bluuebunny/crossref_metadata_2025 huggingface dataset:
UMA REFLEXÃO SOBRE OS CONCEITOS MATEMÁTICOS ENTENDIDOS COMO INSTITUIÇÕES DE SENTIDOS
Authors: Silveira Marisa Rosâni Abreu da
Published: December 2020

Este texto tem o objetivo de apontar o conjunto de conceitos matemáticos entendidos como uma de nossas instituições de sentidos, já que são convenções criadas por nossa sociedade. Para tanto, buscamos, em nossa pesquisa teórica, autores que compreendem a matemática como regras normativas que não dependem da empiria, bem como nascem de necessidades próprias, e não de problemas do cotidiano, mas que podem servir para contextualiza-lo. Nossas análises estão amparadas na filosofiado segundo Wittgenstein e alguns de seus comentadores para tratarmos dos temas das invenções de regras, da gramática da matemática e dos sentidos que emergem do ensino e da aprendizagem da matemática, bem como nas ideias de Descombes, a fim de refletirmos sobre o conceito de instituição de sentidos. Os resultados de nossa investigação acenam para uma necessidade de socializar os conhecimentos matemáticos via ensinamentos em nossas escolas e universidades e concluímos que a herança desses conhecimentos não pode ser sonegada.
SALA DE AULA INVERTIDA: CARACTERIZAÇÃO E REFLEXÕES DAS TRÊS ETAPAS DO MÉTODO NO ENSINO DE MATEMÁTICA
Authors: Dziadzio Silton José , Ferreira Carlos Roberto
Published: December 2020

A Sala de Aula Invertida é um método de ensino que visa à inversão clássica da sala de aula. Os alunos acessam e estudam, reviamente, os conteúdos por meio de recursos digitais, e em sala de aula desenvolvem atividades com aplicação de conceitos abordados no material virtual. Assim, é possível dividir o método em três momentos de execução: antes, durante e após a aula. O artigo busca caracterizar e tecer reflexões sobre as três etapas, com conteúdos de Matemática, em uma turma de 3a série do Ensino Médio. A abordagem inicial dos conteúdos ocorreu por meio de videoaula, e o trabalho em sala de aula foi marcado pela exploração do material virtual em resolução de problemas. Os resultados evidenciam potencialidades no que se refere ao papel ativo dos alunos, ao caráter colaborativo e dinâmico proporcionado durante a aula e, ao fato do professor ser apontado como um mediador do processo de ensino e aprendizagem.
Verification of Finger Joint Stiffness Estimation Method With Soft Robotic Actuator
Authors: Shi Xiang Qian , Heung Ho Lam , Tang Zhi Qiang , Tong Kai Yu , Li Zheng
Published: December 2020

Stroke has been the leading cause of disability due to the induced spasticity in the upper extremity. The constant flexion of spastic fingers following stroke has not been well described. Accurate measurements for joint stiffness help clinicians have a better access to the level of impairment after stroke. Previously, we conducted a method for quantifying the passive finger joint stiffness based on the pressure-angle relationship between the spastic fingers and the soft-elastic composite actuator (SECA). However, it lacks a ground-truth to demonstrate the compatibility between the SECA-facilitated stiffness estimation and standard joint stiffness quantification procedure. In this study, we compare the passive metacarpophalangeal (MCP) joint stiffness measured using the SECA with the results from our designed standalone mechatronics device, which measures the passive metacarpophalangeal joint torque and angle during passive finger rotation. Results obtained from the fitting model that concludes the stiffness characteristic are further compared with the results obtained from SECA-Finger model, as well as the clinical score of Modified Ashworth Scale (MAS) for grading spasticity. These findings suggest the possibility of passive MCP joint stiffness quantification using the soft robotic actuator during the performance of different tasks in hand rehabilitation.
Insulin-Containing Wound Dressing Promotes Diabetic Wound Healing Through Stabilizing HIF-1α
Authors: Yang Peilang , Wang Di , Shi Yan , Li Mingzhong , Gao Min , Yu Tianyi , Liu Dan , Zhang Jie , Wang Jizhuang , Zhang Xiong , Liu Yan
Published: December 2020

HIF-1α is seen as a major regulator during wound healing and controls many wound healing processes, such as angiogenesis, extracellular deposition, and reepithelialization. A diabetic state plays a vicious effect on wound healing, and the destabilization of HIF-1α is a non-negligible factor. Insulin-loaded silk fibroin microparticles were prepared to release insulin by covering the wounds, and this material was proven to promote wound healing in both in vitro and in vivo studies. In this work, we found that this insulin-containing wound dressing could accelerate diabetic wound healing by promoting reepithelialization, angiogenesis, and extracellular matrix, especially collagen deposition. Meanwhile, HIF-1α was stable and accumulated in insulin-containing dressing to group wound cells, which was significantly unstable in the control group. In further studies, we showed that methylglyoxal (MGO), the main form of advanced glycation end products (AGEs), accumulated significantly and caused the destabilization of HIF-1α in the diabetic state. Insulin could alleviate the MGO-induced HIF-1α unstable state and promote HIF-1α target gene expression and its downstream biological effect such as angiogenesis and wound extracellular matrix deposition.
Alteration of Proteotranscriptomic Landscape Reveals the Transcriptional Regulatory Circuits Controlling Key-Signaling Pathways and Metabolic Reprogramming During Tumor Evolution
Authors: Andrieux Geoffroy , Chakraborty Sajib , Das Tonmoy , Boerries Melanie
Published: December 2020

