gebhart/patrepeval huggingface dataset:
Large scale sequencing projects using rapidly prepared double-stranded plasmid DNA (1991)

We have developed a simple rapid plasmid DNA mini-preparation method which yields DNA of sufficient quality to be used in large scale sequencing projects. The method, which is a modification of the alkaline method of Birnboim and Doly (1979), requires less than two hours. We have eliminated the use of organic extractions, RNase digestion and alkaline denaturation of the DNA for annealing of the primer. The proportion of supercoiled plasmid DNA obtained is close to 100%. Greater than 80% of the clones yield at least 500 bp of sequence information per primer. The sequencing reactions from these double-stranded templates can be done on both strands using the universal and reverse sequence primers with the usual two reactions per primer, one to read close to the primer and one to read far from it. Thus, each clone yields at least 1 kb of sequence information. The preparation of the templates and the sequencing reactions can be done in less than three hours so that the sequencing gel can be run the same day.
Synthesis, surface, and cell‐adhesion properties of polyurethanes containing covalently grafted RGD‐peptides (1994)

In an attempt to improve endothelial cell adhesion and growth on a polyurethane copolymer, cell adhesive RGD-containing peptides were grafted to the polymer backbone. Two peptide grafting reaction schemes, including one-step and two-step approaches, were developed. FTIR and amino acid analysis confirmed that coupling of the peptide to the polyurethane backbone was achieved by both the one-step and two-step methods. However, the two-step approach showed a higher peptide coupling efficiency and resulted in better control of the orientation of the grafted peptide. The two-step reaction scheme was used to prepare Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY), Gly-Arg-Gly-Asp-Val-Tyr (GRGDVY), and Gly-Arg-Gly-Glu-Ser-Tyr (GRGESY) peptide-grafted polyurethanes with two different peptide densities (100 and 250 mumol/g polymer). Dynamic contact angle measurements indicated that the surfaces of the peptide-grafted polyurethanes were more hydrophilic than the starting and carboxylated versions of the precursor polyurethane. In addition, the surface hydrophilicity of the peptide-grafted polymers increased with increasing bulk peptide density. Electron spectroscopy for chemical analysis suggested that the grafted peptide was present at the polymer-air interface, in vacuo, for the peptide-grafted polyurethanes. The surface peptide density appeared to correlate with the incorporated peptide density in the bulk. In vitro endothelial cell adhesion experiments showed that, without the presence of serum in culture medium, the GRGDSY- and GRGDVY-grafted polyurethanes dramatically enhanced cell attachment and spreading compared with the starting, carboxylated, and GRGESY-grafted polymers. Increasing the peptide density from 100 to 250 mumol/g polymer for the GRGDSY- and GRGDVY-grafted polyurethanes resulted in an increase in cell attachment. With approximately the same peptide density (100 or 250 mumol/g polymer), the GRGDVY-grafted polymers supported more adherent cells than did the GRGDSY-grafted polymers. Similar trends were observed in the in vitro endothelial cell growth studies using culture medium containing serum and endothelial cell growth supplement. The GRGDSY- and GRGDVY-grafted polyurethanes promoted more cell growth than did the starting polyurethane. However, the presence of adhesive serum proteins and growth factor diminished the differences between the cell-adhesive peptide grafted polymers and the GRGESY-grafted polymers.
A Link between Integral Membrane Protein Expression and Simulated Integration Efficiency (2016)

Integral membrane proteins (IMPs) control the flow of information and nutrients across cell membranes, yet IMP mechanistic studies are hindered by difficulties in expression. We investigate this issue by addressing the connection between IMP sequence and observed expression levels. For homologs of the IMP TatC, observed expression levels vary widely and are affected by small changes in protein sequence. The effect of sequence changes on experimentally observed expression levels strongly correlates with the simulated integration efficiency obtained from coarse-grained modeling, which is directly confirmed using an in vivo assay. Furthermore, mutations that improve the simulated integration efficiency likewise increase the experimentally observed expression levels. Demonstration of these trends in both Escherichia coli and Mycobacterium smegmatis suggests that the results are general to other expression systems. This work suggests that IMP integration is a determinant for successful expression, raising the possibility of controlling IMP expression via rational design.
Identification of novel phosphorylation sites in murine A‐type lamins (1993)

