With the increased availability of sequence data and even of fully sequenced and assembled genomes, phylogeny estimation of very large trees (even of hundreds of thousands of sequences) is now a goal for some biologists. Yet, the construction of these phylogenies is a complex pipeline presenting analytical and computational challenges, especially when the number of sequences is very large. In the last few years, new methods have been developed that aim to enable highly accurate phylogeny estimations on these large datasets, including divide-and-conquer techniques for multiple sequence alignment and/or tree estimation, methods that can estimate species trees from multi-locus datasets while addressing heterogeneity due to biological processes (e.g., incomplete lineage sorting and gene duplication and loss), and methods to add sequences into large gene trees or species trees. Here we present some of these recent advances and discuss opportunities for future improvements.

In this paper, spatial pulse position modulation (SPPM) is used as a case study to investigate the performance of the optical spatial modulation (SM) technique in outdoor atmospheric turbulence (AT). A closed-form expression for the upper bound on the asymptotic symbol error rate (SER) of SPPM in AT is derived and validated by closely-matching simulation results. The error performance is evaluated in weak to strong AT conditions. As the AT strength increases from the weak to strong, the channel fading coefficients become more dispersed and differentiable. Thus, a better error performance is observed under moderate-to-strong AT compared to weak AT. The performance in weak AT can be improved by applying unequal power allocation to make FSO links more distinguishable at the receiver. Receive diversity is considered to mitigate irradiance fluctuation and improve the robustness of the system to turbulence-induced channel fading. The diversity order is computed as half of the number of detectors. Performance comparisons, in terms of energy and spectral efficiencies, are drawn between the SPPM scheme and conventional MIMO schemes such as repetition coding and spatial multiplexing.

The spatial formation of coherent random laser modes in strongly scattering disordered random media is a central feature in the understanding of the physics of random lasers. We derive a quantum field theoretical method for random lasing in disordered samples of complex amplifying Mie resonators which is able to provide self-consistently and free of any fit parameter the full set of transport characteristics at and above the laser phase transition. The coherence length and the correlation volume respectively is derived as an experimentally measurable scale of the phase transition at the laser threshold. We find that the process of stimulated emission in extended disordered arrangements of active Mie resonators is ultimately connected to time-reversal symmetric multiple scattering in the sense of photonic transport while the diffusion coefficient is finite. A power law is found for the random laser mode diameters in stationary state with increasing pump intensity.

The language we use to describe the past can have a strong influence on the audience’s interpretation of our story. In our experiment, we explore, using 3 different conditions, how the framing and language of an accident report can affect the audience’s proposed solutions to manage the problems found. We find that the approach used to create an accident report can have a powerful influence on the audience’s decision making. Whether we are describing an accident in a similar manner to a crime, using a systems approach or we are accepting of multiple stories which are not linear or coherent, the methods we use to capture and communicate the story have a profound impact on the actions decided upon by the reader.

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

Multiple Myeloma (MM) is the second most common type of hematological disease and, although it is rare among patients under 40 years of age, its incidence rises in elderly subject. MM manifestations are usually known with the abbreviation CRAB (hyperCalcemia, Renal failure, Anaemia, and lytic Bone lesions). In particular, the extent of the bone disease is negatively related to a decreased patients’ quality of life and, in general, bone disease in MM increases both morbidity and mortality. The detection of lytic bone lesions on imaging, especially CT and MRI, is becoming crucial from the clinical viewpoint to separate asymptomatic from symptomatic MM patients and the detection of focal lytic lesion in these imaging data is becoming relevant even when no clinical symptoms are present. Therefore, radiology is pivotal in the staging and accurate management of patients with MM even in early phases of the disease. In this review we describe the opportunities offered by quantitative imaging and radiomics in multiple myeloma. At present time there is still high variability in the choice between various imaging methods to study MM patients and high variability in image interpretation with suboptimal agreement among readers even in tertiary centres. Therefore, the potential of medical imaging for patients affected by MM is still to be completely unveiled. In the next years, new insights to study MM with medical imaging will derive from artificial intelligence (AI) and radiomics usage in different bone lesions and from the wide implementations of quantitative methods to report CT and MRI. Eventually, medical imaging data can be integrated with the patient's outcomes with the purpose to find radiological biomarkers for predicting the disease prognostic flow and its therapeutic response.

Missing item responses are prevalent in educational large-scale assessment studies like the programme for international student assessment (PISA). The current operational practice scores missing item responses as wrong, but several psychometricians advocated a model-based treatment based on latent ignorability assumption. In this approach, item responses and response indicators are jointly modeled conditional on a latent ability and a latent response propensity variable. Alternatively, imputation-based approaches can be used. The latent ignorability assumption is weakened in the Mislevy-Wu model that characterizes a nonignorable missingness mechanism and allows the missingness of an item to depend on the item itself. The scoring of missing item responses as wrong and the latent ignorable model are submodels of the Mislevy-Wu model. This article uses the PISA 2018 mathematics dataset to investigate the consequences of different missing data treatments on country means. Obtained country means can substantially differ for the different scaling models. In contrast to previous statements in the literature, the scoring of missing item responses as incorrect provided a better model fit than a latent ignorable model for most countries. Furthermore, the dependence of the missingness of an item from the item itself after conditioning on the latent response propensity was much more pronounced for constructed-response items than for multiple-choice items. As a consequence, scaling models that presuppose latent ignorability should be refused from two perspectives. First, the Mislevy-Wu model is preferred over the latent ignorable model for reasons of model fit. Second, we argue that model fit should only play a minor role in choosing psychometric models in large-scale assessment studies because validity aspects are most relevant. Missing data treatments that countries can simply manipulate (and, hence, their students) result in unfair country comparisons.

The role of pregnancy in multiple sclerosis (MS) is of importance because many patients with MS are young women in the childbearing age who require information to inform their reproductive decisions. Pregnancy is now well-known to be associated with fewer relapses of MS and reduced activity of autoimmune encephalomyelitis (EAE). However, in women with multiple sclerosis, this benefit is not always sufficient to protect against a rebound of disease activity if disease modulating therapy is ceased for pregnancy. There is reason to be concerned that use of assisted reproductive therapies can be associated with relapses of MS. It is thought that the beneficial effects of pregnancy are due to the pregnancy-associated changes in the maternal immune system. There is some evidence of this in human studies and studies of EAE. There is also evidence that having been pregnant leads to better long-term outcome of MS. The mechanism for this is not fully understood but it could result from epigenetic changes resulting from pregnancy or parenthood. Further studies of the mechanisms of the beneficial effects of pregnancy could provide information that might be used to produce new therapies.

A micro decision-making utility model under uncertainty is presented as a complementary foundation for macro coronavirus models. The micro model consists of two functions, a risk averse utility function depending on wellness and a wellness random output which is a function of the input variable called “treatment” consisting of such elements as social distance, washing hands, wearing a face mask, and others. The decision maker selects a level of treatment that maximizes her/his expected utility, given the probabilities of the respective outputs. The focus is on how changes in a person’s psychological attitude towards the macro determined (announced) probabilities affects the optimum results of the model. Such changes create a micro-macro dynamic interaction which is briefly outlined. A short discussion of the model’s behavioral implications for health policy is also given.

While the importance of corporate governance has been broadly acknowledged in global financial markets and academic research, how to devise a practical evaluation system is relatively unexplored. This paper attempts to refine the Corporate Governance Evaluation System (CGES), constructed by the Taiwan Stock Exchange (TWSE) since 2014. The current CGES has several debatable issues in its complicated design (e.g., it comprises over 80 indicators in different types). To resolve those issues, this study invited ten senior domain experts (including several CEOs of financial holding companies) to retrieve 13 essential criteria from the CGES in four dimensions. And this study integrates several multiple criteria decision-making (MCDM) methods (i.e., Decision-making trial and evaluation laboratory (DEMATEL), modified VIKOR, DEMATEL-based analytical network process (DANP)) and the fuzzy evaluation technique to rank the exemplary companies. The obtained ranking is consistent with the one released from the CGES in 2017. This study conducted additional experiments to ensure the robustness of the findings. The newly devised model not only supports the ranking decisions but also provides a managerial guidance for companies to pursue systematic improvements. These findings enrich the understanding of corporate governance and contribute to gaining business sustainability for financial holding companies.

Background: Upper extremities’ function impairments (UEFI) and gait impairment are frequently reported even in the early stages of Multiple Sclerosis (MS) disease. These motor deficits can negatively affect the quality of life (QOL) in MS patient. Exercise has been repeatedly introduced as a beneficial adjuvant therapy for MS, attenuating a wide range of physical and psychological symptoms without any side effects or increased risks of relapse or exacerbation in disease symptoms.Aim: This paper investigates the effect of multi-function swing suspension training (MFSST) program on upper and lower extremities’ function (ULEF), and QOL in MS women according to expanded disability status scale (EDSS) score.Design: Experimental method with a pre-test and post-test design with control group. Setting: The department of Sports Injuries and Corrective Exercise at the Shahid Bahonar University of Kerman.Population: Forty-seven MS women.Methods: Eligible subjects who matched the selection criteria were randomly assigned into three groups as follow: i. Intervention group A (EDSS of 2 – 4), ii. Intervention group B (EDSS of 4.5 – 6.5), and iii. Control group (EDSS of 2 – 6.5). The intervention groups have been trained by the SET program for a duration of 8 weeks. At baseline and after the intervention, the upper extremities’ function (UEF) and the lower extremities’ function (LEF) were assessed by 9-hole peg test (9HPT) and the timed 25-foot walk (T25FW) test, respectively. Moreover, participants’ QOL was measured using the Short Form questionnaire (SF-36).Results: A significant difference was found between the pre-test and post-test variables of walking speed and upper extremity endurance in intervention groups, and between the intervention groups and control group (P < 0.05). Compared to control group, both intervention groups showed improvements in all subscales of QOL, except emotional role limitation score.Conclusions: In summary, these results show that the present protocol of MFSST could be effective in improving ULEF and QOL in MS patients, showing the improvements after 4^th week. Moreover, this protocol was more useful for patients with an EDSS score of more than 4.5. Therefore, it seems that exercise therapy should be considered as a beneficial clinical intervention approach to improve ULEF and QOL in MS patients.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.

