gebhart/patrepeval huggingface dataset:
E2F1 Responds to Ultraviolet Radiation by Directly Stimulating DNA Repair and Suppressing Carcinogenesis (2014)

In response to DNA damage, the E2F1 transcription factor is phosphorylated at serine 31 (serine 29 in mouse) by the ATM or ATR kinases, which promotes E2F1 protein stabilization. Phosphorylation of E2F1 also leads to the recruitment of E2F1 to sites of DNA damage, where it functions to enhance DNA repair. To study the role of this E2F1 phosphorylation event in vivo, a knock-in mouse model was generated, in which serine 29 was mutated to alanine. The S29A mutation impairs E2F1 stabilization in response to ultraviolet (UV) radiation and doxorubicin treatment, but has little effect on the expression of E2F target genes. The apoptotic and proliferative responses to acute UV radiation exposure are also similar between wild-type and E2f1(S29A/) (S29A) mice. As expected, the S29A mutation prevents E2F1 association with damaged DNA and reduces DNA repair efficiency. Moreover, E2f1(S29A/) (S29A) mice display increased sensitivity to UV-induced skin carcinogenesis. This knock-in mouse model thus links the ability of E2F1 to directly promote DNA repair with the suppression of tumor development.
A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases (2018)

A priority for the National Institute of Allergy and Infectious Diseases is development of a universal influenza vaccine providing durable protection against multiple influenza strains. NIAID will use this strategic plan as a foundation for future investments in influenza research.
Scalable parallel preconditioners for an open source cardiac electrophysiology simulation package (2011)

The numerical solution of the bidomain equations is a fundamental tool in the field of computational cardiac electrophysiology. The multi-scale nature of the processes involved and the increasing complexity of the tissue and ionic models of interest make the use of High Performance Computing techniques mandatory. The solution of the linear system arising from the Finite Element discretisation of the bidomain equations is the main bottleneck in terms of performance and parallel scalability. In this work we present and evaluate parallel implementations of two problemspecific block preconditioners, namely BD and LDU, in the framework of the open source cardiac electrophysiology simulation package Chaste. Both rely upon providing a reliable and practical method for calculating the action of the inverse of certain matrix subblocks. Our results show that: a) total execution time can be reduced by using different approximation methods for different matrix subblocks, b) there exists a good correlation between the coefficient Δt=h2 and the cases where BD and LDU outperform generic Algebraic Multigrid (AMG) preconditioning, and c) when applied to simulations with current state-of-the-art cardiac geometries, BD and LDU are over 3 times faster than AMG preconditioning and show similar scaling.
Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy (2016)

The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell-derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell-cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell-cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes.
A CPU chip-on-board module (1994)

A CPU chip-on-board module for low and midrange computers is described. The module consists of a CPU bare chip, 24 SRAM's packaged in SOJ packages, and some decoupling capacitors. The module substrate is a printed circuit board (PCB) made of bismaleimide-triazine resin. The module (156 mm/spl times/58 mm) consists of four signal metal layers and four power/ground metal layers. A square clearance hole (17 mm/spl times/17 mm) for the CPU is formed in the central part of the PCB. A thermal spreading metal is glued to the PCB from the rear side, covering the square hole, and the CPU chip is die-bonded onto the metal plate. The thermal resistance can be made smaller than 2/spl deg/C/W with 0.4 m/s of wind velocity. Numerical analysis of electrical characteristics of the module shows that it can reduce signal delay time from the CPU to cache memories by 10% compared with that of a daughter board type module with the CPU packaged in a pin-grid array package. It is estimated that simultaneously switched noise can be reduced by 60% from that of the daughter board type module.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
APOBEC3A efficiently deaminates methylated, but not TET-oxidized, cytosine bases in DNA (2017)

AID/APOBEC family enzymes are best known for deaminating cytosine bases to uracil in single-stranded DNA, with characteristic sequence preferences that can produce mutational signatures in targets such as retroviral and cancer cell genomes. These deaminases have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine (mC) or TET-oxidized mC bases (ox-mCs), which include 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. One specific family member, APOBEC3A (A3A), has been shown to readily deaminate mC, raising the prospect of broader activity on ox-mCs. To investigate this claim, we developed a novel assay that allows for parallel profiling of activity on all modified cytosines. Our steady-state kinetic analysis reveals that A3A discriminates against all ox-mCs by >3700-fold, arguing that ox-mC deamination does not contribute substantially to demethylation. A3A is, by contrast, highly proficient at C/mC deamination. Under conditions of excess enzyme, C/mC bases can be deaminated to completion in long DNA segments, regardless of sequence context. Interestingly, under limiting A3A, the sequence preferences observed with targeting unmodified cytosine are further exaggerated when deaminating mC. Our study informs how methylation, oxidation, and deamination can interplay in the genome and suggests A3A's potential utility as a biotechnological tool to discriminate between cytosine modification states.
A Multi-View Nonlinear Active Shape Model Using Kernel PCA (1999)

