Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV Env conserved element DNA vaccine alters immunodominance in macaques

ABSTRACT Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV. HIV Env is a highly-glycosylated protein composed of ‘conserved’ and ‘variable’ regions. The latter contains immunodominant epitopes that are frequently targeted by the immune system resulting in the generation of immune escape variants. This work describes 12 regions in HIV Env that are highly conserved throughout the known HIV M Group sequences (Env CE), and are poorly immunogenic in macaques vaccinated with full-length Env expressing DNA vaccines. Two versions of plasmids encoding the 12 Env CE were generated, differing by 0–5 AA per CE to maximize the inclusion of commonly detected variants. In contrast to the full-length env DNA vaccine, vaccination of macaques with a combination of these 2 Env CE DNA induced robust, durable cellular immune responses with a significant fraction of CD8+ T cells with cytotoxic phenotype (Granzyme B+ and CD107a+). Although inefficient in generating primary responses to the CE, boosting of the Env CE DNA primed macaques with the intact env DNA vaccine potently augmented pre-existing immunity, increasing magnitude, breadth and cytotoxicity of the cellular responses. Fine mapping showed that 7 of the 12 CE elicited T cell responses. Env CE DNA also induced humoral responses able to recognize the full-length Env. Env CE plasmids are therefore capable of inducing durable responses to highly conserved regions of Env that are frequently absent after Env vaccination or immunologically subdominant. These modified antigens are candidates for use as prophylactic and therapeutic HIV vaccines.
Poor Pitch Singing: Response of Monotone Singers to a Program of Remedial Training

An experiment was carried out to see whether the musical performance of monotones could be improved by a program of remedial training. A group of 90 children aged 6+ to 8+ years was chosen, all of whom had been rated by their school singing teachers as monotones or droners. The children were randomly assigned to a remedial training group, a traditional training group or a control group. All children in the experiment were assessed on a nine-test pre- and posttest battery of musical recognition and production with single note, interval, melody, and rhythm scales, and a test of free song. Responses were tape-recorded and scored blind by a panel of music teachers who knew neither which group the child was in, nor whether the responses derived from the pre- or posttraining session. A group of 30 normal singing children of the same age was also given the test battery to judge the discriminating powers of the various individual subtests. The remedial training group was given two 30-minute sessions per week for eight weeks and had practice in singing a note within their speaking range. The traditional training group was intended to control for the possibility that extra attention and tuition might by itself improve the child's vocal performance. This group studied contemporary and traditional songs with piano, guitar, and percussion accompaniment for the same length of time. All groups showed significant improvement from pre- to posttest assessment except on the test of single note recognition. The monotone and normal singing groups did not differ on this measure. The remedial group showed greater improvement of single note and interval production than did the other two groups. Their vocal range was extended significantly, but within the eight weeks there was no differential improvement of this group on the test of free song.
Multipath reversed nested Miller compensation with voltage buffer for low-power three-stage amplifiers

A multipath reversed nested Miller compensation (MRNMC) scheme with voltage buffer (MRNMCVB) is presented in this paper. By using an efficient voltage buffer, a low-voltage, low-power, three-stage RNMC amplifier topology suitable for large capacitive load applications is constructed with a noninverting intermediate stage. Moreover, the internal feedback loop introduced by the buffer prevents the reduction in high-frequency gain and extends the bandwidth of the amplifier significantly. Furthermore, a multipath feedforward stage is added to generate a left-half-plane (LHP) zero, which improves the stability of the amplifier and reduces the size of compensation capacitors simultaneously. An optimized MRNMCVB amplifier has been implemented in a 0.35-mum CMOS process. The amplifier driving a 500-pF load capacitor achieves 1.76-MHz unity-gain frequency (UGF), 59deg phase margin, and 0.88-V/mus average slew rate, while dissipating only 45-muW power at a 1.5-V supply. The total capacitor value is just 2.92-pF.
Dynamical Stability and Predictability of Football Players: The Study of One Match

