gebhart/patrepeval huggingface dataset:
A guide to histomorphological evaluation of intestinal inflammation in mouse models. (2014)

Histomorphology remains a powerful routine evaluating intestinal inflammation in animal models. Emphasizing the focus of a given animal study, histopathology can overstate differences between established models. We aimed to systematize histopathological evaluation of intestinal inflammation in mouse models facilitating inter-study comparisons. Samples of all parts of the intestinal tract from well-established mouse models of intestinal inflammation were evaluated from hematoxylin/eosin-stained sections and specific observations confirmed by subsequent immunohistochemistry. Three main categories sufficiently reflected the severity of histopathology independent of the localization and the overall extent of an inflammation: (i) quality and dimension of inflammatory cell infiltrates, (ii) epithelial changes and (iii) overall mucosal architecture. Scoring schemata were defined along specified criteria for each of the three categories. The direction of the initial hit proved crucial for the comparability of histological changes. Chemical noxes, infection with intestinal parasites or other models where the barrier was disturbed from outside, the luminal side, showed high levels of similarity and distinct differences to changes in the intestinal balance resulting from inside events like altered cytokine responses or disruption of the immune cell homeostasis. With a high degree of generalisation and maximum scores from 4-8 suitable scoring schemata accounted specific histopathological hallmarks. Truly integrating demands and experiences of gastroenterologists, mouse researchers, microbiologists and pathologists we provide an easy-to-use guideline evaluating histomorphology in mouse models of intestinal inflammation. Standard criteria and definitions facilitate classification and rating of new relevant models, allow comparison in animal studies and transfer of functional findings to comparable histopathologies in human disease.
Mutations in the Yeast KEX2 Gene Cause a Vma−-Like Phenotype: a Possible Role for the Kex2 Endoprotease in Vacuolar Acidification (1998)

Mutants of Saccharomyces cerevisiae that lack vacuolar proton-translocating ATPase (V-ATPase) activity show a well-defined set of Vma- (stands for vacuolar membrane ATPase activity) phenotypes that include pH-conditional growth, increased calcium sensitivity, and the inability to grow on nonfermentable carbon sources. By screening based on these phenotypes and the inability of vma mutants to accumulate the lysosomotropic dye quinacrine in their vacuoles, five new vma complementation groups (vma41 to vma45) were identified. The VMA45 gene was cloned by complementation of the pH-conditional growth of the vma45-1 mutant strain and shown to be allelic to the previously characterized KEX2 gene, which encodes a serine endoprotease localized to the late Golgi compartment. Both vma45-1 mutants and kex2 null mutants exhibit the full range of Vma- growth phenotypes and show no vacuolar accumulation of quinacrine, indicating loss of vacuolar acidification in vivo. However, immunoprecipitation of the V-ATPase from both strains under nondenaturing conditions revealed no defect in assembly of the enzyme, vacuolar vesicles isolated from a kex2 null mutant showed levels of V-ATPase activity and proton pumping comparable to those of wild-type cells, and the V-ATPase complex purified from kex2 null mutants was structurally indistinguishable from that of wild-type cells. The results suggest that kex2 mutations exert an inhibitory effect on the V-ATPase in the intact cell but that the ATPase is present in the mutant strains in a fully assembled state, potentially capable of full enzymatic activity. This is the first time a mutation of this type has been identified.
Oxygenation in cell culture: Critical parameters for reproducibility are routinely not reported (2018)

Mammalian cell culture is foundational to biomedical research, and the reproducibility of research findings across the sciences is drawing increasing attention. While many components contribute to reproducibility, the reporting of factors that impact oxygen delivery in the general biomedical literature has the potential for both significant impact, and immediate improvement. The relationship between the oxygen consumption rate of cells and the diffusive delivery of oxygen through the overlying medium layer means parameters such as medium depth and cell type can cause significant differences in oxygenation for cultures nominally maintained under the same conditions. While oxygenation levels are widely understood to significantly impact the phenotype of cultured cells in the abstract, in practise the importance of the above parameters does not appear to be well recognized in the non-specialist research community. On analyzing two hundred articles from high-impact journals we find a large majority missing at least one key piece of information necessary to ensure consistency in replication. We propose that explicitly reporting these values should be a requirement for publication.
Predicting sun spots using a layered perceptron neural network (1996)

