gebhart/patrepeval huggingface dataset:
The M-cadherin catenin complex interacts with microtubules in skeletal muscle cells: Implications for the fusion of myoblasts (1999)

M-cadherin, a calcium-dependent intercellular adhesion molecule, is expressed in skeletal muscle cells. Its pattern of expression, both in vivo and in cell culture as well as functional studies, have implied that M-cadherin is important for skeletal muscle development, in particular the fusion of myoblasts into myotubes. M-cadherin formed complexes with the catenins in skeletal muscle cells similar to E-cadherin in epithelial cells. This suggested that the muscle-specific function of the M-cadherin catenin complex might be mediated by additional interactions with yet unidentified cellular components, especially cytoskeletal elements. These include the microtubules which also have been implicated in the fusion process of myoblasts. Here we present evidence that the M-cadherin catenin complex interacts with microtubules in myogenic cells by using three independent experimental approaches. (1) Analysis by laser scan microscopy revealed that the destruction of microtubules by nocodazole leads to an altered cell surface distribution of M-cadherin in differentiating myogenic cells. In contrast, disruption of actin filaments had little effect on the surface distribution of M-cadherin. (2) M-cadherin antibodies coimmunoprecipitated tubulin from extracts of nocodazole-treated myogenic cells but not of nocodazole-treated epithelial cells ectopically expressing M-cadherin. Vice versa, tubulin antibodies coimmunoprecipitated M-cadherin from extracts of nocodazole-treated myogenic cells but not of nocodazole-treated M-cadherin-expressing epithelial cells. (3) M-cadherin and the catenins, but not a panel of control proteins, were copolymerized with tubulin from myogenic cell extracts even after repeated cycles of assembly and disassemly of tubulin. Moreover, neither M-cadherin nor E-cadherin could be found in a complex with microtubules in epithelial cells ectopically expressing M-cadherin. Our data are consistent with the idea that the interaction of M-cadherin with microtubules might be essential to keep the myoblasts aligned during fusion, a process in which both M-cadherin and microtubules have been implicated.
Molecular Mechanisms of the Cytotoxicity of ADP-Ribosylating Toxins (2008)

Bacterial pathogens utilize toxins to modify or kill host cells. The bacterial ADP-ribosyltransferases are a family of protein toxins that covalently transfer the ADP-ribose portion of NAD to host proteins. Each bacterial ADP-ribosyltransferase toxin modifies a specific host protein(s) that yields a unique pathology. These toxins possess the capacity to enter a host cell or to use a bacterial Type III apparatus for delivery into the host cell. Advances in our understanding of bacterial toxin action parallel the development of biophysical and structural biology as well as our understanding of the mammalian cell. Bacterial toxins have been utilized as vaccines, as tools to dissect host cell physiology, and more recently for the development of novel therapies to treat human disease.
Glucagon-Like Peptide-1, But Not Glucose-Dependent Insulinotropic Peptide, Regulates Fasting Glycemia and Nonenteral Glucose Clearance in Mice* (2000)

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) potentiate glucose-stimulated insulin secretion after enteral nutrient ingestion. We compared the relative incretin and nonincretin actions of GLP-1 and GIP in +/+ and GLP-1R-/- mice using exendin(9-39) and immunopurified anti-GIP receptor antisera (GIPR Ab) to antagonize GLP-1 and GIP action, respectively. Both antagonists produced a significant increase in glycemic excursion after oral glucose loading of +/+ mice (P < 0.05 for antagonists us. controls). Exendin(9-39) also increased blood glucose and decreased glucose-stimulated insulin in +/+ mice after ip glucose loading [0.58 +/- 0.02 vs. 0.47 +/- 0.02 ng/ml in saline- vs. exendin(9-39)-treated mice, respectively, P < 0.05]. In contrast, GIPR Ab had no effect on glucose excursion or insulin secretion, after ip glucose challenge, in +/+ or GLP-1R-/- mice. Repeated administration of exendin(9-39) significantly increased blood glucose and reduced circulating insulin levels but had no effect on levels of pancreatic insulin or insulin messenger RNA transcripts. In contrast, no changes in plasma glucose, circulating insulin, pancreatic insulin content, or insulin messenger RNA were observed in mice, 18 h after administration of GIPR Ab. These findings demonstrate that GLP-1, but not GIP, plays an essential role in regulating glycemia, independent of enteral nutrient ingestion in mice in vivo.
Assertion-oriented automated test data generation (1996)