We report the distribution of phosphorylation sites in murine lamins A and C (A-type lamins) in vitro and in vivo followed by reverse-phase high-performance liquid chromatography and microsequencing of peptides spanning the almost complete lamin sequence. We show that two distinct protein kinases, cell-division-cycle-2 kinase (cdc2 kinase) and protein kinase C (PKC), phosphorylate murine A-type lamins at the non-alpha-helical amino- and carboxy-terminal domains in vitro and in vivo. Cdc2 kinase, but not PKC, is capable of inducing depolymerization of the nuclear lamina in permeabilized cells. Accordingly, lamins were proposed to be direct in vivo substrates of cdc2 kinase and PKC with different effects on the lamina dynamics. Analysis of the original A-type lamins revealed phosphorylation of residues Ser5 and Ser392. Residue Ser392 was substoichiometrically phosphorylated in the substrate and by cdc2 kinase in vitro. PKC phosphorylated peptides with its kinase-specific motifs surrounding Ser5, Thr199, Thr416, Thr480 and Ser625. In vivo, a mitosis-specific phosphorylation at the cdc2-kinase-specific phosphoacceptor site Ser392 and of the N-terminal peptide was identified. An interphase-specific phosphorylation at Ser525 matching the PKC consensus sequence and of peptides phosphorylated by unknown kinases was determined. The results lead us to propose that different cyclin-dependent kinase activities act as lamin kinases in mitosis and in interphase. Other kinases may cooperate with cdc2 kinase during reversible disassembly in mitosis and may modulate the supramolecular assembly of lamin filaments.
Performance of noise excitation for unvoiced speech (2005)

Recent interest in nonlinear modeling of speech has brought up the need to re-assess the performance limitations of linear speech models. While nonlinearity is essential in the production mechanism of speech, it need not be reflected in a speech-signal model. This paper addresses the question what perceptual quality can be achieved for unvoiced speech by a linear model with white noise excitation. Formal MOS test results demonstrate that this linear model results in unvoiced speech of high perceptual quality.
Savignygrin, a Platelet Aggregation Inhibitor from the Soft TickOrnithodoros savignyi, Presents the RGD Integrin Recognition Motif on the Kunitz-BPTI Fold (2002)

Savignygrin, a platelet aggregation inhibitor that possesses the RGD integrin recognition motif, has been purified from the soft tick Ornithodoros savignyi. Two isoforms with similar biological activities differ because of R52G and N60G in their amino acid sequences, indicating a recent gene duplication event. Platelet aggregation induced by ADP (IC50, 130 nm), collagen, the thrombin receptor-activating peptide, and epinephrine was inhibited, although platelets were activated and underwent a shape change. The binding of alpha-CD41 (P2) to platelets, the binding of purified alpha(IIb)beta3 to fibrinogen, and the adhesion of platelets to fibrinogen was inhibited, indicating a targeting of the fibrinogen receptor. In contrast, the adhesion of osteosarcoma cells that express the integrin alpha(v)beta3 to vitronectin or fibrinogen was not inhibited, indicating the specificity of savignygrin toward alpha(IIb)beta3. Savignygrin shows sequence identity to disagregin, a platelet aggregation inhibitor from the tick Ornithodoros moubata that lacks an RGD motif. The cysteine arrangement of savignygrin is similar to that of the bovine pancreatic trypsin inhibitor family of serine protease inhibitors. A homology model based on the structure of the tick anticoagulant peptide indicates that the RGD motif is presented on the substrate-binding loop of the canonical BPTI inhibitors. However, savignygrin did not inhibit the serine proteases fXa, plasmin, thrombin, or trypsin. This is the first report of a platelet aggregation inhibitor that presents the RGD motif using the Kunitz-BPTI protein fold.
Oral hyperalimentation in the nutritional management of burned patients. (1985)

Total daily protein and energy requirements for burned adult patients were adapted from Sutherland's formulae and implemented in the Burn Unit at Tygerberg Hospital. Patients were given a high-protein ward diet and oral hyperalimentation, and weekly recording of body mass was used for monitoring. It was found that the high protein and energy intake minimized body mass loss during the period after thermal injury.
Protein-binding polyhedral boranes. 1 (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein-binding polyhedral boranes. 1R. L. Sneath Jr., A. H. Soloway, and A. S. DeyCite this: J. Med. Chem. 1974, 17, 8, 796–799Publication Date (Print):August 1, 1974Publication History Published online1 May 2002Published inissue 1 August 1974https://pubs.acs.org/doi/10.1021/jm00254a003https://doi.org/10.1021/jm00254a003research-articleACS PublicationsRequest reuse permissionsArticle Views66Altmetric-Citations26LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Diagnosis of Trisomy 21 in Fetal Nucleated Erythrocytes from Maternal Blood by Use of Short Tandem Repeat Sequences (2001)

Fluorescent PCR amplification of STRs can detect fetal aneuploidy and may be useful in the setting of poor hybridization efficiency with FISH analysis. These results suggest that combined fetal aneuploidy and single-gene diagnoses by the use of DNA microarrays may be feasible in the near future.
Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion (2013)

