Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationships of APOE Genotypes With Small RNA and Protein Cargo of Brain Tissue Extracellular Vesicles From Patients With Late-Stage AD

Background and Objectives Variants of the apolipoprotein E (APOE) gene are the greatest known risk factors for sporadic Alzheimer disease (AD). Three major APOE isoform alleles, ε2, ε3, and ε4, encode and produce proteins that differ by only 1–2 amino acids but have different binding partner interactions. Whereas APOE ε2 is protective against AD relative to ε3, ε4 is associated with an increased risk for AD development. However, the role of APOE in gene regulation in AD pathogenesis has remained largely undetermined. Extracellular vesicles (EVs) are lipid bilayer–delimited particles released by cells to dispose of unwanted materials and mediate intercellular communication, and they are implicated in AD pathophysiology. Brain-derived EVs (bdEVs) could act locally in the tissue and reflect cellular changes. To reveal whether APOE genotype affects EV components in AD brains, bdEVs were separated from patients with AD with different APOE genotypes for parallel small RNA and protein profile. Methods bdEVs from late-stage AD brains (BRAAK stages 5–6) from patients with APOE genotypes ε2/3 (n = 5), ε3/3 (n = 5), ε3/4 (n = 6), and ε4/4 (n = 6) were separated using our published protocol into a 10,000g pelleted extracellular fraction (10K) and a further purified EV fraction. Counting, sizing, and multiomic characterization by small RNA sequencing and proteomic analysis were performed for 10K, EVs, and source tissue. Results Comparing APOE genotypes, no significant differences in bdEV total particle concentration or morphology were observed. Overall small RNA and protein profiles of 10K, EVs, and source tissue also did not differ substantially between different APOE genotypes. However, several differences in individual RNAs (including miRNAs and tRNAs) and proteins in 10K and EVs were observed when comparing the highest and lowest risk groups (ε4/4 and ε2/3). Bioinformatic analysis and previous publications indicate a potential regulatory role of these molecules in AD. Discussion For patients with late-stage AD in this study, only a few moderate differences were observed for small RNA and protein profiles between APOE genotypes. Among these, several newly identified 10K and EV-associated molecules may play roles in AD progression. Possibly, larger genotype-related differences exist and are more apparent in or before earlier disease stages.
AALEN ADDITIVE MODEL: A APPLICATION FOR DATA OF SINUSITE IN PATIENTS WITH AIDS

Em estudos de sobrevivencia, as vezes, o interesse nao e apenas na distribuicao do tempo de falha. E comum a comparacao de tempos de sobrevivencia de dois ou mais grupos bem como a verificacao do efeito de covariaveis na resposta tanto em engenharia quanto, principalmente, em situacoes clinicas. A maneira mais eficiente de incorporar o efeito desses fatores no estudo e utilizar um modelo estatistico de regressao. Frequentemente em estudos de sobrevivencia o efeito das covariaveis de interesse pode variar ao longo dotempo de duracao do estudo. Estas covariaveis sao denominadas de dependentes do tempo e a inclusao delas na analise pode fornecer resultados mais precisos. Aalen propos um modelo de risco aditivo que apresenta vantagens praticas quando as covariaveis sao acompanhadas ao longo do tempo e os seus valores podem ser modificados durante o estudo. A principal vantagem desse modelo e que atraves de analise grafica e possivel verificar mudancas no tempo na influencia de cada uma das covariaveis. Isto e, analises com este modelo fornecem informacoes detalhadas a respeito da influencia temporal de cada covariavel. Dessa forma o modelo aditivo de Aalen e apresentado neste trabalho com o objetivo de mostrar a sua importância na presenca de covariaveis dependentes do tempo. Um banco de dados real envolvendo pacientes infectados pelo HIV e o tempo ate o desenvolvimento de sinusite e utilizado para ilustrar o ajuste deste modelo.
Mental Health Problems among College Students in India during the COVID-19 Pandemic in the Context of Disruptions in Academics and Interpersonal Relationships

