gebhart/patrepeval huggingface dataset:
Exclusive and Persistent Use of the Entry Coreceptor CXCR4 by Human Immunodeficiency Virus Type 1 from a Subject Homozygous for CCR5 Δ32 (1998)

Individuals who are homozygous for the 32-bp deletion in the gene coding for the chemokine receptor and major human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 (CCR5 -/-) lack functional cell surface CCR5 molecules and are relatively resistant to HIV-1 infection. HIV-1 infection in CCR5 -/- individuals, although rare, has been increasingly documented. We now report that the viral quasispecies from one such individual throughout disease is homogenous, T cell line tropic, and phenotypically syncytium inducing (SI); exclusively uses CXCR4; and replicates well in CCR5 -/- primary T cells. The recently discovered coreceptors BOB and Bonzo are not used. Although early and persistent SI variants have been described in longitudinal studies, this is the first demonstration of exclusive and persistent CXCR4 usage. With the caveat that the earliest viruses available from this subject were from approximately 4 years following primary infection, these data suggest that HIV-1 infection can be mediated and persistently maintained by viruses which exclusively utilize CXCR4. The lack of evolution toward the available minor coreceptors in this subject underscores the dominant biological roles of the major coreceptors CCR5 and CXCR4. This and two similar subjects (R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, and T. Liang, Nat. Med. 3:252-253, 1997; I. Theodoreu, L. Meyer, M. Magierowska, C. Katlama, and C. Rouzioux, Lancet 349:1219-1220, 1997) showed relatively rapid CD4+ T-cell declines despite average or low initial viral RNA load. Since viruses which use CXCR4 exclusively cannot infect macrophages, these data have implications for the relative infection of the T-cell compartment versus the macrophage compartment in vivo and for the development of CCR5-based therapeutics.
Bevölkerungsbezogene Verteilungswerte ausgewählter Laborparameter aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS) (2009)

Der GBE-Beitrag legt die in der KiGGS-Studie beobachteten Perzentil-Verteilungen für wesentliche Laborparameter vor. Mit den Daten steht ein Stichprobenumfang von mehr als 14.000 Blut- und Serumproben zur Verfügung, um die alters- und geschlechtsspezifischen Verläufe der einzelnen Parameter abbilden zu können. Die Vergleichswerte können zukünftig in klinischen und epidemiologischen Untersuchungen als Hintergrundinformation herangezogen werden.
[New roles of glutamate receptors in glias and gliomas]. (2009)

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-typeglutamate-receptor channels (AMPARs) are composed of 4 subunits (GluR1-4); the channels without the GluR2 (GluR-B) subunit are characterized by high Ca2+ permeability. Bergmann glial cells in the cerebellum have Ca(2+)-permeable AMPARs assembled with GluR1 and GluR4. To examine the role of these Ca(2+)-permeable AMPARs, we converted them into Ca(2+)-impermeable receptors by adenoviral-mediated delivery of the GluR2 gene. This resulted in the retraction of the glial processes ensheathing the synapses on Purkinje cell dendritic spines and retard action of the removal of synaptically released glutamate, indicating that glutamate regulates the morphology of glial processes by activating Ca(2+)-permeable AMPARs, and the glial Ca(2+)-permeable AMPARs are indispensable for proper structural and functional interactions between the Bergmann glia and the glutamatergic synapses. Glioblastoma multiforme is the most malignant type of brain tumor. Glioblastoma cells express Ca(2+)-permeable AMPARs assembled from the GluR1 and/or GluR4 subunits, and the conversion of these units to Ca(2+)-impermeable receptors by adenovirus-mediated transfer of the GluR2 gene inhibited cell locomotion and induced apoptosis. In contrast, the overexpression of Ca(2+)-permeable AMPA receptors facilitated migration and proliferation of the tumor cells. Thus, Ca(2+)-permeable AMPA receptors are important in the migration and proliferation of neoplastic glias. The blockage of these receptors may be an attractive therapeutic target for preventing of invasive growth.
Alteration in Apolipoprotein A-I 22-Mer Repeat Order Results in a Decrease in Lecithin:Cholesterol Acyltransferase Reactivity (1997)

