gebhart/patrepeval huggingface dataset:
Atomic Landscapes Beckon Researchers (1996)

At two recent meetings, physicists and chemists explored new strategies for observing conformation changes in individual molecules and etching ever smaller features on computer chips.
Recurrent G-to-A substitution in a single codon of SREBP cleavage-activating protein causes sterol resistance in three mutant Chinese hamster ovary cell lines (1996)

Oxygenated sterols such as 25-hydroxycholesterol kill Chinese hamster ovary cells because they inhibit the proteolytic processing of sterol regulatory element binding proteins (SREBPs), a pair of membrane-bound transcription factors that activate genes controlling cholesterol synthesis and uptake from lipoproteins. The unprocessed SREBPs remain membrane-bound, they cannot activate the cholesterol biosynthetic pathway, and the cells die of cholesterol deprivation. Several sterol-resistant hamster cell lines have been isolated previously by chemical mutagenesis and selection for resistance to killing by 25-hydroxycholesterol. We recently identified the defect in one such cell line (25-RA cells) as a point mutation in a newly discovered membrane protein of 1276 amino acids, designated SREBP cleavage-activating protein (SCAP). The mutation in the 25-RA cells resulted from a G-to-A transition in codon 443 of the SCAP gene, changing aspartic acid to asparagine. Wild-type SCAP, when overexpressed by transfection, stimulates the proteolytic processing of both SREBPs. The D443N substitution is an activating mutation that increases the activity of SCAP and renders it resistant to inhibition by 25-hydroxycholesterol. We here report the identical G-to-A transition in two additional lines of Chinese hamster ovary cells that were mutagenized and isolated by a similar protocol. The three mutations occurred independently as indicated by haplotype analysis of the mutant genes using two intragenic sequence polymorphisms. All three cell lines were mutagenized with alkylating agents (nitrosoethylurea or ethylmethane sulfonate) that favor G-to-A transitions. Nevertheless, the finding of the same nucleotide substitution at the same location in all three cell lines indicates that SCAP may be unique in its ability to stimulate SREBP cleavage, and residue 443 is a crucial determinant of the protein's ability to be inhibited by 25-hydroxycholesterol.
Facile preparation of nuclease resistant 3′ modified oligodeoxynucleotides (1993)

An efficient chemical procedure for the immobilization of carboxylate containing conjugate groups onto controlled pore glass (CPG) is described. The derivatized supports were used in the automated synthesis of an oligodeoxynucleotide (20-mer ODN) containing a 3' phosphodiester linked hexanol, aminohexyl, acridine, or cholesterol group. The stability of the oligomer in a hepatoma cell culture was found to be prolonged two to three fold by the presence of any of the 3' tails. By contrast, an aminohexyl group appended to the 5' terminus of the ODN only marginally improved its nuclease resistance. These data support the notion that antisense ODNs are primarily degraded by 3' exonucleases. Introduction of simple 3' tails which incorporate a normal phosphodiester linkage can increase ODN stability by interfering with these enzymes.
5% Dimethyl sulfoxide (DMSO) and pentastarch improves cryopreservation of cord blood cells over 10% DMSO (2010)

Our data indicate that the lower DMSO concentration with pentastarch represents an improvement in the CB cryopreservation process and could have wider clinical application as an alternate freezing medium over 10% DMSO.
Structure and expression of germline immunoglobulin γ3 heavy chain gene transcripts: implications for mitogen and lymphokine directed class-switching (1990)

We have characterized the structure and expression of transcripts synthesized from the murine germline immunoglobulin gamma 3 heavy chain gene in certain B-lineage cells. The transcripts initiate upstream of the switch gamma 3 region, generating a 5' exon that is spliced to C gamma 3 exons. Expression of this germline transcript is induced when splenic B cells or A-MuLV-transformed pre-B cell lines are cultured in the presence of lipopolysaccharide (LPS). Addition of interleukin-4 (IL-4) to these lipopolysaccharide (LPS) cultures dramatically inhibits induction of the germline gamma 3 transcript. Induction of germline gamma 3 transcripts occurs before the increased accumulation of gamma 3-producing cells and VDJ-gamma 3 mRNA in cultures of splenic B cells. These data provide further evidence that germline CH transcriptional units are important components in the regulation of heavy chain class-switching. In addition, the pre-B cell lines that we describe represent the first example of permanent cell lines that regulate expression of the germline gamma locus in response to LPS plus IL-4 treatment in a manner analogous to normal B cells; therefore these lines should represent an excellent model system to further study the molecular mechanisms by which germline expression is regulated by these agents.
Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study (2017)

