gebhart/patrepeval huggingface dataset:
Targeting exosites on blood coagulation proteases (2005)

The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed in this short revision. Bothrojaracin is a snake venom-derived protein that binds to thrombin exosites 1 and 2. Complex formation impairs several exosite-dependent activities of thrombin including fibrinogen cleavage and platelet activation. Bothrojaracin also interacts with proexosite 1 on prothrombin thus decreasing the zymogen activation by the prothrombinase complex (FXa/FVa). Ixolaris is a two Kunitz tick salivary gland inhibitor, that is homologous to tissue factor pathway inhibitor. Recently it was demonstrated that ixolaris binds to heparin-binding exosite of FXa, thus impairing the recognition of prothrombin by the enzyme. In addition, ixolaris interacts with FX possibly through the heparin-binding proexosite. Differently from FX, the ixolaris-FX complex is not recognized as substrate by the intrinsic tenase complex (FIXa/FVIIIa). We conclude that these inhibitors may serve as tools for the study of coagulation exosites as well as prototypes for new anticoagulant drugs.
ACTOR: A multilingual unit-selection speech synthesis system. (2001)

The ACTOR ® Text-To-Speech (TTS) synthesis system, developed at Loquendo S.p.A., is here described. The system employs a unit-selection concatenative synthesis technique, relying on labeled acoustic databases providing phonetic and prosodic coverage of the intended language/domain and on an original algorithm for run-time selection of the acoustic units to be concatenated. This technique yields high-naturalness and human sounding voices. ACTOR ® is a multi-voice and multi-language system, exploiting different kinds of language dependent knowledge (grammatical, phonetic and prosodic, as well as acoustic) with the support of several development tools (statistical tools for database design, machine learning algorithms, tools for speech signal analysis and phonetic alignment, etc.). 1.
Amino‐acid‐sequence Determination and Biological Activity of Cytin, a Naturally Occurring Specific Chymotrypsin Inhibitor from the Leech Theromyzon tessulatum (1997)

We purified a chymotrypsin inhibitor, designated cytin, from the rhynchobdellid leech Theromyzon tessulatum. This 7.4-kDa peptide was purified to apparent homogeneity by gel-permeation and anion-exchange chromatographies, followed by reverse-phase HPLC. The structure of cytin was determined by reduction, S-beta-pyridilethylation, automated Edman degradation, and electrospray mass spectrometry. Cytin is formed by the association of two protein chains, which are linked by a disulfide bridge. Chain A consists of 43 and chain B of 22 amino acid residues. Chain B exhibits 40-63% sequence similarity with the N-terminal sequences of subtilisin/chymotrypsin inhibitors isolated from barley seeds. Cytin inhibited chymotrypsin (Ki 600 pM) and weakly inhibited trypsin (Ki 350 nM). This chymotrypsin inhibitor, in contrast to others isolated from leeches, does not inhibit elastase or cathepsin G. Furthermore, cytin (10 microM) significantly diminishes the level of human granulocyte and monocyte activation induced by lipopolysaccharide (1 U/ml) in a manner similar to that of aprotinin. These data indicate that this chymotrypsin inhibitor may be biomedically significant.
Purification and characterization of an exo-beta-D-glucosaminidase, a novel type of enzyme, from Nocardia orientalis. (1990)

A new enzyme capable of hydrolyzing chitobiose, which is an induced enzyme, was purified to apparent homogeneity from the culture filtrate of Nocardia orientalis IFO 12806. Biospecific affinity chromatography on chitotriitol-Sepharose CL-4B was effective for purification of this enzyme. It is clearly demonstrated that the enzyme is an exo-hydrolase, removing single glucosamine residues from the nonreducing terminal of a sequence of beta-(1----4)-linked glucosamine chain, such as chitosan and chitooligosaccharides, and therefore characterized as an exo-beta-D-glucosaminidase. The enzyme was found to show maximum activity on chitotetraose, chitopentaose, and their corresponding alcohols and a slight decrease in rate on longer chain lengths of substrates. A significant decrease in rate was observed using p-nitrophenyl beta-D-glucosaminide and chitobiitol as substrates. In the hydrolysis of partially acetylated chitosans, the enzyme appeared to be effective in cleaving glucosamine from the GlcN beta 1----4GlcNAc beta 1----sequence as well as the GlcN beta 1----4GlcN beta 1----sequence. These observations suggest that the second residue from the terminal plays an important role in enzyme activity, but the enzyme permits the replacement of glucosamine at the second residue by N-acetylglucosamine.
Complement inhibition with an anti-C5 monoclonal antibody prevents acute cardiac tissue injury in an ex vivo model of pig-to-human xenotransplantation. (1995)

Prevention of hyperacute xenograft rejection in the pig-to-primate combination has been accomplished by removal of natural antibodies, complement depletion with cobra venom factor, or prevention of C3 activation with the soluble complement inhibitor sCR1. Although these strategies effectively prevent hyperacute rejection, they do not address the relative contribution of early (C3a, C3b) versus late (C5a, C5b-9) activated complement components to xenogeneic organ damage. To better understand the role of the terminal complement components (C5a, C5b-9) in hyperacute rejection, an anti-human C5 mAb was developed and tested in an ex vivo model of cardiac xenograft rejection. In vitro studies demonstrated that the anti-C5 mAb effectively blocked C5 cleavage in a dose-dependent manner that resulted in complete inhibition of both C5a and C5b-9 generation. Addition of anti-C5 mAb to human blood used to perfuse a porcine heart prolonged normal sinus cardiac rhythm from a mean time of 25.2 min in hearts perfused with unmodified blood to 79,296, or > 360 min when anti-C5 mAb was added to the blood at 50 micrograms/ml, 100 micrograms/ml, or 200 micrograms/ml, respectively. In these experiments, activation of the classical complement pathway was completely inhibited. Hearts perfused with blood containing the highest concentration of anti-C5 mAb had no histologic evidence of hyperacute rejection and no deposition of C5b-9. These experiments suggest that the activated terminal complement components C5a and C5b-9, but not C3a or C3b, play a major role in tissue damage in this porcine-to-human model of hyperacute rejection. They also suggest that targeted inhibition of terminal complement activation by anti-C5 mAbs may be useful in clinical xenotransplantation.
Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. (1996)

Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic. We examined the effects of soya consumption on circulating steroid hormones in six healthy females 22-29 years of age. Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of three meals daily for 1 month on a metabolic unit. Daily isoflavone intakes were approximately 100 mg of daidzein (mostly as daidzin) and approximately 100 mg of genistein (mostly as genistin). Serum 17 beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31% (P = 0.09), 81% (P = 0.03), and 49% (P = 0.02), respectively, during soya feeding. Decreases persisted for two or three menstrual cycles after withdrawal from soya feeding. The luteal phase progesterone levels decreased by 35% during soya feeding (P = 0.002). Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30% (P = 0.03). Menstrual cycle length was 28.3 +/- 1.9 days before soymilk feeding, increased to 31.8 +/- 5.1 days during the month of soymilk feeding (P = 0.06), remained increased at 32.7 +/- 8.4 days (P = 0.11) at one cycle after termination of soymilk feeding, and returned to pre-soya diet levels five to six cycles later. These results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.
Moodtrack : practical methods for assembling emotion-driven music (2006)

This thesis presents new methods designed for the deconstruction and reassembly of musical works based on a target emotional contour. Film soundtracks provide an ideal testing ground for organizing music around strict timing and emotional criteria. The approach to media analysis applies Minsky’s ideas of frame-arrays to the context of film music, revealing musical and emotional cue points of a work. Media deconstructions provide a framework for the assembly of new musical material, leading to the creation of soundtracks using musical commonsense.
Detection of Fungi in the Nasal Mucosa Using Polymerase Chain Reaction (2001)

PCR is significantly more sensitive than nasal swab cultures in detecting the presence of fungi in nasal mucosa. In addition, our study suggests that the presence of fungi alone is insufficient to implicate it as the pathogen in chronic sinusitis.
Meta-Graph Based HIN Spectral Embedding: Methods, Analyses, and Insights (2018)

Heterogeneous information network (HIN) has drawn significant research attention recently, due to its power of modeling multi-typed multi-relational data and facilitating various downstream applications. In this decade, many algorithms have been developed for HIN modeling, including traditional similarity measures and recent embedding techniques. Most algorithms on HIN leverage meta-graphs or meta-paths (special cases of meta-graphs) to capture various semantics. Given any arbitrary set of meta-graphs, existing algorithms either consider them as equally important or study their different importance through supervised learning. Their performance largely relies on prior knowledge and labeled data. While unsupervised embedding has shown to be a fundamental solution for various homogeneous network mining tasks, for HIN, it is a much harder problem due to such a presence of various meta-graphs. In this work, we propose to study the utility of different meta-graphs, as well as how to simultaneously leverage multiple meta-graphs for HIN embedding in an unsupervised manner. Motivated by prolific research on homogeneous networks, especially spectral graph theory, we firstly conduct a systematic empirical study on the spectrum and embedding quality of different meta-graphs on multiple HINs, which leads to an efficient method of meta-graph assessment. It also helps us to gain valuable insight into the higher-order organization of HINs and indicates a practical way of selecting useful embedding dimensions. Further, we explore the challenges of combining multiple meta-graphs to capture the multi-dimensional semantics in HIN through reasoning from mathematical geometry and arrive at an embedding compression method of autoencoder with l2,1-loss, which finds the most informative meta-graphs and embeddings in an end-to-end unsupervised manner. Finally, empirical analysis suggests a unified workflow to close the gap between our meta-graph assessment and combination methods. To the best of our knowledge, this is the first research effort to provide rich theoretical and empirical analyses on the utility of meta-graphs and their combinations, especially regarding HIN embedding. Extensive experimental comparisons with various state-of-the-art neural network based embedding methods on multiple real-world HINs demonstrate the effectiveness and efficiency of our framework in finding useful meta-graphs and generating high-quality HIN embeddings.
Systemic alpha‐interferon therapy of multiple sclerosis (1984)