Assertions are recognized as a powerful tool for automatic run time detection of software errors. However, existing testing methods do not use assertions to generate test cases. We present a novel approach of automated test data generation in which assertions are used to generate test cases. In this approach the goal is to identify test cases on which an assertion is violated. If such a test is found then this test uncovers an error in the program. The problem of finding program input on which an assertion is violated may be reduced to the problem of finding program input on which a selected statement is executed. As a result, the existing methods of automated test data generation for white box testing may be used to generate tests to violate assertions. The experiments have shown that this approach may significantly improve the chances of finding software errors as compared to the existing methods of test generation.
Therapeutic Angiogenesis for Treating Cardiovascular Diseases (2012)

Cardiovascular disease is the leading cause of death worldwide and is often associated with partial or full occlusion of the blood vessel network in the affected organs. Restoring blood supply is critical for the successful treatment of cardiovascular diseases. Therapeutic angiogenesis provides a valuable tool for treating cardiovascular diseases by stimulating the growth of new blood vessels from pre-existing vessels. In this review, we discuss strategies developed for therapeutic angiogenesis using single or combinations of biological signals, cells and polymeric biomaterials. Compared to direct delivery of growth factors or cells alone, polymeric biomaterials provide a three-dimensional drug-releasing depot that is capable of facilitating temporally and spatially controlled release. Biomimetic signals can also be incorporated into polymeric scaffolds to allow environmentally-responsive or cell-triggered release of biological signals for targeted angiogenesis. Recent progress in exploiting genetically engineered stem cells and endogenous cell homing mechanisms for therapeutic angiogenesis is also discussed.
Scott Page (2016)

On Aug. 9, 2015, we lost John Holland, computer scientist, psychologist, and complexity scientist. John defined new areas of research and tools for exploring them. Along the way, he made significant contributions in a startlingly unusual range of fields. He gave us new ways to solve problems and changed how many of us think, literally.
Depression, anxiety and acute pain: links and management challenges (2019)

Pain is a subjective experience that is influenced by genetics, gender, social, cultural and personal parameters. Opposed to chronic pain, which by definition has to last for at least 3 months, acute pain is mostly because of trauma, acute medical conditions or treatment. The link between mood disorders and acute pain has proven to be increasingly significant since the link is bi-directional, and both act as risk factors for each other. Depression and anxiety are associated with increased perception of pain severity, whereas prolonged duration of acute pain leads to increased mood dysregulation. Although both depression and anxiety have a proven association with acute pain, the link between depression and acute pain is more thoroughly studied. Pain can be the presenting or sole complaint in depressed patients who present to primary care practices and is often overlooked by clinicians. However, reports on the perception of experimentally-induced pain in depressed patients are mixed, showing both an increased and decreased pain threshold and pain tolerance across various studies. Although less data is published about anxiety and pain, the relationship is consistent across studies as increased anxiety leads to increased severity of pain perceived and decreased pain tolerance. Anxiety as well as fear, stress, and catastrophizing are also shown to be mediators in the causal pathway between pain and disability.
Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon γ (2002)

High doses of IL-10 upregulate the production of IFN-gamma and neopterin. This phenomenon may be responsible for the lack of efficacy of high doses of IL-10 in the treatment of CACD and MCD.
Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates (1991)

Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in mice and primates. To elucidate the mechanisms underlying this phenomenon, serial analyses were performed on megakaryocytes obtained from rhesus monkeys treated for 8 days with 30 micrograms/kg/d of recombinant human IL-6. Platelet counts increased to a maximum of 7.8 x 10(5)/microL with biphasic peaks on days 7 and 12 without significant changes in platelet volumes. Large increases in DNA content were seen by two-color flow cytometry and digital image analysis. Ploidy distribution underwent a significant shift between study days 3 and 11 (P less than .0001) with large increases in the frequency of 64N and 128N megakaryocytes. The modal ploidy increased from the normal 16N to 64N. Megakaryocyte size, as measured by area, was increased 2- to 2.7-fold. On day 3, multiple megakaryocytes were seen in endomitosis, along with an abundance of young cells with wide, organelle-free peripheral zones. The giant megakaryocytes seen on days 5 to 7 exhibited marked membrane hyperplasia that occupied much of the cell. Emperipolesis occurred frequently, as did megakaryocyte cell death. No giant platelets were seen. We conclude that IL-6 significantly alters the process of megakaryocyte maturation and thrombocytopoiesis, and that these effects, at least in the doses of IL- 6 administered, should not be equated with the physiologic mechanisms operative during accelerated platelet production.
Stent Graft Repair Of Abdominal Aortic Aneurysm (2005)

