gebhart/patrepeval huggingface dataset:
The C-terminal Region of Membrane Type Matrix Metalloproteinase Is a Functional Transmembrane Domain Required for Pro-gelatinase A Activation (1995)

We identified a new matrix metalloproteinase (membrane type matrix metalloproteinase (MT-MMP)) that has a potential transmembrane (TM) domain at the C terminus and reported its expression on the surface of invasive tumor cells. The expression of MT-MMP induced specific activation of 72-kDa pro-gelatinase A (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65). Thus, MT-MMP on the cell surface is thought to play an important role in various physiological and pathological processes accompanying tissue remodeling. In this study, we demonstrated that the potential TM domain deduced from the amino acid sequence functions as a membrane linker when it is fused to a secretory protein, tissue inhibitor of matrix metalloproteinases-1. The pro-gelatinase A activation function of MT-MMP was abolished by truncation of the TM domain and recovered by fusing the MT-MMP mutant with the TM domain of interleukin 2 receptor alpha-chain. The truncated MT-MMP was released from the cells into the medium and detected as processed or modified forms. In spite of the deletion of the TM domain some portions of the mutant MT-MMP were still retained on the surface of cells. Thus, MT-MMP has an additional device to keep it on the cell surface. The TM domain however, plays an essential role in the pro-gelatinase A activation function of MT-MMP, probably regulating its fine orientation or the localization that is necessary to interact with substrate.
Calpain-2 as a target for limiting prostate cancer invasion. (2003)

Mortality and morbidity of prostate cancer result from extracapsular invasion and metastasis. This tumor progression depends on active cell motility. Previous studies have shown that calpain-regulated rear detachment enabling forward locomotion is required for cell migration initiated by growth factor and adhesion receptors. Therefore, we asked whether calpain would be a target for limiting tumor progression, using as our model the PA DU-145 human prostate carcinoma cell line and a highly invasive subline, wild-type DU-145, derived from it. In vitro, the calpain-specific inhibitor CI-I (ALLN) and the preferential-but-less-specific inhibitor leupeptin decreased transmigration of both cell lines across a Matrigel barrier. These calpain inhibitors limited epidermal growth factor-induced motility but did not alter the growth rate of the tumor cells, as expected. Antisense down-regulation of the growth factor-activated calpain-2 (m-calpain) isoform also reduced transmigration and cell motility. These in vitro findings were then buttressed by in vivo studies, in which i.p. DU-145 tumor xenografts were treated with leupeptin. Tumor invasion into the diaphragm was reduced by leupeptin treatment for both the PA and wild-type DU-145 cells (from 1.7 to 0.78 for the parental line and 2.3 to 1.2 for the invasive derivative, respectively). Tumor cells of both types engineered to express calpain-2 antisense constructs also demonstrated a similar 50% reduced invasiveness in vivo. Finally, we found by gene expression survey of 53 human prostate tumors and 23 normal prostates that calpain was not up-regulated in relationship to invasiveness or metastatic activity, consistent with expectation from the biological role of this effector. Taken together, these results strongly suggest that epigenetic activation of calpain plays an important role in the invasion of human prostate cancer and that it can be targeted to reduce tumor progression.
InlB, a surface protein ofListeria monocytogenesthat behaves as an invasin and a growth factor (2002)

Molecules from some pathogenic bacteria mimic natural host cell ligands and trigger engulfment of the bacterium after specifically interacting with cell-surface receptors. The leucine-rich repeat (LRR)-containing protein InlB of Listeria monocytogenes is one such molecule. It triggers bacterial entry by interacting with the hepatocyte growth factor receptor (HGF-R or Met) and two other cellular components: gC1q-R and proteoglycans. Recent studies point to significant similarities between the molecular mechanisms underlying InlB-mediated entry into cells and classic phagocytosis. In addition, InlB, in common with HGF, activates signaling cascades that are not involved in bacterial entry. Therefore, studies of InlB may help us to analyze the previously noticed similarities between growth factor receptor activation and phagocytosis.
Structural and functional heterogeneity among peroxidase-negative granules in human neutrophils: identification of a distinct gelatinase- containing granule subset by combined immunocytochemistry and subcellular fractionation (1993)

The existence of separate gelatinase granules in human neutrophils has been a matter of debate in recent years. We have demonstrated that the 135-kD form of neutrophil gelatinase is a complex of 92-kD gelatinase and a novel 25-kD protein termed neutrophil gelatinase-associated lipocalin (NGAL) that, in addition to being complexed with part of the gelatinase, is localized in free form in peroxidase-negative specific granules. Because this association was not appreciated in earlier studies, we decided to reassess the ultrastructural localization of gelatinase using specific antibodies without immunoreactivity towards NGAL. Double-labeling immunogold electron microscopy was performed on frozen thin sections of human neutrophils. Twenty-four percent of all peroxidase-negative granules were labeled with antigelatinase antibody, but not with antilactoferrin antibody. These granules are defined as gelatinase granules. Sixteen percent reacted with antilactoferrin antibody but not with antigelatinase antibody. The rest (60%) reacted with both antibodies. All granules labeling for lactoferrin are defined as specific granules. Gelatinase granules were observed as round and oval forms of considerably smaller size than specific granules, and were less electron dense. Isolated granules obtained by subcellular fractionation were also examined by immunoelectron microscopy. This demonstrated that peroxidase-negative granules comprise a continuum from the most dense granules that contain lactoferrin but no gelatinase to the lightest that contain gelatinase but no lactoferrin. Thus, gelatinase granules do exist as a subpopulation of peroxidase-negative granules and may allow for exocytosis of gelatinase during neutrophil diapedesis without substantial mobilization of other peroxidase- negative granules, ie, specific granules.
Trends in Postoperative Sepsis: Are We Improving Outcomes? (2009)

Sepsis and death were more likely after non-elective than elective surgery. Sepsis and severe sepsis has increased significantly after elective and non-elective procedures over the last 17 years. The hospital mortality rate was reduced significantly after non-elective surgery, but no improvements were found for elective surgery patients who developed sepsis. Disparities in age, sex, and ethnicity and the development of postoperative surgical sepsis were found. Population-based studies may assist in defining temporal trends, disparities, and outcomes in sepsis not elucidated in smaller studies.
Patterns in property specifications for finite-state verification (1999)

Article Patterns in property specifications for finite-state verification Share on Authors: Matthew B. Dwyer Kansas State University, Department of Computing and Information Sciences, Manhattan, KS Kansas State University, Department of Computing and Information Sciences, Manhattan, KSView Profile , George S. Avrunin University of Massachusetts, Department of Mathematics and Statistics, Amherst, MA University of Massachusetts, Department of Mathematics and Statistics, Amherst, MAView Profile , James C. Corbett University of Hawai'i, Department of Information and Computer Science, Honolulu, HI University of Hawai'i, Department of Information and Computer Science, Honolulu, HIView Profile Authors Info & Claims ICSE '99: Proceedings of the 21st international conference on Software engineeringMay 1999 Pages 411–420https://doi.org/10.1145/302405.302672Online:16 May 1999Publication History 956citation2,118DownloadsMetricsTotal Citations956Total Downloads2,118Last 12 Months172Last 6 weeks21 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Mutation of hCDC4 Leads to Cell Cycle Deregulation of Cyclin E in Cancer (2004)

hCDC4, the gene that encodes the F-box protein responsible for targeting cyclin E for ubiquitin-mediated proteolysis, has been found to be mutated in a number of primary cancers and cancer-derived cell lines. We have observed that functional inactivation of hCDC4 does not necessarily correlate with elevated levels of cyclin E in tumors. Here we show, however, that hCDC4 mutation in primary tumors correlates strongly with loss of cell cycle regulation of cyclin E. Similarly, a breast carcinoma-derived cell line mutated for hCDC4 exhibits cell cycle deregulation of cyclin E, but periodic expression is restored by reintroducing hCDC4 via retroviral transduction. Conversely, small interfering RNA-mediated silencing of hCdc4 deregulates cyclin E with respect to the cell cycle. These results indicate that hCdc4 function is an absolute prerequisite for cell cycle regulation of cyclin E levels, and loss of hCdc4 function is sufficient to deregulate cyclin E.
Analysis of antigenic surfaces of proteins (1995)

The processes underlying molecular evolution have proved difficult to understand due to the complexity and obscurity of the selective pressures at work. The strong selective pressure to optimize antigen recognition means that antibody paratopes are more favorable systems than most in which to investigate these processes, as are viral epitopes, which evolve under an inverse pressure, rapidly changing to avoid recognition. Because recognition is a property of the surfaces of these molecules we expect that their evolutionary development may be read in the changes in the 3-dimensional array of chemical groups displayed on their surface. We have analyzed the bulk properties of these surfaces and find that there are significant differences in exposed amino acid preferences among 1) a control group of immunologically secluded proteins, 2) binding surfaces of immunoglobulins, and 3) the outer surfaces of picornaviruses. Compared to the control group, the immunoglobulin complementarity determining regions possess a relative excess of serine residues whereas picornaviruses suppress serine but overuse threonine residues, suggesting that the differing selective pressure has led to perturbations in the population of amino acid types on the surface of these proteins. Although these changes may be rationalized in terms of the structure and chemistry of the different side chains, we suggest that there may be a further, genetic component behind the observations: point mutations in the respective codons for serine and threonine lead to markedly different forms of structural variability. The high rate of reselection observed for these residues is in line with this second mechanism.
Intramolecular C=O···B Interactions in o-Boron Substituted Benzaldehyde, Acetophenone, and Benzophenone (2002)

