1 + 0.5 degrees; FMA improved 1.2 +1.1 degrees). Dental decompensation was achieved by lingual tipping of the lower incisors and palatal root torque of upper incisors. The use of HFV together with Invisalign facilitated achieving these results within a 12+6 month period. In addition, more bone labial to the lower incisors after their lingual movement was noted. In conclusion, the use of HFV concurrent with SmartTrack Invisalign aligners allowed complex tooth movement and forward projection without surgery in non-growing patients with skeletal Class II relationships. The clinical impact and implications of this case series is that the use of HFV facilitates complex orthodontic tooth movement including posterior teeth intrusion and incisor decompensation in addition to increased bone formation labial to lower incisors that may minimize future gum recession due to their labial inclination.

The Human Gut Microbiome is an important host’s component defining its health. These microorganisms are mutualistic symbionts dependent on factors such as host’s age, subsistence models and sociocultural practices, among others. The conjunction of these factors define the microbial ecosystem dynamics. Using a fecal microbiome approach in children, a comparison of two Mexican communities with contrasting lifestyles: “westernized” (Mexico City) and “non-westernized” (Me’phaa indigenous group) was evaluated. The main differences between these two communities are in bacteria associated with different types of diets (high animal protein and refined sugars vs high fiber food, respectively). In addition, the gut microbiome of Me’phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria and Fibrobacteres. In contrast, Mexico City children had less diversity and the exclusive presence of Saccharibacteria phylum which is associated with the degradation of sugar compounds. This comparison allows further exploration of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with westernization lifestyles.

This study aims to identify the factors determining the income of forestry household in South Korea. We examine an empirical analysis using 3-year panel data conducted by the Korea Forest Service charged with maintaining South Korea's forest lands. The hypothesized factors determining the income of forestry household are classified into four types of assets and three types of livelihood strategies. We divided the income of forestry household (IFH) into three elements: forestry income (FI), non-forestry income (NFI), and transfer income (TI). We assessed the influences of household assets and livelihood strategies on each income. A random effect model was used as a statistical analysis with valid 979 of forestry household for three years. We found that household head's age, labor hours, savings, business category, cultivated land size, and region are significantly associated with IFH. Also, FI is influenced by labor capacity, cultivated size, business category, forestry business portfolio, and region while NFI is determined by household head's age, household head's gender, forestry business portfolio, and savings. TI is affected by household head's age, household head's education level, forestry business portfolios, savings, and region. The effect sizes and directions vary across different types of income (IFH, FI, NFI, and TI). The findings show that forestry in South Korea is highly dependent on sustainable assets and strategies. It is therefore expected that the effectiveness of forest policies to increase the income of forestry household would be differed by the source of each income. The results of this study draw attention to the need for an income support policy that should consider the characteristics of household assets and livelihood strategies in order to enhance IFH in South Korea.

We estimated the daily intakes of chlorpyrifos and cypermethrin via ingestion of indoor dust and outdoor soils using the Stochastic Human Exposure and Dose Simulation Model on a probabilistic approach for Taiwan’s homes. Variable information for the daily intake estimation, such as concentration, ingestion rate, body weight, was adopted from previous studies. Monte Carlo simulation was performed with 1,000,000 iterations to simulate a single daily intake, which was shown in terms of percentage of the Acceptable Daily Intake (ADI) of either insecticide. The daily intakes were minimal with a 99% probability; at 99.9th percentile, however, the total intakes leaped to 13.1% and 20.0% of the respective ADIs of chlorpyrifos and cypermethrin. The sensitivity analysis indicated that concentration was the most determinant variable. Compared to the data of daily intakes via dietary ingestion of vegetables derived from a previous study, the estimated intakes by this study were considerable at the highest percentile, which referred to insecticide residues few days after insecticide application. Consequently, the non-dietary ingestion exposure to either insecticide was negligible in most cases; nevertheless, for those with indoor insecticide applications, the daily intakes for young children could be of concern. Frequently home cleaning is recommended to reduce the exposure.

