gebhart/patrepeval huggingface dataset:
Synthesis and Structural Analysis of 1,4,7,10‐Tetraazacyclododecane‐1,4,7,10‐tetraazidoethylacetic Acid (DOTAZA) Complexes (2015)

Abstract Herein, we present the synthesis and structural analysis of metal complexes of enantiomerically pure 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraazidoethylacetic acid (DOTAZA). DOTAZA is a new tunable analog of DOTA, a clinically approved chelator for various pharmaceutically relevant metal ions. In this work, we investigate the complexation chemistry of DOTAZA and report the crystal structures of a number of complexes with pharmaceutically relevant metal ions such as Gd 3+ [magnetic resonance imaging (MRI)], Eu 3+ (luminescence spectroscopy), Y 3+ [positron emission tomography (PET)], In 3+ [single‐photon‐emission computed tomography (SPECT)], and Na + . These structures provide useful information for imaging applications and demonstrate the potential of DOTAZA to form stable complexes. Owing to its clickable azide functionalities, it may be used for the development of tailored imaging reagents that retain the positive complexation chemistry of the parent compound DOTA.
Synthetic activation of caspases: Artificial death switches (1998)

The development of safe vectors for gene therapy requires fail-safe mechanisms to terminate therapy or remove genetically altered cells. The ideal "suicide switch" would be nonimmunogenic and nontoxic when uninduced and able to trigger cell death independent of tissue type or cell cycle stage. By using chemically induced dimerization, we have developed powerful death switches based on the cysteine proteases, caspase-1 ICE (interleukin-1beta converting enzyme) and caspase-3 YAMA. In both cases, aggregation of the target protein is achieved by a nontoxic lipid-permeable dimeric FK506 analog that binds to the attached FK506-binding proteins, FKBPs. We find that intracellular cross-linking of caspase-1 or caspase-3 is sufficient to trigger rapid apoptosis in a Bcl-xL-independent manner, suggesting that these conditional proapoptotic molecules can bypass intracellular checkpoint genes, such as Bcl-xL, that limit apoptosis. Because these chimeric molecules are derived from autologous proteins, they should be nonimmunogenic and thus ideal for long-lived gene therapy vectors. These properties should also make chemically induced apoptosis useful for developmental studies, for treating hyperproliferative disorders, and for developing animal models to a wide variety of diseases.
Antigen Presentation and T Cell Stimulation by Dendritic Cells (2002)

Dendritic cells take up antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto major histocompatibility complex (MHC) class I and II molecules. Dendritic cells then migrate to secondary lymphoid organs and become competent to present antigens to T lymphocytes, thus initiating antigen-specific immune responses, or immunological tolerance. Antigen presentation in dendritic cells is finely regulated: antigen uptake, intracellular transport and degradation, and the traffic of MHC molecules are different in dendritic cells as compared to other antigen-presenting cells. These specializations account for dendritic cells' unique role in the initiation of immune responses and the induction of tolerance.
Effects of Vagus Nerve Stimulation on Sleep‐related Breathing in Epilepsy Patients (2003)

Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.
Clinical aspects of mitochondrial disorders (1992)

Mitochondrial disorders have long been regarded as neuromuscular diseases only. In fact, owing to the ubiquitous nature of the oxidative phosphorylation, a broad spectrum of clinical features should be expected in mitochondrial disorders. Here, we present eight puzzling observations which give support to the view that a disorder of oxidative phosphorylation can give rise to any symptom in any organ or tissue with any apparent mode of inheritance. Consequently, we suggest giving consideration to the diagnosis of a mitochondrial disorder when dealing with an unexplained association of symptoms, with an early onset and a rapidly progressive course involving seemingly unrelated organs. Determination of lactate/pyruvate and ketone body molar ratios in plasma can help to select patients at risk for this condition.
Leucocyte-endothelial cell adhesion in a model of intestinal inflammation. (1995)