The COVID-19 pandemic has led to significant disruptions in daily lives, contributing to mental health problems around the world, with young adults being a particularly vulnerable population for mental health problems (Varma et al., 2021). In the current study, we explored perspectives on how the pandemic had affected their lives, and examined frequency of mental health problems among college students in India during the middle phase of the pandemic. Participants (N = 455, 65% women, Mage = 20.62 years) responded to open-ended questions and completed self-report measures of anxiety, depressive symptoms, emotion dysregulation, and dysfunctional coping, and skills use. Thematic analysis of open-ended responses yielded nine themes across three domains: Major concerns, impact on academics and learning, and impact on relationships. Mental health symptomatology was identified as the most common concern, and approximately 50% of the sample scored above the clinical cut off on the self-report measure for either anxiety or depression, indicating a moderately high level of distress. Difficulties in effectively regulating one’s negative emotions and dysfunctional coping uniquely predicted higher anxiety and depression, whereas adaptive coping predicted lower depression. The findings demonstrate that college students in India are struggling with mental health during the pandemic. Facilitating emotion regulation and coping may be potential targets for intervention.
Genes Whose Gain or Loss of Function Changes Type 1, 2A, 2X, or 2B Muscle Fibre Proportions in Mice—A Systematic Review

Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response to exercise, chronic electrical stimulation, or inactivity. To identify genes whose gain or loss-of-function alters type 1, 2A, 2X, or 2B muscle fibre proportions in mice, we conducted a systematic review of transgenic mouse studies. The systematic review was conducted in accordance with the 2009 PRISMA guidelines and the PICO framework. We identified 25 “muscle fibre genes” (Akirin1, Bdkrb2, Bdnf, Camk4, Ccnd3, Cpt1a, Epas1, Esrrg, Foxj3, Foxo1, Il15, Mapk12, Mstn, Myod1, Ncor1, Nfatc1, Nol3, Ppargc1a, Ppargc1b, Sirt1, Sirt3, Thra, Thrb, Trib3, and Vgll2) whose gain or loss-of-function significantly changes type 1, 2A, 2X or 2B muscle fibre proportions in mice. The fact that 15 of the 25 muscle fibre genes are transcriptional regulators suggests that muscle fibre-specific gene expression is primarily regulated transcriptionally. A reanalysis of existing datasets revealed that the expression of Ppargc1a and Vgll2 increases and Mstn decreases after exercise, respectively. This suggests that these genes help to regulate the muscle fibre adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes. It seems likely that such DNA sequence variants contribute to the large variation of muscle fibre type proportions in the human population.
Target Characterization and Follow-Up Observations in Support of the Kepler Mission

A variety of experiments were carried out to investigate the number and characteristics of the stars to be included in the Kepler Input Catalog. One result of this work was the proposal that the 2MASS Catalog of astrometry and photometry in the infrared be used as the primary source for the initial selection of candidate target stars, because this would naturally decrease the number of unsuitable hot blue stars and would also increase the number of desirable solar-type dwarf stars. Another advantage of the 2MASS catalogue is that the stellar positions have more than adequate astrometric accuracy for the Kepler target selection. The original plan reported in the Concept Study Report was to use the parallaxes and multi-band photometry from the FAME mission to provide the information needed for reliable separation of giants and dwarfs. As a result of NASA's withdrawal of support for FAME an alternate approach was needed. In November 2002 we proposed to the Kepler Science Team that a ground-based multi-band photometric survey could help alleviate the loss of the FAME data. The Science Team supported this proposal strongly, and we undertook a survey of possible facilities for such a survey. We concluded that the SAO's 4Shooter CCD camera on the 1.2-m telescope at the Whipple Observatory on Mount Hopkins, Arizona, showed promise for this work.
Photooxidation of A2E by Blue Light Regulates Heme Oxygenase 1 Expression via NF-κB and Lysine Methyltransferase 2A in ARPE-19 Cells

