gebhart/patrepeval huggingface dataset:
Viral host-range factor C7 or K1 is essential for modified vaccinia virus Ankara late gene expression in human and murine cells, irrespective of their capacity to inhibit protein kinase R-mediated phosphorylation of eukaryotic translation initiation factor 2 (2009)

Vaccinia virus (VACV) infection induces phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha), which inhibits cellular and viral protein synthesis. In turn, VACV has evolved the capacity to antagonize this antiviral response by expressing the viral host-range proteins K3 and E3. This study revealed that the host-range genes K1L and C7L also prevent eIF2alpha phosphorylation in modified VACV Ankara (MVA) infection of several human and murine cell lines. Moreover, C7L-deleted MVA (MVA-DeltaC7L) lacked late gene expression, which could be rescued by the function of host-range factor K1 or C7. It was demonstrated that viral gene expression was blocked after viral DNA replication and that it was independent of apoptosis induction. Furthermore, it was found that eIF2alpha phosphorylation in MVA-DeltaC7L-infected cells is mediated by protein kinase R (PKR) as shown in murine embryonic fibroblasts lacking PKR function, and it was shown that this was not due to reduced E3L gene expression. The block of eIF2alpha phosphorylation by C7 could be complemented by K1 in cells infected with MVA-DeltaC7L encoding a reinserted K1L gene (MVA-DeltaC7L-K1L). Importantly, these data illustrated that eIF2alpha phosphorylation by PKR is not responsible for the block of late viral gene expression. This suggests that other mechanisms targeted by C7 and K1 are essential for completing the MVA gene expression cycle and probably also for VACV replication in a diverse set of cell types.
Development and validation of a rapid, generic measure of disease control from the patient's perspective: the IBD-Control questionnaire (2013)

The IBD-Control is a rapid, reliable, valid and sensitive instrument for measuring overall disease control from the patient's perspective. Unlike existing patient reported outcome measures, its simplicity, ease-of-use and generic applicability make it a candidate for supporting routine care.
Comparative investigations on different polymers for the preparation of fast-dissolving oral films (2010)

Abstract Objectives The aim was to compare different film-forming materials used for the preparation of fast-dissolving oral films. Methods Films were prepared with and without caffeine and caffeine citrate as model drugs. The disintegration/dissolution behaviour of films was investigated using the newly developed slide frame method and Petri dish method. Films were also characterised by dynamic vapour sorption. Key findings All films dissolved within 40 s. Drug-loaded films disintegrated more slowly than the equivalent drug-free formulations. Disintegration/dissolution was fastest with films made from the carboxymethyl cellulose C 30 PA 09 (drug-free &amp;lt; 5 s, drug-loaded &amp;lt; 10 s). Dissolution times for drug-loaded oral films made from C 30 PA 09 and HM 6 PA 2910 (hydroxypropyl methyl cellulose) differed significantly (α= 0.05). Dynamic vapour sorption studies revealed higher water absorption ratios for carboxymethyl cellulose films, and these were sticky and difficult to handle. Conclusions This case study showed that hydroxypropyl methyl cellulose was the most suitable film-forming material for drug-free and caffeine-loaded films, providing fast dissolution films that were not sticky and were easy to handle.
Detection of Outliers in Regression Model for Medical Data (2017)

In regression analysis, an outlier is an observation for which the residual is large in magnitude compared to other&#13;\nobservations in the data set. The detection of outliers and influential points is an important step of the regression&#13;\nanalysis. Outlier detection methods have been used to detect and remove anomalous values from data. In this paper,&#13;\nwe detect the presence of outliers in simple linear regression models for medical data set. Chatterjee and Hadi mentioned that the ordinary residuals are not appropriate for diagnostic purposes; a transformed version of them is preferable. First, we investigate the presence of outliers based on existing procedures of residuals and standardized residuals. Next, we have used the new approach of standardized scores for detecting outliers without the use of predicted values. The performance of the new approach was verified with the real-life data.
Mice deficient in α-actinin-4 have severe glomerular disease (2003)