Interest in neural networks has expanded rapidly in recent years. Selecting the best structure for a given task, however, remains a critical issue in neural-network design. Although the performance of a network clearly depends on its structure, the procedure for selecting the optimal structure has not been thoroughly investigated, it is well known that the number of hidden units must be sufficient to discriminate each observation correctly. A large number of hidden units requires extensive computational time for training and often times prediction results may not be as accurate as expected. This study attempts to apply the principal component analysis (PCA) to determine the structure of a multilayered neural network for time series forecasting problems. The main focus is to determine the number of hidden units for a multilayered feedforward network. One empirical experiment with sunspot data is used to demonstrate the usefulness of the proposed approach.
New Human Immunodeficiency Virus, Type 1 Reverse Transcriptase (HIV-1 RT) Mutants with Increased Fidelity of DNA Synthesis (1999)

Infidelity of DNA synthesis by human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) is a presumptive determinant of HIV-1 hypervariability and is incompletely understood at the mechanistic and structural levels. Amino acid substitution at only three residues, including Asp-76 (Kim, B., Hathaway, T. R., and Loeb, L. A. (1996) Biochemistry 37, 5831-5839), is known to increase fidelity. We report here that substitution at Arg-78 can also increase accuracy. Mutant R78A RT showed reduced primer extension in misincorporation assays lacking a complementary dNTP and exhibited a 9-fold decrease in mutation frequency in the M13mp2 lacZ forward mutation assay. Previous structural studies indicate that Arg-78 and Asp-76 lie in a region that interacts with template nucleotides. Interestingly, R78A RT exhibited 6- to 8-fold decreases in binding affinity (K(d)) for RNA and DNA templates relative to wild type RT. In contrast, D76V RT, which also increases fidelity (Kim et al., 1996), showed a 6- to 7-fold increased affinity. The processivity of R78A RT on both RNA and DNA templates was substantially reduced relative to wild type RT, whereas the processivity of D76V RT was increased. We discuss relationships of fidelity, template binding, and processivity in these and other HIV RT mutants.
Verifying business processes using spin (1998)

We present an application of the Spin model-checker in Testbed, a framework for business\nprocess reengineering. Business processes are described by end-users of Testbed in a graphi-\ncal language with a causality-based semantics, called Amber. The Amber language contains\nvarious constructs describing actions, causality relations, disabling, interaction and hierarchi-\ncal composition. Data entities are modelled as variables that are handled by the business\nprocesses. We present a validation methodology for business processes using model-checking\ntechniques. In this approach, an Amber specification is automatically translated into a state\nmachine description in Promela, which is the input language of the Spin model-checker. The\ncorrectness properties, concerning both the behavioural aspects and the data entities used in\nthe specification, are checked on the resulting Promela program using Spin. A prototype\nverification toolset has been developed and successfully applied to various examples inspired\nfrom industrial Amber specifications.
차기 국어과 교육과정의 발전적 방향 : 국어 문화 교과 담론에 대한 비판적 고찰 (2010)

이 연구에서는 최근 국어과 성격 논쟁의 주요 담론으로 등장한 국어 문화 교과 담론을 비판적으로 검토하였다. 국어 문화 교과 담론은 7차 교육과정을 기점으로 국어과 성격과 목표 진술에 지배적 담론의 하나로 자리 잡기 시작하였다. 2007 개정 교육과정을 분석해 본 결과에 의하면, `성격과 목표` 진술에서 국어 문화 교과는 과도하게 서술되었다. 이는 6차 교육과정 이래로 일관되게 유지되어온 지식과 기능 중심의 `내용 체계 및 내용` 부분의 서술과 일관성을 결여하는 결과를 초래하고 있었다. 국어 문화 교과 담론이 국어과 지배 담론이 되기 위해서는 합리적이고 대안적인 내용 체계의 제시, 학력 향상의 문제에 대한 경험적 증거의 제시, 문학 중심의 교육과정과의 차별성 등을 설명해야 할 것이다. 국어과 교육과정의 성격은 국어과 교육 내용으로서의 직접성, 본질성, 고유성을 두루 갖춘 담론을 중심으로 진술하는 것이 바람직하다. 이러한 조건을 고루 갖춘 담론은 기능 교과 담론이다. 차기 국어과 교육과정의 성격 진술은 기능 교과를 중심으로 서술하고, 이를 중심으로 내용 영역을 통합하는 것이 바람직하다.
A General Strategy for Isolation of Endothelial Cells From Murine Tissues (1997)

