gebhart/patrepeval huggingface dataset:
The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events (2009)

Cell-type and tissue-specific alternative splicing events are regulated by combinatorial control involving both abundant RNA binding proteins as well as those with more discrete expression and specialized functions. Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are recently discovered epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the FGFR2, ENAH, CD44 and CTNND1 transcripts. To catalogue a larger set of splicing events under the regulation of the ESRPs we profiled splicing changes induced by RNA interference-mediated knockdown of ES RP1 and ES RP2 expression in a human epithelial cell line using the splicing sensitive Affymetrix Exon ST1.0 Arrays. Analysis of the microarray data resulted in the identification of over a hundred candidate ESRP regulated splicing events. We were able to independently validate 38 of these targets by RT-PCR. The ESRP regulated events encompass all known types of alternative splicing events, most prominent being alternative cassette exons and splicing events leading to alternative 3' terminal exons. Importantly, a number of these regulated splicing events occur in gene transcripts that encode proteins with well-described roles in the regulation of actin cytoskeleton organization, cell-cell adhesion, cell polarity and cell migration. In sum, this work reveals a novel list of transcripts differentially spliced in epithelial and mesenchymal cells, implying that coordinated alternative splicing plays a critical role in determination of cell type identity. These results further establish ESRP1 and ESRP2 as global regulators of an epithelial splicing regulatory network.
Isolation and characterization of new exon 11‐associated N‐terminal splice variants of the human mu opioid receptor gene (2008)

Alternative splicing of the mu opioid receptor genes to create multiple mu receptor subtypes has been demonstrated in animals and humans. Previously, we identified a number of C-terminal variants in mice, rats and human, followed by several N-terminal variants associated with a new upstream exon in mice (exon 11). Behavioral studies in exon 11 knockout mice suggest an important role for the exon 11 variants in the analgesic actions of heroin and morphine-6beta-glucuronide, but not morphine or methadone. We now have identified a homologous human exon 11 and three similar human exon 11-associated variants, suggesting conservation of exon 11 and its associated variants across species. hMOR-1i has an additional 93 amino acids at the tip of the N-terminus but is otherwise identical to hMOR-1. When expressed in Chinese hamster ovary cells, the additional 93 amino acids in hMOR-1i had little effect on opioid binding, but significantly altered agonist-induced G-protein activation. hMOR-1G1 and hMOR-1G2 predicted six transmembrane domain variants, similar to those seen in mice. The regional expression of these exon 11-associated variants, as determined by RT-PCR, varied markedly, implying region-specific alternative splicing. The presence of exon 11-associated variants in humans raises questions regarding their potential role in heroin and morphine-6beta-glucuronide actions in people as they do in mice.
Excellent room temperature deformability in high strain rate regimes of magnesium alloy (2018)

Magnesium and its alloys have the lowest density among structural metallic materials; thus, this light-weight metal has great potential for reducing the weight, for example, of vehicles and trains. However, due to its crystal structure, deformability is poor; in particular, under compressive stress. In this study, we modified magnesium with bismuth as an alloying element, which has the characteristics of being likely to form precipitates instead of grain boundary segregation. The Mg-Bi binary alloy showed excellent deformability and high absorption of energy in high-strain rate regimes at room temperature via contribution of grain boundary sliding. These properties, which are closely comparable to those of conventional middle-strength aluminum alloys (Al-Mg and Al-Mg-Si series alloys), have never been observed before in magnesium alloys. The development of such properties opens the door for not only academic but also industrial research in magnesium.
Temporal structure in neuronal activity during working memory in Macaque parietal cortex (2000)