Leucocyte-endothelial cell adhesion is modulated by a variety of adhesion glycoprotein expressed on the surface of leucocytes and endothelial cells. Although in vitro studies show that these adhesion molecules mediate the decrease in leucocyte rolling velocity and the increase in leucocyte adherence and emigration associated with inflammation, there are few in vivo data to support this hypothesis. The aim of this study was to assess the role of leucocyte (CD11b/CD18) and endothelial cell (P- and E-selectin) adhesion molecules in mediating the leucocyte-endothelial cell adhesion elicited in rat mesenteric venules during a model of longlasting intestinal inflammation. Indomethacin was injected 48 and 24 hours before the experiment. The mesenteric microcirculation was observed by intravital microscopy in animals treated with monoclonal antibodies (MAb) directed against either P-selectin, E-selectin, or CD11b/CD18. Leucocyte rolling velocity, and the number of adherent and emigrated leucocytes as well as vessel diameter and erythrocyte velocity were monitored in roughly 30 micron diameter postcapillary venules. Indomethacin treatment resulted in mucosal ulceration and granulocyte infiltration, and a corresponding inflammatory response in the mesentery, which was characterised by an increase in the number of adherent (eightfold) and emigrated (sixfold) leucocytes and a reduction (80%) in leucocyte rolling velocity. The indomethacin induced leucocyte-endothelial cell adhesion in mesenteric venules was significantly reduced by treatment with MAbs against either CD11b/CD18 or E-selectin, but not by the P-selectin MAb. These results suggest that both leukocyte (CD11b/CD18) and endothelial cell (E-selectin) adhesion molecules contribute to the granulocyte accumulation in a chronic model of intestinal inflammation.
Hyaluronic Acid- Paclitaxel: Antitumor Efficacy against CD44(+) Human Ovarian Carcinoma Xenografts (2007)

Numerous human tumor types, including ovarian cancer, display a significant expression of the CD44 family of cell surface proteoglycans. To develop tumor-targeted drugs, we have initially evaluated whether the CD44 ligand hyaluronic acid (HA) could serve as a backbone for paclitaxel (TXL) prodrugs. HA-TXL was prepared by modification of previous techniques. The in vitro cytotoxicity of HA-TXL against the CD44(+) human ovarian carcinoma cell lines SKOV-3ip and NMP-1 could be significantly blocked by preincubation with a molar excess of free HA. Female nude mice bearing intraperitoneal implants of NMP-1 cells were treated intraperitoneally with a single sub-maximum tolerated dose dose of HA-TXL or with multiple-dose regimens of paclitaxel (Taxol; Mead Johnson, Princeton, NJ) to determine the effects of these regimens on host survival and intraperitoneal tumor burden, with the latter being assessed by magnetic resonance imaging. NMP-1 xenografts were highly resistant to Taxol regimens, as host survival was only nominally improved compared to controls (T//C approximately 120), whereas single-dose HA-TXL treatment significantly improved survival in this model (T//C approximately 140; P = .004). In both NMP-1 and SKOV-3ip models, MR images of abdomens of HA-TXL-treated mice obtained shortly before controls required humane sacrifice revealed markedly reduced tumor burdens compared to control mice. This study is among the first to demonstrate that HA-based prodrugs administered locoregionally have antitumor activity in vivo.
Visualization of an extracellular mucoid layer of Treponema denticola ATCC 35405 and surface sugar lectin analysis of some Treponema species (1997)

Slime layers and capsules are common amongst medically relevant bacteria. We herein report that Treponema denticola, which has been associated with periodontitis, synthesizes or acquires an extracellular polysaccharide layer that we have observed through electron microscopy using the polysaccharide-specific dye Alcian blue and phosphotungstate. We have also visualized this extracellular layer by dark-field microscopy of Alcian blue-stained spirochete cells. A representative strain of each of the oral spirochete species T. denticola, Treponema vincentii and Treponema socranskii were differentiated by concanavalin A, phaseolus, lotus A and arachis lectins in a microtiter plate immunoassay for the detection of surface sugars.
Vasculature Disruption Enhances Bacterial Targeting of Autochthonous Tumors (2015)

Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has been developed as a vector to deliver therapeutic agents to tumors. The potential of S. Typhimurium in cancer therapy is largely due to its reported propensity to accumulate at greater than 1,000-fold higher concentrations in tumors relative to healthy tissues. In this study, we compared bacterial colonization of tumors in a subcutaneous transplantation model with a more clinically relevant autochthonous tumor model. Following intravenous administration of attenuated S. Typhimurium strain SL3261, we observed approximately 10,000-fold less bacteria in autochthonous tumors that sporadically develop in transgenic BALB-neuT mice compared to tumors developed from subcutaneous transplantation of 4T1 murine breast cancer cells in BALB/c mice. Treatment of BALB-neuT mice with a vasculature-disrupting agent (VDA) prior to bacterial treatment caused necrosis of tumor tissue and significantly increased the bacterial targeting of autochthonous tumors by approximately 1,000-fold. These observations emphasize the importance of appropriate model selection in developing bacteria-based cancer therapies and demonstrate the potential of combining VDA pre-treatment with bacteria to facilitate targeting of clinically relevant tumors.
Secret Key Cryptography Using Graphics Cards (2004)