A rapid, reproducible method for the isolation of murine endothelial cells (ECs) has been developed. Murine ECs were highly enriched by collagenase digestion of mechanically minced lung and subcutaneous sponge implants followed by specific selection with rat anti-mouse CD31 (i.e., PECAM-1) monoclonal antibody-coated magnetic beads (Dynabeads). Pure EC populations were isolated from primary cultures by a second cycle of immunomagnetic selection. The cells from the lung were then cloned by a limiting-dilution method to exclude the possibility of nonendothelial cell contamination. Of the 300 cells plated, 29 clones (approximately 10%) were obtained. The clones were positive for CD31 as measured by flow cytometry, and one clone from the lungs (1G11) and the cells from sponge implants (designated as SIECs) were then subjected to subsequent culture in vitro for 40 and 30 passages (up to 5 months), respectively. Characterization was performed on cells between passage 3 and 10. Both cell types formed contact-inhibited monolayers on gelatin and capillary-like "tubes" on Matrigel. However, 1G11 cells exhibited a "cobblestone" morphology, whereas SIECs had a fibroblast-like appearance at confluence. By flow cytometry and enzyme-linked immunosorbent assay, these cells constitutively expressed CD31, VE-cadherin (cadherin-5), CD34, ICAM-1, VCAM-1, and P-selectin. After stimulation with 30 ng/mL of tumor necrosis factor-alpha, the cells became positive for E-selectin (at 4 hours poststimulation) and the expression of ICAM-1, VCAM-1, and P-selectin was upregulated (after 24 hours of stimulation). The presence of VE-cadherin in 1G11 cells and SIECs was confirmed by fluorescence microscopy and Northern blot analysis. The phenotype and morphology of both cell types were stable during 5 months of culture, and there was no evidence of overgrowth by contaminating cells. Taken together, the approach outlined herein may provide a general strategy for the isolation and culture of ECs from a variety of murine tissues. The general strategy outlined here is simple, effective, and flexible, allowing the inclusion of further positive or negative selection steps.
Human albumin in the management of complications of liver cirrhosis (2012)

Th e use of human albumin in the setting of liver cirrhosis is supported by evidence arising from prospective&#13;\nrandomized trials and meta-analyses. Albumin administration is, therefore widely accepted and recommended&#13;\nby current international guidelines for the prevention of PPCD and acute renal failure in patients with SBP, and&#13;\nthe treatment of HRS as an adjunct to vasoconstrictors. All these complications share the common patho physiological background of reduced eff ective volemia, mainly because of peripheral arterial vasodilation, and the&#13;\nrationale underlying the use of albumin is related to its activity as a plasma expander. However, it is likely that&#13;\nthe benefi cial eff ects of albumin are also linked to its non-oncotic properties, including binding capacity,&#13;\nantioxidant activity, and eff ects on capillary integrity. Th ese eff ects represent the main fi elds of current and&#13;\nfuture research, from which will likely arise further and more appropriate indications for albumin administration&#13;\nin patients with liver disease.
An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform (2014)

Our approach yields high quality sequence data from 16S rRNA gene amplicons using both 250 bp and 300 bp paired-end MiSeq protocols and provides a flexible and cost-effective sequencing option.
NY-ESO-1 may be a potential target for lung cancer immunotherapy. (1999)