The game of football demands new computational approaches to measure individual and collective performance. Understanding the phenomena involved in the game may foster the identification of strengths and weaknesses, not only of each player, but also of the whole team. The development of assertive quantitative methodologies constitutes a key element in sports training. In football, the predictability and stability inherent in the motion of a given player may be seen as one of the most important concepts to fully characterise the variability of the whole team. This paper characterises the predictability and stability levels of players during an official football match. A Fractional Calculus (FC) approach to define a player’s trajectory. By applying FC, one can benefit from newly considered modeling perspectives, such as the fractional coefficient, to estimate a player’s predictability and stability. This paper also formulates the concept of attraction domain, related to the tactical region of each player, inspired by stability theory principles. To compare the variability inherent in the player’s process variables (e.g., distance covered) and to assess his predictability and stability, entropy measures are considered. Experimental results suggest that the most predictable player is the goalkeeper while, conversely, the most unpredictable players are the midfielders. We also conclude that, despite his predictability, the goalkeeper is the most unstable player, while lateral defenders are the most stable during the match.
Higher‐level language deficits resulting from left primary cerebellar lesions

Background: Contemporary neuropsychological studies suggest that cerebellar lesions may impact upon higher‐level cognitive functioning via mechanisms of crossed cerebello‐cerebral diaschisis. Accordingly, right cerebellar lesions have been previously associated with linguistic impairments such as reduced word fluency and agrammatic output. Recently, however, neuroimaging investigations have also identified ipsilateral cerebral hypoperfusion as a consequence of cerebellar lesions, implicating a potential role for the left cerebellum in the mediation of language processes. Aims: The purpose of this research was to investigate the effects of left cerebellar lesions of vascular origin, on general as well as high‐level language skills. Methods & Procedures: Linguistic profiles were compiled for five individuals with left primary cerebellar lesions utilising a comprehensive language test battery. Individual scores relevant to each subtest were compared to a group of non‐neurologically impaired controls. The criterion for anomalous performance was established as ≥ 1.5 SD below the mean of the control group. Outcomes & Results: The findings of this research suggest that higher‐level language deficits may result from left primary cerebellar lesions. All participants demonstrated deficits on measures of word fluency, sentence construction within a set context, producing word definitions, and producing multiple definitions for the same word. Deficits were also noted for several participants on measures of understanding figurative language, forming word associations, identifying and correcting semantic absurdities, and producing synonyms and antonyms. Conclusions: The results presented challenge the notion of a lateralised linguistic cerebellum, supporting a potential role for the left as well as right cerebellar hemispheres in the regulation of language processes, presumably via cerebellar‐basal ganglia/thalamo‐cortical pathways.
Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis.

OBJECTIVES To measure MTX polyglutamates in circulating erythrocytes (E-MTX), mononuclear cells (MNC-MTX) and polymorphs (PMN-MTX) in rheumatoid arthritis (RA) patients and to see whether these correlated with clinical efficacy and side effects. METHODS Sixty-five patients (40F, 25M; mean age 57 yrs.) with RA (ARA revised criteria) who had been on weekly pulse MTX (2.5-37.5 mg) for at least 2 months were entered into this study. The patients were classified as responders (R), partial responders (PR) or non-responders (NR) when blood was sampled for the MTX determination. Side effects since the initiation of MTX were also recorded. MTX-polyglutamates were measured (blinded to clinical details) using an enzymatic assay. RESULTS E-MTX in responders and partial responders were significantly higher (p < 0.001) than in non-responders. Similarly, PMN-MTX were also higher, but the difference was only significant for the R group (p = 0.0019). The differences in concentrations could not be explained on the basis of the dose, which tended to be higher in NR than in R (p = 0.085). The concommitant prednisolone dose was significantly lower in R than in NR (p = 0.001), as were the ESR and CRP (p = 0.007, and p = 0.05 respectively), but the MCV was higher (p = 0.047). E-MTX tended to be higher in patients with side effects, but this difference did not reach statistical significance (p = 0.15). CONCLUSION The results suggest that circulating intracellular levels of MTX polyglutamates in RBC and PMN correlate with clinical efficacy but not with toxicity in patients with RA.
How lizards survived blizzards: phylogeography of the Liolaemus lineomaculatus group (Liolaemidae) reveals multiple breaks and refugia in southern Patagonia and their concordance with other codistributed taxa

