gebhart/patrepeval huggingface dataset:
Synthesis of DNA-Interactive Pyrrolo[2,1-c][1,4]benzodiazepines (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of DNA-Interactive Pyrrolo[2,1-c][1,4]benzodiazepinesDavid E. Thurston and D. Subhas BoseCite this: Chem. Rev. 1994, 94, 2, 433–465Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/cr00026a006https://doi.org/10.1021/cr00026a006research-articleACS PublicationsRequest reuse permissionsArticle Views1225Altmetric-Citations249LEARN 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
Exposure to Ultraviolet Radiation Causes Dendritic Cells/Macrophages to Secrete Immune-Suppressive IL-12p40 Homodimers (2000)

UV-induced immune suppression is a risk factor for sunlight-induced skin cancer. Exposure to UV radiation has been shown to suppress the rejection of highly antigenic UV-induced skin cancers, suppresses delayed and contact hypersensitivity, and depress the ability of dendritic cells to present Ag to T cells. One consequence of UV exposure is altered activation of T cell subsets. APCs from UV-irradiated mice fail to present Ag to Th1 T cells; however, Ag presentation to Th2 T cells is normal. While this has been known for some time, the mechanism behind the preferential suppression of Th1 cell activation has yet to be explained. We tested the hypothesis that this selective impairment of APC function results from altered cytokine production. We found that dendritic cells/macrophages (DC/Mphi) from UV-irradiated mice failed to secrete biologically active IL-12 following in vitro stimulation with LPS. Instead, DC/Mphi isolated from the lymphoid organs of UV-irradiated mice secreted IL-12p40 homodimer, a natural antagonist of biologically active IL-12. Furthermore, when culture supernatants from UV-derived DC/Mphi were added to IL-12-activated T cells, IFN-gamma secretion was totally suppressed, indicating that the IL-12p40 homodimer found in the supernatant fluid was biologically active. We suggest that by suppressing DC/Mphi IL-12p70 secretion while promoting IL-12p40 homodimer secretion, UV exposure preferentially suppress the activation of Th1 cells, thereby suppressing Th-1 cell-driven inflammatory immune reactions.
Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival (2006)

These data imply that increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive tumor phenotype. The known functions of Eph/ephrin signalling in cell de-adhesion and movement may explain the observed correlation of ephrin expression with poor prognosis.
Ipilimumab in the treatment of melanoma (2012)

Ipilimumab, approved by the FDA for patients with advanced or metastatic melanoma based on the overall survival benefit when compared with a peptide vaccine, is a major breakthrough in the treatment of melanoma. While clinicians are embracing this innovative biologic agent, special attentions in patient selection, class-specific immune-related toxicities and their management as well as treatment response evaluation are needed.
Synthetic Protocells Interact with Viral Nanomachinery and Inactivate Pathogenic Human Virus (2011)

We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV) and Hendra (HeV) viruses. In the new approach, artificial cell-like particles (protocells) presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development.
Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. (1998)

Congenic MRL-lpr mice homozygous and heterozygous for the IFN-gamma gene disruption were created to assess the role of this pleotropic cytokine on the lymphoaccumulation and lupus-like disease of Fas-defective mice. Early death was prevented, and glomerulonephritis severely reduced in IFN-gamma-/- mice. Hypergammaglobulinemia was maintained with a switch from IgG2a to IgG1 predominance, but the dramatic decrease in levels of the dominant IgG2a anti-dsDNA autoantibodies was not associated with a compensatory increase in TH2-associated IgG subclasses. Remarkably, early death and glomerulonephritis were also prevented in IFN-gamma+/- mice, although autoantibody levels and glomerular immune deposits were equivalent to IFN-gamma+/+ lpr mice, indicating the importance of additional locally-exerted disease-promoting effects of IFN-gamma. IFN-gamma-/- mice exhibited reduced lymphadenopathy concomitant to a decrease in DN B220(+) T cells. In vivo BrdU labeling showed reduced proliferation of DN B220(+) cells in IFN-gamma-/- vs. IFN-gamma+/+ lpr mice, while enhanced proliferation of all other T cell subsets was unaffected. Macrophages of IFN-gamma-/-lpr mice expressed markedly decreased levels of MHC class I and II molecules compared with controls. Moreover, the heightened expression of MHC class II molecules on proximal tubules of IFN-gamma+/+ lpr mice was significantly reduced in both IFN-gamma-/- and IFN-gamma+/- mice. The data indicate that IFN-gamma hyperproduction is required for lupus development, presumably by increasing MHC expression and autoantigen presentation to otherwise quiescent nontolerant anti-self T cells, and also by promoting local immune and inflammatory processes.
Microscopic correlates of macroscopic optical property changes during thermal coagulation of myocardium (1990)