Dominantly inherited mutations in ACTN4, which encodes alpha-actinin-4, cause a form of human focal and segmental glomerulosclerosis (FSGS). By homologous recombination in ES cells, we developed a mouse model deficient in Actn4. Mice homozygous for the targeted allele have no detectable alpha-actinin-4 protein expression. The number of homozygous mice observed was lower than expected under mendelian inheritance. Surviving mice homozygous for the targeted allele show progressive proteinuria, glomerular disease, and typically death by several months of age. Light microscopic analysis shows extensive glomerular disease and proteinaceous casts. Electron microscopic examination shows focal areas of podocyte foot-process effacement in young mice, and diffuse effacement and globally disrupted podocyte morphology in older mice. Despite the widespread distribution of alpha-actinin-4, histologic examination of mice showed abnormalities only in the kidneys. In contrast to the dominantly inherited human form of ACTN4-associated FSGS, here we show that the absence of alpha-actinin-4 causes a recessive form of disease in mice. Cell motility, as measured by lymphocyte chemotaxis assays, was increased in the absence of alpha-actinin-4. We conclude that alpha-actinin-4 is required for normal glomerular function. We further conclude that the nonsarcomeric forms of alpha-actinin (alpha-actinin-1 and alpha-actinin-4) are not functionally redundant. In addition, these genetic studies demonstrate that the nonsarcomeric alpha-actinin-4 is involved in the regulation of cell movement.
Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp. and Otodectes cynotis (2016)

The efficacy of sarolaner (Simparica™, Zoetis) was evaluated against Demodex spp. in dogs with generalized demodicosis and against Otodectes cynotis (otodectic mange) in dogs with induced infestations. In the first study, 16 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites were randomly assigned to treatment with either sarolaner (2mg/kg) orally on Days 0, 30 and 60, or topical imidacloprid (10mg/kg) plus moxidectin (2.5mg/kg) solution every 7 days from Day 0 to Day 81. For sarolaner-treated dogs, pretreatment mite counts were reduced by 97.1% at 14days and 99.8% by 29 days after the first dose, with no live mites detected thereafter. Weekly imidacloprid plus moxidectin resulted in 84.4 and 95.6% reduction at these two time points, respectively, with no mites detected from Day 74 on. All dogs in both groups showed marked improvement in the clinical signs of demodicosis. In the second study, 32 dogs with induced infestations of O. cynotis were randomly assigned (eight per group) to oral sarolaner (2mg/kg) as a single treatment on Day 0 or as a two dose regime (Days 0 and 30), or a placebo group for each of the dose regimes. Sarolaner administered at 2mg/kg as a single oral dose resulted in a 98.2% reduction at Day 30 and two doses of sarolaner, administered one month apart, resulted in a 99.5% reduction in ear mites at Day 60 compared to placebo controls. There were no treatment related adverse events in either study. In these studies, sarolaner at an oral dose of 2mg/kg was highly effective in reducing the live mite counts associated with a natural infestation of Demodex spp. and an induced infestation of O. cynotis. In addition, the Demodex-infested dogs showed a marked improvement in the clinical signs of generalized demodicosis.
In vivo molecular therapy with p53 adenovirus for microscopic residual head and neck squamous carcinoma. (1995)

Developing gene therapy strategies may allow contemporary medicine to reassess its management of solid malignancies. We have demonstrated previously that the wild-type p53 adenovirus (Ad5CMV-p53) suppressed the growth of established tumors of the head and neck. In this paper we develop a microscopic residual model which mimics the postsurgical environment of head and neck cancer patients with advanced disease. Using this squamous cell carcinoma of the head and neck model, we prevented the establishment of tumors in nude mice in which tumor cells had been s.c. implanted by transiently introducing exogenous wild-type p53 via an adenoviral vector 2 days following tumor cell implantation. These effects were vector dose dependent but independent on the endogenous wild-type or mutated p53 status of the cells. Importantly, karyotypically normal and nontumorigenic fibroblast cell lines are inert to the p53 adenovirus treatment. These results pave the ground work for further development of molecular therapy for head and neck cancer and other solid malignancies.
Thrombosis and shock induced by activating antiplatelet antibodies in human FcγRIIA transgenic mice: the interplay among antibody, spleen, and Fc receptor (2000)

Transgenic mouse lines were created that express FcγRIIA on platelets and macrophages at human physiologic levels, and they were used to explore the consequences in vivo of activating antiplatelet antibodies. Anti-CD9 antibody activated platelets of FcγRIIA transgenic (tg) mice and, following injection in vivo, caused more rapid severe thrombocytopenia than nonactivating antiplatelet antibody. Anti-CD9 injected into FcγRIIA tg crossed with FcR γ-chain knockout (γ-KO) mice caused thrombosis and shock in all mice, and death in 16 of 18 mice. The shock depended on platelet Fc receptor density and antibody dose. On histologic examination, the lung vasculature of anti-CD9–treated FcγRIIA tg × γ-KO mice contained extensive platelet-fibrin thrombi. Thrombosis and shock in FcγRIIA tg mice in the context of the FcR γ-chain knockout suggested the importance of the interplay of intravascular platelet activation and splenic clearance. Reduction of splenic clearance surgically (splenectomy) or functionally (monoclonal antibody treatment) also facilitated anti-CD9–mediated shock in FcγRIIA tg mice. The spleen, which clears nonactivating antibody-coated platelets leading to thrombocytopenia, appears to play a protective role in the thrombosis and shock observed with activating antiplatelet antibody. The data indicate that antibodies, which activate platelets in an FcγRIIA-dependent manner, can lead to thrombosis, shock, and death. Furthermore, antibody titer, platelet Fc receptor density, and splenic clearance are likely important determinants of the outcome.
Analysis of the degradation of high concentrator III-V solar cells (2005)

The implantation of high concentrator III-V solar cells to an industrial scale needs to perform many tests in order to prove their reliability. This task must be undertaken through three different sort of experiments: Accelerated degradation tests, real time degradation tests, and screening tests. An experimental strategy is suggested to achieve the implementation of these devices.
Contributions of protein structure-based drug design to cancer chemotherapy. (1997)

Protein structure-based drug design (SBDD) uses a knowledge of the molecular structure of a target macromolecule, normally obtained by x-ray crystallography, to design potent, selective inhibitors. This technique has played a major role in the design of a number of drugs that have progressed to clinical trials. Most of these compounds have been developed to treat viral diseases and cancer. In the antiviral area, drugs designed by SBDD have been developed for treatment of influenza and acquired immune deficiency syndrome. Three human immunodeficiency virus-I protease inhibitors that were designed at least partially using the x-ray crystal structure of the target enzyme are now approved for sale in the United States. In the anticancer field, no SBDD-designed drugs have yet progressed to market, but several experimental anticancer agents that were designed from a knowledge of the molecular structure of their target enzyme have advanced to clinical trials, of which at least one has shown clinical activity. The present article discusses the strengths and weaknesses of the SBDD approach, and shows its contributions to cancer chemotherapy by discussing rationally designed inhibitors of thymidylate synthase, purine nucleoside phosphorylase, glycinamide ribonucleotide formyltransferase, and matrix metalloproteases.
Estimating the Support of a High-Dimensional Distribution (2001)

Suppose you are given some data set drawn from an underlying probability distribution P and you want to estimate a "simple" subset S of input space such that the probability that a test point drawn from P lies outside of S equals some a priori specified value between 0 and 1. We propose a method to approach this problem by trying to estimate a function f that is positive on S and negative on the complement. The functional form of f is given by a kernel expansion in terms of a potentially small subset of the training data; it is regularized by controlling the length of the weight vector in an associated feature space. The expansion coefficients are found by solving a quadratic programming problem, which we do by carrying out sequential optimization over pairs of input patterns. We also provide a theoretical analysis of the statistical performance of our algorithm. The algorithm is a natural extension of the support vector algorithm to the case of unlabeled data.
The Role of Complement in the Development of Systemic Lupus Erythematosus (2004)

