Miracle-dz/UniFAR-FTUs huggingface dataset:
Approximating prediction error covariances among additive genetic effects within animals in multiple‐trait and random regression models

Summary A method for approximating prediction error variances and covariances among estimates of individual animals genetic effects for multiple-trait and random regression models is described. These approximations are used to calculate the prediction error variances of linear functions of the terms in the model. In the multiple-trait case these are indexes of estimated breeding values, and for random regression models these are estimated breeding values at individual points on the longitudinal scale. Approximate reliabilities for terms in the model and linear functions thereof are compared with corresponding reliabilities obtained from the inverse of the coefficient matrix in the mixed model equations. Results show good agreement between approximate and true values.
Galactomannoproteins of Aspergillus fumigatus

ABSTRACT Galactofuranose-containing molecules have been repeatedly shown to be important antigens among human fungal pathogens, including Aspergillus fumigatus. Immunogenic galactofuran determinants have been poorly characterized chemically, however. We reported here the characterization of two glycoproteins of A. fumigatus with an N-glycan containing galactofuranose. These proteins are a phospholipase C and a phytase. Chemical characterization of the N-glycan indicates that it is a mixture of Hex5-13HexNAc2 oligosaccharides, the major molecular species corresponding to Hex6-8HexNAc2. The N-glycan contained one galactofuranose unit that was in a terminal nonreducing position attached to the 2 position of Man. This single terminal nonreducing galactofuranose is essential for the immunoreactivity of the N-glycans assessed either with a monoclonal antibody that recognizes a tetra-β-1,5-galactofuran chain of galactomannan or with Aspergillus-infected patient sera.
The mRNA decay factor tristetraprolin (TTP) induces senescence in human papillomavirus-transformed cervical cancer cells by targeting E6-AP ubiquitin ligase

The RNA-binding protein tristetraprolin (TTP) regulates expression of many cancer-associated and proinflammatory factors through binding AU-rich elements (ARE) in the 3'-untranslated region (3'UTR) and facilitating rapid mRNA decay. Here we report on the ability of TTP to act in an anti-proliferative capacity in HPV18-positive HeLa cells by inducing senescence. HeLa cells maintain a dormant p53 pathway and elevated telomerase activity resulting from HPV-mediated transformation, whereas TTP expression counteracted this effect by stabilizing p53 protein and inhibiting hTERT expression. Presence of TTP did not alter E6 and E7 viral mRNA levels indicating that these are not TTP targets. It was found that TTP promoted rapid mRNA decay of the cellular ubiquitin ligase E6-associated protein (E6-AP). RNA-binding studies demonstrated TTP and E6-AP mRNA interaction and deletion of the E6-AP mRNA ARE-containing 3'UTR imparts resistance to TTP-mediated downregulation. Similar results were obtained with high-risk HPV16-positive cells that employ the E6-AP pathway to control p53 and hTERT levels. Furthermore, loss of TTP expression was consistently observed in cervical cancer tissue compared to normal tissue. These findings demonstrate the ability of TTP to act as a tumor suppressor by inhibiting the E6-AP pathway and indicate TTP loss to be a critical event during HPV-mediated carcinogenesis.
Earth's Interior from VLBI and Superconducting Gravimeter Data

We analyze VLBI delays back to 1984 from the permanent geodetic network, and ten superconducting gravimeter records from the Global Geodynamic Project spanning more than 7 years. From the former data, we deduce nutation o sets, and from the latter we get gravimetric factors. Comparison of these observed quantities against theoretical expressions of the core and mantle admittance to the tidal potential allows us to estimate Love numbers and resonant frequencies and quality factors of the core. We point out strengths and deficiencies of each technique in their ability to retrieve the Earth's interior parameters.
α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.
A low energy HEVC inverse transform hardware

In this paper, a novel energy reduction technique for High Efficiency Video Coding (HEVC) Inverse Discrete Cosine Transform (IDCT) and Inverse Discrete Sine Transform (IDST) for all transform unit (TU) sizes is proposed. The proposed technique calculates IDCT and IDST only for DC coefficient if the values of several predetermined forward transformed low frequency coefficients in a TU are smaller than a threshold. The proposed technique reduces the computational complexity of IDCT and IDST significantly. It increases the bit rate slightly for most video frames. It decreases the PSNR slightly for some video frames, and it increases the PSNR slightly for some video frames. In this paper, a low energy HEVC 2D inverse transform (IDCT and IDST) hardware for all TU sizes is also designed and implemented using Verilog HDL. In the worst case, the proposed hardware can process 48 Quad HD (3840x2160) video frames per second. The proposed technique reduced the energy consumption of this hardware up to 32%. Therefore, the proposed hardware can be used in portable consumer electronics products that require a real-time HEVC encoder.
An analysis of vector space models based on computational geometry

This paper analyzes the properties, structures and limitations of vector-based models for information retrieval from the computational geometry point of view. It is shown that both the pseudo-cosine and the standard vector space models can be viewed as special cases of a generalized linear model. More importantly, both the necessary and sufficient conditions have been identified, under which ranking functions such as the inner-product, cosine, pseudo-cosine, Dice, covariance and product-moment correlation measures can be used to rank the documents. The structure of the solution region for acceptable ranking is analyzed and an algorithm for finding all the solution vectors is suggested.
Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood–brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3–18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3–12.3), with a 1-year survival rate of 31.6% (95% CI 17.7–46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.
Design of variable-resistance class E inverters for load modulation

Single-switch inverters such as the conventional class E inverter are often highly load sensitive, and maintain zero-voltage switching over only a narrow range of load resistances. This paper introduces a design methodology that enables rapid synthesis of class E inverters that maintain ZVS operation over a wide range of resistive loads. We also show how the proposed methodology relates to circuit transformations on traditional class E designs. The proposed methodology is demonstrated and experimentally validated on a design at 27.12 MHz that operates efficiently over an 8:1 load resistance range.
Modeling and Simulation of a Vehicle Suspension with Variable Damping and Elastic Properties versus the Excitation Frequency

Usual vehicle suspensions employ hydro-pneumatic absorbers (e.g., oil, colloidal and air dampers) mounted in parallel with compression helical springs. Although the damping coefficient of the vehicle suspension is changing versus the excitation frequency, conventional design method is based on simplified models that assume for constant damping and elastic properties. In this work, three types of suspensions were considered and modeled as follows: oil damper mounted in parallel with a compression helical spring, for which a Kelvin-Voigt model, consisted of a dashpot and an elastic element connected in parallel is considered, colloidal damper without attached compression helical spring, for which a Maxwell model, consisted of a dashpot and an elastic element connected in series is considered, and colloidal damper mounted in parallel with a compression helical spring, for which a standard linear model, consisted of a Maxwell unit connected in parallel with an elastic element is considered. Firstly, the vibration transmissibility from the rough road to the vehicle's body for all these suspensions was determined under the constraint that damping varies versus the excitation frequency. Then, the optimal damping and stiffness ratios were decided in order to minimize the transmissibility of vibration from the rough pavement to the vehicle's body. Such results are useful to improve the vehicle's ride-comfort.
Population Structure and Evolution of Rhinoviruses

Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the family Picornaviridae and are divided into three species namely, Rhinovirus A, -B and -C, which are antigenically diverse. Genetic recombination is found to be one of the important causes for diversification of Rhinovirus species. Although emerging lineages within Rhinoviruses have been reported, their population structure has not been studied yet. The availability of complete genome sequences facilitates study of population structure, genetic diversity and underlying evolutionary forces, such as mutation, recombination and selection pressure. Analysis of complete genomes of Rhinoviruses using a model-based population genetics approach provided a strong evidence for existence of seven genetically distinct subpopulations. As a result of diversification, Rhinovirus A and -C populations are divided into four and two subpopulations, respectively. Genetically, the Rhinovirus B population was found to be homogeneous. Intra-species recombination was observed to be prominent in Rhinovirus A and -C species. Significant evidence of episodic positive selection was obtained for several sites within coding sequences of structural and non-structural proteins. This corroborates well with known phenotypic properties such as antigenicity of structural proteins. Episodic positive selection appears to be responsible for emergence of new lineages especially in Rhinovirus A. In summary, the Rhinovirus population is an ensemble of seven distinct lineages. In case of Rhinovirus A, intra-species recombination and episodic positive selection contribute to its further diversification. In case of Rhinovirus C, intra- and inter-species recombinations are responsible for observed diversity. Population genetics approach was further useful to analyze phylogenetic tree topologies pertaining to recombinant strains, especially when trees are derived using complete genomes. Understanding of population structure serves as a foundation for designing new vaccines and drugs as well as to explain emergence of drug resistance amongst subpopulations.
Targeting of cancer-associated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment

Cancer-associated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the small-molecule dipeptidyl peptidase inhibitor PT-100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT-100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT-100 contained lower numbers of tumor-associated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumor-promoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.
How much activity do youth get? A quantitative review of heart-rate measured activity.

OBJECTIVE Recommendations for adult physical activity have shifted from 20 to 60 minutes of continuous vigorous activity 3 to 5 times a week to accumulation of 30 minutes of moderate to vigorous physical activity most days of the week. Variations of these guidelines also have been suggested for children, based on the idea of accumulating moderate to vigorous physical activity throughout the day, rather than attaining vigorous physical activity in continuous blocks. The goal of this study was to assess accumulated amounts of physical activity at different intensities in children. METHODS We reviewed 26 studies (n = 1883) in youth aged 3 to 17 years that used heart-rate recording to measure physical activity in children to determine accumulated daily activity. Included were studies that provided time being active for at least 2 heart rate intensities at or above 120 beats/minute. Descriptive characteristics of the study groups were determined, and the influence of age, gender, and hours and days of observation on the slope of activity time as a function of percentage of heart rate reserve (HRR) was determined using hierarchical linear regression. RESULTS Youth attained 128.0 +/- 45.6, 47.1 +/- 14.9, 29.3 +/- 13.7, and 14.7 +/- 6.0 minutes/day between 20% to 40%, 40% to 50%, 50% to 60%, and greater than 60% HRR, respectively. Age was a significant predictor of the intercept and slope of the physical activity and %HRR relationship. CONCLUSION Youth of all ages attain >60 minutes/day of low-intensity physical activity and approximately 30 minutes/day of activity at traditional cardiovascular fitness training levels of 50% or more of HRR. Recommendations for youth activity are discussed.
Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter

Cholinergic hypofunction is associated with decreased attention and cognitive deficits in the central nervous system in addition to compromised motor function. Consequently, stimulation of cholinergic neurotransmission is a rational therapeutic approach for the potential treatment of a variety of neurological conditions. High affinity choline uptake (HACU) into acetylcholine (ACh)-synthesizing neurons is critically mediated by the sodium- and pH-dependent high-affinity choline transporter (CHT, encoded by the SLC5A7 gene). This transporter is comparatively well-characterized but otherwise unexplored as a potential drug target. We therefore sought to identify small molecules that would enable testing of the hypothesis that positive modulation of CHT mediated transport would enhance activity-dependent cholinergic signaling. We utilized existing and novel screening techniques for their ability to reveal both positive and negative modulation of CHT using literature tools. A screening campaign was initiated with a bespoke compound library comprising both the Pfizer Chemogenomic Library (CGL) of 2,753 molecules designed specifically to help enable the elucidation of new mechanisms in phenotypic screens and 887 compounds from a virtual screening campaign to select molecules with field-based similarities to reported negative and positive allosteric modulators. We identified a number of previously unknown active and structurally distinct molecules that could be used as tools to further explore CHT biology or as a starting point for further medicinal chemistry.
Processes Controlling the Mean Tropical Pacific Precipitation Pattern. Part I: The Andes and the Eastern Pacific ITCZ

Abstract The question of why the intertropical convergence zone (ITCZ) is generally north of the equator in the tropical Pacific is addressed. Experiments with an atmospheric general circulation model coupled to idealized representations of the ocean show that the presence of the Andes is enough to lower sea surface temperature (SST) off the west coast of South America through evaporation, thus promoting a north–south asymmetry, with the ITCZ north of the equator, which is amplified by interactions between the ocean and the atmosphere. The evaporative cooling results mainly from the subsidence of low specific humidity air, which is due in turn to the mechanical effect of the Andes on the zonal mean flow. The positive feedback from low-level clouds on SST is an important factor for the efficiency of the mechanism described. West of 120°W, the presence of the Rockies and Himalayas produces a comparable forcing to that of the Andes, but this is not enough to reverse or neutralize the north–south asymmetry se.
Probabilistic analysis of tree search

Consider the family tree of an age-dependent branching process, where the branches have costs corresponding to birth times. The first-birth problem of Hammersley (1974) then concerns the cost of an optimal (cheapest) node at depth n. Suppose that we must explore the tree so as to find an optimal or nearly optimal node at depth n. We now have a suitable model for analysing the behaviour of tree search algorithms, and we may extend the investigations of Karp and Pearl (1983).
The relationship between word retrieval, drawing, and semantics in people with aphasia

ABSTRACT Background: Word retrieval impairments in aphasia can affect a person’s ability to communicate his or her needs and ideas. Treatment for these deficits typically focuses on restorative and/or compensatory strategies. While traditionally used as a compensatory strategy, emerging evidence suggests that drawing may also have restorative effects on word retrieval by providing an alternate route to accessing the semantic system. However, the current understanding of this theoretical relationship between the semantic system, drawing, and word retrieval abilities is limited. Aims: The study purpose was to examine the relationship among naming, drawing, and semantic feature generation. Additionally, we examined the influence of drawing quality and content, as well as different performances based on aphasia severity. Methods & Procedures: Ten participants with chronic aphasia completed a series of sequenced tasks measuring confrontation naming accuracy before and after drawing and a semantic feature cueing task for target nouns. Outcomes & Results: Participants significantly increased confrontation naming accuracy when they named targets after completing semantic feature cueing then drawing. Additionally, there were moderate negative relationships between semantic content present in participant drawings and drawing quality with the amount of semantic features participants produced. Conclusions: Drawing, combined with a semantic cue task may result in more accurate naming as compared to confrontation naming alone; however, future research is needed to better understand this relationship.
A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy.

BACKGROUND Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4(+) T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4(+) T cells at concentrations achieved in vivo. METHODS We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1-infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4(+) T cells. RESULTS Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). CONCLUSIONS Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug.