Miracle-dz/UniFAR-FTUs huggingface dataset:
The Epstein-Barr Virus miR-BHRF1 microRNAs Regulate Viral Gene Expression in cis

The Epstein-Barr virus (EBV) miR-BHRF1 microRNA (miRNA) cluster has been shown to facilitate B-cell transformation and promote the rapid growth of the resultant lymphoblastoid cell lines (LCLs). However, we find that expression of physiological levels of the miR-BHRF1 miRNAs in LCLs transformed with a miR-BHRF1 null mutant (∆123) fails to increase their growth rate. We demonstrate that the pri-miR-BHRF1-2 and 1–3 stem-loops are present in the 3’UTR of transcripts encoding EBNA-LP and that excision of pre-miR-BHRF1-2 and 1–3 by Drosha destabilizes these mRNAs and reduces expression of the encoded protein. Therefore, mutational inactivation of primiR-BHRF1-2 and 1–3 in the ∆123 mutant upregulates the expression of not only EBNA-LP but also EBNA-LP-regulated mRNAs and proteins, including LMP1. We hypothesize that this overexpression causes the reduced transformation capacity of the ∆123 EBV mutant. Thus, in addition to regulating cellular mRNAs in trans, miR-BHRF1-2 and 1–3 also regulate EBNA-LP mRNA expression in cis. Highlights The EBV miR-BHRF1 microRNAs do not up upregulate B cell growth in trans. EBNA-LP expression is downregulated by pri-miR-BHRF1-2 and 1–3 acting in cis. Loss of miR-BHRF1-2 and 1–3 causes EBNA-LP overexpression and inhibits B cell growth. Novel alternative splicing of EBV Cp/Wp transcripts was identified.
Ecological characterization and infection of Anophelines (Diptera: Culicidae) of the Atlantic Forest in the southeast of Brazil over a 10 year period: Has the behaviour of the autochthonous malaria vector changed?

In the south and southeast of Brazil, autochthonous malaria cases can be found near Atlantic Forest fragments. The transmission is not totally clarified; thus, the behaviour of the possible vectors in those regions must be observed. An entomological and natural infection study was performed on anophelines (Diptera: Culicidae) captured in the municipalities of the mountainous region of Espírito Santo state in 2004-2005. Similarly, between the years 2014 and 2015, 12 monthly collections were performed at the permanent trapping station of the study mentioned above (Valsugana Velha, Santa Teresa, ES). Light traps with CO2 (CO2-baited Center for Disease Control [CDC] traps) were set in open areas, at the edge of the forest (canopy and ground) and inside the forest (canopy and ground), whereas Shannon traps were set on the edge of the forest. A total of 1,414 anophelines were collected from 13 species. Anopheles (Kerteszia) cruzii Dyar and Knab remained the most captured species in the CO2-baited CDC traps set in the forest canopy and was also the vector with the highest prevalence of Plasmodium vivax infection according to molecular PCR techniques. Regarding mosquitoes of the subgenus Nyssorhynchus, P. vivax was found only in abdomens, weakening the hypothesis that this subgenus also plays a role in malaria transmission in this specific region. Sponsorship Espírito Santo Research Foundation (Fundação de Amparo à Pesquisa e Inovação do Espírito Santo – FAPES).
Reply: Neutral tumor evolution?

Mutation, selection and neutral drift shape the cancer evolutionary process. The role of selection has received particular interest, but inferring the presence and strength of selection during tumour growth remains challenging. Recently, we analysed the frequency distribution of subclonal mutations in many cancers and found that in approximately 30% of cases the observed distribution was entirely consistent with a simple model of neutral evolution. Thus, we concluded that neutral evolution, perhaps surprisingly, provides an adequate explanation of the intra-tumour heterogeneity present in a significant proportion of cancers. Tarabichi and colleagues [bioRxiv: 2017/06/30/158006] question the robustness of the method we presented in Williams et al. 2016 to identify neutral cancer evolution from variant allele frequency (VAF) distributions. Their critique has four main points that we address in this document using a simulation approach and a reanalysis of public datasets.
Optimal Heterogeneous Distributed Storage Regenerating Code at Minimum Remote‐Repair Bandwidth Regenerating Point

Recently, a product‐matrix (PM) framework was proposed to construct optimal regenerating codes for homogeneous distributed storage systems (DSSs). In this paper, we propose an extended PM (EPM) framework for coding of heterogeneous DSSs having different repair bandwidths but identical storage capacities. Based on the EPM framework, an explicit construction of minimum remote‐repair bandwidth regenerating (MRBR) codes is presented for a specific heterogeneous DSS, where two geographically different datacenters with associated storage nodes are deployed. The data reconstruction and regeneration properties of the MRBR code are proved strictly. For the purpose of demonstration, an example implementation of MRBR code is provided. The presented MRBR code is the first optimal strict‐regenerating code for heterogeneous DSSs. In addition, our proposed EPM framework can be applied to homogeneous systems also.
Presurgical language fMRI: Current technical practices in epilepsy surgical planning

