gebhart/patrepeval huggingface dataset:
Chemical Induction of Unfolded Protein Response Enhances Cancer Cell Killing through Lytic Virus Infection (2014)

Cancer is difficult to combat. A wide range of oncolytic viruses show promise for killing cancer cells, yet the efficacy of oncolytic killing is low. We searched for host factors enhancing adenovirus cancer cell killing and found that the knockdown of Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF-1) or chemical inhibition of GBF-1 enhanced adenovirus infection by triggering the IRE-1/XBP-1 branch of the unfolded protein response (UPR). IRE-1/XBP-1 promote cell survival and enhanced the levels of the adenoviral immediate early gene product E1A, virus spreading, and killing of cancer cells. Aggressive tumor cells depend on a readily inducible UPR and, hence, present prime targets for a combined strategy involving adenoviruses and small chemicals inducing UPR.
Distant and Lymph Node Metastases of Thyroid Nodules with No Pathological Evidence of Malignancy: A Limitation of Pathological Examination (2008)

Among thyroid nodules arising from follicular cells, benign nodular goiter is thought not to metastasize to regional or distant organs. However, we encountered five cases that were pathologically diagnosed as benign nodular goiter but showed metastasis. The prevalence of benign nodular goiter showing metastasis was 0.17% (5 of 2978 patients). On pathology, there were no detectable signs of carcinoma or follicular adenoma lesions. Two patients showed lymph node metastasis that was pathologically confirmed as metastasis of nodular goiter. One was preoperatively and another was postoperatively detected by ultrasonography. These patients also showed distant metastases that could be ablated by radioiodine. One patient preoperatively showed lung metastasis and the remaining two showed lung and bone metastases and bone metastasis postoperatively. Pathological diagnosis of thyroid nodules has limitations, and cases diagnosed as benign nodular goiter should still undergo careful follow-up.
Value of beat-to-beat blood pressure changes, detected by pulse transit time, in the management of the obstructive sleep apnoea/hypopnoea syndrome (1998)

Two important aspects of a respiratory sleep study are a measure of inspiratory effort and an estimate of the number of arousals. These can be derived from an indirect estimate of beat-to-beat blood pressure (BP), pulse transit time (PTT). This study investigated the reproducibility of inspiratory BP falls (reflecting inspiratory effort), and BP arousals derived from PTT, and the contribution they could make to the management of the obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Overnight PTT was recorded at home in 40 patients being investigated for OSAHS, and a second PTT recording was made in the sleep laboratory with full polysomnography. Patients were divided into three groups according to the severity of their sleep disorder, and a third PTT recording was made at home in 13 patients subsequently established on nasal continuous positive airway pressure (CPAP). The reproducibility between the home and laboratory studies was reasonable (r=0.87 for inspiratory BP falls, r=0.81 for BP arousals). Both derivatives showed a clear progression through the three patient groups, which returned to normal on treatment. The differences between the groups were significant (p<0.001 for inspiratory BP falls, p=0.0014 for BP arousals). Receiver operator characteristic curves, used to compare polysomnography variables and PTT variables, confirmed that the PTT variables were as good as apnoea-hypopnoea index (AHI), >4% arterial oxygen saturation dip rate and electroencephalography micro-arousals at dividing patients into two groups, either requiring nasal CPAP or not requiring CPAP. Pulse transit time can provide a noninvasive estimate of inspiratory effort and a measure of arousals that together document disease severity and response to treatment and may be useful in managing obstructive sleep apnoea/hypopnoea syndrome.
High Occurrence Rate of Glaucoma among Patients with Alzheimer’s Disease (2002)

The purpose of the current study was to reveal the occurrence rate of glaucoma among patients with Alzheimer's disease (AD). All 112 patients of four nursing homes in Upper Bavaria, Germany, who met the diagnostic criteria of probable AD, were incorporated into the study. Visual field defects and/or optic disc cupping compatible with the diagnosis of glaucoma were found in 29 out of 112 patients with AD (25.9%). When compared to a control group (5.2%) and to the prevalence of glaucoma in western countries revealed in a number of glaucoma surveys (2.6-4.7%), patients with AD may have a significantly increased occurrence rate of glaucoma. In addition, ocular hypertension with normal visual fields and normal optic nerve heads was not found in patients with AD. The prevalence of ocular hypertension in the control group was 7.8% and parallels previous surveys. Therefore, we assume that the optic nerve seems to be less resistant to elevated intraocular pressure levels in AD patients.
Experimental Study on the Formation of Zeolites from Obsidian by Interaction with NaOH and KOH Solutions at 150 and 200 °C (1997)

Abstract Experimental alteration of obsidian was performed in 0.001 to 0.5 N NaOH and KOH solutions at 150 and 200 °C for 1 to 30 d. The products were examined by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray analysis (EDX). Changes in chemical composition and pH value of solutions during the reactions were also measured. As the pH of reacting solutions was increased, smectite, phillipsite and rhodesite crystallized progressively in NaOH solutions, while smectite, merlinoite and sanidine grew successively in KOH solutions. In addition, a small amount of less-soluble, poorly ordered boehmite was present as products of all the experiments. Smectite mainly appeared at slightly high pH, Si/Al and Na/K conditions, whereas rhodesite should be produced in extremely high pH, Na/K and Si/Al conditions. Sanidine was also formed in conditions of very high pH and Si/Al and very low Na/K. In intermediate conditions of pH and Si/Al, crystallization of phillipsite was stimulated in solutions of Na/K &gt; 10, while formation of merlinoite was favored in conditions of Na/K &lt; 1.
Stress physiology in crop plants (1979)

Organization and Conduct of Plant Stress Research to Increase Agricultural Productivity (M. Christiansen). Disease Tolerance: Reducing the Impact of Disease-Induced Stress on Crop Yields (H. Mussell and M. Malone). Thigmomorphogenesis: The Effect of Mechanical Perturbation on the Growth of Plants, with Special Reference to Anatomical Changes, the Role of Ethylene, and Interaction with Other Environmental Stresses (M. Jaffe and R. Biro). Differential Aluminum Tolerance in Crop Plants (R. Rhue). Comparative Responses of Field Grown Crops to Phosphate Concentrations in Soil Solutions (R. Fox). Production of Food Plants in Areas Supplied with Highly Saline Water: Problems and Prospects (G. Somers). Salt Resistance in Agricultural Crops. (D. Pasternak et al.). Effects of Freezing and Cold Acclimation on Membrane Structure and Function (P. Steponkus). Cold Resistance and Injury in Winter Cereals (L. Gusta and D. Fowler). Strategies for Altering Chilling Sensitivity as a Limiting Factor in Crop Production (J. Lyons and R. Breidenbach). Frost Hardiness: A Discussion of Possible Molecular Causes of Injury with Particular Reference to Deep Supercooling of Water (M. Burke and C. Stushnoff). Breeding Potatoes for Tolerance to Stress: Heat and Frost (H. Mendoza and R. Estrada). Selecting for Drought and Heat Resistance in Grain Sorghum (C. Sullivan and W. Ross). Drought Stress of Cowpea and Soybean under Tropical Conditions (H. Wein et al.). Effects of Water and Heat Stress on Carbon Metabolism of Plants with C3 and C4 Photosynthesis (D. Lawlor). Air Pollution Stress (L. Weinstein and D. McCune). Drought Resistance and Adaptation to Water Deficits in Crop Plants (N. Turner). Drought Resistance in Cereals--Rice: A Case Study (J. O'Toole and T. Chang). Stomatal Behavior and Breeding for Drought Resistance (H. Jones). Genetic Improvement of Drought Resistance in Crop Plants: A Case for Sorghum (A. Blum). Testing and Selecting for Drought Resistance in Wheat (T. Townley-Smith and E. Hurd). Growth and Development of Chickpeas under Progressive Moisture Stress (A. Sheldrake and N. Saxena). Index.
Global namespace for files (2004)

We propose a name service that enables construction of a uniform, global, hierarchical namespace, a key feature needed to create a file-system grid. Combined with other grid replication and location-lookup mechanisms, it supports independence of position for users and applications as well as transparency of data location in a scalable and secure fashion. This name service enables federation of individual files as well as file-system trees that are exported by a variety of distributed file systems and is extensible to include non-file-system data such as databases or live data feeds. Such a federated namespace for files can be rendered by network file servers, such as NFS (Network File System) or CIFS (Common Internet File System) servers, proxies supporting the NAS (network-attached storage) protocol, or grid data service interfaces. File access proxies, which handle protocol translation, can also include caching and replication support to enhance data access performance. A uniform namespace with global scope and hierarchical ownership allows sharing file data between and within organizations without compromising security or autonomy.
A computational approach to semantic event detection (2003)

We propose a three-level video event detection algorithm and apply it to animal hunt detection in wildlife documentaries. The first level extracts texture, color and motion features, and detects motion blobs. The mid-level employs a neural network to verify whether the motion blobs belong to objects of interest. This level also generates shot summaries in terms of intermediate-level descriptors which combine low-level features from the first level and contain results of mid-level, domain specific inferences made on the basis of shot features. The shot summaries are then used by a domain-specific inference process at the third level to detect the video segments that contain events of interest, e.g., hunts. Event based video indexing, summarization and browsing are among the applications of the proposed approach.
Ester Bond-containing Tea Polyphenols Potently Inhibit Proteasome Activity in Vitro and in Vivo (2001)

It has been discovered that proteasome inhibitors are able to induce tumor growth arrest or cell death and that tea consumption is correlated with cancer prevention. Here, we show that ester bond-containing tea polyphenols, such as (-)-epigallocatechin-3-gallate (EGCG), potently and specifically inhibit the chymotrypsin-like activity of the proteasome in vitro (IC(50) = 86-194 nm) and in vivo (1-10 microm) at the concentrations found in the serum of green tea drinkers. Atomic orbital energy analyses and high performance liquid chromatography suggest that the carbon of the polyphenol ester bond is essential for targeting, thereby inhibiting the proteasome in cancer cells. This inhibition of the proteasome by EGCG in several tumor and transformed cell lines results in the accumulation of two natural proteasome substrates, p27(Kip1) and IkappaB-alpha, an inhibitor of transcription factor NF-kappaB, followed by growth arrest in the G(1) phase of the cell cycle. Furthermore, compared with their simian virus-transformed counterpart, the parental normal human fibroblasts were much more resistant to EGCG-induced p27(Kip1) protein accumulation and G(1) arrest. Our study suggests that the proteasome is a cancer-related molecular target of tea polyphenols and that inhibition of the proteasome activity by ester bond-containing polyphenols may contribute to the cancer-preventative effect of tea.
Metalloproteinase Inhibitors, Nonantimicrobial Chemically Modified Tetracyclines, and Ilomastat BlockBacillus anthracisLethal Factor Activity in Viable Cells (2005)

Lethal toxin, produced by the bacterium Bacillus anthracis, is a major contributor to morbidity and mortality in animals and humans who have contracted anthrax. One component of this toxin, lethal factor (LF), proteolytically inactivates members of the mitogen-activated protein kinase kinase (MAPKK or MEK) family. In this study we show that CMT-300, CMT-308, and Ilomastat, agents initially characterized as matrix metalloproteinase inhibitors which are in early stages of development as pharmaceuticals, effectively inhibit the zinc metalloproteinase activity of LF. All three inhibitors, CMT-300, CMT-308, and Ilomastat, inhibit LF-mediated cleavage of a synthetic peptide substrate based on the N-terminal domain of MEKs. Inhibition of LF-mediated MEK proteolysis by all three agents was also achieved using lysates of the human monocytoid line MonoMac 6 as sources of MAPKKs and visualization of the extent of cleavage after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by detection by Western blotting. Finally, we have demonstrated inhibition of intracellular MEKs in viable human monocytes and MonoMac 6 cells by these agents after incubation of the cells with a reconstituted preparation of recombinant lethal toxin. All three agents are effective inhibitors when incubated with LF prior to exposure to cells, while the CMTs, but not Ilomastat, are also effective when added after LF has already entered the viable cell targets. These results offer promise for strategies to combat effects of the lethal toxin of B. anthracis.
Prodrug Strategies in Anticancer Chemotherapy (2007)

The majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor-specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor-specific characteristics such as low pH or the expression of tumor-associated enzymes. Furthermore, other strategies such as ADEPT (antibody-directed enzyme prodrug therapy) and the design of self-eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.
High Effectiveness of Aerosolized Chick Embryo Fibroblast Measles Vaccine in Seven-Month-Old and Older Infants (1985)

Neither the presence of hypertonic sugar nor the absence of 1% human albumin in the aerosolized chick embryo fibroblast (CEF) measles vaccine was previously found to be responsible for its inadequacy in infants with titers of maternal plaque-neutralizing (PN) antibody at which human diploid cell measles vaccine was immunogenic. Eight weeks after administration of CEF measles vaccine containing 1% human albumin, antibody had developed in all 10 infants 7-10 months old and all 11 children 12-35 months old but in only 26% of 23 infants 3-5 months old and 67% of 9 infants 6 months of age. Failure of antibody development was associated with prevaccination PN antibody titers of greater than or equal to 1:50 (with one exception at a titer of 1:25). The PN antibody response to CEF vaccine (diluted 1:10, approximately 10(5) pfu/ml) in infants under seven months of age (geometric mean titer [GMT], 1:421) was significantly lower (P less than .005) than in older infants (GMT, 1:1,564). At a 1:1,000 dilution of vaccine, only 50% of 10 infants 13-25 months old, 20% of 15 infants 7-10 months old, and none of 8 infants 6 months old developed antibody.
Induction of pulmonary indoleamine 2,3-dioxygenase by interferon. (1981)

Pulmonary indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase(decyclizing)] has been found to be induced (30- to 100-fold) in the mouse after a single intraperitoneal administration of bacterial endotoxin [Yoshida, R. & Hayaishi, O. (1978) Proc. Natl. Acad. Sci. USA 75, 3998-4000] or during in vivo virus infection [Yoshida, R., Urade, Y., Tokuda M. & Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. In the present study, an in vitro system with mouse lung slices was developed in which bacterial endotoxin (5 micrograms/ml)produced an induction (approximately 10-fold) of indoleamine 2,3-dioxygenase. The endotoxin was substituted by interferon from mouse L cells or mouse brain. The pulmonary enzyme activity increased almost linearly for 48 hr after addition of mouse interferon (10(4) units/ml) to lung slices. Interferon from mouse L cells or mouse brain produced a 10- to 15-fold increase in the enzyme activity, whereas that from human leukocytes was all but ineffective. The effect also was observed using highly purified L-cell interferon, prepared by poly(U) affinity column chromatography. When interferon was treated either by heat, alpha-chymotrypsin, or anti-interferon serum, such increase in the enzyme activity was diminished essentially to the same extent as seen in the antiviral activity. The increase in the enzyme activity was blocked when actinomycin D or cycloheximide was added to the slices before interferon treatment. These results suggest that the enzyme induction was produced by interferon and not by possible contaminants in the interferon preparations.
Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells. (1994)

Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia. The function of the recently isolated FACC (Fanconi anemia group C complementing) gene for a subset of this disorder is not yet known. The notion that FACC plays a direct role in DNA repair would predict that the polypeptide should reside in the nucleus. In this study, a polyclonal antiserum raised against FACC was used to determine the subcellular location of the polypeptide. Immunofluorescence and subcellular fractionation studies of human cell lines as well as COS-7 cells transiently expressing human FACC showed that the protein was localized primarily to the cytoplasm under steady-state conditions, transit through the cell cycle, and exposure to crosslinking or cytotoxic agents. However, placement of a nuclear localization signal from the simian virus 40 large tumor antigen at the amino terminus of FACC directed the hybrid protein to the nuclei of transfected COS-7 cells. These observations suggest an indirect role for FACC in regulating DNA repair in this group of Fanconi anemia.
The Drosophila Brahma complex is an essential coactivator for the trithorax group protein Zeste (2000)

The trithorax group (trxG) of activators and Polycomb group (PcG) of repressors are believed to control the expression of several key developmental regulators by changing the structure of chromatin. Here, we have sought to dissect the requirements for transcriptional activation by the Drosophila trxG protein Zeste, a DNA-binding activator of homeotic genes. Reconstituted transcription reactions established that the Brahma (BRM) chromatin-remodeling complex is essential for Zeste-directed activation on nucleosomal templates. Because it is not required for Zeste to bind to chromatin, the BRM complex appears to act after promoter binding by the activator. Purification of the Drosophila BRM complex revealed a number of novel subunits. We found that Zeste tethers the BRM complex via direct binding to specific subunits, including trxG proteins Moira (MOR) and OSA. The leucine zipper of Zeste mediates binding to MOR. Interestingly, although the Imitation Switch (ISWI) remodelers are potent nucleosome spacing factors, they are dispensable for transcriptional activation by Zeste. Thus, there is a distinction between general chromatin restructuring and transcriptional coactivation by remodelers. These results establish that different chromatin remodeling factors display distinct functional properties and provide novel insights into the mechanism of their targeting.
Fecal transplant against relapsingClostridium difficile-associated diarrhea in 32 patients (2012)

Clostridium difficile-associated disease (CDAD) with frequent watery stools, sometimes with painful bowel movements, fever and sickness, is probably the major known cause of antibiotic-associated diarrhea and colitis, most probably depending on a disruption of the normal intestinal balance in the microbiome. In this study, we have inoculated a mixture of fecal microbes--as an enema--originating from a healthy Scandinavian middle-aged donor, regularly re-cultivated under strict anaerobic conditions for more than 10 years, to 32 patients. Twenty-two patients (69%) were durably cured. In those patients receiving the transplant by colonoscopy, four out of five were cured. To the best of our knowledge, this is the first time a fecal culture of microbes has retained the possibility for years to cure a substantial number of patients with CDAD.
Signal-transducing function of Na+-K+-ATPase is essential for ouabain's effect on [Ca2+]iin rat cardiac myocytes (2001)

We showed before that Na+-K+-ATPase is also a signal transducer in neonatal rat cardiac myocytes. Binding of ouabain to the enzyme activates multiple signal pathways that regulate cell growth. The aims of this work were to extend such studies to adult cardiac myocytes and to determine whether the signal-transducing function of Na+/K+-ATPase regulates the well-known effects of ouabain on intracellular Ca2+ concentration ([Ca2+]i). In adult myocytes, ouabain activated protein tyrosine phosphorylation and p42/44 mitogen-activated protein kinases (MAPKs), increased production of reactive oxygen species (ROS), and raised both systolic and diastolic [Ca2+]i. Pretreatment of myocytes with several Src kinase inhibitors, or overexpression of a dominant negative Ras, antagonized ouabain-induced activation of MAPKs and increases in [Ca2+]i. Treatment with PD-98059 (a MAPK kinase inhibitor) or overexpression of a dominant negative MAPK kinase 1 also ablated the effect of ouabain on MAPKs and [Ca2+]i. N-acetyl-cysteine, which blocks the effect of ouabain on ROS, did not prevent the ouabain-induced rise in [Ca2+]i. Clearly, the activation of the Ras/MAPK cascade, but not ROS generation, is necessary for ouabain-induced increases in [Ca2+]i in rat cardiac myocytes.
Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory (1991)

Transgenic mice for the human amyloid precursor protein 695 (APP695) isoform may provide an animal model of Alzheimer's disease (AD). To evaluate this, the spatial learning abilities of transgenic and wild strain mice were compared in the Morris water maze task. The transgenic mice were significantly retarded in initial learning and in learning a new escape location, although in each case they eventually reached control levels. The transgenic mice also showed slower swimming speed and reduced nocturnal activity, which may contribute to their deficit in spatial learning. Preliminary neuropathological investigations failed to reveal amyloid depositions. Thus, a gene dosage effect of APP695 may account for the memory impairment but not the plaque formation associated with AD.