gebhart/patrepeval huggingface dataset:
Proteolytic modification of the heparin-binding affinity of extracellular superoxide dismutase (1993)

The heparin-binding affinity of the tetrameric extracellular superoxide dismutase (EC-SOD) is a result of the cooperative effect of the heparin-binding domains of the subunits, located in the hydrophilic, strongly positively charged C-terminal ends. EC-SOD C, the high-heparin-affinity type, exposed to immobilized trypsin and plasmin was found to rapidly lose its affinity for heparin, without any loss of enzymic activity or major change in molecular mass as judged by size-exclusion chromatography. Heparin and dextran sulphate 5000 inhibited the proteolysis, suggesting that EC-SOD C sequestered by heparan sulphate proteoglycan in vivo is partially protected against proteolysis. The loss of heparin-affinity occurred with the stepwise formation of intermediates, and the pattern upon chromatography on heparin-Sepharose and subsequent immunoblotting was compatible with the notion that the changes are due to sequential truncations of heparin-binding domains from subunits composing the EC-SOD tetramers. A similar pattern with intermediates and apparent truncations has previously been found with EC-SOD of human plasma. The findings show that the unique design of the heparin-binding domain of EC-SOD allows easy modification of the heparin-affinity by means of limited proteolysis, and suggest that such proteolysis is a major contributor to the heterogeneity in heparin-affinity of EC-SOD in mammalian plasma.
RNA-Based Gene Therapy for HIV with Lentiviral Vector–Modified CD34 + Cells in Patients Undergoing Transplantation for AIDS-Related Lymphoma (2010)

AIDS patients who develop lymphoma are often treated with transplanted hematopoietic progenitor cells. As a first step in developing a hematopoietic cell-based gene therapy treatment, four patients undergoing treatment with these transplanted cells were also given gene-modified peripheral blood-derived (CD34(+)) hematopoietic progenitor cells expressing three RNA-based anti-HIV moieties (tat/rev short hairpin RNA, TAR decoy, and CCR5 ribozyme). In vitro analysis of these gene-modified cells showed no differences in their hematopoietic potential compared with nontransduced cells. In vitro estimates of successful expression of the anti-HIV moieties were initially as high as 22% but declined to approximately 1% over 4 weeks of culture. Ethical study design required that patients be transplanted with both gene-modified and unmanipulated hematopoietic progenitor cells obtained from the patient by apheresis. Transfected cells were successfully engrafted in all four infused patients by day 11, and there were no unexpected infusion-related toxicities. Persistent vector expression in multiple cell lineages was observed at low levels for up to 24 months, as was expression of the introduced small interfering RNA and ribozyme. Therefore, we have demonstrated stable vector expression in human blood cells after transplantation of autologous gene-modified hematopoietic progenitor cells. These results support the development of an RNA-based cell therapy platform for HIV.
Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual (2020)

B cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design.
Deep-UV generation by frequency quadrupling of a high-power GaAlAs semiconductor laser (1995)

Tunable UV radiation near 215 nm was produced by frequency quadrupling the 860-nm emission of a mode-locked external-cavity compound semiconductor laser containing a tapered GaAlAs amplifier. A KNbO(3) crystal generated the 430-nm second harmonic, which was doubled by a beta-BaB(2)O(4) crystal, producing tunable UV radiation with as much as 15 microW of average power.
Vibrio cholerae Vaccines (1989)

Several approaches to the development of a safe and effective vaccine against Vibrio cholerae are currently being pursued. These candidate vaccines include (1) live V. cholerae strains attenuated by recombinant DNA techniques; (2) killed whole V. cholerae organisms plus purified cholera enterotoxin B subunit; and (3) cloned V. cholerae antigens in a Salmonella carrier strain. The first two approaches have been the most extensively studied in clinical trials, and all three types of vaccines are administered orally to maximize the stimulation of mucosal immunity. The live attenuated vaccine CVD103-HgR is inexpensive and was effective after a single dose but caused mild diarrhea in 4% of vaccinees. The killed whole cell plus B subunit vaccine is safe but requires the administration of multiple doses. The strong protective immunity conferred by the disease and the rapid progress recently achieved in vaccine development offer encouragement that a successful vaccine will soon be available.
Regulation of gene expression in vivo by liposome-mediated delivery of a purified transcription factor. (1990)

We describe a procedure for assessing the functional activity in vivo of a glucocorticoid receptor derivative, T7X556, a mammalian transcriptional regulator that has been overexpressed in Escherichia coli and purified to homogeneity. The protein was assessed with DOTMA (N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethyl-ammonium chloride) liposomes, which are internalized by cultured mammalian cells. T7X556 protein delivered in this manner localized rapidly to the nucleus and selectively enhanced expression from glucocorticoid response element-linked promoters, properties that are characteristic of this receptor derivative when it is synthesized endogenously in mammalian cells. Thus, in vivo activities of T7X556 were not disrupted by expression in bacteria or by biochemical purification. In general, liposome-mediated delivery may permit functional analyses of proteins that have been expressed in heterologous cells and manipulated in vitro.
Neurologic complications of chemotherapy agents (2007)

Data on prevention and treatment of chemotherapy-induced peripheral neuropathy are limited. Calcium and magnesium infusions for oxaliplatin administration have the most scientific support and are widely used in practice but may interfere with the clinical efficacy of oxaliplatin. Some novel agents, particularly bortezomib, have significant risk of chemotherapy-induced peripheral neuropathy. Animal models are beginning to reveal the mechanisms underlying the impact of individual chemotherapeutic drugs on cognition.
ODDSOC2 Is a MADS Box Floral Repressor That Is Down-Regulated by Vernalization in Temperate Cereals (2010)

In temperate cereals, such as wheat (Triticum aestivum) and barley (Hordeum vulgare), the transition to reproductive development can be accelerated by prolonged exposure to cold (vernalization). We examined the role of the grass-specific MADS box gene ODDSOC2 (OS2) in the vernalization response in cereals. The barley OS2 gene (HvOS2) is expressed in leaves and shoot apices but is repressed by vernalization. Vernalization represses OS2 independently of VERNALIZATION1 (VRN1) in a VRN1 deletion mutant of einkorn wheat (Triticum monococcum), but VRN1 is required to maintain down-regulation of OS2 in vernalized plants. Furthermore, barleys that carry active alleles of the VRN1 gene (HvVRN1) have reduced expression of HvOS2, suggesting that HvVRN1 down-regulates HvOS2 during development. Overexpression of HvOS2 delayed flowering and reduced spike, stem, and leaf length in transgenic barley plants. Plants overexpressing HvOS2 showed reduced expression of barley homologs of the Arabidopsis (Arabidopsis thaliana) gene FLOWERING PROMOTING FACTOR1 (FPF1) and increased expression of RNase-S-like genes. FPF1 promotes floral development and enhances cell elongation, so down-regulation of FPF1-like genes might explain the phenotypes of HvOS2 overexpression lines. We present an extended model of the genetic pathways controlling vernalization-induced flowering in cereals, which describes the regulatory relationships between VRN1, OS2, and FPF1-like genes. Overall, these findings highlight differences and similarities between the vernalization responses of temperate cereals and the model plant Arabidopsis.
The Load Of The Wingate Test: According To The Body Weight Or Lean Body Mass? (2005)

Aim: The purpose of this study was to determine if it was more appropriate assignment of the load of the Wingate test according to the lean body mass in young males. Methods: Wingate tests were performed on a Monark cycle ergometer by using loads of 75, 85, 95 g.kg-1 for the body weight and 90, 100, 110 g.kg-1 for the lean body mass on 24 untrained young males. These loads were applied randomly to the participants. Pedal revolutions for every 5-second were counted during the test and the peak power, the mean power and the fatigue index were calculated. Results: The peak power outputs of the Wingate tests in which 100 and 110 g.kg-1 loads were used for the lean body mass were significantly higher than the peak power outputs obtained from the tests in which 75 g.kg-1 loads were used for the body weight. None of the mean power outputs obtained from the loads was significantly higher than the others. Conclusion: We concluded that assignment of the load of the Wingate test according to the lean body mass would be more appropriate in young males. 100 or 110 g.kg-1 loads for the lean body mass can be used as they result in significantly higher peak power outputs.
Hemodynamic and Antecedent Risk Factors of Early and Late Periventricular/Intraventricular Hemorrhage in Premature Infants (2003)

Early and late P/IVH have distinct and different risk factors. Early P/IVH is associated with vaginal delivery and possibly low Apgar scores. Late P/IVH is associated with antecedent low SVC flow in the first day.
Heat-depolymerizable polycarbonates as electron beam patternable sacrificial layers for nanofluidics (2001)

This research investigates a heat-depolymerizable polycarbonate (HDP) for use as a sacrificial layer in fabricating nanofluidic devices by electron beam lithography. When solid HDP films are heated to 300 °C, the monomer units separate into a nontoxic vapor. This property suggests that a patterned HDP film may be used as a temporary support for another film which is stable at the depolymerization temperature. Heating the structure removes the HDP, leaving a network of nanofluidic tubes without the use of solvents or other chemicals as required in most other sacrificial layer processes. We found that HDP films may be patterned directly by electron beam lithography, followed by immersion in isopropanol to remove HDP from the exposed areas. The patterns are then sputter coated with silicon dioxide at low temperature, provided with access holes for venting, heated to clear out HDP remaining inside the tubes, and injected with fluorescent dye for observation. Tube dimensions of 140 nm height, 1 μm width, and 1 mm length are reported, and fabrication of other structures is discussed.
Rational Design of Peptide Antibiotics by Targeted Replacement of Bacterial and Fungal Domains (1995)

Peptide synthetases involved in the nonribosomal synthesis of peptide secondary metabolites possess a highly conserved domain structure. The arrangement of these domains within the multifunctional enzymes determines the number and order of the amino acid constituents of the peptide product. A general approach has been developed for targeted substitution of amino acid-activating domains within the srfA operon, which encodes the protein templates for the synthesis of the lipopeptide antibiotic surfactin in Bacillus subtilis. Exchange of domain-coding regions of bacterial and fungal origin led to the construction of hybrid genes that encoded peptide synthetases with altered amino acid specificities and the production of peptides with modified amino acid sequences.
Ornithine Decarboxylase- and ras -Induced Cell Transformations: Reversal by Protein Tyrosine Kinase Inhibitors and Role of pp130 CAS (1995)

We have found that overexpression of human ornithine decarboxylase (ODC) induces cell transformation in NIH 3T3 and Rat-1 cells (M. Auvinen, A. Paasinen, L. C. Andersson, and E. Hölttä, Nature (London) 360:355-358, 1992). The ODC-transformed cells display increased levels of tyrosine phosphorylation, in particular of a cluster of 130-kDa proteins. Here we show that one of the proteins with enhanced levels of tyrosine phosphorylation in ODC-overexpressing cells is the previously described p130 substrate of pp60v-src, known to associate also with v-Crk and designated p130CAS. We also studied the role of protein tyrosine phosphorylation in the ODC-induced cell transformation by exposing the cells to herbimycin A, a potent inhibitor of Src-family kinases, and to other inhibitors of protein tyrosine kinases. Treatment with the inhibitors reversed the phenotype of ODC-transformed cells to normal, with an organized, filamentous actin cytoskeleton. Coincidentally, the tyrosine hyperphosphorylation of p130 was markedly reduced, while the level of activity of ODC remained highly elevated. A similar reduction in pp130 phosphorylation and reversion of morphology by herbimycin A were observed in v-src- and c-Ha-ras-transformed cells. In addition, we show that expression of antisense mRNA for p130CAS resulted in reversion of the transformed phenotype of all these cell lines. An increased level of tyrosine kinase activity, not caused by c-Src or c-Abl, was further detected in the cytoplasmic fraction of ODC-transformed cells. Preliminary characteristics of this kinase are shown. These data indicate that p130CAS is involved in cell transformation by ODC, c-ras, and v-src oncogenes, raise the intriguing possibility that p130CAS may be generally required for transformation, and imply that there is at least one protein tyrosine kinase downstream of ODC that is instrumental for cell transformation.
<title>Evaluation of an automatic markup system</title> (1995)

