gebhart/patrepeval huggingface dataset:
Comprehensive analysis of the renal transcriptional response to acute uranyl nitrate exposure (2006)

We report a comprehensive description of the UN induced modifications in gene expression levels, including the identification of genes previously unrelated to ARF. The study of these genes and the metabolisms they control should improve our understanding of toxic ARF and enlighten on the molecular targets for potential therapeutic interventions.
Structure of Hepatitis E Virion-sized Particle Reveals an RNA-dependent Viral Assembly Pathway* (2010)

Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids.
Sustained Correction of X-Linked Severe Combined Immunodeficiency by ex Vivo Gene Therapy (2002)

Ex vivo gene therapy with gamma(c) can safely correct the immune deficiency of patients with X-linked severe combined immunodeficiency.
Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27 (2006)

The immune response to bacterial infections must be tightly controlled to guarantee pathogen elimination while preventing tissue damage by uncontrolled inflammation. Here, we demonstrate a key role of interleukin (IL)-27 in regulating this critical balance. IL-27 was rapidly induced during murine experimental peritonitis induced by cecal ligation and puncture (CLP). Furthermore, mice deficient for the EBI3 subunit of IL-27 were resistant to CLP-induced septic peritonitis as compared with wild-type controls, and this effect could be suppressed by injection of recombinant single-chain IL-27. EBI3-/- mice displayed significantly enhanced neutrophil migration and oxidative burst capacity during CLP, resulting in enhanced bacterial clearance and local control of infection. Subsequent studies demonstrated that IL-27 directly suppresses endotoxin-induced production of reactive oxygen intermediates by isolated primary granulocytes and macrophages. Finally, in vivo blockade of IL-27 function using a newly designed soluble IL-27 receptor fusion protein led to significantly increased survival after CLP as compared with control-treated mice. Collectively, these data identify IL-27 as a key negative regulator of innate immune cell function in septic peritonitis. Furthermore, in vivo blockade of IL-27 is a novel potential therapeutic target for treatment of sepsis.
&#x3B2;-Amyloid, Neuronal Death and Alzheimers Disease (2001)

Alzheimer's disease (AD) is a common neurodegenerative disease that affects cognitive function in the elderly. Large extracellular beta-amyloid (Abeta) plaques and tau-containing intraneuronal neurofibrillary tangles characterize AD from a histopathologic perspective. However, the severity of dementia in AD is more closely related to the degree of the associated neuronal and synaptic loss. It is not known how neurons die and synapses are lost in AD; the current review summarizes what is known about this issue. Most evidence indicates that amyloid precursor protein (APP) processing is central to the AD process. The Abeta in plaques is a metabolite of the APP that forms when an alternative (beta-secretase and then gamma-secretase) enzymatic pathway is utilized for processing. Mutations of the APP gene lead to AD by influencing APP metabolism. One leading theory is that the Abeta in plaques leads to AD because Abeta is directly toxic to the adjacent neurons. Other theories advance the notion that neuronal death is triggered by intracellular events that occur during APP processing or by extraneuronal preplaque Abeta oligomers. Some investigators speculate that in many cases there is a more general disorder of protein processing in neurons that leads to cell death. In the later models, Abeta plaques are a byproduct of the disease process, rather than the direct cause of neuronal death. A direct correlation between Abeta plaque burden and neuronal (or synaptic) loss should occur in AD if Abeta plaques cause AD through a direct toxic effect. However, histopathologic studies indicate that the correlation between Abeta plaque burden and neuronal (or synaptic) loss is poor. We conclude that APP processing and Abeta formation is important to the AD process, but that neuronal alterations that underlie symptoms of AD are not due exclusively to a direct toxic effect of the Abeta deposits that occur in plaques. A more general problem with protein processing, damage due to the neuron from accumulation of intraneuronal Abeta or extracellular, preplaque Abeta may also be important as underlying factors in the dementia of AD.
Solid-to-Liquid Feeding: The Inside(s) Story of Extra-Oral Digestion in Predaceous Arthropoda (1998)

The study of extra-oral digestion is of general interest because it helps explain the success of over 80% of the predaceous families of the phylum Arthropoda (Cohen 1995), the phylum whose members comprise over three-quarters of the known animal species (Wilson 1992). Extra-oral digestion especially is interesting because it involves the integration of several levels of biological organization—biochemical, physiological, morphological, and behavioral adaptations—all within an ecological and evolutionary context. It also is fascinating because it is so alien to our way of eating that it challenges our world-view about what most of us feel is a mundane process.
Photo-Addressed Liquid Crystal SLM with Twisted Nematic ECB (TN-ECB) Mode (1990)

A novel photo-addressed LC-SLM featuring TN-ECB (twisted nematic electrically controlled birefringence) is presented. The LC-SLM consists of an a-Si photoconductor, a dielectric mirror and a TN-ECB liquid crystal layer. TN-ECB is a kind of ECB mode which has been developed by simulating light propagation in a reflective twisted nematic configuration. The features of the LC-SLM are 25 lp/mm resolution, high-speed response of less than 10 ms, and a single polarizer system. The resolution limitation by the dielectric mirror is also discussed.
Effects of target binding kinetics onin vivodrug efficacy: koff, konand rebinding (2016)

Most strikingly, the simulations show that, when rebinding is also taken into account, increasing kon may produce closely the same outcome as decreasing koff when dosing is performed in accordance with the therapeutically most relevant constant [Lmax ]/KD ratio paradigm. Also, under certain conditions, rebinding may produce closely the same outcome as invoking slow diffusion of the drug between the plasma compartment and a target-containing 'effect' compartment. Although the present simulations should only be regarded as a 'proof of principle', these findings may help pharmacologists and medicinal chemists to devise ex vivo and in vitro binding kinetic assays that are more relevant and translatable to in vivo settings.
[Method for ECG classification based on the neural network]. (2008)

The article adopts the BP neural network and probability neural network in classifying four arrhythmias (LBBB, RBBB, Paced Beat, Ventricular Escape Beat) and one normal beat, and their test results of the automatic classification and imitation study are 97.62% and 95.88%, showing an improved efficient classification.
Islet Transplants Face Test of Time (2004)

DIABETESWill the Edmonton protocol, hailed as a possible cure for type I diabetes, hold up in the long run?
An integration-defective U5 deletion mutant of human immunodeficiency virus type 1 reverts by eliminating additional long terminal repeat sequences (1994)

Nonoverlapping deletions that eliminated the 5' (HIV-1US/603del), middle (HIV-1U5/206del), and 3' (HIV-1U5/604del) thirds of the U5 region of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) were studied for their effects on virus replication (transient transfection of HeLa cells) and infectivity (T-cell lines and peripheral blood mononuclear cells). All three mutants exhibited a wild-type phenotype in directing the production and release of virus particles from transfected HeLa cells. In infectivity assays, HIV-1U5/206del was usually indistinguishable from wild-type virus whereas HIV-1U%/603del was unable to infect human peripheral blood mononuclear cells or MT4 and CEM cells. Investigations of HIV-1U5/603del particles revealed a packaging defect resulting in a 10-fold reduction of encapsidated genomic RNA. The HIV-1U5/604del mutant either was noninfectious or exhibited delayed infection kinetics, depending on the cell type and multiplicity of infection. Quantitative competitive PCR indicated that HIV-1U5/604del synthesized normal amounts of viral DNA in newly infected cells. During the course of a long-term infectivity assay, a revertant of the HIV-1U5/604del mutant that displayed rapid infection kinetics emerged. Nucleotide sequence analysis indicated that the original 26-nucleotide deletion present in HIV-1U5/604del had been extended an additional 19 nucleotides in the revertant virus. Characterization of the HIV-1U5/604del mutant LTR in in vitro integration reactions revealed defective 3' processing and strand transfer activities that were partially restored when the revertant LTR substrate was used, suggesting that the reversion corrected a similar defect in the mutant virus.
Molecular Cloning and Characterization Of β‐1,4‐Galactosyltransferase Expressed in Mouse Testis (1997)

Using an affinity-purified antibody against beta-1,4-galactosyltransferase purified from F9 embryonal carcinoma cells, we screened a lambda gt11 expression library constructed from the same cell line. The cDNA clone obtained encoded a 46-kDa protein. Among adult mouse organs, the testis was found to express large amounts of the corresponding mRNA. An antibody against the 46-kDa protein was raised in a rabbit by immunization with a maltose-binding-protein fusion protein produced in Escherichia coli. The affinity-purified antibody against the cloned 46-kDa protein reacted with a 59-kDa protein in sperm extract on western blotting. Among the proteins in the F9 beta-1,4-galactosyltransferase preparation, which were mostly 68-kDa and 59-kDa species, 59-kDa and 50-kDa bands reacted with the antibody against the cloned 46-kDa protein. The cloned 46-kDa protein had type-II transmembrane topology and some blocks of sequence similarity with the known beta-1,4-galactosyltransferase. Furthermore, predicted secondary structures were similar over large portions of the two proteins. The histidine-tagged 46-kDa protein produced in E. coli was partially adsorbed onto a N-acetylglucosamine-Affi-Gel column and eluted by 20 mM N-acetylglucosamine. The histidine-tagged 46-kDa protein, which was purified to homogeneity, had a small, but significant amount of beta-1,4-galactosyltransferase activity. These results strongly suggest that the 46-kDa protein is a beta-1,4-galactosyltransferase.
Elevated expression of eukaryotic translation initiation factor 4E is associated with proliferation, invasion and acquired resistance to erlotinib in lung cancer (2012)

Eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting factor for cap-dependent translation initiation, which is known to regulate oncogenesis. Elevated eIF4E and its negative impact on prognosis in human non-small cell lung cancer (NSCLC) have been reported previously. However, its potential as a therapeutic target and role in regulation of sensitivity to EGFR inhibitors is an area of ongoing investigations. In this study, we detected increased levels of eIF4E in 16 human NSCLC cell lines compared with their normal bronchial epithelial cells. Consistently, human tissue array analysis showed that eIF4E expression was significantly higher in human NSCLC tissues than normal tissues. Inhibition of eIF4E using eIF4E siRNA inhibited the growth and invasion of NSCLC cells. These data suggest that eIF4E overexpression plays a crucial role in positive regulation of the growth and invasion of NSCLC cells. By proteomics, we found that eIF4E levels were elevated in erlotinib-resistant cell lines compared with the sensitive parental cell line. In agreement, assembly of the eIF4F cap complex and several oncogenic proteins regulated by the cap-dependent translation mechanism, were also increased in erlotinib-resistant cells. Thus, erlotinib-resistant cells exhibit elevated eIF4E expression and cap-dependent translation. Inhibition of eIF4F with different means (e.g., gene knockdown) downregulated c-Met expression and partially restored cell sensitivity to erlotinib, suggesting that elevated eIF4E contributes to development of erlotinib resistance, likely through positive regulation of c-Met expression. Taken together, we suggest that elevated eIF4E in NSCLC cells is associated with proliferation, invasion and acquired erlotinib resistance.
Phenotypic and functional analysis of CD4+ NKRP1A+ human T lymphocytes. Direct evidence that the NKRP1A molecule is involved in transendothelial migration (1997)

In this report, we show that among human CD4+ T lymphocytes 5-20% express the C-type lectin molecule NKRP1A. This lymphocyte subset displays a slightly more limited T cell receptor V beta repertoire than the CD4+ NKRP1A- counterpart. CD4+ NKRP1A+ T lymphocytes are characterized by a high expression of beta 1 and beta 2 integrins, thus representing a T lymphocyte subset that can possibly adhere and migrate through vascular endothelium. Indeed, resting CD4+ NKRP1A+ lymphocytes, differently from the CD4+ NKRP1A- subset, migrated across endothelial cell monolayers in a Transwell chamber system. Pretreatment of CD4+ NKRP1A+ T lymphocytes with an anti-NKRP1A monoclonal antibody (mAb) strongly reduced transendothelial migration, suggesting the involvement of the NKRP1A molecule in the transmigration process. Furthermore, cells of the NKRP1A- Jurkat CD4+ T cell line stably transfected with NKRP1A cDNA migrated more rapidly and efficiently than either untransfected or mock-transfected Jurkat cells. Finally, mAb-mediated cross-linking of NKRP1A molecules in CD4+ T lymphocytes induced the up-regulation of the lymphocyte function-associated antigen 1 Mg(2+)-binding site as well as beta 1 and beta 2 integrin chains. Altogether, these findings suggest that the NKRP1A molecule is involved in transendothelial migration of resting CD4+ T lymphocytes.
Pfam: A comprehensive database of protein domain families based on seed alignments (1997)