Abstract The title carbonyl compounds bearing a 4,4-diphenyl-1,3,2-dioxaborolan-2-yl group at the ortho position were prepared to compare the Lewis basicity of carbonyl-oxygen atoms. In the benzoyl and formyl compounds, the intramolecular C=O···B interactions are so weak that no significant changes were observed in the 13C and 11B NMR and IR spectra compared with the reference compounds. For the acetyl compound, the C=O stretching absorption was shifted to lower wavenumber by 18 cm−1 in the IR spectrum because of the coordination. The interaction energy could be estimated to be ca. 27 kJ mol−1 by the variable temperature 1H NMR measurement. These substituent effects are discussed from the viewpoints of Lewis basicity and the conformational stability of the carbonyl moieties with the assistance of the DFT calculations.
Selective analysis of cell‐free DNA in maternal blood for evaluation of fetal trisomy (2012)

Digital analysis of selected regions enables highly accurate, cost efficient, and scalable noninvasive fetal aneuploidy assessment.
Optimal algorithms for bubble sort based non-Manhattan channel routing (1994)

It has been pointed out that, in many cases, results generated by non-Manhattan channel routers will be better than those generated by Manhattan routers. Non-optimal bubble sort based algorithms for non-Manhattan channel routing have been proposed in the literature by also allowing connections in the +45/spl deg/ and /spl minus/45/spl deg/ directions. In this paper, optimal algorithms are proposed for the two-layer and three-layer non-Manhattan channel routing problems based on an identical problem formulation. The time complexities of our algorithms and the existing algorithm (which produces the best results so far) are O(K/sup 2/ * N) and O(K * N/sup 2/), respectively, where N is the number of terminals (i.e., the length) of the channel and N is the number of routing tracks (i.e., the height) in the channel. K is always less than N, and in most cases is much smaller than N. Clearly, a significant improvement in time complexity over the existing algorithm (which produces the best results so far) is achieved, while ensuring optimality.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intraarticular injection of heparin‐binding insulin‐like growth factor 1 sustains delivery of insulin‐like growth factor 1 to cartilage through binding to chondroitin sulfate (2010)

Our findings indicate that after intraarticular injection in rats, HB-IGF-1 is specifically retained in cartilage through its high abundance of CS. Modification of growth factors with heparin-binding domains may be a new strategy for sustained and specific local delivery to cartilage.
The Conversational User Interface (2013)

Work on both the graphical user interface (GUI) and the conversational user interface (CUI) started at about the same time, about 40 years ago. The GUI was a lot easier to implement, and it made computing and information resources available to ordinary people—but over the years it has lost much of its simplicity and charm. The CUI has taken many more years to develop, requiring major scientific and engineering advances in speech, natural language processing, user-modeling, and reasoning, not to mention increases in cost-effective computation. But the infrastructure is now in place for the widespread distribution of conversational interfaces, and we have begun to imagine and create sophisticated ways of exploiting this new mode of interaction. This may well be the “killer app” for deep natural language processing and complex reasoning.
Literacy analysis of National Comprehensive Cancer Network patient guidelines for the most common malignancies in the United States (2017)

Overall, the assessment indicates high demand scores for the readability and complexity of the NCCN patient guidelines and thus that the materials are not quite suitable for the general US adult population. Further input from patient focus groups to address appropriateness and usefulness is critical. Cancer 2018;124:769-74. © 2017 American Cancer Society.
Transcranial Ultrasound from Diagnosis to Early Stroke Treatment – Part 2: Prehospital Neurosonography in Patients with Acute Stroke – The Regensburg Stroke Mobile Project (2012)

Prehospital diagnosis of MCA occlusion in stroke patients is feasible using portable duplex ultrasonography with or without administration of a microbubble contrast agent. Prehospital neurological as well as transcranial vascular assessments during patient transport can be performed by a trained neurologist with high sensitivity and specificity, perhaps opening an additional therapeutic window for sonothrombolysis or neuroprotective strategies.
Modulation of cyclic nucleotides and cyclic nucleotide phosphodiesterases in pancreatic islet beta-cells and intestinal L-cells as targets for treating diabetes mellitus. (2006)

