gebhart/patrepeval huggingface dataset:
Cis-acting regulatory sequences promote high-frequency gene conversion between repeated sequences in mammalian cells (2004)

In mammalian cells, little is known about the nature of recombination-prone regions of the genome. Previously, we reported that the immunoglobulin heavy chain (IgH) mu locus behaved as a hotspot for mitotic, intrachromosomal gene conversion (GC) between repeated mu constant (Cmu) regions in mouse hybridoma cells. To investigate whether elements within the mu gene regulatory region were required for hotspot activity, gene targeting was used to delete a 9.1 kb segment encompassing the mu gene promoter (Pmu), enhancer (Emu) and switch region (Smu) from the locus. In these cell lines, GC between the Cmu repeats was significantly reduced, indicating that this 'recombination-enhancing sequence' (RES) is necessary for GC hotspot activity at the IgH locus. Importantly, the RES fragment stimulated GC when appended to the same Cmu repeats integrated at ectopic genomic sites. We also show that deletion of Emu and flanking matrix attachment regions (MARs) from the RES abolishes GC hotspot activity at the IgH locus. However, no stimulation of ectopic GC was observed with the Emu/MARs fragment alone. Finally, we provide evidence that no correlation exists between the level of transcription and GC promoted by the RES. We suggest a model whereby Emu/MARS enhances mitotic GC at the endogenous IgH mu locus by effecting chromatin modifications in adjacent DNA.
A 1/2-in CCD imager with lateral overflow-gate shutter (1991)

The design considerations and performance of an interline-transfer charge-coupled-device (IL-CCD) imager with a lateral overflow gate shutter are described. A 489(V)-pixel*670(H)-pixel 1/2-in IL-CCD imager is shown to have a variable shutter function, whose shutter speed is controlled successively from 1/60 to 1/15700 s by the timing of the overflow gate pulse. The device requires a low voltage of only 4 V and a simple overflow gate pulse to realize the shutter function without any undesirable die size enlargement. The key technology of the device is the self-aligned photodiode structure, which realizes a complete charge transfer. Combined with a microlens on the photodiode, the device can achieve high-definition or small-die-size imagers because of its high sensitivity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cholix Toxin, a Novel ADP-ribosylating Factor from Vibrio cholerae (2008)

The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC(50) = 4.6 +/- 0.4 ng/ml) and crustaceans (Artemia nauplii LD(50) = 10 +/- 2 mug/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity against ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-A resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.
Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism (2011)

In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.
Characterization of human immunodeficiency virus type 1 gp120 binding to liposomes containing galactosylceramide (1994)

Human immunodeficiency virus type 1 (HIV-1) infects some cell types which lack CD4, demonstrating that one or more alternative viral receptors exist. One such receptor is galactosylceramide (GalCer), a glycosphingolipid distributed widely in the nervous system and in colonic epithelial cells. Using a liposome flotation assay, we found that the HIV-1 surface glycoprotein, gp120, quantitatively bound to liposomes containing GalCer but not to liposomes containing phospholipids and cholesterol alone. Binding was saturable and was inhibited by preincubating liposomes with anti-GalCer antibodies. We observed less efficient binding of gp120 to liposomes containing lactosylceramide, glucosylceramide, and galactosylsulfate, whereas no binding to liposomes containing mixed gangliosides, psychosine, or sphingomyelin was detected. Binding to GalCer was rapid, largely independent of temperature and pH, and stable to conditions which remove most peripheral membrane proteins. By contrast, gp120 bound to lactosylceramide could be removed by 2 M potassium chloride or 3 M potassium thiocyanate, demonstrating a less stable interaction. Removal of N-linked oligosaccharides on gp120 did not affect binding efficiency. However, as previously observed for CD4 binding, heat denaturation of gp120 prevented binding to GalCer. Finally, binding was critically dependent on the concentration of GalCer in the target membrane, suggesting that binding to glycolipid-rich domains occurs and that GalCer conformation may be important for gp120 recognition.
Packaging of optical Fibre Bragg Gratings (2002)

