Miracle-dz/UniFAR-FTUs huggingface dataset:
The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression

The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription elongation factor b (P‐TEFb). Here, we demonstrate that the human 7SK snRNP also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII‐specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. The 7SK snRNA specifically associates with a fraction of RNAPII hyperphosphorylated at Ser5 and Ser7, which is a hallmark of RNAPII engaged in snRNA synthesis. Chromatin immunoprecipitation (ChIP) and chromatin isolation by RNA purification (ChIRP) experiments revealed enrichments for all components of the 7SK snRNP on RNAPII‐specific sn/snoRNA genes. Depletion of 7SK snRNA or Larp7 disrupts LEC integrity, inhibits RNAPII recruitment to RNAPII‐specific sn/snoRNA genes, and reduces nascent snRNA and snoRNA synthesis. Thus, through controlling both mRNA elongation and sn/snoRNA synthesis, the 7SK snRNP is a key regulator of nuclear RNA production by RNAPII.
Rationale for and design of the TRUE‐AHF trial: the effects of ularitide on the short‐term clinical course and long‐term mortality of patients with acute heart failure

The TRUE‐AHF is a randomized, double‐blind, parallel‐group, placebo‐controlled trial which is evaluating the effects of a 48‐h infusion of ularitide (15 ng/kg/min) on the short‐ and long‐term clinical course of patients with acute heart failure. Noteworthy features of the study include the early enrolment of patients following their initial clinical presentation (within 12 h), and entry blood pressure criteria and thresholds for the adjustment of drug infusion rates, which aim to minimize the risk of hypotension. The trial has two primary endpoints: (i) cardiovascular mortality during long‐term follow‐up; and (ii) the clinical course of patients during their index hospitalization. Cardiovascular mortality is evaluated in this event‐driven trial by following all randomized patients for the occurrence of death until the end of the entire study without truncation at an arbitrarily determined early time point. The clinical course during the index hospitalization is evaluated using the hierarchical clinical composite endpoint, which combines information regarding changes in symptoms and the occurrence of in‐hospital worsening heart failure events and death into a single ranked metric that captures interval clinical events and minimizes the likelihood of missing data and confounding due to intensification of background therapy. The design of the TRUE‐AHF trial capitalizes on lessons learned from earlier trials and aims to evaluate definitively the potential benefit of ularitide in patients with acute heart failure.
Local Load Balancing for Globally Efficient Routing in Wireless Sensor Networks

One of the limitations of wireless sensor nodes is their inherent limited energy resource. Besides maximizing the lifetime of the sensor node, it is preferable to distribute the energy dissipated throughout the wireless sensor network in order to minimize maintenance and maximize overall system performance. Any communication protocol that involves synchronization of peer nodes incurs some overhead for setting up the communication. We introduce a new algorithm, e3D (energy-efficient Distributed Dynamic Diffusion routing algorithm), and compare it to two other algorithms, namely directed, and random clustering communication. We take into account the setup costs and analyze the energy-efficiency and the useful lifetime of the system. In order to better understand the characteristics of each algorithm and how well e3D really performs, we also compare e3D with its optimum counterpart and an optimum clustering algorithm. The benefit of introducing these ideal algorithms is to show the upper bound on performance at the cost of astronomical prohibitive synchronization costs. We compare the algorithms in terms of system lifetime, power dissipation distribution, cost of synchronization, and simplicity of the algorithm. Our simulation results show that e3D performs comparable to its optimal counterpart while having significantly less overhead.
Sasquatch: predicting the impact of regulatory SNPs on transcription factor binding from cell- and tissue-specific DNase footprints

In the era of genome-wide association studies (GWAS) and personalized medicine, predicting the impact of single nucleotide polymorphisms (SNPs) in regulatory elements is an important goal. Current approaches to determine the potential of regulatory SNPs depend on inadequate knowledge of cell-specific DNA binding motifs. Here, we present Sasquatch, a new computational approach that uses DNase footprint data to estimate and visualize the effects of noncoding variants on transcription factor binding. Sasquatch performs a comprehensive k-mer-based analysis of DNase footprints to determine any k-mer's potential for protein binding in a specific cell type and how this may be changed by sequence variants. Therefore, Sasquatch uses an unbiased approach, independent of known transcription factor binding sites and motifs. Sasquatch only requires a single DNase-seq data set per cell type, from any genotype, and produces consistent predictions from data generated by different experimental procedures and at different sequence depths. Here we demonstrate the effectiveness of Sasquatch using previously validated functional SNPs and benchmark its performance against existing approaches. Sasquatch is available as a versatile webtool incorporating publicly available data, including the human ENCODE collection. Thus, Sasquatch provides a powerful tool and repository for prioritizing likely regulatory SNPs in the noncoding genome.
Microstructure evolution and phase composition of high-manganese austenitic steels

Purpose: The aim of the paper is to determine the influence of hot-working conditions on microstructure evolution and phase composition of new-developed high-manganese austenitic steels. Design/methodology/approach: Determination of processes controlling strain hardening was carried out in continuous compression test using Gleeble 3800 thermo-mechanical simulator. Evaluation of processes controlling work hardening and occurring after deformation at 900°C were identified by microstructure observations of the specimens solution heat-treated after plastic deformation to a true strain equal 0.23, 0.50 and 0.91. Phase composition of steels was confirmed by X-ray diffraction analysis. Findings: The steels have a fine-grained austenite microstructure with many annealing twins to a temperature of about 1000°C. The initiation of dynamic recrystallization occurs already after true deformation equal 0.29. Participation of fine grains arranged in a matrix of dynamically recovered grains essentially increases after increasing true strain to 0.5. Fully dynamically recrystallized microstructure of steel can be obtained after the true strain equal 0.9. The conditions of hot-working influence phase state of investigated steels. Steel no. 1 keeps stable austenite microstructure independently from conditions of plastic deformation. Steel with initial bi-phase microstructure keeps a certain portion of eyet dependant on conditions of hot-working. Research limitations/implications: To determine in detail the hot-working behaviour of developed steels, a progress of microstructure evolution in subsequent stages of multi-stage compression test should be investigated. Practical implications: The obtained microstructure – hot-working conditions relationships and stress-strain curves can be useful in determination of power-force parameters of hot-rolling for sheets with fine-grained austenitic structures. Originality/value: The hot-working behaviour and microstructure evolution in various conditions of plastic deformation for new-developed high-manganese austenitic steels with Nb and Ti microadditions were investigated.
Forget about forgetting: structural barriers and severe non-adherence to antiretroviral therapy

ABSTRACT HIV infection is now clinically manageable with antiretroviral therapy (ART). However, a significant number of people with HIV do not benefit from ART because of non-adherence. This study examined the use of adherence strategies and barriers to adherence among persons at substantial risk for developing resistant virus (less than 75% adherent). People living with HIV (n = 556) who were less than 95% adherent to ART completed computerized interviews, were screened for active drug use, provided medical records for HIV viral load, and completed unannounced pill counts to monitor ART adherence and an assessment of adherence barriers. Based on pill counts, participants were defined as severely non-adherent (≤75% medications taken) and moderately non-adherent (>75% and <95% adherent). Results showed a broad array of memory devices were used to no avail across non-adherence groups. Individuals who were severely non-adherent were significantly more likely to attribute missing medications due to substance use and structural barriers, including running out of medications, inability to get to pharmacy, and inability to afford medications. Results suggest that interventions focused on memory lapses will be insufficient and should rather concentrate on substance use treatment and providing case management to resolve structural barriers to adherence.
Structured Images for RGB-D Action Recognition

