gebhart/patrepeval huggingface dataset:
Alzheimer’s Disease: The Challenge of the Second Century (2011)

Alzheimer's disease (AD) was first described a little more than 100 years ago. It is the most common cause of dementia with an estimated prevalence of 30 million people worldwide, a number that is expected to quadruple in 40 years. There currently is no effective treatment that delays the onset or slows the progression of AD. However, major scientific advances in the areas of genetics, biochemistry, cell biology, and neuroscience over the past 25 years have changed the way we think about AD. This review discusses some of the challenges to translating these basic molecular and cellular discoveries into clinical therapies. Current information suggests that if the disease is detected before the onset of overt symptoms, it is possible that treatments based on knowledge of underlying pathogenesis can and will be effective.
The Safety and Pharmacokinetics of Recombinant Soluble CD4 (rCD4) in Subjects with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex (1990)

At the dose levels used in this study, rCD4 appears safe and well tolerated. Serum concentrations of rCD4 were achieved that were comparable to concentrations shown to have antiviral activity in vitro. Further studies are indicated to determine whether rCD4 or related molecules will be useful in treating HIV infection.
Functional properties of the individual thioredoxin-like domains of protein disulfide isomerase (1995)

The two thioredoxin-like domains of human protein disulfide isomerase (PDI) have been produced in bacteria as individual soluble, folded protein molecules, and their functional properties have been compared to those of intact PDI. The two individual domains were very similar in their functional properties, and there were no indications of synergy between them, so it is unlikely that they have intrinsically different functions in PDI. Both domains efficiently introduced disulfide bonds into unfolded model proteins and peptides but were less efficient than PDI with folded substrate protein molecules. Relative to PDI, neither domain had substantial activity in catalyzing disulfide bond isomerization. This pattern of activities is very similar to that of the bacterial catalyst DsbA and probably reflects similarities in the catalytic mechanisms of these proteins. The differences in activity between PDI and its thioredoxin-like domains suggest that other features of the PDI molecule are also required for its complete range of thiol-disulfide exchange activities.
Dynamical solvation effects on the cis-trans isomerization reaction: photoisomerization of merocyanine 540 in polar solvents (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamical solvation effects on the cis-trans isomerization reaction: photoisomerization of merocyanine 540 in polar solventsYavuz Onganer, Mary Yin, David R. Bessire, and Edward L. QuitevisCite this: J. Phys. Chem. 1993, 97, 10, 2344–2354Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/j100112a040https://doi.org/10.1021/j100112a040research-articleACS PublicationsRequest reuse permissionsArticle Views333Altmetric-Citations56LEARN 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 options Get e-Alerts
Acoustic radiation forces at liquid interfaces impact the performance of acoustophoresis (2014)

Acoustophoresis is a method well suited for cell and microbead separation or concentration for downstream analysis in microfluidic settings. One of the main limitations that acoustophoresis share with other microfluidic techniques is that the separation efficiency is poor for particle-rich suspensions. We report that flow laminated liquids can be relocated in a microchannel when exposed to a resonant acoustic field. Differences in acoustic impedance between two liquids cause migration of the high-impedance liquid towards an acoustic pressure node. In a set of experiments we charted this phenomenon and show herein that it can be used to either relocate liquids with respect to each other, or to stabilize the interface between them. This resulted in decreased medium carry-over when transferring microbeads (4% by volume) between suspending liquids using acoustophoresis. Furthermore we demonstrate that acoustic relocation of liquids occurs for impedance differences as low as 0.1%.
TNF αDNA vaccination prevents clinical manifestations of experimental antiphospholipid syndrome (2003)

Naked DNA encoding TNFalpha was introduced to BALB/c mice with experimental antiphospholipid syndrome (APS) induced by beta2GPI. Administration of naked DNA encoding TNFalpha resulted in the generation of immunological memory to its gene product, associated with elevated circulating anti-TNFalpha antibodies. Enriched IgG fraction of the mouse anti-TNFalpha was biologically active since it prevented endothelial cell activation by TNFalpha e.g., inhibition of monocyte adhesion to activated endothelial cells (HUVEC). Mice immunized with beta2GPI, vaccinated with TNFalpha DNA at an early stage of disease development, showed decreased titres of circulating anti-beta2GPI antibodies as compared to the group of mice vaccinated with a control naked DNA. The reduction of antiphospholipid antibody production was followed by amelioration of the foetal loss, increased platelet count to normal values as well as normalization of the prolonged aPTT. APS mice which were introduced to the TNFalpha DNA vector at a later stage of the disease development, showed less improvement in their clinical manifestations. The current study suggests a way in which a DNA vaccine can be employed for induction of a protective immunity in experimental APS.
Pharmacokinetics of Levonantradol in Laboratory Animals and Man (1981)

Levonantradol exhibits potent analgetic activity in standard animal tests and appears not to act directly at opiate receptors. It is currently in clinical trials as an analgesic and antiemetic. The pharmacokinetic behavior of levonantradol, administered orally or intramuscularly, has been investigated in man at dose levels of 0.25 to 3.0 mg and in animals at 0.03 to 10 mg/kg, using a specific HPLC/electrochemical assay. Only desacetyllevonantradol is detected in plasma, due to rapid in vivo deacetylation of levonantradol. In man, at the various doses tested, plasma concentrations of desacetyllevonantradol range from less than 5 to 51 ng/ml. Comparable plasma levels and clinical activity occur at nearly identical doses after oral and intramuscular dosing, suggesting good oral absorption in man. In animals, desacetyllevonantradol has a time of peak concentration of 1 to 2 hours and an elimination half-life of 1 to 2 hours. In animals, a tenfold higher oral dose is needed to achieve the same plasma drug levels as that after an intramuscular dose, suggesting extensive first-pass metabolism following oral administration. Little or no evidence for drug accumulation and sex differences in plasma concentrations of desacetyllevonantradol is noted during chronic intramuscular dosing in laboratory animals.
A chemical probe technique for the determination of reactive halogen species in aqueous solution: Part 2 – chloride solutions and mixed bromide/chloride solutions (2006)

Abstract. Although reactive halogen species (X*=X•, •X2-, X2 and HOX, where X=Br, Cl, or I) are important environmental oxidants, relatively little is known about their kinetics in condensed phases such as seawater and sea-salt particles. Here we describe a new technique to determine reactive chlorine and bromine species in aqueous solutions by using allyl alcohol (CH2=CHCH2OH) as a chemical probe. This probe is combined with competition kinetics in order to determine steady state concentrations of X*(aq). In some cases the technique also can be used to determine the rates of formation and lifetimes of X* in aqueous solution. In a companion paper we reported the results of our method development for aqueous solutions containing only bromide (Br-). In this paper, we discuss method development for solutions containing chloride (Cl-) alone, and for solutions containing both bromide and chloride.
Degradation of Micropatterned Surfaces by Cell-Dependent and -Independent Processes (2002)

This paper describes a study to determine the role of active cellular processes in the initial patterning and eventual degradation of different micropatterned substrates. We compared the effects of serum and cell type on the ability of cells to crawl onto the nonadhesive regions of a variety of patterned substrates. Cells initially patterned in the presence of serum onto substrates manufactured using agarose, pluronics, hexa(ethylene glycol), or polyacrylamide as the nonadhesive. While polyacrylamide remained inert and patterned cells for at least 28 days, agarose and pluronics degraded by gradual desorption of the nonadhesive from the surface independently of the presence of cells. Hexa(ethylene glycol) degraded by a time-dependent mechanism that could be accelerated by cell-dependent oxidative processes. In contrast to the other substrates studied, bovine serum albumin (BSA) patterned cells only under serum-free conditions. The serum did not displace BSA from the surface but instead activated cell-secreted proteases that led to degradation of the substrate. These findings illustrate the importance of specific cellular and noncellular processes in the failure of different nonadhesive chemistries commonly used to pattern cells.
Plasminogen Activator Inhibitor-1 in Tumor Growth, Angiogenesis and Vascular Remodeling (2003)

Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of urokinase type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), and as such is thought to play an important role in the regulation of extracellular matrix remodeling. In blood, PAI-1 is bound to the adhesion protein vitronectin and is associated with vitronectin in fibrin clots and the provisional matrix. Elevated levels of PAI-1 are associated with atherosclerosis and an increased thrombotic tendency, while PAI-1 deficiency leads to increased fibrinolysis and bleeding. PAI-1 is also elevated in many solid tumors and is associated with a poor prognosis in cancer. PAI-1 has been shown to be a potent regulator of both vascular cell migration in vitro and of angiogenesis and tumor growth in vivo. PAI-1 can both promote and inhibit tumor growth and angiogenesis. Low concentrations of PAI-1 can stimulate tumor angiogenesis while treatment of animals with high doses of PAI-1 inhibits angiogenesis and tumor growth. Hence, PAI-1 appears to have a multifunctional role in regulating the migratory and fibrinolytic activity of vascular cells, and this, in turn, may help to explain the many varied actions of PAI-1.
Transient Absorption Spectroscopy and Imaging of Individual Chirality-Assigned Single-Walled Carbon Nanotubes (2012)

Femtosecond transient absorption microscopy was employed to study the excited-state dynamics of individual semiconducting single-walled carbon nanotubes (SWNTs) with simultaneously high spatial (∼200 nm) and temporal (∼300 fs) resolution. Isolated SWNTs were located using atomic force microscopy, and Raman spectroscopy was employed to determine the chiral index of select nanotubes. This unique experimental approach removes sample heterogeneity in ultrafast measurements of these complex materials. Transient absorption spectra of the individual SWNTs were obtained by recording transient absorption images at different probe wavelengths. These measurements provide new information about the origin of the photoinduced absorption features of SWNTs. Transient absorption traces were also collected for individual SWNTs. The dynamics show a fast, ∼1 ps, decay for all the semiconducting nanotubes studied, which is significantly faster than the previously reported decay times for SWNT suspensions. We attributed this fast relaxation to coupling between the excitons created by the pump laser pulse and the substrate.
The MF alpha 1 gene of Saccharomyces cerevisiae: genetic mapping and mutational analysis of promoter elements. (1989)

The activity and cell-type specificity of the promoter of the MF alpha 1 gene of Saccharomyces cerevisiae were examined by measuring expression of an MF alpha 1-SUC2 gene fusion in MATa, MAT alpha, and MATa/MAT alpha cells. A high level of invertase activity was observed only in MAT alpha cells. Weak expression occurred in MATa cells when the hybrid gene was carried on a multicopy plasmid or on a centromere-containing plasmid, but not when the hybrid gene was integrated at the normal MF alpha 1 locus. Analysis of a set of 5'-deletions of the promoter region of the MF alpha 1-SUC2 gene on the multicopy plasmid indicated that sequences from -354 to -274 upstream of the translational start site were required for high level expression in MAT alpha cells. Smaller internal deletions and insertions within the promoter region of the MF alpha 1-SUC2 gene were inserted into the genome at the normal MF alpha 1 locus. These mutations further delineated four promoter domains important for expression: (1) two 26 bp elements (-365 to -340 and -312 to -287) with imperfect dyad symmetry; (2) a 40 bp segment (-264 to -226) that lies about 120 bp upstream of the TATA box; and (3) the TATA box itself (-128 to -122). The transcriptional start sites of the normal MF alpha 1 promoter and of a mutant lacking the TATA box were determined. The MF alpha 1 locus was mapped to the left arm of chromosome XVI, about 22 cM centromere-proximal to the PEP4 gene.
Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. (1986)

The c-erbB-2 gene is a v-erbB-related proto-oncogene which is distinct from the gene encoding the epidermal growth factor receptor. By using two independent methods, hybridization of both sorted chromosomes and metaphase spreads with cloned c-erbB-2 DNA, we mapped the c-erbB-2 locus on human chromosome 17 at q21, a specific breakpoint observed in a translocation associated with acute promyelocytic leukemia. Furthermore, we observed amplification and elevated expression of the c-erbB-2 gene in the MKN-7 gastric cancer cell line. These data suggest possible involvement of the c-erbB-2 gene in human cancer.
Specific transcriptional requirements for positive regulation of the anaerobically inducible pfl operon by ArcA and FNR (1993)

Expression of the pfl operon of Escherichia coli is induced 12- to 15-fold by anaerobiosis and transcription is mediated by seven co-ordinately regulated promoters. The 5' non-translated regulatory region of the operon is approximately 450bp in length and contains two of the seven promoters, termed promoter 6 and promoter 7. Site-directed mutagenesis was used to aid the identification of DNA sequences important in directing transcription from the two promoters and to examine the effects such mutations had on the regulation of anaerobic pfl operon expression. Introduction of chromosomal mutations either in the FNR-binding site or -10 region of promoter 6 blocked transcription from this promoter, as determined by primer extension. Similarly, mutation of the -10 region or the putative FNR half-site located at -50 relative to the transcription start site of promoter 7 severely reduced transcription from that promoter. Prevention of transcription from promoter 6 by the -10 box mutation had no influence on promoter 7 transcription. Surprisingly, however, alteration of the FNR-binding site at promoter 6 did reduce transcription from promoter 7. Thus, a cis mutation located 280 bp downstream on the DNA had a profound effect on promoter 7 transcription. This effect would be commensurate with this mutation disrupting an important interaction between proteins bound at promoter 7 with those bound at promoter 6. Primer extension demonstrated that the promoter 7 mutations had no apparent influence on promoter 6 transcription. By using pfl-lacZ gene fusions it could be shown that the FNR-binding site and -10 region mutations at promoter 6 abolished FNR-dependent anaerobic regulation of pfl operon expression. The equivalent mutations at promoter 7 caused a 25% reduction in anaerobic expression. The residual anaerobic expression in such constructs was FNR-, but no longer ArcA-dependent. A construct in which the -10 region of both promoters 6 and 7 was mutated showed no anaerobic induction of pfl operon expression. This indicates that transcription from both promoters is required for maximal anaerobic regulation by ArcA and FNR.
Adaptive geospatially focused crawling (2009)

Location information on the Web is a precious asset for a multitude of applications and is becoming an increasingly important dimension in Web search. Even though more and more Web pages carry location information, they form only a small share of all pages and are scattered over the Web. To efficiently find and index location-related Web content, we propose an efficient crawling strategy that retrieves precisely those pages that are geospatially relevant while minimizing the amount of the non-spatially-relevant pages within the crawled pages. We propose to address this challenge by expanding the technique of focused crawling to exploit location references on Web pages to specifically retrieve geospatial topics on the Web. In this paper, we describe the design and development of a focused crawler with an adaptive geospatial focus that efficiently retrieves and identifies location-relevant documents on the Web. Drawing from geospatial features of both Web pages and the link graph, a crawl strategy based on Bayesian classifiers prioritizes promising links and pages, leading to a faster coverage of the desired geospatial topic as a means for fast creation of precise geospatial Web indexes. We present evaluations of the system's performance and share our findings on the geospatial Web graph and the distribution of location references on the Web.
Patterns of antigenic expression of human glioma cells. (1991)

Gliomas are known to express over a hundred antigens, and no doubt make many more unknown antigens. Major categories of glioma cell antigens include glial antigens, ECM antigens, muscle antigens, melanoma antigens, "tumor-specific" antigens, and cellular proliferation antigens. A strikingly low number of cultured gliomas express glial antigens. They commonly express not only ectodermal, but also mesenchymal ECM antigens. Tumor-specific antigens have been an elusive goal of neuro-oncologists, but there are bright new prospects in need of further study. These include direct screening of hybridoma supernatants on glioma tissue and targeting glycolipids, glycoproteins, and oncogene products. Cellular proliferation antigens will become increasingly important in predicting prognosis of gliomas. Proliferation antigens of cultured gliomas are under intense scrutiny at present. The extent and evolution of antigenic heterogeneity of neoplastic cells in gliomas raise basic biologic questions with profound clinical ramifications. Individual glioma cell lines may generate more than 30 subtypes of cells with minor to major differences in antigen expression. These include expression of antigens representing multiple different cell lineages. Mesenchymal drift is the tendency of gliomas to progressively lose glial and gain mesenchymal features. Models of in vivo mesenchymal drift occur in glioma cell culture where mechanisms are more easily investigated than in situ. Neither exogenous protein absorption nor fibroblast overgrowth explain the phenomenon. Cells with the mesenchymal marker, fibronectin, overgrow GFAP-positive cells during explanation of gliomas. Many of these fibronectin-positive cells express cytologic and growth characteristics of neoplasia. The source of these cells is unknown. A leading candidate for the source of these neoplastic fibronectin-positive cells is the proliferation of vascular and mesenchymal cell elements of glioma tissue commonly called "endothelial proliferations". However, these elements in tissue do not display the same abnormalities of neoplasia as the fibronectin-positive cells in culture. Understanding this "tissue/explant paradox" may solve the conundrum of mesenchymal drift. In the absence of a counterpart in tissue of these neoplastic fibronectin-positive cells so abundant in glioma cell cultures, mechanisms of mesenchymal drift other than overgrowth of neoplastic mesenchyme must be considered. The occurrence of "dual cells" which express antigenic markers of entirely different cellular lineages suggests the possibility that neoplastic glia generate mesenchymal drift by altered gene expression. Various studies which suggest the capacity of cultured gliomas to alter phenotypic expression of their genes are critically examined and their relevance to mesenchymal drift discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
Theaflavin‐3‐Gallate and Theaflavin‐3′‐Gallate, Polyphenols in Black Tea with Prooxidant Properties (2008)

This study compared the in vitro responses of human gingival fibroblasts and of carcinoma cells derived from the tongue to theaflavin-3-gallate (TF-2A) and theaflavin-3'-gallate (TF-2B), polyphenols in black tea. The antiproliferative and cytotoxic effects of the theaflavin monomers were more pronounced to the carcinoma, than to the normal, cells. In phosphate buffer at pH 7.4, the theaflavins generated hydrogen peroxide and the superoxide anion, suggesting that their mode of toxicity may be due, in part, to the induction of oxidative stress. In a cell-free assay, TF-2A and TF-2B reacted directly with reduced glutathione (GSH), in a time- and concentration-dependent manner. Intracellular storages of GSH were depleted on treatment of the cells with the theaflavin monomers. Depletion of intracellular GSH was more extensive with TF-2A than with TF-2B and was more pronounced in the carcinoma, than in the normal, cells. The toxicities of the theaflavins were potentiated when the cells were cotreated with the GSH depleter, d,l-buthionine-[S,R]-sulfoximine. In the presence of catalase, pyruvate and divalent cobalt, all scavengers of reactive oxygen species, the cytotoxicities of the theaflavins were lessened. TF-2A and TF-2B induced lipid peroxidation in the carcinoma cells, whereas in the fibroblasts, peroxidation was evident upon exposure to TF-2A, but not to TF-2B. These studies demonstrated that the black tea theaflavin monomers, TF-2A and TF-2B, act as prooxidants and induce oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.
Generation of two modes of one component of a Zeeman doublet (1990)

Theoretical and experimental investigations were made of the interaction between two modes of one component of a Zeeman doublet in the case when the Lande factors were different for the upper and lower active levels of a laser transition.