Fibre Bragg Gratings (FBGs) are all-fibre optical filters with applications in sensing and telecommunication systems. The packaging of FBGs offers many challenges to the manufacturer as stringent tolerances for wavelength stability of the filter over widely varying environmental operating conditions are required for state of the art Dense Wavelength Division Multiplexing (DWDM) telecommunication systems. This paper presents various processes and packaging techniques that have been developed for FBGs in order to meet these requirements.
Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1‐arrested and bcl‐2‐expressing acute lymphoblastic leukaemia cells (2005)

Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.
Erythrocyte survival is promoted by plasma and suppressed by a Bak-derived BH3 peptide that interacts with membrane-associated Bcl-XL (2002)

Erythrocytes have a defined lifespan in vivo, and the signals that maintain their survival in circulation or trigger their death are unknown. Here, we investigated the control of erythrocyte survival and death in an in vitro culture system where erythrocytes survived for 10 days in serum-free medium in the presence or absence of bovine serum. Death of the cells in culture was correlated with increased exposure of phosphatidylserine and increased levels of intracellular calcium. Cell death could be suppressed by supplementing the medium with human plasma or serum, resulting in a doubling of the lifespan to 20 days. Freshly isolated erythrocytes and cultured erythrocytes were both found to express Bcl-X(L) and, to a lesser extent, Bak in membrane protein extracts. Treatment of the cells with a Bak-derived BH3 peptide fused to the internalization sequence of the antennapedia protein, which has previously been shown to enter cells by diffusion and antagonize Bcl-X(L), resulted in substantial cell death in erythrocyte cultures. BH3-induced death was accompanied by an immediate increase in accumulation of intracellular calcium and could be suppressed by plasma, but not by the caspase inhibitor zVAD. A BH3 peptide mutated at amino acid 78 of full-length Bak required for heterodimerization with Bcl-X(L) had no effect on cell viability or calcium levels. We conclude that the BH3 peptide accelerates erythrocyte death through antagonization of Bcl-X(L). The data suggest that erythrocyte survival is promoted by survival factors in plasma and by membrane-associated Bcl-X(L.)
Bone metastatic LNCaP‐derivative C4‐2B prostate cancer cell line mineralizes in vitro (2001)

These data demonstrate a novel mechanism through which prostate cancer cells may directly contribute to the osteoblastic component that characterize their skeletal metastatic lesions. Prostate 47:212-221, 2001.
Isolation of ribonucleotide reductase from Mycobacterium tuberculosis and cloning, expression, and purification of the large subunit (1994)

Ribonucleotide reductase, an allosterically regulated, cell cycle-dependent enzyme catalyzing a unique step in the synthesis of DNA, the reduction of 2'-ribonucleotides to 2'-deoxyribonucleotides, was purified 500-fold from Mycobacterium tuberculosis Erdman strain through cell disruption, ammonium sulfate fractionation, and dATP-Sepharose affinity column chromatography. As in eucaryotes and certain bacteria and viruses, the M. tuberculosis enzyme consists of two nonidentical subunits, R1 and R2, both of which are required for activity. R1 has a molecular mass of 84 kDa, as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with dATP. The amino acid sequences of the N-terminal peptide and two internal peptides were determined, and a partial R1 gene was isolated by PCR with primers designed from these amino acid sequences. Additional coding sequences were isolated by screening size-selected libraries, and a full-length form of M. tuberculosis R1 was generated by PCR amplification of high-molecular-weight M. tuberculosis DNA and expressed in Eschericnia coli. This coding sequence is 2,169 nucleotides long and contains no introns. The predicted molecular mass of R1 from the DNA sequence is 82,244 Da. Recombinant M. tuberculosis R1, purified to homogeneity, was biochemically active when assayed with extracts of M. tuberculosis enriched for R2.
Efficacy of brimonidine tartrate 0.2% ophthalmic solution in reducing halos after laser in situ keratomileusis (2008)

Alphagan effectively reduced halo size and pupil size in postoperative LASIK patients with night-vision symptoms.
Study of Thermal Aggregation and Gelation of Oat Globulin by Raman Spectroscopy (2003)

Thermal aggregation and gelation of oat globulin were studied by FT‐NIR Raman spectroscopy. The buffer‐soluble aggregates exhibited a Raman spectrum similar to that of the unheated control, whereas the insoluble aggregates showed intensity increases in the tryptophan, C–H bending and C–H stretching bands, and a decrease in the tyrosine doublet ( I 850 / I 830 ), suggesting protein denaturation. However, analysis of the amide I region using Raman Spectral Analysis Package (RASP) program revealed marked decreases in α ‐helical and increases in β ‐sheet structure in both soluble and insoluble aggregates. Similar conformational changes were also observed in the heat‐induced oat globulin gels, and may be attributed to realignment of molecular segments and formation of intermolecular β ‐sheet structures. Thermal gelation under the influence of different chaotropic salts showed some shifts in band positions and changes in band intensity, following the lyotropic series of anions. Several protein structure perturbants, including sodium dodecyl sulfate, dithiothreitol, urea and sodium laurate, were found to affect the Raman spectral characteristics of oat globulin gels. The data suggest that changes in gelling properties of oat globulin by these chemicals may be related to conformational changes of the protein during gelation.
An Essential Role for Rho, Rac, and Cdc42 GTPases in Cell Cycle Progression Through G 1 (1995)

Members of the Rho family of small guanosine triphosphatases (GTPases) regulate the organization of the actin cytoskeleton; Rho controls the assembly of actin stress fibers and focal adhesion complexes, Rac regulates actin filament accumulation at the plasma membrane to produce lamellipodia and membrane ruffles, and Cdc42 stimulates the formation of filopodia. When microinjected into quiescent fibroblasts, Rho, Rac, and Cdc42 stimulated cell cycle progression through G1 and subsequent DNA synthesis. Furthermore, microinjection of dominant negative forms of Rac and Cdc42 or of the Rho inhibitor C3 transferase blocked serum-induced DNA synthesis. Unlike Ras, none of the Rho GTPases activated the mitogen-activated protein kinase (MAPK) cascade that contains the protein kinases c-Raf1, MEK (MAPK or ERK kinase), and ERK (extracellular signal-regulated kinase). Instead, Rac and Cdc42, but not Rho, stimulated a distinct MAP kinase, the c-Jun kinase JNK/SAPK (Jun NH2-terminal kinase or stress-activated protein kinase). Rho, Rac, and Cdc42 control signal transduction pathways that are essential for cell growth.
Autotaxin inhibitors: a patent review (2013)

ATX has been implicated in various pathological conditions, such as cancer, chronic inflammation, neuropathic pain, fibrotic diseases, etc. Although there is an intensive effort on the discovery of potent and selective ATX inhibitors in order to identify novel medicinal agents, up to now, no ATX inhibitor has reached clinical trials. However, the use of ATX inhibitors seems an attractive strategy for the development of novel medicinal agents, for example anticancer therapeutics.
High Performance Fibres from ‘Dog Bone’ Carbon Nanotubes (2007)

The direct spinning of carbon nanotubes yields fibres with distinctly encouraging mechanical properties. While the best strength (2.2 N/tex) and stiffness (160 N/tex) promise competition for established carbon fibres, the maximum energy absorbed at fracture (46 J/g) is somewhat higher. The fibres consist of very long double-walled nanotubes of surprisingly large diameter (in the 5–10 nm range), which collapse to give a dog-bone cross section.
Microbiota dysbiosis and its pathophysiological significance in bowel obstruction (2018)