One frequently cited reason for the lack of wide deployment of cryptographic protocols is the (perceived) poor performance of the algorithms they employ and their impact on the rest of the system. Although high-performance dedicated cryptographic accelerator cards have been commercially available for some time, market penetration remains low. We take a different approach, seeking to exploit {\it existing system resources,} such as Graphics Processing Units (GPUs) to accelerate cryptographic processing. We exploit the ability for GPUs to simultaneously process large quantities of pixels to offload cryptographic processing from the main processor. We demonstrate the use of GPUs for stream ciphers, which can achieve 75\% the performance of a fast CPU. We also investigate the use of GPUs for block ciphers, discuss operations that make certain ciphers unsuitable for use with a GPU, and compare the performance of an OpenGL-based implementation of AES with implementations utilizing general CPUs. In addition to offloading system resources, the ability to perform encryption and decryption within the GPU has potential applications in image processing by limiting exposure of the plaintext to within the GPU.
Suppression of gene silencing: A general strategy used by diverse DNA and RNA viruses of plants (1999)

In transgenic and nontransgenic plants, viruses are both initiators and targets of a defense mechanism that is similar to posttranscriptional gene silencing (PTGS). Recently, it was found that potyviruses and cucumoviruses encode pathogenicity determinants that suppress this defense mechanism. Here, we test diverse virus types for the ability to suppress PTGS. Nicotiana benthamiana exhibiting PTGS of a green fluorescent protein transgene were infected with a range of unrelated viruses and various potato virus X vectors producing viral pathogenicity factors. Upon infection, suppression of PTGS was assessed in planta through reactivation of green fluorescence and confirmed by molecular analysis. These experiments led to the identification of three suppressors of PTGS and showed that suppression of PTGS is widely used as a counter-defense strategy by DNA and RNA viruses. However, the spatial pattern and degree of suppression varied extensively between viruses. At one extreme, there are viruses that suppress in all tissues of all infected leaves, whereas others are able to suppress only in the veins of new emerging leaves. This variation existed even between closely related members of the potexvirus group. Collectively, these results suggest that virus-encoded suppressors of gene silencing have distinct modes of action, are targeted against distinct components of the host gene-silencing machinery, and that there is dynamic evolution of the host and viral components associated with the gene-silencing mechanism.
The Peptidyl-prolyl Isomerase Pin1 Up-regulation and Proapoptotic Function in Dopaminergic Neurons (2013)

Parkinson disease (PD) is a chronic neurodegenerative disease characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra. The pathophysiological mechanisms underlying PD remain unclear. Pin1, a major peptidyl-prolyl isomerase, has recently been associated with certain diseases. Notably, Ryo et al. (Ryo, A., Togo, T., Nakai, T., Hirai, A., Nishi, M., Yamaguchi, A., Suzuki, K., Hirayasu, Y., Kobayashi, H., Perrem, K., Liou, Y. C., and Aoki, I. (2006) J. Biol. Chem. 281, 4117-4125) implicated Pin1 in PD pathology. Therefore, we sought to systematically characterize the role of Pin1 in PD using cell culture and animal models. To our surprise we observed a dramatic up-regulation of Pin1 mRNA and protein levels in dopaminergic MN9D neuronal cells treated with the parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP(+)) as well as in the substantia nigra of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Notably, a marked expression of Pin1 was also observed in the substantia nigra of human PD brains along with a high co-localization of Pin1 within dopaminergic neurons. In functional studies, siRNA-mediated knockdown of Pin1 almost completely prevented MPP(+)-induced caspase-3 activation and DNA fragmentation, indicating that Pin1 plays a proapoptotic role. Interestingly, multiple pharmacological Pin1 inhibitors, including juglone, attenuated MPP(+)-induced Pin1 up-regulation, α-synuclein aggregation, caspase-3 activation, and cell death. Furthermore, juglone treatment in the MPTP mouse model of PD suppressed Pin1 levels and improved locomotor deficits, dopamine depletion, and nigral dopaminergic neuronal loss. Collectively, our findings demonstrate for the first time that Pin1 is up-regulated in PD and has a pathophysiological role in the nigrostriatal dopaminergic system and suggest that modulation of Pin1 levels may be a useful translational therapeutic strategy in PD.
Pancuronium bromide and other steroidal neuromuscular blocking agents containing acetylcholine fragments (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPancuronium bromide and other steroidal neuromuscular blocking agents containing acetylcholine fragmentsW. R. Buckett, C. L. Hewett, and D. S. SavageCite this: J. Med. Chem. 1973, 16, 10, 1116–1124Publication Date (Print):October 1, 1973Publication History Published online1 May 2002Published inissue 1 October 1973https://pubs.acs.org/doi/10.1021/jm00268a011https://doi.org/10.1021/jm00268a011research-articleACS PublicationsRequest reuse permissionsArticle Views666Altmetric-Citations65LEARN 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
Heavy water enhances the antineoplastic effect of 5‐fluoro‐uracil and bleomycin in nude mice bearing human carcinoma (1990)