The proteotranscriptomic landscape depends on the transcription, mRNA-turnover, translation, and regulated-destruction of proteins. Gene-specific mRNA-to-protein correlation is the consequence of the dynamic interplays of the different regulatory processes of proteotranscriptomic landscape. So far, the critical impact of mRNA and protein stability on their subsequent correlation on a global scale remained unresolved. Whether the mRNA-to-protein correlations are constrained by their stability and conserved across mammalian species including human is unknown. Moreover, whether the stability-dependent correlation pattern is altered in the tumor has not been explored. To establish the quantitative relationship between stability and correlation between mRNA and protein levels, we performed a multi-omics data integration study across mammalian systems including diverse types of human tissues and cell lines in a genome-wide manner. The current study illuminated an important aspect of the mammalian proteotranscriptomic landscape by providing evidence that stability-constrained mRNA-to-protein correlation follows a hierarchical pattern that remains conserved across different tissues and mammalian species. By analyzing the tumor and non-tumor tissues, we further illustrated that mRNA-to-protein correlations deviate in tumor tissues. By gene-centric analysis, we harnessed the hierarchical correlation patterns to identify altered mRNA-to-protein correlation in tumors and characterized the tumor correlation-enhancing and -repressing genes. We elucidated the transcriptional regulatory circuits controlling the correlation-enhancing and -repressing genes that are associated with metabolic reprogramming and cancer-associated pathways in tumor tissue. By tightly controlling the mRNA-to-protein correlation of specific genes, the transcriptional regulatory circuits may enable the tumor cells to evolve in varying tumor microenvironment. The mRNA-to-protein correlation analysis thus can serve as a unique approach to identify the pathways prioritized by the tumor cells at different clinical stages. The component of transcriptional regulatory circuits identified by the current study can serve as potential candidates for stage-dependent anticancer therapy.
CD11b Signaling Prevents Chondrocyte Mineralization and Attenuates the Severity of Osteoarthritis
Authors: Ehirchiou Driss , Bernabei Ilaria , Chobaz Véronique , Castelblanco Mariela , Hügle Thomas , So Alexander , Zhang Li , Busso Nathalie , Nasi Sonia
Published: December 2020

Osteoarthritis (OA) is a progressive joint disease that is strongly associated with calcium-containing crystal formation (mineralization) by chondrocytes leading ultimately to cartilage calcification. However, this calcification process is poorly understood and treatments targeting the underlying disease mechanisms are lacking. The CD11b/CD18 integrin (Mac-1 or αMβ2), a member of the beta 2 integrin family of adhesion receptors, is critically involved in the development of several inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. We found that in a collagen-induced arthritis, CD11b-deficient mice exhibited increased cartilage degradation compared to WT control animals. However, the functional significance of CD11b integrin signaling in the pathophysiology of chondrocytes remains unknown. CD11b expression was found in the extracellular matrix and in chondrocytes in both healthy and damaged human and murine articular cartilage. Primary murine CD11b KO chondrocytes showed increased mineralization when inducedin vitroby secondary calciprotein particles (CPP) and quantified by Alizarin Red staining. This increased propensity to mineralize was associated with an increased alkaline phosphatase (Alp) expression (measured by qRT-PCR and activity assay) and an enhanced secretion of the pro-mineralizing IL-6 cytokine compared to control wild-type cells (measured by ELISA). Accordingly, addition of an anti-IL-6 receptor antibody to CD11b KO chondrocytes reduced significantly the calcification and identified IL-6 as a pro-mineralizing factor in these cells. In the same conditions, the ratio of qRT-PCR expression of collagen X over collagen II, and that of Runx2 over Sox9 (both ratio being indexes of chondrocyte hypertrophy) were increased in CD11b-deficient cells. Conversely, the CD11b activator LA1 reduced chondrocyte mineralization, Alp expression, IL-6 production and collagen X expression. In the meniscectomy (MNX) model of murine knee osteoarthritis, deficiency of CD11b led to more severe OA (OARSI scoring of medial cartilage damage in CD11b: 5.6 ± 1.8, in WT: 1.2 ± 0.5,p< 0.05, inflammation in CD11b: 2.8 ± 0.2, in WT: 1.4 ± 0.5). In conclusion, these data demonstrate that CD11b signaling prevents chondrocyte hypertrophy and chondrocyte mineralizationin vitroand has a protective role in models of OAin vivo.
Senescence and Apoptosis During in vitro Embryo Development in a Bovine Model
Authors: Ramos-Ibeas Priscila , Gimeno Isabel , Cañón-Beltrán Karina , Gutiérrez-Adán Alfonso , Rizos Dimitrios , Gómez Enrique
Published: December 2020

According to the World Health Organization, infertility affects up to 14% of couples under reproductive age, leading to an exponential rise in the use of assisted reproduction as a route for conceiving a baby. In the same way, thousands of embryos are produced in cattle and other farm animals annually, leading to increased numbers of individuals born. All reproductive manipulations entail deviations of natural phenotypes and genotypes, with in vitro embryo technologies perhaps showing the biggest effects, although these alterations are still emerging. Most of these indications have been provided by animal models, in particular the bovine species, due to its similarities to human early embryo development. Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. Thus, during in vitro culture, a number of stressful conditions affect embryonic quality and viability, inducing subfertility and/or long-term consequences that may reach the offspring. A high proportion of the embryos produced in vitro are arrested at a species-specific stage of development during the first cell divisions. These arrested embryos do not show signs of programmed cell death during early cleavage stages. Instead, defective in vitro produced embryos would enter a permanent cell cycle arrest compatible with cellular senescence, in which they show active metabolism and high reactive oxygen species levels. Later in development, mainly during the morula and blastocyst stages, apoptosis would mediate the elimination of certain cells, accomplishing both a physiological role in to balancing cell proliferation and death, and a pathological role preventing the transmission of damaged cells with an altered genome. The latter would acquire relevant importance in in vitro produced embryos that are submitted to stressful environmental stimuli. In this article, we review the mechanisms mediating apoptosis and senescence during early embryo development, with a focus on in vitro produced bovine embryos. Additionally, we shed light on the protective role of senescence and apoptosis to ensure that unhealthy cells and early embryos do not progress in development, avoiding long-term detrimental effects.
Identification of Novel Glycolysis-Related Gene Signatures Associated With Prognosis of Patients With Clear Cell Renal Cell Carcinoma Based on TCGA
Authors: Wu Chengjiang , Cai Xiaojie , Yan Jie , Deng Anyu , Cao Yun , Zhu Xueming
Published: December 2020

Objective

The purpose of the present study was to detect novel glycolysis-related gene signatures of prognostic values for patients with clear cell renal cell carcinoma (ccRCC).

Methods

Glycolysis-related gene sets were acquired from the Molecular Signatures Database (V7.0). Gene Set Enrichment Analysis (GSEA) software (4.0.3) was applied to analyze glycolysis-related gene sets. The Perl programming language (5.32.0) was used to extract glycolysis-related genes and clinical information of patients with ccRCC. The receiver operating characteristic curve (ROC) and Kaplan–Meier curve were drawn by the R programming language (3.6.3).

Results

The four glycolysis-related genes (B3GAT3, CENPA, AGL, and ALDH3A2) associated with prognosis were identified using Cox proportional regression analysis. A risk score staging system was established to predict the outcomes of patients with ccRCC. The patients with ccRCC were classified into the low-risk group and high-risk group.

Conclusions

We have successfully constructed a risk staging model for ccRCC. The model has a better performance in predicting the prognosis of patients, which may have positive reference value for the treatment and curative effect evaluation of ccRCC.
Hyperglycemia Decreases Epithelial Cell Proliferation and Attenuates Neutrophil Activity by Reducing ICAM-1 and LFA-1 Expression Levels
Authors: Qiu Dongxu , Zhang Lei , Zhan Junkun , Yang Qiong , Xiong Hongliang , Hu Weitong , Ji Qiao , Huang Jiabing
Published: December 2020

Delayed repair is a serious public health concern for diabetic populations. Intercellular adhesion molecule 1 (ICAM-1) and Lymphocyte function-associated antigen 1 (LFA-1) play important roles in orchestrating the repair process. However, little is known about their effects on endothelial cell (EC) proliferation and neutrophil activity in subjects with hyperglycemia (HG). We cultured ECs and performed a scratch-closure assay to determine the relationship between ICAM-1 and EC proliferation. Specific internally labeled bacteria were used to clarify the effects of ICAM-1 and LFA-1 on neutrophil phagocytosis. Transwell assay and fluorescence-activated cell sorting analysis evaluated the roles of ICAM-1 and LFA-1 in neutrophil recruitment. ICAM-1+/+ and ICAM-1–/– mice were used to confirm the findings in vivo. The results demonstrated that HG decreased the expression of ICAM-1, which lead to the low proliferation of ECs. HG also attenuated neutrophil recruitment and phagocytosis by reducing the expression of ICAM-1 and LFA-1, which were strongly associated with the delayed repair.
Reproductive Biology of Geodia Species (Porifera, Tetractinellida) From Boreo-Arctic North-Atlantic Deep-Sea Sponge Grounds
Authors: Koutsouveli Vasiliki , Cárdenas Paco , Conejero Maria , Rapp Hans Tore , Riesgo Ana
Published: December 2020

Boreo-arctic sponge grounds are essential deep-sea structural habitats that provide important services for the ecosystem. These large sponge aggregations are dominated by demosponges of the genus Geodia (order Tetractinellida, family Geodiidae). However, little is known about the basic biological features of these species, such as their life cycle and dispersal capabilities. Here, we surveyed five deep-sea species of Geodia from the North-Atlantic Ocean and studied their reproductive cycle and strategy using light and electron microscopy. The five species were oviparous and gonochoristic. Synchronous development was observed at individual and population level in most of the species. Oocytes had diameters ranging from 8 μm in previtellogenic stage to 103 μm in vitellogenic stage. At vitellogenic stages, oocytes had high content of lipid yolk entirely acquired by autosynthesis, with no participation of nurse cells. Intense vertical transmission of bacterial symbionts to the oocytes by phagocytosis through pseudopodia was observed, especially in late stages of oogenesis. The density of oocytes within the sponge tissue was on average 10 oocytes/mm2 across all species, higher than that of most temperate and tropical oviparous species studied elsewhere. Spermatic cysts were widespread over the tissue during early stages, or fused in larger cysts, around the canals in later stages, and occupying between 1.5 and 12% of the tissue in males. The reproductive season spanned similar periods for all Geodia spp.: from late spring to early autumn. During the reproductive peak of each species, between 60 and 90% of the population was engaged in reproduction for most species. Given the present hazards that threaten the boreo-arctic tetractinellid sponge grounds, it becomes crucial to understand the processes behind the maintenance and regeneration of populations of keystone deep-sea species in order to predict the magnitude of human impacts and estimate their ability to recover. The information provided in this study will be useful for developing adequate conservation strategies for these vulnerable deep-sea habitats.
The Effect of Asymmetry on Strain Distribution, Microstructure and Texture of Multilayer Aluminum Composites Formed by Roll-Bonding
Authors: Magalhães D. C. C. , Rubert J. B. , Cintho O. M. , Sordi V. L. , Kliauga A. M.
Published: December 2020