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, imaging acquisition, analysis and interpretation and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4 or 5 tasks with a modal run duration of five minutes. Variants of over fifteen protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols were used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.
Metabolic adjustment enhances food web stability

Understanding ecosystem stability is one of the greatest challenges of ecology. Over several decades, it has been shown that allometric scaling of biological rates and feeding interactions provide stability to complex food web models. Moreover, introducing adaptive responses of organisms to environmental changes (e.g. like adaptive foraging that enables organisms to adapt their diets depending on resources abundance) improved species per-sistence in food webs. Here, we introduce the concept of metabolic adjustment, i.e. the ability of species to slow down their metabolic rates when facing starvation and to increase it in time of plenty. We study the reactions of such a model to nutrient enrichment and the adjustment speed of metabolic rates. We found that increasing nutrient enrichment leads to a paradox of enrichment (increase in biomasses and oscillation amplitudes and ultimately extinction of species) but metabolic adjustment stabilises the system by dampening the oscillations. Metabolic adjustment also increases the average biomass of the top predator in a tri-trophic food chain. In complex food webs, metabolic adjustment has a stabilising effect as it promotes species survival by creating a large diversity of metabolic rates. However, this stabilising effect is mitigated in enriched ecosystems. Phenotypic plasticity of organisms must be considered in food web models to better understand the response of organisms to their environment. As metabolic rate is central in describing biological rates, we must pay attention to its variations to fully understand the population dynamics of natural communities.
Identification of additional sources of resistance to Puccinia striiformis f. sp. hordei (PSH) in a collection of barley genotypes adapted to the high input condition

A total of 336 barley genotypes consisting of released cultivars, advanced lines, differentials and local landraces from the ICARDA barley breeding programme were screened for seedling and adult-plant resistances to barley stripe rust pathogen ( Puccinia striiformis f. sp. hordei [PSH]). Seedling resistance tests were undertaken at Shimla, India by inoculating 336 barley genotypes with five prevalent PSH races [Q (5S0), 24 (0S0-1), 57 (0S0), M (1S0) and G (4S0)] in India. Barley genotypes were also evaluated at the adult-plant stage for stripe rust resistance at Durgapura (Rajasthan, India) in 2013 and 2014, and at Karnal (Haryana, India) in 2014 under artificial PSH infection in fields, using a mixture of the five races. Twelve barley genotypes (ARAMIR/COSSACK, Astrix, C8806, C9430, CLE 202, Gold, Gull, Isaria, Lechtaler, Piroline, Stirling, and Trumpf) were resistant to all five PSH races at the seedling and adult-plant stages. Two of these genotypes, Astrix and Trumpf, were part of international differentials and reveal that five races were avirulent to genes Rps4 ( yr4 ) , rp-sAst, rpsTr1 and rpsTr2 . These genes were highly effective against PSH races prevalent in India. The virulence/avirulence formula reported in this study helped to determine the effectiveness of PSH resistance genes against Indian races. Forty-five genotypes showed adult-stage plant resistance (APR) in the field. The identified PSH resistant genotypes may possess novel resistance genes and might serve as potential donors of PSH resistance at seedling and APR in the future. Further research is needed to determine the nature of resistance genes through allelic studies and mapping of these genes.
Digestibility, protein retention rate and ammonia excretion in juvenile fat snook (Centropomus parallelus) fed with different protein levels