A randomized, double-blind, placebo-controlled crossover study tested the efficacy of natural alpha interferon in altering exacerbating-remitting MS. Twenty-four patients with frequent exacerbations were treated for 6-month periods, beginning with either 5 X 10(6) IU of interferon daily or placebo. A 6-month washout period followed each treatment. Exacerbation rates were reduced during interferon and placebo phases compared with pre-study rates; a greater reduction occurred on interferon, particularly following placebo, possibly reflecting a learning phenomenon. Fifteen patients with a strictly exacerbating-remitting course had fewer and milder exacerbations on interferon compared with those on placebo, whereas 9 patients with a progressive component continued to have active disease. These results suggest that interferon might reduce exacerbations in certain patients and indicate guidelines for future trials of interferon in MS.
Leaf photosynthesis in the C4-grassMiscanthusxgiganteus, growing in the cool temperate climate of southern England (1996)

Previous studies have shown that both photoinhibition and low temperature impairment of leaf development occur in C4 species growing in temperate climates. These result in reductions in the maximum quantum efficiency (φ) and the light-saturated rate of CO2 uptake (Asat). The perennial C4-grass Miscanthus × giganteus has been shown to attain high productivity in northern Europe. This study examines and analyses the seasonal variation in photosynthetic gas exchange of M. × giganteus grown in southern England. Although the crop was exposed to chilling temperatures at the start of the season neither Asat nor φ were impaired, when assessed at a measurement temperature of 24°C. Between May and July the mean values of Asat and φ were 34 μmol m−2 s−1 and 0.067, respectively, declining to 20 μmol m−2, s−1 and 0.045 in October. In the field, on clear days between May and July, the typical midday rates of CO2, uptake ranged between 20–27 μmol m−2 S−1, although in late-June a peak mean value of 35 μmol m−2 s−1 was attained. The study shows that under the cool temperate conditions of southern England, M. × giganteus, unlike all C4 species previously examined, is able to realize the photosynthetic potential of the C4 process without suffering any apparent low temperature impairment, except possibly at the very end of the growing season.
Review of checkpoint immunotherapy for the management of non-small cell lung cancer (2018)

Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies against checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1). By blocking these receptors and signals, the immune system can be reactivated to fight the tumor. Immunotherapy for advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of treatment options resulting in improved survival and response rates and has a less severe yet unique toxicity profile when compared to chemotherapy. PD-1 inhibitors, nivolumab and pembrolizumab, and PD-L1 inhibitor, atezolizumab, are currently approved by regulatory authorities for the treatment of advanced NSCLC. This article provides a detailed review of these newer agents, their mechanism of action, side-effect profile, therapeutic indications and current evidence supporting their use in the management of NSCLC.
Contrasting GC-content dynamics across 33 mammalian genomes: Relationship with life-history traits and chromosome sizes (2010)

The origin, evolution, and functional relevance of genomic variations in GC content are a long-debated topic, especially in mammals. Most of the existing literature, however, has focused on a small number of model species and/or limited sequence data sets. We analyzed more than 1000 orthologous genes in 33 fully sequenced mammalian genomes, reconstructed their ancestral isochore organization in the maximum likelihood framework, and explored the evolution of third-codon position GC content in representatives of 16 orders and 27 families. We showed that the previously reported erosion of GC-rich isochores is not a general trend. Several species (e.g., shrew, microbat, tenrec, rabbit) have independently undergone a marked increase in GC content, with a widening gap between the GC-poorest and GC-richest classes of genes. The intensively studied apes and (especially) murids do not reflect the general placental pattern. We correlated GC-content evolution with species life-history traits and cytology. Significant effects of body mass and genome size were detected, with each being consistent with the GC-biased gene conversion model.
Detecting Social Malware and its Ecosystem in Online Social Networks - eScholarship (2012)

Online social networks (OSNs) have become the new vector for cybercrime, and hackers are finding new ways to propagate spam and malware on these platforms, which we refer to as social malware. As we show here, social malware cannot be identified with existing security mechanisms (e.g., URL blacklists), because it exploits different weaknesses and often has different intentions.In this dissertation, we show that social malware is prevalent in Facebook, the largest OSN to date with more then a billion users and develop an efficient and scalable social malware detection system that takes advantage of the social context of posts. We deploy this detection system as a Facebook app called MyPageKeeper to protect Facebook users from social malware. We find that our detection method is both accurate and efficient. Furthermore, we show that, social malware significantly differs from traditional email spam or web-based malware.One of the major factors for enabling social malware is malicious third-party apps. We show that such malicious apps are also widespread in Facebook. Therefore, to identify malicious apps, we ask the question: given a Facebook application, can we determine if it is malicious? Our key contribution in this part is in developing FRAppE--Facebook's Rigorous Application Evaluator--arguably the first tool focused on detecting malicious apps on Facebook. We identify a set of features that help us distinguish malicious apps from benign ones. For example, we find that malicious apps often share names with other apps, and they typically request fewer permissions than benign apps. Then, leveraging these distinguishing features, we show that FRAppE can detect malicious apps with 99.5% accuracy, with no false positives and a low false negative rate (4.1%). Finally, we explore the ecosystem of malicious Facebook apps. We identify mechanisms these apps use to propagate and find that many apps collude and support each other.
Quantitative evaluation by minisequencing and microarrays reveals accurate multiplexed SNP genotyping of whole genome amplified DNA (2003)

Whole genome amplification (WGA) procedures such as primer extension preamplification (PEP) or multiple displacement amplification (MDA) have the potential to provide an unlimited source of DNA for large-scale genetic studies. We have performed a quantitative evaluation of PEP and MDA for genotyping single nucleotide polymorphisms (SNPs) using multiplex, four-color fluorescent minisequencing in a microarray format. Forty-five SNPs were genotyped and the WGA methods were evaluated with respect to genotyping success, signal-to-noise ratios, power of genotype discrimination, yield and imbalanced amplification of alleles in the MDA product. Both PEP and MDA products provided genotyping results with a high concordance to genomic DNA. For PEP products the power of genotype discrimination was lower than for MDA due to a 2-fold lower signal-to-noise ratio. MDA products were indistinguishable from genomic DNA in all aspects studied. To obtain faithful representation of the SNP alleles at least 0.3 ng DNA should be used per MDA reaction. We conclude that the use of WGA, and MDA in particular, is a highly promising procedure for producing DNA in sufficient amounts even for genome wide SNP mapping studies.
An exploration of sentiment summarization (2003)

We introduce the idea of a sentiment summary, a single pas-sage from a document that captures a key aspect of the au-thor’s opinion about his or her subject. Using supervised data from the Rotten Tomatoes website, we examine features that appear to be helpful in locating a good summary sentence. These features are used to fit Naive Bayes and regularized logistic regression models for summary extraction.
Passive transfer of local immunity to influenza virus infection by IgA antibody (1991)

Secretory IgA is presumed to be the mediator of mucosal immunity based on many studies that show a correlation between protection and secretory IgA titers; however, a causal relationship has not yet been established. Classically, passive transfer of antibody has been used to demonstrate causality, but the passive transfer of local immunity with physiologically transported IgA has not been previously reported. In this study mice were injected intravenously with polymeric IgA (pIgA), monomeric IgA (mIgA), or IgG1 mAb specific for the H1 hemaglutinin of PR8 influenza virus. pIgA was shown to be specifically transported into nasal secretions relative to the mIg. The transported pIgA was functional, as evidenced by its ability to bind to virus in an ELISA assay and to protect nonimmune mice against intranasal infection with H1N1 but not H3N2 influenza virus. Intravenous injection of similar virus-neutralizing doses of anti-influenza IgG1 mAb did not protect against nasal viral challenge. IgA-mediated protection could be abrogated by the intranasal administration of antiserum against the alpha chain of IgA. These data demonstrate the passive transfer of local immunity by the i.v. administration of pIgA antibody and show that the IgA in secretions can protect against influenza virus infection. This general approach could provide a model for the evaluation of the role of local IgA in host defense against other pathogens.
[Transobturator urethral suspension: mini-invasive procedure in the treatment of stress urinary incontinence in women]. (2001)

Transobturator tape is an artificial tape designed for urethral suspension to treat female stress urinary incontinence. This tape has two original features: its non-woven polypropylene structure is coated with silicone on the urethral surface in order to limit retraction of polypropylene and to establish a barrier to extension of periurethral fibrosis. transmuscular insertion, through the obturator and puborectalis muscles, reproduces the natural suspension fascia of the urethra while preserving the retropubic space. A preliminary study (40 implantations) confirmed the feasibility of this operation, the low morbidity (one complication: sepsis) and the encouraging results between 3 and 12 months; in the treatment of isolated incontinence (16 patients), no postoperative dysuria has been observed; 15 patients are totally continent and 1 patient is improved; in the treatment of prolapse associated with frank or potential incontinence (24 patients), transient postoperative dysuria was observed in 4 cases, with no postoperative incontinence.