AA1050/AA7050 multilayered composite sheets with a proportion of 1:1 were produced by Accumulative Roll Bonding (ARB) and Asymmetric Accumulative Roll-Bonding (AARB), using up to 8 cycles and intermediate annealing treatments at 500°C. The main purpose was to produce one composite sheet with high strength and moderate ductility, taking advantage of the mechanical properties of these aluminum alloys. Microstructural features were investigated in order to evaluate the potential to achieve a refined microstructure and the development of structural patterns. The strain distributions as a function of friction and asymmetry were simulated by finite element analysis. Texture was evaluated by X-ray diffraction and electron backscatter diffraction. A continuous layer pattern was obtained by ARB, up to 6 cycles but after 8 cycles shear bands fragmented the harder layers. In the early AARB cycles, the bending and necking of the AA7050 layers yielded a wavy-pattern. The shear strain in the AARB process has a strong influence on achieving a wavy-pattern, more than the flow stress differences of the alloys in the composite. Shear texture increased with the degree of the layers’ discontinuity. Different sources of shear contributed to the formation of microstructural patterns: the shear due to asymmetry, the frictional shear at roll-sheet interface and at the central layer interface and the shear at the layers’ interface. In addition, the ARB process achieved a better interfacial adhesion at the middle interface and higher strength and elongation than the AARB process.
COVID-19 Induced Acute Respiratory Distress Syndrome—A Multicenter Observational Study
Authors: Herrmann Johannes , Adam Elisabeth Hannah , Notz Quirin , Helmer Philipp , Sonntagbauer Michael , Ungemach-Papenberg Peter , Sanns Andreas , Zausig York , Steinfeldt Thorsten , Torje Iuliu , Schmid Benedikt , Schlesinger Tobias , Rolfes Caroline , Reyher Christian , Kredel Markus , Stumpner Jan , Brack Alexander , Wurmb Thomas , Gill-Schuster Daniel , Kranke Peter , Weismann Dirk , Klinker Hartwig , Heuschmann Peter , Rücker Viktoria , Frantz Stefan , Ertl Georg , Muellenbach Ralf Michael , Mutlak Haitham , Meybohm Patrick , Zacharowski Kai , Lotz Christopher
Published: December 2020

Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS).

Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included.

Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay.

Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.
Low Cerebrospinal Fluid Levels of Hemopexin Are Associated With Increased Alzheimer's Pathology, Hippocampal Hypometabolism, and Cognitive Decline
Authors: Ashraf Azhaar A. , Dani Melanie , So Po-Wah
Published: December 2020

Brain iron dyshomeostasis is a feature of Alzheimer's disease. Conventionally, research has focused on non-heme iron although degradation of heme from hemoglobin subunits can generate iron to augment the redox-active iron pool. Hemopexin both detoxifies heme to maintain iron homeostasis and bolsters antioxidant capacity via catabolic products, biliverdin and carbon monoxide to combat iron-mediated lipid peroxidation. The aim of the present study was to examine the association of cerebrospinal fluid levels (CSF) hemopexin and hemoglobin subunits (α and β) to Alzheimer's pathological proteins (amyloid and tau), hippocampal volume and metabolism, and cognitive performance. We analyzed baseline CSF heme/iron proteins (multiplexed mass spectrometry-based assay), amyloid and tau (Luminex platform), baseline/longitudinal neuroimaging (MRI, FDG-PET) and cognitive outcomes in 86 cognitively normal, 135 mild-cognitive impairment and 66 Alzheimer's participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) cohort. Multivariate regression analysis was performed to delineate differences in CSF proteins between diagnosis groups and evaluated their association to amyloid and tau, neuroimaging and cognition. A p-value ≤ 0.05 was considered significant. Higher hemopexin was associated with higher CSF amyloid (implying decreased brain amyloid deposition), improved hippocampal metabolism and cognitive performance. Meanwhile, hemoglobin subunits were associated with increased CSF tau (implying increased brain tau deposition). When dichotomizing individuals with mild-cognitive impairment into stable and converters to Alzheimer's disease, significantly higher baseline hemoglobin subunits were observed in the converters compared to non-converters. Heme/iron dyshomeostasis is an early and crucial event in AD pathophysiology, which warrants further investigation as a potential therapeutic target.
Tumor Microenvironment-Stimuli Responsive Nanoparticles for Anticancer Therapy
Authors: Thomas Reju George , Surendran Suchithra Poilil , Jeong Yong Yeon
Published: December 2020