The effects of thermal coagulation on the macroscopic optical transport parameters that govern the distribution of light in tissues were studied. The optical absorption coefficients, pa, and the reduced scattering coefficients, j.ts (1-g), were deduced from measurements of total transmission and total reflectance of HeNe laser radiation ( = 633 and 594 nm) directed to thin slices of dog myocardium heated in vitro. The first optical changes were detected at 45°and, at temperatures above 65°, there was a 2-fold increase in absorption and a 7-fold increase in scattering. Transmission electron microscopy of laser-induced thermally coagulated lesions in rat myocardium (cw argon ion, = 514 nm) revealed ultrastructural alterations that were considered responsible for the increased scattering based on Mie theory. These microscopic alterations included disruption of mitochondria to form aggregates of electron dense granules and granular transformation of thermally coagulated proteins of the sarcomeres and cytoplasm. Our preliminary analyses suggest that the mitochondrial granules and the protein granules contribute to the increased scattering oflight in thermally coagulated myocardium.
Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform NaV1.7 (2019)

Voltage-gated sodium ion channel subtype 1.7 (Na<sub>V</sub>1.7) is a high interest target for the discovery of non-opioid analgesics. Compelling evidence from human genetic data, particularly the finding that persons lacking functional Na<sub>V</sub>1.7 are insensitive to pain, has spurred considerable effort to develop selective inhibitors of this Na<sup>+</sup> ion channel target as analgesic medicines. Recent clinical setbacks and disappointing performance of preclinical compounds in animal pain models, however, have led to skepticism around the potential of selective Na<sub>V</sub>1.7 inhibitors as human therapeutics. In this Perspective, we discuss the attributes and limitations of recently disclosed investigational drugs targeting Na<sub>V</sub>1.7 and review evidence that, by better understanding the requirements for selectivity and target engagement, the opportunity to deliver effective analgesic medicines targeting Na<sub>V</sub>1.7 endures.
Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products (1985)

Hybridomas secreting monoclonal antibodies specific for the adenovirus early region 1A (E1A) proteins were prepared from BALB/c mice immunized with a bacterial trpE-E1A fusion protein. This protein is encoded by a hybrid gene that joins a portion of the Escherichia coli trpE gene and a cDNA copy of the E1A 13S mRNA (Spindler et al., J. Virol. 49:132-141, 1984). Eighty-three hybridomas that secrete antibodies which recognize the immunogen were isolated and single cell cloned. Twenty-nine of these antibodies are specific for the E1A portion of the fusion protein. Only 12 of the monoclonal antibodies can efficiently immunoprecipitate E1A polypeptides from detergent lysates of infected cells. E1A polypeptides were analyzed on one-dimensional, sodium dodecyl sulfate-polyacrylamide gels and two-dimensional, isoelectric focusing polyacrylamide gels. The E1A proteins that are specifically immunoprecipitated by the monoclonal antibodies are heterogeneous in size and charge and can be resolved into approximately 60 polypeptide species. This heterogeneity is due not only to synthesis from multiple E1A mRNAs, but also at least in part to post-translational modification. Several of the monoclonal antibodies divide the E1A polypeptides into immunological subclasses based on the ability of the antibodies to bind to the antigen. In particular, two of the monoclonal antibodies bind to the polypeptides synthesized from the 13S E1A mRNA, but not to other E1A proteins.
Digital Paper™ for reflective displays (2003)

Abstract— Iridigm has produced the first color MEMS‐based reflective display. With dimensions of 240 × 160 pixels at 100 dpi, it exhibits good contrast and high brightness. Response times of 35 μsec have been achieved at exceptionally low power consumption, and there is no active matrix. The status of this technology is discussed.
Randomized Trees for Real-Time Keypoint Recognition (2005)

In earlier work, we proposed treating wide baseline matching of feature points as a classification problem, in which each class corresponds to the set of all possible views of such a point. We used a K-mean plus Nearest Neighbor classifier to validate our approach, mostly because it was simple to implement. It has proved effective but still too slow for real-time use. In this paper, we advocate instead the use of randomized trees as the classification technique. It is both fast enough for real-time performance and more robust. It also gives us a principled way not only to match keypoints but to select during a training phase those that are the most recognizable ones. This results in a real-time system able to detect and position in 3D planar, non-planar, and even deformable objects. It is robust to illuminations changes, scale changes and occlusions.
IMGT, the international ImMunoGeneTics information system(R) (2004)