Background: N-retinylidene-N-retinylethanolamine (A2E) is a component of drusen that accumulates in retinal cells and induces oxidative stress through photooxidation, such as blue light (BL). We found that the heme oxygenase 1 (HMOX1) gene responds sensitively to photooxidation by the BL of A2E in retinal pigment epithelial (RPE) cells, and we sought to identify the transcription factors and coactivators involved in the upregulation of HMOX1 by A2E and BL. Methods: A2E-laden human RPE cells (ARPE-19) were exposed to BL (430 nm). RNA sequencing was performed to identify genes responsive to BL exposure. Chromatin immunoprecipitation and RT-qPCR were performed to determine the regulation of HMOX1 transcription. Clinical transcriptome data were used to evaluate HMOX1 expression in patients with age-related macular degeneration (AMD). Results: In ARPE-19 cells, the expression of HMOX1, one of the NF-κB target genes, was significantly increased by A2E and BL. The binding of RELA and RNA polymerase II to the promoter region of HMOX1 was significantly increased by A2E and BL. Lysine methyltransferase 2A (MLL1) plays an important role in H3K4me3 methylation, NF-κB recruitment, chromatin remodeling at the HMOX1 promoter, and, subsequently, HMOX1 expression. The retinal tissues of patients with late-stage AMD showed significantly increased expression of HMOX1 compared to normal retinal tissues. In addition, the expression levels of MLL1 and HMOX1 in retinal tissues were correlated. Conclusions: Taken together, our results suggest that BL induces HMOX1 expression by activating NF-κB and MLL1 in RPE cells.
[99mTc]Tc-PSMA-T4—Novel SPECT Tracer for Metastatic PCa: From Bench to Clinic

Despite significant advances in nuclear medicine for diagnosing and treating prostate cancer (PCa), research into new ligands with increasingly better biological properties is still ongoing. Prostate-specific membrane antigen (PSMA) ligands show great potential as radioisotope carriers for the diagnosis and therapy of patients with metastatic PCa. PSMA is expressed in most types of prostate cancer, and its expression is increased in poorly differentiated, metastatic, and hormone-refractory cancers; therefore, it may be a valuable target for the development of radiopharmaceuticals and radioligands, such as urea PSMA inhibitors, for the precise diagnosis, staging, and treatment of prostate cancer. Four developed PSMA-HYNIC inhibitors for technetium-99m labeling and subsequent diagnosis were subjected to preclinical in vitro and in vivo studies to evaluate and compare their diagnostic properties. Among the studied compounds, the PSMA-T4 (Glu-CO-Lys-L-Trp-4-Amc-HYNIC) inhibitor showed the best biological properties for the diagnosis of PCa metastases. [99mTc]Tc-PSMA-T4 also showed effectiveness in single-photon emission computed tomography (SPECT) studies in humans, and soon, its usefulness will be extensively evaluated in phase 2/3 clinical trials.
Preclinical Evaluation of the Multiple Tyrosine Kinases Inhibitor Anlotinib in Leukemia Stem Cells

Leukemia stem cells (LSCs) constitute the critical barrier to the cure of acute myeloid leukemia (AML) due to their chemoresistance and immune evasion property. Herein, the role of anlotinib, a multiple tyrosine kinase inhibitor, in killing LSCs and regulating chemoresistance and immune evasion was explored. Anlotinib treatment induced apoptosis of LSC-like cells as well as primary AML LSCs, while sparing the normal mononuclear cells in vitro. Moreover, anlotinib could impair the regeneration capacity of LSCs in the patient-derived leukemia xenograft mouse model. Mechanistically, anlotinib inhibited phosphorylation of c-kit, JAK2/STAT3, and STAT5, and downregulated STAT3 and STAT5 expression. In addition, anlotinib downregulated the anti-apoptotic proteins Bcl-2 and Bcl-xL, and upregulated Bax, thereby enhancing the sensitivity of LSCs to idarubicin in vitro. Intriguingly, anlotinib could also partially rescue the interferon-g production of T cells cocultured with LSCs by downregulating PD-L1 expression. In conclusion, anlotinib showed anti-LSC activity and the potential to enhance the sensitivity to idarubicin and inhibit the immunosuppressive feature of LSCs via JAK2/STAT signaling pathway downregulation in the preclinical study. Our results provided a rational basis for combinatory strategies involving anlotinib and chemotherapy or immunotherapy.
An Approximated Solution to Continuous-Time Stochastic Optimal Control Problems Through Markov Decision Chains

