gebhart/patrepeval huggingface dataset:
AF4 Encodes a Ubiquitous Protein That in Both Native and MLL-AF4 Fusion Types Localizes to Subnuclear Compartments (1998)

Acute leukemia with t(4;11)(q21,q23) translocation results from the in-frame fusion of the MLL to the AF4/FEL gene. In previous studies, we and others demonstrated that AF4 transcripts are present in a variety of hematopoietic and nonhematopoietic human cells. To further study the wild-type and leukemia fusion AF4, we used glutathione S-transferase (GST)-fusion proteins as immunogens to produce rabbit polyclonal antibodies that were specific for normal and chimeric AF4 proteins. Using Western blotting analysis, we demonstrated that the AF4 gene encodes proteins with apparent molecular weight of 125 and 145 kD. A 45-kD protein coprecipitated with AF4 protein in immunoprecipitation. Also, the anticipated MLL-AF4–encoded 240-kD protein was detected in all cell lines with t(4;11) translocations; fusion proteins were present in lesser quantity than the wild-type AF4. The proteins recognized by the antibodies are of the predicted sizes of the AF4 and MLL-AF4–encoded proteins based on previous DNA sequencing analysis. The MLL-AF4 fusion protein had a similar subcellular distribution as AF4. Both t(4;11) and non-t(4;11) leukemic cells showed a similar pattern of punctate nuclear staining in all cell lines tested using confocal immunofluorescence microscopy. AF4 antibodies should be useful for further elucidation of the function of AF4 in normal cellular physiology, as well as the function of MLL-AF4 in leukemogenesis. The antibodies should also be helpful for the diagnosis of the MLL-AF4 fusion proteins in t(4;11) leukemias.
Translational Control by an Upstream Open Reading Frame in the HER-2/neu Transcript (1999)

Overexpression of the HER-2 (neu, erbB-2) receptor results in cellular transformation and is associated with a variety of human cancers. Multiple mechanisms, including gene amplification and transcriptional, post-transcriptional, and translational controls contribute to the regulation of HER-2 expression. One of the components of these regulatory mechanisms is a short upstream open reading frame (uORF) in the HER-2 mRNA that represses downstream translation in a variety of cell types. Here we explore the mechanism by which this uORF exerts its inhibitory effect. As judged by comparisons of protein and mRNA abundance and by polysomal distribution analyses, the uORF represses translation of the HER-2 cistron or of a heterologous reporter gene. Despite its conservation among mammalian species, the peptide sequence of the uORF is not required for this inhibitory effect. Rather, the majority of ribosomes that load on the HER-2 mRNA most likely translate the uORF and are then unable to reinitiate at the downstream AUG codon, in part due to the short intercistronic spacing. A minority of ribosomes gain access to the HER-2 initiation codon either by leaky scanning past the upstream AUG codon or by reinitiating after having translated the uORF despite the short intercistronic region. These results suggest that the HER-2 uORF controls synthesis of this oncoprotein by limiting ribosomal access to downstream initiation sites.
Highlights in the Development of New Antiviral Agents (2002)

The potential of a large variety of new compounds and new strategies for the treatment of virtually all major virus infections has been addressed. This includes, for the treatment of HIV infections, virus adsorption inhibitors (cosalane derivatives, cyanovirin-N), co-receptor antagonists (TAK-779, AMD3100), viral fusion inhibitors (pentafuside T-20, betulinic acid derivatives), viral uncoating inhibitors (azodicarbonamide), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs: emtricitabine, amdoxovir, dOTC, d4TMP prodrugs, tenofovir disoproxil fumarate), non-nucleoside reverse transcriptase inhibitors (NNRTIs: thiocarboxanilide UC-781, capravirine, SJ-3366, DPC 083, TMC 125/R165335), integrase inhibitors (diketo acids), transcription inhibitors (temacrazine, flavopiridol), protease inhibitors (atazanavir, mozenavir, tipranavir); for the treatment of RSV and paramyxovirus infections, viral fusion inhibitors (R170591, VP-14637, NMS03); for the treatment of picornavirus infections, viral uncoating inhibitors (pleconaril); for the treatment of pesti- (hepaci-, flavi-) virus infections, RNA replicase inhibitors (VP-32947); for the treatment of herpesvirus (HSV, VZV, CMV) infections, DNA polymerase inhibitors (A-5021, L- and D-cyclohexenylguanine); for the treatment of VZV infections, bicyclic furopyrimidine analogues; for the treatment of CMV infections, fomivirsen; for the treatment of DNA virus infections at large (papilloma-, polyoma-, herpes-, adeno- and poxvirus infections), cidofovir; for the treatment of influenza, neuraminidase inhibitors (zanamivir, oseltamivir, RWJ-270201); for the treatment of HBV infections, adefovir dipivoxil; for the treatment of HBV and HCV infections, N-glycosylation inhibitors (N-nonyl-deoxynojirimycin); and, finally, IMP dehydrogenase inhibitors and S-adenosylhomocysteine hydrolase inhibitors, for the treatment of various virus infections, including hemorrhagic fever virus infections.
N-Domain–Specific Substrate and C-Domain Inhibitors of Angiotensin-Converting Enzyme (1998)

We used the isolated N- and C-domains of the angiotensin 1-converting enzyme (N-ACE and C-ACE; ACE; kininase II) to investigate the hydrolysis of the active 1-7 derivative of angiotensin (Ang) II and inhibition by 5-S-5-benzamido-4-oxo-6-phenylhexanoyl-L-proline (keto-ACE). Ang-(1-7) is both a substrate and an inhibitor; it is cleaved by N-ACE at approximately one half the rate of bradykinin but negligibly by C-ACE. It inhibits C-ACE, however, at an order of magnitude lower concentration than N-ACE; the IC50 of C-ACE with 100 micromol/L Ang I substrate was 1.2 micromol/L and the Ki was 0.13. While searching for a specific inhibitor of a single active site of ACE, we found that keto-ACE inhibited bradykinin and Ang I hydrolysis by C-ACE in approximately a 38- to 47-times lower concentration than by N-ACE; IC50 values with C-ACE were 0.5 and 0.04 micromol/L. Furthermore, we investigated how Ang-(1-7) acts via bradykinin and the involvement of its B2 receptor. Ang-(1-7) was ineffective directly on the human bradykinin B2 receptor transfected and expressed in Chinese hamster ovary cells. However, Ang-(1-7) potentiated arachidonic acid release by an ACE-resistant bradykinin analogue (1 micromol/L), acting on the B2 receptor when the cells were cotransfected with cDNAs of both B2 receptor and ACE and the proteins were expressed on the plasma membrane of Chinese hamster ovary cells. Thus like other ACE inhibitors, Ang-(1-7) can potentiate the actions of a ligand of the B2 receptor indirectly by binding to the active site of ACE and independent of blocking ligand hydrolysis. This potentiation of kinins at the receptor level can explain some of the well-documented kininlike actions of Ang-(1-7).
Purification of recombinant human tissue factor (1989)

Tissue factor (TF) is a 263 amino acid membrane-bound procoagulant protein that serves as a cofactor for the serine protease factor VII (fVII). Recombinant human TF (rTF) produced in both human kidney 293 cells and Escherichia coli has been immunoaffinity purified by using a TF-specific monoclonal antibody. Recombinant TF produced in 293 cells is glycosylated and migrates on reducing SDS-PAGE with an apparent molecular weight (Mr) of 45K. Some interchain disulfide-bonded rTF dimers are observed under nonreducing conditions. The E. coli produced rTF has a molecular weight of 33K and 35K, with the 33K band missing nine amino acids at the carboxy terminus. Although the E. coli produced rTF does not contain any carbohydrate, it is fully functional in both a chromogenic assay and a one-stage prothrombin time assay. A variant has been constructed wherein the cytoplasmic cysteine (residue 245) has been mutagenized to a serine residue. The amount of disulfide-linked aggregates is dramatically reduced following immunoaffinity purification of this four-cysteine variant (C2455), which is active in the chromogenic and prothrombin time assays.
Speaker verification: a tutorial (1990)

The task of speaker verification, a subset of the general problem of speaker recognition is defined. The feature selection and pattern matching steps of the recognition procedure are examined. Speaker verification system design and performance are discussed, and databases for evaluating them are briefly considered. An example of a speaker verification system is described. An overview of industry research in this area is given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
HIV disease progression in 854 women and men infected through injecting drug use and heterosexual sex and followed for up to nine years from seroconversion (1994)