NY-ESO-1 expression may be analogous to MAGE gene expression in lung cancer lines in terms of frequency and mechanism of transcriptional regulation. Furthermore, NY-ESO-1 can be presented on lung cancer cells for recognition by HLA-restricted cytotoxic T lymphocytes. Further investigation is warranted to determine if NY-ESO-1 can be exploited for the immunotherapy for lung cancer.
Enhanced growth inhibition of squamous cell carcinoma of the head and neck by combination therapy of paclitaxel and opioid growth factor (2005)

This study evaluated the effects of a combination of opioid growth factor (OGF) and paclitaxel on squamous cell carcinoma of the head and neck (SCCHN) using a tissue culture model of human SCCHN. The combination of OGF and paclitaxel was markedly inhibitory to SCCHN proliferation, reducing growth from control levels by 48 to 69% within 48 h. OGF in combination with carboplatin also depressed cell growth. The effect of a combination of OGF and paclitaxel or carboplatin on SCCHN growth was greater than either of the individual compounds. The efficacy of OGF, but not paclitaxel, was mediated by a naloxone-sensitive receptor and completely reversible. OGF, but no other endogenous or exogenous opioid, altered replication of SCCHN. OGF and paclitaxel depressed DNA synthesis, whereas only paclitaxel induced apoptosis. The combination of OGF and paclitaxel also had a supra-additive effect on the growth of another SCCHN, CAL-27, indicating the ubiquity of the combined drug activity. These data suggest that the combination of a biotherapy (OGF) and chemotherapy (paclitaxel and carboplatin) may provide an enhanced antitumor effect with respect to SCCHN.
Single-agent paclitaxel at first relapse following adjuvant chemotherapy for breast cancer. (1995)

The efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was studied in 27 patients who had relapsed following adjuvant/neoadjuvant chemotherapy for breast cancer. Paclitaxel 225 mg/m2 given as a 3-hour infusion is an effective regimen in this poor-prognosis population. It is well tolerated and can be given in an outpatient setting without routine use of granulocyte colony-stimulating factor. It also can be given in repeated cycles without excessive dose reductions or delays. An objective response rate of 54% was obtained. Responses were seen at all disease sites. Future studies must explore a paclitaxel-containing combination regimen to improve response rates further.
HBTU activation for automated Fmoc solid-phase peptide synthesis. (1992)

Excellent results have been obtained for the Fmoc solid-phase syntheses of peptides using the activating reagent 2-(1H-benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate (HBTU). Activation occurs very rapidly in N,N-dimethylformamide and N-methyl-pyrrolidone, optimal solvents for peptide-resin solvation. It has been observed that complete coupling reactions occur in only 10-30 min. Residues such as Arg, Ile, Leu and Val, which often require double coupling by other activation methods, react with high efficiency by single coupling when HBTU is used. The Fmoc/HBTU chemistry has recently been applied to the peptide synthesizers. The incorporation of trityl side-chain protection for Fmoc-Asn and Fmoc-Gln further enhances coupling efficiencies in difficult sequences.
Potential advantage of using non rectangular ground in small antennas featuring wideband impedance match (2007)

Domination of PIFAs could have satisfied demands set by designers of portable terminals for almost a decade. However, any other form of high efficiency antenna featuring a high degree of miniaturization raises interest both in terms of electromagnetic phenomenon explored and in terms of potential practical uses. Furthermore, some subtle details - neglected during research works - may gain a status go or no go factor in mass market uses. Driven with this motivation we put much attention in our studies into antenna miniaturization with other means than barely the PIFA concept. To bandwidth properties in miniature antennas, a paramount importance has an interaction between the ground and the element. Focus on this interaction turned out to be key to invent coaxially fed miniature antennas without any short which is presented in this paper.
Interaction current in $p p \to p p γ$ (2009)