Recovering the shape of any 3D object using multiple 2D views requires establishing correspondence between feature points at different views. How-ever changes in viewpoint introduce self-occlusions, resulting nonlinear vari-ations in the shape and inconsistent 2D features between views. Here we introduce a multi-view nonlinear shape model utilising 2D view-dependent constraint without explicit reference to 3D structures. For nonlinear model transformation, we adopt Kernel PCA based on Support Vector Machines. 1
Cytotoxic Molecule Expression and Epithelial Cell Apoptosis in Oral and Cutaneous Lichen Planus (2004)

FIGURES 19–26. Plonaphacarus cristatus sp. nov.: 19, lateral view of body (legs removed); 20, prodorsum, dorsal view; 21, mentum of infracapitulum; 22, left side of ventral plate; 23–26, trochanter, femur, genu and tibia: 23, leg I; 24, leg II; 25, leg III; 26, leg IV. Scale bars: 19–22=100μm; 23–26=50μm.
Trastuzumab-containing regimens for metastatic breast cancer (2014)

Trastuzumab improved overall survival and progression-free survival in HER2-positive women with metastatic breast cancer, but it also increased the risk of cardiac toxicities, such as congestive heart failure and LVEF decline. The available subgroup analyses are limited by the small number of studies. Studies that administered trastuzumab as first-line treatment, or along with a taxane-based regimen, improved mortality outcomes. The evidence to support the use of trastuzumab beyond progression is limited. The recruitment in three out of seven studies was stopped early and in three trials more than 50% of patients in the control groups were permitted to switch to the trastuzumab arms at progression, making it more difficult to understand the real net benefit of trastuzumab.Trastuzumab is generally used for women with HER2-positive early breast cancer in clinical practice, while women enrolled in most of the trials in the metastatic setting were naive to trastuzumab. The effectiveness of trastuzumab for women relapsing after adjuvant trastuzumab is therefore still an open issue, although it is likely that the majority are being offered it again.
Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist (2014)

CpG DNA, a ligand for Toll-like receptor 9 (TLR9), has been one of the most promising immunotherapeutic agents. Although there are several types of potent humanized CpG oligodeoxynucleotide (ODN), developing "all-in-one" CpG ODNs activating both B cells and plasmacytoid dendritic cells forming a stable nanoparticle without aggregation has not been successful. In this study, we generated a novel nanoparticulate K CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand schizophyllan (SPG), K3-SPG. In sharp contrast to K3 alone, K3-SPG stimulates human peripheral blood mononuclear cells to produce a large amount of both type I and type II IFN, targeting the same endosome where IFN-inducing D CpG ODN resides without losing its K-type activity. K3-SPG thus became a potent adjuvant for induction of both humoral and cellular immune responses, particularly CTL induction, to coadministered protein antigens without conjugation. Such potent adjuvant activity of K3-SPG is attributed to its nature of being a nanoparticle rather than targeting Dectin-1 by SPG, accumulating and activating antigen-bearing macrophages and dendritic cells in the draining lymph node. K3-SPG acting as an influenza vaccine adjuvant was demonstrated in vivo in both murine and nonhuman primate models. Taken together, K3-SPG may be useful for immunotherapeutic applications that require type I and type II IFN as well as CTL induction.
Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer (2017)

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.
Research Review: A new perspective on attention‐deficit/hyperactivity disorder: emotion dysregulation and trait models (2009)

Attention-deficit/hyperactivity disorder (ADHD) is a common example of developmental psychopathology that might be able to be better understood by taking an emotion regulation perspective. As discussed herein, emotion regulation is understood to consist of two component processes, emotion (e.g., positive and negative emotionality) and regulation (e.g., effortful and reactive forms of control), which interact with one another at the behavioral level. Review of work to date suggests that the heterogeneous behavioral category of ADHD may encompass two distinct kinds of inputs: inattentive ADHD symptoms may be primarily associated with breakdowns in the regulation side, whereas hyperactivity-impulsive ADHD symptoms may be associated with breakdowns in the emotionality side. It is argued that breakdowns in control may be a signature for ADHD specifically, while increased negative emotionality may serve as non-specific risk factors for disruptive behavior disorders, explaining their comorbidity. Increased understanding of the interrelations and interactions of component emotion regulation processes may elucidate developmental, sex, and neural mechanisms of ADHD and associated comorbid disruptive disorders.
File processing efficiency on the content addressable file store (1985)