Microbial immune escape represents the primary cause of induced pathogenesis in humans, and it represents a pivotal method used by viral agents to increase their load and suppress key mechanisms of the innate and adaptive immune system. This phenomenon represents the primary factor that led to the onset of the 1918-1920 A(H1N1) Influenza and 2020-2022 COVID-19 pandemics, and it possibly played a major role in the onset of the AIDS pandemic as well. Moreover, repeated incidents of immune evasion could be associated with higher rates of cellular aging (Jackson et al., 2017), most likely due to the consequent increased demands of energy consumption. Highly developed viral immune evasion ultimately indicates the high inner intelligence of human immunity due to reflective and imitative characteristics of reactions that are produced against initial actions. Ribonucleic acid-based viral genomes contain open reading frames, which consist of genes producing sixteen non-structural proteins. Such proteins play a considerable role in desensitizing first-line immunity during cellular infection, and non-structural proteins 1, 10 and 16 have the strongest effects against a healthy expression rate of Type I and Type III Interferon-encoding genes. Type I Interferons consist of IFN-alpha, -beta, -delta, -epsilon, -omega, -tau and -zeta, whilst Type III Interferons consist of IFN-lambda1, -lambda2 and -lambda3, and they act as stimulators of intracellular signalling cascades that in turn lead to the activation and expression of interferon-stimulated genes (Brown et al., 2022). The earlier the interferon-stimulated genes are activated, the lower the extent of pro-inflammatory mediation and overall, the more effective the antiviral immune response will be, given the exponential nature of the viral load increase. Non-structural protein 16 methylates the 5’ cap of the virus, making the pathogen-associated molecular patterns less recognisable by pattern-recognition receptors, and it requires activation by bonding with non-structural protein 10. It is preserved in the S-Adenosyl-L-Methionine pocket of the SARS-CoV-2 genome. Non-structural protein 1 (NS1) directly cleaves the host cell mRNA producing Type I and possibly Type III Interferons, thereby preventing a translation process of the immune proteins. NS1 has recently been found to often be packaged into exosomes once secreted by the viral genome in the cytosol, meaning that exocytosis and paracrine signalling to neighbouring cells before their actual infection is possible. As a result, NS1 is highly capable of silencing the first-line immune responses of uninfected neighbouring cells as well, thereby highlighting the need to adjust the focus of therapeutics and vaccinology toward first-line immunity and further indicating its foundational importance in the support for the development of precise and balanced defenses against microbial agents of concern (EL SAFADI et al., 2022).

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

In Caucasians, basal cell carcinoma, a type of non-melanoma skin cancer, is most often found on the nose. This presents challenges for surgeons due to anatomical, functional, and aesthetic concerns. The study aimed to evaluate the distribution of tumor localization, size, morphological subtypes, surgical outcomes, radicality levels, and their correlation with recurrence rates. The research utilized data from the Hygiene Institute Health Information Centre. A retrospective analysis encompassed 343 cases of nasal skin cancer over a four-year period from January 1, 2019, to December 31, 2022. The research cohort comprised 252 female and 91 male participants, averaging 75,2 years old. Tumors were most found on the left sidewall of the nose (25.4%) and the dorsum (24.8%). The infiltrative morphological subtype was predominant (70.8%). Standard surgical excision with fasciocutaneous plastic was the preferred surgical procedure. Radical excision was achieved in 79.0% of lesions, while 16.9% were incompletely excised. Non-radically excised tumors exhibited a significantly higher recurrence rate (24.1%) compared to those with radical excision (6.3%). In nasal reconstruction, diverse surgical techniques are essential for precise adaptation based on factors like tumor characteristics and patient needs. Despite surgeons' careful adherence to excision guidelines, the potential for non-radical procedures cannot be entirely eliminated.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

There must exist a reformulation of quantum field theory which does not refer to classical time. We propose a pre-quantum, pre-spacetime theory, which is a matrix-valued Lagrangian dynamics for gravity, Yang-Mills fields, and fermions. The definition of spin in this theory leads us to an eight dimensional octonionic space-time. The algebra of the octonions reveals the standard model; model parameters are determined by roots of the cubic characteristic equation of the exceptional Jordan algebra. We derive the asymptotic low energy value 1/137 of the fine structure constant, and predict the existence of universally interacting spin one Lorentz bosons, which replace the hypothesised graviton. Gravity is not to be quantized, but is an emergent four-dimensional classical phenomenon, precipitated by the spontaneous localisation of highly entangled fermions.

Recently, there is a trend among food manufacturers in producing functional foods containing fruit and milk. On the other hand, there is an increasing demand for buffalo milk as an alternative to cow milk. Therefore, the aim of this study was to investigate the impact of adding bael fruit extract on microbial, physiochemical and sensory characteristics of buffalo yoghurt containing the EPS-producing probiotic Lactobacillus rhamnosus GG (LGG) during 21 days of refrigerated storage. Four formulations of buffalo yoghurt: a control yoghurt manufactured with conventional yoghurt culture (CON); a probiotic yoghurt containing Lb. rhamnosus GG plus yoghurt culture (PY); a probiotic yoghurt containing 5% (w/v) bael (PY5); and 10% (w/v) bael (PY10) were evaluated for changes in pH, syneresis, hardness, probiotic viability and sensory attributes during the storage. Control yoghurt experienced significant post acidification and a higher rate of syneresis. Addition of probiotics had a positive effect on post acidification and syneresis rate. Addition of bael did not affect post-acidification, but significantly decreased the level of syneresis. All probiotic formulations maintained LGG counts of >107 cfu/mL and the highest counts were observed in 5% (w/v) bael incorporated yoghurt. Results showed that buffalo yoghurt is an ideal matrix to deliver LGG and 5% bael incorporation would be ideal or symbiotic product development.

Contemporary literature dealing with the governance and exploitation of common-pool natural resources was initiated by Elinor Ostrom in 1990, and has been growing fast ever since. On the contrary, within the same research stream, the study of the presence and economic role of common resources in entrepreneurial organizations is, to date, under-researched. This work endeavors to fill some gaps in this research perspective by: (i) spelling out a new-institutionalist framework for the analysis of the accumulation and governance of common capital resources within organizational boundaries; (ii) considering co-operative enterprises as the organizational form that, on the basis of historical record, and of behavioral and institutional characteristics, demonstrated to be most compatible with a substantial role for common and non-divided asset-ownership and with its governance thereof; (iii) evidencing and explaining the strong connection between cooperative longevity and the presence of non-divided asset ownership. The economic forces influencing the optimal level of self-financed common capital resources in co-operatives are enquired. Conclusions to the paper evidence the main reasons why the new approach can better explain than preceding ones the economic sustainability and longevity of cooperative enterprises.

Extramammary Paget disease (EMPD) is an uncommon adenocarcinoma of apocrine gland-rich areas, presenting significant diagnostic challenges due to its nonspecific clinical appearance and frequent misidentification as benign, inflammatory skin conditions. Traditional diagnostic methods such as biopsy are invasive and uncomfortable, often required repeatedly due to high recurrence rates. Dermoscopy and non-invasive imaging techniques have been used but provide limited diagnostic accuracy due to their constraints in depth penetration and resolution. Recent advancements in imaging technologies, such as line-field confocal optical coherence tomography (LC-OCT), show promise in enhancing diagnostic precision while minimizing invasive procedures. LC-OCT merges high-resolution imaging with deep penetration capabilities, capturing detailed horizontal and vertical skin images akin to histopathology. This study evaluated the diagnostic performance of LC-OCT in detecting EMPD and its recurrence in 17 clinically suspicious anogenital regions, belonging to 6 patients. Data were collected prospectively at patient bedside by an LC-OCT expert with poor training for EMPD; and, then, reviewed retrospectively by an independent LC-OCT expert with adequate training for EMPD and no concerns about time. The prospective examination yielded 64.7%-accuracy, 71.4%-sensitivity, and 33.3%-specificity. The retrospective analysis achieved 94.1%-accuracy, 100%-sensitivity, and 66.7%-specificity, with the only false positive case being a difficult-to-diagnose concomitant presentation of a lichen sclerosus et atrophicus. Despite the need for specialized training, our results suggest that LC-OCT represents a valuable tool for accurately identifying EMPD and improve its management by reducing unnecessary biopsies. Further studies are needed to standardize its clinical application.

