Miracle-dz/UniFAR-FTUs huggingface dataset:
Organization and expression of the immediate early genes of human cytomegalovirus

The immediate early genes of human cytomegalovirus were characterized according to map location, RNA transcripts, and translation products. Three regions in the large unique component (0.709 to 0.751 map units) were transcribed in the presence of an inhibitor of protein synthesis (anisomycin). A single size class of polyadenylated mRNA, 1.95 kilobases (kb), was transcribed abundantly relative to the other size classes. The predominant 1.95-kb viral RNA was transcribed from right to left on the prototype arrangement of the viral genome and spanned a region of approximately 2.8 kb (0.739 to 0.751 map units). This mRNA codes for a 75,000-dalton protein that represents the predominant immediate early protein detected in infected cells. Immunoprecipitation of viral proteins synthesized in vitro as well as in vivo demonstrated that the predominant immediate early protein is synthesized as a protein of 75,000 daltons, but is presumably modified in vivo, resulting in a broad banding pattern ranging from 75,000 to 68,000 daltons. A different immediate early viral gene (0.732 to 0.739 map units) is transcribed from left to right at relatively low levels. The 3' ends of the above viral RNAs terminate at approximately 230 base pairs apart in the region of approximately 0.739 map units. Five RNA size classes ranging from 2.25 to 1.10 kb were detected, but the 1.75-kb and 1.40-kb RNA size classes were more abundant from this region. At least four minor proteins are coded by these mRNAs, with apparent molecular weights ranging from 56,000 to 16,500. Last, a 1.95-kb mRNA was transcribed from a third region (0.709 to 0.728 map units). This viral mRNA was present at relatively low concentration and coded for a minor protein of 68,000 daltons. Since immediate early gene expression of human cytomegalovirus is dominated by the synthesis of an mRNA from the region of 0.739 to 0.751 map units that codes for the predominant immediate early protein found in the infected cell, we hypothesize that this protein is the major regulatory protein influencing the switch from restricted to extensive transcription.
Potentiation of neurotoxicity of Lathyrus sativus by manganese: Alterations in blood–brain barrier permeability

Environmental factors have been speculated to play an important role in potentiating the neurotoxicity of Lathyrus sativus (LS). Hence, blood–brain barrier permeability and neurotoxicity studies were carried out in manganese- and LS-exposed animals. Dietary feeding of LS (80%) plus Mn (0.4 mg/100 g diet) for 90 days to guinea pigs showed significant (p < 0.05) decrease in brain nucleotidase and ATPase activities when compared to control or LS alone treated groups. Combined treatment of LS and Mn showed a significant (p < 0.05) decrease in neuronal aryl hydrocarbon hydroxylase (36–40%), ethoxyresorufin-O-deethylase (40–45%), glutathione-S-transferase (27–31%), and quinone reductase (24–25%) activities when compared to control and LS alone treated animals. Lipid peroxidation, a marker for membrane damage, was found to be relatively more enhanced (58–141%) along with significant (p < 0.05) depletion of GSH levels in LS+Mn-treated animals when compared to control, Mn alone, and LS alone treated groups. The neuronal catalase activity of lathyrus plus Mn-treated animals showed a pronounced decrease (37–49%) when compared to control, Mn, and lathyrus alone treated groups. On the contrary, glutathione peroxidase in brain of Mn and lathyrus alone treated animals indicated a respective increase (p < 0.05) of 18% and 20%, while the combined effect of lathyrus plus Mn exhibited an increase of almost 50% when compared to control guinea pigs. Single parenteral administration of Mn (15 mg/kg b.wt) to guinea pigs followed by single oral intubation of β-N-oxalyl-L-α, β-diamino propionic acid (ODAP, 75 mg/guinea pig) resulted in a significant increase (143%) in neuronal ODAP content. ODAP (50 mg/kg,iv) treatment to mice pretreated with MnCl2 (10 mg/kg b.wt for 3 days or 40 mg/kg b.wt for 1 day), caused an enhancement in blood–brain barrier (BBB) permeability (129–196%), while ODAP and Mn alone showed relatively less enhancement (66–87%). The lumbar region of LS+Mn showed a number of vacuolated areas of variegated size and chromatolytic neurons, along with a few degenerated neurons. These results suggest that Mn may potentiate the neurotoxicity of lathyrus/ODAP by altering the BBB permeability.
CMCS: Current-Mode Clock Synthesis

