gebhart/patrepeval huggingface dataset:
Erep: An editable, high-level representation for geometric design and analysis (1992)

We propose a high-level, generative, textual representation for featurebased solid modeling, which we call Erep. We argue that such a representation should be independent of an underlying core solid modeler, and give some criteria it should satisfy. Such an Erep allows archiving geometric designs in a form that is both editable and translatable to any solid modeling system. Furthermore, the representation serves as a global schema by which to federate different modeling systems, and is extensible in a natural way to a representation from which to derive analysis representations and process plans. By federating with finite-element analysis packages, in particular, our approach offers closing the design-analysis feedback loop that previously required a manual link. 'Supported in part by ONR Contract N00014-90-J-1599, NSF Grant CCR 86-19817, and NSF Grant ECD 88-03017. t While on leave in the Department of Computer Sciences, Purdue University. Partially supported by a NATO Scientific Programme fellowship and by a fellowship of the Spanish Ministerio de Ed ucaci6n y Ciencia
Activation of c‐Jun N‐terminal kinase during ischemia and reperfusion in mouse liver (1997)

We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.
Investigation of alternative method for nitrification in constructed wetlands (1997)

Nitrification of secondary effluent using a variant of the vertical flow bed system was investigated. In this vertical flow bed oxygen required for the nitrification process is supplied by a passive air pump. The passive air pump is based on a fill and draw cycle, where oxygen depleted air is removed from the system and fresh air is introduced. Each volume of effluent drained is displaced by an equal volume of fresh air. Experimental results of nitrification and the corresponding oxygen consumption show good agreement with theoretical calculations based on physico-chemical considerations.
Exploiting Conformational Dynamics in Drug Discovery: Design of C-Terminal Inhibitors of Hsp90 with Improved Activities (2014)

The interaction that occurs between molecules is a dynamic process that impacts both structural and conformational properties of the ligand and the ligand binding site. Herein, we investigate the dynamic cross-talk between a protein and the ligand as a source for new opportunities in ligand design. Analysis of the formation/disappearance of protein pockets produced in response to a first-generation inhibitor assisted in the identification of functional groups that could be introduced onto scaffolds to facilitate optimal binding, which allowed for increased binding with previously uncharacterized regions. MD simulations were used to elucidate primary changes that occur in the Hsp90 C-terminal binding pocket in the presence of first-generation ligands. This data was then used to design ligands that adapt to these receptor conformations, which provides access to an energy landscape that is not visible in a static model. The newly synthesized compounds demonstrated antiproliferative activity at ∼150 nM concentration. The method identified herein may be used to design chemical probes that provide additional information on structural variations of Hsp90 C-terminal binding site.
Identification of the Active Site Nucleophile in Jack Bean α-Mannosidase Using 5-Fluoro-β-l-Gulosyl Fluoride (1998)

Mannosidases play a key role in the processing of glycoproteins and thus are of considerable pharmaceutical interest and indeed have emerged as targets for the development of anti-cancer therapies. Access to useful quantities of the mammalian enzymes has not yet been achieved; therefore, jack bean mannosidase, a readily available enzyme, has become the model system. However, the relevance of this enzyme has not been demonstrated, nor is anything known about the active site structure of this, or any other, mannosidase. Hydrolysis by this enzyme occurs with net retention of sugar anomeric configuration; thus, a double displacement mechanism involving a mannosyl-enzyme intermediate is presumably involved. Two new mechanism-based inhibitors, 5-fluoro-alpha-D-mannosyl fluoride and 5-fluoro-beta-L-gulosyl fluoride, which function by the steady state trapping of such an intermediate, have been synthesized and tested. Both show high affinity for jack bean alpha-mannosidase (Ki' = 71 and 86 microM, respectively), and the latter has been used to label the active site nucleophile. The labeled peptide present in a peptic digest of this trapped glycosyl-enzyme intermediate was identified by neutral loss scans on an electrospray ionization triple quadrupole mass spectrometer. Comparative liquid chromatographic/mass spectrometric analysis of peptic digests of labeled and unlabeled enzyme samples confirmed the unique presence of this peptide of m/z 1180.5 in the labeled sample. The label was cleaved from the peptide by treatment with ammonia, and the resultant unlabeled peptide was purified and sequenced by Edman degradation. The peptide identified contained only one candidate for the catalytic nucleophile, an aspartic acid. This residue was contained within the sequence Gly-Trp-Gln-Ile-Asp-Pro-Phe-Gly-His-Ser, which showed excellent sequence similarity with regions in mammalian lysosomal and Golgi alpha-mannosidase sequences. These mammalian alpha-mannosidases belong to family 38 (or class II alpha-mannosidases) in which the Asp in the above sequence is totally conserved. This finding therefore assigns jack bean alpha-mannosidase to family 38, validating it as a model for other pharmaceutically interesting enzymes and thereby identifying the catalytic nucleophile within this family.
HIV Env-mediated, CCR5-dependent depletion of human Vgamma2Vdelta2 T cells (105.33) (2011)

Abstract Human Vgamma2Vdeta2 T cells are depleted during HIV infection. The majority of cells in this population are CD4-negative and do not support productive HIV infection; the mechanism for depleting them remains unknown. We noted recently that macaques immunized with an HIV R5-tropic gp120, also experienced severe Vgamma2Vdelta2 T cell depletion. A subsequent in vitro study showed that several different R5-tropic gp120, including those from Bal, ADA, YU2 and CN54 strains, induced human Vgamma2Vdelta2 T cell death that was inhibited by a CCR5 binding antagonist (Maraviroc) and a Caspase 8 inhibitor. The Vgamma2Vdelta2 may be especially vulnerable to cell death because they express high levels of CCR5 that could be modulated by Rapamycin treatment with a consequent reduction in Env-mediated cell killing. We have observed R5-tropic gp120 induced Vgamma2Vdelta2 T cell depletion both in vivo and in vitro, which was mediated by CCR5 receptor and Caspase 8 signaling pathway. We have identified a potential mechanism for Vgamma2Vdelta2 T cell depletion in HIV disease.
Effect of Terminal (Dry) Heat Treatment on Non-Enveloped Viruses in Coagulation Factor Concentrates (1994)

Terminal dry heat treatment effectively inactivated hepatitis A virus (HAV) and canine parvovirus added to high-purity factor VIII. After 24 h at 80°C, HAV in- fectivity was reduced by ≥4.3 log(10) TCID(50), as measured in a newly developed infectivity assay. The same reduction in virus titer was achieved after 2 h and before 6 h at 90°C. Inactivation of hepatitis A virus was also seen in the freezedrying step prior to heat treatment with an approximately 2.0 log(10) reduction in titer. Similar results were obtained with a high-purity factor IX concentrate. Canine parvovirus was also inactivated at both temperatures, with residual infectivity being undetected after 48 hat 80°C or 10 hat 90°C. Canine parvovirus was not affected by lyophilisation. Canine parvovirus measurements by PCR did not reflect the levels of infectivity measured by the tissue-culture-based method. The addition of the terminal dry heat treatment to solvent/detergent could effectively eliminate the potential contamination of solvent/detergent-treated coagulation factor concentrates by non-lipid-enveloped vimses. However, careful evaluation for any increased induction of non-antigens for factor VIII, as a consequence of such treatment, is needed before use in patients can be recommended.
Transparent Conductors from Carbon Nanotubes LBL-Assembled with Polymer Dopant with π−π Electron Transfer (2011)

Single-walled carbon nanotube (SWNT) and other carbon-based coatings are being considered as replacements for indium tin oxide (ITO). The problems of transparent conductors (TCs) coatings from SWNT and similar materials include poor mechanical properties, high roughness, low temperature resilience, and fast loss of conductivity. The simultaneous realization of these desirable characteristics can be achieved using high structural control of layer-by-layer (LBL) deposition, which is demonstrated by the assembly of hydroethyl cellulose (HOCS) and sulfonated polyetheretherketone (SPEEK)-SWNTs. A new type of SWNT doping based on electron transfer from valence bands of nanotubes to unoccupied levels of SPEEK through π-π interactions was identified for this system. It leads to a conductivity of 1.1 × 10(5) S/m at 66 wt % loadings of SWNT. This is better than other polymer/SWNT composites and translates into surface conductivity of 920 Ω/◻ and transmittance of 86.7% at 550 nm. The prepared LBL films also revealed unusually high temperature resilience up to 500 °C, and low roughness of 3.5 nm (ITO glass -2.4 nm). Tensile modulus, ultimate strength, and toughness of such coatings are 13 ± 2 GPa, 366 ± 35 MPa, and 8 ± 3 kJ/m(3), respectively, and exceed corresponding parameters of all similar TCs. The cumulative figure of merit, ∏(TC), which included the critical failure strain relevant for flexible electronics, was ∏(TC) = 0.022 and should be compared to ∏(TC) = 0.006 for commercial ITO. Further optimization is possible using stratified nanoscale coatings and improved doping from the macromolecular LBL components.
Passive Conductivity Detection for Capillary Electrophoresis (2004)

A passive electrochemical detection principle that can be applied to capillary electrophoresis is presented. The separation electrical field is used to generate a potential difference between two electrodes located along the channel. For constant-current electrophoresis, the generated signal is proportional to the resistance of the solution passing between the two electrodes. Contrary to conductivity detectors that are ac driven and need to be decoupled from the separation field, the passive detection directly takes advantage of the separation field. The signal is simply measured by a high-impedance voltmeter. The detection concept has been validated by numerical simulations showing how the magnitude of the signal is related to the ratio between the electrode distance and the length of the sample plug. As a proof of the principle, this detection concept has been demonstrated by the electrophoretic separation of three alkali ions on a polymer microchip. Based on preliminary results, a detection limit of 20 microM and a dynamic range of up to 3 orders of magnitude have been achieved.
Large-scale clinical validation of biomarkers for pancreatic cancer using a mass spectrometry-based proteomics approach (2017)

We performed an integrated analysis of proteomic and transcriptomic datasets to develop potential diagnostic markers for early pancreatic cancer. In the discovery phase, a multiple reaction monitoring assay of 90 proteins identified by either gene expression analysis or global serum proteome profiling was established and applied to 182 clinical specimens. Nine proteins (P < 0.05) were selected for the independent validation phase and quantified using stable isotope dilution-multiple reaction monitoring-mass spectrometry in 456 specimens. Of these proteins, four proteins (apolipoprotein A-IV, apolipoprotein CIII, insulin-like growth factor binding protein 2 and tissue inhibitor of metalloproteinase 1) were significantly altered in pancreatic cancer in both the discovery and validation phase (P < 0.01). Moreover, a panel including carbohydrate antigen 19-9, apolipoprotein A-IV and tissue inhibitor of metalloproteinase 1 showed better performance for distinguishing early pancreatic cancer from pancreatitis (Area under the curve = 0.934, 86% sensitivity at fixed 90% specificity) than carbohydrate antigen 19-9 alone (71% sensitivity).Overall, we present the panel of robust biomarkers for early pancreatic cancer diagnosis through bioinformatics analysis that combined transcriptomic and proteomic data as well as rigorous validation on a large number of independent clinical samples.
A hydride generator system for a 1-kW inductively coupled plasma (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA hydride generator system for a 1-kW inductively coupled plasmaJ. David. Hwang, Gary D. Guenther, and John P. DiomiguardiCite this: Anal. Chem. 1989, 61, 3, 285–288Publication Date (Print):February 1, 1989Publication History Published online1 May 2002Published inissue 1 February 1989https://pubs.acs.org/doi/10.1021/ac00178a021https://doi.org/10.1021/ac00178a021research-articleACS PublicationsRequest reuse permissionsArticle Views58Altmetric-Citations14LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia (2007)

CD39 is expressed and active on CLL cells. Enzyme activity is higher in earlier stages of CLL and decreased enzyme activity may be associated with worsening disease. These results suggest that CD39 may play a role in the pathogenesis of malignancy and protect CLL patients from thrombotic events.
Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer (2015)

Tumors often contain hypoxic regions resistant to chemo- and radiotherapy. TH-302 (T) is an investigational hypoxia-activated prodrug that selectively releases the DNA cross-linker bromo-isophosphoramide mustard under hypoxic conditions. This study evaluated the efficacy and safety profile of combining T with gemcitabine (G) and nab-paclitaxel (nP) in human pancreatic ductal adenocarcinoma (PDAC) xenograft models in mice. Antitumor activity of the G + nP + T triplet was assessed and compared with T-alone or the G + nP doublet in the Hs766t, MIA PaCa-2, PANC-1, and BxPC-3 PDAC xenograft models. Efficacy was assessed by tumor growth kinetic analysis. Body weight, blood cell counts, blood chemistry, and the von Frey neuropathy assay were analyzed to evaluate safety profiles. Pharmacodynamic changes after the treatment were determined by immunohistochemistry of cell proliferation, DNA damage, apoptosis, hypoxia, and tumor stroma density. The G + nP + T triplet exhibited enhanced efficacy compared with T-alone or the G + nP doublet. Compared with vehicle (V), G + nP induced body weight loss, reduced neutrophil and lymphocyte counts, increased the levels of liver function parameters, and induced neurotoxicity. However, when T was added to G + nP, there was no statistically increased impairment compared to G + nP. The triplet significantly increased DNA damage, apoptosis, and tumor necrosis. Furthermore, the triplet further inhibited cell proliferation and reduced stroma density and intratumoral hypoxia. The triplet combination of G + nP + T exhibited superior efficacy but additive toxicity was not evident compared to the G + nP doublet in this study. This study provides a translational rationale for combining G, nP, and T in the clinical setting to assess efficacy and safety. A Phase I clinical trial of the triplet combination is currently underway (NCT02047500).
Clinical review: Sepsis and septic shock - the potential of gene arrays (2012)