There seems to be little evidence for appreciable differences in the natural course of HIV infection between men and women followed up from the time of seroconversion.
In vitro selection of a novel catalytic RNA: characterization of a sulfur alkylation reaction and interaction with a small peptide. (1996)

An in vitro RNA selection for catalytic activity was used to co-select for binding activity to a small peptide. 5'-phosphorothioate-modified RNA (GMPS-RNA) sequences were selected from a randomized pool of oligoribonucleotides for their ability to accelerate a halide substitution reaction with N-bromoacetyl-bradykinin (BrBK). One RNA selected shows a 2,420-fold increase in rate of reaction with BrBK relative to the starting pool. This reaction is specifically inhibited by free bradykinin (Ki 230 microM), indicating that interactions with bradykinin contribute to the rate enhancement. Inhibition of the reaction by the peptide requires both the amino- and carboxy-terminal arginine residues of the peptide for optimal inhibition activity. Reaction with N-bromoacetamide is not enhanced, indicating that the intrinsic reactivity of the 5' phosphorothioate is not increased in the selected RNA. Through 3'-end boundary analysis, much of the catalytic activity of the selected GMPS-RNA is shown to reside in a hairpin structure in the selected region of the molecule. This hairpin structure is also implicated in the recognition of the peptide substrate.
β2-Adrenergic Receptor Signaling in the Cardiac Myocyte is Modulated by Interactions With CXCR4 (2010)

Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation, metastasis, and embryonic development. We previously demonstrated a nonchemotactic role for one such chemokine pair, stromal cell-derived factor-1α and its G-protein coupled receptor, CXCR4. Stromal cell-derived factor-1/CXCR4 are expressed on cardiac myocytes and have direct consequences on cardiac myocyte physiology by inhibiting contractility in response to the nonselective β-adrenergic receptor (βAR) agonist, isoproterenol. As a result of the importance of β-adrenergic signaling in heart failure pathophysiology, we investigated the underlying mechanism involved in CXCR4 modulation of βAR signaling. Our studies demonstrate activation of CXCR4 by stromal cell-derived factor-1 leads to a decrease in βAR-induced PKA activity as assessed by cAMP accumulation and PKA-dependent phosphorylation of phospholamban, an inhibitor of SERCA2a. We determined CXCR4 regulation of βAR downstream targets is β2AR-dependent. We demonstrated a physical interaction between CXCR4 and β2AR as determined by coimmunoprecipitation, confocal microscopy, and BRET techniques. The CXCR4-β2AR interaction leads to G-protein signal modulation and suggests the interaction is a novel mechanism for regulating cardiac myocyte contractility. Chemokines are physiologically and developmentally relevant to myocardial biology and represent a novel receptor class of cardiac modulators. The CXCR4-β2AR complex could represent a hitherto unknown target for therapeutic intervention.
Strain influenced indium composition distribution in GaN/InGaN core-shell nanowires (2010)

The optical properties, indium concentration and distribution, defect morphology, and strain distribution of GaN/InGaN coaxial nanowires grown by metal organic chemical vapor deposition were investigated using spatially resolved cathodoluminescence, scanning transmission electron microscopy, and finite element analysis. The results indicate that InGaN layers with 40% or greater indium incorporation and low defect density can be achieved. The indium distribution in the InGaN shell layer was measured and qualitatively correlated with the calculated strain distribution. The three-dimensional compliance of the GaN nanowire leads to facile strain relaxation in the InGaN heteroepitaxial layer, enabling high indium incorporation and high crystalline quality.
Cigarette smoke metal‐catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules (2005)

Smoking is a significant risk factor for development of atherosclerosis. However, the pathophysiology of smoking-mediated vessel wall damage is not understood. With tools ranging from analytical chemistry to cell biology, we show that cigarette smoke contains metals that catalyze the direct oxidation of cellular proteins by smoke oxidants. Oxidation of cellular proteins causes a loss of microtubule function, culminating in microtubule depolymerization and proteasome-dependent degradation of alpha-tubulin. As a consequence of the microtubule collapse, cytoskeletal structures as well as intermediate filaments break down, leading finally to a contraction of vascular endothelial cells. We observed a smoke extract-induced, calpain-dependent degradation of the intracellular form of platelet-endothelial cell adhesion molecule 1/CD31, as well as a release of P-selectin/CD62P, IL-6, and IL-8 from endothelial cells into the supernatant. Increased levels of soluble CD62P and IL-6 are well known to be associated with smoking in humans. Increased permeability of the vascular endothelium is a crucial event in atherogenesis. This work highlights the compounds and mechanisms by which cigarette smoke induces leakiness of the vascular endothelium.
Flat Projection for 3-D (2006)

The two challenges for three-dimensional (3-D) display are designing the optics for wide fields of view, and delivering pixels at the rates needed to support this. Getting such pixel rates at low cost is merely an extension of the key challenge for two-dimensional (2-D) displays,and the cost advantage of projection in this respect over alternatives increases considerably at the data rates needed for 3-D. Both 2-D and 3-D projection concepts are bulky, so the authors describe how to project images within a flat panel. Flat projection is not only inexpensive: it can generate virtual as well as real images, and allows the screen to take images and input from the viewer as well as vice versa. Real images are created by pointing a projector into a wedge-shaped light guide, and either the projector or the screen can be shuttered in order to time-multiplex a 3-D image on a large screen. Virtual images are created by pointing a projector into a slab embossed with a grating and can deliver the collimated illumination needed if a liquid crystal display is to time-multiplex a 3-D image with the high off-screen resolution provided by holograms.
Stability and release of topical tranexamic acid liposome formulations. (2003)

Tranexamic acid (TA) has been claimed to have whitening effects. The effects of TA contents (5% and 10%) and charges on the stability and release of TA entrapped in hydrogenated soya phosphatidylcholine/cholesterol/charged lipid [dicetyl phosphate (-) or stearylamine (+)] liposomes at molar ratios of 7:2:1(-) and 7:2:1 (+) were investigated. The TA contents were determined spectrophotometrically at 415 nm, following derivatization with 2,4,6-trinitrobenzosulfonic acid. Stability and leakage of TA from liposomes were characterized at 4 degrees, 30 degrees and 45 degrees C for 90 days. The leakage rates of TA in negative liposomes were lower than those in positive liposomes. The TA in all liposome formulations was relatively stable, as > 90% of total drug remained after up to two months. The release of TA from liposomes was examined using vertical Franz diffusion cells at 37 degrees C for 24 h. The release rates of TA from all liposome formulations were approximately 3 times lower than those from solutions. Charges appeared to affect the physical stability, leakage, and shelf life of TA in liposomes, whereas TA concentrations seemed to affect the release of TA. The 7:2:1 (10% TA,-) liposome was the best formulation, due to its small size, low leakage, high stability, and prolonged and sustained release profile.
Near-infrared light propagation in an adult head model II Effect of superficial tissue thickness on the sensitivity of the near-infrared spectroscopy signal (2003)

It is important for near-infrared spectroscopy (NIRS) and imaging to estimate the sensitivity of the detected signal to the change in hemoglobin that results from brain activation and the volume of tissue interrogated for a specific source-detector fiber spacing. In this study light propagation in adult head models is predicted by Monte Carlo simulation to investigate the effect of the superficial tissue thickness on the partial optical path length in the brain and on the spatial sensitivity profile. In the case of source-detector spacing of 30 mm, the partial optical path length depends mainly on the depth of the inner skull surface whereas the spatial sensitivity profile is significantly affected by the thickness of the cerebrospinal fluid layer. The mean optical path length that can be measured by time-resolved experiments increases when the skull thickness increases whereas the partial mean optical path length in the brain decreases when the skull thickness increases. These results indicate that it is not appropriate to use the mean optical path length as an alternative to the partial optical path length to compensate the NIRS signal for the difference in sensitivity caused by variation of the superficial tissue thickness.
Bumptrees for Efficient Function, Constraint and Classification Learning (1990)