In a high-performance VLSI design, the clock network consumes a significant amount of power. While most existing methodologies use voltage-mode (VM) signaling, these clock distributions lose a tremendous amount of dynamic power to charge/discharge the large global clock capacitance. New circuit approaches for current-mode (CM) clocking save significant clock power, but have been limited to only symmetric networks, while most application specific integrated circuits have asymmetric clock distributions. In this paper, we propose the first CM clock synthesis (CMCS) methodology to reduce the overall clock network power with low skew. The method can integrate with traditional clock routing followed by transmitter and receiver sizing. We validate the proposed methodology using ISPD 2009 and 2010 industrial benchmarks using an extracted SPICE model distributed in 1.4–275.6-mm<sup>2</sup> area and consists of 81–2249 sinks. This methodology saves 39%–84% average power with similar skew on the benchmarks using 45-nm CMOS technology simulation of clock frequencies range from 1–3 GHz. In addition, the CMCS methodology takes <inline-formula> <tex-math notation="LaTeX">$2.4-9.1\times $ </tex-math></inline-formula> less running time and consumes 20%–26% less transistor area compared with synthesized, buffered VM clock distributions.
Insulin-like growth factor I improves height in growth hormone insensitivity: two years' results.

Thirty-one patients with growth hormone insensitivity syndrome (GHIS) and 2 with GH gene deletion (age 11.2 (3.7-22.9) years; BA (GP) 8.2 years; height -6.5 +/- 1.6 SDS) were recruited for the multicenter study. At birth, length was more retarded (-1.38 SDS) than weight (-0.56 SDS). The rhIGF-I dose was 40-120 micrograms/kg BW twice daily s.c. In 26 patients, first year HV increased from 3.9 +/- 1.8 to 8.5 +/- 2.1 cm/year (delta (d) HT SDS 0.8 +/- 0.5). In 18 patients, second year HV was 6.4 +/- 2.2 cm/year (dHT SDS 0.4 +/- 0.5). There was normal progression of puberty. Mean progression of BA was 1.2 and 1.5 years/year during the first and second year. There was no dose effect of IGF-I on growth. Weight-for-height index (WHI) and skinfold thickness were significantly correlated at start, 12 and 24 months (r = 0.83, 0.87 and 0.79). Changes in WHI were positively correlated with dHT SDS during the first and second year (r = 0.54, 0.56). Serum IGF-I rose, IGF-II decreased, and IGFBP-3 remained constant. Adverse events were (number of occasions): headache (21) (early); hypoglycemia (13); papilloedema (1) (reversible); Bell's palsy (1) (reversible); lipohypertrophy (7) (late); tonsillectomy/adenoidectomy (3) (late). The results show that there is effective long-term treatment of GHIS with systemically administered IGF-I and support the view that IGFBPs play an important role in the action of IGF-I.
Resistance Analysis of the Hepatitis C Virus NS5A Inhibitor BMS-790052 in an In Vitro Replicon System