The international ImMunoGeneTics information system (IMGT) (http://imgt.cines.fr), created in 1989, by the Laboratoire d'ImmunoGenetique Moleculaire LIGM (Universite Montpellier II and CNRS) at Montpellier, France, is a high-quality integrated knowledge resource specializing in the immunoglobulins (IGs), T cell receptors (TRs), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune systems (RPI) that belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT includes several sequence databases (IMGT/LIGM-DB, IMGT/PRIMER-DB, IMGT/PROTEIN-DB and IMGT/MHC-DB), one genome database (IMGT/GENE-DB) and one three-dimensional (3D) structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages (IMGT Marie-Paule page), and interactive tools. IMGT data are expertly annotated according to the rules of the IMGT Scientific chart, based on the IMGT-ONTOLOGY concepts. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in normal physiological and pathological situations. IMGT is used in medical research (autoimmune diseases, infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research, biotechnology related to antibody engineering (phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (clonalities, detection and follow up of residual diseases) and therapeutical approaches (graft, immunotherapy and vaccinology). IMGT is freely available at http://imgt.cines.fr.
Considering defense in depth for software applications (2004)

Despite efforts to develop processes and technologies that enhance software application security, to date, no one has found a "silver-bullet" solution or set of solutions that solve this complex problem - and there don't appear to be any on the horizon. As a result, perhaps researchers and developers should consider a defense-in-depth strategy and determine if it provides a more resilient and cost-effective approach to application security than a single line of defense. The best defense-in-depth strategy for software source and binary code would intertwine application defenses in such a manner that each defensive technique interlocks with and supports all the others. Of necessity, this conceptualization for interlocking defense Would not relieve the development team of the need to maintain best practices for secure software development and software development in general.
Selective Surface Functionalization of Silicon Nanowires via Nanoscale Joule Heating (2007)

In this letter, we report a novel approach to selectively functionalize the surface of silicon nanowires located on silicon-based substrates. This method is based upon highly localized nanoscale Joule heating along silicon nanowires under an applied electrical bias. Numerical simulation shows that a high-temperature (>800 K) with a large thermal gradient can be achieved by applying an appropriate electrical bias across silicon nanowires. This localized heating effect can be utilized to selectively ablate a protective polymer layer from a region of the chosen silicon nanowire. The exposed surface, with proper postprocessing, becomes available for surface functionalization with chemical linker molecules, such as 3-mercaptopropyltrimethoxysilanes, while the surrounding area is still protected by the chemically inert polymer layer. This approach is successfully demonstrated on silicon nanowire arrays fabricated on SOI wafers and visualized by selective attachment of gold nanoparticles.
The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. (1992)

Resistance against the cytotoxic actions of tumor necrosis factor alpha (TNF) is an active process requiring the synthesis of TNF-inducible proteins. The specific TNF-induced proteins so far identified (manganese superoxide dismutase and plasminogen activator inhibitor type 2) as having a role in resistance against TNF cytotoxicity are able to confer only partial protection to cells, suggesting that other genes are involved. A20 is a TNF-induced primary response gene which encodes a novel zinc finger protein. In this report we demonstrate that A20 protein is induced by TNF in a variety of cells. A survey of A20 expression in human breast carcinoma cell lines that are either sensitive or resistant to TNF cytotoxicity revealed increased expression of A20 message and protein in TNF-resistant cells. Constitutive expression of A20 after stable transfection of NIH 3T3 and WEHI 164 cells results in significant, but partial, resistance to TNF cytotoxicity. This work gives additional support to a role for TNF-induced immediate early response genes in protecting cells from TNF-induced death.
Microembolization techniques of vascular occlusion: radiologic, pathologic, and clinical correlation. (1981)

Vascular occlusion is described using microemboli of a predetermined size for the treatment of neoplastic conditions with a "capillary barrier." Particulated microemboli of either 40--60 micron Gelfoam powder or 200--1,000 micron polyvinyl alcohol foam (PVA) are best. Fluid embolic agents such as silicone fluid are used in lesions without a capillary barrier. The radiographic, pathologic, and clinical results in three patients are described in detail. Microembolization is useful in the treatment of neoplastic conditions for it produces tumor necrosis in addition to hemostasis.
Effect of Dehydroepiandrosterone and the Antiestrogen EM-800 on Growth of Human ZR-75-1 Breast Cancer Xenografts (1998)

DHEA and EM-800 independently suppressed the growth of E1-stimulated ZR-75-1 xenograft tumors in nude mice. Administration of DHEA at the defined doses did not alter the inhibitory effect of EM-800.
Label-free detection of small-molecule–protein interactions by using nanowire nanosensors (2005)

Development of miniaturized devices that enable rapid and direct analysis of the specific binding of small molecules to proteins could be of substantial importance to the discovery of and screening for new drug molecules. Here, we report highly sensitive and label-free direct electrical detection of small-molecule inhibitors of ATP binding to Abl by using silicon nanowire field-effect transistor devices. Abl, which is a protein tyrosine kinase whose constitutive activity is responsible for chronic myelogenous leukemia, was covalently linked to the surfaces of silicon nanowires within microfluidic channels to create active electrical devices. Concentration-dependent binding of ATP and concentration-dependent inhibition of ATP binding by the competitive small-molecule antagonist STI-571 (Gleevec) were assessed by monitoring the nanowire conductance. In addition, concentration-dependent inhibition of ATP binding was examined for four additional small molecules, including reported and previously unreported inhibitors. These studies demonstrate that the silicon nanowire devices can readily and rapidly distinguish the affinities of distinct small-molecule inhibitors and, thus, could serve as a technology platform for drug discovery.
Infusion of cytomegalovirus (CMV)–specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy (2002)

We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8 stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom one was infected by a CMV strain that was genotypically ganciclovir resistant, had received unsuccessful antiviral chemotherapy for more than 4 weeks. CMV-specific lines had been prepared by repetitive stimulation with CMV antigen, which increased the percentage of CMV-specific T cells and ablated alloreactivity completely even against patients mismatched for 1 to 3 HLA antigens. After transfer of 10(7) T cells/m(2) at a median of 120 days (range, 79-479 days) after transplantation, no side effects were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped significantly in all 7 evaluable patients, with a maximal reduction after a median of 20 days (range, 5-31 days). In 2 patients with high virus load, the antiviral effect was only transient. One of these patients received a second T-cell infusion, which cleared the virus completely. At a median of 11 days after transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and an increase in CMV-specific CD4(+) T cells was demonstrated in 5 patients. In 6 patients, 1.12 to 41 CMV-specific CD8(+) T cells/microL blood were detected at a median of 13 days after transfer, with an increase in all patients lacking CMV-specific CD8(+) T cells prior to transfer. Hence, anti-CMV cellular therapy was successful in 5 of 7 patients, whereas in 2 of 7 patients, who received an intensified immune suppression at the time of or after T-cell therapy, only transient reductions in virus load were obtained.
Protein–protein interactions: General trends in the relationship between binding affinity and interfacial buried surface area (2013)

Protein-protein interactions play key roles in many cellular processes and their affinities and specificities are finely tuned to the functions they perform. Here, we present a study on the relationship between binding affinity and the size and chemical nature of protein-protein interfaces. Our analysis focuses on heterodimers and includes curated structural and thermodynamic data for 113 complexes. We observe a direct correlation between binding affinity and the amount of surface area buried at the interface. For a given amount of surface area buried, the binding affinity spans four orders of magnitude in terms of the dissociation constant (Kd ). Across the entire dataset, we observe no obvious relationship between binding affinity and the chemical composition of the interface. We also calculate the free energy per unit surface area buried, or "surface energy density," of each heterodimer. For interfacial surface areas between 500 and 2000 Å(2) , the surface energy density decreases as the buried surface area increases. As the buried surface area increases beyond about 2000 Å(2) , the surface energy density levels off to a constant value. We believe that these analyses and data will be useful for researchers with an interest in understanding, designing or inhibiting protein-protein interfaces.
A surface on the androgen receptor that allosterically regulates coactivator binding (2007)

Current approaches to inhibit nuclear receptor (NR) activity target the hormone binding pocket but face limitations. We have proposed that inhibitors, which bind to nuclear receptor surfaces that mediate assembly of the receptor's binding partners, might overcome some of these limitations. The androgen receptor (AR) plays a central role in prostate cancer, but conventional inhibitors lose effectiveness as cancer treatments because anti-androgen resistance usually develops. We conducted functional and x-ray screens to identify compounds that bind the AR surface and block binding of coactivators for AR activation function 2 (AF-2). Four compounds that block coactivator binding in solution with IC(50) approximately 50 microM and inhibit AF-2 activity in cells were detected: three nonsteroidal antiinflammatory drugs and the thyroid hormone 3,3',5-triiodothyroacetic acid. Although visualization of compounds at the AR surface reveals weak binding at AF-2, the most potent inhibitors bind preferentially to a previously unknown regulatory surface cleft termed binding function (BF)-3, which is a known target for mutations in prostate cancer and androgen insensitivity syndrome. X-ray structural analysis reveals that 3,3',5-triiodothyroacetic acid binding to BF-3 remodels the adjacent interaction site AF-2 to weaken coactivator binding. Mutation of residues that form BF-3 inhibits AR function and AR AF-2 activity. We propose that BF-3 is a previously unrecognized allosteric regulatory site needed for AR activity in vivo and a possible pharmaceutical target.