gebhart/patrepeval huggingface dataset:
The Intracellular and Extracellular Fate of Oligodeoxyribonucleotides in Tissle Culture Systems (1989)

Abstract In this study, we analyzed the intracellular and extracellular stability of an oligdeoxyribonucleotide (oligo 293) which exhibits antiviral activity against Herpes Simplex Virus Type 1 (HSV-1) in tissue culture. The uptake and stability of oligo 293 varied when cell type or internucleoside linkage was changed.
Development of Naftifine Hydrochloride Alcohol-Free Niosome Gel (2008)

Marketed topical gels of the antifungal drug naftifine hydrochloride contain 50% alcohol as cosolvent. Repeated exposure to alcohol could be detrimental to skin. The aim of this study is to develop an alcohol-free niosome gel containing 1% naftifine hydrochloride. Niosomes were prepared and formulation variables were optimized to achieve maximum entrapment coupled with stability. Maximum drug entrapment and niosome stability entailed imparting a negative charge to the vesicles where entrapment efficiency reached 50%. Niosomes were incorporated into a hydroxyethylcellulose gel. The final gel contained a total drug concentration of 1% (wt/wt) half of which was entrapped in the niosomes. The results suggest the potential usefulness of the niosome gel.
Analogous Interactions in Initiating Complexes of the Classical and Lectin Pathways of Complement (2009)

The classical and lectin pathways of complement activation neutralize pathogens and stimulate key immunological processes. Both pathways are initiated by collagen-containing, soluble pattern recognition molecules associated with specific serine proteases. In the classical pathway, C1q binds to Ab-Ag complexes or bacterial surfaces to activate C1r and C1s. In the lectin pathway, mannan-binding lectin and ficolins bind to carbohydrates on pathogens to activate mannan-binding lectin-associated serine protease 2. To characterize the interactions leading to classical pathway activation, we have analyzed binding between human C1q, C1r, and C1s, which associate to form C1, using full-length and truncated protease components. We show that C1r and C1s bind to C1q independently. The CUB1-epidermal growth factor fragments contribute most toward binding, but CUB2 of C1r, but not of C1s, is also important. Each C1rs tetramer presents a total of six binding sites, one for each of the collagenous domains of C1q. We also demonstrate that subcomponents of the lectin and classical pathways cross-interact. Thus, although the stoichiometries of complexes differ, interactions are analogous, with equivalent contacts between recognition and protease subcomponents. Importantly, these new data are contrary to existing models of C1 and enable us to propose a new model using mannan-binding lectin-mannan-binding lectin-associated serine protease interactions as a template.
Toward a canine model of atopic dermatitis: amplification of cytokine‐gene transcripts in the skin of atopic dogs (1999)

The objectives of the present study were to characterize and compare the repertoire of cytokine-genes transcribed in skin homogenates obtained from normal dogs and dogs with atopic dermatitis (AD) using a reverse-transcriptase polymerase chain reaction and canine-specific cytokine-gene primers. Whereas IL-4 and IL-5 cytokine-gene transcripts were detected more commonly in atopic skin biopsy homogenates, IL-2 mRNA was amplified more often from normal control specimens. IFN-gamma mRNA was detected in 5/29 atopic specimens, 4 of them obtained from the only dog with chronic skin lesions. One-fourth of atopic samples exhibited clear type-2 cytokine profiles; the remainder did not demonstrate polarized repertoires. Conversely, type-1 cytokine profiles were characterized in one-fourth of normal control specimens. The present study establishes, for the first time, the transcription of type-2 cytokine-genes in the skin of dogs with AD. Future experiments investigating the cellular origin and dynamics of allergic cytokine-gene transcription are needed to confirm whether or not canine AD could be considered an immunological model for a human disease.
Combinatorial activities of ionic silver and sodium hexametaphosphate against microorganisms associated with chronic wounds (2011)

The antimicrobial and anti-biofilm potency of silver hydrogels was markedly enhanced by the incorporation of polyphosphate.
Circulating free DNA, p53 antibody and mutations of KRAS gene in endometrial cancer (2009)

This study was conducted to evaluate the significance of circulating free DNA (CFDNA), p53 antibody (p53-Ab) and mutations of KRAS gene in the development of endometrial cancer (EC). A total of 109 patients with EC (87 patients with Type I and 22 patients with Type II) took part in this study. KRAS mutations and CFDNA were detected by means of the PCR-RFLP and enriched by the PCR-RFPL method. ELISA was used to analyze plasma p53-Ab. Tissue expression of P53 protein was evaluated immunohistochemically (IHC). The frequency of KRAS mutations was especially high in Grade 2 of Type I EC. CFDNA was frequently detected in patients with early stage of Type II EC at a low level of grade. It is noteworthy that the p53-Ab positive rate increased in the higher grade of Type I tumors. A significant difference in the number of cases with the p53-Ab was found in the advanced stage of Type I tumors. The frequency of KRAS and p53-Ab correlates with tumor stage only in the Type I EC. Plasma CFDNA and p53-Ab offer a chance to develop a procedure for EC Type II diagnosis. The association between tumor cells related to CFDNA and p53-Ab with Type II tumor suggests that it might potentially serve as a marker in predicting the prognosis and offers a possibility to individualize treatment regimen.
Growth-inhibitory effect of a streptococcal antitumor glycoprotein on human epidermoid carcinoma A431 cells: involvement of dephosphorylation of epidermal growth factor receptor. (2001)

