gebhart/patrepeval huggingface dataset:
Differing roles for zinc fingers in DNA recognition: Structure of a six-finger transcription factor IIIA complex (1998)

The crystal structure of the six NH2-terminal zinc fingers of Xenopus laevis transcription factor IIIA (TFIIIA) bound with 31 bp of the 5S rRNA gene promoter has been determined at 3.1 A resolution. Individual zinc fingers are positioned differently in the major groove and across the minor groove of DNA to span the entire length of the duplex. These results show how TFIIIA can recognize several separated DNA sequences by using fewer fingers than necessary for continuous winding in the major groove.
RHD Genotyping from Maternal Plasma: Guidelines and Technical Challenges (2008)

Rhesus D (RhD) blood group incompatibility between mother and fetus can occasionally result in maternal alloimmunization where the resultant anti-D can cross the placenta and attack the fetal red cells, which in worse case scenarios can cause fetal anemia and ultimately death. Fetal RHD genotyping was introduced in the mid-1990s after the molecular characterization of the RH genes as an aid to the clinical management of these cases. Initially, these tests used fetal DNA extracted invasively from chorionic villus and amniocyte samples. RHD genotyping of fetuses carried by RhD-negative women has become the first large-scale application of noninvasive prenatal diagnosis (NIPD). Initially the real-time polymerase chain reaction (PCR)-based tests were devised to characterize free fetal DNA in maternal plasma and serum, and RHD genotyping was a convenient assay to develop this exciting new technology, because the accuracy of tests could easily be confirmed after the simple RhD phenotyping of fetal cord blood cells after birth. "First generation" RHD genotyping tests were based on the incorrect concept that all D-negative phenotypes were caused by a complete RHD gene deletion. Thus, it was a relatively simple task to develop diagnostic PCR strategies based on the detection of RHD where D-negative genomes will completely lack RHD. Subsequent research into the molecular basis of D-negative phenotypes revealed that a significant number of D-negative genomes possess fragments of, or mutated RHD genes, the most notable of which is the RHD pseudogene found in Africans. Thus, more comprehensive RHD genotyping tests have evolved to differentiate these alleles, and are more appropriate in the diagnosis of multi-ethnic population groups such as those found in Europe and North America. Many European Union countries have suggested the mass application of RHD NIPD for all fetuses carried by D-negative women. This is of clear benefit, because most RhD prophylaxis programs have switched to antenatal administration. This will help conserve anti-D stocks and it will prevent unnecessary administration of a human-derived blood product to a vulnerable patient group. Although anti-D stocks are inherently safe, there is a moral obligation to eliminate unnecessary administration of it because there have been instances of hepatitis C infection due to contamination. Furthermore, as yet undescribed viruses may be contaminants of blood products. Mass-scale RHD NIPD will shortly be implemented in several countries in the European Community as a consequence.
Proteasome-Mediated Degradation of the Papillomavirus E2-TA Protein Is Regulated by Phosphorylation and Can Modulate Viral Genome Copy Number (2000)

The bovine papillomavirus E2 proteins regulate viral transcription, replication, and episomal genome maintenance. We have previously mapped the major phosphorylation sites of the E2 proteins to serine residues 298 and 301 and shown that mutation of serine residue 301 to alanine leads to a dramatic (10- to 20-fold) increase in viral DNA copy number. In this study we analyzed how phosphorylation regulates E2 protein function. S301 is located in a PEST sequence; these sequences are often found in proteins with a short half-life and can be regulated by phosphorylation. We show here that the E2 protein is ubiquitinated and degraded by the proteasome. Mutation of serine 301 to alanine increases the half-life of E2 from approximately 50 min to 160 min. Furthermore, the A301 E2 protein shows greatly reduced ubiquitination and degradation by the proteasome. These results suggest that the E2 protein level is regulated by phosphorylation, which in turn determines viral episomal copy number.
Atrial remodeling in atrial fibrillation and association between microRNA network and atrial fibrillation (2011)

Atrial fibrillation (AF) remains one of the leading causes of morbidity and mortality in the world which are related to palpitations, fainting, congestive heart failure or stroke. The mechanism for atrial fibrillation has been identified as electrical remodeling, structure remodeling and intracellular calcium handling remodeling. microRNAs (miRNAs) have recently emerged as one of the important factors in regulating gene expression. So far, thousands of miRNA genes have been found in diverse animals with the function of regulating cell death, cell proliferation, haematopoiesis and even participate in the processing of cardiovascular disease. In this review, we summarize the mechanism of AF and the association of microRNAs network with AF. We provide a potential perspective of miRNAs as the therapeutic target for AF.
Determinants of membrane protein topology. (1987)

The topology of the integral membrane protein MalF, which is required for maltose transport in Escherichia coli, has been analyzed using fusions of alkaline phosphatase (EC 3.1.3.1). The properties of such fusion strains support a MalF structure previously proposed on theoretical grounds. Several transmembrane segments within MalF can act as signal sequences in exporting alkaline phosphatase. Other transmembrane sequences, in conjunction with cytoplasmic domains, can stably anchor alkaline phosphatase in the cytoplasm. Our results suggest that features of the amino acid sequence (possibly the positively charged amino acids) of the cytoplasmic domains of membrane proteins are important in anchoring these domains in the cytoplasm. These studies in conjunction with our earlier results show that alkaline phosphatase fusions to membrane proteins can be an important aid in analyzing membrane topology and its determinants.
Duplicated copies of the bovine JH locus contribute to the Ig repertoire (2004)

We report the cloning and analysis of a bovine JH locus comprising a DQ52 segment, six JH segments and sequence to a 5' H chain intronic enhancer. The contig was mapped to BTA 11 and evidence was found for rearrangement of the sixth JH segment at a low but detectable frequency. In contrast, the fourth segment present at a second copy of the bovine JH locus mapping to BTA 21 was found to rearrange at high-frequency, forming FR4 in the majority of bovine Ig H chains. The data thus show that bovine H chains can be generated from segments at two distinct genomic locations. Further investigation should establish if rearrangement takes place at each locus or if the participating segments are brought together from different chromosomal locations by less conventional processes (for example by gene conversion or trans-chromosomal rearrangement).
Production of Retroviral Constructs for Effective Transfer and Expression of T-cell Receptor Genes using Golden Gate Cloning (2015)

Here we present an improved strategy for producing T-cell receptor (TCR)-expressing retroviral vectors using a Golden Gate cloning strategy. This method takes advantage of the modular nature of TCR genes by directly amplifying TCR α and β variable regions from RNA or cDNA, then cloning and fusing them with their respective constant region genes resident in a retroviral TCR expression vector. Our one-step approach greatly streamlines the TCR vector production process in comparison to the traditional three-step procedure that typically involves cloning whole TCR genes, producing a TCR expression cassette, and constructing a retroviral construct. To date, we have generated TCR vectors that transferred seven functional human/rhesus macaque TCRs into primary T cells. The approach also holds promise for the assembly of other genes with defined variable regions, such as immunoglobulins.
Genetic Basis of Developmental Malformations of the Cerebral Cortex (2004)

Widespread use of noninvasive brain imaging techniques, in particular magnetic resonance imaging, has led to increased recognition of genetic disorders of cortical development in recent years. The causative genes for many of these disorders have been identified through a combination of detailed clinical and radiological analyses and molecular genetic approaches. These disease genes have been found to affect different steps of cortical development, including proliferation of neuronal progenitor cells, neuronal migration, and maintaining integrity of the pial surface. In many cases, syndromes with similar clinical phenotypes are caused by genes with related biochemical functions. In this article, we review the recent advances in molecular genetic studies of the disorders of cortical development. The identification and functional studies of the genes associated with these developmental disorders will likely lead to improvement in diagnosis and facilitate our understanding of the mechanisms of cortical development.
PERHEXILINE MALEATE IN THE TREATMENT OF SEVERE ANGINA PECTORIS (1979)