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.
The Parkinson Disease Gene LRRK2: Evolutionary and Structural Insights (2006)

Mutations in the human leucine-rich repeat kinase 2 (LRRK2) gene are associated with both familial and sporadic Parkinson disease (PD). LRRK2 belongs to a gene family known as Roco. Roco genes encode for large proteins with several protein domains. Particularly, all Roco proteins have a characteristic GTPase domain, named Roc, plus a domain of unknown function called COR. In addition, LRRK2 and several other Roco proteins also contain a protein kinase domain. In this study, I use a combination of phylogenetic and structural analyses of the COR, Roc, and kinase domains present in Roco proteins to describe the origin and evolutionary history of LRRK2. Phylogenetic analyses using these domains demonstrate that LRRK2 emerged from a duplication that occurred after the protostome-deuterostome split. The duplication was followed by the acquisition by LRRK2 proteins of a specific type of N-terminal repeat, described here for the first time. This repeat is absent in the proteins encoded by the paralogs of LRRK2, called LRRK1 or in protostome LRRK proteins. These results suggest that Drosophila or Caenorhabditis LRRK genes may not be good models to understand human LRRK2 function. Genes in the slime mold Dictyostelium discoideum with structures very similar to those found in animal LRRK genes, including the protein kinase domain, have been described. However, phylogenetic analyses suggest that this structural similarity is due to independent acquisitions of distantly related protein kinase domains. Finally, I confirm in an extensive sequence analysis that the Roc GTPase domain is related but still substantially different from small GTPases, such as Rab, Ras, or Rho. Modeling based on known kinase structures suggests that mutations in LRRK2 that cause familiar PD may alter the local 3-dimensional folding of the LRRK2 protein without affecting its overall structure.
Highly Active Iron and Cobalt Catalysts for the Polymerization of Ethylene (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTHighly Active Iron and Cobalt Catalysts for the Polymerization of EthyleneBrooke L. Small, Maurice Brookhart, and Alison M. A. BennettView Author Information Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290 DuPont Central Research and Development Experimental Station, Wilmington, Delaware 19880-0328 Cite this: J. Am. Chem. Soc. 1998, 120, 16, 4049–4050Publication Date (Web):April 14, 1998Publication History Received20 January 1998Published online14 April 1998Published inissue 1 April 1998https://pubs.acs.org/doi/10.1021/ja9802100https://doi.org/10.1021/ja9802100rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views14440Altmetric-Citations1303LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Catalysts,Ethylene polymerization,Hydrocarbons,Ligands,Polymers Get e-Alerts
An elementary proof of the strong converse theorem for the multiple-access channel (1982)

In [1] we determined the capacity region of the multiple–access channel (MAC) by proving a coding theorem and its weak converse. Recently Dueck [2] proved a strong converse theorem in the sense of Wolfowitz [3]. His proof uses the Ahlswede–Gács–Körner [4] method of “blowing up decoding sets ” in conjunction with a new “wringing technique”.
Microsoft Windows NT Server Administrator's Bible (1999)

This package is aimed at network administrators, discussing every facet of the NT Enterprise Edition with updated information on the option pack. The CD-ROM contains third-party components for improved NT networking, such as Octopus, Diskeeper, Superdisk-NT, GoldFax and Netshield demo.