One predominant application of OCR is the recognition of full text documents for information retrieval. Modern retrieval systems exploit both the textual content of the document as well as its structure. The relationship between textual content and character accuracy have been the focus of recent studies. It has been shown that due to the redundancies in text, average precision and recall is not heavily affected by OCR character errors. What is not fully known is to what extent OCR devices can provide reliable information that can be used to capture the structure of the document. In this paper, we present a preliminary report on the design and evaluation of a system to automatically markup technical documents, based on information provided by an OCR device. The device we use differs from traditional OCR devices in that it not only performs optical character recognition, but also provides detailed information about page layout, word geometry, and font usage. Our automatic markup program, which we call Autotag, uses this information, combined with dictionary lookup and content analysis, to identify structural components of the text. These include the document title, author information, abstract, sections, section titles, paragraphs, sentences, and de-hyphenated words. A visual examination of the hardcopy is compared to the output of our markup system to determine its correctness.
The group A streptococcal dipeptide permease (Dpp) is involved in the uptake of essential amino acids and affects the expression of cysteine protease (1998)

The majority of characterized bacterial dipeptide permeases (Dpp) are membrane-associated complexes of five proteins belonging to the ABC-transporter family. They have been found to be involved in the uptake of essential amino acids, haem production, chemotaxis and sporulation. A 5.8 kb genomic DNA fragment of the serotype M49 group A streptococcal (GAS) strain CS101 was sequenced and found to contain five putative GAS Dpp genes (dppA to dppE). Deduced amino acid sequences exhibited 17-54% similarity to corresponding ABC-transporter sequences. The operon organization of the five genes was confirmed by transcriptional analysis, and a shorter, more abundant, dppA-only transcript was detected similar to that found in the GAS oligopeptide permease (Opp) system. Insertional inactivation was used to create serotype M2 and M49 strains that did not express the dppD and dppEATPase genes or nearly the entire operon. In feeding experiments with di- to hexapeptides, the wild-type strain grew with each peptide tested. The dpp mutants were unable to grow on dipeptides, whereas hexapeptides did not sustain the growth of opp mutants. Expression of the dpp operon was induced approximately fourfold in late exponential growth phase. In addition, a striking increase in the dppA to dppA-E ratio from 5:1 to more than 20:1 occurred during late exponential growth phase in complex medium. Growth in chemically defined medium (CDM) supplemented with various dipeptides specifically induced the expression of dpp and reduced both the dppA to dppA-E and oppA to oppA-F mRNA ratios. Expression of the virulence factor SpeB (major cysteine protease) was reduced eightfold in dpp mutants, whereas dpp expression was decreased about fourfold in a Mga virulence regulator mutant. Taken together, these data indicate a correlation between levels of intracellular essential amino acids and the regulation of virulence factor expression.
Matrix Metalloproteinases and Atherogenesis in Dependence of Age (2006)

MMPs navigate the behavior of vascular wall cells in different AS stages, in adaptive remodeling, in normal aging and in non-atherosclerotic vessel disease. The clinical relevance of a disturbance in the MMP/TIMP balance is demonstrated firstly by the initiation of AS due to migration and proliferation of intima cells and secondly in the collagenolysis, necrotic transformation and apoptosis of existing fibrous lesions resulting in instabile rupture proned plaques. Investigations into the genetic typing of MMPs and the results of experimental gene deficiency models have significantly contributed to the clarification of these facts.
Absence of integrin-mediated TGFβ1 activation in vivo recapitulates the phenotype of TGFβ1-null mice (2007)