Databases of multiple sequence alignments are a valuable aid to protein sequence classification and analysis. One of the main challenges when constructing such a database is to simultaneously satisfy the conflicting demands of completeness on the one hand and quality of alignment and domain definitions on the other. The latter properties are best dealt with by manual approaches, whereas completeness in practice is only amenable to automatic methods. Herein we present a database based on hidden Markov model profiles (HMMs), which combines high quality and completeness. Our database, Pfam, consists of parts A and B. Pfam-A is curated and contains well-characterized protein domain families with high quality alignments, which are maintained by using manually checked seed alignments and HMMs to find and align all members. Pfam-B contains sequence families that were generated automatically by applying the Domainer algorithm to cluster and align the remaining protein sequences after removal of Pfam-A domains. By using Pfam, a large number of previously unannotated proteins from the Caenorhabditis elegans genome project were classified. We have also identified many novel family memberships in known proteins, including new kazal, Fibronectin type III, and response regulator receiver domains. Pfam-A families have permanent accession numbers and form a library of HMMs available for searching and automatic annotation of new protein sequences.
A 3D simultaneous source field test processed using alternating projections: a new active separation method (2012)

ABSTRACT In 2008, a wide azimuth simultaneous source (SimSrc) 3D data set was acquired over an area coinciding with an existing conventional wide azimuth survey. Using two (nearly) simultaneous sources provided twice the number of shots, an increased shot density and twice the fold for essentially the same acquisition time. Although the improved sampling for the SimSrc data was predicted to yield improvements in processes such as 3D multiple attenuation and migration, cross‐talk between the sources was a concern. Cross‐talk can be suppressed by known techniques such as separation algorithms that estimate the individual shots and thereby separate SimSrc records into their constituent shots. However, separation algorithms available at the time suffered from aliasing and were not effective for severely shot‐aliased data such as those encountered in the experimental data set, which had a 75‐m in‐line shot spacing, half that typical for wide azimuth geometries. In this paper we present a new separation technique called the Alternating Projection Method (APM), which is demonstrated to be robust in the presence of aliasing. Through comparisons with conventional wide azimuth data we show that 3D multiple removal and migration are both aided by the increase in shots. Moreover, the high quality of the APM separated data indicates that prestack products such as migration angle gathers will have better quality than was achieved a few years ago using a passive separation approach. We found that by carefully selecting and tailoring the method's projection operators, excellent separation results can be achieved efficiently.
Cloning and sequencing of a gene coding for an extracellular dextransucrase (DSRB) fromLeuconostoc mesenteroidesNRRL B-1299 synthesizing only a Î±(1â6) glucan (1998)

The coding region for a novel Leuconostoc mesenteroides NRRL B-1299 dextransucrase gene (dsrB) was isolated and sequenced. Using degenerate primers homologous to a conserved region present in dextransucrases from Streptococcus (GTFs) and L. mesenteroides NRRL B-512F (DSRS) and conserved amino acid sequences located in the N-terminal catalytic region of these enzymes, about 60% of the DSRB encoding gene was isolated. Two sites, BamHI and HindIII, were identified which allowed one 0.5-kbp probe to be obtained to isolate the 5' and the 3' ends of dsrB. The nucleotide sequence of the dsrB gene was determined and found to consist of an open reading frame (ORF) of 4521 base pairs (bp) coding for a 1507-amino acid protein with an M1 of 168,511. The amino acid sequence is very close to that of DSRS. Like DSRS, the dextran produced appeared to be composed of only alpha (1-6) glucosidic bonds, and the oligosaccharides synthesized in the presence of acceptor maltose were also composed of alpha (1-6) linked glucosyl residues in addition to the maltosyl residue. DSRB thus appears to be a novel dextransucrase from L. mesenteroides NRRL B-1299. DSRB produces a dextran different from the typical dextran containing alpha (1-6) and alpha (1-2) linkages produced when this strain is grown in the presence of sucrose.
A simple method for directional transcriptome sequencing using Illumina technology (2009)