Apolipoprotein A-I contains eight 22-amino acid and two 11-amino acid tandem repeats that comprise 80% of the mature protein. These repeating units are believed to be the basic motif responsible for lipid binding and lecithin:cholesterol acyltransferase (LCAT) activation. Computer analysis indicates that despite a fairly high degree of compositional similarity among the tandem repeats, significant differences in hydrophobic and amphipathic character exist. Our previous studies demonstrated that deletion of repeat 6 (143-164) or repeat 7 (165-186) resulted in a 98-99% reduction of LCAT activation as compared with wild-type apoA-I. To determine the effects of substituting one of these repeats with a more hydrophobic repeat we constructed a mutant apoA-I protein in which residues 143-164 (repeat 6) were replaced with repeat 10 (residues 220-241). The cloned mutant protein, 10F6 apoA-I, was expressed and purified from an Sf-9 cell baculoviral system and then analyzed using a number of biophysical and biochemical techniques. Recombinant complexes prepared at a 100:5:1 molar ratio of L-alpha-dimyristoylphosphatidylcholine:cholesterol:wild-type or 10F6 apoA-I showed a doublet corresponding to Stokes diameters of 114 and 108 A on nondenaturing 4-30% polyacrylamide gel electrophoresis. L-alpha-Dimyristoylphosphatidylcholine 10F6 apoA-I complexes had a 5-6-fold lower apparent Vmax/apparent Km as compared with wild-type apoA-I containing particles. As expected, monoclonal antibody epitope mapping of the lipid-free and lipid-bound 10F6 apoA-I confirmed that a domain expressed between residues 143 and 165 normally found in wild-type apoA-I was absent. The region between residues 119 and 144 in 10F6 apoA-I showed a marked reduction in monoclonal antibody binding capacity. Therefore, we speculate that the 5-6-fold lower LCAT reactivity in 10F6 compared with wild-type apoA-I recombinant particles results from increased stabilization within the 121-165 amino acid domain due to more stable apoprotein helix phospholipid interactions as well as from conformational alterations among adjacent amphipathic helix repeats.
Evaluation of a eucalyptus-based repellent against Anopheles spp. in Tanzania. (1996)

A eucalyptus-based insect repellent (PMD) with the principal active ingredient p-menthane-3,8-diol was evaluated in the field in comparison with deet. In human landing catches in Tanzania, 3 formulations of PMD were tested against Anopheles gambiae and An. funestus. Repellents, applied to the legs and feet at doses chosen as used in practice, gave complete protection from biting for between 6 and 7.75 h, depending upon the formulation type, with no significant difference between PMD and deet in terms of efficacy and duration of protection.
Hybrid Si/III&#x2013;V lasers with adiabatic coupling (2011)

We report on hybrid Si/III-V lasers with adiabatic coupling. The proposed architectures, based on adiabatic mode transformers, allow laser mode to experience maximal gain available in the III-V region while maintaining a high coupling efficiency (>;95%) to Si-waveguides. Hybrid Fabry-Pérot and racetrack lasers are presented.
A network of dopaminergic gene variations implicated as risk factors for schizophrenia (2007)

We evaluated the hypothesis that dopaminergic polymorphisms are risk factors for schizophrenia (SZ). In stage I, we screened 18 dopamine-related genes in two independent US Caucasian samples: 150 trios and 328 cases/501 controls. The most promising associations were detected with SLC6A3 (alias DAT), DRD3, COMT and SLC18A2 (alias VMAT2). In stage II, we comprehensively evaluated these four genes by genotyping 68 SNPs in all 478 cases and 501 controls from stage I. Fifteen (23.1%) significant associations were found (p < or = 0.05). We sought epistasis between pairs of SNPs providing evidence of a main effect and observed 17 significant interactions (169 tests); 41.2% of significant interactions involved rs3756450 (5' near promoter) or rs464049 (intron 4) at SLC6A3. In stage III, we confirmed our findings by genotyping 65 SNPs among 659 Bulgarian trios. Both SLC6A3 variants implicated in the US interactions were overtransmitted in this cohort (rs3756450, p = 0.035; rs464049, p = 0.011). Joint analyses from stages II and III identified associations at all four genes (p(joint) < 0.05). We tested 29 putative interactions from stage II and detected replication between seven locus pairs (p < or = 0.05). Simulations suggested our stage II and stage III interaction results were unlikely to have occurred by chance (p = 0.008 and 0.001, respectively). In stage IV we evaluated rs464049 and rs3756450 for functional effects and found significant allele-specific differences at rs3756450 using electrophoretic mobility shift assays and dual-luciferase promoter assays. Our data suggest that a network of dopaminergic polymorphisms increase risk for SZ.
Enriched Intestinal Stem Cell Seeding Improves the Architecture of Tissue-Engineered Intestine (2015)

The novel filtration system described can effectively and efficiently isolate ISC-containing crypts. TEI produced from ISC-containing crypts has an improved morphology that is similar to native intestine.
IL-4 induces functional cell-surface expression of CXCR4 on human T cells. (1998)

Here we report that IL-4 specifically enhances cell surface expression of CXCR4 on resting peripheral and cord blood T cells. Whereas polarized Th2 clones express variable levels of CXCR4, expression of this receptor is undetectable on polarized Th1 clones but can be induced on the latter cells as well, following short-term culture in the presence of IL-4. The IL-4-induced CXCR4 is functional since interaction with its ligand, stromal-derived factor (SDF)-1, activates the p42 MAP-kinase ERK-2. In addition, although CXCR4 expression is down-regulated following stimulation of T cells and T cell clones via CD28 or CD3 and CD2 cell surface molecules, respectively, it is re-induced by IL-4. These data indicate an important role for IL-4 in rendering CD4+ T cells susceptible to infection with HIV via CXCR4, as well as in promoting SDF-1-induced migration of these cells.
1999 Volvo Award Winner in Basic Science Studies (1999)

The results of this study suggest that the intervertebral disc is an appropriate site for adenovirus-mediated transfer of exogenous genes and subsequent production of therapeutic growth factors. Gene therapy therefore may have useful applications for study of the basic science of the intervertebral disc and for clinical management of degenerative disc disease.
Transient Assay System for the Analysis ofPR-1aGene Promoter in Tobacco BY-2 Cells (2004)

In order to develop a rapid and versatile assay system suitable for the analysis of regulated expression of tobacco pathogenesis-related protein 1a (PR-1a) gene, we investigated the use of the transient gene expression system in tobacco BY-2 cells by microprojectile bombardment. Using dual luciferase assay as a reporter gene expression detection system, we observed significant induction of PR-1a promoter activity by salicylic acid (SA) treatment. On the other hand, treatment with 4-hydroxybenzoic acid (4-HBA) resulted in no detectable increase in luciferase activity. Co-expression of a trans-acting factor, the NPR1/NIM1 protein of Arabidopsis, resulted in the induction of higher expression levels of the PR-1a promoter. These results suggest that the assay system is applicable for the analysis of factors involved in the regulated expression of SA-inducible defense-related genes.
Macrobicycles based on cyclen and cyclam containing 1,3-disubstituted adamantane moiety (2012)

derivatives of cyclen and cyclam obtained according to previously described procedures were introduced in a palladium-catalyzed reaction with 1,3bis(aminomethyl)adamantane and 1,3-bis(2-aminoethyl)adamantane to produce macrobicycles in moderate yields. The formation of tricyclic cyclodimers was observed in many cases. Tetrabenzyl derivatives of cyclen and cyclam were synthesized from the corresponding dibenzyl derivatives and reacted with 1,3-bis(2-aminoethyl)adamantane to give macrobicyclic products in similar yields.
The genetic and environmental sources of body mass index variability: the Muscatine Ponderosity Family Study. (1991)

The role of genetic and environmental factors in determining the variability in body mass index (BMI; kg/m2) was investigated in 1,302 relatives identified through 284 schoolchildren from Muscatine, IA. BMI levels were first adjusted for variability in age, by gender and by relative type. There was significant familial aggregation of adjusted BMI in the pedigrees, as indicated by inter- and intraclass correlation coefficients significantly different from zero. A mixture of two normal distributions fit the adjusted BMI data better than did a single normal distribution. Genetic and environmental models that could explain both the familial aggregation and the mixture of normal distributions were investigated using complex segregation analysis. There was strong support for a single recessive locus with a major effect that accounted for almost 35% of the adjusted variation in BMI. Polygenic loci accounted for an additional 42% of the variation. Approximately 23% of the adjusted variation was not explained by genetic factors. For spouses living in the same household, their shared environment accounted for 12% of their variation. For siblings living in the same household, their shared environment accounted for 10% of their variation. While shared environments contributed to variation in adjusted BMI, more than 75% of the variation was explained by genetic factors that include a single recessive locus. Approximately 6% of the individuals in the population from which these pedigrees were sampled are predicted to have two copies of the recessive gene, while 37% of the individuals are predicted to have one copy of the gene.
Impairment of the Transient Pupillary Light Reflex inRpe65−/−Mice and Humans with Leber Congenital Amaurosis (2004)

Pupillometry was used to quantify visual impairment and to probe transmission of retinal signals to higher nervous centers in a murine model of LCA and in patients with LCA. Mouse results were consistent with a dominant role of image-forming photoreceptors driving the early phase of the TPLR when elicited by short-duration stimuli. The objective and noninvasive nature of the TPLR measurement, and the observed post-treatment change toward normal in the animal model supports the notion that this may be a useful outcome measure in future therapeutic trials of LCA.
Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields (2016)

Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.
High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma (2015)

Solute Carrier Family 1, member 5 (SLC1A5), also named as ASCT2, a major glutamine transporter, is highly expressed in various malignancies and plays a critical role in the transformation, growth and survival of cancer cells. The aim of this study was to assess the clinical significance of SLC1A5 in patients with clear-cell renal cell carcinoma (ccRCC). SLC1A5 expression was evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier method was conducted to compare survival curves. Univariate and multivariate Cox regression models were applied to assess the impact of prognostic factors on overall survival (OS). A nomogram was then constructed on the basis of the independent prognosticators identified on multivariate analysis. The predictive ability of the models was compared using Receiver operating characteristic (ROC) analysis. Our data indicated that high expression of SLC1A5 was significantly associated with advanced TNM stage, higher Fuhrman grade and shorter OS in ccRCC patients. Multivariate analysis confirmed that SLC1A5 was an independent prognosticator for OS. A nomogram integrating SLC1A5 and other independent prognosticators was constructed, which showed a better prognostic value for OS than TNM staging system. In conclusion, high SLC1A5 expression is an independent predictor of adverse clinical outcome in ccRCC patients after surgery.
EuPaGDT: a web tool tailored to design CRISPR guide RNAs for eukaryotic pathogens (2015)

