gebhart/patrepeval huggingface dataset:
Representation of rearranged VH gene segments in the human adult antibody repertoire. (1995)

The heavy chain variable region composition of the human adult Ab repertoire is poorly defined, but recent evidence suggests that peripheral blood B cells may express a nonstochastic assortment of VH genes. In this study, the contribution of individual VH gene segments to the human Ab repertoire has been assessed. As a measure of VH gene utilization, the frequency of occurrence of eight individual VH3 gene segments contained in rearrangements was assessed in the peripheral blood B cells of two adult subjects. In addition, the frequency of occurrence of rearrangements containing nine individual VH4 gene segments was analyzed in one of the subjects. More than 2500 independent rearrangements were analyzed. For controls, amplifications and subsequent identification of nonrearranged VH3 and VH4 genes from the same individuals were also performed. The results of this germ-line analysis indicated that approximately 25 VH3 gene segments and nine VH4 gene segments could be amplified quantitatively. However, usage of elements was not uniform; one VH3 element, V3-23, and one VH4 element, V4-34, were represented among rearrangements more frequently than were other members of their respective families. This pattern of VH utilization was apparent in B cells isolated from the same subject after an 8-mo interval, indicating the relative stability of the repertoire over time. These results indicate that the adult human Ab repertoire is dominated by a few VH genes demonstrating a pattern of nonrandom utilization that could involve preferential rearrangement and/or receptor-dependent selection.
Profile scanning for three-dimensional structural patterns in protein sequences (1988)

Profile analysis measures the similarity between a target sequence and a group of aligned sequences (the probe). The probe sequences are used to produce a position-specific scoring table (the profile) that can be aligned with any sequence (the target) using standard dynamic programming methods. We are developing a library of profiles, each describing a different structural motif. This allows any target sequence to be rapidly scanned for the presence of structural motifs. Levels of significance for the comparison of target sequences with the profile are determined in advance, permitting an objective decision to be made as to whether a protein is likely to possess a structural motif.
Antileukemic Principles Isolated from Euphorbiaceae Plants (1976)

Extracts of Euphorbia esula L. and Croton tiglium L., two members of the Euphorbiaceae which have been used widely in folk medicine for treating cancers, showed antileukemic activity against the P-388 lymphocytic leukemia in mice. Systematic fractionation of the extract of Euphorbia esula L. led to characterization of a major antileukemic component as the new diterpenoid diester, ingenol 3,20-dibenzoate. Similar fractionation of Croton oil led to characterization of phorbol 12-tiglate 13-decanoate as an active principle.
Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype (2002)

Insufficient oxygen and nutrient supply often restrain solid tumor growth, and the hypoxia-inducible factors (HIF) 1 alpha and HIF-2 alpha are key transcription regulators of phenotypic adaptation to low oxygen levels. Moreover, mouse gene disruption studies have implicated HIF-2 alpha in embryonic regulation of tyrosine hydroxylase, a hallmark gene of the sympathetic nervous system. Neuroblastoma tumors originate from immature sympathetic cells, and therefore we investigated the effect of hypoxia on the differentiation status of human neuroblastoma cells. Hypoxia stabilized HIF-1 alpha and HIF-2 alpha proteins and activated the expression of known hypoxia-induced genes, such as vascular endothelial growth factor and tyrosine hydroxylase. These changes in gene expression also occurred in hypoxic regions of experimental neuroblastoma xenografts grown in mice. In contrast, hypoxia decreased the expression of several neuronal/neuroendocrine marker genes but induced genes expressed in neural crest sympathetic progenitors, for instance c-kit and Notch-1. Thus, hypoxia apparently causes dedifferentiation both in vitro and in vivo. These findings suggest a novel mechanism for selection of highly malignant tumor cells with stem-cell characteristics.
PREVENTT: preoperative intravenous iron to treat anaemia in major surgery: study protocol for a randomised controlled trial (2015)

ISRCTN67322816--registered 9 October 2012. ClinicalTrials.gov identifier: NCT01692418.
Type-2 pericytes participate in normal and tumoral angiogenesis (2014)

Tissue growth and function depend on vascularization, and vascular insufficiency or excess exacerbates many human diseases. Identification of the biological processes involved in angiogenesis will dictate strategies to modulate reduced or excessive vessel formation. We examine the essential role of pericytes. Their heterogeneous morphology, distribution, origins, and physiology have been described. Using double-transgenic Nestin-GFP/NG2-DsRed mice, we identified two pericyte subsets. We found that Nestin-GFP(-)/NG2-DsRed(+) (type-1) and Nestin-GFP(+)/NG2-DsRed(+) (type-2) pericytes attach to the walls of small and large blood vessels in vivo; in vitro, type-2, but not type-1, pericytes spark endothelial cells to form new vessels. Matrigel assay showed that only type-2 pericytes participate in normal angiogenesis. Moreover, when cancer cells were transplanted into Nestin-GFP/NG2-DsRed mice, type-1 pericytes did not penetrate the tumor, while type-2 pericytes were recruited during its angiogenesis. As inhibition of angiogenesis is a promising strategy in cancer therapy, type-2 pericytes may provide a cellular target susceptible to signaling and pharmacological manipulation in treating malignancy. This work also reports the potential of type-2 pericytes to improve blood perfusion in ischemic hindlimbs, indicating their potential for treating ischemic illnesses.
Flux Treated Pd&ndash;Cu&ndash;Ni&ndash;P Amorphous Alloy Having Low Critical Cooling Rate (1997)

A Pd40Cu30Ni10P20 alloy subjected to B2O3 flux treatment was found to have a low critical cooling rate (Rc) of 0.100 K/s for glass formation and a large sample thickness (tmax) of 72 mm by the water quenching process. The Rc and tmax exceed largely those (Rc=1.57 K/s, tmax=40 mm) for the Pd–Cu–Ni–P alloy without the flux treatment. It is concluded that the flux treatment causes a significant increase in the thermal stability of the supercooled liquid. The glass transition temperature (Tg) remains unchanged in the fluxed state, but the crystallization temperature (Tx) increases by 7 K, leading to the extension of the supercooled liquid region defined by ΔTx(=Tx−Tg) to 98 K which is larger than that (91 K) for the non-fluxed sample. The decrease in Rc and the increases in tmax and ΔTx for the fluxed sample are presumably due to the suppression of heterogeneous nucleation for crystallization resulting from the increase in the degree of cleanness of the molten alloy. Besides, the Pd–Cu–Ni–P amorphous alloy has lower Rc and melting temperature (Tm) and larger tmax, ΔTx and Tg⁄Tm values, as compared with those for Pd40Ni40P20 alloy. The larger glass-forming ability for the Pd–Cu–Ni–P alloy is presumably due to the increase in the degree of the satisfaction of the three empirical rules for the achievement of larger glass-forming ability resulting from the more systematic change in atomic size in the order Pd>>Cu>Ni>>P and the generation of Cu–Pd and Cu–P atomic pairs with negative heats of mixing. There is no appreciable difference in the Tg, Tx and crystallization behavior between the cast 72 mmφ amorphous ingot and melt-spun amorphous ribbon. The finding of the fluxed Pd40Cu30Ni10P20 alloy with the lower Rc and larger tmax values is promising for the future development of bulk amorphous alloys.
Molecular imaging and targeted drug delivery: merging medical paradigms (2004)

Advances in molecular biology and cellular biochemistry are providing new opportunities for diagnostic medical imaging. Molecular imaging provides an opportunity to "see" the earliest biochemical signatures of disease in vivo analogous to microscopic detection of epitopes with immunohistochemistry techniques. Previously the province of nuclear medicine, today numerous, highly active research programs can be found for all clinically relevant imaging modalities. In many instances, these emerging site-directed imaging agents also incorporate therapeutic agents for drug delivery, allowing noninvasive confirmation and quantification of the targeted therapeutic dose. We have developed a novel multi-modal site-targeted contrast agent for sensitive and specific imaging of molecular epitopes and local therapy, which illustrates the key features of these emerging platform technologies. Targeted nanoparticles are applicable to ultrasound, nuclear, CT, and magnetic resonance imaging and have been used to detect a variety of epitopes expressed on angiogenic vessels, thrombus, and within vascular walls. Moreover, this particular targeted agent can deposit a therapeutic payload through a unique mechanism termed "contact-facilitated delivery". The combined benefits of molecular imaging and therapeutic systems are merging and will potentially alter many current clinical paradigms in the next decade.
Rituximab Immunotherapy for Non-Hodgkin's Lymphoma (1999)

