gebhart/patrepeval huggingface dataset:
Purification and Characterization of an Activator Protein for the Degradation of Glycolipids GM2and GA2by Hexosaminidase A (1979)

The activator protein for the degradation of glycolipids GM2 and GA2 by hexosaminidase A was purified some 2 500-fold from normal human kidney. It has a molecular weight of approximately 25 000 is heat-stable up to 60 degrees C, possesses an isoelectric point of pH 4.8 and is digestible by proteases. Enzymic degradation of the lipid substrates in the presence of this activator proceeds optimally at pH 4.2. The mode of action of the activator was also studied: the protein most probably complexes lipid molecules and presents them to the enzyme which otherwise cannot attack the aggregates formed by the lipids in aqueous solution. The hydrolysis of water-soluble synthetic substrates is not affected by the activator protein. The activator is highly specific for hexosaminidase A: hydrolysis of glycolipids GA2 and GM2 by the hexosaminidase B isoenzyme is almost not enhanced by this protein. The isoenzymes' lipid substrate specificity measured in the presence of the activator is entirely different from that obtained with detergents and can satisfactorily account for the lipid storage pattern observed in patients with variant forms of infantile GM2- gangliosidosis.
<title>Light-emitting diode source for photodynamic therapy</title> (1993)

Lasers have traditionally been the preferred light source for activation of the photosensitizing agents used in photodynamic therapy (PDT). Their monochromaticity, high power, and the ability to couple that high power into optical fibers have dictated their use. There are however, many potential applications for PDT which do not require fiberoptic light delivery, and thus, need not incur the high cost associated with the use of laser systems. Treatment of skin cancer, cervical cancer, and cancers in the oral cavity could be effectively treated with alternative light sources, which would greatly reduce the cost of treatment. This paper will describe the features of a preclinical light emitting diode (LED) based source for photodynamic therapy, designed and built by PDT Systems. The results of an animal study, using the photosensitizer SnET2 activated at 660 nm, which compared the efficacy of PDT performed with a dye laser system with that of the LED system will be presented. Future plans for a clinical version of the LED system will also be discussed.
The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis (2015)

The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.
Advertising, Brand Knowledge and Attitudinal Loyalty in Low-Income Markets: Can Advertising Make a Difference at the 'Bottom-of-the-Pyramid'? (2011)

As the world's attention is shifting towards emerging markets, the issue of marketing to low-income segments at the proverbial 'bottom-of-the-pyramid' is attracting renewed attention. Brand loyalty and its relationship with advertising in those markets deserves particular enquiry as many studies have examined the role of advertising in building brand loyalty in developed markets, but similar work in emerging markets appears scant. This study investigates outdoor advertising that can be used to build attitudinal brand loyalty among low-income consumers in South Africa. In addition, the association of brand knowledge with attitudinal brand loyalty is examined. Based on the authors' conceptualisation that brand awareness drives brand knowledge, which in turn supports attitudinal brand loyalty, the relationship was tested between cognitive image, affective image, brand affect and brand trust, by using variance-based structural equation modelling. The results support advertising as a strong driver in creating attitudinal brand loyalty in this market, while brand knowledge, brand affect and brand trust all exhibit significance in this relationship. These results demonstrate the value of advertising in low-income markets.
AutoScale (2012)

Energy costs for data centers continue to rise, already exceeding $15 billion yearly. Sadly much of this power is wasted. Servers are only busy 10--30% of the time on average, but they are often left on, while idle, utilizing 60% or more of peak power when in the idle state. We introduce a dynamic capacity management policy, AutoScale , that greatly reduces the number of servers needed in data centers driven by unpredictable, time-varying load, while meeting response time SLAs. AutoScale scales the data center capacity, adding or removing servers as needed. AutoScale has two key features: (i) it autonomically maintains just the right amount of spare capacity to handle bursts in the request rate; and (ii) it is robust not just to changes in the request rate of real-world traces, but also request size and server efficiency. We evaluate our dynamic capacity management approach via implementation on a 38-server multi-tier data center, serving a web site of the type seen in Facebook or Amazon, with a key-value store workload. We demonstrate that AutoScale vastly improves upon existing dynamic capacity management policies with respect to meeting SLAs and robustness.
Somatic Gene Transfer of Human ApoA-I Inhibits Atherosclerosis Progression in Mouse Models (1999)

Somatic gene transfer of human apoA-I prevents the development of atherosclerosis in the mouse model.
Pax-2 controls multiple steps of urogenital development (1995)