A number of cortical structures are reported to have elevated single unit firing rates sustained throughout the memory period of a working memory task. How the nervous system forms and maintains these memories is unknown but reverberating neuronal network activity is thought to be important. We studied the temporal structure of single unit (SU) activity and simultaneously recorded local field potential (LFP) activity from area LIP in the inferior parietal lobe of two awake macaques during a memory-saccade task. Using multitaper techniques for spectral analysis, which play an important role in obtaining the present results, we find elevations in spectral power in a 50--90 Hz (gamma) frequency band during the memory period in both SU and LFP activity. The activity is tuned to the direction of the saccade providing evidence for temporal structure that codes for movement plans during working memory. We also find SU and LFP activity are coherent during the memory period in the 50--90 Hz gamma band and no consistent relation is present during simple fixation. Finally, we find organized LFP activity in a 15--25 Hz frequency band that may be related to movement execution and preparatory aspects of the task. Neuronal activity could be used to control a neural prosthesis but SU activity can be hard to isolate with cortical implants. As the LFP is easier to acquire than SU activity, our finding of rich temporal structure in LFP activity related to movement planning and execution may accelerate the development of this medical application.
Modification of a rumen fluid priming technique for measuring in vitro neutral detergent fiber digestibility (2009)

Recently, we developed an alternate method to measure in vitro neutral detergent fiber (NDF) digestibility (ivNDFD) based on a primed rumen fluid inoculum. Pretreating rumen fluid inoculum with cellulose and holding the inoculum until it generated 0.3 mL of gas/mL of rumen fluid before inoculating forage samples improved ivNDFD assay repeatability but depressed ivNDFD means. Our objective in this study was to determine if pretreating rumen fluid with a mixture of carbohydrates and urea would affect the ivNDFD mean and variance. We also used the modified procedure as a reference assay to calibrate near-infrared reflectance spectroscopy (NIRS) to predict 24-, 30-, and 48-h ivNDFD. Two experiments were completed. In experiment A, 3 ivNDFD assays modified from the method of Goering and Van Soest were evaluated over 24, 28, 48, 54, and 72 h by using dried, ground alfalfa (1 mm) or wheat straw (0.5 g) sealed in Ankom F57 forage fiber bags. Bags were placed individually in 125-mL Erlenmeyer flasks and incubated with Goering and Van Soest media and 10 mL of rumen fluid. Rumen fluid was collected before feeding from 2 cannulated cows fed a high-forage diet and was prepared in 1 of 3 ways: 1) pooled rumen fluid was strained and used immediately to inoculate flasks (modified Goering and Van Soest method); 2) strained, pooled fluid was combined with buffer, reducing solution, and 1.25 mg of primer/mL of rumen fluid and allowed to produce 0.12 mL of gas/mL of rumen fluid before sample inoculation [Combs-Goeser (CG) method]; or 3) the CG method was used without the primer mixture (unprimed method). The assay was repeated 5 times, with 5 time points (24, 28, 48, 54, and 72 h) and 2 subsamples per time point for each method. Neutral detergent fiber was analyzed using an Ankom(200) forage fiber analyzer and ivNDFD was determined as follows: ivNDFD (% of NDF) = 100 x [(NDF(0h) - NDF(residue))/(NDF(0h))]. Results were analyzed using a mixed model procedure, and data were blocked by method to obtain repetition sums of squares, which were compared by an F-test to assess interassay error. Repetition sums of squares were reduced with the CG method compared with the Goering and Van Soest method (19 vs. 228), and mean ivNDFD estimates were similar at 28, 48, and 54 h. In experiment B, 24-, 30-, and 48-h ivNDFD data for 54 feeds were determined in triplicate using the CG method, and corresponding samples were then scanned with an NIRS instrument. Calibrations were computed using partial least squares regression techniques. The NIRS calibration equation R(2) values were 0.93, 0.93, and 0.89 for 24-, 30-, and 48-h ivNDFD. Results suggest that the modified ivNDFD method using rumen fluid primed with a mixture of carbohydrate and urea (CG method) reduced interassay error.
Method for generating acoustical voice signals for persons extremely hard of hearing and a device for implementing this method (1982)

First Page
Optical phase‐sensitive amplification of higher‐order QAM signal with single Mach–Zehnder amplitude modulator (2020)

Abstract An optical phase‐sensitive amplifier (PSA) has the potential of low‐noise optical amplification. A frequency non‐degenerate PSA (ND‐PSA) can amplify arbitrary modulation formats including higher‐order QAM. The ND‐PSA requires a co‐propagating phase conjugated light (idler light) that has been conventionally created with an optical phase conjugator at the transmitter side. We propose a transmitter configuration using simultaneous signal generation of both a signal and its idler by double‐sideband modulation for transmission systems with ND‐PSAs. The proposed scheme provides a simple configuration with a single Mach–Zehnder amplitude modulator without optically creating the idler light. We performed experiments using 16QAM, 32QAM, and probabilistically shaped 256QAM signals. As a result, a phase‐sensitive amplification with each modulation format was successfully demonstrated using the proposed transmitter configuration.
Temperature-Dependent Vector Hysteresis Model for Permanent Magnets (2014)