Gradients of smooth functions with non-independent variables are relevant for exploring complex models and for the optimization of functions subjected to constraints. In this paper, we investigate new and simple approximations and computations of such gradients by making use of independent, central and symmetric variables. Such approximations are well-suited for applications in which the computations of the gradients are too expansive or impossible. The derived upper-bounds of the biases of our approximations do not suffer from the curse of dimensionality for any $2$-smooth function, and theoretically improve the known results. Also, our estimators of such gradients reach the optimal (mean squared error) rate of convergence (i.e., $\mathcal{O}(N^{-1})$) for the same class of functions. Numerical comparisons based on a test case and a high-dimensional PDE model show the efficiency of our approach.

DNA damage causes the mutations that are the principal source of genetic variation. DNA damage detection and repair mechanisms therefore play a determining role in generating the genetic diversity on which natural selection acts. Speciation, it is commonly assumed, occurs at a rate set by the level of standing allelic diversity in a population. The process of speciation is driven by a combination of two evolutionary forces: genetic drift and ecological selection. Genetic drift takes place under conditions of relaxed selection, and results in a balance between rates of mutation and rates of genetic substitution. These two processes, drift and selection, are necessarily mediated by a variety of mechanisms guaranteeing genome stability in any given species. One of the outstanding questions in evolutionary biology concerns the origin of the widely varying phylogenetic distribution of biodiversity across the tree of life, and how the forces of drift and selection contribute to shaping that distribution. The following examines some of the molecular mechanisms underlying genome stability and the adaptive radiations that are associated with biodiversity and the widely varying species richness and evenness in the different eukaryotic lineages.

Proteins in biological systems function at the interface of single molecule and bulk chemistry and thus provide novel insights into the basic physical chemistry of scaling and emergent phenomena. For example, a binary mechanical model based on the chemistry of muscle contraction unifies molecular mechanics and thermodynamics and provides an explicit solution to the Gibbs paradox. Using the same model system, here I show that chemical activities of molecular states have no effect on chemical kinetics or energetics. Specifically, while the concentration or number of molecules in a molecular state is widely thought to contribute to reaction free energies, here I show that it is not the physical presence of molecules that pushes a reaction forward but the number of microstates, , accessible in a chemical state that pulls a reaction toward equilibrium with an entropic force down an entropic funnel. With the derivation of an entropic contribution to chemical kinetics, I develop a novel chemical kinetic formulation that fully describes the chemical thermodynamics of both equilibrium and non-equilibrium reactions in terms of an a priori system reaction energy landscape.

In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

Exosomes, a subset of extracellular vesicles, have emerged as pivotal mediators of intercellular communication, revolutionizing our comprehension of cellular interactions. Their diverse cargo, comprising proteins, nucleic acids, and bioactive molecules, plays a crucial role in various physiological and pathological processes. In the intricate landscape of adult neurogenesis, exosomes wield significant influence, actively participating in the generation of new neurons within the adult mammalian brain. Originating predominantly from non-niche cells, these vesicles contribute substantially to the regulation of neuroinflammation, thereby impacting neurogenesis and offering therapeutic promise for neurological disorders. In the specific context of Parkinson's disease (PD), exosomes assume a multifaceted role, prominently implicated in the propagation of α-synuclein oligomers and the orchestration of neuroinflammation. Stem cell-derived exosomes present themselves as promising therapeutic agents, capable of reshaping the microenvironment, repairing neuronal damage, and mitigating apoptosis. The ongoing exploration of exosomes continues to unravel intricate biological processes, paving the way for innovative medical interventions and treatments, particularly within the challenging landscape of neurodegenerative diseases such as PD. The comprehensive understanding of exosomal functions holds the potential to advance our therapeutic approaches, offering new avenues for intervention and treatment strategies in the realm of neurodegenerative disorders.

Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.