Obesity and diabetes are associated with excess caloric intake and reduced energy expenditure resulting in a negative energy balance. The incidence of diabetes has reached epidemic proportions, and childhood diabetes and obesity are increasing alarmingly. Therefore, it is important to develop safe, easily deliverable, and economically viable treatment alternatives for these diseases. Here, we provide data supporting the candidacy of probiotics as such a therapeutic modality against obesity and diabetes. Probiotics are live bacteria that colonize the gastrointestinal tract and impart beneficial effects for health. However, their widespread prescription as medical therapies is limited primarily because of the paucity of our understanding of their mechanism of action. Here, we demonstrate that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models. VSL#3 suppressed body weight gain and insulin resistance via modulation of the gut flora composition. VSL#3 promoted the release of the hormone GLP-1, resulting in reduced food intake and improved glucose tolerance. The VSL#3-induced changes were associated with an increase in the levels of a short chain fatty acid (SCFA), butyrate. Using a cell culture system, we demonstrate that butyrate stimulated the release of GLP-1 from intestinal L-cells, thereby providing a plausible mechanism for VSL#3 action. These findings suggest that probiotics such as VSL#3 can modulate the gut microbiota-SCFA-hormone axis. Moreover, our results indicate that probiotics are of potential therapeutic utility to counter obesity and diabetes.
Functional changes in dorsal root ganglion cells after chronic nerve constriction in the rat (1995)

1. We studied the effects of a chronic nerve constriction on the evoked responses in dorsal root fibers in the rat to norepinephrine and to thermal stimuli applied either to the dorsal root ganglion (DRG) or the site of nerve injury. We recorded a total of 59 C fibers, 15 A delta-fibers, and 46 A beta-fibers from the L5 dorsal root of the rats 11-52 days after a loose ligation of the ipsilateral sciatic nerve. Most fibers were identified by the presence of spontaneous activity (SA) that originated partially at and/or proximal to the injury site. In addition, we recorded 20 C fibers, 1 A delta-fiber, and 28 A beta-fibers from the dorsal roots of normal, uninjured neurons. 2. In nerve-injured rats, the SA of some C fibers was generally increased by cooling and decreased by heating either site. In contrast, the SA of most A beta-fibers was increased by heating either the injury site or the DRG. Cooling the DRG decreased SA in A beta-fibers, whereas cooling the injury site typically had no effect. Excitatory responses were not evoked in any fiber group when the same thermal stimuli were applied to the nerve or DRG tested in normal, uninjured rats. 3. Norepinephrine (< 0.5 mM) applied either to the injury site or the DRG increased the SA of most C fibers and A delta-fibers but only a minority of A beta-fibers in previously injured nerves. The threshold concentration for excitation of the DRG somata of C fibers was 0.01 mM. No effects were found for fibers in uninjured nerves. 4. The effect of norepinephrine was blocked by a pretreatment with yohimbine, an alpha 2-blocker, but not with prazosin, an alpha 1-blocker. 5. Stimulation of the sympathetic trunk (L2-L3) excited most C fibers and a minority of A beta-fibers. In contrast, the SA of a minority of C fibers and A beta-fibers was depressed during sympathetic stimulation. 6. After a chronic nerve constriction the DRG becomes a source of abnormal activity modulated by sympathetically released norepinephrine acting on alpha 2 receptors in DRG somata. This neuropathic activity may contribute to cutaneous pain and hyperalgesia.
A unique population of circulating autoantibodies promotes central nervous system remyelination (1998)

In previous studies we demonstrated that the humoral immune response directed against unique central nervous system (CNS) antigens enhanced CNS remyelination in the Theiler's virus experimental model of multiple sclerosis (MS). To expand on this observation, a mouse IgM kappa monoclonal antibody (mAb) which enhances CNS remyelination, was raised against normal mouse spinal cord homogenate. Characterization of this mAb revealed that it is polyreactive towards variety of intracellular antigens but also reacts to an unidentified surface antigen on oligodendrocytes. The mAb is encoded by germline immunoglobulin genes without somatic mutations consistent with the observation that it is a natural autoantibody. Recently we generated another mouse IgM kappa mAb raised against normal spinal cord homogenate, which also promotes CNS remyelination. Further characterization revealed that both mAbs which promote remyelination have similar binding characteristics. Conventionally Abs which recognize normal CNS components, especially oligodendrocytes or myelin, have been considered to be a disease marker or be involved in the pathogenesis of MS. However, we have identified a unique population of circulating autoantibodies which are beneficial for myelin repair. Therefore this observation indicates the need to reevaluate autoantibody production against myelin components in CSF and blood as markers of disease activity versus repair in MS.
RETRACTED ARTICLE: A new inducible transgenic mouse model for C9orf72-associated GGGGCC repeat expansion supports a gain-of-function mechanism in C9orf72-associated ALS and FTD (2014)

Hukema, Renate K; Riemslagh, Fréderike W; Melhem, Shamiram; van der Linde, Herma C; Severijnen, Lies-Anne Wfm; Edbauer, Dieter; Maas, Alex; Charlet-Berguerand, Nicolas; Willemsen, Rob; van Swieten, John C
Automated generation of heuristics for biological sequence comparison (2005)

This system allows rapid implementation of heuristics approximating to many complex alignment models, and has been incorporated into the freely available sequence alignment program, exonerate.
Early Mesozoic tectonic history of the boundary area, east‐central Alaska (1985)

Thrust faulting in the Yukon‐Tanana Upland of east‐central Alaska has long been hypothesized, but few thrust faults have been definitely identified. In the Boundary area near the international border between Alaska and Canada metamorphic rocks of the amphibolite facies have been thrust over rocks of the greenschist facies. Subordinate thrust faults and imbrication occur within both groups of rocks. Brecciation, slickensides, slickenfibers, rootless, isoclinally folded quartz bands, and abrupt lithologic changes from gneiss and amphibolite to quartz‐white mica‐chlorite schist characterize the thrust zone. Ultramafic rocks occur locally on or near the thrust plane. Thrusting is postulated to have occurred when a terrane composed of the amphibolite facies rocks converged with rocks along the continental margin of North America in Late Triassic and Early Jurassic time.
Subcloning, nucleotide sequence, and expression of trkG, a gene that encodes an integral membrane protein involved in potassium uptake via the Trk system of Escherichia coli (1991)

The trkG gene encodes a component of the K+ uptake system Trk and is located at 30.5 min inside the lambdoid prophage region rac of the Escherichia coli chromosome. trkG was subcloned, its nucleotide sequence was determined, and its product was identified in a minicell system. The open reading frame of 1,455 bp encodes a hydrophobic membrane protein with a calculated molecular weight of 53,493 that is predicted to contain up to 12 transmembrane helices. The trkG gene product behaved as a hydrophobic membrane protein; it was found exclusively in the membrane fraction of the minicells and its migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was anomalous, indicating an apparent molecular weight of 35,000. The trkG gene contains an exceptionally high proportion of infrequently used codons, raising the question of the origin of this gene. trkG does not appear to be a prophage gene since no similarity was observed between the nucleotide sequence of trkG or the amino acid sequence of its product and the sequences of genes or proteins from bacteriophage lambda.
Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma (2016)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28-120) and 38 (range 19-66) in responsive patients. Missense mutations of TP53 were exclusive in 50% (3/6) of refractory patients and involved the DNA-binding domain of TP53. All missense mutations of TP53 were accompanied by copy number deletions. RAB11FIP5, PRKCB, PRDM15, FNBP4, AHR, CEP128, BRE, DHX16, MYO6, and NMT1 mutations were recurrent in refractory patients. MYD88, B2M, SORCS3, and WDFY3 mutations were more frequent in refractory patients than in responsive patients. REL-BCL11A fusion was found in two refractory patients; one had both fusion and copy number gain. Recurrent copy gains of POU2AF1, SLC1A4, REL11, FANCL, CACNA1D, TRRAP, and CUX1 with significantly increased average expression were found in refractory patients. The expression profile revealed enriched gene sets associated with treatment resistance, including oxidative phosphorylation and ATP-binding cassette transporters. In conclusion, this study integrated both genomic and transcriptomic alterations associated with refractory DLBCL and found several treatment-resistance alterations that may contribute to refractoriness.
Clinical Decision Support Systems for the Practice of Evidence-based Medicine (2001)

Although the promise of clinical decision support system-facilitated evidence-based medicine is strong, substantial work remains to be done to realize the potential benefits.
Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome (2013)

Accumulating evidence demonstrates the intimate association between human hosts and the gut microbiome. Starting at birth, the sterile gut of the newborn acquires a diverse spectrum of microbes, needed for immunological priming. However, current practices (caesarean sections, use of formula milk) deprive newborns from being exposed to this broad spectrum of microbes. Unnecessary use of antibiotics and excessive hygienic precautions (e.g. natural versus chlorinated drinking water) together with the Western diet further contribute to a decreased microbial diversity in the adult gut. This has been correlated with recurrent Clostridium difficile infection, inflammatory bowel diseases and obesity, among others. A healthy gut microbiome is thus characterized by a diverse network of metabolically interacting microbial members. In this context, we review several existing and novel approaches to manage the gut microbiome. First, prebiotic compounds should be re-defined in the sense that they should enhance the ecological biodiversity rather than stimulating single species. Recent studies highlight that structurally different polysaccharides require specific primary degraders but also enhance a similar network of secondary degraders that benefit from cross-feeding. A faecal transplantation is a second approach to restore biodiversity when the microbiota is severely dysbiosed, with promising results regarding C. difficile-associated disease and obesity-related metabolic syndromes. A final strategy is the introduction of key microbial network units, i.e. pre-organized microbial associations, which strengthen the overall microbial network of the gut microbiome that supports human health.