STAT3 is an oncoprotein which has been shown to contribute to drug resistance in multiple myeloma (MM). Nonetheless, the clinical utility of STAT3 inhibitors in treating MM has been limited, partly related to some of their pharmacologic properties. To overcome these challenges, our group had previously packaged STAT3 inhibitors using a novel formulation of nanoparticles (NP) and found encouraging results. In this study, we aimed to further improve the pharmacologic properties of these NP by decorating them with monoclonal anti-CD38 antibodies. NP loaded with S3I-1757 (a STAT3 inhibitor), labeled as S3I-NP, were generated. S3I-NP decorated with anti-CD38 (labeled as CD38-S3I-NP) were found to have a similar nanoparticular size, drug encapsulation and loading as S3I-NP. The release of S3I-1757 at 24 hours was also similar between the two formulations. Using Cy5.5 labeling of the NP, we found that the decoration of anti-CD38 on these NP significantly increased the cellular uptake by two MM cell lines (p<0.001). Accordingly, CD38-S3I-NP showed a significantly lower inhibitory concentration at 50% (IC50) compared to S3I-NP in two IL6-stimulated MM cell lines (p<0.001). In a xenograft mouse model, CD38-S3I-NP significantly reduced the tumor size by 4 folds compared to S3I-NP on day 12 after drug administration (p=0.006). The efficacy of CD38-S3I-NP in suppressing STAT3 phosphorylation in the xenografts was confirmed by using immunocytochemistry and western blot analysis. In conclusion, our study suggests that the decoration of anti-CD38 on NP loaded with STAT3 inhibitors can further improve their therapeutic effects against MM.

Studies on N balance due to N inputs and outputs and soil N retention to measure cropping system performance and environmental sustainability are limited due to the complexity of measurements of some parameters. We measured N balance based on N inputs and outputs and soil N retention under dryland agroecosystem affected by cropping system and N fertilization from 2007 to 2011 in the northern Great Plains, USA. Cropping systems were conventional tillage barley (Hordeum vulgaris L.)-fallow (CTB-F), no-tillage barley-fallow (NTB-F), no-tillage barley-pea (Pisum sativum L.) (NTB-P), and no-tillage continuous barley (NTCB). Nitrogen rates to barley were 0, 40, 80, and 120 kg N ha-1. Total N input due to N fertilization, pea N fixation, soil N mineralization, atmospheric N deposition, nonsymbiotic N fixation, and crop seed N and total N output due to grain N removal, denitrification, volatilization, N leaching, gaseous N (NOx) emissions, surface runoff, and plant senescence were 28 to 37% greater with NTB-P and NTCB than CTB-F and NTB-F. Total N input and output also increased with increased N rate. Nitrogen sequestration rate at 0 to 10 cm averaged 22 kg N ha-1 yr-1 for all treatments. Nitrogen deficit ranged from 5 to 16 kg N ha-1 yr-1, with greater deficits for CTB-F and NTB-P and higher N rates. Because of increased grain N removal and reduced N loss to the environment and N fertilizer requirement, NTB-P with 40 kg N ha-1 can enhance agronomic performance and environmental sustainability while reducing N inputs compared to other management practices.

In recent years, autonomous robots have proven capable of solving tasks in complex environments. In particular, robot manipulations in activities of daily living (ADL) for service robots have been in wide use. However, manipulations such as loading a dishwasher or folding laundry are difficult to automate robustly. In addition, manipulations of grasping multiple objects in domestic environments present difficulty. To perform those applications better, we developed robotic systems based on shared autonomy by combining the cognitive skills of a human operator with autonomous robot behaviors. In this work, we present techniques for integration of a shared autonomy system for assistive mobile manipulation and new strategies to support users in the domestic environment. We demonstrate that the robot can grasp multiple objects with random size at known and unknown table heights. Specifically, we developed three strategies for manipulation. From experimental results, we observed that the first strategy has the highest success rate (70% for random objects) up to 70 cm table height. Two other strategies perform better for 80 cm to 100 cm table height. The success rate of the second and third strategies shows an average 63.3% and 73.3%, respectively, for grasping random objects. We also demonstrated these strategies using two intuitive interfaces, a visual interface in rviz and a voice user interface with speech recognition, which are suitable for elderly people. In addition, the robot can select strategies automatically in random scenarios, which make the robot intelligent and able to make decisions independently in the environment. We obtained interesting results showing that the robot adapts to the environmental variation automatically. After these experimental demonstrations, our robot shows the capabilities for employment in domestic environments to perform actual tasks.

This paper presents a configuration of dual output single phase current source inverter with 6 switches for microgrid applications. The inverter is capable of delivering power to two independent set of loads of equal voltages or different voltages at the load end. The control strategy is based on Integral Sliding Mode Control (ISMC). The remote monitoring of the inverter is performed with cyber infrastructure. The cyber physical test bench is developed based on Reconfigurable I/O processor (NI MyRIO-1900) for control and monitoring of the inverter. The inverter prototype is tested in cyber physical test bench in laboratory conditions. The performance of the inverter is analyzed and monitored through the remote system. Also, the inverter is analyzed with different voltage conditions.

At 100% penetration, intermittent renewable energy causes outages. To flatten the leaping supply and demand curves of renewable energy, an energy storage medium and carrier are required. The Hydrogen energy stotrage system (HydESS), which combines a proton exchange membrane (PEM)-based water electrolysis (WE) system and a fuel cell (FC), has the quickest response time, the longest duration, and the greatest storage capacity. HOMER tools for techno-economic analysis are used to evaluate the HydESS hybrid system. Kyiv, Ukraine, is appealing due to its spatial-temporal wind speed, solar irradiance, and energy security. With an LCOE of $0.245 kWh−1 and 9.3% fuel cell power output, the most feasible solution is onshore wind turbine-coupled PEMFC HydESS. As a result 1,000-kW wind power, 250-kW PEMFC, 250-kW PEMWE, and 441-kW BESS are optimized to serve a 3,900 kWh day academic residence load. When compared to a diesel generator and a BESS, the hybrid HydESS reduces CO2 emissions by 4,132 tons over a 25-year period. The LCOE of a hybrid HydESS system is determined by the SOFC lifetime rather than the PEMFC's 2% difference between 40,000 and 50,000 h with the same rated power. This study recommends accelerating PEMFC development with fluctuation-endurable materials and design.

Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbour pathophysiological roles in myelin disease. Many myelin proteins share common attributes, including small size, high hydrophobicity, multifunctionality, longevity, and intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin and correlate these with their various functions, including susceptibility to post-translational modifications, function in protein-protein and protein-membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved.

The development of mobile technology and internet mobile offers new possibilities in both rehabilitation and for patients’ assessment in a longitudinal and MS management perspective. However, because the mobile health applications (mHealth) have only been developed recently, the level of evidence supporting the use of mHealth in patients with multiple sclerosis (pwMS) is currently unclear. Therefore, this study aims to list and describe the different mHealth available for rehabilitation and self-assessment of pwMS and to define the level of evidence supporting these interventions for functioning problems categorized within the International Classification of Functioning, Disability and Health (ICF). 36 studies, performed with 22 different mHealth, were included in this review, 30 about rehabilitation and 6 for self-assessment, representing 3,091 patients. For rehabilitation, most of the studies were focusing on cognitive function and fatigue. Concerning the efficacy we found a small but significant effect of the use of mHealth for cognitive training (SMD = 0.28 [0.12 ; 0.45]) and moderate effect for fatigue (SMD = 0.61 [0.47 ; 0.76]). mHealth is a promising tool in pwMS but more studies are needed to validate these solutions in the others ICF categories. More replications studies are also needed as most of the mHealth have only been assessed in one single study.

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

(1) Background: Evidence-based policymaking requires data about the local population's socioeconomic status (SES) at detailed geographical level, however, such information is often not available, or is too expensive to acquire. Researchers have proposed solutions to estimate SES indicators by analyzing Google Street View images, however, these methods are also resource-intensive, since they require large volumes of manually labeled training data. (2) Methods: We propose a methodology for automatically computing surrogate variables of SES indicators using street images of parked cars and deep multiple instance learning. Our approach does not require any manually created labels, apart from data already available by statistical authorities, while the entire pipeline for image acquisition, parked car detection, car classification, and surrogate variable computation is fully automated. The proposed surrogate variables are then used in linear regression models to estimate the target SES indicators. (3) Results: We implement and evaluate a model based on the proposed surrogate variable at 30 municipalities of varying SES in Greece. Our model has $R^2=0.76$ and a correlation coefficient of $0.874$ with the true unemployment rate, while it achieves a mean absolute percentage error of $0.089$ and mean absolute error of $1.87$ on a held-out test set. Similar results are also obtained for other socioeconomic indicators, related to education level and occupational prestige. (4) Conclusions: The proposed methodology can be used to estimate SES indicators at the local level automatically, using images of parked cars detected via Google Street View, without the need for any manual labeling effort.

A regional organisation (RO) is a group of states that, through the formation of mutual relation-ships, work together for shared regional goals such as economic growth, social welfare, security, and democracy. The Association of South East Asian Nations (ASEAN) is one such organisation, of interest because of its operative paradoxes. However, current theory to study ROs is both fragmented across the field of study, and inadequate. Taking ROs to be complex adaptive systems, diagnosing ROs requires theory that can to explore their hidden aspects. The metacybernetics framework enables the creation of a critical realism configurative a-priori inquiry approach to theory building, the configurations providing coordinative schemas able to respond to predefined complex modelling needs. To analyse ROs using metacybernetics, we offer a derivative schema, Cultural Agency Theory (CAT). Currently this is limited to exploring modes of information acquisition processes through cognitive style, and until now has had no inherent mechanism to explore social relationships as is required to explore ROs. To enable CAT to explore such relationships, we configure the Tönnies social organisation paradigm for CAT. Mindset Agency Theory (MAT) is a specific elaboration of CAT, and creates an empirical setting for the set of formative traits that de-fine an RO character. A related derivative of CAT is that of Multiple Identity Theory (MIT) which enables organisational pathologies to be explored in terms of identity conflicts. Thes multifaceted paradigm provides a relatively simple approach to the RO diagnosis, in particular in terms of stability/coherence. This paper is in two parts. In this part 1, the CAT theory will be further developed through the joint configuration of Tönnies social organisation paradigm allowing its pathologies to be diagnosed. In part 2 of the paper, the theory will be applied to ASEAN and the diagnosis will show that it is an inherently incoherent organisation

Human endogenous retroviruses (HERVs) are ancient retroviral DNA sequences established into germline. They contain regulatory elements and encoded proteins few of which may provide benefits to hosts when co-opted as cellular genes. Their tight regulation is mainly achieved by epigenetic mechanisms which can be altered by environmental factors, e.g. viral infections, leading to HERV activation. Aberrant expression of HERVs associates with neurological disease, such as multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS), inflammatory processes and neurodegeneration. This review summarizes recent advances on the epigenetic mechanisms controlling HERV expression and the pathogenic effects triggered by HERV derepression. The article ends describing new promising therapies targeting HERV elements, one of which, temelimab, has completed phase II trials with encouraging results in treating MS. The information gathered here may turn helpful in the design of new strategies to unveil epigenetic failures behind HERV-triggered disease, opening new possibilities for druggable targets and/or for extending the use of temelimab to treat other associated diseases.

