gebhart/patrepeval huggingface dataset:
Pulmonary Effects of Chronic Exposure to Liposome Aerosols in Mice (1993)

Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage-directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991).
Development and characterization of APRIL antagonistic monoclonal antibodies for treatment of B-cell lymphomas (2011)

APRIL (A proliferation-inducing ligand) is a TNF family member that binds two TNF receptor family members, TACI and BCMA. It shares these receptors with the closely related TNF family member, B-cell activating factor (BAFF). Contrary to BAFF, APRIL binds heparan sulfate proteoglycans (HSPGs), which regulates cross-linking of APRIL and efficient signaling. APRIL was originally identified as a growth promoter of solid tumors, and more recent evidence defines APRIL also as an important survival factor in several human B-cell malignancies, such as chronic lymphocytic leukemia (CLL). To target APRIL therapeutically, we developed two anti-human APRIL antibodies (hAPRIL.01A and hAPRIL.03A) that block APRIL binding to BCMA and TACI. Their antagonistic properties are unique when compared with a series of commercially available monoclonal anti-human APRIL antibodies as they prevent in vitro proliferation and IgA production of APRIL-reactive B cells. In addition, they effectively impair the CLL-like phenotype of aging APRIL transgenic mice and, more importantly, block APRIL binding to human B-cell lymphomas and prevent the survival effect induced by APRIL. We therefore conclude that these antibodies have potential for further development as therapeutics to target APRIL-dependent survival in B-cell malignancies.
Urinary Water-Soluble Vitamins and Their Metabolite Contents as Nutritional Markers for Evaluating Vitamin Intakes in Young Japanese Women (2008)

Little information is available to estimate water-soluble vitamin intakes from urinary vitamins and their metabolite contents as possible nutritional markers. Determination of the relationships between the oral dose and urinary excretion of water-soluble vitamins in human subjects contributes to finding valid nutrition markers of water-soluble vitamin intakes. Six female Japanese college students were given a standard Japanese diet in the first week, the same diet with a synthesized water-soluble vitamin mixture as a diet with approximately onefold vitamin mixture based on Dietary Reference Intakes (DRIs) for Japanese in the second week, with a threefold vitamin mixture in the third week, and a sixfold mixture in the fourth week. Water-soluble vitamins and their metabolites were measured in the 24-h urine collected each week. All urinary vitamins and their metabolite levels except vitamin B(12) increased linearly in a dose-dependent manner, and highly correlated with vitamin intake (r=0.959 for vitamin B(1), r=0.927 for vitamin B(2), r=0.965 for vitamin B(6), r=0.957 for niacin, r=0.934 for pantothenic acid, r=0.907 for folic acid, r=0.962 for biotin, and r=0.952 for vitamin C). These results suggest that measuring urinary water-soluble vitamins and their metabolite levels can be used as good nutritional markers for assessing vitamin intakes.
BRI2 Interacts with Amyloid Precursor Protein (APP) and Regulates Amyloid β (Aβ) Production (2005)

Transmembrane proteins BRI2 and amyloid precursor protein (APP) co-localize with amyloid beta (Abeta) lesions in sporadic Alzheimer disease and mutations in both precursor proteins are linked to early-onset familial cases of cerebral amyloidosis associated with dementia and/or cerebral hemorrhage. A specific interaction between BRI2 and APP was unveiled by immunoprecipitation experiments using transfected and non-transfected cells. The use of deletion mutants further revealed that stretches 648-719 of APP751 and 46-106 of BRI2, both inclusive of the full transmembrane domains, are sufficient for the interaction. Removal of most of the APP and BRI2 extracellular domains without affecting the interaction implies that both proteins interact when are expressed on the same cell membrane (cis) rather than on adjacent cells (trans). The presence of BRI2 had a modulatory effect on APP processing, specifically increasing the levels of cellular APP as well as beta-secretase-generated COOH-terminal fragments while decreasing the levels of alpha-secretase-generated COOH-terminal fragments as well as the secretion of total APP and Abeta peptides. Determining the precise molecular pathways affected by the specific binding between APP and BRI2 could result in the identification of common therapeutic targets for these sporadic and familial neurodegenerative disorders.
A Convenient Preparation of 5-Iodo-1,4-disubstituted-1,2,3-triazole: Multicomponent One-Pot Reaction of Azide and Alkyne Mediated by CuI−NBS (2008)

The system of CuI and NBS was found to provide both I (+) and Cu (+) for the first time. An efficient method for preparation of 5-iodo-1,4-disubstituted-1,2,3-triazole was achieved by multicomponent one-pot reaction of azides with alkynes in the presence of the novel CuI and NBS catalytic system. The high tolerance of various sensitive groups revealed the potential applications of this method in organic synthesis and drug discovery.
Stereo Matching with Color-Weighted Correlation, Hierarchical Belief Propagation, and Occlusion Handling (2009)

