gebhart/patrepeval huggingface dataset:
Influence of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) on the localization of cathepsin B and cathepsin L in human lung tumor cells. (1997)

Cathepsins B and L are catabolic lysosomal enzymes but are likely candidates for extracellular proteolysis in normal and malignant processes. The signal mediator 12(S)-HETE selectively triggers a shot-gun release of cathepsin B. We have therefore investigated the intracellular distribution of cathepsins in unstimulated and 12(S)-HETE-stimulated tumor cells. Cathepsins B and L have only limited colocalization, which is found in the regions of synthesis and sorting (endoplasmic reticulum, Golgi, trans Golgi network). Treatment by 12(S)-HETE scatters cathepsin B but not cathepsin L and proform of cathepsin B. Colocalization with both mannose 6-phosphate receptors is very limited for both cathepsins. But extensive colocalization of cathepsin B and the endosomal/lysosomal marker CD63 (LIMP-I) documents the main fraction of the enzyme in these compartments. The supposed non-lysosomal fraction of cathepsin B is very likely the secretable material which follows a regulated secretory pathway. Storage and regulated secretion in tumor cells support extracellular proteolysis as a means in invasion which may lead to metastasis. But the mechanisms by which cells might acquire and eventually apply this means is still unknown.
Chemistry of 1,2,3‐thiadiazole. IV. Synthesis of [1]benzoxepino‐[3,4‐d][1,2,3]thiadiazole, [1]benzothiepino‐[3,4‐d][1,2,3]thiadiazole, [1]benzoxepino[4,3‐d][1,2,3]thiadiazole, [1]benzoxepino[4,3‐d]oxazole and [1]benzoxepino[4,3‐d]oxazole. Four novel heterocycles (1981)

Abstract Starting from the readily available 4‐bromomethy‐5‐carbethoxy 1,2,3‐thiadiazole (V), 5‐bromomethy‐4‐carbethoxy‐1,2,3‐thiadiazole (IX) and ethyl 2‐aryl‐5‐bromomethyloxazole‐4‐carboxylate (XIV), 4,10‐dihydro‐10‐oxo[1]benzoxepino[3,4‐ d ][1,2,3]thiadiazole (Ia), 4,10‐dihydro‐10‐oxo[1]benzothiepino[3,4‐ d ][1,2,3]thiadiazole (Ib), 4,10‐dihydro‐4‐oxo[1]benzothiepino[4,3‐ d ] [1,2,3]thiazole (II), 2‐aryl‐4,10‐dihydro‐4‐oxo[1]benzoxepino[4,3‐ d ]oxazoles (XIXa‐XIXc) and 2‐aryl‐4,10‐dihydro‐4‐oxo[1]benzothiepino[4,3‐ d ]oxazoles (XIXd‐XIXf) were prepared.
Interleukin-4 and Interleukin-13 Signaling Connections Maps (2003)

Cytokines are inflammatory mediators important in responding to pathogens and other foreign challenges. Interleukin-4 (IL-4) and IL-13 are two cytokines produced by T helper type 2 cells, mast cells, and basophils. In addition to their physiological roles, these cytokines are also implicated in pathological conditions such as asthma and allergy. IL-4 can stimulate two receptors, type I and type II, whereas IL-13 signaling is mediated only by the type II receptor (see the STKE Connections Maps). These cytokines activate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascades, which may contribute to allergic responses. In addition, stimulation of the phosphatidylinositol 3-kinase (PI3K) pathway through recruitment of members of the insulin receptor substrate family may contribute to survival and proliferation.
Influence of heat input/multiple passes and post weld heat treatment on strength/electrochemical characteristics of friction stir weld joint (2017)

The V-95 and D-19 precipitation hardened Russian aluminum alloys are widely used in the Russian aircraft industry and these alloys are not weldable by conventional fusion weld techniques. This paper intends to evaluate the effect of spindle and weld speed on joint strength characteristics of a single pass (SP) and double pass (DP) friction stir lap weld through a common heat index and to analyze the effect of retrogression and re-ageing treatment (RRA) on joint strength and corrosion characteristics. The strength characteristics were analyzed by welding and shear testing of specimens and corrosion susceptibility of joint through immersion in EXCO solution as per ASTM G34. The trials revealed that the joint strength of the welded alloy is inversely proportional to the heat index and the DP weld provided significantly higher strength than an SP weld. The heat affected zone of the joint was found most sensitized to corrosion. The RRA treatment was found to improve the strength of the joints welded with higher heat input while it slightly degraded the joint strength for low heat input welds. The corrosion characteristics of the welded joint is also significantly improved by the post weld RRA treatment.
Purification and biochemical characterization of a human autocrine growth factor produced by Epstein-Barr virus-transformed B cells. (1987)

Autocrine growth factor for Epstein-Barr virus-transformed human B cells (aBGF), a protein that is constitutively produced by the human EBV-transformed B cell line 5/2, has been purified from serum-free conditioned medium. The purification involved sequential ammonium sulfate precipitation, ion exchange chromatography, gel filtration, and reversed-phase high performance liquid chromatography. The purified protein has a m.w. of 16,000 in NaDodSO4/polyacrylamide gel electrophoresis and an isoelectric point between 7.0 and 8.0. The relative molecular mass 16,000 form exists in equilibrium with dimeric and tetrameric forms. aBGF supports the growth of EBV-transformed B cells, which have been deprived of their own conditioned medium. The purified aBGF is fully effective at 0.5 ng/ml and has no interleukin 1 activity in the lymphocyte activation factor assay. Because several randomly selected lines of EBV-transformed cells and one EBV-negative lymphoma cell line both produce aBGF activity and show growth dependency on aBGF and because stimulation of normal B cells with anti-immunoglobulin M is increased by aBGF, we propose that aBGF has general significance for growth control of human B cells.
Investigation of acid oil as a source of biodiesel (2008)

Acid oil which is a byproduct of vegetable oil industry has been investigated for its suitability as a source of biodiesel, as it is economic and readily available in considerable quantities at most of vegetable oil refinery sites. The biodiesel from acid oil is produced by a new type of ED3R esterification process developed at the Institute. Fuel properties of biodiesel thus produced are compared with standard biodiesel and diesel fuel. Blends of biodiesel and diesel fuel are prepared. Fuel property variations of biodiesel blends produced are reported.
RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1α release, and efficient paracrine dendritic cell activation (2015)

Previous studies have shown that cervical cancer cells only release low levels of pro-inflammatory cytokines owing to infection with human papillomaviruses. This results in low immunogenicity of the cancer cells. The viral dsRNA analog PolyIC has been suggested as a promising adjuvant for cervical cancer immunotherapy. However, little is known about the molecular requirements resulting in successful immune activation. Here, we demonstrate that stimulation of cervical cancer cells with PolyIC induced necroptotic cell death, which was strictly dependent on the expression of the receptor-interacting protein kinase RIPK3. Necroptotic cancer cells released interleukin-1α (IL-1α), which was required for powerful activation of dendritic cells (DC) to produce IL-12, a cytokine critical for anti-tumor responses. Again both, IL-1α release and DC activation, were strictly dependent on RIPK3 expression in the tumor cells. Of note, our in situ analyses revealed heterogeneous RIPK3 expression patterns in cervical squamous cell carcinomas and adenocarcinomas. In summary, our study identified a novel RIPK3-dependent mechanism that explains how PolyIC-treatment of cervical cancer cells leads to potent DC activation. Our findings suggest that the RIPK3 expression status in cervical cancer cells might critically influence the outcome of PolyIC-based immunotherapeutic approaches and should therefore be assessed prior to immunotherapy.
σ1Receptors Are Involved in the Visceral Pain Induced by Intracolonic Administration of Capsaicin in Mice (2013)

These results suggest that σ1 receptors play a role in the mechanisms underlying capsaicin-induced visceral pain and raise novel perspectives for their potential therapeutic value.
A novel bioluminogenic assay for α‐chymotrypsin (1995)

The use of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin as a novel substrate for alpha-chymotrypsin has been demonstrated. The kinetic parameters determined are KM = 0.38 mmol/L, kcat = 6.5 s-1 and kcat/kM = 17,100 (L/mol s). The test principle of the coupled assay is the release of aminoluciferin by enzymatic cleavage of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin. Aminoluciferin is oxidized, with light emission, by firefly luciferase (Photinus pyralis) and can be quantified in a luminometric assay. The detection limit for chymotrypsin was found to be 0.3 ng per assay. 6-(N-acetyl-L-phenylalanyl)-aminoluciferin has been synthesized as an example for a new class of highly sensitive substrates. By modification of the peptide residue these new substrates may be suitable for ultrasensitive detection of different proteinases.
Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5 (2008)

Phosphatidylinositol 3-phosphate (PI(3)P) plays an important role in insulin-stimulated glucose uptake. Insulin promotes the production of PI(3)P at the plasma membrane by a process dependent on TC10 activation. Here, we report that insulin-stimulated PI(3)P production requires the activation of Rab5, a small GTPase that plays a critical role in phosphoinositide synthesis and turnover. This activation occurs at the plasma membrane and is downstream of TC10. TC10 stimulates Rab5 activity via the recruitment of GAPEX-5, a VPS9 domain-containing guanyl nucleotide exchange factor that forms a complex with TC10. Although overexpression of plasma membrane-localized GAPEX-5 or constitutively active Rab5 promotes PI(3)P formation, knockdown of GAPEX-5 or overexpression of a dominant negative Rab5 mutant blocks the effects of insulin or TC10 on this process. Concomitant with its effect on PI(3)P levels, the knockdown of GAPEX-5 blocks insulin-stimulated Glut4 translocation and glucose uptake. Together, these studies suggest that the TC10/GAPEX-5/Rab5 axis mediates insulin-stimulated production of PI(3)P, which regulates trafficking of Glut4 vesicles.
The influence of bulk nonradiative recombination in the wide band-gap regions of molecular beam epitaxially grown GaAs-AlxGa1−xAs DH lasers (1978)

It is shown that bulk nonradiative recombination near the heterojunctions in the wide-band-gap regions is probably an important contributor to the higher threshold current densities of the best state-of-the-art molecular beam epitaxial GaAs-AlxGa1−xAs DH lasers over similar geometry liquid-phase epitaxial lasers. This recombination probably is at least part of the cause of the large recombination velocity (measured as interfacial recombination velocity) in molecular beam epitaxial heterostructures.
The Role of the Bed Nucleus of the Stria Terminalis in Stress-Induced Inhibition of Pulsatile Luteinising Hormone Secretion in the Female Rat (2010)

The bed nucleus of the stria terminalis (BNST) occupies a central position in the neural circuitry regulating the hypothalamic-pituitary-adrenocortical axis response to stress. The potential role of the BNST in stress-induced suppression of the gondotrophin-releasing hormone (GnRH) pulse generator, the central regulator of the reproductive system, was assessed by examining the effects of micro-infusion of corticotrophin-releasing factor (CRF) or its antagonist into the BNST on pulsatile luteinising hormone (LH) secretion or stress-induced inhibition of LH pulses, respectively. Ovariectomised oestrogen-treated rats were implanted chronically with bilateral cannulae in the dorsolateral BNST and i.v. catheters. CRF (25, 50 or 100 pmol in 200 nl of artificial cerebrospinal fluid) administered bilaterally into the BNST resulted in a dose-dependent decrease in LH pulse frequency, and induced Fos expression in glutamic acid decarboxylase immunostained neurones in the medial preoptic area. These results suggest that the activation of hypothalamic GABAergic neurones in response to intra-BNST administration of CRF may be involved in the suppression of LH pulses. Furthermore, administration of CRF antagonist (280 pmol astressin-B, three times at 20-min intervals) into the BNST effectively blocked the suppression of pulsatile LH secretion in response to restraint (1 h) but not hypoglycaemic (0.25 U insulin/kg, i.v.) stress. These data suggest that CRF innervation of the dorsolateral BNST plays a key, but differential, role in stress-induced suppression of the GnRH pulse generator.
Spin Hall Effect in the Presence of Spin Diffusion (2000)

Hirsch [Phys. Rev. Lett. 83, 1834 (1999)] recently proposed a spin Hall effect based on the anomalous scattering mechanism in the absence of spin-flip scattering. Since the anomalous scattering causes both anomalous currents and a finite spin-diffusion length, we derive the spin Hall effect in the presence of spin diffusion from a semiclassical Boltzmann equation. When the formulation is applied to certain metals and semiconductors, the magnitude of the spin Hall voltage due to the spin accumulation is found to be much larger than that of magnetic multilayers. An experiment is proposed to measure this spin Hall effect.
Vaxfectin™-Formulated Influenza DNA Vaccines Encoding NP and M2 Viral Proteins Protect Mice against Lethal Viral Challenge (2007)

Next generation influenza vaccines containing conserved antigens may enhance immunity against seasonal or pandemic influenza virus strains. Using a plasmid DNA (pDNA)-based vaccine approach, we systematically tested combinations of NP, M1, and M2 antigens derived from consensus sequences for protection against lethal influenza challenge and compared formulations for adjuvanting low pDNA vaccine doses. The highest level of protection at the lowest pDNA doses was provided by Vaxfectin-formulated NP + M2. Vaxfectin adjuvanticity was confirmed with a low dose of HA pDNA. These promising proof-of-concept data support the clinical development of Vaxfectin-formulated pDNA encoding NP + M2 consensus proteins.
Expression of macrophage procoagulant activity in murine systemic lupus erythematosus. (1986)

To explore the induction of monocyte/macrophage procoagulant activity in autoimmune disease, the BXSB murine model of systemic lupus erythematosus was studied. Splenic macrophage procoagulant activity rose coincident with age and the development of glomerulonephritis from 38 +/- 6 mU/10(6) macrophages at 1 mo to a maximum of 29,000 +/- 15,000 mU at 4 mo. Macrophages from 1-mo-old mice could be induced to express a 1,000-fold increase in monocyte/macrophage procoagulant activity when incubated with lymphocytes or lymphocyte supernatants from 5-mo-old mice. Plasma from 5-mo-old but not from 1-mo-old mice was able to induce the production of the lymphokine by cells from 1-mo-old animals. This lymphokine was not interleukin 1,2, or gamma interferon. We conclude that induction of monocyte/macrophage procoagulant activity parallels disease development in the male BXSB mouse, is dependent on the interaction between lymphocytes and plasma factors, and may be important in mediation of injury in lupus nephritis.
Atrial Natriuretic Hormone Has Biological Effects in Man at Physiological Plasma Concentrations* (1988)

Whether atrial natriuretic hormone (ANH) has biological effects at physiological plasma levels in man is not known. Accordingly, we investigated the effects of a 3-h low dose infusion of human ANF (0.75 pmol/kg.min; i.e. 0.0023 micrograms/kg.min) in six normal men, whose sodium intake was normal while sitting, in a single blind, random order, placebo-controlled study. The ANF infusions induced changes in plasma ANH concentrations entirely within the range for normal subjects. The small increases in plasma ANH values were associated with a significant rise in urinary excretion of sodium, magnesium, calcium, and cGMP. PRA and plasma aldosterone concentrations uniformly decreased to 50% and 64% of placebo values, respectively. Systolic and mean arterial pressures fell significantly from preinfusion values during the ANH infusions. These findings constitute strong evidence that ANH is a hormone of physiological significance in the regulation of body fluid volumes in normal man.
Commentary Pathogenesis of rheumatoid arthritis: how early is early? (2005)

Studies of cytokine expression in rheumatoid arthritis have provided key insights into the pathogenesis of disease and have offered clues for effective therapy. Patterns of T-cell products in chronic rheumatoid synovitis suggest that T helper type 1 cells contribute to the perpetuation of disease. However, there is no guarantee that the mechanisms of late disease are identical to very early rheumatoid arthritis. Evaluation of the cytokine profile at the earliest time points after onset of symptoms could identify novel targets that prevent progression to chronic arthritis. Development of hypotheses to explain the pathogenesis of chronic rheumatoid arthritis (RA), including the interesting new study by Raza and colleagues [1], has been a wondrous adventure. Virtually every immune cell type and inflammatory mediator has been implicated in the disease process at one
A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer (2016)

Perioperative mFOLFOX6 was a tolerable and effective regimen for gastric cancer. The ypTNM stage was an independent predictor of survival. GHR ⩾50%/<50% could be used as a surrogate marker for selecting a postoperative chemotherapy regimen.
Automatic Learning of A Supervised Classifier for Patent Prior Art Retrieval (2010)