Strategies for constructing a Markov decision chain approximating a continuous-time finite-horizon optimal control problem are investigated. Some simple, analytically soluble, examples are treated and low computational complexity is reported. Extensions to the method and implementation are discussed. In particular, relevance of the approximated solution to a stochastic renewable resource valuation problem is examined.
Multiscale spatially explicit modelling of livestock depredation by reintroduced tiger (Panthera tigris) to predict con�ict risk probability

Context: Spatial modelling of human-carnivore con�ict has recently gained traction, and predictive maps have become a great tool to understand the distribution of present and future con�ict risk. However, very few such studies consider scale and use appropriate spatial modelling tools. Objectives: We aimed to understand the ecological predictors of human-tiger (Panthera tigris) con�ict and predict livestock predation risk by reintroduced tigers in Panna Tiger Reserve, Central India. By modelling livestock kill as a function of various tiger relevant ecological variables at multiple scales employing spatially explicit statistical tools. Methods: We used geostatistical modelling to create raster layers of covariates (prey, cover, human activities), following which we did univariate scaling. We then modelled livestock loss by tiger using spatial Generalized Additive Model (geoGAM), predicted and mapped con�ict risk probability. Results: We found that prey and shrub cover, both selected at a �ne scale, were key ecological determinants of human-tiger con�ict. Prey showed an inverse relationship with livestock predation and shrub nonlinear; livestock predation increasing with an increase in shrub cover but decreasing beyond a certain point. Thus, in habitats where optimum ambush cover is available but prey presence is low at �ne-scale, carnivores are more likely to depredate domestic livestock since livestock have lost most of their anti-predator behaviours. Conclusions: Livestock kill by tiger is a culmination of predator choice and foraging tactics, and prey vulnerability and defence mechanism. The spatially explicit predation risk map produced in this study can guide adequate human-tiger con�ict prevention measures.
Reduction of Threshold Current Density for Current-Driven Domain Wall Motion using Shape Control

We investigated the aspect ratio (thickness/width) dependence of the threshold current density required for current-driven domain wall (DW) motion in Ni81Fe19 nanowires. It has been shown theoretically that the threshold current density is proportional to the product of the hard-axis magnetic anisotropy K⊥ and the DW width λ [G. Tatara and H. Kohno: Phys. Rev. Lett. 92 (2004) 086601]. We show experimentally that K⊥ can be controlled by the magnetic shape anisotropy in the case of Ni81Fe19 nanowires, and that the threshold current density increases as K⊥·λ increases. We succeeded in reducing the threshold current density by half using the shape control.
Exploring Cosmology via Large Scale Structure

This thesis presents a study of the large-scale structure (LSS) of the Universe as evidenced in observations of the cosmic microwave background (CMB) and in galaxy redshift surveys. We first investigate several anomalies reported in the Wilkinson Microwave Anisotropy Probe (WMAP) CMB temperature map. In particular, we have used the Planck Early Data Release to test the WMAP beam profiles. We confirm that stacked beam profiles at Q, V and particularly at W, appear wider than expected when compared to the Jupiter beam, normalised either directly to the radio source profiles or using Planck fluxes. We also find that the WMAP source fluxes demonstrate possible non-linearity with Planck fluxes. Additionally, we find that the stacked Sunyaev-Zel'dovich (SZ) decrements of galaxy clusters observed by Planck are in agreement with the WMAP data. We find that there is no evidence for a WMAP SZ deficit as has previously been reported. We conclude that beam profile systematics can have significant effects on the CMB power spectrum with potentially important implications for Cosmology parameter fitting. We have also mapped the local density field using K and r limited galaxy redshift distributions and number counts from the 6dF Galaxy Redshift Survey (6dFGS), Two Micron All Sky Survey (2MASS), Galaxy And Mass Assembly (GAMA) and Sloan Digital Sky Survey (SDSS) redshift surveys. We find evidence for significant galaxy underdensities in three large regions of the high latitude sky. This is in agreement with the corresponding peculiar velocities which are not compatible with recovering the CMB rest frame in the volume probed. We therefore conclude that there is some consistent evidence from both counts and Hubble diagrams for a `Local Hole' with a ≈ 150h−1Mpc under-density that deeper counts and redshifts in the Northern Galactic cap suggest may extend to ≈ 300h−1 Mpc.
Internal corporate governance mechanisms and earnings manipulation practices in MENA countries