A lightweight image encryption algorithm based on chaos induction via a 5-dimensional hyperjerk oscillator (5DHO) is presented. First, the dynamics of our 5DHO network is investigated and shown to exhibit up to five coexisting hidden attractors in the state space that depend exclusively on the system’s initial values. Further, a simple implementation of the circuit was used to validate its ability to exhibit chaotic dynamical properties. Second, an Arduino UNO platform is used to confirm the usability of our oscillator in digital implementation of the system. Finally, an efficient image encryption application is executed using the proposed chaotic networks based on the use of permutation-substitution sequences. The superior qualities of the proposed strategy are traced to the dynamic set of keys used in the substitution process which heralds the generation of the final ciphered image. Based on the results obtained from the entropy analysis (7.9976), NPCR values (99.62), UACI tests (33.69) and encryption execution time for 512x512 images (0.1179 sec), the proposed algorithm is adjudged to be fast and robust to differential and statistical attacks relative to similar approaches.

This study explored father involvement as a social determinant of child health within the context of macro-environmental changes in Mongolia. Using data for children aged 3-4 from UNICEF’s Multiple Indicator Cluster Surveys, this cross-sectional analysis examined the association between father presence and engagement with child health and educational outcomes. Multivariate regression modeling was employed to identify associations between father presence, engagement, and child outcomes including fever, respiratory illness, diarrhea and preschool attendance. In unadjusted analyses, father engagement was associated with higher odds of pre-school attendance (OR=1.12; 95% CI 1.04-1.20) but not with child illness (OR=1.04; 95% CI 0.95-1.14). Father engagement was no longer associated with pre-school attendance after controlling for potentially confounding variables (ORadj = 0.95; 95% CI 0.88-1.03). Unadjusted and adjusted analyses showed that father presence was not associated with acute illness or preschool attendance. Results also suggest that a larger proportion of children were engaged in activities by their mother compared to their father or other adults. Data indicate that father presence and engagement were not associated with child illness or pre-school attendance. Factors such as maternal education, household wealth, and region of residence are stronger predictors of preschool attendance and should continue to be considered for promoting child health and development in Mongolia.

The research problem was formulated as a question: are demand-supply shocks affecting the opening up of a negative or positive output gap? The hypothesis was formulated: demand-supply shocks have a significant impact on the opening up and deepening of the negative output gap, thereby causing real GDP to shrink or potential GDP to grow. The spatial range applies to Poland and the time period - 2008:Q1-2019:Q4. The methodology consists of three stages: the first is the decomposition of the time series using the TRAMO/SEATS on the components: seasonality, trend-cycle, irregular; the second - the decomposition of the trend-cycle component using the Hodrick-Prescott filter into two separate components; the third is the calculation of the output gap; forecast with VECM and IRF approximation. The ouput gap is in the range of - 11% to +10%. After cleaning it, the shock elements are between -2.2% and 2%. Demand-supply shocks open up and widen the negative output gap. Based on forecasts, the output gap will be positive by the end of 2022, close to 0% (optimal scenario), rising to 5% (optimistic scenario) and negative, deepening to -4% (pessimistic scenario). Two of these scenarios point to a growing risk of secular stagnation.

The renewable energy source plays a major role in the grid side power production. The stability analysis is very essential in the renewable energy converters. In this paper the bifurcation is analyzed in ZETA converter and Continuous input and output(CIO) power Buck Boost converter. The ZETA converter gives positive step down and step up output voltage and the CIO power converter gives the negative step up and step down output voltage. These converters are used in the DC micro grid with renewable energy as the source. The current mode control technique is applied to analyze the bifurcation behavior and the reference current is taken as the bifurcation parameter. When the reference current is varied, both the converters loses its stability and it enters into chaotic region through period doubling bifurcation. The simulation results are presented to study the performance behavior of both the converters. The stability region of both the converters are determined by deriving the Monodromy matrix approach.

Circadian rhythms misalignment is associated with hypertension. The aim of the study was to evaluate the concentration of selected clock proteins- cryptochrome 1 (CRY1) and circadian locomotor output cycles kaput (CLOCK) and to determine their relationships with biochemical and anthropometric parameters and lifestyle elements (diet, physical activity, quality of sleep) in hypertensive patients. In 25 female with hypertension (HT) and 49 non-hypertensive women (NHT), the CRY1 and CLOCK concentrations, total antioxidant status (TAS), lipid profile and glycemia were conducted. Blood pressure and anthropometric measurements, nutritional, exercise and sleep analyses were performed. In HT the CRY1 level was 40.2% lower than in the NHT. No differences were noted in CLOCK concentration between groups. The study showed no relationship between CRY1 or CLOCK concentrations and glucose or lipids profile, amount of physical activity and sleep quality, although CRY1 was associated with some anthropometric parameters. There was a negative correlation between the CLOCK concentration and the amount of saturated fatty acids consumed (24h) in HT. That indicates the possible influence of the diet on the CLOCK level. In a detailed prognosis of the risk of hypertension, it is worth considering the measurement of the level of CRY1 in populations with abnormal anthropometric indices.

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). This suggests that dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.

Mediterranean catchments are characterized by significant spatial and temporal hydrological variability caused by the interaction of natural as well human-induced abiotic and biotic factors. This study investigates the (non-)linearity rainfall-runoff relationship at multiple temporal scales in representative small Mediterranean catchments (i.e., < 10 km2) to achieve a better understanding of the hydrological response. Rainfall-runoff relationship was evaluated in 44 catchments at annual and event –203 events in 12 of these 44 catchments– scales. A linear rainfall-runoff relation was observed at annual scale with higher scatter in pervious than impervious catchments. Larger scattering was observed at event scale, although pervious lithology and agricultural land use promoted significant rainfall-runoff linear relations in winter and spring. These relationships were particularly analysed during five hydrological years in Es Fangar catchment (3.35 km2; Mallorca, Spain) as a temporal downscaling to assess intra-annual variability in which antecedent wetness conditions played a significant role in runoff generation.

Dengue is one of the life-threatening common neglected tropical diseases of the world, yet to develop any therapeutic for its treatment and prevention. Although there is a licensed vaccine reported, but becomes less efficacious due to the presence of multiple serovars of the dengue virus (DENV). Thus, an efficacious dengue vaccine potent to work against all the serovars is very crucial and time-demanding. Here we used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine, targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the promiscuous epitopes revealed the robust immune response against multiple serovars of the DENV and various ethnicities. Final vaccine constructs comprising of B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at N-terminal of the construct with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable, and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. In addition, disulfide engineering was coped to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR8 complex showed minimum deformability. Finally, in silico cloning approach of the vaccine construct within an expression vector (pET28a+) assure good expression. Proposed vaccine may give novel insights for treatment of dengue patients.

Traditional discrimination techniques for Euler deconvolution use only the color spectrums of structural indexes, without considering the spatial distribution characteristics and inherent relationships among the Euler solutions to separate adjacent causative sources. In the present study, a new approach was developed for discriminating uncorrelated Euler solutions from coherent solutions based on the focusing levels indicated by the probability density distributions generated using multivariate kernel density estimations (KDE). A novel multiple coverage technique was proposed by using a series of different sized moving windows over gridded gravity data, which formed tight clusters of Euler solutions for different sized causative sources. The results of the probability density distributions were obtained using a 3-D KDE method for the Euler solution subsets {x, y, z} of synthetical models, and real data from a survey conducted in British Columbia (Canada) which had successfully established more credible and meaningful geological models when compared with three other subsets.

Energy and institutional quality are two factors that determine economic output, but these two factors are often neglected in the search for economic output. Therefore, this study examines the relative importance of energy use and its interaction with institutional quality for economic output. We employ a robust econometric estimation technique on a panel sample of 21 African countries between 2002-2019. Our results show that energy use is significant and negatively related to economic output while moderating terms of institutional quality are significantly associated with economic output, but the direction of the association depends on the specific quality. We find the moderating term control of corruption and government effectiveness to be negative and significantly associated with economic output, whilst political stability, regulatory quality, rule of laws, voice, and accountability positively impact. Our results imply that improved economic output is possible when there are specific institutional strategies.

Bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and similarly to the other cetaceans represent the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary and expression study of Tursiops truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged TRA and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the CDR-IMGT of the dolphin variable V alpha and beta domains were identified. According to comparative modelisation, the atome pair contact sites analysis between the human MH1 grove (G) domains and the TR V domains confirms conservation of the structure of the dolphin TR/pMH.

In this paper, a metal cutting machine position control have been designed and simulated using Matlab/Simulink Toolbox successfully. The open loop response of the system analysis shows that the system needs performance improvement. Static output feedback and full state feedback H₂ controllers have been used to increase the performance of the system. Comparison of the metal cutting machine position using static output feedback and full state feedback H₂ controllers have been done to track a set point position using step and sine wave input signals and a promising results have been analyzed.

In this paper, initially a mathematical model is formulated for transient frequency of power system considering time delays which occur while transmitting the control signals in open communication infrastructure. Time delay negligence in a power system leads to improper measurement of frequency variation in power system. The study of impact of time delays on the stability of power system is performed by estimating the decay rate of frequency wave form using Kalman Filter (KF). In power system, there is a possibility of multiple time delays. This paper also focusses on developing Interacting Multiple Model (IMM) Algorithm with multiple model space using Kalman Filter (KF) as state estimator tool. The multiple time delays in power system is considered as multiple model space. The result shows that KF provides better estimate of correct model for a particular input-set. The qualitative properties of Riccati difference equation (RDE) in terms of state error covariance of IMMKF are also analyzed and presented.