Cancer is a disease that affects a large number of people all over the world. For treating cancer, nano-drug delivery system has been introduced recently with objective of increasing therapeutic efficiency of chemotherapeutic drug. The main characteristics of this system are the encapsulation of the insoluble chemotherapeutic cargo, increasing the period of circulation in the body, as well as the delivery of the drug at that specific site. Currently, the nano-drug delivery system based on the stimuli response is becoming more popular because of the extra features for controlling the drug release based on the internal atmosphere of cancer. This review provides a summary of different types of internal (pH, redox, enzyme, ROS, hypoxia) stimuli-responsive nanoparticle drug delivery systems as well as perspective for upcoming times.
Nanotechnology-Based Approaches for the Detection of SARS-CoV-2
Authors: Gupta Ritika , Sagar Poonam , Priyadarshi Nitesh , Kaul Sunaina , Sandhir Rajat , Rishi Vikas , Singhal Nitin Kumar
Published: December 2020

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic has been validated as an extreme clinical calamity and has affected several socio-economic activities globally. Proven transmission of this virus occurs through airborne droplets from an infected person. The recent upsurge in the number of infected individuals has already exceeded the number of intensive care beds available to patients. These extraordinary circumstances have elicited the need for the development of diagnostic tools for the detection of the virus and, hence, prevent the spread of the disease. Early diagnosis and effective immediate treatment can reduce and prevent an increase in the number of cases. Conventional methods of detection such as quantitative real-time polymerase chain reaction and chest computed tomography scans have been used extensively for diagnostic purposes. However, these present several challenges, including prolonged assay requirements, labor-intensive testing, low sensitivity, and unavailability of these resources in remote locations. Such challenges urgently require fast, sensitive, and accurate diagnostic techniques for the timely detection and treatment of coronavirus disease 2019 (COVID-19) infections. Point-of-care biosensors that include paper- and chip-based diagnostic systems are rapid, cost-effective, and user friendly. In this article nanotechnology-based potential biosensors for SARS-CoV-2 diagnosis are discussed with particular emphasis on a lateral flow assay, a surface-enhanced Raman scattering-based biosensor, a localized surface plasmon resonance-based biosensor, Förster resonance energy transfer, an electrochemical biosensor, and artificial intelligence-based biosensors. Several biomolecules, such as nucleic acids, antibodies/enzymes, or aptamers, can serve as potential detection molecules on an appropriate platform, such as graphene oxide, nanoparticles, or quantum dots. An effective biosensor can be developed by using appropriate combinations of nanomaterials and technologies.
Role of NDE1 in the Development and Evolution of the Gyrified Cortex
Authors: Soto-Perez Jaseph , Baumgartner Marybeth , Kanadia Rahul N.
Published: December 2020

An expanded cortex is a hallmark of human neurodevelopment and endows increased cognitive capabilities. Recent work has shown that the cell cycle-related gene NDE1 is essential for proper cortical development. Patients who have mutations in NDE1 exhibit congenital microcephaly as a primary phenotype. At the cellular level, NDE1 is essential for interkinetic nuclear migration and mitosis of radial glial cells, which translates to an indispensable role in neurodevelopment. The nuclear migration function of NDE1 is well conserved across Opisthokonta. In mammals, multiple isoforms containing alternate terminal exons, which influence the functionality of NDE1, have been reported. It has been noted that the pattern of terminal exon usage mirrors patterns of cortical complexity in mammals. To provide context to these findings, here, we provide a comprehensive review of the literature regarding NDE1, its molecular biology and physiological relevance at the cellular and organismal levels. In particular, we outline the potential roles of NDE1 in progenitor cell behavior and explore the spectrum of NDE1 pathogenic variants. Moreover, we assessed the evolutionary conservation of NDE1 and interrogated whether the usage of alternative terminal exons is characteristic of species with gyrencephalic cortices. We found that gyrencephalic species are more likely to express transcripts that use the human-associated terminal exon, whereas lissencephalic species tend to express transcripts that use the mouse-associated terminal exon. Among gyrencephalic species, the human-associated terminal exon was preferentially expressed by those with a high order of gyrification. These findings underscore phylogenetic relationships between the preferential usage of NDE1 terminal exon and high-order gyrification, which provide insight into cortical evolution underlying high-order brain functions.
Canonical Quantum Gravity, Constructive QFT, and Renormalisation
Authors: Thiemann Thomas
Published: December 2020

The canonical approach to quantum gravity has been put on a firm mathematical foundation in the recent decades. Even the quantum dynamics can be rigorously defined, however, due to the tremendously non-polynomial character of the gravitational interaction, the corresponding Wheeler–DeWitt operator-valued distribution suffers from quantisation ambiguities that need to be fixed. In a very recent series of works, we have employed methods from the constructive quantum field theory in order to address those ambiguities. Constructive QFT trades quantum fields for random variables and measures, thereby phrasing the theory in the language of quantum statistical physics. The connection to the canonical formulation is made via Osterwalder–Schrader reconstruction. It is well known in quantum statistics that the corresponding ambiguities in measures can be fixed using renormalisation. The associated renormalisation flow can thus be used to define a canonical renormalisation programme. The purpose of this article was to review and further develop these ideas and to put them into context with closely related earlier and parallel programmes.
Meaning-Making Through Creativity During COVID-19
Authors: Kapoor Hansika , Kaufman James C.
Published: December 2020

The COVID-19 pandemic resulted in an abrupt change in routines and livelihoods all around the world. This public health crisis amplified a number of systemic inequalities that led to populations needing to grapple with universally difficult truths. Yet some individuals, firms, and countries displayed resilient and creative responses in coping with pressing demands on healthcare and basic sanity. Past work has suggested that engaging in creative acts can be an adaptive response to a changing environment. Therefore, the purpose of this paper is to describe how entities at the personal, community, and national levels cultivated and expressed creativity in an effort to make meaning during COVID-19. By overlaying the Four C model of creativity on such responses, we aim to (a) to connect mini, little, Pro, and Big creative behaviors with our attempts to make meaning of the ongoing COVID-19 pandemic, and (b) to suggest how engaging in creative expression can be used to guard against the adverse consequences of this outbreak. Acknowledging that this time has been and continues to be distressing and filled with uncertainty, we propose some ways of making sense of current events by applying original thinking across domains. Further, we propose how engaging in creativity can serve to buffer against the negative effects of living through the pandemic.
Characteristics of the Tumor Microenvironment That Influence Immune Cell Functions: Hypoxia, Oxidative Stress, Metabolic Alterations
Authors: Augustin Ryan C. , Delgoffe Greg M. , Najjar Yana G.
Published: December 2020

Immunotherapy (IMT) is now a core component of cancer treatment, however, many patients do not respond to these novel therapies. Investigating the resistance mechanisms behind this differential response is now a critical area of research. Immune-based therapies, particularly immune checkpoint inhibitors (ICI), rely on a robust infiltration of T-cells into the tumor microenvironment (TME) for an effective response. While early efforts relied on quantifying tumor infiltrating lymphocytes (TIL) in the TME, characterizing the functional quality and degree of TIL exhaustion correlates more strongly with ICI response. Even with sufficient TME infiltration, immune cells face a harsh metabolic environment that can significantly impair effector function. These tumor-mediated metabolic perturbations include hypoxia, oxidative stress, and metabolites of cellular energetics. Primarily through HIF-1-dependent processes, hypoxia invokes an immunosuppressive phenotype via altered molecular markers, immune cell trafficking, and angiogenesis. Additionally, oxidative stress can promote lipid peroxidation, ER stress, and Treg dysfunction, all associated with immune dysregulation. Finally, the metabolic byproducts of lipids, amino acids, glucose, and cellular energetics are associated with immunosuppression and ICI resistance. This review will explore these biochemical pathways linked to immune cell dysfunction in the TME and highlight potential adjunctive therapies to be used alongside current IMT.
Stokes Equation in a Semi-Infinite Region: Generalization of the Lamb Solution and Applications to Marangoni Flows
Authors: Koleski Goce , Bickel Thomas
Published: December 2020

We consider the creeping flow of a Newtonian fluid in a hemispherical region. In a domain with spherical or nearly spherical geometry, the solution of the Stokes equation can be expressed as a series of spherical harmonics. However, the original Lamb solution is not complete when the flow is restricted to a semi-infinite space. The general solution in hemispherical geometry is then constructed explicitly. As an application, we discuss the solutions of Marangoni flows due to a local source at the liquid–air interface.
Analysis of Vertical Micro Acceleration While Standing Reveals Age-Related Changes
Authors: Minamisawa Tadayoshi , Chiba Noboru , Inoue Kaori , Nakanowatari Tatsuya , Suzuki Eizaburo
Published: December 2020

In this study, we investigated the fluctuation characteristics of micro vertical acceleration of center of mass (vCOMacc) in standing and examined the usefulness of vCOMacc as an aging marker for standing control abilities. Sixteen young and 18 older adults participated in this experiment. Data for vCOMacc were calculated as the vertical ground reaction force value divided by each participant’s body mass using a force plate. The COMacc frequency structure was determined using the continuous wavelet transform to analyze the relative frequency characteristics. For time domain analysis, we determined the root mean square (RMS) and maximum amplitude (MA) of the integrated power spectral density. We also analyzed the correlation between vCOMacc and lower limb muscle activity. The relative frequency band of vCOMacc was higher in older than young adults, and the time domain indicators were sufficient to distinguish the effects of aging. Regarding the relationship between vCOMacc during standing and muscle activity, a correlation was found with the soleus muscle in young adults, while it was moderately correlated with the gastrocnemius muscle in older adults. The cause of vCOM may be related to differences in muscle activity, and vCOMacc may be utilized to more easily assess the effects of aging in standing control.
Preliminary Study of the Effects of Eccentric-Overload Resistance Exercise on Physical Function and Torque Capacity in Chronic Kidney Disease
Authors: Gollie Jared M. , Patel Samir S. , Scholten Joel D. , Harris-Love Michael O.
Published: December 2020