The nucleon-nucleon bremsstrahlung reaction is investigated based on a fully gauge-invariant relativistic meson-exchange model approach. In order to account consistently for the complicated part of the interaction current (which at present is too demanding to be calculated explicitly), a generalized contact current is introduced following the approach of Haberzettl, Nakayama, and Krewald [Phys. Rev. C74, 045202 (2006)]. The contact interaction current is constructed phenomenologically such that the resulting full bremsstrahlung amplitude satisfies the generalized Ward-Takahashi identity. The formalism is applied to describe the high-precision proton-proton bremsstrahlung data at 190 MeV obtained at KVI [H. Huisman et al., Phys. Rev. C65, 031001(R) (2002)]. The present results show good agreement with the data, thus removing the longstanding discrepancy between the theoretical predictions and experimental data. The present investigation, therefore, points to the importance of properly taking into account the interaction current for this reaction.
Alginate-modifying enzymes: biological roles and biotechnological uses (2015)

Alginate denotes a group of industrially important 1-4-linked biopolymers composed of the C-5-epimers β-D-mannuronic acid (M) and α-L-guluronic acid (G). The polysaccharide is manufactured from brown algae where it constitutes the main structural cell wall polymer. The physical properties of a given alginate molecule, e.g., gel-strength, water-binding capacity, viscosity and biocompatibility, are determined by polymer length, the relative amount and distribution of G residues and the acetyl content, all of which are controlled by alginate modifying enzymes. Alginate has also been isolated from some bacteria belonging to the genera Pseudomonas and Azotobacter, and bacterially synthesized alginate may be O-acetylated at O-2 and/or O-3. Initially, alginate is synthesized as polymannuronic acid, and some M residues are subsequently epimerized to G residues. In bacteria a mannuronan C-5-epimerase (AlgG) and an alginate acetylase (AlgX) are integral parts of the protein complex necessary for alginate polymerization and export. All alginate-producing bacteria use periplasmic alginate lyases to remove alginate molecules aberrantly released to the periplasm. Alginate lyases are also produced by organisms that utilize alginate as carbon source. Most alginate-producing organisms encode more than one mannuronan C-5 epimerase, each introducing its specific pattern of G residues. Acetylation protects against further epimerization and from most alginate lyases. An enzyme from Pseudomonas syringae with alginate deacetylase activity has been reported. Functional and structural studies reveal that alginate lyases and epimerases have related enzyme mechanisms and catalytic sites. Alginate lyases are now utilized as tools for alginate characterization. Secreted epimerases have been shown to function well in vitro, and have been engineered further in order to obtain enzymes that can provide alginates with new and desired properties for use in medical and pharmaceutical applications.
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines (1988)

Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.
Artificial neural networks in medicine (1994)

This Technology Brief provides an overview of artificial neural networks (ANN). A definition and explanation of an ANN is given and situations in which an ANN is used are described. ANN applications to medicine specifically are then explored and the areas in which it is currently being used are discussed. Included are medical diagnostic aides, biochemical analysis, medical image analysis and drug development.
Sequestration of Epidermal Growth Factor Receptors in Non-caveolar Lipid Rafts Inhibits Ligand Binding (2002)

Cholesterol depletion has been shown to increase mitogen-activated protein kinase activation in response to stimulation with epidermal growth factor (EGF) (Furuchi, T., and Anderson, R. G. W. (1998) J. Biol. Chem. 273, 21099-21104). However, the underlying mechanisms are unknown. We show that cholesterol depletion increases EGF binding, whereas cholesterol loading lowers EGF binding. Based on binding analyses, we demonstrate that the observed changes in EGF binding are caused by alterations in the number of EGF receptors available for ligand binding, whereas the affinity of the receptor for EGF remains unaltered. We also show by immunofluorescence that in unstimulated cells the EGF receptor is localized in non-caveolar lipid rafts containing the ganglioside GM1 and that patching of these rafts by cholera toxin B-chain causes co-patching of EGF receptors. Experiments with solubilization in different detergents at 4 degrees C show that the association of the EGF receptor with these rafts is sensitive to Triton X-100 extraction but insensitive to extraction with another non-ionic detergent, Brij 58. Furthermore, experiments with cholesterol-depleted cells show that the association is cholesterol-dependent. We propose that non-caveolar lipid rafts function as negative regulators of EGF receptor signaling by sequestering a fraction of the EGF receptors in a state inaccessible for ligand binding.