gebhart/patrepeval huggingface dataset:
ATP-Sensitive K+Channels, Adenosine, and Nitric Oxide–Mediated Mechanisms Account for Coronary Vasodilation During Exercise (1998)

We previously reported that combined blockade of adenosine receptors and ATP-sensitive K+ channels (K+(ATP) channels) blunted but did not abolish the response of coronary blood flow to exercise. This study tested the hypothesis that the residual increase in coronary flow in response to exercise after adenosine receptor and K+(ATP) channel blockade is dependent on endogenous NO. Dogs were studied at rest and during a four-stage treadmill exercise protocol under control conditions, during K+(ATP) channel blockade with glibenclamide (50 microg x kg(-1) x min(-1) i.c.) in the presence of adenosine receptor blockade with 8-phenyltheophylline (8-PT, 5 mg/kg i.v.), and after the addition of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA, 1.5 mg/kg i.c.). During control conditions, coronary blood flow was 49 +/- 3 mL/min at rest and increased to 92 +/- 8 mL/min at peak exercise. LNNA alone or in combination with 8-PT did not alter resting coronary flow and did not impair the normal increase in flow during exercise, indicating that when K+(ATP) channels are intact, neither NO nor adenosine-dependent mechanisms are obligatory for maintaining coronary blood flow. Combined K+(ATP) channel and adenosine blockade decreased resting coronary flow to 27 +/- 3 mL/min (P<.05), but exercise still increased flow to 45 +/- 5 mL/min (P<.05). The subsequent addition of LNNA further decreased resting coronary flow to 20 +/- 2 mL/min and markedly blunted exercise-induced coronary vasodilation (coronary vascular conductance, 0.20 +/- 0.03 mL x min(-1) x mm Hg(-1) at rest versus 0.24 +/- 0.04 mL x min(-1) x mm Hg(-1) during the heaviest level of exercise; P=.22), so that coronary flow both at rest and during exercise was below the control resting level. The findings suggest that K+(ATP) channels are critical for maintaining coronary vasodilation at rest and during exercise but that when K+(ATP) channels are blocked, both adenosine and NO act to increase coronary blood flow during exercise. In the presence of combined K+(ATP) channel blockade and adenosine receptor blockade, NO was able to produce approximately one quarter of the coronary vasodilation that occurred in response to exercise when all vasodilator systems were intact.
Assured Forwarding PHB Group (1999)

This document defines a general use Differentiated Services (DS) [Blake] Per-Hop-Behavior (PHB) Group called Assured Forwarding (AF). The AF PHB group provides delivery of IP packets in four independently forwarded AF classes. Within each AF class, an IP packet can be assigned one of three different levels of drop precedence. A DS node does not reorder IP packets of the same microflow if they belong to the same AF class.
Targeting the LOX / hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy (2015)

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1-Cre Kras(G12D/+) Trp53(R172H/+) (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor-free survival in KPC mice with early-stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease.
Cancer chemoprevention by the antioxidant tempol acts partially via the p53 tumor suppressor (2005)

We previously demonstrated that the nitroxide antioxidant tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) increased latency to tumorigenesis and doubled (100%) the lifespan of Atm-deficient mice, a mouse model of ataxia telangiectasia, which displays accelerated oxidative damage and stress. Tempol treatment of cancer-prone p53-deficient mice resulted in a small but significant (25%) increase in lifespan by prolonging latency to tumorigenesis, demonstrating that existing oxidative stress and damage are not necessary for the chemopreventative effects of tempol. However, the relatively small effect on latency in p53-deficient mice and the finding that tempol-mediated resistance to oxidative insult was p53-dependent suggested a more direct role of p53 in the chemopreventative effects of tempol. Surprisingly, tempol treatment specifically increased serine 18 phosphorylation of p53 (but not gamma-H2AX) and p21 expression in primary thymocytes in vitro in a p53-dependent fashion. Inhibition of phosphoinositide 3-kinase (PI3K) family members suggested that SMG-1 was responsible for the tempol-mediated enhancement of p53 serine 18 phosphorylation. These data suggest that the chemopreventative effect of tempol is not solely due to the reduction of oxidative stress and damage but may also be related to redox-mediated signaling functions that include p53 pathway activation.
ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms (2017)