EnglishThe aim of this study was to determine the level of dietary crude protein (CP) (480, 400, 440, 520 and 560g kg-1) in rations for juvenile II fat snook (Centropomus parallelus) that best promotes protein absorption and lower excretion of nitrogenous products. Three experiments were conducted: the first assessed the protein retention rate; the second evaluated ammonia excretion; and the third determined the best digestibility coefficient. The estimated protein retention rate showed a positive quadratic response to dietary CP with maximum retention at the 510.20g kg-1 protein level, and increasing levels of protein resulted in a greater total ammonia excretion rate in water. The mean apparent protein digestibility coefficient values increased with increasing levels of dietary protein up to 520g kg-1, where they stabilized. As determined by regression, the level of dietary CP that promotes the best digestibility was 495.62g kg-1. Key words: crude digestible protein; fish culture; nitrogen excretion; diet portuguesO objetivo da pesquisa foi determinar o nivel de proteina bruta na dieta (400, 440, 480, 520 e 560g kg-1), nas racoes de juvenis II de robalo-peva (Centropomus parallelus), que promove melhor absorcao de proteina e menor excrecao de produtos nitrogenados. Foram realizados tres experimentos. O primeiro avaliou a taxa de retencao de proteina, o segundo a excrecao de amonia, e o terceiro determinou o melhor coeficiente de digestibilidade. Os dados foram analisados por meio de regressao exponencial. A taxa de retencao proteica, calculada pela equacao, apresentou efeito quadratico positivo e o maximo de retencao com 510,20g kg-1 de proteina na dieta. O aumento dos niveis de proteina resultou em maiores taxas de excrecao de amonia total na agua. Os valores medios dos coeficientes de digestibilidade aparente da proteina foram aumentando com o aumento da proteina dietetica ate o nivel de 520g kg-1 onde se estabilizou. O nivel de proteina bruta na dieta, determinado pela equacao de regressao, que promove a melhor digestibilidade e de 495,62g kg-1. Palavras-chave: proteina bruta digestivel; piscicultura; excrecao nitrogenada; dieta
Üniversite Öğrencilerinin Bilgi Okuryazarlığı Becerilerindeki Zorlanma Düzeyleri Üzerine Bir Araştırma

Information Literacy is the set of skills needed to find, retrieve, analyze, and use information from a variety of sources. Educational institutions have the primary responsibility for providing the students with these skills. In this regard universities have to develop information literacy programs to equip students with the information and skills required. This study examines the challenges that the students faced in terms of information literacy related issues. A questionnaire was applied to 262 post graduate students of Hacettepe University in order to collect the data for this study. Collected data were analyzed by using “t-test” and “one-way variant analysis” methods.
The evaluation of text quality: expert-focused and reader-focused methods compared

The authors compare a reader-focused text evaluation with an expert-focused evaluation by technical writers and subject/audience experts. The experts were asked to predict the problems readers had signaled in a government brochure about alcohol. On average, they predicted less than 15% of the reader problems and produced a lot of new problem detections. In addition, the experts showed little mutual agreement in their problem detections. Their results suggest that a reader-focused evaluation should not be substituted for an expert-focused evaluation. The paper ends with a discussion of methodological issues for this type of research.
Macro-op scheduling and execution

High-performance microprocessors must attain two elusive goals that are often at odds with each other: high operating frequency that demands a minimum amount of logic per pipeline stage, and a high degree of concurrency in the form of instruction-level and memory-level parallelism, which tends to increase the amount of activity required to execute each instruction. The logic required to implement all of this complexity can be broken down into more and more pipeline stages to achieve higher operating frequency, but this comes at the cost of additional power, pipeline latch overhead, and erosion in IPC due to increased branch and scheduling penalties. One promising approach to overcoming this limitation and simplifying the control logic overhead in an out-of-order processor is to move from the conventional instruction-level processing towards coarse-grained instruction processing that amortizes these over-heads over a set of two or more instructions. This thesis proposes and evaluates two microarchitectural techniques that perform coarse-grained instruction processing in super-scalar, out-of-order processors: Macro-op Scheduling and Macro-op Execution . This thesis makes three main contributions. First, it presents the concept of coarse-grained instruction processing, which reduces the hardware overhead involved in coordinating all of the concurrent actions in a modern out-of-order can be applied to a program for coarse-grained instruction processing, and shows that a significant portion of the instructions can be processed together in groups without requiring fine-grained controls for scheduling and execution. Third, it demonstrates that the proposed techniques for coarse-grained instruction processing enable complexity and performance benefits in an out-of-order superscalar processor.
Corrigendum to: Statistical mechanics of cell decision-making: the cell migration force distribution

Cell decision-making is the cellular process of responding to microenvironmental cues. This can be regarded as the regulation of cell’s intrinsic variables to extrinsic stimuli. Currently, little is known about the principles dictating cell decision-making. Regarding cells as Bayesian decision-makers under energetic constraints, I postulate the principle of least microenvironmental uncertainty (LEUP). This is translated into a free-energy principle and I develop a statistical mechanics theory for cell decision-making. I exhibit the potential of LEUP in the case of cell migration. In particular, I calculate the dependence of cell locomotion force on the steady state distribution of adhesion receptors. Finally, the associated migration velocity allows for the reproduction of the cell anomalous diffusion, as observed in cell culture experiments.
Specification: The Pattern that Signifies Intelligence

Specification denotes the type of pattern that highly improbable events must exhibit before one is entitled to attribute them to intelligence. This paper analyzes the concept of specification and shows how it applies to design detection (i.e., the detection of intelligence on the basis of circumstantial evidence). Always in the background throughout this discussion is the fundamental question of Intelligent Design (ID): Can objects, even if nothing is known about how they arose, exhibit features that reliably signal the action of an intelligent cause? This paper reviews, clarifies, and extends previous work on specification in my books The Design Inference and No Free Lunch.
Cytogenetic Damage in Individuals Exposed to Vehicular Pollution