Irreversible thermal demagnetization effects can sometimes play a significant role in, for instance, rotating Preisach model (PM) machines. Modeling such phenomena requires field simulation methods such as finite element (FE) analysis in combination with a temperature-dependent vector hysteresis model. This paper explores the feasibility of applying a formalism for temperature-dependent structural hysteresis to magnetics. The net magnetization is expressed as a superposition of contributions from plays. By allowing the anhysteretic curve and the coercivity to depend on temperature, irreversible thermal effects resembling experiments emerge automatically without additional assumptions or adjustable parameters. Incorporating this temperature dependence has negligible impact on the computational efficiency or complexity of the model.
Antigens of <i>Mycobacterium tuberculosis</i> Expressed during Preclinical Tuberculosis: Serological Immunodominance of Proteins with Repetitive Amino Acid Sequences (2001)

Four antigens of Mycobacterium tuberculosis that are expressed in vivo after aerosol infection but prior to the development of clinical tuberculosis (TB) in rabbits were identified by immunoscreening of an expression library of M. tuberculosis genomic DNA with sera obtained 5 weeks postinfection. Three of the proteins identified, PirG (Rv3810), polymorphic GC-repetitive sequence (PE-PGRS; Rv3367), and proline-threonine repetitive protein (PTRP) (Rv0538), have multiple tandem repeats of unique amino acid sequences and have characteristics of surface or secreted proteins. The fourth protein, MtrA (Rv3246c), is a response regulator of a putative two-component signal transduction system, mtrA-mtrB, of M. tuberculosis. All four antigens were recognized by pooled sera from TB patients and not from healthy controls, confirming their in vivo expression during active infection in humans. Three of the antigens (PE-PGRS, PTRP, and MtrA) were also recognized by retrospective preclinical TB sera obtained, prior to the clinical manifestation of TB, from human immunodeficiency virus-TB patients, suggesting that they are potential candidates for devising diagnostic tests for active, preclinical TB.
Multi-scale anatomical awareness improves the accuracy of the real-time electric field estimation (2021)

Induced electric fields (E-field) of a coil within target areas are substantial for precise trans cranial therapy. The fast and precise estimation of a stimulation is essential for a navigation system. However, high accuracy and low time consumption are rarely satisfied at the same time in previous models. In this paper, we present an anatomical-awareness model to integrate binary, explicit anatomical structures as mediate variables. Multi-scale attention blocks are also introduced to capture the anatomical variations. The presented model mitigates the anatomy-related errors. The presented architecture not only reduces the mean relative errors of E-field to about 7%, but also has the characteristics of low time consumption, which makes it suitable for a real-time navigation system.
Molecular cloning of a gene encoding an arabinogalactan-protein from pear (Pyrus communis) cell suspension culture. (1994)

Arabinogalactan-proteins (AGPs) are proteoglycans containing a high proportion of carbohydrate (typically > 90%) linked to a protein backbone rich in hydroxyproline (Hyp), Ala, Ser, and Thr. They are widely distributed in plants and may play a role in development. The structure of the carbohydrate of some AGPs is known in detail but information regarding the protein backbone is restricted to a few peptide sequences. Here we report isolation and partial amino acid sequencing of the protein backbone of an AGP. This AGP is a member of one of four major groups of AGPs isolated from the filtrate of pear cell suspension culture. A cDNA encoding this protein backbone (145 amino acids) was cloned; the deduced protein is rich in Hyp, Ala, Ser, and Thr, which together account for > 75% of total residues. It has three domains, an N-terminal secretion signal, a central hydrophilic domain containing all of the Pro residues, and a hydrophobic C-terminal domain that is predicted to be a transmembrane helix. Approximately 93% of the Pro residues are hydroxylated and hence are potential sites for glycosylation.
All-Weather Deep Outdoor Lighting Estimation (2019)

