gebhart/patrepeval huggingface dataset:
Stress Induction of GRP78/BiP and Its Role in Cancer (2006)

GRP78, also referred to as BiP, is a central regulator of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, ER Ca(2+)-binding and controlling the activation of trans-membrane ER stress sensors. Further, due to its anti-apoptotic property, stress induction of GRP78 represents an important pro-survival component of the unfolded protein response. GRP78 is induced in a wide variety of cancer cells and cancer biopsy tissues. Recent progress, utilizing overexpression and siRNA approaches, establishes that GRP78 contributes to tumor growth and confers drug resistance to cancer cells. The discovery of GRP78 expression on the cell surface of cancer cells further leads to the development of new therapeutic approaches targeted against cancer, in particular, hypoxic tumors where GRP78 is highly induced. Progress has also been made in understanding how Grp78 is induced by ER stress. The identification of the transcription factors interacting with the ER stress response element leads to the discovery of multiple pathways whereby mammalian cells can sense ER stress and trigger the transcription of Grp78. In addition, advances have been made in understanding how Grp78 expression is regulated in the context of chromatin modification. This review summarizes the transcriptional regulation of Grp78, the molecular basis for the cytoprotective function of GRP78 and its role in cancer progression, drug resistance and potential future cancer therapy.
CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer. (2000)

CpG island hypermethylation is a frequent epigenetic event in cancer. We have recently developed an array-based method, called differential methylation hybridization (DMH), allowing for a genome-wide screening of CpG island hypermethylation in breast cancer cell lines (T. H-M. Huang et al., Hum. Mol. Genet., 8: 459-470, 1999). In the present study, DMH was applied to screen 28 paired primary breast tumor and normal samples and to determine whether patterns of specific epigenetic alterations correlate with pathological parameters in the patients analyzed. Amplicons, representing a pool of methylated CpG DNA derived from these samples, were used as hybridization probes in an array panel containing 1104 CpG island tags. Close to 9% of these tags exhibited extensive hypermethylation in the majority of breast tumors relative to their normal controls, whereas others had little or no detectable changes. Pattern analysis in a subset of CpG island tags revealed that CpG island hypermethylation is associated with histological grades of breast tumors. Poorly differentiated tumors appeared to exhibit more hypermethylated CpG islands than their moderately or well-differentiated counterparts (P = 0.041). This early finding lays the groundwork for a population-based DMH study and demonstrates the need to develop a database for examining large-scale methylation data and for associating specific epigenetic signatures with clinical parameters in breast cancer.
Long-Term Effects of FloSeal™ Packing After Endoscopic Sinus Surgery (2005)

FS appears to be associated with scar tissue formation and may be incorporated into recovering mucosa. Use of FS may increase the degree of postoperative care required after ESS.
Effect of acrylamide on the cytoskeleton and apoptosis of bovine lens epithelial cells (2006)

Acrylamide, a known disrupter of intermediate filaments, has been used to produce the collapse of vimentin filaments in bovine lens epithelial (BEL) cells, and its potential modulation of staurosporine-induced apoptosis has been investigated. In BEL cells, short treatments with acrylamide caused the collapse of vimentin filaments and microtubules and the almost complete disappearance of stress fibers, with thick f-actin bundles remaining in the cell periphery. Actin organization was less affected in cells pretreated with colchicine and in spreading cells, suggesting that extended microtubules and vimentin filaments are required for acrylamide to produce its maximal effects. Acrylamide alone slightly increased apoptosis compared to controls. However, simultaneous exposure to acrylamide and staurosporine for 8h produced significantly less apoptosis than staurosporine alone, and preincubation with acrylamide followed by staurosporine markedly reduced apoptosis at 8 and 24h of treatment. Acrylamide seems therefore to have a dual effect on BEL cell survival.
Distribution and physical properties of BCA200, a Mr 200,000 glycoprotein selectively associated with human breast cancer. (1989)

Of 122 mouse monoclonal antibodies selective for human breast cancer, 13 immunoprecipitated an acidic glycoprotein from SK-Br-3 and ZR-75-30 human breast cancer cells. The antigen (BCA200) migrates with an apparent molecular weight of 200,000 on reducing and 180,000 on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting a single polypeptide chain with a folded domain stabilized by a disulfide bond. Cross-blocking and sandwich immunoassays detected at least three distinct antigenic determinants on BCA200. Scatchard experiments measured 1,000,000 to 5,000,000 antigen copies per SK-Br-3 cell. The tissue distribution of BCA200 was studied using two monoclonals to different epitopes. Neither antibody stained any cells in human blood. When frozen sections of 20 normal human tissues were immunoperoxidase stained, the only positive structures were mucinous glands of colon, transitional epithelium of bladder, sweat glands of skin, and acinar epithelium of breast. Antibody 454C11 stained 16 of 21 breast tumor frozen sections and 9 of 12 breast cancer cell lines, while antibody 520C9 stained 5 of 20 breast tumors and 4 of 10 breast cancer lines. Cross-reaction was observed with lung, prostatic, pancreatic, endometrial, and ovarian cancer, but not with lymphoma, melanoma, colon, stomach, bladder, or esophageal cancer. When conjugated to ricin A chain, 10 of 13 antibodies produced immunotoxins selectively cytotoxic to SK-Br-3 breast cancer cells.
Preform fiber architecture for ceramic-matrix composites (1989)

Similar to the steel frames in a skyscraper, fiber architectures are the structural backbone of a composite. Starting with linear assemblies of fibers in continuous and/or discrete form, these microfiber beams can be organized into two-and three-dimensional structures by means of interlacing, intertwining, or interlooping. This article discusses fiber architecture. The role of fiber architecture in designing composites are illustrated through an examination of the structural features and the properties of ceramic-matrix composites (CMC) reinforced by textile structures.
L.E.D. Wavelength Division Multiplexing (1986)

LED wavelength multiplexing with spectral narrowing enables to reduce the material dispersion effect and increases transmission distance of a broadband link (50 MHz Bandwith) by more than 50 %.
Improved electrochemical detection of a transthyretin synthetic peptide in the nanomolar range with a two-electrode system integrated in a glass/PDMS microchip (2014)

An alternative to a three-electrode set-up for electrochemical detection and analysis in microfluidic chips is described here. The design of the electrochemical sensor consists of the surface of the glass substrate covered with a PDMS block which bears the microfluidic channels. A band microelectrode which acts as a working electrode surrounded by a large counter electrode is obtained at the micrometric level to propose a simple and efficient sensing area for on-a-chip analysis. The counter-electrode with a surface area about 22-fold greater than the working-microelectrode can also be considered as a pseudo reference since its current density is low and thus limits the potential variations around the rest potential. To this purpose, the [Fe(III)(CN)₆]³⁻/[Fe(II)(CN)₆]⁴⁻ redox couple was used in order to set a reference potential at 0 V since both electrodes were platinum. The electrochemical microchip performance was characterized using differential pulse voltammetric (DPV) detection and quantification of the optically multi-labelled transthyretin synthetic peptide mimicking a tryptic fragment of interest for the diagnosis of familial transthyretin amyloidosis (ATTR). The limit of detection of the peptide by the working microelectrode was 25 nM, a value 100-fold lower than the one reported with conventional capillary electrophoresis coupled with laser-induced fluorescence under the same analytical conditions.
Induced Maturation and Spawning of the Chinese Catfish Clarias fuscus (1989)

Abstract Chinese catfish ( Clarias fuscus ) were successfully spawned in Hawaii using human chorionic gonadotropin (HCG) at dosage rates of two and four international units (IU) per gram body weight. Fish not injected with HCG did not produce viable eggs. Successful spawns with HCG occurred between May and October. Hatch rates of up to 80% were obtained during June, July, and August for those fish given either a 2 or 4 IU per gram body weight injection of HCG. Fish spawned in either May or October yielded significantly higher hatch rates when injected with 4 rather than 2 IU per gram body weight. Fish held at elevated temperatures (28 to 30 C) prior to the normal spawning season developed significantly larger oocyte diameters, 60 days earlier than fish held under ambient temperature conditions (21.5 to 24 C). Photoperiod manipulation at ambient temperature conditions was associated with earlier oocyte maturation, but photoperiod effects were much less important than temperature.
Ontology learning and its application in software-intensive projects (2016)

Software artifacts, such as requirements, design, source code, documentation, and safety-related artifacts are typically expressed using domain-specific terminology. Automated tools which attempt to analyze software artifacts in order to perform tasks such as trace retrieval and maintenance, domain analysis, program comprehension, or to service natural language queries, need to understand the vocabulary and concepts of the domain in order to achieve acceptable levels of accuracy. Domain concepts can be captured and stored as an ontology. Unfortunately, constructing ontologies is extremely time-consuming and has proven hard to automate. This dissertation proposes a novel approach for semi-automated ontology building that leverages user-defined trace links to identify candidate domain facts. It uses a variety of web-mining, Natural Language Processing, and machine learning techniques to filter and rank the candidate facts, and to assist the user in building a domain-specific ontology. The benefits of the constructed ontology are described and evaluated within the context of automated trace link creation.
Nrf2‐deficient mice are highly susceptible to cigarette smoke‐induced emphysema (2005)

Inflammation, protease/anti-protease imbalance and oxidative stress play important roles in the pathogenesis of emphysema. Nrf2 counteracts oxidative tissue damage and inflammation through transcriptional activation via the anti-oxidant responsive element (ARE). To clarify the protective role of Nrf2 in the development of emphysema, the susceptibility of Nrf2-knockout mice to cigarette smoke (CS)-induced emphysema was examined. In Nrf2-knockout mice, emphysema was first observed at 8 weeks and exacerbated by 16 weeks following CS-exposure, whereas no pathological abnormalities were observed in wild-type mice. Neutrophilic lung inflammation and permeability lung damage were significantly enhanced in Nrf2-knockout mice 8 weeks after CS-exposure. Importantly, neutrophil elastase activity in bronchoalveolar lavage fluids was markedly higher in Nrf2-knockout mice preceding the pronounced neutrophil accumulation. The expression of secretory leukoprotease inhibitor, a potent inhibitor of neutrophil elastase, was inducible in wild-type, but not in Nrf2-knockout mice. This protease/anti-protease imbalance, together with the lack of inducible expression of ARE-regulated anti-oxidant/anti-inflammatory genes, may explain the predisposition of Nrf2-knockout mice to neutrophilic inflammation. Indeed, specific activators of Nrf2 induced the expression of the SLPI gene in macrophages. These results indicate that Nrf2 protects against the development of emphysema by regulating not only the oxidant/anti-oxidant balance, but also inflammation and the protease/anti-protease balance.
The information bottleneck method (2000)

A fundamental problem in formalizing our intuitive ideas about information is to provide a quantitative notion of “meaningful ” or “relevant ” information. It is argued in this paper that information theory, in particular lossy source compression, provides a natural quantitative approach to the question of “relevant
S-Nitrosohemoglobin Is Unstable in the Reductive Erythrocyte Environment and Lacks O2/NO-linked Allosteric Function (2002)

Our previous results run counter to the hypothesis that S-nitrosohemoglobin (SNO-Hb) serves as an in vivo reservoir for NO from which NO release is allosterically linked to oxygen release. We show here that SNO-Hb undergoes reductive decomposition in erythrocytes, whereas it is stable in purified solutions and in erythrocyte lysates treated with an oxidant such as ferricyanide. Using an extensively validated methodology that eliminates background nitrite and stabilizes erythrocyte S-nitrosothiols, we find the levels of SNO-Hb in the basal human circulation, including red cell membrane fractions, were 46 +/- 17 nm in human arterial erythrocytes and 69 +/- 11 nm in venous erythrocytes, incompatible with the postulated reservoir function of SNO-Hb. Moreover, we performed experiments on human red blood cells in which we elevated the levels of SNO-Hb to 10,000 times the normal in vivo levels. The elevated levels of intra-erythrocytic SNO-Hb fell rapidly, independent of oxygen tension and hemoglobin saturation. Most of the NO released during this process was oxidized to nitrate. A fraction (25%) was exported as S-nitrosothiol, but this fraction was not increased at low oxygen tensions that favor the deoxy (T-state) conformation of Hb. Results of these studies show that, within the redox-active erythrocyte environment, the beta-globin cysteine 93 is maintained in a reduced state, necessary for normal oxygen affinity, and incapable of oxygen-linked NO storage and delivery.
Annealing ambient controlled deep defect formation in InP (2004)

Deep defects in annealed InP have been investigated by deep level transient capacitance spectroscopy (DLTS), photo induced current transient spectroscopy (PICTS) and thermally stimulated current spectroscopy (TSC). Both DLTS results of annealed semiconducting InP and PICTS and TSC results of annealed semi-insulating InP indicate that InP annealed in phosphorus ambient has five defects, while InP annealed in iron phosphide ambient has two defects. Such a defect formation phenomenon is explained in terms of defect suppression by the iron atom diffusion process. The correlation of the defects and the nature of the defects in annealed InP are discussed based on the results.
Construction of recombinant E. coli Nissle 1917 (EcN) strains for the expression and secretion of defensins (2012)

The probiotic Escherichia coli strain Nissle 1917 (EcN) is one of the few probiotics licensed as a medication in several countries. Best documented is its effectiveness in keeping patients suffering from ulcerative colitis (UC) in remission. This might be due to its ability to induce the production of human β-defensin 2 (HBD2) in a flagellin-dependent way in intestinal epithelial cells. In contrast to ulcerative colitis, for Crohn's disease (CD) convincing evidence is lacking that EcN might be clinically effective, most likely due to the genetically based inability of sufficient defensin production in CD patients. As a first step in the development of an alternative approach for the treatment of CD patients, EcN strains were constructed which were able to produce human α-defensin 5 (HD5) or β-defensin 2 (HBD2). For that purpose, codon-optimized defensin genes encoding either the proform with the signal sequence of human α-defensin 5 (HD5) or the gene encoding HBD2 with or without the signal sequence were cloned in an expression vector plasmid under the control of the T7 promoter. Synthesis of the encoded defensins was shown by Western blots after induction of expression and lysis of the recombinant EcN strains. Recombinant mature HBD2 with an N-terminal His-tag could be purified by Ni-column chromatography and showed antimicrobial activity against E. coli, Salmonella enterica serovar Typhimurium and Listeria monocytogenes. In a second approach, that part of the HBD2 gene which encodes mature HBD2 was fused with the yebF gene. The resulting fusion protein YebFMHBD2 was secreted from the encoding EcN mutant strain after induction of expression. Presence of YebFMHBD2 in the medium was not the result of leakage from the bacterial cells, as demonstrated in the spent culture supernatant by Western blots specific for β-galactosidase and maltose-binding protein. The dialyzed and concentrated culture supernatant inhibited the growth of E. coli, S. enterica serovar Typhimurium and L. monocytogenes in radial diffusion assays as well as in liquid culture. This demonstrates EcN to be a suitable probiotic E. coli strain for the production of certain defensins.
Molecular analysis of the M protein of Streptococcus equi and cloning and expression of the M protein gene in Escherichia coli (1987)

A Streptococcus equi gene bank was constructed in the bacteriophage lambda gt11 cloning vector, and hybrid phage plaques were screened with S. equi M protein antiserum. A hybrid phage expressing the S. equi M protein (lambda gt11/SEM7) was identified and lysogenized into Escherichia coli Y1089. The cloned M protein appeared in immunoblots as three polypeptides with relative molecular weights of 58,000, 53,000, and 50,000. When reacted with S. equi M protein antiserum in an agar double-diffusion assay, the cloned M protein formed a line of identity with a protein in an acid extract of S. equi. Furthermore, lambda gt11/SEM7 protein inhibited opsonization of S. equi by antiserum to S. equi M protein. In addition, the recombinant protein expressed determinants of the antigen in the immune complexes of purpura hemorrhagica. Native M protein obtained from S. equi and recombinant M protein showed very similar molecular weight distributions on immunoblots, appearing as multiple closely spaced bands with molecular weights ranging from 52,000 to 60,000. Antisera prepared separately against each of the acid-extracted polypeptides shown to be important in serum bactericidal responses (molecular weight, 29,000) and nasopharyngeal local antibody responses (molecular weights, 41,000 and 46,000) of the horse each reacted with all three polypeptides in an acid extract. Moreover, antisera against protoplasts and against recombinant M protein of S. equi also reacted with these polypeptides. These results suggest that the entire M protein molecule of S. equi is present in these preparations and that the fragments in acid extracts carry overlapping segments.
Disulfide bonds, their stereospecific environment and conservation in protein structures (2004)

We studied the specificity of the non-bonded interaction in the environment of 572 disulfide bonds in 247 polypeptide chains selected from the Protein Data Bank. The preferred geometry of interaction of peptide oxygen atoms is along the back of the two covalent bonds at the sulfur atom of half cystine. With aromatic residues the geometries that direct one of the sulfur lone pair of electrons into the aromatic pi-system are avoided; an orientation in which the sulfide plane is normal or inclined to the aromatic plane and on top of its edge is normally preferred. The importance of the S...aromatic interaction is manifested in the high degree of its conservation across members in homologous protein families. These interactions, while providing extra overall stability to the native fold and reducing the accessibility of the disulfide bond and thereby preventing exchange reactions, also set the orientation of the conserved aromatic rings for further interactions and binding to another molecule. The conformational features and the mode of interactions of disulfide bridges should be useful for molecular design and protein engineering experiments.
Extremely low resistance nonalloyed ohmic contacts on GaAs using InAs/InGaAs and InAs/GaAs strained-layer superlattices (1988)

Employing a structure consisting of n+-InAs/InGaAs and InAs/GaAs strained-layer superlattices (SLS’s) grown by molecular beam epitaxy on GaAs films, nonalloyed contact resistances less than 8.5×10−8 Ω cm2 have been obtained. Self-consistent simulations show that these extremely small nonalloyed contact resistances are due to the suppression of the depletion depth in the GaAs channel and tunneling through the SLS layer. Similar structures on InGaAs channels have led to nonalloyed specific contact resistances of about 1.5×10−8 Ω cm2. These results represent the smallest figures reported for these important material systems.
Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions (2014)

// Berglind O. Einarsdottir 1,4 , Roger Olofsson Bagge 1,4 , Joydeep Bhadury 1,4 , Henrik Jespersen 2,4 , Jan Mattsson 1,4 , Lisa M. Nilsson 1,4 , Katarina Truv&eacute; 5 , Marcela D&aacute;vila L&oacute;pez 4,5 , Peter Naredi 1,4 , Ola Nilsson 3,4 , Ulrika Stierner 2,4 , Lars Ny 2,4 and Jonas A. Nilsson 1,4 1 Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden 2 Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden 3 Department of Biomedicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden 4 Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden 5 The Bioinformatics Core Facility at the University of Gothenburg, Gothenburg, Sweden Correspondence: Jonas Nilsson, email: // Keywords : melanoma, mouse models, patient-derived xenografts Received : August 18, 2014 Accepted : September 07, 2014 Published : September 08, 2014 Abstract The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.