gebhart/patrepeval huggingface dataset:
Worldwide Evaluation of DNA Sequencing Approaches for Identification of Drug Resistance Mutations in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase (1999)

A panel (ENVA-1) of well-defined blinded samples containing wild-type and mutant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase was analyzed by automated DNA sequencing in 23 laboratories worldwide. Drug resistance mutations at codons 41, 215, and 184 were present in the panel samples at different ratios to the wild type. The presence of mutant genotypes was determined qualitatively and quantitatively. All laboratories reported the presence of sequence heterogeneities at codons 41, 215, and 184 in one or more of the panel samples, though not all reported the correct codon genotypes. Two laboratories reported a mutant genotype in samples containing only the wild type, whereas two and three laboratories failed to detect the mutant genotypes at codons 41 and 215, respectively, in a completely mutant DNA population. Mutations present at relative concentrations of 25% of the total DNA population were successfully identified by 13 of 23, 10 of 23, and 16 of 23 labs for codons 41, 215, and 184Val, respectively. For more than 80% of those laboratories that qualitatively detected the presence of a mutation correctly, the estimated wild type/mutant ratio was less than 25% different from the input ratio in those samples containing 25 to 50% or 75% mutant input. This first multicenter study on the quality of DNA sequencing approaches for identifying HIV-1 drug resistance mutations revealed large interlaboratory differences in the quality of the results. The application of these procedures in their current state would in several cases lead to inaccurate or even incorrect diagnostic results. Therefore, proper quality control and standardization are urgently needed.
4‐Amino‐3‐pyridiniochinolin‐2(1H)‐on‐chloride und 3,4‐Diaminochinolin‐2(1H)‐one (1991)

4‐Amino‐3‐pyridinioquinolin‐2(1 H )‐one Chlorides and 3,4‐Diaminoquinolin‐2(1 H )‐ones N ;‐(Chloroacetyl)anthranilonitriles 1 react with the pyridines 2 to form the 4‐amino‐3‐pyridinioquinolin‐2(1 H )‐one chlorides 4 , which are converted into the pyrido[ 1 ',2′ : 1,2]imidazo[5,4‐c]‐ quinolin‐6(5H)‐ones 6 in the presence of sodium hydroxide or by cyclooxidation with bromine. Treatment of 4 with hydrazine hydrate yields the 3,4‐diaminoquinolin‐2(1 H )‐ones 9 . Analogously to other o‐diamines the substituted imidazo [4,5‐c]‐ quinolinones 12 , the pyrazino[2,3‐c]quinolinones 13, 14 , the 1,2,5‐thiadiazolo[3,4‐c]quinolin‐4‐one 15a and the 1,2,5‐selena‐diazolo[3,4‐c]quinolin‐4‐one 15b are obtainable from 9a . With chloroacetyl chloride 9a provides the oxazino[2,3‐b]quinolin‐2‐one 11 .
Human monoclonal rheumatoid factors: incidence of cross-reactions with tissue components and correlation with VH gene usage. (1994)

Human monoclonal antibodies with rheumatoid factor (RF) activity, derived from lymphocytes from the synovial tissue of rheumatoid arthritis (RA) patients and the peripheral blood of healthy individuals were examined for cross-reactivity with tissue and cellular antigens. The majority of IgM RF from RA patients (68%) showed reactivity with at least one component, and were frequently multispecific. A very significantly smaller proportion (28%) of the RF derived from healthy individuals demonstrated reactivities against tissue/cellular antigens (P = 0.004). RF from RA patients most commonly reacted with gastric glands (61%), nuclei (50%) and smooth muscle (50%), whereas RF from healthy donors most commonly reacted with gastric glands (20%), smooth muscle (16%), endothelium (16%) and glomeruli (16%). The most striking difference between the two groups was the reactivity with nuclear components, demonstrated by 50% of the RA RF, but by none of the healthy donor RF. As the two groups of antibodies share the same specificity for IgG Fc, but show differences in variable region segment usage, we investigated the relationship between VH gene usage and tissue/cell cross-reactivity using these antibodies and anti-blood group antibodies. Antibodies using VH3 or VH4 gene segments showed a very significantly greater frequency of tissue/cell reactions than those using VH1 (P = 0.0095 and 0.0004 respectively).
Insulin Glargine: a review 8 years after its introduction (2009)

Insulin Glargine was the first long-acting insulin analog produced by recombinant DNA technology, approved for use by the US FDA in April 2000 and by the European Agency for the Evaluation of Medicinal Products in June, 2000. It has become the most widely used insulin in the USA owing to its long duration of action without a pronounced peak. The principal advantage of insulin Glargine over neutral protamine Hagedorn (NPH) insulin is in a lower frequency of hypoglycemic reactions, thus affording improved safety. It is used in both type 1 and type 2 diabetes, usually as a single daily dose. In type 2 patients, it is often the first insulin introduced as a single daily dose. Although insulin Glargine is typically administered as a single nighttime dose, it can be given in the morning or at any other time convenient for the patient. In labile type 1 diabetes, it is often most effective given as two daily injections. In obese, insulin-resistant patients, it may be best to administer insulin Glargine in two separate doses, owing to the high volumes of injected insulin required. Insulin Glargine does not treat postprandial hyperglycemia. It is necessary to supplement with short-acting insulin at mealtimes to control glucose surges after meals. Insulin Glargine is effective in hospitalized and postsurgical patients on account of its lack of pronounced insulin peaks and long duration of action. Although there is considerable use of Glargine in pregnant diabetic women, there is no definitive study to confirm its benefits. Insulin Glargine is thought to coprecipitate supplementary short-acting insulins when co-administered in the same syringe. Therefore, more injections are typically needed in the usual treatment regimen for insulin requiring diabetes. In many cases, constant basal insulin levels may be achieved with multiple overlapping doses of NPH insulin given together with short-acting insulin at mealtimes. Such a therapy may be less costly, but the major advantage of insulin Glargine remains the greater safety of a lower frequency of hypoglycemic reactions.
Response Surface Optimization of Hydrolysis Processing for Cordyceps militaris (2012)

In order to convert Cordyceps militaris which was a kind of food resouce into a convenient edible form,following experiments were carried out.First,papain was chosen as the enzyme to hydrolyze C.militaris from different kind of proteinase,in which degree of hydrolysis was designed as the target index.Response surface analysis(RSA) was applied to optimize the conditions of enzymatic hydrolysis for C.militaris processing.According to the principle of Box-Behnken central composite design,enzymatic hydrolysis time,enzymeatic hydrolysis temperature,and enzyme dosage were chosen as factors to process the three-factor and three-level central composite design.By response surface analysis,the optimum conditions for enzymatic hydrolysis was obtained as follows:enzymatic hydrolysis time 11.85 h,enzymatic temperature 60.92 ℃,enzyme dosage 1.02%,under which the highest hydrolysis degree reached with estimated value and verified value being 61.27% and 60.76%,respectively.These results demonstrated the validity of this hydrolysis process.
Developmental stage-specific regulation of atrial natriuretic factor gene transcription in cardiac cells. (1994)

Cardiac myocytes undergo a major genetic switch within the first week of postnatal development, when cell division ceases terminally and many cardiac genes are either activated or silenced. We have developed stage-specific cardiocyte cultures to analyze transcriptional control of the rat atrial natriuretic factor (ANF) gene to identify the mechanisms underlying tissue-specific and developmental regulation of this gene in the heart. The first 700 bp of ANF flanking sequences was sufficient for cardiac muscle- and stage-specific expression in both atrial and ventricular myocytes, and a cardiac muscle-specific enhancer was localized between -136 and -700 bp. Deletion of this enhancer markedly reduced promoter activity in cardiac myocytes and derepressed ANF promoter activity in nonexpressing cells. Two distinct domains of the enhancer appeared to contribute differentially to cardiac specificity depending on the differentiation stage of the myocytes. DNase I footprinting of the enhancer domain active in differentiated cells revealed four putative regulatory elements including an A+T-rich region and a CArG element. Deletion mutagenesis and promoter reconstitution assays revealed an important role for the CArG-containing element exclusively in cardiac cells, where its activity was switched on in differentiated myocytes. Transcriptional activity of the ANF-CArG box correlated with the presence of a cardiac- and stage-specific DNA-binding complex which was not recognized by the c-fos serum response element. Thus, the use of this in vitro model system representing stage-specific cardiac development unraveled the presence of different regulatory mechanisms for transcription of the ANF gene during cardiac differentiation and may be useful for studying the regulatory pathways of other genes that undergo switching during cardiac myogenesis.
Geometry Reduction in Room Acoustics Modeling (2008)

The complexity of a room model affects to the computational resources required to model its acoustics by means of geometrical acoustics modeling methods. Thus, a method for reducing the geometry of the room models is presented for static room geometries. The topology of the model is simplified in a process where the model is first decomposed into a volumetric structure. The surface is reconstructed by utilizing this structure, and subsequently simplified by merging coplanar regions. The results of the method are verified by extracting room acoustical attributes from the original and reduced models with the ODEON room acoustics prediction software. It is shown that the most important acoustic properties have been preserved, even with relatively high reduction rates.
Inhibition of endometrial carcinoma cell cultures by a synthetic androgen. (1985)

This paper describes the dose-response inhibitory effects of a synthetic androgen, methyltrienolone, on the growth of a grade II endometrial adenocarcinoma in vitro. Derived from a nude mouse heterotransplant, this cell line has maintained the morphological characteristics of the original human tumor, remains tumorigenic in the nude mouse, forms colonies on soft agar, and exhibits low levels of estrogen receptors. Data reported in this paper indicate that the cells contain androgen binding sites. At low doses of 0.25 micrograms/ml methyltrienolone had no effect on these cells, whereas at 1.0 and 10.0 micrograms/ml there was significant dose dependent inhibition of cell growth and an increase in the cell doubling time. Both testosterone and dihydrotestosterone were not inhibitory to the cells except at high doses where inhibition was slight. Methyltrienolone was not inhibitory to normal human foreskin fibroblast cultures tested as a control for cytotoxicity of the synthetic androgen. These data suggest that androgens may play a role in the treatment of tumors not responsive to conventional forms of hormonal therapy.
Augmented Hageman factor and prolactin titers, enhanced cold activation of factor VII, and spontaneous shortening of prothrombin time in survivors of myocardial infarction. (1987)

Hyperestrogenemia has been implicated in the pathophysiology of myocardial infarction. Because marked augmentation of the titer of Hageman factor is brought about by the administration of estrogens in humans and by prolactin or estrogen infusion in hypophysectomized rats, we measured the plasma concentrations of estradiol, prolactin, and clotting factors participating in surface-mediated reactions of coagulation in survivors of myocardial infarction. We observed higher titers of Hageman factor, prolactin, and high molecular weight kininogen but no significant change in estradiol or prekallikrein in survivors of myocardial infarction compared with controls. The titer of Hageman factor tended to be directly associated with the prolactin titer. We also report an increase in factor VII activity and spontaneous shortening of prothrombin time in the cold-stored plasma of survivors of myocardial infarction. In such individuals as well as in the control group, the titer of Hageman factor appeared to be responsible for half of the observed increase in factor VII activity and two thirds of the observed shortening of prothrombin time. These data indicate that although the titer of Hageman factor strongly influences the cold activation of factor VII, other factors may affect these phenomena.
In the Absence of Type III Receptor, the Transforming Growth Factor (TGF)-β Type II-B Receptor Requires the Type I Receptor to Bind TGF-β2 (2004)

Transforming growth factor beta (TGF-beta) ligands exert their biological effects through type II (TbetaRII) and type I receptors (TbetaRI). Unlike TGF-beta1 and -beta3, TGF-beta2 appears to require the co-receptor betaglycan (type III receptor, TbetaRIII) for high affinity binding and signaling. Recently, the TbetaRIII null mouse was generated and revealed significant non-overlapping phenotypes with the TGF-beta2 null mouse, implying the existence of TbetaRIII independent mechanisms for TGF-beta2 signaling. Because a variant of the type II receptor, the type II-B receptor (TbetaRII-B), has been suggested to mediate TGF-beta2 signaling in the absence of TbetaRIII, we directly tested the ability of TbetaRII-B to bind TGF-beta2. Here we show that the soluble extracellular domain of the type II-B receptor (sTbetaRII-B.Fc) bound TGF-beta1 and TGF-beta3 with high affinity (K(d) values = 31.7 +/- 22.8 and 74.6 +/- 15.8 pm, respectively), but TGF-beta2 binding was undetectable at corresponding doses. Similar results were obtained for the soluble type II receptor (sTbetaRII.Fc). However, sTbetaRII.Fc or sTbetaRII-B.Fc in combination with soluble type I receptor (sTbetaRI.Fc) formed a high affinity complex that bound TGF-beta2, and this complex inhibited TGF-beta2 in a biological inhibition assay. These results show that TGF-beta2 has the potential to signal in the absence of TbetaRIII when sufficient TGF-beta2, TbetaRI, and TbetaRII or TbetaRII-B are present. Our data also support a cooperative model for receptor-ligand interactions, as has been suggested by crystallization studies of TGF-beta receptors and ligands. Our cell-free binding assay system will allow for testing of models of receptor-ligand complexes prior to actual solution of crystal structures.
Wallstent deployment to salvage dialysis graft thrombolysis complicated by venous rupture: early and intermediate results. (1997)

Treatment of venous ruptures using Wallstents is a safe alternative to intentional graft thrombosis. The patency rates of these devices are similar to those of venous stents placed for other indications.
Improved performances of spot multiple peptide synthesis. (1997)

We have developed a new software for the design of peptides to be prepared by the manual Spot synthesis method. It covers most of the common protocols for epitope mapping and offers flexibility for planning the experiment. We have also quantified the coupling efficiencies of three different coupling methods for the synthesis of four model decapeptides. The DIC/HOBT procedure was superior (mean coupling yield per cycle: 87% to 91%) to methods using pentafluorophenyl esters of Fmoc amino acids. All four peptides prepared by the three different coupling protocols were reactive with their cognate monoclonal antibody. Finally, using the best coupling method, we synthesized peptides of increasing length (10 to 29 residues) bearing the model epitope AcPGK at the N terminus and showed that peptides of up to 29 residues were immunoreactive.
Influence of smoking parameters on the delivery of tobacco-specific nitrosamines in cigarette smoke—a contribution to relative risk evaluation (1989)

The influence of the smoking parameters (puff profile, puff duration, puff volume, puff frequency) on the delivery of tobacco-specific nitrosamines (TSNAs) in mainstream smoke was investigated for six different cigarette brands, including filter cigarettes with very low to medium smoke yields and non-filter cigarettes with high and very high smoke yields. The puff profile did not influence the TSNA yields. The puff duration also had no remarkable influence on the TSNA delivery with the exception of a non-filter cigarette made of dark tobaccos. The puff volume and the puff frequency significantly influenced the TSNA yields. Increasing puff volume and frequency resulted in increasing TSNA values. The total volume drawn through a cigarette was calculated. The dependency of the TSNA delivery on the total volume was almost linear at least up to a total volume of approximately 500 ml/cigarette. The TSNA yield was the same for the same total volume no matter whether the total volume was due to a changing puff volume or a changing puff frequency. The total volume drawn through a cigarette is the main responsible factor for the TSNA delivery in mainstream smoke. Total volume data from smokers of low- and medium-tar cigarettes are used to calculate TSNA intake. The different smoking behaviour observed for smokers of low-tar and low-nicotine cigarettes as compared to standard smoking conditions is discussed with respect to the TSNA dependency on smoke parameters.
General I and Q data processing on a multichannel AO system (1986)

A multichannel space-integrating acoustooptic (AO) correlator is discussed with attention to its frequency selectivity and its ability to produce complex correlations. General I and Q channel data are considered. By using two properly tilted acoustooptic cells, the system allows frequency selectivity, a complex correlator, and coherent and noncoherent demodulation. By using one multichannel AO cell, we achieve minicorrelations, and by properly adding several such correlations we can process signals of larger duration and time–bandwidth product. Applications for this architecture in synchronization and demodulation are described and include its use in processing frequency-hopped encoded data.
Insights into the Catalytic Mechanism of Tyrosine Phenol-lyase from X-ray Structures of Quinonoid Intermediates (2008)