We present a neural network that predicts HDR outdoor illumination from a single LDR image. At the heart of our work is a method to accurately learn HDR lighting from LDR panoramas under any weather condition. We achieve this by training another CNN (on a combination of synthetic and real images) to take as input an LDR panorama, and regress the parameters of the Lalonde-Matthews outdoor illumination model. This model is trained such that it a) reconstructs the appearance of the sky, and b) renders the appearance of objects lit by this illumination. We use this network to label a large-scale dataset of LDR panoramas with lighting parameters and use them to train our single image outdoor lighting estimation network. We demonstrate, via extensive experiments, that both our panorama and single image networks outperform the state of the art, and unlike prior work, are able to handle weather conditions ranging from fully sunny to overcast skies.
Abstract 712: Detection of lung cancer by assay of novel methylated DNA markers in plasma (2017)

Abstract Purpose: Lung cancer is the leading cause of cancer deaths worldwide. Most present symptomatically at late stage with high lethality. Early detection reduces mortality but accurate and readily accessible tools for population screening are limited. By whole methylome sequencing, we have identified novel methylated DNA markers (MDMs) for lung cancer in tissue (Giakoumopoulos et al. ASCO 2016). Using top candidate MDMs in the present study, we now explore their clinical accuracy for lung cancer detection when assayed from plasma. Experimental Procedures: Archival plasmas from two independent study groups were tested in blinded fashion. Lung cancer cases and controls (apparently healthy smokers) for each group were balanced on age and sex (Group 1: 64 cases, 231 controls; Group 2: 23 cases, 80 controls). Using multiplex PCR followed by QuARTS (Quantitative Allele-Specific Real-time Target and Signal amplification) assay, a post-bisulfite quantification of MDMs on DNA extracted from plasma was performed. We selected 31 MDM candidates for initial evaluation in Group 1 (1 ml plasma/patient); top individual MDMs were subsequently tested in Group 2 to identify optimal MDM panels for lung cancer detection (2 ml/patient). Results: From Group 1 analyses, 13 high performance MDMs were selected for further testing (CYP26C1, SOBP, SUCLG2, SHOX2, ZDHHC1, NFIX, FLJ45983, HOXA9, B3GALT6, ZNF781, SP9, BARX1, EMX1) with individual areas under the receiver operator curve (AUCs) ranging from 0.593 to 0.939. Discrimination by individual MDMs was corroborated in Group 2 in which data was analyzed using two methods: a logistic regression fit and a regression partition tree approach. The logistic fit model identified a 4-marker panel (ZNF781, BARX1, EMX1, and SOBP) with an AUC of 0.96 and an overall sensitivity of 91% and 90% specificity. Analysis of the data using a regression partition tree approach identified 4 markers (ZNF781, BARX1, EMX1, and HOXA9) with AUC of 0.93 and an overall sensitivity of 96% and specificity of 94%. For both approaches, B3GALT6 was used as a standardizing marker of total DNA input. Conclusion: A panel of MDMs assayed in plasma achieved high sensitivity and specificity for all types of lung cancer. Further clinical evaluation and validation of this promising panel in larger patient groups are clearly indicated. Citation Format: Hatim T. Allawi, Maria Giakoumopoulos, Evan Flietner, Austin Oliphant, Carla Volkmann, Brian Aizenstein, Tamara Sander, Drew Eckmayer, Ashley Poenitzsch Strong, Melissa Gray, Barry Berger, Tracy Yab, William Taylor, Douglas Mahoney, John B. Kisiel, David E. Midthun, David A. Ahlquist, Graham P. Lidgard. Detection of lung cancer by assay of novel methylated DNA markers in plasma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 712. doi:10.1158/1538-7445.AM2017-712
Defibrillation Thresholds Are Lower with Smaller Storage Capacitors (1995)