Background and Aim: Multiple sclerosis (MS) is known as an autoimmune disease and a chronic inflammatory condition, inducing a wide variety of mood affective disorders, including depression and feelings of hopelessness in many aspects of patients’ quality of life (QoL). In view of the positive side effects of spirituality and spiritual care on finding appropriate strategies for further adaptation, this study aimed to determine the impact of group spiritual care (GSC) on levels of hope in patients suffering from MS. Materials and Methods: This clinical trial was conducted on a total number of 96 patients with MS, referring to the National Multiple Sclerosis Society (NMSS) in the city of Zahedan, Iran. Following sample selection via the convenience sampling technique, the patients meeting the inclusion criteria were randomized into two groups, i.e., intervention and control. The data collection tools for this purpose included a demographic information form and the Adult Hope Scale (AHS, Snyder et al. 1991), completed by the subjects at the pre- and post-intervention stages. As well, the intervention group received five sessions of GSC during three weeks but the control group members only talked over daily issues along with their mental health problems. The data were also analyzed using the SPSS Statistics software (ver. 14). Results: The Kruskal-Wallis test results revealed that the GSC intervention could have a significant positive effect on raising hope in the patients with MS (p<0.001). Moreover, a significant growth was observed in the scores of hope dimensions including agency and pathway (p<0.001). Conclusion: GSC can effectively boost levels of hope in patients suffering from MS in all dimensions. Therefore, it is recommended to utilize this type of care in order to nurture hope in such individuals.

The involvement of macular function in its preganglionic elements, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group), 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery of BCVA (MS-ON-P Group). MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0-5° (R1), 5-10° (R2), 10-15° (R3), 15-20° (R4), 20- 25° (R5), and from retinal sectors [superior, nasal, inferior and temporal] between 0-15° and 0- 25°. In MS-ON-P Group, mean mfERG RADs detected from R1 (0-5°) and from the central nasal quadrant (0-15°) were significantly reduced (p<0.01) with respect to those of Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.

A very high parking occupancy can negatively influence the traffic performance of an area by causing very long cruising times. A very low parking occupancy, on the other hand, is inefficient from a space utilization perspective. Thus, this paper proposes a framework to compute the optimal parking occupancy rate over a given time horizon based on a macroscopic traffic and parking model. This rate is set high enough to ensure an efficient usage of the parking infrastructure. However, it should also guarantee a high likelihood of finding parking in order to eliminate the drivers’ time wasted in cruising for parking and the added congestion it causes. The model outputs are based on small data collection efforts and low computational costs, and they can be generated without complex simulation software using a simple numerical solver. Multiple vehicle types are included into our methodology allowing us to generate insights about the optimal parking occupancy with or without differentiated parking (i.e., parking for specific vehicles, such as fuel and electric vehicles). In times of a modal shift towards electric vehicles, cities can use our model to evaluate how much parking supply (with battery charging opportunities) they would like to dedicate to electric vehicles in order to achieve optimal traffic and parking results, and whether a differentiated or semi-differentiated parking policy is desirable. We illustrate our framework in a case study of a central area within the city of Zurich, Switzerland, showing the traffic and parking impacts (e.g., average searching time for parking, total revenue created by parking fees, optimal parking occupancy rate) for different proportions of fuel and electric vehicles in the parking demand and/or supply. Our results confirm that optimal occupancy rates are between and for most realistic scenarios. We then discuss how these rates might change depending on various demand and supply relationships, and according to different parking policies. We show that equal proportions between electric vehicles in the demand and their parking spaces in the supply lead to the best traffic performance in the area. We also provide the tools for cities to analyze their loss in performance if they do not react, e.g., to an increasing demand for electric vehicles over time. Moreover, we illustrate how some of these risks can be mitigated by having more flexible parking policies, e.g., allowing electric vehicles to use parking spaces for fuel vehicles.

In this study, in order to explore the failure mode of ZnO varistors under multiple lightning stroke, a 5-pulse 8/20 μs nominal lightning current with pulse intervals of 50 ms was applied to the ZnO varistors. Scanning electron microscopy (SEM) and X-ray diffractometry (XRD) were used to analyze the microstructure of the material. The failure processes of ZnO varistors caused by multiple lightning impulse current were described. The performance changes of ZnO varistors after multiple lightning impulses were analyzed from macro and micro perspectives. According to the results of this study’s experiments, the macroscopic failure mode of the ZnO varistors after multiple lightning impulse was that the electrical parameters deteriorate rapidly with the increase of the number of impulse groups, and finally destroyed by side-corner cracking. The microstructural examination indicated that after the multiple lightning strokes, the proportion of Bi in the several crystal phases had been converted, the grain size of ZnO varistors became smaller, and the white intergranular phase (Bi-rich grain boundary layer) increased significantly. The failure mechanism was thermal damage and grain boundary structure damage caused by temperature gradient thermal stress generated by multiple lightning current.

Multiple myeloma (MM) is an incurable, diverse cancer in which abnormal plasma cells produce and release monoclonal immunoglobulin (Ig), also known as monoclonal protein or M protein. MM is always preceded by monoclonal gammaglobulinemia of unknown significance (MGUS) and smoldering multiple myeloma (SMM). Diagnosis of MM is made from a bone marrow sample, which involves analysis of the appearance of plasma cells. Quantification of CD138+ plasma cells in core biopsies is performed using techniques such as immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and conventional cytogenetics. Urinalysis includes total protein by immunofixation and 24-hour urine by serum protein electrophoresis. FISH probes should detect the presence of at least del 13, del 17p, t(4;14), t(11;14), t(14;16), and 1q21 amplifications. Indeed, next-generation sequencing (NGS) has become an increasingly important tool in the diagnosis and treatment of MM. It can be used to identify genetic mutations, copy number changes, and clonal structures to help determine disease prognosis and treatment strategies. NGS can identify subclonal populations of cancer cells that are resistant to therapy and may lead to disease relapse, and can be used to identify potential targets for personalized therapy. For example, NGS can identify mutations in genes involved in drug resistance, enabling the selection of drugs that may be more effective in treating a patient's cancer. This systematic review analyzes 182 papers to determine the position and role of NGS in the diagnosis of MM. We first analyze the platforms and sample types used in the selected studies, and then start discussing the results.

Multiple sclerosis (MS) is a debilitating disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective sheath (myelin) that covers the nerve fibers, causing communication problems between the brain and the rest of the body. Eventually the disease can cause permanent damage or nerve damage. The signs and symptoms of MS are very different and depend on the extent of the nerve damage and which nerves are affected. Some people with severe MS may lose the ability to walk independently or completely, while others may experience a long recovery period without any new symptoms. Most people with MS have a relapsing-remitting illness. They experience periods of new symptoms or recurrences that occur over days or weeks and usually improve somewhat or completely. Following these recurrences, there are periods of recovery that can last for months or even years. In this Project, we used some methods of machine learning in order to evaluate the precision and accuracy of Methods to Predict and classification of Multiple Sclerosis with different stages. In order to calculate accuracy, precision, recall Fscore we used some different method such as Art Fuzzy, SVM, Decision tree to compare the classes two by two. To improve the results we used the method of Adaptive fuzzy optimization. we used two options Genetic algorithm and particle swarm optimization.

Recently, several research groups have reported on anomalous enhancement of the self-field critical currents, Ic(sf,T), at low temperatures in superconductor/Dirac-cone material/superconductor (S/DCM/S) junctions. Some papers attributed the enhancement to the low-energy Andreev bound states arising from winding of the electronic wave function around DCM. In this paper, Ic(sf,T) in S/DCM/S junctions have been analyzed by two approaches: modified Ambegaokar-Baratoff and ballistic Titov-Beenakker models. It is shown that the ballistic model is an inadequate tool to analyze experimental data from S/DCM/S junctions. The primary mechanism for limiting superconducting current in S/DCM/S junctions is different from the conventional view that the latter is the maximum value within the order parameter phase variation. Thus, there is a need to develop a new model for self-field critical currents in S/DCM/S systems.

Breast cancer is a leading cause of death among women. Conventional screening methods, such as mammography, and ultrasound diagnosis are expensive and have significant limitations. Digital Image Elasto Tomography (DIET) is a new noninvasive breast cancer screening system that has a potential to be a low cost and reliable breast cancer screening tool. It is based on modal analysis of the breast mass, and stereographic 3D image analysis to detect the stiffer abnormal tissues. However, camera sensor noise, especially Gaussian noise is a major source of Optical Flow (OF) error in this approach to tumor detection. This work studies the performance of different conventional filters, including the standard Gaussian filter tool to remove this noise and produce more robust screening results. A radical approach, Multiple Frame Noise Removal (MFNR) is proposed, for use in this type of medical image processing instead of a Gaussian filter or other typical image noise removal tools. Its a multiple frame noise removal method where Probability Density Function (PDF) of noise is extracted from the multiple images by characterizing the same pixel positions in multiple images. The noise becomes deterministic, and hence easily removed. The proposed algorithm was applied to a data set from 10 phantom breast tests with a prototype DIET system, and 10 in-vivo samples from healthy women. Comparisons were made to an optimal Gaussian filter form that is commonly used. Reductions in OF error using these digitally imaged data sets was used to compare performance. Refinement of the images for medical applications requires higher PSNR, which was successfully achieved by using MFNR algorithm. In this study, the algorithm was used to improve the imaging results of a DIET system. The conventional wisdom that states that noise removal and detail preservation are contrasting effects is

World Health Organization (WHO) provides the guideline for managing the Particulate Matter (PM) level because when the PM level is higher, it threats the human health. For managing PM level, the procedure for measuring PM value is needed firstly. We use Tapered Element Oscillating Microbalance (TEOM)-based PM measuring sensors because it shows higher cost-effectiveness than Beta Attenuation Monitor (BAM)-based sensor. However, TEOM-based sensor has higher probability of malfunctioning than BAM-based sensor. In this paper, we call the overall malfunction as an anomaly, and we aim to detect anomalies for the maintenance of PM measuring sensors. We propose a novel architecture for solving the above aim that named as Hypothesis Pruning Generative Adversarial Network (HP-GAN). We experimentally compare the several anomaly detection architectures to certify ours performing better.

Soil quality assessment based on crop yields and identification of key indicators of it can be used for better management of agricultural production. In the current research, the weighted additive soil quality index (SQIw), factor analysis (FA) and multiple linear regression (MLR) method are used to assess the soil quality of rainfed winter wheat fields with two soil orders on 53.20 km2 of agricultural land in western Iran. A total of 18 soil quality indicators were determined for 100 soil samples (0-20 cm depth) from two soil orders (Inceptisols and Entisols). The soil properties measured were: pH, soil texture, organic carbon (OC), cation exchange capacity (CEC), electrical conductivity (EC), soil microbial respiration (SMR), carbonate calcium equivalent (CCE), soil porosity (SP), bulk density (BD), exchangeable sodium percentage (ESP), mean weight diameter (MWD), available potassium (AK), total nitrogen (TN), available phosphorus (AP), available Fe (AFe), available Zn (AZn), available Mn (AMn), and available Cu (ACu). Mean wheat grain yield for the two years for all of the 100 sampling sites was also gathered. The SQIw was calculated using two weighting methods (FA and MLR) and maps were created using a digital soil mapping framework. The soil indicators taken in the minimum data set (MDS) were AK, clay, CEC, AP, SMR, and sand. The correlation between the MLR weighting technique (SQI-M) and the rainfed wheat yield (r=0.62) was slightly larger than that the correlation of yield with the FA weighted technique (SQI-F) (r=0.58). Results showed that the means of both SQI-M and SQI-F and rainfed wheat yield for Inceptisols were higher than for Entisols although these differences were not statistically significant. Both SQI-M and SQI-F showed that areas with Entisols had lower proportions of good soil quality grades (Grade I and II), and higher proportions of poor soil quality grades (Grade IV and V) compared to Inceptisols. Based on these results, soil type must be considered for soil quality assessment in future studies to maintain and enhance soil quality and sustainable production. The overall soil quality of the study region was of poor and moderate grades. To improve soil quality, it is therefore recommended that effective practices such as the implementation of scientific integrated nutrient management involving the combined use of organic and inorganic fertilizers in rainfed wheat fields be promoted.

A progressive and chronic neurological condition called MSA (Multiple System Atrophy) is characterized clinically by varying degrees of dysautonomia, cerebellar ataxia, and parkinsonism. The concept of mitochondrial dysregulation in MSA is one perspective in handling this neurodegenerative disease. Damage to functional mitochondria is driven by the presence of ɑ-Synuclein-induced mitochondrial localization. The goal of MSA treatment up until now has been to reduce symptoms. One of the innovations in the treatment of MSA could be the novel idea based on mitochondrial reprogramming pathways. Mitochondrial reprogramming can be done in various ways in which the use of hydrogen, magnesium and low-dose hydrogen peroxide.

Background: This work aimed to undertake a bibliometric analysis of the Rubella virus. Medical studies were conducted between 2000 and 2022 to discover trends, dynamics, and research outputs in the industry. Methods:A bibliometric study was performed using R software to determine research characteristics indexed worldwide and published in Rubella research in medical studies. The Rubella virus was chosen as the subject in the PUBMED database, and 374 papers from the previous two decades were reviewed. Results: There was an increase in the number of publications after 2003. The United States was the most essential countryamong all which had the most contributions on Rubella Virus. Conclusion:Rubella research has increased in the medical profession over the previous decade, with the United States leading to publications in this field.

Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the disturbance of reduction-oxidation (redox) homeostasis such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring a battery of reactive chemical species, oxidative enzymes, antioxidative enzymes and degradation products helps evaluate the redox status of MS patients to expedite building personalized treatment plans for the sake of better quality of life.

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Photovoltaic (PV) generation is potentially uncertain. Probabilistic PV generation forecasting methods have been proposed with prediction intervals (PIs). However, several studies have dealt with geographically distributed PVs in a certain area. In this study, a two-step probabilistic forecast scheme is proposed for geographically distributed PV generation forecasting. Each step of the proposed scheme adopts ensemble forecasting based on three different machine-learning methods. In this case study, the proposed scheme was compared with conventional non-multistep forecasting. The proposed scheme improved the reliability of the PIs and deterministic PV forecasting results through 30 days of continuous operation with real data in Japan.

Introduction: This study aimed to validate the psychometric properties of the German eHealth Impact Questionnaire (eHIQ-G), which is divided into two independently administered and scored parts. Methods: 162 people with MS browsed one of two possible websites containing information on MS and completed an online survey. Internal consistency was assessed by Cronbach’s alpha and structural validity by Confirmatory Factor Analysis. Construct validity was examined by assessing correlations with the eHealth Literacy Questionnaire and the General Self-Efficacy Scale. Moreover, the mean difference of the eHIQ-G score between the two websites was investigated. Results: Cronbach’s alpha for the eHIQ-G subscales ranged from .833 to .885. The eHIQ-G part 1 achieved acceptable levels of goodness-of-fit indices, whereas the fit for the eHIQ-G part 2 was poor and likewise for the alternative modified models. The correlations with the reference instruments were 0.08 – 0.62 and as expected. Older age was related with lower eHIQ-G part 1 score, whereas no significant effect was found for education. Although not significant, the website ‘AMSEL’ reached higher mean scores on eHIQ part 2. Conclusion: The eHIQ-G has good internal consistency, and sufficient structural and construct validity. It will facilitate the measurement of the impact of websites providing health information.

Recently, Kayyalha et al. (Phys. Rev. Lett., 2019, 122, 047003) reported on anomalous enhancement of the self-field critical currents, I_c (sf,T), at low temperatures in Nb/BiSbTeSe₂-nanoribbon/Nb Josephson junctions. The enhancement was attributed to the low-energy Andreev bound states arising from winding of the electronic wave function around the circumference of the topological insulator BiSbTeSe₂ nanoribbon. In this paper, we show that identical enhancement in I_c(sf,T) and in the upper critical field, B_c2(T), at approximately same reduced temperatures, were reported by several research groups in atomically thin junctions based on a variety of Dirac-cone materials (DCM) earlier. Our analysis shows that in all these S/DCM/S systems the enhancement is due to a new superconducting band opening. Taking in account that several intrinsic superconductors also exhibit the effect of new superconducting band(s) opening when sample thickness becomes thinner than the out-of-plane coherence length, we strength our previous proposal that there is a new phenomenon of additional superconducting band(s) opening in atomically thin films.

Sequence alignment and comparison through pairwise, multiple, global and local techniques are the main principles that underpin comparative genomics. However, most of the algorithms used are alignment-based which imposed some limitations on their use and application. In an attempt to provide an alignment-free alternative approaches, a methodology of comparative optinalysis and statistical mirroring was used and adopted to provide a suitable alternative for multiple genomic sequence comparison. In this article, methods comparison with MUSCLE, MUFFT, Clustal Omega, and T-Coffee was designed to assess the suitability and statistical power of statistical mirroring as an alternative method for multiple genomic sequences comparison using different sets of logically generated biological sequence datasets with different problems and computational complications. The results of the comparisons validate that statistical mirroring is a suitable alignment-free alternative approach for multiple genomic sequence comparison. The applied method (statistical mirroring) distinguishes itself over MUSCLE, MUFFT, Clustal Omega, and T-Coffee in specificity to a position-specific changes, specificity to a base-specific changes, cladogram and phylogenetic linearity, alignment independency, computational simplicity, and limit of input capacity.

Mechanical power and motion are often transmitted by the gear-rotor-bearing system. When there are fitting clearances between the housing and outer ring in bearings, complex vibration responses will be generated, which makes the operating status difficult to identify. Therefore, for analyzing dynamic responses, a dynamic model of gear-rotor-bearing systems with bearing fitting clearances is proposed. In the model, the bearing system with fitting clearances and gear pair system are combined, and the coupling relationship is determined by the gyroscopic mo-tion of the shaft. The friction force and collision force caused by fitting clearances are also con-sidered, which are simulated by the Coulomb friction model and Hertz theory. The result shows that the meshing stiffness will also be excited by the bearing displacement. When there are fit-ting clearances on the bearing, the amplitude modulation of the bearing outer raceway to the system time-domain response is intensified, and the multiple harmonic frequency of bearings and gear pairs are generated on the spectrum, as well as defect frequencies of gear pairs. As the fitting clearance is increased, the higher multiple harmonic responses will be caused. Although the response amplitude of the gearbox is increased by raising the input speed, multiple harmon-ic responses are suppressed, which makes the system mainly vibrate at the fundamental fre-quency. Then, the dynamic model and the vibration analysis are experimentally verified.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared 15 SCs and their derivatives (tetrahydrocannabinol [THC], naphthoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.

A regional organisation (RO) is a group of states that, through the formation of mutual relationships, work together for shared regional goals such as economic growth, social welfare, security, and democracy. The Association of South East Asian Nations (ASEAN) is one such organisation, of interest because of its operative paradoxes. However, current theory to study ROs is both fragmented across the field of study, and inadequate. Taking ROs to be complex adaptive systems, diagnosing ROs requires theory that can to explore their hidden aspects. The metacybernetics framework enables the creation of a critical realism configurative a-priori inquiry approach to theory building, the configurations providing coordinative schemas able to respond to predefined complex modelling needs. To analyse ROs using metacybernetics, we offer a derivative schema, Cultural Agency Theory (CAT). Currently this is limited to exploring modes of information acquisition processes through cognitive style, and until now has had no inherent mechanism to explore social relationships as is required to explore ROs. To enable CAT to explore such relationships, we configure the Tönnies social organisation paradigm for CAT. Mindset Agency Theory (MAT) is a specific elaboration of CAT, and creates an empirical setting for the set of formative traits that de-fine an RO character. A related derivative of CAT is that of Multiple Identity Theory (MIT) which enables organisational pathologies to be explored in terms of identity conflicts. This multifaceted paradigm provides a relatively simple approach to the RO diagnosis, in particular in terms of stability/coherence. This paper is in two parts. In this part 1, the CAT theory will be further developed through the joint configuration of Tönnies social organisation paradigm allowing its pathologies to be diagnosed. In part 2 of the paper, the theory will be applied to ASEAN and the diagnosis will show that it is an inherently incoherent organisation.

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

High-energy small electron beams generated by linear accelerators are used for radiotherapy of localized superficial tumors. The aim of the present study is to assess the dosimetric performance under small radiation therapy electron beams of the novel PTW microSilicon detector by comparison with commercially available dosimeters. Relative dose measurements of circular fields with 20, 30, 40 and 50 mm aperture diameters were performed for 4 to 12 MeV energy range of electron beams generated by an Elekta Synergy linac. Percentage depth dose, transverse profiles and output factors normalized to the 10 × 10 cm2 reference field were measured. All dosimetric data were collected in a PTW MP3 motorized water phantom at SSD of 100cm by using the novel PTW microSilicon detector. The PTW diode E and the PTW microDiamond were also used in all beam aperture for benchmarking. Data for the biggest field size were also measured by the PTW Advanced Markus ionization chamber.Measurements performed by the microSilicon are in good agreement with the reference values for all the tubular applicators and beam energies, within the stated uncertainties. This confirms the reliability of the microSilicon detector for relative dosimetry of small radiation therapy electron beams collimated by tubular applicators.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Obesity has become a rising global health problem affecting adults’ quality of life. The objective of this study was to describe the prevalence of obesity in Indonesian adults based on the cluster of islands. The study was also aimed to identify the risk factors of obesity in each island cluster. This study analysed secondary data of Indonesian Basic Health Research 2018. Our data for analysis comprised 688,638 adults (>=15 years) randomly selected using proportionate to population size throughout Indonesia. We included 20 variables for sociodemographic and obesity-related risk factors for analysis. Obese status was defined using Body Mass Index (BMI) >= 27.5 kg/m2. Our current study defined seven major islands cluster as the unit analysis consisting of 34 provinces in Indonesia. Descriptive analysis was conducted to determine the characteristics of the population and to calculate the prevalence of obesity within provinces in each of the island’s clusters. Multivariate logistic regression analyses to calculate odds ratios (ORs) was performed using R version 3.6.3. The study results showed that all island clusters had at least one province with an obesity prevalence of more than 20%. Six out of twenty variables, comprising four diet factors (consumption of sweet food, high-salt food, meat food, and carbonated drinks) and two other factors (mental health disorders and smoking behaviour), varied across the island clusters. In conclusion, there was a variation of obesity prevalence of the provinces within and between island clusters. Variation of risk factors raised in each cluster island suggested the government rethink and reframe the intervention to address obesity.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

In the development and growth of family businesses, succession is an unsolvable problem, which is also a popular focus of academic research. For a family firm, succession may be a strategic decision but also a long-term and intricate "footrace." It will have a significant impact on the long-term viability of a family firm if it is not handled appropriately. This study mainly explores the influences of family business owners' intergenerational succession intention on their family firms’ innovation strategy in China. In addition, this study further examines the moderating role of the institutional environment in the above relationship. Therefore, the data in this article comes from a survey of 271 family businesses in eight different regions of China. Also, this paper can aid the smooth transition of intergenerational transmission of small and medium-sized family businesses in addition to the untroubled development of technological innovation activities. Specifically, the institutional environment plays a negative moderating role in the relationship between family succession, radical succession, technological innovation, and a positive regulating role in the relationship between single equity succession and technological innovation.

A study about influence of heat input on welding defects in vertical upward welding position for dissimilar material and thickness using a new variation of TIG welding torch is done with support of advanced inspection methods SEM and EBSD. With vertical upward welding position, control heat input plays an important role to keep the weld stabilization without defects. On the other hand, TIG welding process using a conventional TIG torch (conventional TIG welding process) has low efficiency and it is difficult to control heat input with high accuracy. So, it is considered that using conventional TIG torch is still a challenge for welding thin plates. In this case, a new variation of TIG torch has been developed. This torch used a constricted nozzle to improve plasma arc characteristics. As a result, it can control efficiently the heat input to prevent the excessive or insufficiency for joining thin sheets. For evaluation of welding quality, advanced examination methods SEM and EBSD were applied to directly observe the welding defects. From the results, the formation mechanism of blowhole inside weld zone in case of welding dissimilar material and thickness was discussed. It is pointed out that when sufficient welding current, the change from weld zone to base metal is uniform, no welding defects such as blowhole was seen. However, in case of low welding current, the thinner base metal is insufficient fusion and the change between weld zone and base metal is not uniform. The blowhole was observed at SS400 material side.

As of today, 20 disease modifying drugs (DMD) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgement and experience of neurologists and the evaluation of therapeutic response can only be obtained by monitoring clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, the aim of this study is to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing-remitting courses. These patients were characterized on the basis of their age, sex, presence of oligoclonal bands, therapy and MRI lesion load at onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data we generated a few simulation scenarios for each patient, including those who matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which really occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

Multiple sclerosis (MS) and necrotizing periodontitis (NP) are two diseases whose aetiology and pathophysiology do not seem to have a common link; however, the treatment of MS with monoclonal antibodies and the decrease in humoral immunity that this entails can be a trigger or an aggravation in patients who present NP. We present a clinical case of NP in which its clinical manifestations, treatment and evolution during therapy with ocrelizumab are reflected. During the evolution of the case, a rapid progression of NP was evidenced. During her evolution, the patient suffered bilateral pneumonia due to COVID requiring treatment with corticosteroids and antibiotics, which led to clinical relief of her NP. Given this important clinical finding, we consider of great interest the regulated dental monitoring of those patients with MS before, during and after the administration of monoclonal antibodies to prevent periodontal deterioration.

This paper studies the integrated design problems of control and guidance with parameter uncertainties, target disturbances, input constraints and actuator faults. Firstly, based on the integrated design idea of the missile guidance and control, the auxiliary variable is used to establish and transform it into a cascade system with input constraints, actuator faults and disturbances of unknown upper bounds. Secondly, the adaptive anti-saturation dynamic surface fault-tolerant controller is designed by using the back-stepping method, adaptive control, auxiliary system and tracking differentiator. By introducing the tracking differentiator and tangent barrier Lyapunov function, the computational explosion problem in the traditional back-stepping method is avoided and the angle of attack can be guaranteed in prospective range, respectively. Finally, the theoretical proof of the designed control strategy is given to ensure that the states of the closed-loop system are bounded. At the same time, the digital simulation of the maneuvering target of different maneuvering forms is carried out, which further illustrate the effectiveness and robustness of the designed control schemes.

The purpose of the study is to empirically analyze the effect of quality of governance on tax revenue in South Africa. This is done by analyzing a time series dataset covering 1996 to 2020. The study used voice and accountability, regulatory quality, government effectiveness, control of corruption, political stability and rule of law as proxies of quality of governance. Multiple regression analysis was performed to test hypotheses. Based on the regression results, all quality of governance variables in South Africa have a negative effect on tax revenue except corruption control. The findings of this study also include policy recommendations. The government of South Africa must design and implement effective ways to combat poor governance, which results in a tax revenue shortfall.

Aiming at the problem that the performance of Adaptive Kalman filter estimation will be affected when the statistical characteristics of the process and measurement noise matrix are inaccurate and time-varying in the linear Gaussian state-space model, an algorithm of Multi-fading factor and update monitoring strategy adaptive Kalman filter based variational Bayesian is proposed. Inverse Wishart distribution is selected as the measurement noise model, the system state vector and measurement noise covariance matrix are estimated with the variational Bayesian method. The process noise covariance matrix is estimated by the maximum a posteriori principle, and the update monitoring strategy with adjustment factors is used to maintain the positive semi-definite of the updated matrix. The above optimal estimation results are introduced as time-varying parameters into the multiple fading factors to improve the estimation accuracy of the one-step state predicted covariance matrix. The application of the proposed algorithm in target tracking is simulated. The results show that compared with the current filters, the proposed filtering algorithm has better accuracy and convergence performance, and realizes the simultaneous estimation of inaccurate time-varying process and measurement noise covariance matrices.

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.

Multiple lines of evidence indicate that CD8$^+$ T cells are important in the control of HIV-1 (HIV) replication. However, CD8$^+$ T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8$^+$ T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8$^+$ T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8$^+$ T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8$^+$ T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8$^+$ T cells in the chronic infection. The breadth of HIV-specific CD8$^+$ T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8$^+$ T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8$^+$ T-cell responses and the presence of intra- and interclonal competition between multiple CD8$^+$ T-cell responses; such competition may limit the magnitude of CD8$^+$ T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8$^+$ T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Rapid post-earthquake damage diagnosis of bridges can guide decision-making for emergency response management and recovery. This can be facilitated using digital technologies to remove the barriers of manual post-event inspections. Prior mechanics-based Finite Element (FE) models can be used for post-event response simulation using the measured ground motions at nearby stations; however, the damage assessment outcomes would suffer from uncertainties in structural and soil material properties, input excitations, etc. For instrumented bridges, these uncertainties can be reduced by integrating sensory data with prior models through a model updating approach. This study presents a sequential Bayesian model updating technique, through which a linear/nonlinear FE model, including soil-structure interaction effects, and the foundation input motions are jointly identified from measured acceleration responses. The efficacy of the presented model updating technique is first examined through a numerical verification study. Then, seismic data recorded from the San Rogue Canyon Bridge in California are used for a real-world case study. Comparison between the free-field and the foundation input motions reveals valuable information regarding the soil-structure interaction effects at the bridge site. Moreover, the reasonable agreement between the recorded and estimated bridge responses shows the potentials of the presented model updating technique for real-world applications. The updated FE model is considered as the digital twin of the bridge and can be used to analyze the bridge and monitor the structural response at element, section, and fiber levels to diagnose the location and severity of any potential damage mechanism.

Life cycle assessment (LCA) is used frequently as a decision support tool for evaluating different design choices of products based on their environmental impacts. A life cycle usually comprises several phases of varying timespan. The amount of emissions generated from different life cycle phases of a product could be significantly different from one another. In conventional LCA, the emissions generated from the life cycle phases of a product are aggregated at the inventory analysis stage, which is then used as an input for life cycle impact assessment. However, when the emissions are aggregated, the temporal variability of inventory data is ignored, which may result in inaccurate environmental impact assessment. Besides, the conventional LCA does not consider the environmental impact of circular products with multiple use cycles. It poses difficulties in identifying the hotspots of emission-intensive activities with the potential to mislead conclusions and implications for both practice and policy. To address this issue and to analyse the embedded temporal variations in inventory data in a CE context, the paper proposes to calculate the emission intensity for each life cycle phase. It is argued that calculating and comparing emission intensity, based on the timespan and amount of emissions for individual life cycle phases, at the inventory analysis stage of LCA offers a complementary approach to the traditional aggregate emission-based LCA approach. In a circular scenario, it helps to identify significant issues during different life cycle phases and the relevant environmental performance improvement opportunities through product, business model and supply chain design.

Assuming the Multiple Point Principle (MPP) as a new law of Nature, we considered the existence of the two degenerate vacua of the Universe: a) the first Electroweak (EW) vacuum at $v_1\approx 246$ GeV—“true vacuum”, and b) the second Planck scale “false vacuum” at $v_2 \sim 10^{18}$ GeV. In these vacua, we investigated different topological defects. The main aim of the paper is an investigation of the black-hole-hedgehogs configurations as defects of the false vacuum. In the framework of the $f(R)$ gravity, described by the Gravi-Weak unification model, we considered a black-hole solution, which corresponds to a “hedgehog”—global monopole, that has been “swallowed” by the black-hole with mass core $M_{BH}\sim 10^{18}$ GeV and radius $\delta\sim 10^{-21}$ GeV$^{-1}$. Considering the results of the hedgehog lattice theory in the framework of the $SU(2)$ Yang-Mills gauge-invariant theory with hedgehogs in the Wilson loops, we have used the critical value of temperature for the hedgehogs’ confinement phase ($T_c\sim 10^{18}$ GeV). This result gave us the possibility to conclude that the SM shows a new physics (with contributions of the $SU(2)$-triplet Higgs bosons) at the scale $\sim 10$ TeV. This theory predicts the stability of the EW-vacuum and the accuracy of the MPP.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN and XBP1). mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival.

Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its response to therapy is the identification of driver mutations. The introduction of gene expression profiling (GEP) in MM was an important step in elucidating the molecular heterogeneity of MM and its clinical relevance. Since some mutations in myeloma occur in non-coding regions, studies based on the analysis of mRNA provide more comprehensive information on the oncogenic pathways and mechanisms relevant to MM biology. In this review, we discuss the role of gene expression profiling in understanding the biology of multiple myeloma together with the clinical manifestation of the disease, as well as its impact on treatment decisions and future directions.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Apathy in patients with Parkinson's disease (PD) is one of the least studied manifestations of a wide range of neuropsychiatric disorders (PND). The frequency of apathy in PD, according to various researchers, is 17–80%. Structural and neurochemical changes associated with PD are considered as the leading pathophysiological factors of apathy. Possible general pathophysiological mechanisms of apathy and hypokinesia, depression, executive (frontal) cognitive functions, sleep disorders in PD are discussed. The basis of the pathophysiological commonality of apathy, hypokinesia, and executive functions is probably bilateral disturbances in the functional connections of the stratum and dorsolateral, medial parts of the prefrontal cortex. The combination of apathy and depression in PD may be due to dysfunction of the structures of the limbic system and the medial orbital prefrontal cortex responsible for motivational determined behavior. The variability of the relationship between apathy and hypokinesia, depression, cognitive impairments, sleep disorders at different stages of PD may be associated with the phenomenological heterogeneity of apathy.Apathy worsens the quality of life, makes a significant contribution to disorders of both household and social adaptation of PD patients. It is promising to study the possibility of correcting apathy using dopaminergic therapy. Against the background of the appointment of pramipexole (1.5-3.0 mg / day) to 20 patients with PD (middle stage, according to Hen-Yar-2.5) to correct movement disorders after 4-6 weeks of therapy, a statistically significant positive dynamics of apathy were noted. According to the total assessment of the scale of apathy SE Starkstein (AS). As a result of the study, no statistically significant correlation was found between the dynamics of the total apathy indicator and the dynamics of motor symptoms of PD according to the unified rating scale for assessing PD (“Motor functions”), which, we believe, indicates an independent effect of pramipexole therapy in relation to motivational disorders.

This paper will discuss the application of statistic modeling to interpret a health system crisis in Sri Lanka due to COVID- 19.A strong focus on the preventive approach and the contact tracing with the utilization of available resources in a rational manner describes Sri Lanka’s response towards COVID- 19 prevention and mitigation. The early contact tracing, preemptive quarantining, isolation, and treatment were implemented as a concerted effort. This approach, proven efficient during the early phase of the pandemic, was sustainable when there was a rapid increase in the COVID- 19 patients since July 2021, exceeding the health system capacity.The country’s COVID- 19 situation during the period from 01st of August 2021 to 31st of October 2021 was taken into consideration. Variables used for analysis were; total number of cases, recovered cases, comorbid and O₂ dependent patients, ICU patients, and deaths. The regression model was applied to analyze the data by using the EViews 12 (x64) software application.The correlation coefficients of all the independent variables under consideration implies that they have a strong positive relationship with the number of deaths occurred during the said period. According to the computed multiple linear regression model, the number of positive cases and O₂ dependents have a positive relationship with the dependent variable. Further, the Durbin- Watson stat value of the model and multicollinearity test reflect that it is free from serial correlation thereby the model is fit. From the perspective of epidemiological control, these findings highlight the importance of keeping the number of cases within the limits of health system capacity.

We are concerned with the use of some classical spectral collocation methods as well as with the new software system Chebfun in order to compute high order (index) eigenpairs of singular as well as regular Schrodinger eigenproblems. We want to highlight both the qualities as well as the shortcomings of these methods and evaluate them vis-a-vis the usual ones. In order to resolve a boundary singularity we use Chebfun with the simple domain truncation technique. Although this method is equally easy to apply with spectral collocation, things are more nuanced in the case of these methods. A special technique to introduce boundary conditions as well as a coordinate transform which maps an unbounded domain to a nite one are the ingredients. A challenging set of "hard" benchmark problems, for which usual numerical methods (f. d., f. e. m., shooting etc.) fail, are analysed. In order to separate "good"and "bad"eigenvalues we estimate the drift of the set of eigenvalues of interest with respect to the order of approximation and/or scaling of domain parameter. It automatically provides us with a measure of the error within which the eigenvalues are computed and a hint on numerical stability. We pay a particular attention to problems with almost multiple eigenvalues as well as for problems with a mixed (continuous) spectrum. In the latter case we try to numerically highlight its existence. Special attention will be paid to the higher eigenpairs (the pair of eigenvalue and the corresponding eigenfunction approximated by an eigenvector spanning its nodal values).

Since the beginning of the mass immunization with COVID-19 vaccines of patients with multiple sclerosis, many data on the efficacy and safety of these vaccines have been produced. Considering that MS is an autoimmune disease whose pathology can be explained by an altered immune system and that some DMTs seem to be able to decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety in terms of AEFIs occurrence and the antibody response after the third dose of COVID-19 vaccines in people with MS. Third doses were administered from October 2021 to January 2022. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. The majority of patients (n=193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

Keywords: Chemical Intolerance, Drug Intolerance, Food Intolerance, QEESI, BREESI, Multiple Chemical Sensitivity, Toxicant-induced Loss of Tolerance, Prevalence

To investigate the dynamics of land surface temperature (LST) in Afghanistan in the period 2000-2021 and to assess the impact of such factors as soil moisture, precipitation, and vegetation coverage on it, remotely sensed soil moisture data from Land Data Assimilation System (FLDAS), precipitation data from Climate Hazards Group Infra-Red Precipitation with Station (CHIRPS), and NDVI and LST from Moderate Resolution Imaging Spectroradiometer (MODIS) were downloaded and correlations between them were analyzed using the regression method. The result shows that the LST in Afghanistan has a slightly decreasing, but insignificant trend during the study period (R=0.2, p-value=0.25), while vegetation coverage, precipitation, and soil moisture had an increasing trend. It was revealed that soil moisture has the highest impact on LST (R=0.7, p-value=0.0007), and the soil moisture, precipitation, and vegetation coverage explain almost 80% of spring (R2=0.73) and summer (R2=0.76) LST variability in Afghanistan. The LST variability analysis done separately for Afghanistan’s rivers subbasins shows that the LST of the Amu Darya subbasin had an upward trend in the study period, while for the Kabul subbasin the trend was downward.

Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p &lt; 0.0001), and showed positive correlation with disease progression (r = 0.394, p &lt; 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

We investigated the response of the Manila clam Venerupis philippinarum to possible temperature and salinity changes in a holding facility. First, clams were exposed to four temperatures for 15 days. Valve closure and survival of clams exposed to seawater at 18℃ were higher than that of those exposed to seawater at 24℃. Second, clams were exposed to six salinities for 15 days. Survival of clams exposed to two salinity fluctuation conditions (24–30 and 27–24 psu) was lower than that of clams exposed to constant 30 psu conditions. Valve closures of clams exposed to constant low salinity conditions (24 psu) and two salinity fluctuation conditions (24–30 and 27–24 psu) were higher than of those exposed to constant 30 psu conditions. Lastly, clams were exposed to two different temperatures and three different salinities conditions for 8 days. Valve closure and survival decreased significantly under the combination of 24℃ and 18 psu. These results suggest that an increase in temperature or a wider range of salinity fluctuations are detrimental to the survival of the Manila clam. The synergistic effect of temperature and salinity stressors may decrease the survival period of clams compared to the effect of a single stressor.

The amount and spatial distribution of foliage in a tree canopy have fundamental functions in ecosystems as they affect energy and mass fluxes through photosynthesis and transpiration. They are usually described by the Leaf Area Index (LAI) and the Leaf Area Density (LAD), which can be measured through a variety of methods, including voxel-based methods applied to LiDAR point clouds. A theoretical study recently compared the numerical errors arising from different voxel-based estimation methods for Plant Area Density (PAD) based on Beer’s law-based, contact frequency and Maximum-Likelihood Estimation, showing that the bias-corrected Maximum Likelihood Estimator was theoretically the most efficient. However, this earlier study i) ignored wood volumes; ii) neglected vegetation clumping inside the voxel; iii) ignored instrument characteristics in terms of effective footprint, iv) was limited to a single viewpoint. In practice, retrieving LAD from PAD is not straightforward, vegetation is not randomly distributed in volumes of interest, beams are divergent and forestry plots are usually sampled from more than one viewpoint, to mitigate the effect of occlusion. In the present short communication, we extend the previous efficient formulation to actual field conditions to i) account for the presence of both wood volumes and wood hits, ii) rigorously include correction terms for vegetation and instrument characteristics, iii) integrate multiview data. A numerical comparison with other methods commonly used to combine information from different viewpoints led to error reduction, especially in poorly-explored volumes, which are frequent in actual canopies. Beyond its concision, completeness and efficiency, this new formulation -which can be applied to multiview TLS, but also UAV LiDAR scanning - can help reducing errors in LAD estimation.