The purpose of this preliminary study was to describe changes in physical function and torque capacity in adults with chronic kidney disease (CKD) in response to a novel progressive eccentric-overload resistance exercise (ERE) regime. Participants included men (n = 4) diagnosed with CKD according to estimated glomerular filtration rate (eGFR) between 59 and 15 mL/kg/1.73 m2 and not requiring dialysis. Physical function was determined by the Short Physical Performance Battery (SPPB), five repetitions of a sit-to-stand (STS) task, and timed-up and go (TUG). Knee extensor strength was assessed using both isometric and isokinetic contractions and performance fatigability indexes were calculated during a 30-s maximal isometric test and a 30-contraction isokinetic test at 180°/second. None of the patients exhibited significant worsening in their health status after training. Participants demonstrated improvements in several measures of physical function and torque capacity following 24 sessions of ERE. Following training, performance fatigability remained relatively stable despite the increases in torque capacity, indicating the potential for greater fatigue resistance. These findings provide initial evidence for ERE as a potential treatment option to combat declines in physical function and neuromuscular impairments in people with CKD. Future research is required to determine optimal progression strategies for maximizing specific neuromuscular and functional outcomes when using ERE in this patient population.
Attention-Based Fully Gated CNN-BGRU for Russian Handwritten Text
Authors: Abdallah Abdelrahman , Hamada Mohamed , Nurseitov Daniyar
Published: December 2020

This article considers the task of handwritten text recognition using attention-based encoder–decoder networks trained in the Kazakh and Russian languages. We have developed a novel deep neural network model based on a fully gated CNN, supported by multiple bidirectional gated recurrent unit (BGRU) and attention mechanisms to manipulate sophisticated features that achieve 0.045 Character Error Rate (CER), 0.192 Word Error Rate (WER), and 0.253 Sequence Error Rate (SER) for the first test dataset and 0.064 CER, 0.24 WER and 0.361 SER for the second test dataset. Our proposed model is the first work to handle handwriting recognition models in Kazakh and Russian languages. Our results confirm the importance of our proposed Attention-Gated-CNN-BGRU approach for training handwriting text recognition and indicate that it can lead to statistically significant improvements (p-value < 0.05) in the sensitivity (recall) over the tests dataset. The proposed method’s performance was evaluated using handwritten text databases of three languages: English, Russian, and Kazakh. It demonstrates better results on the Handwritten Kazakh and Russian (HKR) dataset than the other well-known models.
Candida duobushaemulonii: An Old But Unreported Pathogen
Authors: Jurado-Martín Irene , Marcos-Arias Cristina , Tamayo Esther , Guridi Andrea , de Groot Piet W. J. , Quindós Guillermo , Eraso Elena
Published: December 2020

Candidiasis caused by species of the Candida haemulonii complex (Candida haemulonii and Candida duobushaemulonii) and closely related species, Candida auris and Candida pseudohaemulonii are increasing. These species often show reduced susceptibility to antifungal drugs, such as azoles and amphotericin B or, less frequently, echinocandins. However, conventional phenotypic identification methods are unable to accurately differentiate these species and, therefore, their prevalence may have been underestimated. In this study, 150 isolates that were probably misidentified were reanalyzed using two novel PCR approaches. We found that one isolate previously identified in 1996 as Candida intermedia was C. duobushaemulonii, being one of the oldest isolates of this species described to date. We also found that this isolate had reduced susceptibility to fluconazole, itraconazole, and amphotericin B.
Characterization of Sporidiobolus ruineniae A45.2 Cultivated in Tannin Substrate for Use as a Potential Multifunctional Probiotic Yeast in Aquaculture
Authors: Kanpiengjai Apinun , Khanongnuch Chartchai , Lumyong Saisamorn , Kummasook Aksarakorn , Kittibunchakul Suwapat
Published: December 2020

At present, few yeast species have been evaluated for their beneficial capabilities as probiotics. Sporidiobolus ruineniae A45.2, a carotenoid-producing yeast, was able to co-produce cell-associated tannase (CAT), gallic acid and viable cells with antioxidant activity when grown in a tannic acid substrate. The aim of this research study was to identify the potential uses of S. ruineniae A45.2 obtained from a co-production system as a potential feed additive for aquaculture. S. ruineniae A45.2 and its CAT displayed high tolerance in pH 2.0, pepsin, bile salts and pancreatin. Furthermore, its viable cells were characterized by moderate hydrophobicity, high auto-aggregation and moderate co-aggregation with Staphylococcus aureus, Salmonella ser. Thyphimurium and Streptococcus agalactiae. These attributes promoted S. ruineniae A45.2 as a multifunctional probiotic yeast. In addition, the intact cells possessed antioxidant activities in a 100–150 μg gallic acid equivalent (GAE)/mL culture. Remarkably, the fermentation broth demonstrated higher antioxidant activity of 9.2 ± 1.8, 9.0 ± 0.9, and 9.8 ± 0.7 mg GAE/mL culture after FRAP, DPPH and ABTS assays, respectively. Furthermore, higher antimicrobial activity was observed against Bacillus cereus, Staphylococcus aureus and Strep. agalactiae. Therefore, cultivation of S. ruineniae A45.2 with a tannic acid substrate displayed significant potential as an effective multifunctional feed additive.
Accommodating Probability to Durability as Facing the Onset of Biological Phenomena from Within
Authors: Matsuno Koichiro
Published: December 2020