ABSTRACT BMS-790052 is the most potent hepatitis C virus (HCV) inhibitor reported to date, with 50% effective concentrations (EC50s) of ≤50 pM against genotype 1 replicons. This exceptional potency translated to rapid viral load declines in a phase I clinical study. By targeting NS5A, BMS-790052 is distinct from most HCV inhibitors in clinical evaluation. As an initial step toward correlating in vitro and in vivo resistances, multiple cell lines and selective pressures were used to identify BMS-790052-resistant variants in genotype 1 replicons. Similarities and differences were observed between genotypes 1a and 1b. For genotype 1b, L31F/V, P32L, and Y93H/N were identified as primary resistance mutations. L23F, R30Q, and P58S acted as secondary resistance substitutions, enhancing the resistance of primary mutations but themselves not conferring resistance. For genotype 1a, more sites of resistance were identified, and substitutions at these sites (M28T, Q30E/H/R, L31M/V, P32L, and Y93C/H/N) conferred higher levels of resistance. For both subtypes, combining two resistance mutations markedly decreased inhibitor susceptibility. Selection studies with a 1b/1a hybrid replicon highlighted the importance of the NS5A N-terminal region in determining genotype-specific inhibitor responses. As single mutations, Q30E and Y93N in genotype 1a conferred the highest levels of resistance. For genotype 1b, BMS-790052 retained subnanomolar potency against all variants with single amino acid substitutions, suggesting that multiple mutations will likely be required for significant in vivo resistance in this genetic background. Importantly, BMS-790052-resistant variants remained fully sensitive to alpha interferon and small-molecule inhibitors of HCV protease and polymerase.
Can Individual Investors Use Option Strategies andthe Tax Code to Their Advantage?

This article tests whether high-income earners can earn excess risk-adjusted returns by annually exploiting the asymmetric U.S. tax treatment of long-term capital gains and losses using at-the-money (ATM) options. In this article, we run an initial analysis that tests the returns of the previous 50 years, from 1966 through 2015, that buys $3,000 of one-year ATM call options on the S&P 500 (SPY) to determine excess risk-adjusted returns for individuals of various taxable income levels. Additionally, we run a Monte Carlo simulation, based on long-term historical returns, standard deviations, and correlations, to test the robustness of the initial results for a risk-neutral investor. We find that call options can provide increased annual performance returns for all income levels. Furthermore, we conclude that these strategies also provide excess risk-adjusted returns for high-income earners in the 28% and higher income tax brackets.
Bethlem myopathy: long-term follow-up identifies COL6 mutations predicting severe clinical evolution

Objective Mutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype correlations and long-term follow-up description in BM remain scarce. Methods We retrospectively evaluated the long-term clinical evolution, and genotype-phenotype correlations in 35 genetically identified BM patients (23 index cases). Results Nineteen patients showed a typical clinical picture with contractures, proximal weakness and slow disease progression while 11 presented a more severe evolution. Five patients showed an atypical presentation, namely a limb girdle muscle weakness in 2 and a congenital myopathy pattern with either no contractures, or only limited to ankles, in 3 of them. Pathogenic COL6A1-3 mutations were mostly missense or in frame exon-skipping resulting in substitutions or deletions. Twenty one different mutations were identified including 12novel ones. The mode of inheritance was, autosomal dominant in 83% of the index patients (including 17% (N=4) with a de novo mutation), recessive in 13%, and undetermined in one patient. Skipping of exon 14 of COL6A1 was found in 35% of index cases and was mostly associated with a severe clinical evolution. Missense mutations were detected in 39% of index cases and associated with milder forms of the disease. Conclusions Long-term follow-up identified important phenotypic variability in this cohort of 35 BM patients. However, worsening of the functional disability appeared typically after the age of 40 in 47% of our patients, and was frequently associated with COL6A1 exon 14 skipping.
Popularity and Asset Pricing

Less-popular securities have lower prices but higher expected returns. In the efficient market framework, this is usually a risk that is disliked. Behavior finance posits numerous investor biases (e.g., affect) under which prices are determined by emotional sentiment. Popularity unifies both approaches by pricing security characteristics according to how much they are rationally or irrationally (emotionally) liked. Characteristics that are relatively permanently disliked result in pricing discounts and return premiums. A linear, popularity-based pricing equation is suggested.
Long‐term effects of prenatal stress and postnatal handling on age‐related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat

There is growing evidence that stress during prenatal and postnatal periods of life can modify adaptive capacities in adulthoods. The hypothalamo–pituitary–adrenal axis may mediate an animal's responses to perinatal stressful events and thus serve as a neurobiological substrate of the behavioural consequences of these early events. However, little is known about the long‐term effects of prenatal stressors throughout the entire life of the animals. The focus of the present study was to examine the long‐term influences of a prenatal and postnatal stress on glucocorticoid secretion and cognitive performance. Prenatal stress of rat dams during the last week of pregnancy and postnatal daily handling of rat pups during the first 3 weeks of life were used as stressors. The long‐term effects of these manipulations were analysed using a longitudinal approach throughout the entire life of the animals, and were repeatedly tested in adulthood (4–7 months), middle age (13–16 months) and in later life (20–24 months). The study demonstrated that prenatal stress and postnatal handling induced opposite effects on both glucocorticoid secretion and cognitive performance. Prenatal stress accelerated the age‐related hypothalamo–pituitary–adrenal axis dysfunctions; indeed, circulating glucocorticoids levels of prenatally stressed middle‐aged animals are similar to old control ones, and also induced cognitive impairments. In contrast, postnatal handling protected from the age‐related neuroendocrine and behavioural alterations. These results show that the altered glucocorticoid secretion induced by early environmental manipulations is primary to the cognitive alterations observed only later in life and could be one cause of age‐related memory deficits.
An In-Shoe Harvester With Motion Magnification for Scavenging Energy From Human Foot Strike

The aim of this study was to develop an in-shoe magnetic harvester that could be embedded in a shoe to scavenge mechanical energy from human foot strike for conversion into electricity, thereby serving as a sustainable power source for portable or wearable electronic devices. The allowed displacement of the shoe heel in the vertical direction was extremely small; therefore, a special trapezoidal slider mechanism was employed to amplify the displacement of a footstep. To compensate for the low-frequency foot strike, a gear train was used to accelerate the motion that finally drove a microgenerator to produce electricity. Two sets of springs were employed to provide a restoring force for the trapezoidal slider mechanism that enabled the harvester to generate electricity during the return trip. The in-shoe harvester could be embedded in a shoe heel such that the human foot step was not hindered during activity. Experiments indicated that the harvester could generate an average power output of approximately 1 W during normal walking. Compared to harvesters from previous studies, the harvester in this study can generate a higher power output.
BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer

Purpose: Current prostate cancer management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TIC-tailored therapies appears to be a promising approach. Experimental Design: We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient-derived prostate cancer cells and xenograft models to characterize the effects of pharmacologic inhibitors of BMI-1. Results: We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell–like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacologic inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor–directed therapies, without toxic effects on normal tissues. Conclusions: Our data offer a paradigm for targeting TICs and support the development of BMI-1–targeting therapy for a more effective prostate cancer treatment. Clin Cancer Res; 22(24); 6176–91. ©2016 AACR.
A 28 nm Embedded Split-Gate MONOS (SG-MONOS) Flash Macro for Automotive Achieving 6.4 GB/s Read Throughput by 200 MHz No-Wait Read Operation and 2.0 MB/s Write Throughput at Tj of 170$^{\circ}$ C

First-ever 28 nm embedded split-gate MONOS (SG-MONOS) flash macros have been developed to increase memory capacity embedded in micro controller units and to improve performance over wide junction temperature range from -40°C to 170 °C as demanded strongly in automotive uses. Much attention has been paid to the degradation of the reliability characteristics along with the process shrinkage. Temperature-adjusted word-line overdrive scheme improves random read access frequency by 15% and realizes both of 6.4 GB/s read throughput by 200 MHz no-wait random access of code flash macros and more than ten times longer TDDB lifetime of WL drivers. Temperature-adaptive step pulse erase control (TASPEC) improves the TDDB lifetime of dielectric films between metal interconnect layers by three times. TASPEC is particularly useful for a data flash macro with one million rewrite cycles. Source-side injection (SSI) program with negative back-bias voltage achieves 63% reduction of program pulse time and, consequently, realizes 2.0 MB/s write throughput of code flash macros. A spread spectrum clock generation and a clock phase shift technique are introduced for charge pump clock generation in order to suppress EMI noise due to high write throughput of code flash macros, and peak power of EMI noise is reduced by 19 dB.
Home chemotherapy for children with cancer

A program was established in which the parents of children with cancer were trained to administer intravenous chemotherapy to the children in their homes. The main objectives of this program (Home Intravenous Chemotherapy by Parents [HICP]) were to improve the quality of life for children with cancer and their parents and to decrease the cost of medical care for these children by decreasing the number of clinic visits and hospital stays intended solely for the administration of chemotherapy. Twenty‐four months of experience with this program indicates that with a close communication network and a good working relationship among a home care organization (HCO), the parents of the patient, a pediatric oncology nurse, and an attending pediatric oncologist, many chemotherapeutic agents can be safely administered to these children by their parents in their homes. The patients and their parents are enthusiastic about this program because of the valuable time saved and the increased participation in care. In addition, this program greatly decreases the cost of medical care for these children.
Arachidonic acid metabolites in carrageenin-induced equine inflammatory exudate.

The presence of cyclooxygenase products of arachidonic acid metabolism in carrageenin-induced inflammatory exudate was investigated in ponies using two models. In the first model, an inflammatory response was stimulated by injecting carrageenin into subcutaneously implanted polypropylene tissue cages and exudates were collected at five predetermined times between 3 and 48 h. In the second model, exudates were harvested at 6, 12 and 24 h from carrageenin-impregnated polyester sponges which had also been inserted beneath the skin. Prostaglandin (PG) E2, thromboxane (TX) B2 and the stable breakdown-product of prostacyclin (PGI2), 6-keto-PGF1 alpha, in exudates were measured by radio-immunoassay (RIA); PGE2-like and PGF2 alpha-like activities were bioassayed following an acid-lipid extraction technique which provided a recovery rate of 78%. Agreement between RIA and bioassay was within acceptable limits. In Model 1, using RIA, mean PGE2 concentration reached 197 ng X ml-1 at 12 h decreasing to less than 12 ng X ml-1 at 24 h. Mean TXB2 and 6-keto-PGF1 alpha levels were highest at 48 h (22.3 and 34.2 ng X ml-1, respectively) after considerable fluctuations and with wide standard errors prior to this time. In the sponge model, however, PGE2 levels were surprisingly low for each group (mean 12.8 ng X ml-1 at 12 h) and TXB2 and 6-keto-PGF1 alpha were similarly lower (means of 3.3 and 8.1 ng X ml-1 respectively at 12 h). Mean total leucocyte counts and total protein concentrations were increased in both models after carrageenin stimulus. PGF2 alpha was not detected in measurable quantities in any exudate. (ABSTRACT TRUNCATED AT 250 WORDS)
Forecasting UK Income Tax

The literature on forecasting tax revenues focuses on the need for a body of competing forecasts independent of government, to limit potential political bias. The Office for Budget Responsibility does provide detailed independent forecasts for the UK but there are limited alternatives. The literature on appropriate techniques for forecasting detailed tax revenues is under-developed. In many countries tax revenue forecasts are embedded in a more extensive macro-economic forecasting model. These models lack sufficient precision for revenue forecasting revenues for several specific taxes. Such models are too involved to support a body of competing independent forecasts. In consequence there is an established need for single equation revenue forecasts for specific taxes to complement the macro-economic approach. This study considers the use of a number of (mainly) time series forecasting techniques. We find Recurrent Singular Spectrum Analysis (RSSA) to perform the best of the techniques considered.
Building sustainable leadershp for inclusive school communities: A case of Muslim parents

This study explores how Muslim parents in the Greater Toronto Area are engaged in their children’s education and the challenges they face in trying to engage with the public school system. The public schools in Ontario are secular by law and free from any religious affiliation. They are however encouraged to find ways to accommodate the religious practices of students and parents of the Islamic faith and other faiths. Using a qualitative methodology, twelve Muslim parents selected from ethnically diverse backgrounds were interviewed. Data was collected and analyzed utilizing constant comparative method. Four major themes emerged from the data which focused on the centrality of religion in these parents’ households. Implications point towards the need for a culturally responsive policy that integrate Muslim values, cultural and religious beliefs in schools, which will make Ontario a stronger province that encourages people of all cultures and diversities to succeed and thrive.