This paper presents an effective yet simple video representation for RGB-D based action recognition. It proposes to represent a depth map sequence into three pairs of structured dynamic images at body, part and joint levels respectively through bidirectional rank pooling. Different from previous works that applied one Convolutional Neural Network (ConvNet) for each part/joint separately, one pair of structured dynamic images is constructed from depth maps at each granularity level and serves as the input of a ConvNet. The structured dynamic image not only preserves the spatial-temporal information but also enhances the structure information across both body parts/joints and different temporal scales. In addition, it requires low computational cost and memory to construct. This new representation, referred to as Spatially Structured Dynamic Depth Images (S2DDI), aggregates from global to fine-grained levels motion and structure information in a depth sequence, and enables us to fine-tune the existing ConvNet models trained on image data for classification of depth sequences, without a need for training the models afresh. The proposed representation is evaluated on five benchmark datasets, namely, MSRAction3D, G3D, MSRDailyActivity3D, SYSU 3D HOI and UTD-MHAD datasets and achieves the state-of-the-art results on all five datasets.
Ionization potentials and excitation energies of the alkali-metal atoms by the relativistic coupled-cluster method.

Ground- and excited-state energies, as well as ionization potentials and electron affinities, are calculated for all the alkali-metal atoms Li\char21{}Fr by the relativistic Fock-space coupled-cluster method. The coupled-cluster singles and doubles approximation, which includes single and double virtual excitations in a self-consistent manner, is implemented. The no-pair Dirac-Coulomb-Breit Hamiltonian is taken as the starting point. Rather extensive basis sets of balanced Gaussian spinors are used to span the atomic orbitals. The average error for the ionization potentials is 0.09% and for excitation energies 0.2%. Electron affinities are less accurate, particularly for the heavier atoms, with errors of 4\char21{}9 % for K, Rb, and Cs.
Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role

Within the last decade, several folate-based radiopharmaceuticals for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been evaluated; however, there is still a lack of suitable 18F-folates for clinical PET imaging. Herein, we report the synthesis and evaluation of two novel 18F-folates employing strain-promoted and copper-catalyzed click chemistry. Furthermore, the influence of both click-methods on lipophilicity and pharmacokinetics of the 18F-folates was investigated. 18F-Ala-folate and 18F-DBCO-folate were both stable in human serum albumin. In vitro studies proved their high affinity to the folate receptor (FR). The lipophilic character of the strain-promoted clicked 18F-DBCO-folate (logD = 0.6) contributed to a higher non-specific binding in cell internalization studies. In the following in vivo PET imaging studies, FR-positive tumors could not be visualized in a maximum intensity projection images. Compared with 18F-DBCO-folate, 18F-Ala-folate (logD = −1.4), synthesized by the copper-catalyzed click reaction, exhibited reduced lipophilicity, and as a result an improved in vivo performance and a clear-cut visualization of FR-positive tumors. In view of high radiochemical yield, radiochemical purity and favorable pharmacokinetics, 18F-Ala-folate is expected to be a promising candidate for FR-PET imaging.
Crash of automotive side member subjected to oblique loading

This paper presents the crash behavior analysis of automotive side member represented by aluminum square column subjected to oblique loading via finite element method. In crash research, energy absorption capacity is greatly affected by the deformation pattern, thus the collapse behavior and deformation pattern of this column is studied and observed. Effect of the geometrical parameters and loading angle, effect of these parameters on crashworthiness parameters that is specific energy absorption (SEA) and crush force efficiency (CFE) are explored. Observation on deformation pattern of the column shows that the bending is more apparent at the upper end for loading angle of 5 to 15 and at the bottom end for loading angle of 20 to 30. Results also show that SEA and CFE have less effected on the variation of column width. Ultimately, an equation that is expressed as a function of length and thickness is proposed to estimate crashworthiness parameters.
Bacterial Community Profile of the Gut Microbiota Differs between Hypercholesterolemic Subjects and Controls

The role of gut microbiota in the development of metabolic illnesses has been abundantly demonstrated. Recent studies suggest that gut microbiota alterations may also be related to the development of hypercholesterolemia. Therefore, we aimed to assess differences in the gut bacterial community profiles between hypercholesterolemic subjects and controls. Thirty cases diagnosed with hypercholesterolemia and 27 normocholesterolemic controls were included. A fasting whole blood sample was obtained to determine the lipid profile. In parallel, stool samples were collected and total DNA was isolated to assess the bacterial community profiles by denaturing gradient gel electrophoresis (DGGE). In addition, the Richness, Shannon-Weaver, and Simpson indexes were used to evaluate the richness and diversity of bacterial communities. As expected, serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol were significantly higher in the cases compared with controls. Moreover, DGGE analysis showed a lower richness and diversity of bacterial communities in hypercholesterolemic subjects. In conclusion, our results showed differences in the profiles of bacterial communities between hypercholesterolemic subjects and controls, suggesting a possible role of the gut microbiota in the development of hypercholesterolemia.
Is There an Association of Epidural Corticosteroid Injection With Postoperative Surgical Site Infection After Surgery for Lumbar Degenerative Spine Disease?

Study Design. Retrospective study. Objective. To assess the relation between exposure to epidural steroid injection (ESI) before surgery and occurrence of surgical site infection (SSI) for degenerative lumbar spine conditions. Summary of Background Data. The effect of local ESI on the occurrence of SSI is controversial. Methods. Patients who underwent surgery for degenerative lumbar spine conditions at two centers between 2005 and 2015 were identified. Primary outcome measure was SSI within 90 days requiring surgical intervention. Results. A total of 5311 patients (age 57 ± 16 years) were analyzed of which 945 (18%) had at least one ESI within 90 days of surgery. One hundred thirty-four (2.5%) patients developed an SSI requiring reoperation. No association of exposure or dose-response relationship was identified between ESI and SSI for any of the time periods (90-, 30-, and 30–90-day). Five (1.7%) of the 290 patients who had at least one ESI within 30 days before surgery had a postoperative infection compared to 129 (2.6%) of the 5021 in the non-ESI group (unadjusted odds ratio: 0.67, 95% CI: 0.27–1.64, P = 0.376). Fifteen (2.0%) of the 761 patients who had at least one ESI within 30 to 90 days before surgery had a postoperative infection, compared to 119 (2.6%) of the 4550 in the non-ESI group (unadjusted odds ratio: 0.75, 95% CI: 0.44–1.29, P = 0.296). Conclusion. In this retrospective study we investigated whether an ESI and its timing influences the postoperative risk of an SSI. We found no association—exposure or dose-response relationship—between ESI and postoperative infection, even after adjusting for potential confounders, for any of the time periods (90-, 30-, and 30–90-day ESI). In addition, we did find that longer hospital stay, greater EBL, posterior approach, and drain placement were associated with higher infection rates. Level of Evidence: 3
Parental Occupational Exposure to Heavy Metals and Welding Fumes and Risk of Testicular Germ Cell Tumors in Offspring: A Registry-Based Case–Control Study

Background: Data are scarce on the association between prenatal/preconception environmental exposure and testicular germ cell tumor (TGCT) in offspring. We examined parental occupational exposures to heavy metals and welding fumes in relation to TGCT in offspring in a registry-based case–control study (NORD-TEST Study). Methods: We identified TGCT cases diagnosed at ages 14–49 years in Finland (1988–2012), Norway (1978–2010), and Sweden (1979–2011) through nationwide cancer registries. These cases were individually matched by country and year of birth to controls selected from population registries. Information on parental occupations was retrieved from censuses. From this, we estimated prenatal/preconception exposures of chromium, iron, nickel, lead, and welding fumes (all three countries), and cadmium (Finland only) for each parent using job-exposure matrices specifying prevalence (P) and mean exposure level (L). Exposure indices were calculated as a product of P and L (P × L), and exposure categories were based on P × L or different combinations of P and L. Results: The study comprised 8,112 cases and 26,264 controls. We observed no statistically significant TGCT risk associated with presence of heavy metals/welding fumes (P × L > 0) and no dose-response relationship (Ptrend ≥ 0.32). A statistically significant elevated TGCT risk was found in paternal exposure category where both P and L of chromium were high (vs. no chromium; OR = 1.37, 95% confidence interval; 1.05–1.79). Conclusions: Our study provides little evidence of associations between parental exposures to heavy metals/welding fumes and TGCT in offspring with the potential exception of high paternal chromium exposure. Impact: Further research on paternal chromium exposure is warranted. Cancer Epidemiol Biomarkers Prev; 25(10); 1426–34. ©2016 AACR.
Mapping the Human Memory B Cell and Serum Neutralizing Antibody Responses to Dengue Virus Serotype 4 Infection and Vaccination

ABSTRACT The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses responsible for dengue fever and dengue hemorrhagic fever. People exposed to DENV develop antibodies (Abs) that strongly neutralize the serotype responsible for infection. Historically, infection with DENV serotype 4 (DENV4) has been less common and less studied than infections with the other three serotypes. However, DENV4 has been responsible for recent large and sustained epidemics in Asia and Latin America. The neutralizing antibody responses and the epitopes targeted against DENV4 have not been characterized in human infection. In this study, we mapped and characterized epitopes on DENV4 recognized by neutralizing antibodies in people previously exposed to DENV4 infections or to a live attenuated DENV4 vaccine. To study the fine specificity of DENV4 neutralizing human antibodies, B cells from two people exposed to DENV4 were immortalized and screened to identify DENV-specific clones. Two human monoclonal antibodies (MAbs) that neutralized DENV4 were isolated, and their epitopes were finely mapped using recombinant viruses and alanine scan mutation array techniques. Both antibodies bound to quaternary structure epitopes near the hinge region between envelope protein domain I (EDI) and EDII. In parallel, to characterize the serum neutralizing antibody responses, convalescence-phase serum samples from people previously exposed to primary DENV4 natural infections or a monovalent DENV4 vaccine were analyzed. Natural infection and vaccination also induced serum-neutralizing antibodies that targeted similar epitope domains at the EDI/II hinge region. These studies defined a target of neutralizing antigenic site on DENV4 targeted by human antibodies following natural infection or vaccination. IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever and dengue hemorrhagic fever. People exposed to primary DENV infections develop long-term neutralizing antibody responses, but these principally recognize only the infecting serotype. An effective vaccine against dengue should elicit long-lasting protective antibody responses to all four serotypes simultaneously. We and others have defined antigenic sites on the envelope (E) protein of viruses of dengue virus serotypes 1, 2, and 3 targeted by human neutralizing antibodies. The epitopes on DENV4 E protein targeted by the human neutralizing antibodies and the mechanisms of serotype 4 neutralization are poorly understood. Here, we report the properties of human antibodies that neutralize dengue virus serotype 4. People exposed to serotype 4 infections or a live attenuated serotype 4 vaccine developed neutralizing antibodies that bound to similar sites on the viral E protein. These studies have provided a foundation for developing and evaluating DENV4 vaccines.
Characterizing ASP Inferences by Unit Propagation

Computational approaches to Satisfiability Checking (SAT) and Answer Set Programming (ASP) have many aspects in common. In fact, the basic algorithms of ASP solvers are very similar to the Davis-Logemann-Loveland procedure (DLL) for SAT. The major difference lies in the inference rules, which are more complex in ASP. In this paper, we provide a generic framework, based on concepts from Constraint Processing (CSP), which allows us to view ASP inferences as forms of unit propagation. We develop declarative characterizations of ASP solvers nomore++ and smodels in terms of constraints. By putting ASP solving into a common context with SAT and CSP, we shed new light on ASP solving techniques and their relationships to neighboring fields.