Life distinguishes itself from non-life in taking advantage of the cohesion of temporal origin which non-life cannot afford. The temporal cohesion letting the local participants adhere to each other in a contemporaneous manner refers to an instance of the precedent product being pulled into the subsequent production. Setting the precedent is equivalent to preparing the conditions for the subsequent to follow. A concrete implementation of the cohesion of temporal origin, compared with the spatial cohesion common in physics, is found in the natural construction of a reaction cycle with use of the temporal affinity exerted from the immediate local environment. That construction is a temporally local phenomenon in the experiential domain, rather than in the theoretical. The cohesion originating in the local environment is due to the local act of measurement by the environment. A major component of the local environment to each reactant in the reaction cycle is the cycle itself. The cohesion specific to the reaction cycle rests upon the fact that every reaction product from the upstream production in the cycle comes to be fed upon by the immediate downstream production. Every production constituting the reaction cycle is temporally adjacent to and contemporaneous with the similar others residing in the whole cycle, in sharp contrast to the case of the open-ended linear chain of reaction. One externalist scheme of appreciating the internalist enterprise of constructing a durable reaction cycle in a contemporaneous manner may become possible as referring to the Bayesian probability. The durable reaction cycle may be made actual with probability unity under the condition that the products from the preceding production come with the protocol for the similar production to come subsequently.
Risk Factors and Severity of Gastrointestinal Parasites in Selected Small Ruminants from Malaysia
Authors: Paul Bura Thlama , Jesse Faez Firdaus Abdullah , Chung Eric Lim Teik , Che’Amat Azlan , Mohd Lila Mohd Azmi
Published: December 2020

The productivity of smallholder sheep and goat flocks is constrained by high morbidity and mortality of young stock due to helminthosis and coccidiosis. We hypothesized that gastrointestinal parasites are prevalent and may cause severe infections amongst small ruminants in Malaysia. A cross-sectional survey was conducted between March and December 2019 to investigate the prevalence, risk factors, and levels of infection with gastrointestinal strongyle and coccidia in selected smallholder goat flocks in Negeri Sembilan, Malaysia. A total of 257 blood and fecal samples and management data were collected from four farms in Negeri Sembilan. Gastrointestinal parasites were detected by routine sodium chloride floatation, and the McMaster technique was used to quantify the fecal eggs/oocysts per gram outputs (EPG/OPG). The severity of infection was classified as mild (50–799), moderate (800–1200), or severe (>1200). The packed cell volume (PCV) was determined by microhematocrit centrifugation and classified as anemic or non-anemic. Coprological examination revealed an overall prevalence of 78.6% (CI = 72.74–83.44) and 100% flock level prevalence of strongyle and coccidia infection among goats from Negeri Sembilan with a higher infection in flock A-Lenggeng (95.6%) than B-Senawang (87.3%), D-Mendom (80.6%), or C-Seremban (60.0%). The co-infections of strongyle + Eimeria (50.6; CI = 44.50 to 56.64) were more common than single infections of either strongyle (16.7%; CI = 12.66 to 21.78) or Eimeria (4.3%; CI = 2.41 to 7.50). Quantitative analysis has revealed different (p < 0.05) patterns of EPG/OPG in various categories of goats. In total, there were 49.8% mild, 8.6% moderate, and 13.6% severe infections of strongyle and 40.1% mild, 6.6% moderate, and 19.8% severe infections of coccidia among goats. The mean PCV of goats with severe strongyle infection (24.60 ± 0.85) was significantly (p < 0.05) lower than the moderate (26.90 ± 1.15), or mild (28.23 ± 0.50) infections and the uninfected (30.4 ± 0.71). There were increased odds of infection with strongyle and coccidia among female (OR = 3.2) and adult (OR = 11.0) goats from smallholder flocks in Negeri Sembilan. In conclusion, gastrointestinal strongyles and coccidia occur at high frequency among smallholder goats, and there is a higher risk of infection amongst the adult and female stock.
PENDAPATAN NON HALAL SEBAGAI SUMBER DANA KEBAJIKAN PADA BANK UMUM SYARIAH
Authors: Ernawati Ernawati
Published: December 2020

Penelitian ini bertujuan untuk mengetahui pemanfaatan pendapatan non halal pada bank umum syariah sebagai dana kebajikan.  Data penelitian bersumber dari  hasil publikasi  statistik perbankan syariah Otoritas Jasa Keuangan (OJK), dan laporan tahunan bank umum syariah tahun 2018, dengan  sampel 10 (sepuluh) bank. Data yang diperoleh ditabulasi berdasarkan permasalahan yang dianalisis, dan diolah lebih lanjut dengan bantuan persentase dan grafik. Temuan penelitian menunjukkan bahwa sumber pendapatan non halal bank umum syariah terdiri dari pendapatan bunga, dan pendapatan denda/pinalti. Pendapatan tersebut tidak diakui sebagai milik bank umum syariah, namun diperlakukan sebagai dana kebajikan yang dialokasikan untuk kepentingan kegiatan sosial. Besarnya share  pendapatan non halal terhadap total dana kebajikan cukup tinggi, atau sebesar 55,62 persen. Meskipun dana kebajikan ini digunakan untuk tujuan sosial, namun  perlu terus diminimisasi bahkan dihindari, sebagaimana keputusan BNIS untuk menghilangkan kebijakan denda keterlambatan angsuran. Pada sisi lain, pendapatan jasa giro dapat dihindari melalui ketersediaan layanan khusus wadiah (titipan) bagi penempatan dana bank syariah pada bank konvensional. Produk wadiah ini tidak berbasis bunga maupun bagi hasil, namun berfungsi  sebagai titipan.