Bowel obstruction (OB) causes local and systemic dysfunctions. Here we investigated whether obstruction leads to alterations in microbiota community composition and total abundance, and if so whether these changes contribute to dysfunctions in OB. Partial colon obstruction was maintained in rats for 7 days. The mid colon and its intraluminal feces - proximal to the obstruction - were studied. OB did not cause bacterial overgrowth or mucosa inflammation, but induced profound changes in fecal microbiota composition and diversity. At the phylum level, the 16S rRNA sequencing showed a significant decrease in the relative abundance of Firmicutes with corresponding increases in Proteobacteria and Bacteroidetes in OB compared with sham controls. Daily treatment using broad spectrum antibiotics dramatically reduced total bacterial abundance, but increased the relative presence of Proteobacteria. Antibiotics eliminated viable bacteria in the spleen and liver, but not in the mesentery lymph node in OB. Although antibiotic treatment decreased muscle contractility in sham rats, it had little effect on OB-associated suppression of muscle contractility or inflammatory changes in the muscle layer. In conclusion, obstruction leads to marked dysbiosis in the colon. Antibiotic eradication of microbiota had limited effects on obstruction-associated changes in inflammation, motility, or bacterial translocation.
Molecular Mechanisms in Morpholino−DNA Surface Hybridization (2010)

Synthetic nucleic acid mimics provide opportunity for redesigning the specificity and affinity of hybridization with natural DNA or RNA. Such redesign is of great interest for diagnostic applications where it can enhance the desired signal against a background of competing interactions. This report compares hybridization of DNA analyte strands with morpholinos (MOs), which are uncharged nucleic acid mimics, to the corresponding DNA-DNA case in solution and on surfaces. In solution, MO-DNA hybridization is found to be independent of counterion concentration, in contrast to DNA-DNA hybridization. On surfaces, when immobilized MO or DNA "probe" strands hybridize with complementary DNA "targets" from solution, both the MO-DNA and DNA-DNA processes depend on ionic strength but exhibit qualitatively different behaviors. At lower ionic strengths, MO-DNA surface hybridization exhibits hallmarks of kinetic limitations when separation between hybridized probe sites becomes comparable to target dimensions, whereas extents of DNA-DNA surface hybridization are instead consistent with limits imposed by buildup of surface (Donnan) potential. The two processes also fundamentally differ at high ionic strength, under conditions when electrostatic effects are weak. Here, variations in probe coverage have a much diminished impact on MO-DNA than on DNA-DNA hybridization for similarly crowded surface conditions. These various observations agree with a structural model of MO monolayers in which MO-DNA duplexes segregate to the buffer interface while unhybridized probes localize near the solid support. A general perspective is presented on using uncharged DNA analogues, which also include compounds such as peptide nucleic acids (PNA), in surface hybridization applications.
A list of candidate cancer biomarkers for targeted proteomics. (2007)

We have compiled from literature and other sources a list of 1261 proteins believed to be differentially expressed in human cancer. These proteins, only some of which have been detected in plasma to date, represent a population of candidate plasma biomarkers that could be useful in early cancer detection and monitoring given sufficiently sensitive specific assays. We have begun to prioritize these markers for future validation by frequency of literature citations, both total and as a function of time. The candidates include proteins involved in oncogenesis, angiogenesis, development, differentiation, proliferation, apoptosis, hematopoiesis, immune and hormonal responses, cell signaling, nucleotide function, hydrolysis, cellular homing, cell cycle and structure, the acute phase response and hormonal control. Many have been detected in studies of tissue or nuclear components; nevertheless we hypothesize that most if not all should be present in plasma at some level. Of the 1261 candidates only 9 have been approved as "tumor associated antigens" by the FDA. We propose that systematic collection and large-scale validation of candidate biomarkers would fill the gap currently existing between basic research and clinical use of advanced diagnostics.
CCR5 Binds Multiple CC-Chemokines: MCP-3 Acts as a Natural Antagonist (1999)