This study has the objective of examining how internal corporate governance mechanisms are related to earnings manipulation, measured by real-based earnings manipulation (REM) and accrual-based earnings manipulation (AEM). The internal corporate governance mechanisms discussed in this study signify two main kinds of board characteristics (board size and board independence) and three main kinds of ownership structure (institutional ownership, foreign ownership and business group affiliation). The study models were examined from eight countries selected from the Middle East and North Africa (MENA) region. A total of 480 non-financial firms listed between 2012 and 2019 were examined. Based on panel data-based generalised methods of moments (GMM) estimation, the findings showed that institutional ownership in MENA nations limits the use of REM and AEM. Additionally, we found that larger boards are more likely to participate in REM practices. Board independence has a positive association with REM and AEM. The results also reveal that business group affiliation has a significant effect on both methods of earnings manipulation. Foreign ownership does not seem to significantly impact either of the two manipulation methods. Finally, these results help regulators and policymakers pursue reforms to enhance national governance quality in the MENA region.
Two-dimensional Quantum Field Models (with applications to Lattice Statistical Mechanics)

Two dimensional toy models display, in a gentler setting, manysalient aspects of Quantum Field Theory. Here I discuss a concrete two dimensional case, the Thirring model, which illustrates several important concepts of this theory: the anomalous dimension of the fields; the exact solvability; the anomalies of the Ward-Takahashi identities. Besides, I give a glimpse of the decisive role that this model plays in the study of an apparently unrelated topic: correlation critical exponents of two dimensional lattice systems of Statistical Mechanics.
Impact of COVID-19 Outbreak on Women Quality of Life in Indonesia

The COVID-19 outbreak and its designated policy conveyed unprecedented impacts on the life of women. This study aims to assess women’s quality of life (QOL) during the pandemic. This cross-sectional study was conducted in Java and Sulawesi, as both sites implemented the large-scale social restriction policy. The Indonesian version of the WHO Quality of Life Instrument, Short Form (WHOQOL-BREF) was used to collect the QOL data. The whole questionnaire was self-administered online by 191 women using Google Form. Descriptive analysis and Mann-Whitney test were carried out to analyze the data in statistical software. Overall, women who were involved in this study conveyed a relatively moderate quality of life (4.08 + 0.76 SD). The highest and lowest mean scores of QOL were observed in the social relationship (78.3 + 17.05 SD) and physical health domain (60.8 + 10.76SD). Family monthly income and type of family were significantly associated with environmental health (p0.05). Astoundingly, during the outbreak women described high satisfaction on social relationship. These results may advocate policy in regards to women’s welfare.
On the tail of the daily rainfall probability distribution: Exponential-type, power-type or something else?

While the traditional choice to describe the wet-day daily rainfall is the two-parameter Gamma distribution, many other distributions have been proposed and used, e.g., the twoand threeparameter Log-Normal, the Generalized Logistic, the Pearson Type III, the Pareto and the Generalized Pareto, the threeand four-parameter Kappa distributions, and many more. The asymptotic behaviour of the upper tails of these probability distributions may be generally categorized in two families: the exponential-type and the power-type tail families, where the latter family does not have all moments finite. However, there are exceptions such as the Lognormal family and the so-called stretched-exponential-tail family, which are generally acknowledged to be heavy-tailed, yet all their moments exist. The upper tail of the distribution governs both the magnitude and the frequency of the extreme events with the exponential-type distribution tails generating more “mild” and infrequent extremes compared to the power-type tails. This emphasizes the importance to assess correctly the tail behaviour and also to theoretically justify it. In general, the exponential-type distribution tails are the most commonly assumed; however, in the last years there is a shift towards the power-type-tail distributions. In this study, we investigate the assumption that the tail belongs to the stretched-exponential-type family that seems to be the “middle” way between exponentialand power-type tails. Finally, we use real-world daily rainfall datasets to examine this assumption empirically and to compare the performance of each tail family.