The multifunctional cytokine transforming growth factor (TGF) beta1 is secreted in a latent complex with its processed propeptide (latency-associated peptide [LAP]). TGFbeta1 must be functionally released from this complex before it can engage TGFbeta receptors. One mechanism of latent TGFbeta1 activation involves interaction of the integrins alpha v beta6 and alpha v beta8 with an RGD sequence in LAP; other putative latent TGFbeta1 activators include thrombospondin-1, oxidants, and various proteases. To assess the contribution of RGD-binding integrins to TGFbeta1 activation in vivo, we created a mutation in Tgfb1 encoding a nonfunctional variant of the RGD sequence (RGE). Mice with this mutation (Tgfb1(RGE/RGE)) display the major features of Tgfb1(-/-) mice (vasculogenesis defects, multiorgan inflammation, and lack of Langerhans cells) despite production of normal levels of latent TGFbeta1. These findings indicate that RGD-binding integrins are requisite latent TGFbeta1 activators during development and in the immune system.
Synthesis of δ-(α-aminoadipyl)cysteinylvaline and its role in penicillin biosynthesis (1976)

1. The stereoisomers of delta-(alpha-aminoadipyl)-L-cysteinylvaline (LLD, LLL and DLD) were synthesized from valine labelled with 3H in its methyl groups or in the alpha position. L-Cysteinyl-D-[4,4'-3H]valine was also synthesized. 2. 3H was incorporated into a compound that behaved like penicillin N when the LLD tripeptide containing either a methyl- or an alpha-labelled valine residue was incubated with a cell-free system prepared by lysis of protoplasts of Cephalosporium acremonium. 3. Incorporation was not observed under these conditions from the labelled all-L- or DLD-tripeptide, from L-cysteinyl-D-[4,4'-3H]valine, or of Penicillium chrysogenum appeared to be the LLD isomer, like that from C. acremonium. 5. These findings are discussed in relation to penicillin biosynthesis.
[Weekly administration of paclitaxel and pirarubicine for recurrent breast cancer]. (2003)

The therapeutic efficacy of weekly coadministration of paclitaxel (TXL) and pirarubicin (THP) on docetaxel (TXT)- and epirubicin-resistant recurrent breast cancer, adverse reactions caused by this therapy, and the possibility of ambulatory treatment using it were evaluated. The present study was conducted in 11 patients with recurrent breast cancer with pretreatment with CEF and TXT. The site of recurrence was the lung in 9 patients, lymphnodes in 2, bones in 1, liver in 1 and local foci in 1. One cycle consisted of 20 mg/m2 of THP followed by 80 mg/m2 of TXL 4 h later, repeated three times every other week. Three to six cycles were conducted in each patient. An anti-emetic drug was administered before administration of THP as short premedication. Dexamethasone (16 mg; i.v.) and d-chlorpheniramine maleate (12 mg; p.o.) were administered 1 h before administration of TXL and ranitidine (100 mg; i.v.) was administered 30 min before administration of TXL. Ubidecarenone (30 mg/day; p.o.) was administered for 3 days. The response rate was 27.3% with a rating of PR in 3 patients, NC in 6, and PD in 2. Adverse reactions observed included transient facial hot flushes, alopecia grade 1 or milder grade 1 symptoms, and peripheral nerve damage. No adverse reactions such as myocardial disorders or congestive heart failure were noted. Grade 3 and grade 2 neutropenia occurred in 1 and 6 patients, respectively, and 4 patients were admitted for treatment of this. In conclusion, the short premedication was useful, and this was thought to make it possible to conduct ambulatory treatment with TXL + THP in some patients. The response rate of 27.3%, however, was not satisfactory. It will be necessary to clarify the characteristics of this therapy by administering it to a wider spectrum of patients.
The keystroke-level model for user performance time with interactive systems (1980)

There are ~eg:N ms:poets of aser~emt,xu{er ~rforma~ce tha~ sys*em designers sh~d sys~emarka{~ ~ e r. This arlic|e prop~yses a ~im~}e m~eL the Neys{T{.>ke-Levd Medea, for predkd~g o
Elevated cerebrospinal fluid levels of substance p in patients with the fibromyalgia syndrome (1994)

SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms.