gebhart/patrepeval huggingface dataset:
Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. (1990)

The recently-described p59 protein has been shown to be associated with untransformed steroid receptors present in rabbit uterus and rat liver cytosols (Tai, P. K., Maeda, Y., Nakao, K., Wakim, N. G., Duhring, J. L., and Faber, L. E. (1986) Biochemistry 25, 5269-5275; Renoir, J.-M., Radanyi, C., Faber, L. E., and Baulieu, E.-E. (1990) J. Biol. Chem. 265, 10740-10745), while a smaller version of this protein (p56) interacts with glucocorticoid receptors in human IM-9 cell cytosols (Sanchez, E. R., Faber, L. E., Henzel, W. J., and Pratt, W. B. (1990) Biochemistry 29, 5145-5152). In addition to interacting with glucocorticoid receptors, the p56 protein of IM-9 cell cytosol is also found as part of a large heteromeric complex that contains both the 70-kDa and 90-kDa heat shock proteins (hsp70 and hsp90, respectively). Given this association of p56 with the two major stress proteins, I have speculated that p56 may itself be a heat shock protein. In this paper, the effect of heat stress on the rate of synthesis of p56 is determined. Intact IM-9 cells were exposed to 37 or 43 degrees C for 4 h, followed by pulse-labeling with [35S]methionine. Analysis of whole cytosolic extracts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography reveal an increased rate of radiolabeling for hsp70, hsp90, hsp100, ad hsp110, but no heat-inducible protein of smaller relative molecular mass is detected. However, immune-purification of p56 from normal and heat-stressed cytosols with the EC1 monoclonal antibody results in the presence of a 56-kDa protein that exhibits an increased rate of synthesis in response to heat stress. The results of two-dimensional gel Western blots employing the EC1 antibody demonstrate that this heat-inducible protein is indeed the EC1-reactive p56 protein and that the induction effect is not due to unequal yields of p56 during immune-purification. Heat stress has no effect on the composition of the p56.hsp.70.hsp90 complex, except that the complex derived from heat shocked-cells contains both the constitutive and heat-inducible forms of hsp70. Induction of p56 also occurs in IM-9 cells subjected to chemical stress (sodium arsenite). It is proposed that p56 is a steroid receptor-associated heat shock protein which can now be termed hsp56. Like hsp90, hsp56 likely serves in some vital cellular role apart from any specific function it provides in steroid receptor action.
Synthesis of a New PHEMA/PEO Enzymatically Biodegradable Hydrogel (2006)

Abstract Summary: We report the synthesis of a new enzymatically degradable gel based on PHEMA and PEO crosslinking macromonomer. The crosslinker contains the tripeptide sequence Gly‐Gly‐Leu, which is a substrate for proteases such as subtilisin or chymotrypsin. The crosslinker was obtained by the coupling reaction of succinyl‐glycyl‐glycyl‐leucine with 2‐aminoethyl‐terminated PEO chains ( $\overline M _{\rm w}$ = 3 400) and subsequent esterification of the hydroxyl endgroup with methacryloyl chloride. It was characterized by SEC and 1 H NMR. Enzymatic cleavage of the crosslinking macromonomer was showed by SEC. The macromonomer was copolymerized with HEMA to yield hydrogel that is stable in a physiological buffer. Enzymatic assay showed that this gel is degraded in the presence of a bacterial protease (subtilisin). The degradation is complete within 50 d at 37 °C. This new gel is a good candidate for drug‐delivery systems where the release can be triggered by the presence of bacterial proteases. PHEMA crosslinked with MA‐PEG‐SucGGL‐PEO‐MA and its degradation by subtilisin. magnified image PHEMA crosslinked with MA‐PEG‐SucGGL‐PEO‐MA and its degradation by subtilisin.
Major Histocompatibility Complex Class II Molecules Can Protect from Diabetes by Positively Selecting T Cells with Additional Specificities (1998)

Insulin-dependent diabetes is heavily influenced by genes encoded within the major histocompatibility complex (MHC), positively by some class II alleles and negatively by others. We have explored the mechanism of MHC class II-mediated protection from diabetes using a mouse model carrying the rearranged T cell receptor (TCR) transgenes from a diabetogenic T cell clone derived from a nonobese diabetic mouse. BDC2.5 TCR transgenics with C57Bl/6 background genes and two doses of the H-2(g7) allele exhibited strong insulitis at approximately 3 wk of age and most developed diabetes a few weeks later. When one of the H-2(g7) alleles was replaced by H-2(b), insulitis was still severe and only slightly delayed, but diabetes was markedly inhibited in both its penetrance and time of onset. The protective effect was mediated by the Abetab gene, and did not merely reflect haplozygosity of the Abetag7 gene. The only differences we observed in the T cell compartments of g7/g7 and g7/b mice were a decrease in CD4(+) cells displaying the transgene-encoded TCR and an increase in cells expressing endogenously encoded TCR alpha-chains. When the synthesis of endogenously encoded alpha-chains was prevented, the g7/b animals were no longer protected from diabetes. g7/b mice did not have a general defect in the production of Ag7-restricted T cells, and antigen-presenting cells from g7/b animals were as effective as those from g7/g7 mice in stimulating Ag7-restricted T cell hybridomas. These results argue against mechanisms of protection involving clonal deletion or anergization of diabetogenic T cells, or one depending on capture of potentially pathogenic Ag7-restricted epitopes by Ab molecules. Rather, they support a mechanism based on MHC class II-mediated positive selection of T cells expressing additional specificities.
[Exploitation of expression profiles: examples in oncology]. (2002)

The analysis of biological processes has been revolutionized by the emergence of the DNA array technology. As cellular biological events are controlled by gene expression, their modulations are markers of the cellular activity. These modulations can be indicative of either a physiological process or a pathological one. Monitoring of the expression levels of thousands of genes simultaneously, the expression profiling method is based upon comparative studies where the identification of the differentially expressed genes in two samples is aimed. The two samples under study may be compared temporally or following drug treatment, they may also originate from different sources, e.g. normal versus pathological samples. In that case, gene expression profiling is conducted for diagnostics purposes or therapy monitoring, and offers an opportunity to identify new drug targets. Using different examples, we describe the potentialities of this approach in oncology.
Multiple leadless pacemakers implanted in the right ventricle of swine (2016)

Multiple leadless pacemakers implanted in the RV do not appear to impact cardiac function. Therefore, it appears safe to implant multiple leadless pacemakers in the same heart.
ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool (2010)

ZiFiT (Zinc Finger Targeter) is a simple and intuitive web-based tool that provides an interface to identify potential binding sites for engineered zinc finger proteins (ZFPs) in user-supplied DNA sequences. In this updated version, ZiFiT identifies potential sites for ZFPs made by both the modular assembly and OPEN engineering methods. In addition, ZiFiT now integrates additional tools and resources including scoring schemes for modular assembly, an interface with the Zinc Finger Database (ZiFDB) of engineered ZFPs, and direct querying of NCBI BLAST servers for identifying potential off-target sites within a host genome. Taken together, these features facilitate design of ZFPs using reagents made available to the academic research community by the Zinc Finger Consortium. ZiFiT is freely available on the web without registration at http://bindr.gdcb.iastate.edu/ZiFiT/.
Low-Temperature Surface Cleaning of GaAs by Electron Cyclotron Resonance (ECR) Plasma (1989)

Low-temperature surface cleaning of GaAs by electron cyclotron resonance (ECR) plasma is carried out. Pure hydrogen is used for the cleaning gas, and ECR plasma is transported to the substrate surface by a divergent magnetic field. In situ reflection high-energy electron diffraction (RHEED) observation reveals that surface cleaning of GaAs can be successfully performed at temperatures as low as 300°C. The interface between the substrate and GaAs grown layer prepared after plasma cleaning is found by SIMS measurement to be cleaner than that prepared by thermal treatment and MBE growth.
Mesh simplification with smooth surface reconstruction (1998)

In this work, a new method for mesh simplification and surface reconstruction specifically designed for the needs of CAD/CAM engineering design and analysis is introduced. The method simplifies the original free-form face model by first constructing restricted curvature deviation regions, generating a boundary conforming finite element quadrilateral mesh of the regions, and then fitting a smooth surface over the quadrilateral mesh using the plate energy method. It is more general in scope than existing methods because it handles models with free-form faces and non-manifold geometry, not just triangular or polygonal faces. It produces a high-quality quadrilateral mesh which is suited for both finite element analysis and CAD/CAM. The smooth surface obtained by energy functional stabilization over limited curvature regions preserves the number of quadrilateral elements, and is best suited for surface modeling. The method is illustrated by building of several free-form surfaces from an arbitrary topology mesh.
A novel quantitative 'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias. (1996)

Telomerase activation is important for carcinogenesis. However, the timing and magnitude of the activation during cancer development are unknown. In this study, a new PCR-based method for measuring telomerase activity was developed and shown to be very useful for quantitative analysis of human telomerase. Using this assay, blood or bone marrow cells from healthy donors, and patients with chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) were examined as to their relative activity. Telomerase activity present in normal peripheral blood cells was generally very low. However, significant activity was detected occasionally in samples derived from younger healthy donors. Striking telomerase activation was observed at the time of the blastic crisis in CML: no samples from chronic phase cases showed significant activity, while all cases with a well established crisis showed strong activity. Most AML cases were telomerase-positive. Quantitative analyses revealed that the relative titer varied among the AML patients, from as low as found in normal cells to as high as found in cell lines. However, a tendency that the activity was higher in relapsed cases than in fresh ones was suggested. In summary, telomerase was activated during the progression of the clinical stages in leukemias. This observation suggests that shortened telomeres and increased telomerase activity might be necessary for cancer cells to undergo clonal evolution towards more malignant phenotypes in advanced stages.
Natural language dialogue service for appointment scheduling agents (1997)

Appointment scheduling is a problem faced daily by many individuals and organizations. Cooperating agent systems have been developed to partially automate this task. In order to extend the circle of participants as far as possible we advocate the use of natural language transmitted by email. We describe COSMA, a fully implemented German language server for existing appointment scheduling agent systems. COSMA can cope with multiple dialogues in parallel, and accounts for differences in dialogue behaviour between human and machine agents. NL coverage of the sublanguage is achieved through both corpus-based grammar development and the use of message extraction techniques.
The bifunctional protein DCoH/PCD, a transcription factor with a cytoplasmic enzymatic activity, is a maternal factor in the rat egg and expressed tissue specifically during embryogenesis (1998)

The bifunctional protein DCoH/PCD is both a cytoplasmatic enzyme (PCD) involved in the tetrahydrobiopterin regeneration and a transcription coactivator (DCoH). Originally detected in liver cell nuclei, it forms a 2:2 heterotetrameric complex with the nuclear transcription factors HNF1alpha and the variant form HNF1beta and enhances their transcriptional potential. To address the role of DCoH in tissue specific and developmental gene regulation we analyzed its spatial and temporal expression pattern in the rat. DCoH might have a function in tissue specific gene expression mediated by HNF1 in the adults and in the developing embryo as it is found in the kidney and the liver, organs known to contain HNF1. In addition DCoH is a maternal factor in the rat egg lacking HNF1 transcription factors. The maternal protein enters the cell nuclei at the 8-cell stage suggesting a role in early embryonic gene regulation and excluding a cytoplasmatic enzymatic function. Evidence for a HNF1 independent function of DCoH is also given by the fact that DCoH is present in the eyes (pigmented epithelium) and the brain (ependym cells) of the rat embryos, cell types lacking HNF1 proteins. The tightly regulated expression pattern of DCoH in distinct cell types originating from endo- meso- and ectoderm is conserved between the rat and the frog indicating a fundamental role for DCoH in early gene regulation among the vertebrates.
Adverse Skin Reactions to Anti-TNF-Alpha Monoclonal Antibody Therapy (2003)

Various adverse cutaneous reactions to anti-TNF-alpha monoclonal antibody have been reported. In clinical studies with infliximab (Remicade) adverse drug reactions were most frequently reported in the respiratory system and in the skin and appendages. We describe here 6 patients receiving anti- TNF-alpha therapy (infliximab) for Crohn's disease or rheumatoid arthritis who consulted our out-patient department for adverse cutaneous reactions between November 1999 and February 2002. The following diagnoses were made: leukocytoclastic vasculitis, lichenoid drug reaction, perniosis-like eruption (2 patients), superficial granuloma annulare and acute folliculitis.
Shortlisting of cultivable herbal plants in the Bhabhar region of the Garhwal Himalaya, Uttarakhand, India. (2011)

The success of any economically viable herbal cultivation programme lies in the appropriate selection of he r- bal plants. Many things will have to be considered in selecting herbs viz. adaptability in natural environment, economic demand in herbal industry and agroclimatic aspects. The present work embodies the results of the scrutiny of herbal composition of popular branded Ayurvedic medicines. In addition, with the help of field survey and available literature, plants were identified which are naturally growing in different habitats of the Bhabhar region of the Garhwal Himalaya, Uttarakhand. On the basis of utility in herbal medicines and their ability to grow n aturally, plants are further shortlisted for the cultivation. The prominent herbs recommended are: Aloe barbadensis, Bacopa monnieri, Boerhavia diffusa, Plumbago zeylanica, Tinospora cordifolia, Withania somnifera etc. The promotion of cultivation of these useful herbs would ensure sustainable biodiversity conservation and alleviation in the economic conditions of the rural people of the Bhabhar region of Garhwal Himalaya.
Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin (2004)

To determine the role of respiratory epithelial cells in the inflammatory response to inhaled endotoxin, we selectively inhibited NF-kappa B activation in the respiratory epithelium using a mutant I kappa B-alpha construct that functioned as a dominant negative inhibitor of NF-kappa B translocation (dnI kappa B-alpha). We developed two lines of transgenic mice in which expression of dnI kappa B-alpha was targeted to the distal airway epithelium using the human surfactant apoprotein C promoter. Transgene expression was localized to the epithelium of the terminal bronchioles and alveoli. After inhalation of LPS, nuclear translocation of NF-kappa B was evident in bronchiolar epithelium of nontransgenic but not of transgenic mice. This defect was associated with impaired neutrophilic lung inflammation 4 h after LPS challenge and diminished levels of TNF-alpha, IL-1 beta, macrophage inflammatory protein-2, and KC in lung homogenates. Expression of TNF-alpha within bronchiolar epithelial cells and of VCAM-1 within peribronchiolar endothelial cells was reduced in transgenic animals. Thus targeted inhibition of NF-kappa B activation in distal airway epithelial cells impaired the inflammatory response to inhaled LPS. These data provide causal evidence that distal airway epithelial cells and the signals they transduce play a physiological role in lung inflammation in vivo.
Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling (2010)

Due to its common dysregulation in epithelial-based cancers and extensive characterization of its role in tumor growth, epidermal growth factor receptor (EGFR) is a highly validated target for anticancer therapies. There has been particular interest in the development of monoclonal antibodies (mAbs) targeting EGFR, resulting in two approved mAb-based drugs and several others in clinical trials. It has recently been reported that treatment with combinations of noncompetitive mAbs can induce receptor clustering, leading to synergistic receptor down-regulation. We elucidate three key aspects of this phenomenon. First, we show that highly potent combinations consisting of two noncompetitive mAbs that target EGFR domain 3 reduce surface receptor levels by up to 80% with a halftime of 0.5-5 h in both normal and transformed human cell lines to an extent inversely proportional to receptor density. Second, we find the mechanism underlying down-regulation to be consistent with recycling inhibition. Third, in contrast to the agonism associated with ligand-induced down-regulation, we demonstrate that mAb-induced down-regulation does not activate EGFR or its downstream effectors and it leads to synergistic reduction in migration and proliferation of cells that secrete autocrine ligand. These new insights will aid in ongoing rational design of EGFR-targeted antibody therapeutics.
Mining metrics to predict component failures (2006)

What is it that makes software fail? In an empirical study of the post-release defect history of five Microsoft software systems, we found that failure-prone software entities are statistically correlated with code complexity measures. However, there is no single set of complexity metrics that could act as a universally best defect predictor. Using principal component analysis on the code metrics, we built regression models that accurately predict the likelihood of post-release defects for new entities. The approach can easily be generalized to arbitrary projects; in particular, predictors obtained from one project can also be significant for new, similar projects.
Common features of the NAD‐binding and catalytic site of ADP‐ribosylating toxins (1994)

Computer analysis of the three-dimensional structure of ADP-ribosylating toxins showed that in all toxins the NAD-binding site is located in a cavity. This cavity consists of 18 contiguous amino acids that form an alpha-helix bent over a beta-strand. The tertiary folding of this structure is strictly conserved despite the differences in the amino acid sequence. Catalysis is supported by two spatially conserved amino acids, each flanking the NAD-binding site. These are: a glutamic acid that is conserved in all toxins, and a nucleophilic residue, which is a histidine in the diphtheria toxin and Pseudomonas exotoxin A, and an arginine in the cholera toxin, the Escherichia coli heat-labile enterotoxins, the pertussis toxin and the mosquitocidal toxin of Bacillus sphaericus. The latter group of toxins presents an additional histidine that appears important for catalysis. This structure suggests a general mechanism of ADP-ribosylation evolved to work on different target proteins.
Structured Video Computing (1994)

Video is becoming increasingly important for multimedia applications, but computers should let us do more than just watch.We propose a way for computers to structure video and several new interfaces that make it easier to browse and search.
Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation (2007)

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropin-releasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.
Biomechanical evaluation of rotator cuff fixation methods (1989)

Initial fixation strength and failure mode for various rotator cuff reattachment techniques (variations of the McLaughlin technique) were evaluated. Repair methods included standard suture (control), reinforced suture [expanded polytetrafluoroethylene (PTFE) patch and polydioxanone (PDS) tape augmentation] and stapling (nonarthroscopic and arthroscopic soft-tissue staples). The average strength of intact rotator cuff tissue (supraspinatus tendon) was also determined. The different rotator cuff repairs, including at least one control, were performed on fresh-frozen human cadaver shoulder pairs. Repairs were tested to failure in pure tension with the shoulder fixed in 60 degrees of abduction. Load and displacement data were normalized to controls, grouped according to failure modes, and statistically analyzed. The two basic failure modes observed were 1) bone failure, or suture tearing through the bone (indicating weak bone stock) and 2) tendon failure, or suture tearing of the rotator cuff. Gross comparisons between intact and repaired tendons indicated that the intact tendon was two to three times stronger than the repaired tendon. Based on the mode of failure and lack of increased strength after repair, the use of staples for cuff attachment is discouraged. PDS tape suture reinforcement did not increase fixation strength. In contrast, PTFE patch suture augmentation demonstrated statistically higher initial failure loads than did the control and was of specific benefit for shoulders with weak bone stock.
Impurity Identification in Process Chemistry by Mass Spectrometry (2011)

This chapter contains sections titled: Introduction Experimentation Applications Concluding Remarks Acknowledgments References