An antitumor glycoprotein [streptococcal acidic glycoprotein (SAGP)] purified from an extract of Streptococcus pyogenes inhibited the growth of human epidermoid carcinoma A431 cells overexpressing epidermal growth factor receptor (EGFR) in a time- and a concentration-dependent manner. The antiproliferative effect of SAGP was diminished by preincubating the cells with pertussis toxin and by coadministration of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases (PTPases). Western blot analysis showed that the immunoreactivity of a M(r) 170,000 band of cell lysate to antiphosphotyrosine antibody was reduced by SAGP, and the effect was abolished by sodium orthovanadate. The phosphotyrosine level of the precipitant with anti-EGFR antibody was reduced by SAGP, which was abolished by preincubation with pertussis toxin or by a coadministration with sodium orthovanadate. The PTPase activity transiently increased in the lysate of cells incubated with SAGP and was inhibitable by sodium orthovanadate. Additionally, preincubation of serum-starved A431 cells with SAGP decreased the epidermal growth factor-induced tyrosine phosphorylation of EGFR, and the effect of SAGP was sodium orthovanadate sensitive. These findings indicate that dephosphorylation of the M(r) 170,000 EGFR by activation of PTPase(s) may be responsible in part for the antiproliferative effect of SAGP on A431 cells.
Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity (2017)

Unwanted immune responses against protein therapeutics can reduce efficacy or lead to adverse reactions. T-cell responses are key in the development of such responses, and are directed against immunodominant regions within the protein sequence, often associated with binding to several allelic variants of HLA class II molecules (promiscuous binders). Herein, we report a novel computational strategy to predict 'de-immunized' peptides, based on previous studies of erythropoietin protein immunogenicity. This algorithm (or method) first predicts promiscuous binding regions within the target protein sequence and then identifies residue substitutions predicted to reduce HLA binding. Further, this method anticipates the effect of any given substitution on flanking peptides, thereby circumventing the creation of nascent HLA-binding regions. As a proof-of-principle, the algorithm was applied to Vatreptacog α, an engineered Factor VII molecule associated with unintended immunogenicity. The algorithm correctly predicted the two immunogenic peptides containing the engineered residues. As a further validation, we selected and evaluated the immunogenicity of seven substitutions predicted to simultaneously reduce HLA binding for both peptides, five control substitutions with no predicted reduction in HLA-binding capacity, and additional flanking region controls. In vitro immunogenicity was detected in 21·4% of the cultures of peptides predicted to have reduced HLA binding and 11·4% of the flanking regions, compared with 46% for the cultures of the peptides predicted to be immunogenic. This method has been implemented as an interactive application, freely available online at http://tools.iedb.org/deimmunization/.
The Key Role of Macrophages in the Immunopathogenesis of Inflammatory Bowel Disease (2000)

Macrophages are important in the host's immunological and inflammatory responses. There is a large population of these cells in the normal intestinal mucosa where they represent the major antigen presenting cell population capable of determining the type of T cell responses that develop to luminal antigens. Studies suggest that the normal intestinal macrophages cannot be easily induced to mediate acute inflammatory responses. In active inflammatory bowel disease there is an increase in the mucosal macrophage population, derived from circulating monocytes. These recruited macrophages are phenotypically different from the resident population of cells and play a major role in mediating the chronic mucosal inflammation seen in patients with ulcerative colitis and Crohn's disease. They secrete many cytokines that are important in the proinflammatory responses, such as interleukin (IL)-1, IL-6, IL-8, IL-12, IL-18, and tumor necrosis factor-alpha. They also release reactive metabolites of oxygen and nitrogen and proteases that degrade the extracellular matrix. Macrophages also appear to be important during resolution of inflammation and repair of the intestinal mucosa that occurs during disease remission.
Scaling up concurrent main-memory column-store scans (2015)

Main-memory column-stores are called to efficiently use modern non-uniform memory access (NUMA) architectures to service concurrent clients on big data. The efficient usage of NUMA architectures depends on the data placement and scheduling strategy of the column-store. Most column-stores choose a static strategy that involves partitioning all data across the NUMA architecture, and employing a stealing-based task scheduler. In this paper, we implement different strategies for data placement and task scheduling for the case of concurrent scans. We compare these strategies with an extensive sensitivity analysis. Our most significant findings include that unnecessary partitioning can hurt throughput by up to 70%, and that stealing memory-intensive tasks can hurt throughput by up to 58%. Based on our analysis, we envision a design that adapts the data placement and task scheduling strategy to the workload.
17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells (2003)

Mutations in the proto-oncogene c-kit cause constitutive kinase activity of its product, KIT protein, and are associated with human mastocytosis and gastrointestinal stromal tumors (GISTs). Although currently available tyrosine kinase inhibitors are effective in the treatment of GISTs, there has been limited success in the treatment of mastocytosis. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin antibiotic, which binds to heat shock protein 90 (hsp90) causes destabilization of various hsp90-dependent kinases important in oncogenesis. Treatment with 17-AAG of the mast cell line HMC-1.2, harboring the Asp816Val and Val560Gly KIT mutations, and the cell line HMC-1.1, harboring a single Val560Gly mutation, causes both the level and activity of KIT and downstream signaling molecules AKT and STAT3 to be down-regulated following drug exposure. These data were validated using Cos-7 cells transfected with wild-type and mutated KIT. 17-AAG promotes cell death of both HMC mast cell lines. In addition, neoplastic mast cells isolated from patients with mastocytosis, incubated with 17-AAG ex vivo, are selectively sensitive to the drug compared to the mononuclear fraction. These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer.
Cost-Effectiveness of Asenapine in the Treatment of Patients with Bipolar I Disorder with Mixed Episodes in an Italian Context (2014)

Results from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.
Object-Oriented Functional Spreadsheets (1997)

. The spreadsheet is one of the most successful computer applications. This popularity derives from an intuitive user interface which both closely mimics traditional bookkeeping and allows non-programmers to develop simple numerical applications. Unfortunately, the current user interface is frustrating and limiting: we believe that the computational model can be simplified to improve usability for non-programmers, extended to provide additional functionality, redesigned to facilitate reuse (to improve performance and integrity), and embedded in an environment which supports a spreadsheet inheritance hierarchy. We propose a new spreadsheet paradigm which incorporates many functional programming features such as higher-order functions, a strong type system, curried partial applications, referential transparency and lazy evaluation. It also incorporates many object-oriented programming features such as a class hierarchy, inheritance, overloading, overriding, subsumption, and dynamic desp...
Direct Effect of Sodium Iodate on Neurosensory Retina (2014)

Systematic characterization of changes associated with NaIO3 injection revealed a large variability in the severity of toxicity induced. Treatment with >20 mg/kg NaIO3 induced visual dysfunction associated with rapid suppression of phototransduction genes and induced oxidative stress in photoreceptors. These results suggest that NaIO3 can directly alter photoreceptor function and survival.
[Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson's disease]. (2002)

A rapid and excessive increase in extracellular dopamine(DA) after L-DOPA administration is considered one of the major causes for L-DOPA-induced peak-dose dyskinesia. Therefore, inhibition of excessive rise in L-DOPA-derived DA is likely to be an ideal treatment for L-DOPA-induced dyskinesia. Based on our previous experimental studies that 8-OH-DPAT, a potent 5-HT1A agonist, attenuates an increase in L-DOPA-induced extracellular DA in the striatum of the rat model of Parkinson's disease, we hypothesized that L-DOPA-induced dyskinesia in patients with Parkinson's disease is alleviated by a 5-HT1A agonist. In the present study, we administered tandospirone citrate, a selective 5-HT1A agonist, to patients with Parkinson's disease suffering from L-DOPA-induced dyskinesia. Tandospirone(15-60 mg/day) was administered to 10 patients with L-DOPA-induced peak-dose dyskinesia. Twelve weeks after tandospirone treatment, duration of dyskinesia, subjective and objective severity of dyskinesia, and parkinsonian features were evaluated. Severity of dyskinesia was decreased in 5 patients; among these, 3 patients experienced slight worsening of parkinsonian features. Four patients showed no change in dyskinesia; among these, 2 patients showed worsening of parkinsonian features. One patient had slight worsening of dyskinesia without any change in parkinsonian features. The present study demonstrated that tandospirone is effective in alleviating L-DOPA-induced dyskinesia in 50% of the patients. However, at the same time 50% patients showed slight worsening of parkinsonian features. Both the anti-dyskinetic effect and the worsening of parkinsonian features are thought to be induced by tandospirone's potent 5-HT1A agonistic activity. Diverse effect of tandospirone may be caused by its partial agonist activity on 5-HT1A receptors, or may indicate that other causes for the expression of dyskinesia exist apart from excessive rise in brain DA levels. Administration of a 5-HT1A agonist is a choice for patients with dyskinesia if the care is taken so as not to induce worsening of parkinsonian features. Further studies such as double-blind trials are needed to confirm the usefulness of a 5-HT1A agonist for L-DOPA-induced dyskinesia.
A novel HBV antisense RNA gene delivery system targeting hepatocellular carcinoma (2003)

AFP-enhancing 4-element complex could deliver HBV antisense RNA targeting on hepatocarcinoma and inhibit both HBV and liver tumor cells in vitro and in vivo.
The absolute bioavailability and metabolic disposition of the novel antimigraine compound zolmitriptan (311C90) (1997)

The data suggest that zolmitriptan undergoes first-pass metabolism and this is more extensive in men than in women. Zolmitriptan has suitable bioavailability for an acute oral migraine treatment and there are no significant unidentified metabolites in man.
Creating a desired lighting pattern with an LED array (2008)

An array of spatially distributed LEDs can produce a desired illumination pattern by individually modulating each LED. A target image can be the desired lighting pattern so that the software could find the best solution to match it. Given a desired illuminance distribution on a target surface, the luminous flux of each single LED that most closely matches the desired distribution must be determined. We review a constrained least squares method for this problem. We show how the quality of the rendering depends on the number of LEDs, array-target distance, and the size of the illuminated area. In particular, as we observed, there is an optimum illumination distance, which is proportional to the square root of the target size and varies inversely with a power of the number of LEDs.
Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series (2006)

The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.
The causal relation between human papillomavirus and cervical cancer (2002)

The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
High-power heating of spherical tori by use of magnetic reconnection (2014)

A novel high-power heating experiment of spherical tori (ST) has been developed in the TS-3 reconnection device using magnetic reconnection of merging STs. This method enables us to inject whole magnetic and thermal energies of a colliding ST into a target ST within short reconnection time. The maximum heating power of 15 MW was obtained in our low-field (0.03–0.08 T) and small-scale (R < 0.2 m) merging experiment. This heating energy is provided mostly by anomalous ion heating effect of magnetic reconnection. The ion heating energy and the merging speed increases with decreasing the q-value (B t component) of the ST. This heating effect causes the β-values of STs to increase by factor 2–3.
Detection of Aberrant Methylation of Four Genes in Plasma DNA for the Detection of Breast Cancer (2006)

These data suggest that epigenetic markers in plasma may be of interest for detection of breast cancer. Identification of additional breast cancer specific methylated genes with higher prevalence in early stage cancers would improve this approach.
Effective activation energy in the Bi-Sr-Ca-Cu-O systems (1993)

Magnetic relaxation in the Bi-Sr-Ca-Cu-O systems was investigated over a wide temperature regime. Previously reported studies of the effective activation energy, U, have been controversial in terms of temperature and field dependence of the critical current density, j/sub c/. The authors considered the temperature dependence of j/sub c/ and constructed the U-j (or M) curves for the Bi-Sr-Ca-Cu-O system. They found that at a constant driving force and temperature, U is considerably higher for 2245 samples than for 2223 samples. This enhancement can be attributed to the flux pinning from finely dispersed calcium- and copper-rich precipitates.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Substrate-dependent negative selection in plants using a bacterial cytosine deaminase gene (1993)

The inability of many higher eukaryotes to convert 5-fluorocytosine to cytotoxic 5-fluorouracil presents the possibility of using the bacterial cytosine deaminase codA gene for negative selection. In transformed plant callus, expression of codA results in cell death on 5-fluorocytosine. In transgenic tobacco and Lotus japonicus plants the substrate-dependent negative marker segregates as a single dominant gene, and on 5-fluorocytosine CodA+ seedlings stop growing at the early seedling stage. Positive selection of CodA+ tobacco on the pyrimidine biosynthetic inhibitor N-(phosphonacetyl)-l-aspartate was obtained, by pyrimidine salvage from external cytosine. Activity of cytosine deaminase was determined by conversion of labelled cytosine to uracil followed by separation in thin layer chromatography. The codA marker therefore provides substrate-dependent negative and positive selection, together with cytosine deaminase reporter activity.
Blood-brain barrier in vitro models and their application in toxicology (2004)

International audience
TULAREMIA (1945)

In the period from Jan. 1, 1928 to July 1, 1944, 225 casesof tularemia were observed in the Charity Hospital of Louisiana at New Orleans. As this is a large series of cases to be studied in a single institution, analysis of these cases from the clinical point of view seems worth while. We shall not attempt an exhaustive survey of the literature, as it is believed that the size of this group of cases will provide a representative sampling of the difficulties in diagnosis and treatment of tularemic infections in general. It is doubtful whether tularemia is a growing disease in incidence as well as in morbidity and mortality. The apparent increase in some sections of the country is probably based on a more general awareness and increasing recognition of the disease. The diagnosis of tularemia is to be considered in any acute febrile illness, and the remarkable similarity