gebhart/patrepeval huggingface dataset:
Inhibition of Ced-3/ICE-related Proteases Does Not Prevent Cell Death Induced by Oncogenes, DNA Damage, or the Bcl-2 Homologue Bak (1997)

There is increasing evidence for a central role in mammalian apoptosis of the interleukin-1 beta-converting enzyme (ICE) family of cysteine proteases, homologues of the product of the nematode "death" gene, ced-3. Ced-3 is thought to act as an executor rather than a regulator of programmed cell death in the nematode. However, it is not known whether mammalian ICE-related proteases (IRPs) are involved in the execution or the regulation of mammalian apoptosis. Moreover, an absolute requirement for one or more IRPs for mammalian apoptosis has yet to be established. We have used two cell-permeable inhibitors of IRPs, Z-Val-Ala-Asp.fluoromethylketone (ZVAD.fmk) and t-butoxy carbonyl-Asp.fluoromethylketone (BD.fmk), to demonstrate a critical role for IRPs in mammalian apoptosis induced by several disparate mechanisms (deregulated oncogene expression, ectopic expression of the Bcl-2 relative Bak, and DNA damage-induced cell death). In all instances, ZVAD.fmk and BD.fmk treatment inhibits characteristic biochemical and morphological events associated with apoptosis, including cleavage of nuclear lamins and poly-(ADP-ribose) polymerase, chromatin condensation and nucleosome laddering, and external display of phosphatidylserine. However, neither ZVAD.fmk nor BD.fmk inhibits the onset of apoptosis, as characterized by the onset of surface blebbing; rather, both act to delay completion of the program once initiated. In complete contrast, IGF-I and Bcl-2 delay the onset of apoptosis but have no effect on the kinetics of the program once initiated. Our data indicate that IRPs constitute part of the execution machinery of mammalian apoptosis induced by deregulated oncogenes, DNA damage, or Bak but that they act after the point at which cells become committed to apoptosis or can be rescued by survival factors. Moreover, all such blocked cells have lost proliferative potential and all eventually die by a process involving cytoplasmic blebbing.
Gene Silencing in Androgen-Responsive Prostate Cancer Cells from the Tissue-Specific Prostate-Specific Antigen Promoter (2004)

Abstract The success of gene therapy using a RNA interference approach relies on small interfering RNA (siRNA) expression from a highly tissue-specific RNA polymerase II promoter rather than from ubiquitous RNA polymerase III. Accordingly, we have developed a prostate-specific vector that expresses siRNAs from the human prostate-specific antigen promoter, a RNA polymerase II promoter. Our data demonstrate androgen-dependent and tissue-specific siRNA-mediated gene silencing in the androgen-responsive prostate cancer cell line, LNCaP. The biological significance was evidenced by altered apoptotic activity through the inhibition of the apoptosis-related regulatory gene. These results demonstrate that siRNA-mediated gene silencing from a tissue-specific RNA polymerase II promoter could be a potential tool for tissue-specific gene therapy.
The accuracy of Norton's empirical approximations for groundwave attenuation (1983)

In his papers on the numerical evaluation of the Sommerfeld surface wave attenuation, Norton gave the results primarily in graphical and tabular form, but he also included some empirical approximations. These approximate expressions are simple and readily programmed on hand calculators, while the exact expression involves the complementary error function with complex argument. The accuracy of the approximations is therefore of practical interest; the results of numerical checks of the accuracy of the various approximate expressions are reported here.
Cytokine-Directed Therapy in Asthma (2004)

Increasing evidence of the pathological roles of multiple cytokines in orchestrating and perpetuating inflammation in asthma has prompted the evaluation of novel anti-cytokine therapies. Anti-IL-5 antibody markedly reduces peripheral blood and airway eosinophils, but does not appear to be effective in symptomatic asthma. Inhibition of IL-4, despite promising early results in asthma has been discontinued and blocking IL-13 might be more effective. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery produces side effects. Inhibition of TNF-alpha may be useful in severe asthma. Agents that target IL-13 are still early in the development process. Many chemokines are involved in the inflammatory response of asthma and several small molecule inhibitors of chemokine receptors are in development. CCR3 antagonists, which block eosinophil chemotaxis, are in clinical development for asthma therapy. Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side effects with these non-specific inhibitors may be reduced by the inhaled route.
The launching of radial cylindrical surface waves by a circumferential slot (1959)

The efficiency with which radial cylindrical surface waves may be launched by a circumferential slot is investigated theoretically and experimentally. The radius of the slot has been found to affect the launching efficiency very little. An optimum efficiency of about 68% is obtainable with a slot of 2cm radius above a 58-ohm reactive surface.
Peptide, Peptidomimetic, and Small-molecule Antagonists of the p53–HDM2 Protein–Protein Interaction (2006)

Modulation of intracellular protein-protein interactions has been - and remains - a challenging goal for the discovery and development of small-molecule therapeutic agents. Progress in the pharmacological targeting and understanding at the molecular level of one such interaction that is relevant to cancer drug research, viz. that between the tumour suppressor protein p53 and its negative regulator HDM2, is reviewed here. The first X-ray crystal structure of a complex between a small peptide from the trans-activation domain of p53 and the N-terminal domain of HDM2 was reported almost 10 years ago. The nature of this interaction, which involves just three residue side chains in the p53 peptide ligand and a compact hydrophobic binding pocket in the HDM2 receptor, together with the attractive concept of reactivating the anti-proliferative functions of p53 in tumour cells, has spurned a great deal of effort aimed at finding drug-like antagonists of this interaction. A variety of approaches, including both structure-guided peptidomimetic and de novo design, as well as high through-put screening campaigns, have provided a wealth of leads that might be turned into actual drugs. There is still some way to go as far as optimisation and preclinical development of such leads is concerned, but it is clear already now that antagonists of the p53-HDM2 protein-protein interaction have a good chance of ultimately being successful in providing a new anti-cancer therapy modality, both in monotherapy and to potentiate the effectiveness of existing chemotherapies.
Oral Manifestation of Secondary Syphilis in Ethnic Chinese: 21 case reports. (2001)

A total of 21 cases of secondary syphilis presenting mostly as painless oral lesions in ethnic Chinese are reported. All the patients were first diagnosed on presentation with oral lesions. Three cases were initially misdiagnosed as oral candidosis but confirmed as syphilitic infection after biopsy and serology. The most common site of the lesion was the tongue. The significance of oral manifestations of syphilis and the dentist's role in the early diagnosis of syphilis is discussed.
Plasma Kallikrein-Kinin System in Patients with Uncomplicated Sepsis and Septic Shock-Comparison with Cardiogenic Shock (1987)

Alterations of the kallikrein-kinin system consistent with activation and increased consumption have been reported in septic patients and it has been suggested that this activation could contribute to the development of septic shock. The aim of this work was to confirm these alterations in septic patients and to investigate the possible existence of similar changes in subjects developing cardiogenic shock secondary to myocardial infarction as a model of non septic shock. Patients with septic shock, especially in fatal cases, showed a highly significant decrease in levels of factor XII, prekallikrein, high molecular weight kininogen (HMW-kininogen), alpha 2-macroglobulin (alpha 2-M) and antithrombin III (AT-III). C1-esterase inhibitor (C1-INH) activity was increased in uncomplicated sepsis but came back to normal or was slightly decreased in septic shock. Components and inhibitors of the kallikrein-kinin system were within normal limits in patients with cardiogenic shock. Our findings support the idea of a contribution of the kallikrein-kinin system to the development of septic shock though this system does not seem to play a significant role in the pathogenesis of cardiogenic shock or seem to be altered as a consequence of it.
A Role for a Helical Connector between Two Receptor Binding Sites of a Long-chain Peptide Hormone (2000)

The conformational freedom of single-chain peptide hormones, such as the 41-amino acid hormone corticotropin releasing factor (CRF), is a major obstacle to the determination of their biologically relevant conformation, and thus hampers insights into the mechanism of ligand-receptor interaction. Since N- and C-terminal truncations of CRF lead to loss of biological activity, it has been thought that almost the entire peptide is essential for receptor activation. Here we show the existence of two segregated receptor binding sites at the N and C termini of CRF, connection of which is essential for receptor binding and activation. Connection of the two binding sites by highly flexible epsilon-aminocaproic acid residues resulted in CRF analogues that remained full, although weak agonists (EC(50): 100-300 nM) independent of linker length. Connection of the two sites by an appropriate helical peptide led to a very potent analogue, which adopted, in contrast to CRF itself, a stable, monomer conformation in aqueous solution. Analogues in which the two sites were connected by helical linkers of different lengths were potent agonists; their significantly different biopotencies (EC(50): 0.6-50 nM), however, suggest the relative orientation between the two binding sites rather than the maintenance of a distinct distance between them to be essential for a high potency.
Query clustering using click-through graph (2009)

In this paper we describe a problem of discovering query clusters from a click-through graph of web search logs. The graph consists of a set of web search queries, a set of pages selected for the queries, and a set of directed edges that connects a query node and a page node clicked by a user for the query. The proposed method extracts all maximal bipartite cliques (bicliques) from a click-through graph and compute an equivalence set of queries (i.e., a query cluster) from the maximal bicliques. A cluster of queries is formed from the queries in a biclique. We present a scalable algorithm that enumerates all maximal bicliques from the click-through graph. We have conducted experiments on Yahoo web search queries and the result is promising.
Novel fingerprint scanning arrays using polysilicon TFT's on glass and polymer substrates (1997)

Novel fingerprint scanning arrays based upon capacitance sensing have been made. Each sensor element consists of a capacitor electrode and two poly-Si thin film transistors for addressing and read out. The devices were fabricated on glass, polyimide and polyethersulphone substrates using a low temperature (<250/spl deg/C) process.
Electrochemically Triggered Assembly of Films: A One‐Pot Morphogen‐Driven Buildup (2011)

Polymers that “click”: A polymer film is obtained by the CuI-catalyzed Sharpless click reaction between two polymers, bearing either azide or alkyne groups, both present simultaneously in a CuII solution (see picture). The CuI morphogen is generated at an electrode by applying an adequate potential. This concept can be extended to supramolecular films formed by coordination complexes. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Moderate Hypothermia in the Treatment of Patients With Severe Middle Cerebral Artery Infarction (1998)

Moderate hypothermia in the treatment of severe cerebral ischemia is not associated with severe side effects. Moderate hypothermia can help to control critically elevated ICP values in severe space-occupying edema after MCA stroke and may improve clinical outcome in these patients.
Role of STAT2 in the Alpha Interferon Signaling Pathway (1995)

We have isolated U6A, a mutant cell line which lacks the STAT2 subunit of the transcription factor interferon (IFN)-stimulated gene factor 3 (ISGF3). The response of U6A cells to IFN-alpha is almost completely defective, but the response to IFN-gamma is normal. Complementation of U6A cells with a cDNA encoding STAT2 restores the IFN-alpha response, proving that STAT2 is required in this pathway. Binding of IFNs to their receptors triggers tyrosine phosphorylation and activation of the receptors, JAK family kinases, STAT1, and STAT2. In IFN-alpha-treated U6A cells, phosphorylation of the essential tyrosine kinases TYK2 and JAK1 is normal, but the phosphorylation of STAT1 is weak. A mutant STAT2 protein in which the phosphorylated tyrosine at position 690 is changed to phenylalanine does not restore normal phosphorylation of STAT1 in response to IFN-alpha. The dependence of STAT1 phosphorylation on the presence of STAT2 but not vice versa (T. Improta, C. Schindler, C. M. Horvath, I. M. Kerr, G. R. Stark, and J. E. Darnell, Jr., Proc. Natl. Acad. Sci. USA 91:4776-4780, 1994) indicates that in the formation of ISGF3, these two proteins may be phosphorylated sequentially in response to IFN-alpha and that phosphorylated STAT2 may be required to allow unphosphorylated STAT1 to bind to the activated IFN-alpha receptor.
In VitroAntiviral Characteristics of HIV-1 Attachment Inhibitor BMS-626529, the Active Component of the Prodrug BMS-663068 (2012)

BMS-663068 is the phosphonooxymethyl prodrug of BMS-626529, a novel small-molecule attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4(+) T cells. The activity of BMS-626529 is virus dependent, due to heterogeneity within gp120. In order to better understand the anti-HIV-1 spectrum of BMS-626529 against HIV-1, in vitro activities against a wide variety of laboratory strains and clinical isolates were determined. BMS-626529 had half-maximal effective concentration (EC(50)) values of <10 nM against the vast majority of viral isolates; however, susceptibility varied by >6 log(10), with half-maximal effective concentration values in the low pM range against the most susceptible viruses. The in vitro antiviral activity of BMS-626529 was generally not associated with either tropism or subtype, with few exceptions. Measurement of the binding affinity of BMS-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life. Finally, in two-drug combination studies, BMS-626529 demonstrated additive or synergistic interactions with antiretroviral drugs of different mechanistic classes. These results suggest that BMS-626529 should be active against the majority of HIV-1 viruses and support the continued clinical development of the compound.
Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma (2016)

Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms (complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis) and direct apoptosis with crosslinking. These mechanisms may also target nonplasma cells that express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulations. Peripheral blood (PB) and bone marrow (BM) from patients with relapsed/refractory myeloma from 2 daratumumab monotherapy studies were analyzed before and during therapy and at relapse. Regulatory B cells and myeloid-derived suppressor cells, previously shown to express CD38, were evaluated for immunosuppressive activity and daratumumab sensitivity in the myeloma setting. A novel subpopulation of regulatory T cells (Tregs) expressing CD38 was identified. These Tregs were more immunosuppressive in vitro than CD38-negative Tregs and were reduced in daratumumab-treated patients. In parallel, daratumumab induced robust increases in helper and cytotoxic T-cell absolute counts. In PB and BM, daratumumab induced significant increases in CD8(+):CD4(+) and CD8(+):Treg ratios, and increased memory T cells while decreasing naïve T cells. The majority of patients demonstrated these broad T-cell changes, although patients with a partial response or better showed greater maximum effector and helper T-cell increases, elevated antiviral and alloreactive functional responses, and significantly greater increases in T-cell clonality as measured by T-cell receptor (TCR) sequencing. Increased TCR clonality positively correlated with increased CD8(+) PB T-cell counts. Depletion of CD38(+) immunosuppressive cells, which is associated with an increase in T-helper cells, cytotoxic T cells, T-cell functional response, and TCR clonality, represents possible additional mechanisms of action for daratumumab and deserves further exploration.
Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus. (1991)

The fine specificity of a reference human anti-Ro/SSA autoantibody-containing serum has been analyzed by using sequential overlapping octapeptides from the human 60-kDa Ro/SSA antigen. From preliminary data, the most antigenic octapeptide in the carboxyl-terminal 120 amino acid residues of Ro/SSA shares seven of eight amino acids with the nucleocapsid (N) protein from the Indiana serotype of vesicular stomatitis virus. A sequence comparison of Ro/SSA and N has unexpectedly revealed six small peptides shared by Ro/SSA and N. Fine specificity analysis with 531 octapeptides from the Ro/SSA sequence demonstrates that five of the six shared small peptides are bound by anti-Ro/SSA (P = 0.00017). A more powerful association is not present in 12,476 protein sequences similarly evaluated. In addition, the inclusion of single-residue gaps in Ro/SSA enlarges the sequence similarity of Ro/SSA and N for three of the five small shared antigenic peptides. This additional level of sequence similarity between Ro/SSA and N is unlikely to be the result of chance (P less than 0.0002). While a number of models may explain these data, including independent immune responses to N and Ro/SSA, these results are also consistent with anti-Ro/SSA autoantibodies being the consequence of a specific viral exposure.
Nerve Growth Factor Activation of Nuclear Factor κB through Its p75 Receptor Is an Anti-apoptotic Signal in RN22 Schwannoma Cells (2000)

Recent evidence indicates that nerve growth factor (NGF) produces its effects through signaling contributions from both TrkA and the p75 receptor. In contrast to its trophic actions through TrkA, NGF binding to p75 has been shown to activate programmed cell death through a mechanism involving the stress kinase JNK. However, this receptor also activates nuclear factor κB (NF-κB), the role of which has yet to be determined. We investigated the function of p75-mediated NF-κB stimulation in regulating cell survival in the rat schwannoma cell line RN22, which expresses p75, but not TrkA. Gel shift assays demonstrated activation of NF-κB in response to NGF within 30 min and lasting at least 4 h. NGF also stimulated JNK in the cells (detected by <i>in vitro</i> kinase assays) with a similar time course. Preventing activation of NF-κB with the specific inhibitor SN50 resulted in NGF-induced cell loss. Similarly, transfection of the cells with a mutant form of the endogenous NF-κB inhibitor (IκBαΔN), which cannot be degraded and therefore remains bound to NF-κB, preventing its activation, resulted in a significant increase in the number of apoptotic cells following NGF treatment. These results suggest that NGF activation of NF-κB through the p75 receptor promotes survival, counterbalancing the pro-apoptotic signal.
Fine-scale detection of population-specific linkage disequilibrium using haplotype entropy in the human genome (2010)

The haplotype entropy method is powerful for detecting population-specific LD embedded in short regions and should contribute to further studies aiming to decipher the evolutionary histories of modern humans.
Integrated Microfluidic System Enabling Protein Digestion, Peptide Separation, and Protein Identification (2001)

An integrated platform is presented for rapid and sensitive protein identification by on-line protein digestion and analysis of digested proteins using electrospray ionization mass spectrometry or transient capillary isotachophoresis/capillary zone electrophoresis with mass spectrometry detection. A miniaturized membrane reactor is constructed by fabricating the microfluidic channels on a poly(dimethylsiloxane) substrate and coupling the microfluidics to a poly(vinylidene fluoride) porous membrane with the adsorbed trypsin. On the basis of he large surface area-to-volume ratio of porous membrane media, adsorbed trypsin onto the poly(vinylidene fluoride) membrane is employed for achieving ultrahigh catalytic turnover. The extent of protein digestion in a miniaturized membrane reactor can be directly controlled by the residence time of protein analytes inside the trypsin-adsorbed membrane, the reaction temperature, and the protein concentration. The resulting peptide mixtures can either be directly analyzed using electrospray ionization mass spectrometry or further concentrated and resolved by electrophoretic separations prior to the mass spectrometric analysis. This microfluidic system enables rapid identification of proteins in minutes instead of hours, consumes very little sample (nanogram or less), and provides on-line interface with upstream protein separation schemes for the analysis of complex protein mixtures such as cell lysates.
Effect of Liberibacter Infection (Huanglongbing or “Greening” Disease) of Citrus on Orange Juice Flavor Quality by Sensory Evaluation (2010)

Assumptions that juice made from oranges harvested from Huanglongbing (from infection with Liberibacter sp.) affected trees is off-flavored appeared to be generally more true for Hamlin juice than for Midsweet or Valencia, especially for Hamlin juice made from symptomatic fruit. For Midsweet and Valencia, flavor differences between juice made from fruit harvested from diseased or healthy trees varied greatly between trees, season, and even processing method. Under a commercial processing situation, where juice is blended from several varieties, seasons, and multiple locations, it is expected that off-flavor will not be a major problem.