Over the past decade several investigators have applied microarray technology and related bioinformatic approaches to clinical sepsis and septic shock, thus allowing for an assessment of how, or if, this branch of genomic medicine has meaningfully impacted the field of sepsis research. The ability to simultaneously and efficiently measure the steady-state mRNA abundance of thousands of transcripts from a given tissue source (that is, 'transcriptomics') has provided an unprecedented opportunity to gain a broader, genome-level 'picture' of complex and heterogeneous clinical syndromes such as sepsis. A trancriptomic approach to sepsis and septic shock is technically challenging on multiple levels, but nonetheless modest, tangible advances are being realized. These include a genome-level understanding of the complexity of sepsis and septic shock, identification of novel candidate pathways and targets for potential intervention, discovery of novel, candidate diagnostic and stratification biomarkers, and the ability to stratify patients into clinically relevant, expression-based subclasses. The challenges moving forward include robust validation studies, standardization of technical approaches, standardization and further development of analytical algorithms, and large-scale collaborations.
Contributions of authors (2007)

The medium-term survival with this type of femoral component is unsatisfactory, with a high rate of aseptic loosening. The surviving prostheses had a good clinical outcome.
Solvent-dependent aggregation of a water-soluble poly(fluorene) controls energy transfer to chromophore-labeled DNA (2004)

The solvent-dependent aggregation properties of a water-soluble cationic poly(fluorene) were studied and used to control fluorescence resonance energy transfer to Texas Red-labeled DNA.
Analysis of fibronectin receptor function with monoclonal antibodies: roles in cell adhesion, migration, matrix assembly, and cytoskeletal organization. (1989)

We have developed two rat mAbs that recognize different subunits of the human fibroblast fibronectin receptor complex and have used them to probe the function of this cell surface heterodimer. mAb 13 recognizes the integrin class 1 beta polypeptide and mAb 16 recognizes the fibronectin receptor alpha polypeptide. We tested these mAbs for their inhibitory activities in cell adhesion, spreading, migration, and matrix assembly assays using WI38 human lung fibroblasts. mAb 13 inhibited the initial attachment as well as the spreading of WI38 cells on fibronectin and laminin substrates but not on vitronectin. Laminin-mediated adhesion was particularly sensitive to mAb 13. In contrast, mAb 16 inhibited initial cell attachment to fibronectin substrates but had no effect on attachment to either laminin or vitronectin substrates. When coated on plastic, both mAbs promoted WI38 cell spreading. However, mAb 13 (but not mAb 16) inhibited the radial outgrowth of cells from an explant on fibronectin substrates. mAb 16 also did not inhibit the motility of individual fibroblasts on fibronectin in low density culture and, in fact, substantially accelerated migration rates. In assays of the assembly of an extracellular fibronectin matrix by WI38 fibroblasts, both mAbs produced substantial inhibition in a concentration-dependent manner. The inhibition of matrix assembly resulted from impaired retention of fibronectin on the cell surface. Treatment of cells with mAb 16 also resulted in a striking redistribution of cell surface fibronectin receptors from a streak-like pattern to a relatively diffuse distribution. Concomitant morphological changes included decreases in thick microfilament bundle formation and reduced adhesive contacts of the streak-like and focal contact type. Our results indicate that the fibroblast fibronectin receptor (a) functions in initial fibroblast attachment and in certain types of adhesive contact, but not in the later steps of cell spreading; (b) is not required for fibroblast motility but instead retards migration; and (c) is critically involved in fibronectin retention and matrix assembly. These findings suggest a central role for the fibronectin receptor in regulating cell adhesion and migration.
Defense against man-in-the-middle attack in client-server systems (2002)

The deployment of several client-server applications over the Internet and emerging networks requires the establishment of the client's integrity. This is necessary for the protection of copyright of distributed material and, in general, for protection from loss of "sensitive" (secret) information. Clients are vulnerable to powerful man-in-the-middle attacks through viruses, which are undetectable by conventional anti-virus technology. We describe such powerful viruses and show their ability to lead to compromised clients, that cannot protect copyrighted or "sensitive " information. We introduce a methodology based on simple hardware devices, called "spies", which enables servers to establish client integrity, and leads to a successful defense against viruses that use man-in-the-middle attacks.
Acute myelogenous leukemia: recent advances in therapy (1987)

Abstract Results of treatment of AML have improved over the last decade. With modern remission induction chemotherapy, most patients achieve complete remission. The median remission duration is now 1 to 2 years, and a substantial fraction of patients achieve long-term disease-free survival. Bone marrow transplantation provides an improved antileukemic effect compared with chemotherapy alone, and it is the treatment of choice for selected groups of patients. The major limitation is the risk of transplant-related mortality. Most patients are not currently eligible for bone marrow transplants because of advanced age or lack of a histocompatible donor. Autologous marrow transplantation may be effective in selected setting, but this remains investigational at present. Substantial improvement in results of treatment of AML requires the development of new and effective chemotherapeutic agents that are non-cross-resistant with available drugs. Results of bone marrow transplantation may substantially improve if innovative measures to prevent major complications are successful.