Amino acid transformations catalyzed by a number of pyridoxal 5'-phosphate (PLP)-dependent enzymes involve abstraction of the Calpha proton from an external aldimine formed between a substrate and the cofactor leading to the formation of a quinonoid intermediate. Despite the key role played by the quinonoid intermediates in the catalysis by PLP-dependent enzymes, limited accurate information is available about their structures. We trapped the quinonoid intermediates of Citrobacter freundii tyrosine phenol-lyase with L-alanine and L-methionine in the crystalline state and determined their structures at 1.9- and 1.95-A resolution, respectively, by cryo-crystallography. The data reveal a network of protein-PLP-substrate interactions that stabilize the planar geometry of the quinonoid intermediate. In both structures the protein subunits are found in two conformations, open and closed, uncovering the mechanism by which binding of the substrate and restructuring of the active site during its closure protect the quinonoid intermediate from the solvent and bring catalytically important residues into positions suitable for the abstraction of phenol during the beta-elimination of L-tyrosine. In addition, the structural data indicate a mechanism for alanine racemization involving two bases, Lys-257 and a water molecule. These two bases are connected by a hydrogen bonding system allowing internal transfer of the Calpha proton.
Fabrication of Modularly Functionalizable Microcapsules Using Protein-Based Technologies (2016)

Proteins are desirable building blocks to create self-assembled, spatially defined structures and interfaces on length-scales that are inaccessible by traditional methods. Here, we describe a novel approach to create functionalized monolayers using the proteins BslA and SpyCatcher/SpyTag. BslA is a bacterial hydrophobin whose amphiphilic character underlies its ability to assemble into a monolayer at both air/water and oil/water interfaces. We demonstrate that Bsa1A having the SpyTag peptide fused at the N- or C-terminus does not affect the formation of such monolayers. We establish the creation of stable oil-in-water microcapsules using BslA, and also show the fabrication of capsules outwardly displaying the reactive SpyTag peptide by fusing it to the C-terminus of BslA. Such capsules can be covalently labeled by reacting the surface-displayed SpyTag with SpyCatcher fused to any desired protein. We demonstrate this principle by labeling microcapsules using green fluorescent protein (GFP). All components are genetically encodable, the reagents can be readily prepared in large quantities, and all reactions occur at ambient temperature in aqueous solution. Thus, this straightforward, modular, scalable strategy has myriad potential applications in the creation of novel, functional materials, and interfaces.
Pseudotypes of human T-cell leukemia virus types 1 and 2: neutralization by patients' sera. (1984)

Pseudotypes of vesicular stomatitis virus (VSV) bearing envelope antigens of human T-cell leukemia virus (HTLV) types 1 and 2 were prepared by propagating VSV in cells lines productively infected with HTLV. Plaque assays of VSV (HTLV) pseudotypes were employed to determine the presence of (i) HTLV receptors on cells and (ii) neutralizing antibodies in the serum of patients with adult T-cell leukemia-lymphoma (ATLL). Cell surface receptors for HTLV-1 and HTLV-2 were found on nonlymphoid cells of human and mammalian origin. Neutralizing antibodies specific to VSV(HTLV-1) were found in sera of ATLL patients in titers varying from 1:50 to 1:30,000 and did not correlate closely with antibody titers for internal viral antigens. Sera from ATLL patients in the United Kingdom (Caribbean immigrants), United States, and Japan completely neutralized VSV (HTLV-1), indicating that the HTLV isolates from these distinct geographic regions represent a single envelope serotype. Neutralization of VSV (HTLV-1) was more specific and more sensitive than assays of syncytium inhibition. No cross-neutralization was observed between bovine leukosis virus and HTLV, and only limited cross-reaction was found for envelope antigens of HTLV-1 and HTLV-2. These studies show that VSV (HTLV) pseudotypes can be readily used to screen for neutralizing antibodies in patients' sera and to distinguish HTLV envelope serotypes.
Intravitreal injection analysis at the Bascom Palmer Eye Institute: evaluation of clinical indications for the treatment and incidence rates of endophthalmitis (2010)

In this series, the incidence of culture-positive endophthalmitis after intravitreal injection of vascular agents in an outpatient setting was very low. We believe that following a standardized injection protocol, adherence to sterile techniques and proper patient follow-up are determining factors for low incidence rates.
HIV-1 detection by nested PCR and viral culture in fresh or cryopreserved postmortem skin: potential implications for skin handling and allografting. (1997)

These data suggest that nested PCR on postmortem skin samples can detect HIV more reliably than on blood. They also demonstrate the potential viral infectivity of fresh or stored skin postmortem samples in HIV infected patients. They underscore the need for caution during the handling of skin tissue from HIV infected cadavers and confirm the potential risk related to accidental allografting of HIV contaminated skin.