Present implantable cardioverter defibrillators use a wide range of capacitance values for the storage capacitor. However, the optimal capacitance value is unknown. We hypothesized that a smaller capacitor, by delivering its charge in a time closer to the heart chronaxie, should lower the defibrillation threshold (DFT). We compared the energy required to defibrillate 10 open-chest dogs, after 15 seconds of ventricular fibrillation, with a monophasic, time-truncated waveform delivered from either a 85-microF or a 140-microF capacitor. Shocks were delivered through a pair of 14-cm2 epicardial patch electrodes: The two capacitors were randomly tested twice with each dog using a modified 3-reversal method for each DFT determination. The average stored and delivered DFT energies for the 85-microF capacitor were 6.0 +/- 1.7 joules and 5.2 +/- 1.5 joules, respectively, compared to 6.7 +/- 1.7 joules and 6.0 +/- 1.5 joules for the 140-microF capacitor (P = 0.01 and P = 0.004, respectively). The mean leading edge voltages were higher, the pulse duration shorter, and the mean impedance lower for the 85-microF capacitor. The impedance was inversely related to the pulse duration and the voltage decay suggesting that, at least in part, the mechanism of improved defibrillation could be accounted for by the waveform electrical characteristics. There was an equal number of episodes of postshock bradyarrhythmias and tachyarrhythmias following discharges from each capacitor. Moreover, there was no relationship between the likelihood of these arrhythmias and either the initial voltage or the delivered current nor there was a higher number of episodes of postshock hypotension following the smaller capacitor discharges.(ABSTRACT TRUNCATED AT 250 WORDS)
ChemInform Abstract: A New Synthesis of 3‐Amino‐1‐aryl‐2‐pyrazolin‐5‐ones. (1984)

Abstract Aus β‐Nitropropionsäureethylester (I) entstehen in Gegenwart von Alkoholat mit Diazoniumsalzen (II) die Hydrazone (III), die nach katalytischer Hydrierung zu (IV) zu den Pyrazolinonen (V) cyclokondensieren.
An Arginine-Rich Motif in the ORF2 Capsid Protein Regulates the Hepatitis E Virus Lifecycle and Interactions with the Host Cell (2021)

Abstract Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. Hepatitis E is usually asymptomatic and self-limiting but it can become chronic in immunocompromised patients and is associated with increased fulminant hepatic failure and mortality rates in pregnant women. HEV genome encodes three proteins including the ORF2 protein that is the viral capsid protein. Interestingly, HEV produces 3 isoforms of the ORF2 capsid protein which are partitioned in different subcellular compartments and perform distinct functions in the HEV lifecycle. Notably, the infectious ORF2 (ORF2i) protein is the structural component of virions, whereas the genome-free secreted and glycosylated ORF2 proteins likely act as a humoral immune decoy. Here, by using a series of ORF2 capsid protein mutants expressed in the infectious genotype 3 p6 HEV strain as well as chimeras between ORF2 and the CD4 glycoprotein, we demonstrated how an Arginine-Rich Motif (ARM) located in the ORF2 N-terminal region controls the fate and functions of ORF2 isoforms. We showed that the ARM controls ORF2 nuclear translocation, promoting regulation of host antiviral responses. This motif also regulates the dual topology and functionality of ORF2 signal peptide, leading to the production of either cytosolic infectious ORF2i or reticular non-infectious glycosylated ORF2 forms. It serves as maturation site of glycosylated ORF2 by cellular proteases, and promotes ORF2-host cell membrane interactions. The identification of ORF2 ARM as a unique central regulator of the HEV lifecycle uncovers how viruses settle strategies to condense their genetic information and hijack cellular processes. Author summary Hepatitis E virus (HEV) is the major cause of acute viral hepatitis worldwide. Although infection with HEV is usually self-resolving, it can cause up to 30% mortality in pregnant women in the third trimester. There is no specific treatment nor universal vaccine to fight against HEV. In our study, we focused on the HEV ORF2 capsid protein which is produced as different forms that perform distinct functions in the HEV lifecycle. The infectious ORF2i form is the structural component of virions, while the other forms likely act as an immune decoy. Herein, we deciphered the molecular determinants of ORF2 multifunctionality. We identified an Arginine-Rich Motif (ARM) located in the ORF2 N-terminal region that controls the subcellular localization, the fate and functions of ORF2 forms. It also promotes ORF2-host cell interactions. Our observations highlight the ORF2 ARM as a unique central regulator of ORF2 addressing that finely controls the HEV lifecycle.