The file processing efficiency of the ICL Search Engine CAFS (Content Addressable File Store) is studied by means of detailed simulation experiments. The suitability of CAFS to different file structures and processing operations is critically assessed, and processing environments have been identified where the use of CAFS offers only marginal benefits and where it is actually counter-productive. We also provide concrete recommendations concerning the optimal deployment of CAFS as well as guidelines for the tuning of its performance parameters. In addition, the strengths and weaknesses of the CAFS architecture are assessed and some improvements to its current design are proposed.
Ceramide‐rich platforms in transmembrane signaling (2010)

Recent evidence suggests that ceramide regulates stress signaling via reorganization of the plasma membrane. The focus of this review will be to discuss the mechanism by which acid sphingomyelinase (ASMase)-generated ceramide initiates transmembrane signaling in the plasma membrane exoplasmic leaflet. In particular, we review the unique biophysical properties of ceramide that render it proficient in formation of signaling domains termed ceramide-rich platforms (CRPs), and the role of CRPs in the pathophysiology of various diseases. The biomedical significance of CRPs makes these structures an attractive therapeutic target.
A high throughput in-loop de-blocking filter supporting H.264/AVC BP/MP/HP video coding (2008)

This paper presents a high throughput VLSI architecture for H.264/AVC in-loop de-blocking filter (ILF) supporting baseline, main, and high profile (BP/MP/HP) video decoding targeted at HDTV applications. We develop a 4×4/8×8 filter and a buffer management scheme to perform the various coding tools in H.264 de-blocking filter for supporting the coding tools of picture adaptive frame/field (PAFF) coding, macroblock adaptive frame/field (MBAFF) coding, and 8×8 transform coding. In particular, we adopt two local buffers to store the reference MB pair data and reschedule the internal pixels when switching the filtering operations on the horizontal and vertical edges without writing it out to the external memory. Adopting TSMC 0.13μm CMOS technology, we implement the proposed design with the cost of 36.9K gates and 672 bytes of local memory when operating at 225 MHz. Moreover, the proposed design achieves the data throughput rate of 260 cycles per MB in average, which meets the real-time processing requirement for H.264 16VGA (2560×1920)@30fps video decoding.
The Amino-terminal Portion of the JAK2 Protein Kinase Is Necessary For Binding and Phosphorylation of the Granulocyte-Macrophage Colony-stimulating Factor Receptor β Chain (1995)

The binding of granulocyte-macrophage colony stimulating factor (GM-CSF) to its receptor stimulates JAK2 protein kinase activation, protein phosphorylation, and JAK2 association with the beta c chain of the GM-CSF receptor. To better understand how different domains of the JAK2 function to regulate association and phosphorylation of the beta c receptor, the minimal portion of the beta c receptor necessary for JAK2 binding has been determined. Using glutathione S-transferase (GST) fusion proteins expressing different portions of the membrane-proximal domain of the beta c chain, we demonstrate that JAK2 binds to amino acids 458-495, but showed little binding to fusion proteins containing amino acids 483-559, 483-530, or 458-484. The GST-beta c 458-495 bound equally well to the wild type (WT) JAK2, a carboxyl-terminal deletion of JAK2 removing the protein kinase domain (amino acids 1000-1129), and a deletion of the kinase-like domain (amino acids 523-746). However, an amino-terminal JAK2 deletion (amino acids 2-239) markedly reduced binding to this GST-beta c. Far Western blotting demonstrated that a GST fusion protein containing amino acids 1-294 of JAK2, but not fusion proteins containing amino acids 295-522, 523-746, or 747-1127, bound GST-beta c 458-559. When the JAK2 WT and deletions were transiently expressed along with the alpha and beta c subunits of the GM-CSF receptor and the cells were treated with GM-CSF, the following results were obtained: 1) WT JAK2 phosphorylated the beta c subunit in a GM-CSF-dependent manner, 2) the kinase-like domain deletion phosphorylated the beta c subunit, and 3) both the kinase domain deletion and the amino-terminal deletion failed to stimulate phosphorylation of the beta c subunit. Therefore, phosphorylation of the beta c subunit requires the binding of JAK2 through its amino terminus.
Controlled Release of Fertilizer Minerals by Incapsulating Membranes: I. Factors Influencing the Rate of Release (1962)

Abstract The availability of nutrients from inorganic fertilizer salts can be regulated through coating such materials. The release rate was investigated in several elution and leaching experiments. The release approached linearity for a considerable period; thereafter the rate dropped off. The release rate was largely independent of the pH of the elutant and of the soil pH. An increase in temperature from 10° to 20°C. almost doubled the initial release rate. The release could be regulated very efficiently through the coating thickness. There was an effect of ionic species, nitrate and ammonia being given off more rapidly than potassium or phosphates. The release was only slightly reduced under sterile conditions. It was concluded that diffusion is the most likely release mechanism and proposed that discrepancies such as the high Q 10 value could be explained through possible changes in membrane properties. Coated fertilizers thus possess the properties required for regulation of the availability of nutrients: they may reduce leaching losses and provide a steady prolonged nutrient supply to plants.
Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors (2011)

Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.
Chianti: a change impact analysis tool for Java programs (2005)

Chianti is a change impact analysis tool for Java that is implemented in the context of the eclipse environment. Chianti analyzes two versions of a Java program, decomposes their difference into a set of atomic changes, and a partial order inter-dependences of these changes is calculated. Change impact is then reported in terms of affected (regression or unit) tests whose execution behavior may have been modified by the applied changes. For each affected test, Chianti also determines a set of affecting changes that were responsible for the test's modified behavior. This latter step of isolating failure inducing changes for one specific test from irrelevant changes can be used as a debugging technique in situations where a test fails unexpectedly after a long editing session.
DC-Voltage-Induced Thermal Shift of Bias Point in&lt;tex&gt;$hboxLiNbO_3$&lt;/tex&gt;Optical Modulators (2004)

Increasing thermal shift of a bias point is observed when dc voltage is applied to z-cut LiNbO/sub 3/ (LN) modulators having asymmetric design; whereas, stable thermal shift is observed in symmetric x-cut LN modulators. A growth of the thermal shift depends upon the amplitude, polarity, and duration of the applied voltage and constitutes a new criterion to reliability modeling of LN modulators.
Arginine infusion in patients with septic shock increases nitric oxide production without haemodynamic instability (2014)

Arginine deficiency in sepsis may impair nitric oxide (NO) production for local perfusion and add to the catabolic state. In contrast, excessive NO production has been related to global haemodynamic instability. Therefore, the aim of the present study was to investigate the dose-response effect of intravenous arginine supplementation in post-absorptive patients with septic shock on arginine-NO and protein metabolism and on global and regional haemodynamics. Eight critically ill patients with a diagnosis of septic shock participated in this short-term (8 h) dose-response study. L-Arginine-HCl was continuously infused [intravenously (IV)] in three stepwise-increasing doses (33, 66 and 99 μmol·kg-1·h-1). Whole-body arginine-NO and protein metabolism were measured using stable isotope techniques, and baseline values were compared with healthy controls. Global and regional haemodynamic parameters were continuously recorded during the study. Upon infusion, plasma arginine increased from 48±7 to 189±23 μmol·l-1 (means±S.D.; P<0.0001). This coincided with increased de novo arginine (P<0.0001) and increased NO production (P<0.05). Sepsis patients demonstrated elevated protein breakdown at baseline (P<0.001 compared with healthy controls), whereas protein breakdown and synthesis both decreased during arginine infusion (P<0.0001). Mean arterial and pulmonary pressure and gastric mucosal-arterial partial pressure of carbon dioxide difference (Pr-aCO2) gap did not alter during arginine infusion (P>0.05), whereas stroke volume (SV) increased (P<0.05) and arterial lactate decreased (P<0.05). In conclusion, a 4-fold increase in plasma arginine with intravenous arginine infusion in sepsis stimulates de novo arginine and NO production and reduces whole-body protein breakdown. These potential beneficial metabolic effects occurred without negative alterations in haemodynamic parameters, although improvement in regional perfusion could not be demonstrated in the eight patients with septic shock who were studied.
<i>pnp</i> resonant tunneling light emitting transistor (1992)

A pnp bipolar resonant tunneling transistor is realized using a base consisting of an n-type modulation doped quantum-well layer next to a double-barrier tunneling structure. Electrons are injected from the quantum-well base layer into the tunneling structure, leading to quantum-well light emission when they recombine with holes from the emitter. This optical output, which is modulated by the base voltage, persists in the negative differential resistance region of the current-voltage characteristics where the hole current is in oscillation. This opens possibilities for using this transistor as a high frequency electro-optical heterodyne convertor.