Cyclic 3'5'-AMP (cAMP) is an important physiological amplifier of glucose-induced insulin secretion by the pancreatic islet beta-cell. In the beta-cell, cAMP is formed by the activity of adenylyl cyclase, especially in response to the incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic peptide. cAMP may also play a similar role in regulating GLP-1 secretion from intestinal L-cells. cAMP influences many steps involved in glucose-induced insulin secretion and may be important in regulating pancreatic islet beta-cell differentiation, growth and survival. cAMP itself is rapidly degraded in the pancreatic islet beta-cell by cyclic nucleotide phosphodiesterase enzymes. This review will discuss the possibility of targeting cAMP mechanisms in the treatment of type 2 diabetes mellitus, in which insulin release in response to glucose is impaired.
Predicting population coverage of T-cell epitope-based diagnostics and vaccines (2006)

We have developed a web-based tool to predict population coverage of T-cell epitope-based diagnostics and vaccines based on MHC binding and/or T cell restriction data. Accordingly, epitope-based vaccines or diagnostics can be designed to maximize population coverage, while minimizing complexity (that is, the number of different epitopes included in the diagnostic or vaccine), and also minimizing the variability of coverage obtained or projected in different ethnic groups.
Reciprocal oxylipin‐mediated cross‐talk in the Aspergillus–seed pathosystem (2007)

In Aspergilli, mycotoxin production and sporulation are governed, in part, by endogenous oxylipins (oxygenated, polyunsaturated fatty acids and metabolites derived therefrom). In Aspergillus nidulans, oxylipins are synthesized by the dioxygenase enzymes PpoA, PpoB and PpoC. Structurally similar oxylipins are synthesized in seeds via the action of lipoxygenase (LOX) enzymes. Previous reports have shown that exogenous application of seed oxylipins to Aspergillus cultures alters sporulation and mycotoxin production. Herein, we explored whether a plant oxylipin biosynthetic gene (ZmLOX3) could substitute functionally for A. nidulans ppo genes. We engineered ZmLOX3 into wild-type A. nidulans, and into a DeltappoAC strain that was reduced in production of oxylipins, conidia and the mycotoxin sterigmatocystin. ZmLOX3 expression increased production of conidia and sterigmatocystin in both backgrounds. We additionally explored whether A. nidulans oxylipins affect seed LOX gene expression during Aspergillus colonization. We observed that peanut seed pnlox2-3 expression was decreased when infected by A. nidulansDeltappo mutants compared with infection by wild type. This result provides genetic evidence that fungal oxylipins are involved in plant LOX gene expression changes, leading to possible alterations in the fungal/host interaction. This report provides the first genetic evidence for reciprocal oxylipin cross-talk in the Aspergillus-seed pathosystem.
Structure‐based mutational analyses in FGF7 identify new residues involved in specific interaction with FGFR2IIIb (2003)

Receptor binding specificity is an essential element in regulating the diverse activities of fibroblast growth factors (FGFs). FGF7 is ideal to study how this specificity is conferred at the structural level, as it interacts exclusively with one isoform of the FGF-receptor (FGFR) family, known as FGFR2IIIb. Previous mutational analysis suggested the importance of the beta4/beta5 loop of FGF7 in specific receptor recognition. Here a theoretical model of FGFR2IIIb/FGF7 complex showed that this loop interacts with the FGFR2IIIb unique exon. In addition, the model revealed new residues that either directly interact with the FGFR2IIIb unique exon (Asp63, Leu142) or facilitate this interaction (Arg65). Mutations in these residues reduced both receptor binding affinity and biological activity of FGF7. Altogether, these results provide the basis for understanding how receptor-binding specificity of FGF7 is conferred at the structural level.
Cardiac Sympathetic Afferent Denervation Attenuates Cardiac Remodeling and Improves Cardiovascular Dysfunction in Rats With Heart Failure (2014)

The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympathoexcitation in chronic heart failure (CHF). Increased sympathoexcitation is positively related to mortality in patients with CHF. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here, we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. To delete the transient receptor potential vanilloid 1 receptor-expressing CSAR afferents selectively, epicardial application of resiniferatoxin (50 μg/mL), an ultrapotent analog of capsaicin, was performed during myocardium infarction surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of resiniferatoxin largely prevented the elevated left ventricle end-diastolic pressure, lung edema, and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart, and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that resiniferatoxin attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and transforming growth factor-β receptor I in CHF rats. Pressure-volume loop analysis showed that resiniferatoxin reduced the end-diastolic pressure volume relationships in CHF rats, indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF.