gebhart/patrepeval huggingface dataset:
Noncytolytic Control of Viral Infections by the Innate and Adaptive ImmuneResponse (2001)

This review describes the contribution of noncytolytic mechanisms to the control of viral infections with a particular emphasis on the role of cytokines in these processes. It has long been known that most cell types in the body respond to an incoming viral infection by rapidly secreting antiviral cytokines such as interferon alpha/beta (IFN-alpha/beta). After binding to specific receptors on the surface of infected cells, IFN-alpha/beta has the potential to trigger the activation of multiple noncytolytic intracellular antiviral pathways that can target many steps in the viral life cycle, thereby limiting the amplification and spread of the virus and attenuating the infection. Clearance of established viral infections, however, requires additional functions of the immune response. The accepted dogma is that complete clearance of intracellular viruses by the immune response depends on the destruction of infected cells by the effector cells of the innate and adaptive immune system [natural killer (NK) cells and cytotoxic T cells (CTLs)]. This notion, however, has been recently challenged by experimental evidence showing that much of the antiviral potential of these cells reflects their ability to produce antiviral cytokines such as IFN-gamma and tumor necrosis factor (TNF)-alpha at the site of the infection. Indeed, these cytokines can purge viruses from infected cells noncytopathically as long as the cell is able to activate antiviral mechanisms and the virus is sensitive to them. Importantly, the same cytokines also control viral infections indirectly, by modulating the induction, amplification, recruitment, and effector functions of the immune response and by upregulating antigen processing and display of viral epitopes at the surface of infected cells. In keeping with these concepts, it is not surprising that a number of viruses encode proteins that have the potential to inhibit the antiviral activity of cytokines.
The validity of an essay test of clinical judgment (1990)

Log in or Register Subscribe to journalSubscribe Get new issue alertsGet alerts Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. Subscribe to eTOC Secondary Logo Journal Logo All Articles Images Videos Podcasts Blogs Advanced Search Toggle navigation Subscribe Register Login Articles & Issues Current IssuePrevious IssuesPublished Ahead-of-Print Collections Editorials of Laura Weiss Roberts, MD, MAAM Last PageCOVID-19 and Medical EducationAddressing Race and Racism in Medical EducationeBooksView All For Authors Submit a ManuscriptInformation for AuthorsLanguage Editing ServicesAuthor Permissions Journal Info About the JournalAbout the AAMCJournal MastheadSubmit a ManuscriptAdvertising InformationSubscription ServicesReprints and Back IssuesClassified AdsRights and PermissionsFor ReviewersFor MediaFor Trainees All Articles Images Videos Podcasts Blogs Advanced Search
Transforming DNA sequences of human hepatocellular carcinomas, their distribution and relationship with hepatitis B virus sequence in human hepatomas. (1988)

Several related human transforming DNA sequences, hhc, and a putative normal liver homologue, c-hhc, have been molecularly cloned from the genomic DNAs of individual African and Asian hepatomas and from normal liver respectively. hhcM (Mahlavu) and hhcK3 (Korean), but not c-hhc, transformed NIH3T3 cells in DNA-mediated gene transfer assays. Transformed cells were found tumorigenic in athymic NIH Swiss nu/nu mice. In view of recent epidemiological studies implicating hepatitis B virus (HBV) infection early in life as causative for the eventual development of primary hepatocellular carcinoma in humans in Southeast Asia, the Far-East, and certain areas of Africa, we hereby analyzed the relationship between these hhcs and HBV in a survey of 20 hepatomas for DNA sequences homologous to hhcM and HBV by sequential hybridizations against [32p]hhcM and [32p]HBV probes. hhcM related DNA sequence were found highly amplified in 80% of the 20 hepatomas but HBV DNA sequence was rare or low. hhcM lends itself as a marker for human hepatomas. However, overall results indicated that patients with integrated HBV DNA sequences showed high copy number of hhcM sequence. Furthermore, EcoR1-restricted hepatoma DNAs showed that HBV and hhcM DNA sequences resided at different fragments in hepatomas. Our results suggest that HBV contributes to hepatocarcinogenesis probably via an activation mechanism involving possibly an integration or transient interaction of HBV DNA with hepatocyte DNA sequences, leading to recombination and eventual amplifications of the hhcM sequence in Mahlavu.
Optimization of Perturb and Observe Maximum Power Point Tracking Method (2005)