High-throughput sequencing of cDNA has been used to study eukaryotic transcription on a genome-wide scale to single base pair resolution. In order to compensate for the high ribonuclease activity in bacterial cells, we have devised an equivalent technique optimized for studying complete prokaryotic transcriptomes that minimizes the manipulation of the RNA sample. This new approach uses Illumina technology to sequence single-stranded (ss) cDNA, generating information on both the direction and level of transcription throughout the genome. The protocol, and associated data analysis programs, are freely available from http://www.sanger.ac.uk/Projects/Pathogens/Transcriptome/. We have successfully applied this method to the bacterial pathogens Salmonella bongori and Streptococcus pneumoniae and the yeast Schizosaccharomyces pombe. This method enables experimental validation of genetic features predicted in silico and allows the easy identification of novel transcripts throughout the genome. We also show that there is a high correlation between the level of gene expression calculated from ss-cDNA and double-stranded-cDNA sequencing, indicting that ss-cDNA sequencing is both robust and appropriate for use in quantitative studies of transcription. Hence, this simple method should prove a useful tool in aiding genome annotation and gene expression studies in both prokaryotes and eukaryotes.
A cytogeneticist's perspective on genomic microarrays (2004)

The identification of cytogenetic imbalance is an important component of clinical genetics. About 1 in 154 newborns has a chromosome abnormality. Conventional cytogenetic analysis has enabled the identification of microscopic alterations of the chromosomes. The development of fluorescence in situ hybridization (FISH) and other molecular methodologies has made possible the identification of submicroscopic aberrations. An additional development was comparative genomic hybridization (CGH), a method that directly compares two genomes for DNA copy differences. As first developed, the substrate for CGH analysis is normal metaphase chromosomes. Recently, CGH has been applied to microarrays (array CGH) constructed from large insert clones to identify chromosome imbalance. Array CGH has many advantages over conventional cytogenetic and molecular cytogenetic techniques. Array CGH can be comprehensive (genome-wide), high resolution, amenable to automation, rapid, and sensitive. We anticipate that array CGH will be employed in the clinical cytogenetics laboratory in the near future and will lead to the identification of the chromosomal basis of new syndromes and existing genetic conditions.
Atrial fibrillation in heart failure: what should we do? (2015)

Heart failure (HF) and atrial fibrillation (AF) are two conditions that are likely to dominate the next 50 years of cardiovascular (CV) care. Both are increasingly prevalent and associated with high morbidity, mortality, and healthcare cost. They are closely inter-related with similar risk factors and shared pathophysiology. Patients with concomitant HF and AF suffer from even worse symptoms and poorer prognosis, yet evidence-based evaluation and management of this group of patients is lacking. In this review, we evaluate the common mechanisms for the development of AF in HF patients and vice versa, focusing on the evidence for potential treatment strategies. Recent data have suggested that these patients may respond differently than those with HF or AF alone. These results highlight the clear clinical need to identify and treat according to best evidence, in order to prevent adverse outcomes and reduce the huge burden that HF and AF are expected to have on global healthcare systems in the future. We propose an easy-to-use clinical mnemonic to aid the initial management of newly discovered concomitant HF and AF, the CAN-TREAT HFrEF + AF algorithm (Cardioversion if compromised; Anticoagulation unless contraindication; Normalize fluid balance; Target initial heart rate <110 b.p.m.; Renin-angiotensin-aldosterone modification; Early consideration of rhythm control; Advanced HF therapies; Treatment of other CV disease).
Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria (2005)

Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.