In this paper, we formulate a stereo matching algorithm with careful handling of disparity, discontinuity and occlusion. The algorithm works with a global matching stereo model based on an energy-minimization framework. The global energy contains two terms, the data term and the smoothness term. The data term is first approximated by a color-weighted correlation, then refined in occluded and low-texture areas in a repeated application of a hierarchical loopy belief propagation algorithm. The experimental results are evaluated on the Middlebury data sets, showing that our algorithm is the top performer among all the algorithms listed there.
Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. (1995)

Synthetic peptide analogues of sequences in the HER-2 protooncogene (HER-2) were selected based on the presence of HLA-A2.1 anchor motifs to identify the epitopes on HER-2 recognized by ovarian tumor-reactive CTL. 19 synthetic peptides were evaluated for recognition by four HLA-A2 ovarian-specific cytotoxic T lymphocyte (CTL) lines obtained from leukocytes associated with ovarian tumors. The nonapeptide E75 (HER-2, 369-377:KIFGSLAFL) was efficient in sensitizing T2 cells for lysis by all four CTL lines. This peptide was specifically recognized by cloned CD8+ CTL isolated from one of the ovarian-specific CTL lines. E75-pulsed T2 cells inhibited lysis by the same CTL clone of both an HLA-A2+ HER-2high ovarian tumor and a HER-2high cloned ovarian tumor line transfected with HLA-A2, suggesting that this or a structurally similar epitope may be specifically recognized by these CTL on ovarian tumors. Several other HER-2 peptides were recognized preferentially by one or two CTL lines, suggesting that both common and private HER-2 epitopes may be immunogenic in patients with ovarian tumors. Since HER-2 is a self-antigen, these peptides may be useful for understanding mechanisms of tumor recognition by T cells, immunological tolerance to tumor, and structural characterization of tumor antigens.
Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13 (2007)

Tissue remodeling with fibrosis is a predominant pathophysiological mechanism of many human diseases. Systemic sclerosis is a rare, often lethal, disorder of unknown etiology manifested by dermal fibrosis (scleroderma) and excessive connective tissue deposition in internal organs. Currently, there are no available antifibrotic therapeutics, a reflection of our lack of understanding of this process. Animal models of scleroderma are useful tools to dissect the transcription factors and cytokines that govern fibrosis. A disproportionate increase of type 2 cytokines, like TGF-beta and IL-4, more than type 1 cytokines, like IFN-gamma, is thought to underlie the pathogenesis of scleroderma. In this study, we show that mice deficient in the transcription factor T-box expressed in T cells (T-bet), a master regulator of type 1 immunity, display increased sensitivity to bleomycin-induced dermal sclerosis. Despite the well-established role of T-bet in adaptive immunity, we also show that RAG2(-/-) mice, which lack T and B cells, are vulnerable to bleomycin-induced scleroderma and that RAG2/T-bet double-deficient mice maintain the increased sensitivity to bleomycin observed in T-bet(-/-) mice. Furthermore, overexpression of T-bet in T cells does not affect the induction of skin sclerosis in this model. Lastly, we show that IL-13 is the profibrotic cytokine regulated by T-bet in this model. Together, we conclude that T-bet serves as a repressor of dermal sclerosis through an IL-13-dependent pathway in innate immune cells. T-bet, and its transcriptional network, represent an attractive target for the treatment of systemic sclerosis and other fibrosing disorders.
RESEARCHES ON HYDANTOINS. SYNTHESIS OF THE SOPORIFIC, 4,4-PHENYLETHYL-HYDANTOIN(NIRVANOL) (1922)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRESEARCHES ON HYDANTOINS. SYNTHESIS OF THE SOPORIFIC, 4,4-PHENYLETHYL-HYDANTOIN(NIRVANOL)William T. ReadCite this: J. Am. Chem. Soc. 1922, 44, 8, 1746–1755Publication Date (Print):August 1, 1922Publication History Published online1 May 2002Published inissue 1 August 1922https://pubs.acs.org/doi/10.1021/ja01429a017https://doi.org/10.1021/ja01429a017research-articleACS PublicationsRequest reuse permissionsArticle Views369Altmetric-Citations58LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
mRNA cap-binding protein: cloning of the gene encoding protein synthesis initiation factor eIF-4E from Saccharomyces cerevisiae. (1987)