Urogenital system development in mammals requires the coordinated differentiation of two distinct tissues, the ductal epithelium and the nephrogenic mesenchyme, both derived from the intermediate mesoderm of the early embryo. The former give rise to the genital tracts, ureters and kidney collecting duct system, whereas mesenchymal components undergo epithelial transformation to form nephrons in both the mesonephric (embryonic) and metanephric (definitive) kidney. Pax-2 is a transcriptional regulator of the paired-box family and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. We report here that Pax-2 homozygous mutant newborn mice lack kidneys, ureters and genital tracts. We attribute these defects to dysgenesis of both ductal and mesenchymal components of the developing urogenital system. The Wolffian and Müllerian ducts, precursors of male and female genital tracts, respectively, develop only partially and degenerate during embryogenesis. The ureters, inducers of the metanephros are absent and therefore kidney development does not take place. Mesenchyme of the nephrogenic cord fails to undergo epithelial transformation and is not able to form tubules in the mesonephros. In addition, we show that the expression of specific markers for each of these components is de-regulated in Pax-2 mutants. These data show that Pax-2 is required for multiple steps during the differentiation of intermediate mesoderm. In addition, Pax-2 mouse mutants provide an animal model for human hereditary kidney diseases.
A Base‐Labile Group for 2′‐OH Protection of Ribonucleosides: A Major Challenge for RNA Synthesis (2008)

A novel methodology that disrupts the dogma “RNA synthesis is incompatible with a whole base-labile strategy” has been developed. In this strategy (see scheme), 2′-OH groups are protected by pivaloyloxymethyl groups, compatible with standard base-labile protections for nucleobases and phosphates. Protecting groups are removed in a short two-step all-base procedure to afford RNA efficiently, rapidly, and in high purity without chain rupture or isomerization.
Channeling effects during focused-ion-beam micromachining of copper (2000)

The rapid introduction of copper metallization for semiconductor devices has prompted increased research into focused-ion-beam micromachining of copper. Studies with the aim of increasing the material removal rate of Cu by focused-ion-beam micromachining have been complicated by variable micromachining behavior apparently resulting from differing Cu film morphologies produced by the various Cu deposition procedures. This work examined the micromachining behavior of thin copper films produced by physical-vapor deposition (PVD) and electroplating, as well as single-crystal copper samples. PVD copper films were found to be preferentially textured along 〈111〉, with a columnar grain structure. Channeling effects within this type of grain structure provide a geometric enhancement of the material removal rate of 30% when the sample normal is tilted 12° from the incident ion beam, regardless of sample rotation. Single-crystal (111) copper was found to exhibit similar material removal rate enhancement (averaged over 360° rotation) when tilted 12°, verifying that the etching enhancement observed in the PVD films is directly related to their 〈111〉 texture. Compared to the PVD film, electroplated (EP) copper thin films contained a significantly more random grain orientation. Consequently, the EP films did not exhibit any appreciable variation in material removal rate beyond the expected cosine dependence when tilted with respect to the incident Ga+ beam normal. Micromachining of the electroplated films, which have larger randomly oriented grains, results in grain decoration due to preferential etching producing severe micromachining-induced topography.
Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. II. Identification of cAMP and glucocorticoid regulatory domains. (1986)

Hormonal regulatory elements within the phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) promoter region were mapped using a series of 5' deletions linked to the amino-3'-glycosyl phosphotransferase structural gene. These deletion mutants were stably transfected into the genome of FTO-2B hepatoma cells. A 47-base pair region of the PEPCK promoter was identified which was essential for stimulation by dibutyryl cAMP. A 12-base pair core sequence (CTTACGTCAGAG) within this region shows significant homology with sequences in four other cAMP-regulated genes. There are two glucocorticoid regulatory elements within the promoter, as well as an inhibitory element which depresses the level of basal gene transcription. The deletion of this inhibitory sequence prevents the induction of the chimeric gene by dexamethasone. The existence of the hormone regulatory domains within the PEPCK promoter was confirmed by attaching these elements upstream of the heterologous Herpes simplex virus thymidine kinase structural gene, containing its own promoter.
A procedure for the rapid preparation of mitochondria from rat liver (1982)

A technique for the rapid preparation of mitochondria from rat liver is described. Tissue fractionation is performed by a single centrifugation step with a discontinuous Percoll density gradient. Total preparation times of 5--6 min are achieved by using this method. The mitochondrial fraction obtained is relatively free of contaminating organelles, as judged by marker-enzyme activity determinations. Mitochondria isolated by Percoll-density-gradient centrifugation differ from mitochondria obtained by differential centrifugation [Taylor, Prpić, Exton & Bygrave (1980) Biochem. J. 188, 443--450] in that the former exhibit a higher acceptor control ratio and a higher calcium content. Values obtained for the protonmotive force are not significantly different between the two preparations. The technique described may be widely applicable for studies requiring the rapid preparation of functionally intact and relatively uncontaminated mitochondria.
Convergence of miRNA Expression Profiling, α-Synuclein Interacton and GWAS in Parkinson's Disease (2011)

miRNAs were recently implicated in the pathogenesis of numerous diseases, including neurological disorders such as Parkinson's disease (PD). miRNAs are abundant in the nervous system, essential for efficient brain function and play important roles in neuronal patterning and cell specification. To further investigate their involvement in the etiology of PD, we conducted miRNA expression profiling in peripheral blood mononuclear cells (PBMCs) of 19 patients and 13 controls using microarrays. We found 18 miRNAs differentially expressed, and pathway analysis of 662 predicted target genes of 11 of these miRNAs revealed an over-representation in pathways previously linked to PD as well as novel pathways. To narrow down the genes for further investigations, we undertook a parallel approach using chromatin immunoprecipitation-sequencing (ChIP-seq) analysis to uncover genome-wide interactions of α-synuclein, a molecule with a central role in both monogenic and idiopathic PD. Convergence of ChIP-seq and miRNomics data highlighted the glycosphingolipid biosynthesis and the ubiquitin proteasome system as key players in PD. We then tested the association of target genes belonging to these pathways with PD risk, and identified nine SNPs in USP37 consistently associated with PD susceptibility in three genome-wide association studies (GWAS) datasets (0.46≤OR≤0.63) and highly significant in the meta-dataset (3.36×10⁻⁴<p <1.94×10⁻³). A SNP in ST8SIA4 was also highly associated with PD (p = 6.15×10⁻³) in the meta-dataset. These findings suggest that several miRNAs may act as regulators of both known and novel biological processes leading to idiopathic PD.
A one-pot synthesis of sulfenamides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA one-pot synthesis of sulfenamidesD. H. R. Barton, Robert H. Hesse, Anthony C. O'Sullivan, and M. M. PechetCite this: J. Org. Chem. 1991, 56, 23, 6702–6704Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/jo00023a040https://doi.org/10.1021/jo00023a040research-articleACS PublicationsRequest reuse permissionsArticle Views488Altmetric-Citations19LEARN 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
Hydrogel Droplet Microfluidics for High-Throughput Single Molecule/Cell Analysis (2016)

Heterogeneity among individual molecules and cells has posed significant challenges to traditional bulk assays, due to the assumption of average behavior, which would lose important biological information in heterogeneity and result in a misleading interpretation. Single molecule/cell analysis has become an important and emerging field in biological and biomedical research for insights into heterogeneity between large populations at high resolution. Compared with the ensemble bulk method, single molecule/cell analysis explores the information on time trajectories, conformational states, and interactions of individual molecules/cells, all key factors in the study of chemical and biological reaction pathways. Various powerful techniques have been developed for single molecule/cell analysis, including flow cytometry, atomic force microscopy, optical and magnetic tweezers, single-molecule fluorescence spectroscopy, and so forth. However, some of them have the low-throughput issue that has to analyze single molecules/cells one by one. Flow cytometry is a widely used high-throughput technique for single cell analysis but lacks the ability for intercellular interaction study and local environment control. Droplet microfluidics becomes attractive for single molecule/cell manipulation because single molecules/cells can be individually encased in monodisperse microdroplets, allowing high-throughput analysis and manipulation with precise control of the local environment. Moreover, hydrogels, cross-linked polymer networks that swell in the presence of water, have been introduced into droplet microfluidic systems as hydrogel droplet microfluidics. By replacing an aqueous phase with a monomer or polymer solution, hydrogel droplets can be generated on microfluidic chips for encapsulation of single molecules/cells according to the Poisson distribution. The sol-gel transition property endows the hydrogel droplets with new functionalities and diversified applications in single molecule/cell analysis. The hydrogel can act as a 3D cell culture matrix to mimic the extracellular environment for long-term single cell culture, which allows further heterogeneity study in proliferation, drug screening, and metastasis at the single-cell level. The sol-gel transition allows reactions in solution to be performed rapidly and efficiently with product storage in the gel for flexible downstream manipulation and analysis. More importantly, controllable sol-gel regulation provides a new way to maintain phenotype-genotype linkages in the hydrogel matrix for high throughput molecular evolution. In this Account, we will review the hydrogel droplet generation on microfluidics, single molecule/cell encapsulation in hydrogel droplets, as well as the progress made by our group and others in the application of hydrogel droplet microfluidics for single molecule/cell analysis, including single cell culture, single molecule/cell detection, single cell sequencing, and molecular evolution.
Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones (1992)

The effects exerted on the in vitro development of purified protein derivative (PPD)-specific or Dermatophagoides pteronyssinus group I (Der p I)-specific T cell lines (TCL) and T cell clones (TCC) by IL-4 or IFN-gamma addition or neutralization in human PBMC cultures were examined. PBMC from two normal individuals, which were stimulated with PPD and then cultured in IL-2 alone, developed into PPD-specific TCL and TCC able to produce IFN-gamma and IL-2 but not IL-4 and IL-5 (Th1-like). IFN-gamma or anti-IL-4 antibody addition in bulk cultures before cloning did not influence the PPD-specific TCL profile of cytokine production. In contrast, the addition of IL-4 resulted in the development of PPD-specific TCL and TCC able to produce not only IFN-gamma and IL-2 but also IL-4 and IL-5. PBMC from one atopic Der p I-sensitive patient, which were stimulated with Der p I and then cultured in IL-2 alone, developed into Der p I-specific TCL and TCC able to produce IL-5 and large amounts of IL-4 but no IFN-gamma (Th2-like). The addition in bulk cultures, before cloning, of either IFN-gamma or anti-IL-4 antibody markedly inhibited the development of Der p I-specific T cells into IL-4- and IL-5-producing TCL. Accordingly, the development into Der p I-specific Th2-like TCC was significantly reduced by the addition of IFN-gamma in bulk culture and was virtually suppressed by the presence of both IFN-gamma and anti-IL-4 antibody. These data suggest that the presence or the absence of IL-4 and IFN-gamma in bulk cultures of PBMC before cloning may have strong regulatory effects on the in vitro development of human CD4+ T cells into Th1 or Th2 clones.
PRODUCTION OF TYPE-SPECIFIC C ANTIGEN IN VIRUS-FREE HAMSTER TUMOR CELLS INDUCED BY ADENOVIRUS TYPE 12 (1964)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR (2009)

Clinical resistance to epidermal growth factor receptor (EGFR) inhibition in lung cancer has been linked to the emergence of the EGFR T790M resistance mutation or amplification of MET. Additional mechanisms contributing to EGFR inhibitor resistance remain elusive. By applying combined analyses of gene expression, copy number, and biochemical analyses of EGFR inhibitor responsiveness, we identified homozygous loss of PTEN to segregate EGFR-dependent and EGFR-independent cells. We show that in EGFR-dependent cells, PTEN loss partially uncouples mutant EGFR from downstream signaling and activates EGFR, thereby contributing to erlotinib resistance. The clinical relevance of our findings is supported by the observation of PTEN loss in 1 out of 24 primary EGFR-mutant non-small cell lung cancer (NSCLC) tumors. These results suggest a novel resistance mechanism in EGFR-mutant NSCLC involving PTEN loss.
Expression of E-Cadherin During Osteoclast Formation: A Morphological Study (2008)

It is well known that osteoclasts are derived from multinuclear cells by cell–cell fusion of mononuclear preosteoclasts; however, what molecules are required for osteoclast cell–cell fusion and the role of multinucleation remain uncharacterized.The aim of this work is to clarify a possible mechanism of E-cadherin belonging to the formation of osteoclasts starting from a co-culture model during different temporal steps. As a model of osteoclastogenesis, we used a monocyte/macrophage cell line RAW 264.7 type CRL 2278 cocultured with murine osteoblasts type CRL 12,257. The mechanisms responsible for the fusion process are known in many systems, but it is unclear in the formation of osteoclasts. In other systems in which cell fusion plays a role during the differentiation, it has been shown that this process is regulated from cadherins, which are adhesion proteins. Usually, E-cadherin has been associated with homotypic cell–cell interactions, but it has been shown that E-cadherin might be involved in interaction between different cell types or even different cell adhesion molecules. Our model suggests that E-cadherin is involved in the early steps of osteoclast differentiation at the stage of fusion and multinucleation of osteoclast precursors. (The J Histotechnol 31:51, 2008)Submitted December 26, 2007; accepted with revisions April 30, 2008
Biologically Based Pharmacodynamic Models: Tools For Toxicological Research And Risk Assessment (1991)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More