There are approximately 23 million patients with heart failure (HF) worldwide. The prognosis of patients with HF is still poor and a prospective approach for preventing and treating HF is necessary. The number of HF patients in Japan has been increasing since 1950 mainly because of a rapidly aging population. Furthermore, westernized dietary pattern, reduced physical activity, and obesity have become prominent, particularly in younger Japanese men. There is an increasing trend of diabetes and dyslipidemia, and the prevalence of smoking and hypertension continues to remain high. One of the largest HF cohorts in Japan, the CHART Studies, showed that coronary artery disease (CAD) was the most frequent etiology of HF currently. Thus, prospective strategies including accurate risk stratification, effective prevention of disease progression through evidence-based treatments, optimally personalized treatment particularly in elderly individuals, and life-long control of CAD risk factors are required to manage HF in Japan.
Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A (2001)

Protein kinases of the DYRK (‘dual-specificity tyrosine-regulated kinase’) family are characterized by a conserved Tyr-Xaa-Tyr motif (Tyr-319–Tyr-321) in a position exactly corresponding to the activation motif of the mitogen-activated protein kinase (MAP kinase) family (Thr-Xaa-Tyr). In a molecular model of the catalytic domain of DYRK1A, the orientation of phosphorylated Tyr-321 is strikingly similar to that of Tyr-185 in the known structure of the activated MAP kinase, extracellular-signal-regulated kinase 2. Consistent with our model, substitution of Tyr-321 but not of Tyr-319 by phenylalanine markedly reduced the enzymic activity of recombinant DYRK1A expressed in either Escherichia coli or mammalian cells. Direct identification of phosphorylated residues by tandem MS confirmed that Tyr-321, but not Tyr-319, was phosphorylated. When expressed in COS-7 cells, DYRK1A was found to be fully phosphorylated on Tyr-321. A catalytically inactive mutant of DYRK1A contained no detectable phosphotyrosine, indicating that Tyr-321 is autophosphorylated by DYRK1A. MS identified Tyr-111 and Ser-97 as additional autophosphorylation sites in the non-catalytic N-terminal domain of bacterially expressed DYRK1A. Enzymic activity was not affected in the DYRK1A-Y111F mutant. The present experimental data and the molecular model indicate that the activity of DYRK1A is dependent on the autophosphorylation of a conserved tyrosine residue in the activation loop.
Staphylococcus aureus Protein A Binds to Osteoblasts and Triggers Signals That Weaken Bone in Osteomyelitis (2011)

Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients is poorly understood. We describe here for the first time that the major virulence factor of S. aureus, protein A (SpA) binds directly to osteoblasts. This interaction prevents proliferation, induces apoptosis and inhibits mineralisation of cultured osteoblasts. Infected osteoblasts also increase the expression of RANKL, a key protein involved in initiating bone resorption. None of these effects was seen in a mutant of S. aureus lacking SpA. Complementing the SpA-defective mutant with a plasmid expressing spa or using purified protein A resulted in attachment to osteoblasts, inhibited proliferation and induced apoptosis to a similar extent as wildtype S. aureus. These events demonstrate mechanisms through which loss of bone formation and bone weakening may occur in osteomyelitis patients. This new information may pave the way for the development of new and improved therapeutic agents to treat this disease.
Kinetic Energy Model of Two-Phase Debris Flow (2011)

A numerical model for two-phase debris flows is developed in this paper, on the basis of understanding of the physical characteristics of debris flows from field investigations and experiments. Employing a moving coordinate, the kinetic energy equation of gravel particles in unit volume in debris flow is developed by considering the potential energy of the particles, energy from the liquid phase, energy consumption due to inner friction-collision between the particles, energy dispersion through collisions between particles, energy for inertia force, energy consumption due to the friction with the rough bed and energy consumption at the debris front. The model is compared with measured results of two-phase debris flow experiments and the calculated velocity profiles agree well with the measured profiles. The gravel's velocity at the debris flow head is much smaller than that of particles in the following part and the velocity profile at the front of the debris flow wave is almost linear, but the profile in the main flow shows an inverse 's' shape. This is because the gravel particles in the main flow accelerate as they receive energy from the gravitational energy and flowing liquid and decelerate as they transmit the energy to the debris flow head and consume energy due to collision with the channel bed.
A 55Gb/s directly modulated 850nm VCSEL-based optical link (2012)

We report a directly modulated 850nm VCSEL-based Optical link operating at 55Gb/s. This is the highest modulation rate for VCSEL-based link of any wavelength.