Abstract CCR5 was first characterized as a receptor for MIP-1, MIP-1β, and RANTES, and was rapidly shown to be the main coreceptor for M-tropic human immunodeficiency virus (HIV)-1 strains and simian immunodeficiency virus (SIV). Chemokines constitute a rapidly growing family of proteins and receptor-chemokine interactions are known to be promiscuous and redundant. We have therefore tested whether other CC-chemokines could bind to and activate CCR5. All CC-chemokines currently available were tested for their ability to compete with [125I]-MIP-1β binding on a stable cell line expressing recombinant CCR5, and/or to induce a functional response in these cells. We found that in addition to MIP-1β, MIP-1, and RANTES, five other CC-chemokines could compete for [125I]-MIP-1β binding: MCP-2, MCP-3, MCP-4, MCP-1, and eotaxin binding was characterized by IC50 values of 0.22, 2.14, 5.89, 29.9, and 21.7 nmol/L, respectively. Among these ligands, MCP-3 had the remarkable property of binding CCR5 with high affinity without eliciting a functional response, MCP-3 could also inhibit the activation of CCR5 by MIP-1β and may therefore be considered as a natural antagonist for CCR5. It was unable to induce significant endocytosis of the receptor. Chemokines that could compete with high affinity for MIP-1β binding could also compete for monomeric gp120 binding, although with variable potencies; maximal gp120 binding inhibition was 80% for MCP-2, but only 30% for MIP-1β. MCP-3 could compete efficiently for gp120 binding but was, however, found to be a weak inhibitor of HIV infection, probably as a consequence of its inability to downregulate the receptor.
Skin grafting for venous leg ulcers (2013)

Bilayer artificial skin, used in conjunction with compression bandaging, increases venous ulcer healing compared with a simple dressing plus compression. Further research is needed to assess whether other forms of skin grafts increase ulcer healing.
Cation exchange and glycoside binding in cultured rat heart cells (1979)

The Na/K-exchange characteristics, ouabain-binding kinetics, and Na pump turnover rates of synchronously contracting monolayers of neonatal rat myocardial cells were studied. The cells exchange Na rapidly (T1/2 = 35 s) with a mean Na flux of approximately 25 (pmol/cm2)/s. The half time (T1/2) of K exchange is much longer (12 min); the mean K flux is 13 (pmol/cm2)/s. Active Na/K transport, as measured by K influx, is relatively ouabain sensitive, and 10(-6) M ouabain produces half-maximal inhibition. Ouabain (10(-2)M) inhibits 60% of the Na efflux and 75% of the K influx. The cells bind [3H]ouabain rapidly (T1/2 = 8 min), but release it very slowly (T1/2 = 11 h), and both the amount bound and the rate of binding were inversely proportional to extracellular K. Specific [3H]ouabain binding demonstrates saturation reaching a maximum of 1.6 x 10(6) molecules per cell at 2 x 10(-7) M [3H]ouabain. From cell surface area and ouabain-sensitive flux measurements, the Na pump density was calculated at 720/micrometer2 with an individual pump turnover rate of 50/s. Thus the studies indicate that despite their neonatal origin, the behavior of the Na pump in these cells is very similar to that in other mammalian tissues.
Dye-Sensitized Solar Cells Made by Using a Polysilsesquioxane Polymeric Ionic Fluid as Redox Electrolyte (2007)

Dye-sensitized solar cells have been made by using electrolytes based on a polysilsesquioxane ionic fluid. This is a nanocomposite organic−inorganic material synthesized by the sol−gel route using 1-methyl-3-[3-(trimethoxy-λ4-silyl)propyl]-1H-imidazolium iodide as precursor. This compound is an imidazolium iodide derivatized with covalent attachment of a trimethoxysilane group. Condensation was obtained by formic acid solvolysis at 120 °C in the absence of water. The obtained materials have been characterized by IR, 29Si NMR and conductivity measurements. Cells have been constructed by using several variants of the above electrolyte and have been characterized by current−voltage measurements.