Abstract Cytogenetic investigations on peripheral blood lymphocytes of 50 individuals exposed to different air pollutants on the road sides was made. This was compared to an equal number of exposed and matched controls w.r. t. age, sex, smoking and drinking habit and social status. The mitotic index (MI), chromosomal aberrations (CA), Sister Chromatid Exchanges (SCE) and satellite associations (SA) were analysed. All the parameters showed a significant increase (P<0.01) in the exposed sample compared with the controls, viz. MI, 3.75-6.80; CA 0.96-2.98; SCE 3.92-8.18 and SA 6.18-14.50. The occurence of the DG type of satellite association was highest and that of 3D type lowest. The frequencies of all the parameters also showed elevation with duration of exposure. MI however, showed decrease after continous increase upto 15 years of exposure. The vehicular fumes were thus found to be genotoxic.
Sensory neuropathy-causing mutations in ATL3 cause aberrant ER membrane tethering

The ER is a complex network of sheets and tubules that are continuously reshaped, fused and broken apart. The relevance of this remodeling process is underscored by the fact that mutations in atlastins (ATL), the proteins mediating ER fusion in mammalia, lead to neurodegenerative disease. While the mechanism of ATL-mediated membrane fusion has gained a lot of attention, how defects in this process lead to neurodegeneration is largely unknown. Here we show that the HSAN-causing ATL3 variants retain their dimerization-dependent GTPase activity, but are unable to form the stable crossover dimer necessary for membrane fusion. Instead they promote aberrant membrane tethering. This leads to a collapse of the ER network characterized by bundles of ER tubules running in parallel, as observed by volume electron microscopy and transmission electron microscopy in patient derived fibroblasts. Given the redundancy of the three ATL proteins in membrane fusion, this enhanced ER membrane tethering likely represents a major contribution to the axonal degeneration observed in patients.
Sex-related differences in behavioral and amygdalar responses to compound facial threat cues

During face perception, we integrate facial expression and eye gaze to take advantage of their shared signals. For example, fear with averted gaze provides a congruent avoidance cue, signaling both threat presence and its location, whereas fear with direct gaze sends an incongruent cue, leaving threat location ambiguous. It has been proposed that the processing of different combinations of threat cues is mediated by dual processing routes: reflexive processing via magnocellular (M) pathway and reflective processing via parvocellular (P) pathway. Because growing evidence has identified a variety of sex differences in emotional perception, here we also investigated how M and P processing of fear and eye gaze might be modulated by observer’s sex, focusing on the amygdala, a structure important to threat perception and affective appraisal. We adjusted luminance and color of face stimuli to selectively engage M or P processing and asked observers to identify emotion of the face. Female observers showed more accurate behavioral responses to faces with averted gaze and greater left amygdala reactivity both to fearful and neutral faces. Conversely, males showed greater right amygdala activation only for M-biased averted-gaze fear faces. In addition to functional reactivity differences, females had greater bilateral amygdala volumes, which positively correlated with behavioral accuracy for M-biased fear. Conversely, in males only the right amygdala volume was positively correlated with accuracy for M-biased fear faces. Our findings suggest that M and P processing of facial threat cues is modulated by functional and structural differences in the amygdalae associated with observer’s sex.
The lamellipodium is a myosin independent mechanosensor

The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young’s modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity. Rather, we find that cell spreading on soft substrates is inhibited due to reduced nascent adhesion formation within the lamellipodium. Cells on soft substrates display normal leading edge protrusion activity, but these protrusions are not stabilized due to impaired adhesion assembly. Enhancing integrin-ECM affinity through addition of Mn2+ recovers nascent adhesion assembly and cell spreading on soft substrates. Using a computational model to simulate nascent adhesion assembly, we find that biophysical properties of the integrin-ECM bond are optimized to stabilize interactions above a threshold matrix stiffness that is consistent with the experimentally observations. Together these results suggest that myosin II-independent forces in the lamellipodium are responsible for mechanosensation by regulating new adhesion assembly, which in turn, directly controls cell spreading. This myosin II-independent mechanism of substrate stiffness sensing could potentially regulate a number of other stiffness sensitive processes. Significance Statement Cell physiology can be regulated by the mechanics of the extracellular environment. Here, we demonstrate that cell spreading is a mechanosensitive process regulated by weak forces generated at the cell periphery and independent of motor activity. We show that stiffness sensing depends on the kinetics of the initial adhesion bonds that are subjected to forces driven by protein polymerization. This work demonstrates how the binding kinetics of adhesion molecules are sensitively tuned to a range of forces that enable mechanosensation.