Complement has both beneficial and deleterious roles in the pathogenesis of systemic lupus erythematosus (SLE). On the one hand, patients with SLE present with decreased complement levels and with complement deposition in inflamed tissues, suggestive of a harmful role of complement in the effector phase of disease. On the other hand, homozygous deficiency of any of the classical pathway proteins is strongly associated with the development of SLE. There are two main hypotheses to explain these observations. The first invokes an important role for complement in the physiological waste-disposal mechanisms of dying cells and immune complexes. The second hypothesis is based around the role of complement in determining the activation thresholds of B and T lymphocytes, with the proposal that complement deficiency causes incomplete maintenance of peripheral tolerance. These two hypotheses are not mutually exclusive. In addition, there is evidence for a contribution from other genetic factors in determining the phenotype of disease in the absence of complement.
Predicting Molecular Interactions in silico: II. Protein-Protein and Protein- Drug Docking (2004)

This article reviews the docking field starting from basic docking algorithms and describing the latest advances. We present the algorithmic framework and classify the state of-the-art methods. We point out the bottlenecks of the methods, like flexibility, absence of absolute scoring functions and explain what types of information can potentially be added to improve the results.
A lens and aperture camera model for synthetic image generation (1981)

This paper extends the traditional pin-hole camera projection geometry, used in computer graphics, to a more realistic camera model which approximates the effects of a lens and an aperture function of an actual camera. This model allows the generation of synthetic images which have a depth of field, can be focused on an arbitrary plane, and also permits selective modeling of certain optical characteristics of a lens. The model can be expanded to include motion blur and special effect filters. These capabilities provide additional tools for highlighting important areas of a scene and for portraying certain physical characteristics of an object in an image.
Detection of receptor ligands by monitoring selective stabilization of aRenillaluciferase‐tagged, constitutively active mutant, G‐protein‐coupled receptor (2001)

The wild-type beta2-adrenoceptor and a constitutively active mutant of this receptor were C-terminally tagged with luciferase from the sea pansy Renilla reniformis. C-terminal addition of Renilla luciferase did not substantially alter the levels of expression of either form of the receptor, the elevated constitutive activity of the mutant beta2-adrenoceptor nor the capacity of isoprenaline to elevate cyclic AMP levels in intact cells expressing these constructs. Treatment of cells expressing constitutively active mutant beta2-adrenoceptor-Renilla luciferase with antagonist/inverse agonist ligands resulted in upregulation of levels of this polypeptide which could be monitored by the elevated luciferase activity. The pEC50 for ligand-induced luciferase upregulation and ligand affinity to bind the receptor were highly correlated. Similar upregulation could be observed following sustained treatment with agonist ligands. These effects were only observed at a constitutively active mutant of the beta2-adrenoceptor. Co-expression of the wild-type beta2-adrenoceptor C-terminally tagged with the luciferase from Photinus pyralis did not result in ligand-induced upregulation of the levels of activity of this luciferase. Co-expression of the constitutively active mutant beta2-adrenoceptor-Renilla luciferase and an equivalent mutant of the alpha1b-adrenoceptor C-terminally tagged with green fluorescent protein allowed pharmacological selectivity of adrenoceptor antagonists to be demonstrated. This approach offers a sensitive and convenient means, which is amenable to high throughput analysis, to monitor ligand binding to a constitutively active mutant receptor. As no prior knowledge of receptor ligands is required this approach may be suitable to identify ligands at orphan G protein-coupled receptors.
Pharmacokinetics of glucosamine in the dog and in man. (1986)

The pharmacokinetics, organ distribution, metabolism and excretion of glucosamine were studied in the dog giving uniformly labelled [14C]-glucosamine (sulfate), i.v. or orally, in single doses. Immediately after i.v. administration, the radioactivity in plasma is due to glucosamine, and freely diffuses into organs and tissues. This radioactivity disappears quickly from plasma (initial t1/2 = 13 min, terminal t1/2 = 118 min). After 30-60 min the radioactivity in plasma is no longer due to glucosamine, but is incorporated into alpha- and beta-globulins. The protein-incorporated radioactivity is found already 20-30 min after i.v. administration, reaches a peak after 8 h and then slowly disappears, with a t1/2 = 2.9 days. Of the administered radioactivity, more than 34% is excreted in the urine, mainly as glucosamine, and 1.7% is excreted in the feces. Radioactivity is excreted also as [14C]-CO2 in the expired air. The radioactivity, after i.v. administration, diffuses rapidly from blood into the body. Some organs show an active uptake of radioactivity, e.g. the liver and the kidney. Other tissues, such as the articular cartilage, also have an active uptake. In most other organs the radioactivity found can be explained by passive diffusion processes from plasma. After oral administration of a single dose of [14C]-glucosamine the radioactivity is quickly and almost completely absorbed from the gastrointestinal tract. The pattern of disappearance, metabolic transformation, tissue distribution and excretion of the radioactivity are consistent with those found after i.v. administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromosome Evolution of Near-Haploid Clones in an Established Human Acute Lymphoblastic Leukemia Cell Line (NALM-16)<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref><xref ref-type="fn" rid="FN4">4</xref> (1980)

A cell line has been established from blood lymphoblasts of a female patient with acute lymphoblastic leukemia (ALL) shown to have near-haploid (27 chromosomes) cells in the bone marrow. The findings about the cell line were: 1) The frequency of near-haploid cells in culture decreased with time from 98.2% when the culture was started to 5.4% 15 months later. 2) Most of the other cells except the near-haploid ones were hyperdiploid, i.e., duplicates of the cells with near-haploid chromosome constitutions. 3) Chromosome evolution was seen in the near-haploid clones. The possible ancestor clone (clone A) had 27 chromosomes, one of each pair except no.10, 14, 18, and 21, which were disomic. A suggested evolution process is: clone A yields clone B (26 chromosomes: clone A, -no.10) yields clone C (27 chromosomes: clone B, +X) yields clone D (26 chromosomes: clone C, -no.21), clone E (28 chromosomes: clone C, +NO.20). Clone B and D, each with 26 chromosomes, appeared to contain the lowest number of chromosomes, appeared to contain the lowest number of chromosomes ever described for human somatic cell clones in vitro. 4) Changes in the constitutions of the hyperdiploid cell clones were preceded by evolution and changes in the near-haploid clones. 5) In near-haploid cells with 2 X-chromosomes, 1 exhibited late DNA replication; in hyperdiploid cells with 3-5 X-chromosomes, 2 were non-late DNA-replicating. 6) Fresh (uncultured) and cultured leukemia cells were antigenically typical non-T, non-B or common type ALL cells (positive for la-like and null-type ALL antigens and negative for surface membrane immunoglobulin).
Interchain Disulfide Bonding in Human IgG2 Antibodies Probed by Site-Directed Mutagenesis (2009)

Human IgG2 exists as a mixture of disulfide-linked structural isoforms that can show different activities. To probe the contribution of specific cysteine residues to the formation of structural isoforms, we characterized a series of Cys-->Ser mutant IgG2 recombinant monoclonal antibodies, focused on the first C(H)1 cysteine and the first two hinge cysteines. These residues participate in the formation of structural isoforms that have been noted by nonreduced capillary sodium dodecyl sulfate polyacrylamide gel electrophoresis, reversed-phase high-performance liquid chromatography, and cation exchange chromatography. We show that single Cys-->Ser mutants can greatly reduce heterogeneous disulfide bonding in human IgG2 and maintain in vitro activity. The data demonstrate the feasibility of applying site-directed mutagenesis to reduce disulfide bond heterogeneity in human IgG2 while preserving the activity of this therapeutically important class of human antibodies.