A new class of data structures called “bumptrees ” is described. These structures are useful for efficiently implementing a number of neural network related operations. An empirical comparison with radial basis functions is presented on a robot arm mapping learning task. Applica-tions to density estimation, classification, and constraint representation and learning are also outlined. 1 WHAT IS A BUMPTREE? A bumptree is a new geometric data structure which is useful for efficiently learning, rep-resenting, and evaluating geometric relationships in a variety of contexts. They are a natural generalization of several hierarchical geometric data structures including oct-trees, k-d trees, balltrees and boxtrees. They are useful for many geometric learning tasks including approximating functions, constraint surfaces, classification regions, and probability densi-ties from samples. In the function approximation case, the approach is related to radial basis function neural networks, but supports faster construction, faster access, and more flexible
Effect of Growth Factors on Cell Proliferation by Human Nasal Septal Chondrocytes Cultured in Monolayer (1994)

In the field of reconstructive surgery, autologous cartilage grafting is commonly performed to reconstruct skeletal defects. Because of the limited supply of fresh autologous cartilage many investigators concentrate on in vitro production of cartilage tissue. Several growth factors regulate the metabolism and activation of cartilage cells. In order to enhance the culture conditions for cartilage cells, the aim of our investigations was to characterize the influence of transforming growth factor (TGF)-beta, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on the proliferation of differentiated human nasal septal chondrocytes. The isolated cells were cultured in monolayer using DMEM with and without 10% FCS. The cell proliferation was assessed using tritiated thymidine. We measured an increase of the proliferation rates when the different growth factors were added. The most important stimulatory effect was due to bFGF and the less to EGF. If all growth factors were added together a fivefold increase in the proliferative activity of the cells was achieved. The effects were further enhanced by factors present in fetal calf serum. We conclude that the culture conditions for cell expansion for cartilage engineering can be optimized employing growth factors.
Distribution of plasma cells and other cells containing immunoglobulin in the respiratory tract of normal man and class of immunoglobulin contained therein. (1976)

The anatomical distribution of plasma cells and other cells containing immunoglobulin in the respiratory tract, and the relative proportions of the immunoglobulin classes have been estimated on necropsy tissues from nine adult human subjects without respiratory disease, five non-smokers and four smokers, none of whom had cough or sputum. Cell counts on multiple sections stained by immunofluorescent methods for the presence of immunoglobulin were carried out on the upper trachea, main bronchus, and lower lobe bronchus. Cells containing immunoglobulin were found mostly in the submucous glands but were also present in the lamina propria of the tracheal and bronchial epithelium. These cells were present in the greatest concentration in the main bronchus and were always present in the lobar bronchus and, in most subjects, in the upper trachea. The cells were not always present round small bronchi and bronchioles and were virtually absent from alveolar walls. Cells containing IgA were much more numerous than those containing other immunoglobulin classes in all subjects except one, in whom IgG and IgE cells were equally numerous. Two subjects appeared to be significantly different from the rest. One non-smoking subject had a marked deficiency of IgA cells at all sampling sites, and one smoker had a marked excess of IgA cells. In spite of these two subjects there was no significant difference between smokers and non-smokers except in the lobar bronchus where the smokers had significantly more IgA cells than the non-smokers.
Quantitative Assessment of the Epithelial and Inflammatory Cell Populations in Large Airways of Normals and Individuals With Cystic Fibrosis (1996)

Nasal and bronchial brushings and bronchial biopsies were evaluated from patients with cystic fibrosis (CF) and from normal subjects to quantify epithelial and inflammatory cell types. Epithelial in both groups were dominated by ciliated cells. The relative proportions of epithelial cells recovered by brushing and biopsy were similar, but with more basal cells from biopsies than from brushings. In nasal brushings, the numbers and percentages of epithelial subtypes were similar in both groups. In bronchial brushings, the number of recovered cells was 2.5-fold increased in the CF group compared with that in the normal group because of large numbers of neutrophils. The proportion of ciliated cells was lower in the CF group than in the normal group. Thus, even though the CF transmembrane conductance regulator mutations are expressed similarly in the nasal and bronchial epithelium in CF, the consequences are different, with little inflammation and no changes in the proportions of epithelial cells in the nasal epithelium, compared with marked neutrophil inflammation on the epithelial surface and significant changes in epithelial populations in the large airways. Airway brushing permits repetitive evaluation of the airway epithelium in CF, a useful methodology in the assessment of new therapies for this disorder.