We have isolated genomic and cDNA clones encoding protein synthesis initiation factor eIF-4E (mRNA cap-binding protein) of the yeast Saccharomyces cerevisiae. Their identity was established by expression of a cDNA in Escherichia coli. This cDNA encodes a protein indistinguishable from purified eIF-4E in terms of molecular weight, binding to and elution from m7GDP-agarose affinity columns, and proteolytic peptide pattern. The eIF-4E gene was isolated by hybridization of cDNA to clones of a yeast genomic library. The gene lacks introns, is present in one copy per haploid genome, and encodes a protein of 213 amino acid residues. Gene disruption experiments showed that the gene is essential for growth.
The novel lectin‐like protein CHB1 is encoded by a chitin‐inducible Streptomyces olivaceoviridis gene and binds specifically to crystalline α‐chitin of fungi and other organisms (1994)

The chb1 gene, which encodes the unique lectin-like alpha-chitin-binding protein CHB1 of Streptomyces olivaceoviridis, was cloned. Transformants of Streptomyces lividans harbouring the plasmid pCHB10 overproduced the extracellular CHB1 protein; the protein showed neither enzymatic nor antifungal activity. Biochemical analyses and immunofluorescence microscopy indicated that CHB1 binds strongly to alpha-chitin, but neither to chitosan and beta-chitin, nor to various types of cellulose. Within hyphae of fungi, the relative location of crystalline chitin was visualized with fluorescein-labelled CHB1. These studies suggest that the new protein could serve as a tool to identify alpha-chitin within different organisms. The chb1 gene consists of a reading frame of 603 bp and its transcription occurred only if the Streptomyces strain was cultivated with chitin as the sole carbon source. The deduced mature CHB1 protein (18.7 kDa) shows no apparent similarity to any known protein. Within a region containing 100 residues of the deduced CHB1 protein, four tryptophan and two asparagine residues as well as one glycine and one cysteine residue were identified, the relative positions of which are analogous to those of several cellulose-binding domains of bacterial glycohydrolases. The results of spectroscopical studies suggest a possible involvement of tryptophan residues in the interaction of CHB1 with alpha-chitin.
Angiotensin II may be useful for the treatment of hypotension in distributive shock, but a safe and efficacious dose is unknown (2014)

Patients with distributive shock who require high-dose vasopressors have a high mortality. Vasopressors belong to two classes: catecholamines and vasopressin analogs. Each class has limitations. Patients receiving catecholamines often develop tachyphylaxis and metabolic complications (for example, lactic acidosis). Vasopressin analogs can cause mesenteric or myocardial ischemia and oliguria. Angiotensin II (ATII) is an endogenous peptide that increases blood pressure and aldosterone production. Preclinical data suggest a role for ATII in the treatment of sepsis-associated acute kidney injury. ATII may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. This is the first randomized clinical trial to date which seeks to evaluate ATII for use in distributive shock.
Topical Delivery of Erythromycin from Various Formulations: An in Vivo Hairless Mouse Study (1996)

Topical products containing erythromycin, a macrolide antibiotic with poor aqueous solubility, are usually formulated as high alcohol content solutions or gels. In this study, we evaluated the deposition of erythromycin base into various strata of hairless mouse skin following topical in vivo application from various low- and nonalcoholic formulations. The formulations tested included nonionic liposomal formulation composed of glyceryl dilaurate, cholesterol, and polyoxyethylene-10-stearyl either at a weight ratio of 57:15:28, two nonionic oil-in-water (o/w) liposomal emulsions containing isopropyl myristate or light mineral oil as the oil phase, a conventional o/w emulsion, a 40% hydroalcoholic solution, and two commercially available topical products. Eight hours after topical administration of these formulations, the efficiency of uptake of erythromycin into the living skin strata was in the order: liposomal isopropyl myristate emulsion > > liposomal mineral oil emulsion > > nonionic liposomes approximately Emgel approximately Theramycin-Z > > conventional emulsion > > hydroalcoholic solution. Alcohol-free liposomal systems are shown to be as efficient as high alcohol content products in facilitating permeation of erythromycin through the stratum corneum into living skin tissue.
A Savings Based Ant System For The Vehicle Routing Problem (2002)

In this paper we study the merit of using the well known Savings algorithm within the framework of an Ant System to tackle the Vehicle Routing Problem (VRP). First, we show the influence of the pheromone information on the solution quality, by comparing the Ant System with a randomized implementation of the Savings algorithm. Second, we evaluate our approach on benchmark data sets. Finally, we provide numerical results about the average and worst case behavior of our algorithm.
High-Dimensional Sparse Factor Modeling: Applications in Gene Expression Genomics (2008)

We describe studies in molecular profiling and biological pathway analysis that use sparse latent factor and regression models for microarray gene expression data. We discuss breast cancer applications and key aspects of the modeling and computational methodology. Our case studies aim to investigate and characterize heterogeneity of structure related to specific oncogenic pathways, as well as links between aggregate patterns in gene expression profiles and clinical biomarkers. Based on the metaphor of statistically derived "factors" as representing biological "subpathway" structure, we explore the decomposition of fitted sparse factor models into pathway subcomponents and investigate how these components overlay multiple aspects of known biological activity. Our methodology is based on sparsity modeling of multivariate regression, ANOVA, and latent factor models, as well as a class of models that combines all components. Hierarchical sparsity priors address questions of dimension reduction and multiple comparisons, as well as scalability of the methodology. The models include practically relevant non-Gaussian/nonparametric components for latent structure, underlying often quite complex non-Gaussianity in multivariate expression patterns. Model search and fitting are addressed through stochastic simulation and evolutionary stochastic search methods that are exemplified in the oncogenic pathway studies. Supplementary supporting material provides more details of the applications, as well as examples of the use of freely available software tools for implementing the methodology.
Enteropathic arthritis: how do the joints talk with the gut? (2001)

Enteropathic arthritis is a label for conditions in which gut pathology is believed to be of pathogenic importance for the developing joint disease. Impaired barrier function, as well as immunogenetic mechanism, are implicated. Recent publications have highlighted strong new support for the homing of lymphocytes from the gut mucosa to joint tissue, persistence of antigen- and cytokine-based immune deficiency. A convincing argument was made for the interesting observation that two distinct types of joint involvement with different class II HLA backgrounds occur in patients with inflammatory bowel disease. A new mechanism implicating dimeric HLA-B27 heavy chains in the pathogenesis of enteropathic arthritis is also presented. Despite evidence for persisting antigen presence, antimicrobial therapy seems ineffective in reactive arthritis.
Entorhinal cortex pathology in Alzheimer's disease (1991)

The anatomical distribution of pathological changes in Alzheimer's disease, although highly selective for only certain brain areas, can be widespread at the endstage of the illness and can affect many neural systems. Propriety for onset among these is a question of importance for clues to the etiology of the disease, but one that is formidable without an experimental animal model. The entorhinal cortex (Brodmann's area 28) of the ventromedial temporal lobe is an invariant focus of pathology in all cases of Alzheimer's disease with selective changes that alter some layers more than others. The authors' findings reveal that it is the most heavily damaged cortex in Alzheimer's disease. Neuroanatomical studies in higher mammals reveal that the entorhinal cortex gives rise to axons that interconnect the hippocampal formation bidirectionally with the rest of the cortex. Their destruction in Alzheimer's disease could play a prominent role in the memory deficits that herald the onset of Alzheimer's disease and that characterize it throughout its course.
Initializing Bayesian Hyperparameter Optimization via Meta-Learning (2015)

Model selection and hyperparameter optimization is crucial in applying machine learning to a novel dataset. Recently, a subcommunity of machine learning has focused on solving this problem with Sequential Model-based Bayesian Optimization (SMBO), demonstrating substantial successes in many applications. However, for computationally expensive algorithms the overhead of hyperparameter optimization can still be prohibitive. In this paper we mimic a strategy human domain experts use: speed up optimization by starting from promising configurations that performed well on similar datasets. The resulting initialization technique integrates naturally into the generic SMBO framework and can be trivially applied to any SMBO method. To validate our approach, we perform extensive experiments with two established SMBO frameworks (Spearmint and SMAC) with complementary strengths; optimizing two machine learning frameworks on 57 datasets. Our initialization procedure yields mild improvements for low-dimensional hyperparameter optimization and substantially improves the state of the art for the more complex combined algorithm selection and hyperparameter optimization problem.
Linear and order statistics combiners for reliable pattern classification (1996)

vi Table of Contents viii List of Figures xiii List of Tables xiv List of Symbols xvii List of Acronyms xx Chapter 1. Introduction 1 Chapter 2. Background and Related Research 8 2.1 Introduction : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 8 2.2 Generalization : : : : : : : : : : : : : : : : : : : : : : : : : : : : 9 2.3 Statistical Background : : : : : : : : : : : : : : : : : : : : : : : : 13 2.4 Regularization : : : : : : : : : : : : : : : : : : : : : : : : : : : : 16 2.5 Motivation for Combining : : : : : : : : : : : : : : : : : : : : : : 18 2.6 Historical sketch : : : : : : : : : : : : : : : : : : : : : : : : : : : 19 viii 2.6.1 Survey of Recent Literature : : : : : : : : : : : : : : : : : 19 2.6.2 Belief and Evidence Combining : : : : : : : : : : : : : : : 22 2.6.3 Economic Forecasting : : : : : : : : : : : : : : : : : : : : 23 2.6.4 Stacked Generalization : : : : : : : : : : : : : : : : : : : : 23 2.6.5 Ensemble Methods : : : : : : : : : : : : : : : : : : : : : ...