Recent development of CRISPR-Cas9 genome editing has enabled highly efficient and versatile manipulation of a variety of organisms and adaptation of the CRISPR-Cas9 system to eukaryotic pathogens has opened new avenues for studying these otherwise hard to manipulate organisms. Here we describe a webtool, Eukaryotic Pathogen gRNA Design Tool (EuPaGDT; available at http://grna.ctegd.uga.edu), which identifies guide RNA (gRNA) in input gene(s) to guide users in arriving at well-informed and appropriate gRNA design for many eukaryotic pathogens. Flexibility in gRNA design, accommodating unique eukaryotic pathogen (gene and genome) attributes and high-throughput gRNA design are the main features that distinguish EuPaGDT from other gRNA design tools. In addition to employing an array of known principles to score and rank gRNAs, EuPaGDT implements an effective on-target search algorithm to identify gRNA targeting multi-gene families, which are highly represented in these pathogens and play important roles in host-pathogen interactions. EuPaGDT also identifies and scores microhomology sequences flanking each gRNA targeted cut-site; these sites are often essential for the microhomology-mediated end joining process used for double-stranded break repair in these organisms. EuPaGDT also assists users in designing single-stranded oligonucleotides for homology directed repair. In batch processing mode, EuPaGDT is able to process genome-scale sequences, enabling preparation of gRNA libraries for large-scale screening projects.
Plasma Procalcitonin in Sepsis and Organ Failure (2001)

CRP is increased by inflammatory disease as well as infection and is therefore not a good indicator of infection in patients with severe SIRS. On the other hand, PCT is a good indicator of severity of sepsis and organ failure in patients with severe SIRS since PCT levels correlated with sepsis and SOFA scores. PCT level is useful for diagnosis of sepsis and as an indicator of severity of organ failure in patients with SIRS.
In Vivo Selective Measurement of {1−13C}‐Glucose Metabolism in Tumors by Heteronuclear Cross Polarization (1995)

Selective detection of (1-13C)-glucose and its glycolytic product, (3-13C)-lactate, was achieved by selective 13C NMR spectroscopy with 1H cross polarization. The total sensitivity of conventional broadband experiments was retained, and peak intensities were at least equivalent to those obtained with the inverse detection technique (i.e., 1H(13C)) for single proton resonances. A key advantage of the method is that it maintains the specific absorption rate (SAR) within FDA limits of 5 W/kg by reducing power deposition during decoupling. In this study we have monitored the kinetics of metabolism of 13C-labeled glucose to lactate following intravenous infusion of 0.55 ml of 0.18 M labeled glucose. Physiological effects were minimized by a) maintaining total plasma glucose concentrations below 20 mM throughout the course of NMR experiment and b) by avoiding significant heating of the tumor.
The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid (1972)

A method is given for small-scale preparation of DNA from 1.0-1.5g of adult rat tissues. The product from brain or liver is characterized by base ratios and phosphorus content which accord with reported values for rat tissue. It is reasonably free of RNA, protein and glycogen. It contains 5-hydroxymethylcytosine at a content of about 15% of the total cytosine bases present. 5-Hydroxymethylcytosine is also demonstrable in mouse and frog brain DNA and in the crude cytidylic acid fractions obtained from RNA hydrolysates of rat brain and liver. 5-Hydroxymethylcytosine is identified by paper chromatography, u.v. spectra in acid and alkaline solutions and by its conversion into 5-hydroxymethyluracil.
Physical Parameters and Biological Stability of Yttrium(III) Diethylenetriaminepentaacetic Acid Derivative Conjugates (1998)

The solution equilibria, acid dissociation, and serum stability of a series of Y(III) complexes of DTPA ligands functionalized with p-nitrobenzyl, methyl, and trans-cyclohexyl substituents were studied. The thermodynamic stability of the complexes studied ranged from log K = 21.53 to 24.7. Acid dissociation rates were found to decrease as the substitution on the carbon backbone increased, and significant differences in dissociation rates were observed for the Y(III) complexes of a pair of diasteriomeric cyclohexyl-DTPA ligands. While one diastereomer was found to have the slowest acid dissociation rate of the entire DTPA series, it was remarkably labile in both serum stability and in vivo studies.
A Protease‐Based Strategy for the Controlled Release of Therapeutic Peptides (2010)

A polypeptide containing an albumin-binding domain (ABD), an amino acid sequence linker, and glucagon-like peptide-1 (GLP-1), a potential antidiabetic agent, is designed to slowly release GLP-1 through sequential cleavage by native plasma proteases (see picture). The half-life of the polypeptide in the bloodstream is extended by its association with human serum albumin (HSA).