Abstract Oncogenic ALK fusions occur in several types of cancer and can be effectively treated with ALK inhibitors; however, ALK fusions and treatment response have not been characterized in malignant melanomas. Recently, a novel isoform of ALK (ALKATI) was reported in 11% of melanomas but the response of melanomas expressing ALKATI to ALK inhibition has not been well characterized. We analyzed 45 melanoma patient-derived xenograft models for ALK mRNA and protein expression. ALK expression was identified in 11 of 45 (24.4%) melanomas. Ten melanomas express wild-type (wt) ALK and/or ALKATI and one mucosal melanoma expresses multiple novel EML4-ALK fusion variants. Melanoma cells expressing different ALK variants were tested for response to ALK inhibitors. Whereas the melanoma expressing EML4-ALK were sensitive to ALK inhibitors in vitro and in vivo, the melanomas expressing wt ALK or ALKATI were not sensitive to ALK inhibitors. In addition, a patient with mucosal melanoma expressing ALKATI was treated with an ALK/ROS1/TRK inhibitor (entrectinib) on a phase I trial but did not respond. Our results demonstrate ALK fusions occur in malignant melanomas and respond to targeted therapy, whereas melanomas expressing ALKATI do not respond to ALK inhibitors. Targeting ALK fusions is an effective therapeutic option for a subset of melanoma patients, but additional clinical studies are needed to determine the efficacy of targeted therapies in melanomas expressing wt ALK or ALKATI. Mol Cancer Ther; 17(1); 222–31. ©2017 AACR.
Zur Chemie des Indols, VI. α.β′‐Diindolylmethane und ‐methene. Der Urorosein‐Chromophor (1969)

Abstract Urorosein entsteht durch Polykondensation von Indolyl‐(3)‐glykolsäure und anschließende Oxydation, wobei sich der α.β′‐Diindolylmethen‐Chromophor bildet. α.β′‐Diindolylmethen ( 1 – 5 ) werden durch Reaktion von α‐freien und β‐freien Indolen mit Glyoxylsäure, α.β′‐Diindolymethene ( 10 – 12 ) aus α‐Formyl‐indolen mit β‐freien Indolen gewonnen. Oxo‐β.β′‐ ( 13 – 16 ) und Oxo‐α.β′‐diindolylmethene ( 17 – 20 ) entstehen aus β‐bzw. α‐Formyl‐indolen mit Oxindolen.
A Partial Structural and Functional Rescue of a Retinitis Pigmentosa Model with Compacted DNA Nanoparticles (2009)

Previously we have shown that compacted DNA nanoparticles can drive high levels of transgene expression after subretinal injection in the mouse eye. Here we delivered compacted DNA nanoparticles containing a therapeutic gene to the retinas of a mouse model of retinitis pigmentosa. Nanoparticles containing the wild-type retinal degeneration slow (Rds) gene were injected into the subretinal space of rds(+/-) mice on postnatal day 5. Gene expression was sustained for up to four months at levels up to four times higher than in controls injected with saline or naked DNA. The nanoparticles were taken up into virtually all photoreceptors and mediated significant structural and biochemical rescue of the disease without histological or functional evidence of toxicity. Electroretinogram recordings showed that nanoparticle-mediated gene transfer restored cone function to a near-normal level in contrast to transfer of naked plasmid DNA. Rod function was also improved. These findings demonstrate that compacted DNA nanoparticles represent a viable option for development of gene-based interventions for ocular diseases and obviate major barriers commonly encountered with non-viral based therapies.
Spray developer for ZEP 7000 (2000)

ZEP7000 has been successfully used as EB resist for high-end photomask manufacturing where high dry etching resistance, high sensitivity and high resolution are required. ZED-500 is the common developer use din spray development process and ZED-750 for puddle development process. These developers are designed to suite particularly for dry etching pattern profile. In this paper, we introduce a new developer, ZED- 450 which performs equivalent to ZED-500 while requiring either lower dosage or shorter development time in spray development process.
Functional bowel disorders and functional abdominal pain (2020)

The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient's pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.Keywords: functional bowel disorder; functional constipation; functional diarrhea; irritable bowel syndrome; functional abdominal pain; functional abdominal bloating; Rome II
Generation of genetically modified rats from embryonic stem cells (2010)

At present, genetically modified rats have not been generated from ES cells because stable ES cells and a suitable injection method are not available. To monitor the pluripotency of rat ES cells, we generated Oct4-Venus transgenic (Tg) rats via a conventional method, in which Venus is expressed by the Oct4 promoter/enhancer. This monitoring system enabled us to define a significant condition of culture to establish authentic rat ES cells based on a combination of 20% FBS and cell signaling inhibitors for Rho-associated kinase, mitogen-activated protein kinase, TGF-beta, and glycogen synthase kinase-3. The rat ES cells expressed ES cell markers such as Oct4, Nanog, Sox2, and Rex1 and retained a normal karyotype. Embryoid bodies and teratomas were also produced from the rat ES cells. All six ES cell lines derived from three different rat strains successfully achieved germline transmission, which strongly depended on the presence of the inhibitors during the injection process. Most importantly, high-quality Tg rats possessing a correct transgene expression pattern were successfully generated via the selection of gene-manipulated ES cell clones through germline transmission. Our rat ES cells should be sufficiently able to receive gene targeting as well as Tg manipulation, thus providing valuable animal models for the study of human diseases.
The p53-mdm-2 autoregulatory feedback loop. (1993)

The p53 protein can bind to a set of specific DNA sequences, and this may activate the transcription of genes adjacent to these DNA elements. The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm-2 gene can be regulated by the level of wild-type p53 protein. The mdm-2 protein, in turn, can complex with p53 and decrease its ability to act as a positive transcription factor at the mdm-2 gene-responsive element. In this way, the mdm-2 gene is autoregulated. The p53 protein regulates the mdm-2 gene at the level of transcription, and the mdm-2 protein regulates the p53 protein at the level of its activity. This creates a feedback loop that regulates both the activity of the p53 protein and the expression of the mdm-2 gene.
Differential activation of human immunodeficiency virus type 1 and 2 transcription by specific T-cell activation signals (1993)

The human immunodeficiency virus type 1 (HIV-1) and HIV-2 enhancers are induced differentially by physiologic T-cell activation signals. In contrast to that of HIV-1, HIV-2 transcription was quite responsive to stimulation of T cells by antigen presentation but weakly induced by tumor necrosis factor alpha. Like tumor necrosis factor alpha, expression of cloned NF-kappa B subunits strongly activated the HIV-1, but not the HIV-2, enhancer. The differences in response to these physiologic T-cell activation pathways may contribute to the differences in persistence of HIV-1 and HIV-2 infection.
Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase. (1991)

The MET proto-oncogene encodes a transmembrane tyrosine kinase receptor for HGF (p190MET). In this work, p190MET was immunoprecipitated, allowed to phosphorylate in the presence of [gamma-32P]ATP, and digested with trypsin. A major phosphopeptide was purified by reverse phase chromatography. The phosphorylated tyrosine was identified as residue 1235 (Tyr1235) by Edman covalent radiosequencing. A synthetic peptide derived from the corresponding MET sequence was phosphorylated by p190MET in an in vitro assay and coeluted in reverse phase chromatography. Tyr1235 lies within the tyrosine kinase domain of p190MET, within a canonical tyrosine autophosphorylation site that shares homology with the corresponding region of the insulin, CSF-1 and platelet-derived growth factor receptors, and of p60src and p130gag-fps. The p190MET kinase is constitutively phosphorylated on tryosine in a gastric carcinoma cell line (GTL16), due to the amplification and overexpression of the MET gene. Metabolic labeling of GTL-16 cells with [32P]orthophosphate followed by immunoprecipitation and tryptic phosphopeptide mapping of p190MET showed that Tyr1235 is a major site of tyrosine phosphorylation in vivo as well. Since phosphorylation activates p190MET kinase, we propose a regulatory role for Tyr1235.
Dye-Capped Gold Nanoclusters:  Photoinduced Morphological Changes in Gold/Rhodamine 6G Nanoassemblies (2000)

Au nanoparticles (particle diameter ∼2 nm) prepared by thiocyanate reduction method are too small to exhibit the characteristic surface plasmon band. Addition of Rhodamine 6G (Rh 6G) to the colloidal gold solution brings about significant changes in the absorption spectrum. Two distinct peaks appear at 507 and 537 nm. Close packing of the cationic dye molecules on the gold surface induces intermolecular and intercluster interactions. Furthermore, the adsorption of the cationic dye on the gold surface results in surface charge neutralization causing the Au/dye assembly to aggregate. When the Au/Rh-6G solution was subjected to 532 nm laser pulse irradiation for long time intervals, we observed distinct changes in the absorption spectrum due to morphological changes. A growth in the particle size (5−20 nm) is observed as a result of melting and fusion of gold nanoparticles. The photoinduced morphological changes have been elucidated using picosecond laser flash photolysis. The multiphoton process leading to fusion of particles occurs with a rate constant of 7 × 108 s-1. The indirect role of Rh-6G in assisting the fusion of gold nanoparticles is discussed.
Quantum-well reflectivity and exciton-polariton dispersion (1992)

We prove that reflectivity measurements as a function of angle of incidence allow the measurement of the exciton-polariton modes in quantum wells. The resonant polaritons at ${\mathit{k}}_{\mathrm{?}}$${\mathit{k}}_{0}$=\ensuremath{\omega}/v manifest themselves as peaks in the reflectivity while surface polaritons at ${\mathit{k}}_{\mathrm{?}}$&gt;${\mathit{k}}_{0}$ manifest themselves as dips in the attenuated total reflection. A comparison of the reflectivities with polarization perpendicular and parallel to the plane of incidence allows us to detect the different polariton modes and to measure the dispersion relation. We also give expressions to compute reflectivity and transmission for the case of multiple quantum wells, including the effects of multiple reflections. Examples are given for standard reflectivity of GaAs/${\mathrm{Al}}_{\mathit{x}}$${\mathrm{Ga}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$As quantum wells and for attenuated total reflection of CuCl/${\mathrm{CaF}}_{2}$ quantum wells.
A dose‐point‐kernel model for a low energy gamma‐emitting stent in a heterogeneous medium (2001)