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Although 5-year survival rates in the first-line setting range from 60% to 70%, up to 50% of patients become refractory to or relapse after treatment. Published analyses of large-scale outcome data from patients with refractory DLBCL are limited. SCHOLAR-1, an international, multicohort retrospective non-Hodgkin lymphoma research study, retrospectively evaluated outcomes in patients with refractory DLBCL which, for this study, was defined as progressive disease or stable disease as best response at any point during chemotherapy (>4 cycles of first-line or 2 cycles of later-line therapy) or relapsed at ≤12 months from autologous stem cell transplantation. SCHOLAR-1 pooled data from 2 phase 3 clinical trials (Lymphoma Academic Research Organization-CORAL and Canadian Cancer Trials Group LY.12) and 2 observational cohorts (MD Anderson Cancer Center and University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence). Response rates and overall survival were estimated from the time of initiation of salvage therapy for refractory disease. Among 861 patients, 636 were included on the basis of refractory disease inclusion criteria. For patients with refractory DLBCL, the objective response rate was 26% (complete response rate, 7%) to the next line of therapy, and the median overall survival was 6.3 months. Twenty percent of patients were alive at 2 years. Outcomes were consistently poor across patient subgroups and study cohorts. SCHOLAR-1 is the largest patient-level pooled retrospective analysis to characterize response rates and survival for a population of patients with refractory DLBCL.
Microinjection of pp60v-src into Xenopus oocytes increases phosphorylation of ribosomal protein S6 and accelerates the rate of progesterone-induced meiotic maturation. (1984)

Microinjection of purified pp60v-src into Xenopus oocytes caused the phosphorylation of ribosomal protein S6 on serine residues and also increased total protein phosphorylation, with almost a two-fold increase in the percentage of phosphotyrosine present. In addition, pp60v-src accelerated the time course of progesterone-induced oocyte maturation, suggesting that the biochemical pathway influenced by pp60v-src is related to that induced by progesterone.
Effect of L‐Phenylalanine methyl ester on the colony formation of hematopoietic progenitor cells from human bone marrow (1991)

We have previously shown that L-phenylalanine methyl ester (PME) is capable of removing monocytes and enhancing the growth of hematopoietic colonies from human peripheral blood (PB) mononuclear cells (MNC). In the present study, we further compared the effect of PME on the colony formation of bone marrow (BM) and PB. Low density (less than or equal to 1.077 g/ml) MNC were obtained by Ficoll-diatrizoate density gradient centrifugation. Granulocyte/macrophage colony-forming units (CFU-gm) and erythroid burst-forming units (BFU-e) were cultured in agarose with conditioned media (CM) and/or interleukin 3 (IL-3), granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage-CSF (GM-CSF). Treatment of BM MNC with 5 mM PME for 15 min at room temperature yielded a nucleated cell recovery of 44.8 +/- 5.0% (mean +/- SE; N = 8). CFU-gm were enriched 2.7-fold (range 2.0 to 4.8). Using CM or CM supplemented with G-CSF or GM-CSF has minimal effect on the enrichment. Leukocyte differentials revealed that 94.3 +/- 3.05% of the monocytes, as well as 91.2 +/- 1.60% of the cells in the neutrophilic maturation series were removed by PME. Incubation for 40 min in PME abolished CFU-gm formation. BFU-e were not enriched by the PME treatment. In contrast, 40 min incubation of PB MNC produced higher enrichment of CFU-gm than that obtained from 15 min of treatment, although lower cell recovery was obtained with the longer treatment time. In conclusion, we have demonstrated that phagocytic cells can be removed from BM or PB MNC by PME treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Empirical estimation of protein-induced DNA bending angles: applications to λ site-specific recombination complexes (1988)

Protein-induced DNA bending is an important element in the structure of many protein-DNA complexes, including those involved in replication, transcription, and recombination. To understand these structures, the path followed by the DNA in each complex must be established. We have generated an empirical relation between the degree of bending and the altered electrophoretic mobility in polyacrylamide gels that allows estimation of protein-induced bends. This technique has been used to analyze 17 different protein-DNA complexes formed by six proteins including the four proteins involved in lambda site-specific recombination. The simplicity of this technique should make it useful in estimating angles for the construction of models of protein-DNA complexes and readily applicable to many systems where questions of higher-order structure are important for understanding function.
On-line process fault diagnosis using neural network techniques (1992)