Patagonia was shaped by a complex geological history, including the Miocene uplift of the Andes, followed by volcanism, marine introgressions, and extreme climatic oscillations during Pliocene–Pleistocene glaciation–deglaciation cycles. The distributional patterns and phylogenetic relationships of southern patagonian animals and plants were affected in different ways, and those imprints are reflected in the seven phylogeographic breaks and eight refugia that have been previously proposed. In this study, we estimated time‐calibrated phylogenetic/phylogeographic patterns in lizards of the Liolaemus lineomaculatus group and relate them to historical Miocene‐to‐Pleistocene events of Patagonia and the previously proposed phylogeographic patterns. Individuals from 51 localities were sequenced for the mitochondrial marker (cyt‐b) and a subsample of individuals from each mitochondrial lineage was sequenced for one nuclear (LDA12D) and one slow evolving mitochondrial gene (12S). Our analyses revealed strong phylogeographic structure among lineages and, in most cases, no signal of demographic changes through time. The lineomaculatus group is composed of three strongly supported clades (lineomaculatus, hatcheri and kolengh + silvanae), and divergence estimates suggested their origins associated with the oldest known Patagonian glaciation (7–5 Ma); subsequent diversification within the lineomaculatus clade coincided with the large Pliocene glaciations (~3.5 Ma). The lineomaculatus clade includes nine strongly genetically and geographically structured lineages, five of which are interpreted as candidate species. Our findings suggest that some Liolaemus lineages have persisted in situ, each of them in a different refugium, through several glaciation–deglaciation cycles without demographic fluctuations. We also summarize and update qualitative evidence of some shared phylogeographic breaks and refugia among plants, rodents and lizards.
Organizing English Learner Instruction in New Immigrant Destinations

In the context of shifting demographics and standards-based reform, school districts in new immigrant destinations are charged with designing infrastructures that support teaching and learning for English learners (ELs) in core academic subjects. This article uses qualitative data and social network analysis to examine how one district in the midwestern United States organized EL instruction. After describing the district’s infrastructure for elementary EL education, we examine how this infrastructure supported teachers’ work practice—the practices in which teachers engage with one another—as operationalized around instructional advice and information networks. Findings reveal that teachers’ opportunities to learn about EL instruction varied significantly by the school subject and that these differences were directly related to the way in which the district built its EL educational infrastructure.
How Concerned, Afraid and Hopeful Are We? Effects of Egoism and Altruism on Climate Change Related Issues

The idea that concerns for and emotional reactions to climate change may be due to environment-related egoism and altruism was tested. Participants assessed as “high” on egoism were shown to be more concerned for myself-related issues and afraid of the climate change impact on their local environment, indicating a self-benefit goal motive. Participants assessed as “high” on altruism were those more concerned for issues related to others and nature and more afraid and less hopeful for the whole world, indicating a pro-social goal motive in this group of individuals. This indicates that environment-related value orientations of egoism and altruism may prompt concerns and convey feelings differently about the climate change issue. Accordingly, when encouraging sustainable development, policy and pro-environmental actions, we have to bear in mind people’s world views grounded in environment-related selfishness vs. unselfishness; indicating different goal-directed motives in climate change decision making.
Anterior cingulate cortex-related connectivity in first-episode schizophrenia: a spectral dynamic causal modeling study with functional magnetic resonance imaging

Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, spectral DCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions.
Occupational injury among hospital patient-care workers: what is the association with workplace verbal abuse?

OBJECTIVE To test the association between workplace abuse exposure and injury risk among hospital workers. We hypothesized that exposed workers would have higher injury rates than unexposed workers. METHODS Survey of direct-care workers (n = 1,497) in two hospitals. Exposure to workplace abuse was assessed through self-report; occupational injury reports were extracted from employee records. We tested associations between non-physical workplace violence and injury using log-binomial regression and multilevel modeling. RESULTS Adjusted prevalence ratio (PR) for injury associated with being yelled at was 1.52 (95% CI 1.19, 1.95); for experiencing hostile/offensive gestures 1.43 (1.11, 1.82); and for being sworn at 1.41 (1.09, 1.81). In analyses by injury subtypes, musculoskeletal injuries were more strongly associated with abuse than were acute traumatic injuries. Associations operated on group and individual levels and were most consistently associated with abuse perpetrated by patients. CONCLUSION Exposure to workplace abuse may be a risk factor for injuries among hospital workers.
Preparing Teachers for the Transition of Students with Disabilities Through Community-Based Instruction

Increasing demand for effective transition programs for individuals with disabilities has created a need for more comprehensive teacher preparation. Community and service learning experiences may be effective ways to accomplish this task. This article describes the planning and implementation of an on-campus transition project for students with disabilities and its impact on preservice teachers who participated in the project as job-sampling mentors. Data sources included university student journals, instructor field notes, course assignments, and open-ended questionnaires. Emergent themes indicated that university students gained new expectations of individuals with disabilities, became more aware of attitudes toward and treatment of individuals with disabilities, supported the benefits of first hand experience, and learned ways to teach individuals with disabilities. The perspectives of the university instructor and implications for teacher preparation programs are discussed.
Epigenetic Regulation and Functional Characterization of MicroRNA-142 in Mesenchymal Cells

The transcripts encoded by the microRNA mir-142 gene are highly active in hematopoietic cells, but expressed at low levels in many other cell types. Treatment with the demethylating agent 5-Aza-2′-deoxycytidine increased both the 1,636 nucleotide primary transcript and mature miR-142-5p/3p in mesenchymal cells, indicating that mir-142 is epigenetically repressed by DNA methylation. The transcription start site was determined to be located 1,205 base pairs upstream of the precursor sequence within a highly conserved CpG island. In addition, a second CpG island overlapped with the precursor. A TATA-box, several promoter-proximal elements and enrichment of conserved transcription factor binding sites within the first 100 base pairs upstream of the transcription start site, suggests that this region represents the core/proximal mir-142 promoter. Moreover, both CpG islands were heavily methylated in mesenchymal cells, having low levels of miR-142-5p/3p, and unmethylated in hematopoietic cells where both miRNAs were abundantly expressed. We show that treatment with 5-Aza-2′-deoxycytidine significantly reduced the DNA methylation of the upstream CpG island, which led to increased expression, and that in vitro DNA methylation of the upstream region of the mir-142 precursor repressed its transcriptional activity. When overexpressed, miR-142-5p/3p reduced proliferation of cells with epigenetic silencing of endogenous mir-142. This finding is interesting as miR-142-5p/3p have been reported to be deregulated in tumors of mesenchymal origin. We provide the first experimental evidence that transcription of mir-142 is directly repressed by DNA methylation. In addition, we discovered that the antisense strand of mir-142 might act as a precursor for functional mature antisense miRNAs. Thus, our study expands the current knowledge about the regulation of mir-142 and function of miR-142-5p/3p, and adds novel insight into the rapidly increasing field of microRNA regulation.
Prognostic significance of epidermal growth factor receptor in locally advanced esophageal squamous cell carcinoma for patients receiving chemoradiotherapy

The aim of the current study was to investigate the prognostic significance of epidermal growth factor receptor (EGFR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving concurrent chemoradiotherapy (CCRT). In total, 47 patients with locally advanced ESCC who were treated with CCRT were included in the present study. The chemotherapeutics comprised of 5-fluorouracil (750–1,000 mg/m2/day; days one to five) and cisplatin (30 mg/m2/day; days one to three) in combination with radiation therapy (~60 Gy), which was performed as the initial treatment. EGFR expression was compared with the clinicopathological features, local recurrence, metastasis status and overall survival (OS). Overall, EGFR overexpression (percentage of immunoreactive tumor cells, ≥50%) was identified in 59.6% of the patients. The median survival time (MST) of the EGFR-positive group was 15 months and the MST of the EGFR-negative group was 23.5 months. A significant correlation was observed between EGFR overexpression and poor OS (P=0.024). EGFR overexpression was found to exhibit a correlation with lymph node metastasis (P=0.011), but no correlation was identified with other clinicopathological features. In addition, a correlation was identified between OS and gender (P=0.021), age (P=0.018), depth of invasion stage (P=0.035) and tumor location (P=0.023). EGFR overexpression determined by pretreatment biopsy may be a clinically useful biomarker for predicting the OS of ESCC patients.
Localization in Seeded PageRank

Seeded PageRank is an important network analysis tool for identifying and studying regions nearby a given set of nodes, which are called seeds. The seeded PageRank vector is the stationary distribution of a random walk that randomly resets at the seed nodes. Intuitively, this vector is concentrated nearby the given seeds, but is mathematically non-zero for all nodes in a connected graph. We study this concentration, or localization, and show a sublinear upper bound on the number of entries required to approximate seeded PageRank on all graphs with a natural type of skewed-degree sequence---similar to those that arise in many real-world networks. Experiments with both real-world and synthetic graphs give further evidence to the idea that the degree sequence of a graph has a major influence on the localization behavior of seeded PageRank. Moreover, we establish that this localization is non-trivial by showing that complete-bipartite graphs produce seeded PageRank vectors that cannot be approximated with a sublinear number of non-zeros.