Maximum power point tracking (MPPT) techniques are used in photovoltaic (PV) systems to maximize the PV array output power by tracking continuously the maximum power point (MPP) which depends on panels temperature and on irradiance conditions. The issue of MPPT has been addressed in different ways in the literature but, especially for low-cost implementations, the perturb and observe (P&O) maximum power point tracking algorithm is the most commonly used method due to its ease of implementation. A drawback of P&O is that, at steady state, the operating point oscillates around the MPP giving rise to the waste of some amount of available energy; moreover, it is well known that the P&O algorithm can be confused during those time intervals characterized by rapidly changing atmospheric conditions. In this paper it is shown that, in order to limit the negative effects associated to the above drawbacks, the P&O MPPT parameters must be customized to the dynamic behavior of the specific converter adopted. A theoretical analysis allowing the optimal choice of such parameters is also carried out. Results of experimental measurements are in agreement with the predictions of theoretical analysis.
HIV‐1 Infection in Zambian Children Impairs the Development and Avidity Maturation of Measles Virus–Specific Immunoglobulin G after Vaccination and Infection (2009)

Lower antibody quality and quantity in HIV-infected children after measles vaccination raise challenges for assuring the long-term protection of these children. Antibody quality in children receiving antiretroviral therapy requires assessment.
Expanding the repertoire of pyrrolidyl PNA analogues for DNA/RNA hybridization selectivity: aminoethylpyrrolidinone PNA (aepone-PNA) (2003)

New PNA analogues derived from aminoethylpyrrolidin-5-one backbone show stabilization of aepone-PNA:DNA hybrids and destabilization of the corresponding RNA hybrids compared to unmodified PNA.
An Anti-CD3 Single-chain Immunotoxin with a Truncated Diphtheria Toxin Avoids Inhibition by Pre-existing Antibodies in Human Blood (1995)

Diphtheria toxin (DT) is often used in the construction of immunotoxins. One potential problem using DT-based immunotoxins is the pre-existing anti-DT antibodies present in human blood due to vaccination. The present study examined the effect of human serum with pre-existing anti-DT antibodies on the toxicity of UCHT1-CRM9, an immunotoxin directed against CD3 molecules on T-lymphocytes. Sera with detectable anti-DT antibodies at 1:100 or greater dilutions inhibited the immunotoxin toxicity. Experiments with radio-labeled UCHT1-CRM9 indicate that anti-DT antibodies partially block its binding to the cell surface as well as inhibit the translocation from the endosome to the cytosol. The inhibitory effect could be adsorbed using a full-length DT mutant or B-subfragment. A C-terminal truncation mutant could not adsorb the inhibitory effect, suggesting that the last 150 amino acids contain the epitope(s) recognized by the inhibitory antibodies. Therefore, an anti-CD3 single-chain immunotoxin, sFv-DT390, was made with a truncated DT. The IC50 of sFv-DT390 was 4.8 x 10(-11) M, 1/16 the potency of the divalent UCHT1-CRM9. More importantly, sFv-DT390 toxicity was only slightly affected by the anti-DT antibodies in human sera.
ChemInform Abstract: SYNTHESIS OF 5,7‐DIAMINOPYRAZOLO(1,5‐A)PYRIMIDINES (1985)

Abstract Die Kondensation des Ma‐ ‐ londiimidsäurediethylesters (I) mit Aminopyrazolen (H) führt zum im Titel genannten Heterocyclus (III).
Proteins in Mesoporous Silicates (2008)

Mesoporous silicates (MPS) have an ordered pore structure with dimensions comparable to many biological molecules. They have been extensively explored as supports for proteins and enzymes in biocatalytic applications. Since their initial discovery, novel syntheses methods have led to precise control over pore size and structure, particle size, chemical composition, and stability, thus allowing the adsorption of a wide variety of biological macromolecules, such as heme proteins, lipases, antibody fragments, and proteases, into their structures. This Review discusses the application of ordered, large-pore, functionalized mesoporous silicates to immobilize proteins for biocatalysis.
Depletion of B Cells in Murine Lupus: Efficacy and Resistance (2007)

In mice, genetic deletion of B cells strongly suppresses systemic autoimmunity, providing a rationale for depleting B cells to treat autoimmunity. In fact, B cell depletion with rituximab is approved for rheumatoid arthritis patients, and clinical trials are underway for systemic lupus erythematosus. Yet, basic questions concerning mechanism, pathologic effect, and extent of B cell depletion cannot be easily studied in humans. To better understand how B cell depletion affects autoimmunity, we have generated a transgenic mouse expressing human CD20 on B cells in an autoimmune-prone MRL/MpJ-Fas(lpr) (MRL/lpr) background. Using high doses of a murine anti-human CD20 mAb, we were able to achieve significant depletion of B cells, which in turn markedly ameliorated clinical and histologic disease as well as antinuclear Ab and serum autoantibody levels. However, we also found that B cells were quite refractory to depletion in autoimmune-prone strains compared with non-autoimmune-prone strains. This was true with multiple anti-CD20 Abs, including a new anti-mouse CD20 Ab, and in several different autoimmune-prone strains. Thus, whereas successful B cell depletion is a promising therapy for lupus, at least some patients might be resistant to the therapy as a byproduct of the autoimmune condition itself.
Glutamate excitotoxicity and therapeutic targets for amyotrophic lateral sclerosis (2007)

Two forms of amyotrophic lateral sclerosis (ALS) are known, the familial (FALS), due in part to mutations in superoxide dismutase 1 (SOD1), and the sporadic (SALS), which accounts for > 90% of all cases. The cause of SALS is not known, but excitotoxicity due to overactivation of glutamate receptors may mediate the motor neuron degeneration in the spinal cord, which is the hallmark of this disease. Overactivation of calcium-permeable alpha-amino-3-hydroxy-5-isoxazole propionate receptors lacking the subunit glutamate receptor 2, leading to an increase in calcium cytoplasmic concentration, seems to play an important role in the mechanism of neuronal death. The knowledge of this mechanism, in addition to other factors, provides several possible targets for therapeutic strategies that are reviewed in this article. Some of these strategies have proven to be partially effective in both human mutant superoxide dismutase 1 transgenic rodents (FALS model) and the few existing in vivo models of spinal motor neurodegeneration induced by excitotoxicity (SALS models), although observable benefits are still to be shown in clinical trials.
Interactive video asset retrieval using sketched queries (2014)

We present a new algorithm for searching video repositories using free-hand sketches. Our queries express both appearance (color, shape) and motion attributes, as well as semantic properties (object labels) enabling hybrid queries to be specified. Unlike existing sketch based video retrieval (SBVR) systems that enable hybrid queries of this form, we do not adopt a model fitting/optimization approach to match at query-time. Rather, we create an efficiently searchable index via a novel space-time descriptor that encapsulates all these properties. The real-time performance yielded by our indexing approach enables interactive refinement of search results within a relevance feedback (RF) framework; a unique contribution to SBVR. We evaluate our system over 700 sports footage clips exhibiting a variety of clutter and motion conditions, demonstrating significant accuracy and speed gains over the state of the art.
Context sensitivity in the detection of changes in facial emotion (2016)

In social contexts, reading subtle changes in others' facial expressions is a crucial communication skill. To measure this ability, we developed an expression-change detection task, wherein a series of pictures of changes in an individual's facial expressions within contextual scenes were presented. The results demonstrated that the detection of subtle changes was highly sensitive to contextual stimuli. That is, participants identified the direction of facial-expression changes more accurately and more quickly when they were 'appropriate'-consistent with the valence of the contextual stimulus change-than when they were 'inappropriate'. Moreover, individual differences in sensitivity to contextual stimuli were correlated with scores on the Toronto Alexithymia Scale, a commonly used measure of alexithymia tendencies. These results suggest that the current behavioural task might facilitate investigations of the role of context in human social cognition.
A New Photocleavable Linker in Solid-Phase Chemistry for Ether Cleavage (2000)

We have designed a new linker (1) for the solid-phase synthesis that cleaves ether bonds photolytically. The linker was prepared in nine steps and anchored to the support via an amide bond. Photocleavage is a two-step process in which the immobilized alcohols are released by photolytic generation of a radical that undergoes a spontaneous beta-bond scission. The pivaloyl linker (1) was found to cleave off alcohols in high yields and purities. Only traces of acid (pH approximately 5.5) are necessary for an efficient cleavage.
Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases. (1992)

The mammalian shc gene encodes two overlapping proteins of 46 and 52 kDa, each with a C-terminal Src homology 2 (SH2) domain and an N-terminal glycine/proline-rich sequence, that induce malignant transformation when overexpressed in mouse fibroblasts. p46shc, p52shc, and an additional 66-kDa shc gene product become highly tyrosine phosphorylated in Rat-2 cells transformed by the v-src or v-fps oncogene. Experiments using temperature-sensitive v-src and v-fps mutants indicate that Shc tyrosine phosphorylation is rapidly induced upon activation of the v-Src or v-Fps tyrosine kinases. These results suggest that Shc proteins may be directly phosphorylated by the v-Src and v-Fps oncoproteins in vivo. In cells transformed by v-src or v-fps, or in normal cells stimulated with epidermal growth factor, Shc proteins complex with a poorly phosphorylated 23-kDa polypeptide (p23). Activated tyrosine kinases therefore regulate the association of Shc proteins with p23 and may thereby control the stimulation of an Shc-mediated signal transduction pathway. The efficient phosphorylation of Shc proteins and the apparent induction of their p23-binding activity in v-src- and v-fps-transformed cells are consistent with the proposition that the SH2-containing Shc polypeptides are biologically relevant substrates of the oncogenic v-Src and v-Fps tyrosine kinases.
Conditional Expression of RNase P in the CyanobacteriumSynechocystis sp. PCC6803 Allows Detection of Precursor RNAs (2001)

We have constructed a strain (CT1) that expresses RNase P conditionally with the aim to analyze the in vivo tRNA processing pathway and the biological role that RNase P plays in Synechocystis 6803. In this strain, the rnpB gene, coding for the RNA subunit of RNase P, has been placed under the control of the petJ gene promoter (P(petJ)), which is repressed by copper, cell growth, and accumulation of RNase P RNA is inhibited in CT1 after the addition of copper, indicating that the regulation by copper is maintained in the chimerical P(petJ)-rnpB gene and that RNase P is essential for growth in Synechocystis. We have analyzed several RNAs by Northern blot and primer extension in CT1. Upon addition of copper to the culture medium, precursors of the mature tRNAs are detected. Furthermore, our results indicate that there is a preferred order in the action of RNase P when it processes a dimeric tRNA precursor. The precursors detected are 3'-processed, indicating that 3' processing can occur before 5' processing by RNase P. The size of the precursors suggests that the terminal CCA sequence is already present before RNase P processing. We have also analyzed other potential RNase P substrates, such as the precursors of tmRNA and 4.5 S RNA. In both cases, accumulation of larger than mature size RNAs is observed after transferring the cells to a copper-containing medium.
Local Rule-Based Explanations of Black Box Decision Systems (2018)

The recent years have witnessed the rise of accurate but obscure decision systems which hide the logic of their internal decision processes to the users. The lack of explanations for the decisions of black box systems is a key ethical issue, and a limitation to the adoption of machine learning components in socially sensitive and safety-critical contexts. %Therefore, we need explanations that reveals the reasons why a predictor takes a certain decision. In this paper we focus on the problem of black box outcome explanation, i.e., explaining the reasons of the decision taken on a specific instance. We propose LORE, an agnostic method able to provide interpretable and faithful explanations. LORE first leans a local interpretable predictor on a synthetic neighborhood generated by a genetic algorithm. Then it derives from the logic of the local interpretable predictor a meaningful explanation consisting of: a decision rule, which explains the reasons of the decision; and a set of counterfactual rules, suggesting the changes in the instance's features that lead to a different outcome. Wide experiments show that LORE outperforms existing methods and baselines both in the quality of explanations and in the accuracy in mimicking the black box.
The Amino Acid Sequence of a Hong Kong Influenza Haemagglutinin Light (HA2) Chain (1980)

The amino acid sequence of the Hong Kong haemagglutinin light chang (HA2:222 residues) is nearly complete, lacking only the definition of a highly aggregated region near the carboxyl terminal end of the chain. This unsequenced area of approx. 25 residues occurs near the carboxyl terminal end of cyanogen bromide peptide CN-I, whose structure determination is discussed in this paper. All 1/2-cystine residues present in HA2 occur in CN-I, as a proximal cluster involving residues 137, 144 and 148, and as a distal cluster involving four other 1/2-cystine within peptides. The single glycosylated asparagine in HA2 also occurs in CN-I; the carbohydrates moiety is complex. The structure of HA2 is discussed in terms of its properties, and compared with published data from haemagglutinins from other influenza strains.
Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz (1998)

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague-Dawley rats were exposed daily to sidestream cigarette smoke in a whole-body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.
Impact of ustekinumab on health‐related quality of life in Japanese patients with moderate‐to‐severe plaque psoriasis: Results from a randomized, double‐blind, placebo‐controlled phase 2 / 3 trial (2012)

This study evaluates the effect of ustekinumab on health-related quality of life (HRQoL) in Japanese patients with moderate-to-severe plaque psoriasis through 64 weeks. A total of 158 patients were randomized to receive subcutaneous injections of ustekinumab 45 mg (n = 64) or 90 mg (n = 62) at weeks 0, 4, and every-12-weeks, or placebo (n = 32) with crossover to ustekinumab at week 12. Secondary study endpoints included change in Dermatology Life Quality Index (DLQI) at week 12. Other assessments included the 36-item Short Form health survey to assess Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and Psoriasis Disability Index (PDI), a psoriasis-specific instrument to assess HRQoL. Baseline demographic and disease characteristics were similar across randomized treatment groups. Ustekinumab-treated patients had significantly greater mean improvements in DLQI from baseline to week 12 (45 mg: 8.0 ± 6.5; 90 mg: 7.4 ± 6.5) than placebo-treated patients (0.3 ± 5.3; P < 0.0001 for each), and these improvements were maintained through week 64. Also at week 12, significant improvements from baseline in PDI scores were observed in ustekinumab-treated patients (45 mg: 8.6 ± 9.6; 90 mg: 12.0 ± 11.8) compared with placebo-treated patients (-0.1 ± 4.2). Improvements in the PCS (45 mg: 7.8 ± 14.5; 90 mg: 5.1 ± 12.0) and MCS (45 mg: 5.3 ± 9.8; 90 mg: 5.8 ± 10.5) scores were also observed in ustekinumab-treated patients at week 12. Placebo-treated patients who crossed-over to ustekinumab achieved improvements in HRQoL comparable to those observed in patients originally randomized to ustekinumab. Ustekinumab significantly improves HRQoL in Japanese patients with moderate-to-severe plaque psoriasis through week 64.