Rituximab, a chimeric monoclonal antibody targeting the CD20 antigen on B lymphocytes, is now the standard treatment for relapsed, low-grade or follicular non-Hodgkin's lymphoma.
Online and Linear-Time Attention by Enforcing Monotonic Alignments (2017)

Recurrent neural network models with an attention mechanism have proven to be extremely effective on a wide variety of sequence-to-sequence problems. However, the fact that soft attention mechanisms perform a pass over the entire input sequence when producing each element in the output sequence precludes their use in online settings and results in a quadratic time complexity. Based on the insight that the alignment between input and output sequence elements is monotonic in many problems of interest, we propose an end-to-end differentiable method for learning monotonic alignments which, at test time, enables computing attention online and in linear time. We validate our approach on sentence summarization, machine translation, and online speech recognition problems and achieve results competitive with existing sequence-to-sequence models.
Transcriptional profiling of MCF7 breast cancer cells in response to 5‐Fluorouracil: Relationship with cell cycle changes and apoptosis, and identification of novel targets of p53 (2006)

The availability of oral precursors of 5-Fluorouracil (5-FU) and its favorable results in treating advanced breast cancer have renewed the interest in the molecular mechanisms underlying its cytotoxicity. We have compared the changes in cell cycle and cell death parameters induced by 2 different concentrations of 5-FU (IC50 and IC80) in the breast adenocarcinoma cell line MCF7. G1/S cell cycle arrest was associated with both concentrations, whereas cell death was mainly induced after IC80 5-FU. These changes were correlated with gene expression assessed by cDNA microarray analysis. Main findings included an overexpression of p53 target genes involved in cell cycle and apoptosis (CDKN1A/p21, TP53INP, TNFRSF6/FAS and BBC3/PUMA), and significant repression of Myc. High dose 5-FU also induced a higher regulation of the mitochondrial death genes APAF1, BAK1 and BCL2, and induction of genes of the ID family. Furthermore, we establish a direct causal relationship between p21, ID1 and ID2 overexpression, increased acetylation of histones H3 and H4 and binding of p53 to their promoters as a result of 5-FU treatment. The relevance of these findings was further studied after interfering p53 expression in MCF7 cells (shp53 cells), showing a lower induction of both, ID1 and ID2 transcripts, after 5-FU when compared with MCF7 shGFP control cells. This molecular characterization of dose- and time-dependent modifications of gene expression after 5-FU treatment should provide a resource for future basic studies addressing the molecular mechanisms of chemotherapy in breast cancer.
Characterization of cloned aortic smooth muscle cells from young rats. (1994)

Clones were derived by dilute plating from cultured aortic smooth muscle cells of 12-day-old rats. Clones Pup I to III resemble uncloned smooth muscle cultures from aortas of rat pups and from adult rat neointimas. They have a cobblestone morphology and proliferate in plasma-derived serum. By Northern analysis they contain platelet-derived growth factor B chain (PDGF-B) mRNA and high levels of CYPIA1, elastin, and osteopontin mRNAs, and they lack platelet-derived growth factor alpha-receptor (PDGF-alpha R) mRNA. In contrast, Pup V resembles smooth muscle cultures derived from uninjured adult rat arteries. It has an elongated morphology and proliferates poorly in plasma-derived serum. This clone expresses PDGF-alpha R mRNA, low levels of elastin and osteopontin mRNAs, and lacks CYPIA1 and PDGF-B mRNAs. Pup IV and VI have most of the properties of Pup I to III. We conclude that uncloned pup cultures are heterogeneous, but that the growth properties and gene expression pattern described for the uncloned culture is characteristic of individual clones within the population.
Protective monoclonal antibodies to Chlamydia trachomatis serovar- and serogroup-specific major outer membrane protein determinants (1989)

Monoclonal antibodies exhibiting Chlamydia trachomatis serovar specificity (serovar A, B-Ba, or C) and serogroup specificity (B, intermediate, or C serogroup) were produced and characterized. These antibodies reacted with the major outer membrane protein, recognized epitopes located at the chlamydial cell surface, and passively neutralized chlamydial toxicity for mice. The antibodies should be useful reagents for defining the molecular structure of these protective epitopes, a necessary step toward the development of a subunit or recombinant C. trachomatis vaccine.
A Novel Risk Factor for a Novel Virus: Obesity and 2009 Pandemic Influenza A (H1N1) (2011)

half of Californians ≥ 20 years of age hospitalized with 2009 H1N1 infection were obese. Extreme obesity was associated with increased odds of death. Obese adults with 2009 H1N1 infection should be treated promptly and considered in prioritization of vaccine and antiviral medications during shortages.
Hydrophobically Modified Poly(acrylic acid) Using 3‐Pentadecylcyclohexylamine: Synthesis and Rheology (2005)

Abstract Summary: Hydrophobically modified poly(acrylic acid) was synthesized using 3‐pentadecylcyclohexylamine (3‐PDCA), which was in turn synthesized from 3‐pentadecylphenol, one of the components of cashew‐nut shell liquid (CNSL), a renewable resource material. 1 H NMR spectra confirmed the incorporation of 3‐PDCA onto PAA and a series of HMPs with three different molar concentrations, viz ≅ 3, 5 and 7 mol‐% of 3‐PDCA, were synthesized. An increase in viscosity with increasing hydrophobic content was observed by rheological measurements. The critical association concentrations were determined using an Ubbelohde viscometer and a controlled stress rheometer. The stability of HMPs towards temperature and shear was studied. Rheological measurements showed that there was a steady increase in viscosity with increase in hydrophobe content due to the formation of reversible networks. These polymers exhibited gel‐like behavior at low concentrations (≥2 wt.‐%) with an apparent yield stress (ca. 10 Pa) and showed shear thinning properties (non‐Newtonian). However, below a critical concentration, c [ η ], they showed Newtonian behavior. η sp of unmodified and modified PAA‐Na at various polymer concentrations. magnified image η sp of unmodified and modified PAA‐Na at various polymer concentrations.
Measurement of ultrasonic forces for particle–liquid separations (1997)

Abstract The magnitude and direction of the ultrasonic radiation forces that act on individual particles in a standing‐wave field were determined using a microscope‐based imaging system. The forces are calculated from measured particle velocities assuming that the drag force, given by Stokes' law, is exactly counterbalanced by the imposed ultrasonic forces. The axial primary radiation force was found to vary sinusoidally with axial position and to be proportional to the local acoustic energy density, as predicted by theory. The magnitude of the transverse primary force was determined by two independent methods to be about 100‐fold weaker than the axial force. Separation concepts exploiting the transverse force for cell retention have been successful despite the great disparity in magnitude between the axial and transvers‐force components. This may be explained by the reduced hydrodynamic forces on aggregated particles in transverse flow due to their alignment in the sound field.
Resolution of Bacterial Proteins by Polyacrylamide Gel Electrophoresis on Slabs (1974)

The application of a method of electrophoretic protein analysis to the investigation of the total protein composition of Salmonella typhimurium is described. It involves electrophoresis of many samples simultaneously on a thin slab of acrylamide gel, in the presence of sodium dodecyl sulfate, with the discontinuous buffer system of Laemmli ((1970) Nature 227, 680–685). Up to about 25 samples can be run simultaneously, thus improving both efficiency and ability to compare patterns. The sensitivity of the method for detection of changes both in soluble proteins and the insoluble membrane proteins of the cell is shown. Membrane preparations from the wild type strain and many different mutant strains have been analyzed. The major membrane proteins observed and their relationship to proteins described in the literature are discussed. The marked changes detected in a variety of mutant strains and under a variety of growth conditions are also discussed, either as to their specific meaning or as evidence of the effectiveness of the method. Solubilization artifacts concerning the proteins of the outer cell membrane are presented. The membrane fractions from two Escherichia coli strains have also been analyzed.
Comparative effectiveness of artemisinin suppositories and oral quinine in children with acute falciparum malaria (1991)

Journal Article Comparative effectiveness of artemisinin suppositories and oral quinine in children with acute falciparum malaria Get access Tran Tinh Hien, Tran Tinh Hien 1Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam Search for other works by this author on: Oxford Academic PubMed Google Scholar Dong Thi Hoai Tam, Dong Thi Hoai Tam 2Department of Infectious Diseases, Medical School of Ho Chi Minh City, Vietnam Search for other works by this author on: Oxford Academic PubMed Google Scholar Ngo Thi Kim Cue, Ngo Thi Kim Cue 2Department of Infectious Diseases, Medical School of Ho Chi Minh City, Vietnam Search for other works by this author on: Oxford Academic PubMed Google Scholar Keith Arnold Keith Arnold 3Roche Asian Research Foundation, Hong Kong Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 85, Issue 2, March-April 1991, Pages 210–211, https://doi.org/10.1016/0035-9203(91)90024-S Published: 01 March 1991 Article history Received: 07 September 1990 Revision received: 12 November 1990 Accepted: 14 November 1990 Published: 01 March 1991
IgA and Other Immunoglobulins from the European Hedgehog (1971)

Abstract Hedgehog serum and exocrine secretions contain, besides IgM and two subclasses of IgG, a protein which cross-reacts with an antiserum against human IgA. Hedgehog serum IgA comprises a large proportion of molecules having a molecular size in the range of the 9 to 10S dimer of a 7S unit. The electronegative charge of hedgehog's serum IgA resembles that of human serum IgA as shown by its behavior upon DEAE-chromatography and electrophoresis. IgA was found to be the immunoglobulin having the highest secretion-to-serum concentration ratio in saliva and bile, and also to be the immunoglobulin produced by the majority of plasma cells in the lamina propria of the hedgehog's intestinal mucosa.
C2,N6-Disubstituted adenosines: synthesis and structure-activity relationships (1989)

Extracellular adenosine receptors have been divided into two major subtypes, called A1 and A2. Substitution of the adenosine molecule with appropriate groups at C2 or N6 is known to impart selectivity for the A2 receptor over the A1 receptor. In the present study, we investigated whether substitution at both C2 and N6 would have additive effects on the A2/A1 affinity ratio, thereby providing compounds with greater A2 selectivity than presently available agents. Disappointingly, additivity appeared to hold only when an A1-selective group was present at N6. For instance, 2-(phenylamino) substitution of the A1-selective agonist N6-cyclopentyladenosine resulted in a 70-fold shift in selectivity in favor of the A2 receptor, but the same substitution applied to the A2-selective agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine resulted in a 100-fold loss of affinity with no change in A2 selectivity.
General Reactions of Pyrazole Compounds (1967)

This chapter contains sections titled: Oxidation Reactions Reduction of the Pyrazole Ring Cleavage of the Pyrazole Ring Alkylation and Dealkylation Reactions of the Pyrazole Ring
The Effect of Remote Ischaemic Preconditioning on Myocardial Injury in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery (2010)

In several recent clinical trials on cardiac surgery patients, remote ischaemic preconditioning (RIPC) showed a powerful myocardial protective effect. However the effect of RIPC has not been studied in patients undergoing off-pump coronary artery bypass graft surgery. We evaluated whether RIPC could induce myocardial protection in off-pump coronary artery bypass graft surgery patients. Patients undergoing elective off-pump coronary artery bypass graft surgery were randomly allocated to the RIPC (n = 65) or control group (n = 65). After induction of anaesthesia, RIPC was induced by four cycles of five-minute ischaemia and reperfusion on the upper limb using a pneumatic cuff. Anaesthesia was maintained with sevoflurane, remifentanil and vecuronium. Myocardial injury was assessed by troponin I before surgery and 1, 6, 12, 24, 48 and 72 hours after surgery. There were no statistical differences in troponin I levels between RIPC and control groups (P = 0.172). Although RIPC reduced the total amount of troponin I (area under the curve of troponin increase) by 26%, it did not reach statistical significance (RIPC group 53.2 +/- 72.9 hours x ng/ml vs control group 67.4 +/- 97.7 hours x ng/ml, P = 0.281). In this study, RIPC by upper limb ischaemia reduced the postoperative myocardial enzyme elevation in off-pump coronary artery bypass graft surgery patients, but this did not reach statistical significance. Further study with a larger number of patients may be needed to fully evaluate the clinical effect of RIPC in off-pump coronary artery bypass graft surgery patients.