A neural-network based on-line fault-diagnosis system for industrial processes is presented in this paper. A multi-layer feed-forward neural network is developed and trained with symptom-fault pairs from experience of the operation of a process or from simulation analysis of that process. The trained network can be used to diagnose faults in that it can associate the abnormalities in on-line measurements with corresponding faults. Compared with diagnosis systems based on expert-systems techniques, which have several limitations such as the time consuming nature of developing the knowledge base and the inability to cope with situations not presented in the knowledge base, the neural-network based fault-diagnosis system is easy to develop and performs robustly. The feasibility of applying such a diagnosis system to industrial processes is demonstrated by applying it to a pilot-scale mixing process and in a simulation study of a continuously-stirred tank reactor (CSTR) system. A series of experiments is carried out to investigate the performance of the neutral-network based on-line diagnosis system and it is shown that it can perform satisfactorily with partially incorrect and partially unavailable information. Therefore, to some extent, the system can tolerate measurement noise and model-plant mismatch.
Prospective Evaluation of Skin Surface Electropotentials in Japanese Patients with Suspicious Breast Lesions (1996)

The biofield breast examination (BBE) is a new, noninvasive and cost-effective method for diagnosing breast lesions currently undergoing multicenter evaluation in the USA and Europe. The test analyzes subtle differences in electrical potential caused by dysregulated epithelial proliferation. This report summarizes a prospective evaluation of BBE in a population of 101 patients with suspicious breast lesions scheduled either for open surgical biopsy or fine needle aspiration biopsy. Of the 101 patients included in the study, 49 were found to have a breast malignancy and 52 were found to have a benign breast lesion. BBE correctly identified 44 of 49 biopsy-proven cancers (sensitivity=90%) and correctly indicated no cancer in 31 of 52 biopsy-proven benign cases (specificity=60%). Sensitivity increased to 95% for cancers less than 2.5 cm in size. These results indicate that BBE may be an effective adjunctive test to help to resolve abnormalities discovered by physical examination or other screening methods.
Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells (2012)

We show that anti-CD20 IgA antibodies have original therapeutic properties against lymphoma cells, with strong direct effects, ability to recruit neutrophils for cell cytotoxicity and even recruitment of complement, although largely through an indirect way.
Optimizing Fragment and Scaffold Docking by Use of Molecular Interaction Fingerprints (2006)

Protein-ligand interaction fingerprints have been used to postprocess docking poses of three ligand data sets: a set of 40 low-molecular-weight compounds from the Protein Data Bank, a collection of 40 scaffolds from pharmaceutically relevant protein ligands, and a database of 19 scaffolds extracted from true cdk2 inhibitors seeded in 2230 scaffold decoys. Four popular docking tools (FlexX, Glide, Gold, and Surflex) were used to generate poses for ligands of the three data sets. In all cases, scoring by the similarity of interaction fingerprints to a given reference was statistically superior to conventional scoring functions in posing low-molecular-weight fragments, predicting protein-bound scaffold coordinates according to the known binding mode of related ligands, and screening a scaffold library to enrich a hit list in true cdk2-targeted scaffolds.
Robotic Assisted Microsurgery (RAMS): Application in Plastic Surgery (2008)

Surgical robotic technology is now on the cusp of revolutionizing microsurgical capabilities. With the latest advancements in the field of RAMS, the armamentarium available to the plastic surgeons will be greatly expanded. The advantages are self evident. The use of RAMS technology during microsurgery will greatly improve the microsurgical outcome by providing surgeons with greater precision, elimination of hand tremors, increased range of motion and enhanced 3-D visualization. With the continued evolution of robotic surgical technology the robots are expected to become smaller, faster, lighter and dexterous with exponentially increased application in micro-vascular surgery. The robots despite of technical advancements are never likely to replace the highly evolutionized human hand. The robots r ather than replacing the human hand will help to retain the benefits of the human hand along with its superlative optimization to achieve the goal of optimal precision and predictability. By combining the robotic technology with human skills, the RAMS system will allow the performance of more precise and more dexterous operations to the zenith. The present surgical training programmes must include some robotic training in their curriculum keeping in the mind its exploding potential and future use by the present and next generations of microsurgeons.
Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. (1992)

The individual nutrients arginine, RNA, and omega-3 fatty acids improve immune function, but prospective trials have not demonstrated their effects on clinical outcome. Patients (n = 85) who underwent operation for upper gastrointestinal malignancies were randomized to receive the supplemental diet or a standard enteral diet after surgery. Clinical patient characteristics were similar between the two groups. Mean caloric intakes (1421 vs 1285 kcal/day) were similar between groups. Mean nitrogen intakes (15.6 vs 9.0 gm/day) and nitrogen balances (-2.2 vs -6.6 gm/day) measured in the first 20 patients were significantly greater in the supplemented group than in the standard group (p = 0.05). In vitro lymphocyte mitogenesis was measured in the first 31 patients and was decreased on postoperative day 1 in both groups, but normal levels were regained only in the supplemented group. In the cohort of 77 eligible patients, infectious and wound complications occurred significantly less often (11% vs 37%) in the supplemented group than in the standard group (p = 0.02). Linear logistic models for infectious/wound complications with control for the amount of nitrogen suggested (p = 0.10) dietary treatment as the major factor. Mean length of stay in the hospital was significantly shorter (p = 0.01) for the supplemented group (15.8 +/- 5.1 days) than for the standard group (20.2 +/- 9.4 days). These results suggest that postoperative enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids instead of a standard enteral diet significantly improved immunologic, metabolic, and clinical outcomes in patients with upper gastrointestinal malignancies who were undergoing major elective surgery.
Common Vascular Changes in the Jugular Vein of Saline Controls in Continuous Infusion Studies in the Beagle Dog (2004)

This review was performed to assess the nature and incidence of procedure-related background changes in control dogs receiving saline by continuous infusion, and to compare them with data from a similar review previously done in Cynomolgus monkeys. Data were collected from 14 dog studies performed over an 8-year period (i.e., 86 animals in total). The review was restricted to lesions at the injection site, in the lungs and at the catheter'sentry point. The most frequently seen changes were endothelial hyperplasia (67.4%) and intimal thickening at the injection site (80.2%) and interstitial pneumonitis in the lungs (52.6%), all seen at a higher incidence in dogs than in primates. Although incidences of thrombosis at the injection site were similar in both dogs (27.9%) and monkeys (34.1 %), the incidences of thromboemboli and secondary infarction in the lungs were much higher in dogs. This suggests that dogs have a greater propensity to thrombus formation and fragmentation at the injection site. However the fact that the femoral vein is used in monkeys and the jugular vein in dogs may explain this difference. The larger diameter of the jugular vein in the dog with its greater turbulence of blood flow possibly predisposes to fragmentation and dispersal of thrombi.
An open‐label, crossover study of a new phosphate‐binding agent in haemodialysis patients: ferric citrate (2002)

Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.
Regulation of Metabolism in Transgenic Plants (1995)

This review discusses how genetically manipulated plants are being used to study the regulation of metabolism in plants, using carbohydrate metabolism as an example. The molecular tools required are introduced, including the history of Agrobacterium tumefaciens-mediated gene transfer and other transformation techniques, the availability of promoters to achieve a specific or induced expression, strategies to target proteins to subcellular compartments of the cell, and the use of antisense or cosuppression to inhibit expression of endogenous genes. A discussion then follows of how such plants can be used in biochemical and physiological experiments to identify and quantify the importance of enzymes and processes that control metabolic fluxes, storage, and growth. These results are leading to a reassessment of ideas about metabolic regulation and have consequences for design of bioengineering strategies in plants. Emerging commercial applications are also surveyed.
Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders (2002)

T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4(+) and CD8(+) T cell clones through the detection and quantification of T cell receptor (TCR) alpha or beta chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders.
Association of serum interleukin‐33 level and the interleukin‐33 genetic variant with Japanese cedar pollinosis (2008)

Our results support a role for IL-33 in the pathogenesis of JC pollinosis.
An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro (1989)

One-cell CF-1 x B6SJLF1/J embryos, which usually exhibit a 2-cell block to development in vitro, have been cultured to the blastocyst stage using CZB medium and a glucose washing procedure. CZB medium is a further modification of modified BMOC-2 containing an increased lactate/pyruvate ratio of 116, 1 mM-glutamine and 0.1 mM-EDTA but lacking glucose. Continuous culture of one-cell embryos in CZB medium allowed 83% of embryos to develop beyond the 2-cell stage of which 63% were morulae at 72 h of culture, but blastocysts did not develop. However, washing embryos into CZB medium containing glucose after 48 h of culture (3-4-cell stage) was sufficient to allow development to proceed, with 48% of embryos reaching the blastocyst stage by 96 h of culture. Exposure of embryos to glucose was only necessary from the 3-4-cell stage through the early morula stage since washing back into medium CZB without glucose at 72 h of culture still promoted the development of 50% of embryos to the blastocyst stage. The presence of glucose in this medium for the first 48 h of culture (1-cell to 4-cell stage) was detrimental to embryo development. Glutamine, however, exerted a beneficial effect on embryo development from the 1-cell to the 4-cell stage although its presence was not required for development to proceed during the final 48 h of culture. Blastocysts which developed under optimum conditions contained an average of 33.7 total cells. The in-vitro development of 1-cell embryos beyond the 2-cell stage in response to the removal of glucose and the addition of glutamine to the culture medium suggests that glucose may block some essential metabolic process, and that glutamine may be a preferred energy substrate during early development for these mouse embryos.