A computer dose model for a low energy gamma-emitting stent in a heterogeneous medium is described. The method is based on the Sievert model which is adapted to the dose-point-kernel (DPK) model to compute the dose distribution about filtered gamma sources (Sievert-DPK model). The new gamma stent model can take into account effects such as the metallic wire attenuation and the presence of dense calcified plaque in a stented artery. The Sievert-DPK model is tested against numerical simulations around cylindrical shell sources with dimensions comparable to those of a stent using a Monte Carlo transport code. For low energy gamma sources (Cs-131 and Pd-103), it is shown that the Sievert-DPK model is consistent with the Monte Carlo results to about 5%-10% for distances up to 5 mm from the cylindrical surface and 2.5 mm beyond the cylinder edges. These results indicate that the Sievert-DPK model may be useful to predict the dose in intravascular therapy applications for heterogeneous systems consisting of soft tissue, metal and dense plaque.
Three-dimensional x-ray imaging with off-axis x-ray zone plate (1995)

Fresnel zone plates are now routinely used to produce two dimensional x‐ray images of organic and inorganic specimens. We describe one possible approach of achieving three‐dimensional x‐ray imaging which utilizes non‐circular Fresnel zone plates. This approach is ideally suited for applications in the x‐ray laser community where specimen and zone plate alignment must be performed off lines.
Mitochondrial Proteins That Regulate Apoptosis and Necrosis Are Induced in Mouse Fatty Liver (1999)

Fatty liver is common in nonalcoholic, obese individuals and in lean people who consume alcohol chronically. Although fatty liver is typically benign, a subset of individuals with steatosis develop steatohepatitis and eventually cirrhosis. The disparate outcomes of fatty liver suggest that it reflects a generally beneficial, adaptive response to obesity or alcohol-related stress, but may also increase hepatocyte vulnerability to other challenges. Thus, both protective factors (e.g., Bcl-2 and Bcl-xL) and factors that promote hepatocyte death by apoptosis (e.g., Bax) or necrosis (e.g., UCP2) may be increased in fatty livers. To evaluate this possibility, hepatocyte apoptosis, necrosis, and the expression of factors that regulate cellular viability were assessed in two models of fatty liver (i.e., genetically obese [ob/ob] mice and ethanol [EtOH]-fed lean mice). Findings in mice with fatty livers were compared with lean, control mice that did not have hepatic steatosis. Immunohistochemistry showed striking induction of hepatocyte proteins that promote (e.g., Bax) and inhibit (e.g., Bcl-2 and Bcl-xL) apoptosis in both groups with fatty liver. Both models of fatty liver also increased hepatic transcripts for UCP2, a mitochondrial uncoupling protein, and the protein itself was induced in ob/ob hepatocytes. Despite the up-regulation of factors that threaten cell viability, hepatocyte death was not increased in either ob/ob or EtOH-fed mice, confirming that the liver's protective responses were sufficient under the conditions studied. However, if UCP2 induction reduces the efficiency of adenosine triphosphate (ATP) synthesis, this initially harmless response might enhance the vulnerability of hepatocytes to necrosis.
Tumor-derived lactic acid modulates dendritic cell activation and antigen expression (2005)

The tumor milieu can influence dendritic cell (DC) differentiation. We analyzed DC differentiation in a 3-dimensional tumor model and propose a new mechanism of DC modulation by the tumor environment. Monocytes were cultured in the presence of IL-4 and GM-CSF within multicellular tumor spheroids (MCTSs) generated from different tumor cell lines. Monocytes invaded the MCTSs and differentiated into tumor-associated dendritic cells (TADCs). The antigen expression was altered on TADCs independent of the culture conditions (immature/mature DCs, Langerhans cells) and IL-12 secretion was reduced. Supernatants of MCTSs could partially transfer the suppressive effect. Conditioned media from urothelial carcinoma cell lines contained high levels of M-CSF and IL-6, both cytokines known to modulate DC differentiation. In contrast, melanoma and prostate carcinoma MCTS cocultures produced little M-CSF and IL-6, but high levels of lactic acid. Indeed, addition of lactic acid during DC differentiation in vitro induced a phenotype comparable with TADCs generated within melanoma and prostate carcinoma MCTSs. Blocking of lactic acid production in melanoma MCTS cocultures reverted the TADC phenotype to normal. We therefore conclude that tumor-derived lactic acid is an important factor modulating the DC phenotype in the tumor environment, which may critically contribute to tumor escape mechanisms.