Perhexiline maleate was used as a prophylactic agent in 26 patients suffering from severe angina pectoris. The mean duration of treatment was 8.9 months, with a maximum of 28 months. Fifteen patients experienced a reduction in frequency of attacks to less than one-third of their previous level; six experienced a reduction to two-thirds of their previous level; no patient showed an increase in attack rates. During the period of study, there was one death. Frequently observed side effects included dizziness, gastrointestinal irritation and malaise. One patient developed clinically apparent hepatic dysfunction which resolved on withdrawal of perhexiline maleate, but recurred after rechallenge with a lower dose of the drug; the results of liver function tests in five others showed mild abnormalities. One patient developed peripheral neuropathy after taking perhexiline maleate for 18 months, but this resolved in two months after cessation of therapy. Good responses to perhexiline maleate were observed in patients who were concurrently treated with beta-adrenoreceptor blocking drugs.
Susceptibility of different leukocyte cell types to Vaccinia virus infection (2004)

When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.
Comparison of various methods and reagents for species identification of Staphylococcus aureus positive or negative for the mecA gene (1993)

The reliability of various methods for species identification of Staphylococcus aureus was evaluated. A total of 135 coagulase-positive (SA) or -negative (SS) staphylococcal isolates were tested, including methicillin-resistant (MR) and -susceptible (MS) strains. When the nuc gene which encodes the S. aureus thermonuclease (TNase) was amplified in a multiplex PCR simultaneously with the mecA gene which encodes for the MR-associated penicillin-binding protein 2a of staphylococci, the nuc amplification showed full agreement with the results of the coagulase test. TNase detected by an enzymatic method or as protein in a sandwich ELISA identified S. aureus with nearly the same precision as the PCR. The Staphylase, Monostaph and Staphaurex agglutination kits were all reliable for identification of MSSA, but not for MRSA. Most of the negative MRSA strains were identified by the Pastorex agglutination kit, in which reagents for fibrinogen receptor and protein A detection have been supplemented with antibodies for capsular polysaccharides of the serotypes 5 and 8. These results show that detection of the nuc gene or its TNase product is highly reliable for identification of both MRSA and MSSA strains, while various widely used agglutination kits do not show the same reliability for identification of MRSA strains.
BRCA1-Associated Protein 1 Interferes with BRCA1/BARD1 RING Heterodimer Activity (2008)

The breast and ovarian tumor suppressor BRCA1 constitutes a RING heterodimer E3 ligase with BARD1. BRCA1-associated protein 1 (BAP1) is a ubiquitin COOH-terminal hydrolase that was initially identified as a protein that bound to the RING finger domain of BRCA1. However, how BAP1 contributes to the E3 activity of BRCA1/BARD1 is unclear. Here, we report that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of BRCA1/BARD1. Domains comprised by residues 182-365 of BAP1 interact with the RING finger domain of BARD1, and surface plasmon resonance spectroscopy (BIAcore) analyses showed that BAP1 interferes with the BRCA1/BARD1 association. The perturbation resulted in inhibition of BRCA1 autoubiquitination and NPM1/B23 ubiquitination by BRCA1/BARD1. Although BAP1 was capable of deubiquitinating the polyubiquitin chains mediated by BRCA1/BARD1 in vitro, a catalytically inactive mutant of BAP1, C91S, still inhibited the ubiquitination in vitro and in vivo, implicating a second mechanism of action. Importantly, inhibition of BAP1 expression by short hairpin RNA resulted in hypersensitivity of the cells to ionizing irradiation and in retardation of S-phase progression. Together, these results suggest that BAP1 and BRCA1/BARD1 coordinately regulate ubiquitination during the DNA damage response and the cell cycle.
A Larynx Area in the Human Motor Cortex (2007)

The map of the human motor cortex has lacked a representation for the intrinsic musculature of the larynx ever since the electrical stimulation studies of Penfield. In addition, there has been no attempt to localize this area using neuroimaging techniques. Because of the central importance of laryngeal function to vocalization, we sought to localize an area controlling the intrinsic muscles of the larynx by using functional magnetic resonance imaging and to place this area in a somatotopic context. We had subjects perform a series of oral tasks designed to isolate elementary components of phonation and articulation, including vocalization of a vowel, lip movement, and tongue movement. In addition, and for the first time in a neuroimaging study, we had subjects perform "glottal stops," in other words forced closure of the glottis in the absence of vocalizing. The results demonstrated a larynx-specific area in the motor cortex that is activated comparably by vocal and nonvocal laryngeal tasks. Converging evidence suggests that this area is the principal vocal center of the human motor cortex. Finally, the location of this larynx area is strikingly different from that reported in the monkey. We discuss the implications of this observation for the evolution of vocal communication in humans.
Automated Instrumentation for Comprehensive Isotachophoresis−Capillary Zone Electrophoresis (2000)

An automated comprehensive isotachophoresis-capillary zone electrophoresis (ITP-CZE) system is described. The sample is focused in the first capillary by ITP and injected repeatedly into the second smaller diameter capillary for more rapid CZE separation. Since only small portions of the concentrated zones are sequentially injected for CZE separation, overloading was not observed. Moreover, the sensitivity is enhanced because all of the concentrated zones are analyzed and the results are summed. A single detector (only for the CZE dimension) is required, and accurate timing for CZE injection is not necessary. The system was evaluated using a mixture of angiotensins. The effect of addition of leading electrolyte at the junction of the ITP and CZE capillaries before each CZE run on comprehensive ITP-CZE peak area was studied, and leading electrolyte volumes between 7 and 11 microL led to the best sensitivity. Under optimized conditions, a detection limit of approximately 5 nM could be achieved by injecting 10 microL of angiotensin solution.
Impact evaluation of staff learning in East Asia and Pacific, and South Asia regions (2003)

This phase I report summarizes three separate activities undertaken during FY03 and is structured in the following four sections. Chapter 2 begins with an overview of the World Bank staff learning programs, the context for the current evaluation and the study's scope and objectives. It then describes the evaluation methodology, including evaluation questions, approach and implementation. Terms and concepts used in this evaluation are also reviewed in this chapter. Drawing on HR training records, Chapter 3 presents a descriptive analysis of EAP and SAR regional staff learning participation over the past four years (FY99-02). Chapter 4 presents the result of a web-based staff survey focusing on individual learning experiences, motivations and perceptions, including perceived benefits of participating in the learning. The reasons for staff non-participation in learning and factors that may affect staff utilization of their knowledge and skills gained from learning are also examined in this chapter. Additionally, this chapter presents a summary of telephone interviews with regional managers, focusing on their perception of learning and the impact of learning on team performance and productivity. 1.5 The final chapter offers conclusions and recommendations that are drawn from the study findings.
First hospital outbreak of the globally emerging Candida auris in a European hospital (2016)

This ongoing outbreak with genotypically closely related <i>C. auris</i> highlights the importance of appropriate species identification and rapid detection of cases in order to contain hospital acquired transmission.
Progress is slow, but... (1993)

The objective of this study was to assess the major etiologic categories of epilepsy in a rural district of the Lao PDR. Thirty-one newly identified patients with confirmed active epilepsy were compared with 124 controls, matched for gender, age and village residence. Risk factors for epilepsy were investigated with particular focus on cysticercosis serology. A history of head trauma (OR=4.7, p=0.05), family history of epilepsy (OR=12.8, p=0.03), and the use of human feces to fertilize domestic vegetable gardens (OR=4.9, p=0.04) were significantly associated with epilepsy. The study did not confirm any direct relation between epilepsy and cysticercosis serology. The cysticercosis seroprevalence was nil in the epilepsy group. This is the first study in the Lao PDR on epilepsy risk factors representing important data for the subregion. Parasitic, environmental, and behavioral factors of this traditional population deserve further studies to explain the missing link between epilepsy and cysticercosis.
The Role of the CD28 Receptor During T Cell Responses to Antigen (1993)

The CD28 receptor is stimulated during the contact of T cells with antigen-presenting cells. A counter-receptor for CD28 is the B7 molecule expressed on activated B cells, dendritic cells, and macrophages. B7 also binds to CTLA-4, a receptor that is structurally related to CD28. CTLA-4 is expressed in low copy number by T cells only after activation, but it binds B7 with approximately 20-fold higher affinity than CD28. Inhibition of B7-CD28 interactions blocks immune responses in vitro and in vivo. Therefore, CD28 receptor stimulation is required for T cell responses to antigens and for B cell responses to T-dependent antigens. During T cell responses to antigens, CD28 receptor stimulation may be required to prevent clonal inactivation or anergy. CD28 receptor ligation induces tyrosine phosphorylation of specific substrates, including phospholipase C gamma 1, and triggers both calcium-dependent and calcium-independent signals. The CD28 costimulatory receptor represents a novel target for immunosuppressive drugs.
CRC-Aided Decoding of Polar Codes (2012)

CRC (cyclic redundancy check)-aided decoding schemes are proposed to improve the performance of polar codes. A unified description of successive cancellation decoding and its improved version with list or stack is provided and the CRC-aided successive cancellation list/stack (CA-SCL/SCS) decoding schemes are proposed. Simulation results in binary-input additive white Gaussian noise channel (BI-AWGNC) show that CA-SCL/SCS can provide significant gain of 0.5 dB over the turbo codes used in 3GPP standard with code rate 1/2 and code length 1024 at the block error probability (BLER) of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</sup> . Moreover, the time complexity of CA-SCS decoder is much lower than that of turbo decoder and can be close to that of successive cancellation (SC) decoder in the high SNR regime.
Activity of MM-398, Nanoliposomal Irinotecan (nal-IRI), in Ewing's Family Tumor Xenografts Is Associated with High Exposure of Tumor to Drug and High SLFN11 Expression (2015)

In pediatric solid tumor xenografts, nal-IRI demonstrated higher systemic and tumor exposures to SN-38 and improved antitumor activity compared with the current clinical formulation of irinotecan. Clinical studies of nal-IRI in pediatric solid tumors (especially EFT) and correlative studies to determine if SLFN11 expression can serve as a biomarker to predict nal-IRI clinical activity are warranted.
Angiogenesis-Independent Endothelial Protection of Liver: Role of VEGFR-1 (2003)

The vascular endothelium was once thought to function primarily in nutrient and oxygen delivery, but recent evidence suggests that it may play a broader role in tissue homeostasis. To explore the role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vascular endothelial growth factor (VEGF) receptor activation on mouse hepatocyte growth. Delivery of VEGF-A increased liver mass in mice but did not stimulate growth of hepatocytes in vitro, unless LSECs were also present in the culture. Hepatocyte growth factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte growth. Selective activation of VEGF receptor-1 (VEGFR-1) stimulated hepatocyte but not endothelial proliferation in vivo and reduced liver damage in mice exposed to a hepatotoxin. Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders.
Iron Deficiency Anemia, β-Thalassemia Minor, and Anemia of Chronic Disease (2008)

We observed increased numbers of an infrequently referenced poikilocyte, the prekeratocyte, in iron deficiency anemia (IDA) compared with beta-thalassemia minor and anemia of chronic disease (ACD) and, therefore, chose to quantify these cells and other morphologic features in these anemias. Prekeratocytes were observed in 31 (78%) of 40 IDAs vs 11 (37%) of 30 beta-thalassemias (P = .001) and 5 (13%) of 40 ACDs (P < .001) and averaged 0.78 per 1,000 RBCs in IDA vs 0.21 in beta-thalassemia (P < .001) and 0.075 in ACD (P < .001). Pencil cells also were more commonly seen and more numerous in IDAs than in beta-thalassemia or ACD. Target cells were present in most IDAs and thalassemia and in similar numbers. Basophilic stippling was seen in only 5 (17%) of the beta-thalassemias. Our results lend quantitative support to prekeratocytes and pencil cells as morphologic features favoring the diagnosis of IDA but fail to support the diagnostic usefulness of target cells and basophilic stippling in discriminating IDA and beta-thalassemia minor.