Technology: Endovascular abdominal aortic aneurysm repair Use: The tremendous enthusiasm within the international vascular community for endovascular aneurysm repair is evidenced by widespread clinical investigations and numerous reports in the literature. 1–5 The device used for the procedure consists of a balloon-expandable metal stent covered with a dacron graft. The stent is introduced through the femoral artery within a delivery system and is passed up the iliac artery into the aorta. It is then deployed and fixed in position within the aneurysm by balloon expansion of the stent, thus excluding the abdominal aortic aneurysm from circulation. History: Endovascular grafting of abdominal aneurysms, first reported clinically in 1991, 1
GOstat: find statistically overrepresented Gene Ontologies within a group of genes (2004)

Our program GOstat is accessible via the Internet at http://gostat.wehi.edu.au
A Furosemide-Sensitive K+–Cl−Cotransporter Counteracts Intracellular Cl−Accumulation and Depletion in Cultured Rat Midbrain Neurons (1999)

Efficacy of postsynaptic inhibition through GABAA receptors in the mammalian brain depends on the maintenance of a Cl- gradient for hyperpolarizing Cl- currents. We have taken advantage of the reduced complexity under which Cl- regulation can be investigated in cultured neurons as opposed to neurons in other in vitro preparations of the mammalian brain. Tightseal whole-cell recording of spontaneous GABAA receptor-mediated postsynaptic currents suggested that an outward Cl- transport reduced dendritic [Cl-]i if the somata of cells were loaded with Cl- via the patch pipette. We determined dendritic and somatic reversal potentials of Cl- currents induced by focally applied GABA to calculate [Cl-]i during variation of [K+]o and [Cl-] in the patch pipette. [Cl-]i and [K+]o were tightly coupled by a furosemide-sensitive K+-Cl- cotransport. Thermodynamic considerations excluded the significant contribution of a Na+-K+-Cl- cotransporter to the net Cl- transport. We conclude that under conditions of normal [K+]o the K+-Cl- cotransporter helps to maintain [Cl-]i at low levels, whereas under pathological conditions, under which [K+]o remains elevated because of neuronal hyperactivity, the cotransporter accumulates Cl- in neurons, thereby further enhancing neuronal excitability.
[New progress in precision diagnosis of prostate cancer]. (2016)

The morbidity of prostate cancer presents an obvious ascending tendency. Early diagnosis plays a crucial role in the diagnosis and treatment of prostate cancer. However, the methods widely used for its diagnosis mostly lack high specificity and sensitivity. This review introduces four methods for the detection of prostate cancer, which are PCA3 and TMPRSS2:ERG, the Kallikrein panel, MRGB, and the STHLM3 model, all based on molecular biology and superior to the traditional methods in both specificity and sensitivity. These methods are expected to contribute to the realization of precision diagnosis of prostate cancer.
Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. (1978)

Graded doses of 0.6, 1.3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.
Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. (1993)

E2F is a mammalian transcription factor that appears to play an important role in cell cycle regulation. While at least two proteins (E2F-1 and DP-1) with E2F-like activity have been cloned, studies from several laboratories suggest that additional homologs may exist. A novel protein with E2F-like properties, designated E2F-2, was cloned by screening a HeLa cDNA library with a DNA probe derived from the DNA binding domain of E2F-1 (K. Helin, J. A. Lees, M. Vidal, N. Dyson, E. Harlow, and A. Fattaey, Cell 70:337-350, 1992). E2F-2 exhibits overall 46% amino acid identity to E2F-1. Both the sequence and the function of the DNA and retinoblastoma gene product binding domains of E2F-1 are conserved in E2F-2. The DNA binding activity of E2F-2 is dramatically enhanced by complementation with particular sodium dodecyl sulfate-polyacrylamide gel electrophoresis-purified components of HeLa cell E2F, and anti-E2F-2 antibodies cross-react with components of purified HeLa cell E2F. These observations are consistent with a model in which E2F binds DNA as a heterodimer of two distinct proteins, and E2F-2 is functionally and immunologically related to one of these proteins.
Purification of Tryptase From a Human Mast Cell Line (1990)

The neutral protease tryptase has been isolated from a human mast cell line, HMC-1. The HMC-1 line was established from the peripheral blood of a patient with mast cell leukemia and maintained as continuously proliferating clones in vitro and as solid mast cell tumors in nude mice. HMC-1-derived tryptase was purified by sequential chromatography on Dowex 1, DEAE 5 PW, and heparin-agarose. Purified tryptase has an apparent molecular weight of 150,000, as determined by molecular sieve HPLC, but migrates as a doublet of bands of 32/35,000 on SDS-PAGE gels. Maximal enzymatic activity was observed at pH 8.5. Cleavage of tosyl-L-arginine methyl ester by purified tryptase was inhibited by dansyl-L-glutamyl-glycyl-L-arginine chloromethyl ketone 2 HCl, HgCl2, tosyl-L-lysine chloromethyl ketone, leupeptin, and PMSF but not by benzamidine, aprotinin, tosyl-L-phenyl-alanine chloromethyl ketone, soybean trypsin inhibitor, human plasma, ovomucoid inhibitor, or lima bean trypsin inhibitor. Microsequencing of purified tryptase yielded an amino terminal sequence that was identical to that previously reported for human pituitary-derived tryptase.
Further investigations on the porcine lymphoma C-type particle (PLCP) and the possible biological significance of the virus in pigs. (1978)

The possible biological significance of the procine lymphoma C-type particle (PLCP) was investigated serologically. The screening of 1 200 field sera of apparently normal breeder pigs, performed with an immunodiffusion test, revealed negative results. The same results were obtained with sera from a herd with hereditary lymphosarcoma and with sera from experimentally infected piglets. In cases of doubtful precipitation lines additional tests with a more sensitive indirect immunofluorescence assay were performed. In no case a specific cytoplasmic fluorescence could be observed. The same sera of the 1 200 pigs were tested with BLV antigen as well as 350 bovine sera from BLV-positive cattle were tested with PLCP antigen. A possible antigenic relationship between BLV and PLCP could not be detected by the assays mentioned above. Purified PLCP was compared in SDS-PAGE with MuLV, FeLV, and BLV. The electrophoretical pattern presents suggestive evidence for a typical oncornavirus polypeptide composition. Apart from the presumable major internal protein with a molecular weight of 28 000 d, three low molecular weight proteins appeared at 12 000 d, 11 000 d, and 10 000 d. High molecular weight proteins could not be detected yet. The antigenic specificity of these bands has still to be confirmed.
Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice. (1991)

Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor.
Amine-terminated silicon nanoparticles: synthesis, optical properties and their use in bioimaging (2009)

Very stable and bright emitting amine-terminated Si nanoparticles (NPs) with different alkyl chain lengths between the Si core and amine end-group are synthesized. The obtained NPs have a spherical shape and homogeneous size distribution (1.57 ± 0.24 nm). Their emission can be tuned from the UV to the blue spectral region, in a controllable fashion, by only changing the alkyl spacer length. The emission quantum yields are ∼12% for all synthesized Si NPs. Excited state lifetimes are in the ns range and point to a direct band gap excitation. NH2-terminated Si NPs exhibit an exceptional stability over a wide pH range (1–13) and high temperatures (120 °C). The diffusion coefficient of prepared Si NPs is determined by fluorescence correlation spectroscopy (FCS) to be 3.3 × 10−10 m2 s−1. The derived size of Si NPs from mobility corresponds to 1.4 nm which is in a good agreement with the size obtained by transmission electron microscopy (TEM). Prepared Si NPs are shown to be highly suitable for bioimaging studies as they are readily taken up by BV2 cells. Si NPs are located in the cells cytosol. Proliferation of stained BV2 cells is observed and showed that newly formed cells are also stained with Si NPs, indicating their minimal toxicity. By using Si NPs it is possible to stain multiple cell generations by only staining the mother cells.