Objective: The purpose of this study was to investigate the effects of Crocin on brain neuroterophins, cognition, sensory and motor dysfunction and compare to fingolimod effects in experimental model of demyelination with Ethidium Bromide EB in female Wistar rats. Methods: Animals were assigned in to 8 groups; Sham, Sham operated (ShOp), EAE, crocin treated (Cr5,10,20 mg/kg), Vehicle, Fingolompd (Fing) and fingolimod + crocin (Cr+Fing). Demyelination was induced by single dose injection of 10 μl of EB 0.1% into the fourth ventricle of the brain. Crocin and fingolimod were applied for 21 days, daily, oral gavage. BDNF, NGF1, nerve conduction velocities, tail flake latency, balance and behavioral variables were sampled and analyzed by paired t-test and ANOVA test with repeated post hoc measurements. Results: The results showed that crocin improves all studied factors, but remarkable imrovments were observed in dosage of 10 mg/kg. Crocin (10mg/kg) and fingolimod (1mg/kg) significantly improved cognition variables in open field test, sensory and motor nerve conduction velocity, tail flick latency and clinical signs (p<005). In addition, applying of crocin co-administered with fingolimod led to significant increases in all assessed factors, greater than crocin or fingolimod intervention alone (α≤0.001). Conclusion: Based on the current findings, crocin can improve the level of brain neurotrophins, exploratory behavior and nerve conduction after demyelination as close as fingolimod results. So, crocins can be considered as a neuro supportive agent in the management of degenerative diseases maybe similar to fingolimod mechanism.

This paper focuses on the combination of the method of moments and the wire-grid approximation as an effective computational technique for modeling symmetrical antennas with low computational cost and quite accurate results. The criteria and conditions for the use of wire-grid surface approximation from various sources are presented together with new recommendations for modeling symmetrical antenna structures using the wire-grid approximation. These recommendations are used to calculate the characteristics of biconical and horn antennas at different frequencies. The results obtained using different grid and mesh settings are compared to those obtained analytically. Moreover, the results are compared to those obtained using the finite difference time domain numerical method, as well as the measured ones. All results are shown to be in a good agreement. The used recommendations for building a symmetrical wire-grid of those symmetrical antenna elements provided the most advantageous parameters of the grid and mesh settings and the wire radius, which are able to give a quite accurate results with low computational cost. Additionally, the known equal area rule was modified for a rectangular grid form. The obtained radiation patterns of a conductive plate using both the original rule and the modified one are compared with the electrodynamic analysis results. It is shown that the use of the modified rule is more accurate when using a rectangle grid form.

Background: Neurosarcoidosis is a great mimic, and its distinction from multiple sclerosis and other disorders can be particularly troublesome. We investigated whether cerebrospinal fluid (CSF) examination could help distinguish these two conditions and propose new diagnostic criteria. Methods: Stringent hierarchical diagnostic criteria were formulated. These were then applied prospectively to 531 neurological patients in whom neurosarcoidosis entered the differential diagnosis. The CSF total protein (TP), white cell count (WCC) and angiotensin-converting enzyme (ACE) levels were measured. The CSF and serum IgG patterns after isoelectric focusing were compared. Not all CSF parameters were measured in every patient. Results: 85/531 (16%) cases examined were diagnosed with neurosarcoidosis. Only 22 of these 85 (26%) met stringent diagnostic criteria. Intrathecal synthesis of oligoclonal IgG was evident in only 1/19 (5%) who fulfilled these criteria compared to 19/59 (32%) cases who did not (p = 0.03). CSF TP levels > 1g/L were more common in patients meeting the stringent criteria compared to the remainder of the patients, i.e. 11/22 (50%) vs 14/58 (24%) (p<0.05). Eleven out of 20 cases (55%) fulfilling stringent criteria had elevated CSF WCCs, and 6/12 cases (50%) had raised CSF ACE, neither significantly different from the remaining cases. Mean CSF TP, WCC, and ACE levels did not differ significantly between any groups of patients. Interpretation: Large elevations in CSF total protein, white cell count, and ACE occur in neurosarcoidosis but are rare in multiple sclerosis. However, the diagnostic use of these tests is limited since minimal changes may occur in both conditions. In contrast, intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is very uncommon in neurosarcoidosis whilst occurring in 95-98% of cases of multiple sclerosis. This observation implies that the immunopathogenesis of the two disorders is quite different. We suggest caution in diagnosing neurosarcoidosis when intrathecal oligoclonal IgG synthesis is detected. We propose new diagnostic criteria for neurosarcoidosis for future research.

We introduce the Transformation Flower Approach (TFA), a Theory of Change that attends to multiple value creation and institutional change as a dual design challenge. We highlight how the TFA integrates social scientific theories and models relevant for transformative change (in particular focusing on pathways, leverage points, governance, power, and values) and demonstrate its practical value by an application to the ongoing transformation of the Dutch food system. By providing a holistic, transdisciplinary and practically relevant approach that aims to support new social contract formation, the TFA goes beyond other transformative change approaches. Based on the notion of pathways, it offers a toolbox that aids in working towards desired futures, involving both incumbents and challengers in an effort to harness untapped yet proximal potentials in a forward-looking way. By embracing an innovation approach, it not only promises to circumvent resistance to change, but also serves as a step-by-step approach to identify options for multiple value creation and effective cooperation. We demonstrate the analytical and practical value of the TFA by discussing action perspectives at various levels and scales in the context of the Dutch food system transition, including (1) area-oriented approaches, (2) acceleration agendas for specific transformation pathways, and (3) actor-specific transformation flowers. In developing these, we emphasize the importance of interdependencies between leverage points. Our approach helps to identify opportunities to link transformative options (the what), actors (the who) and levers (the how) in dynamic interaction to embark on transformative pathways.

This paper proposes a model to evaluate business projects to get into an incubator, allowing to rank them in order of selection priority. The model combines the Momentum method to build prospective scenarios and the Multiple Criteria Decision Making (MCDM) method TOPSIS-2N to rank the alternatives. Six business projects were evaluated to be incubated. The Momentum method made it possible for us to create an initial core of criteria for the evaluation of incubation projects. The TOPSIS-2N method supported the decision to choose the company to be incubated by ranking the alternatives in order of relevance. Our evaluation model has improved the existing models used by incubators. This model can be used and / or adapted by any incubator to evaluate the business projects to be incubated. The set of criteria for the evaluation of incubation projects is original and the use of prospective scenarios with a MCDM method to evaluate companies to be incubated does not exist in the literature.

The formation of high-melting-point Cu₆Sn₅ interconnections is crucial to overcome the collapse of Sn-based micro-bumps and produce reliable intermetallic interconnections in three-dimensional (3D) package. However, because of the multiple reflows in 3D package manufacturing, Cu₆Sn₅ interconnections will experience the cyclic polymorphic transitions in the solid state. The repeated and abrupt change in the Cu₆Sn₅ lattice due to the cyclic polymorphic transitions can cause extreme strain oscillations, producing damages at the surface and in the interior of the Cu₆Sn₅ matrix. Moreover, because of the polymorphic-transition-induced grain splitting and superstructure phase formation, the reliability of Cu₆Sn₅ interconnections will thus face great challenges in 3D package. In addition, the Cu₆Sn₅ polymorphic transition is structure-dependent, and the η′↔η polymorphic transition will occur at the surface while the η′↔ηs↔η polymorphic transition will occur in the deep matrix. Our results can provide in-depth understandings of structural evolution and damage mechanism of Cu₆Sn₅ interconnections in real 3D package manufacturing.

Guessing effects frequently occur in testing data in educational or psychological applications. Different item response models have been proposed to handle guessing effects in dichotomous test items. However, it has been pointed out in the literature that the oftenemployed three-parameter logistic model poses implausible assumptions regarding the guessing process. The four-parameter guessing model has been proposed as an alternative to circumvent these conceptual issues. In this article, the four-parameter guessing model is compared with alternative item response models for handling guessing effects through a simulation study and an empirical example. It turned out that model selection for item response models should be rather based on the AIC than the BIC. However, the RMSD item fit statistic used with typical cutoff values was found to be ineffective in detecting misspecified item response models. Furthermore, sufficiently large sample sizes are required for sufficiently precise item parameter estimation. Moreover, it is argued that the criterion of statistical model fit should not be the sole criterion of model choice. The item response model used in operational practice should be valid with respect to the meaning of the ability variable and the underlying model assumptions. In this sense, the four-parameter guessing model could be the model of choice in educational large-scale assessment studies.

Non-orthogonal multiple access (NOMA) has been investigated to support massive connectivity for Internet-of-things (IoT) networks. However, since most IoT devices suffer from limited power and decoding capabilities, it is not desirable to pair a large number of devices simultaneously, which encourages two-user NOMA grouping. Additionally, most existing techniques have not considered the diversity in the target QoS of IoT devices, which may lead to spectrum inefficiency. Few investigations have partially considered that issue by using an order-based power allocation (OPA) approach, where the power is allocated according to the order to the user's target throughput within a priority-based NOMA (PNOMA) group. However, this does not fully capture the effects of diversity in the values of the users' target throughputs. In this work, we handle both problems by considering a throughput-based power allocation (TPA) approach, that captures the QoS diversity, within a three-users PNOMA group as a compromise between spectral efficiency and complexity. Specifically, we investigate the performance of a time-division PNOMA (TD-PNOMA) scheme, where the transmission time is divided into two-time slots with two-users per PNOMA group. The performance of such TD-PNOMA is compared with a fully PNOMA (F-PNOMA) scheme, where the three users share the whole transmission time, in terms of the ergodic capacity under imperfect successive interference cancellation (SIC). The results reveal the superiority of TPA compared with OPA approach in both schemes, besides that the throughput of both schemes can outperform each other under imperfect SIC based on the transmit signal-to-noise ratio and the deployment scenarios.

Multiple mRNA isoforms of the same gene are produced via alternative splicing, a biological mechanism that regulates protein diversity while maintaining genome size. Alternatively spliced mRNA isoforms of the same gene may sometimes have very similar sequence, but they can have significantly diverse effects on cellular function and regulation. The products of alternative splicing have important and diverse functional roles, such as response to environmental stress, regulation of gene expression, human heritable and plant diseases. The mRNA isoforms of the same gene, such as the apoptosis associated CASP3 gene, can have dramatically different functions. The shorter mRNA isoform product CASP3-S inhibits apoptosis, while the longer CASP3-L mRNA isoform promotes apoptosis. Despite the functional importance of mRNA isoforms, very little has been done to annotate their functions. The recent years have however seen the development of several computational methods aimed at predicting mRNA isoform level biological functions. These methods use a wide array of proteo-genomic data to develop machine learning-based mRNA isoform function prediction tools. In this review, we discuss the computational methods developed for predicting the biological function at the individual mRNA isoform level.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.