gebhart/patrepeval huggingface dataset:
Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis: effects of treatment with cyclosporin A (Neoral). (2002)

These data suggest a dynamic process of T cell recruitment in the joints of RA patients. This process, possibly due to activation and subsequent infiltration of new T cell clones, apparently is influenced by CSA treatment. Synovial tissue T cells were no longer detected after 16 weeks' CSA treatment in 3 patients. In the other CSA treated patients, new T cell clones infiltrated, while other clones were persistently represented in the joints. These data may have important consequences for the design of T cell targeted therapies for RA.
Solution structures of human transforming growth factor .alpha. derived from 1H NMR data (1990)

The 600-MHz 1H NMR spectrum of the des-Val-Val mutant of human transforming growth factor alpha (TGF-alpha) was reassigned at pH = 6.3. The conformation space of des-Val-Val TGF-alpha was explored by distance geometry embedding followed by restrained molecular dynamics refinement using NOE distance constraints and some torsion angle constraints derived from J-couplings. Over 80 long-range NOE constraints were found by completely assigning all resolved cross-peaks in the NOESY spectra. Low NOE constraint violations were observed in structures obtained with the following three different refinement procedures: interactive annealing in DSPACE, AMBER 3.0 restrained molecular dynamics, and dynamic simulated annealing in XPLOR. The segment from Phe15 to Asp47 was found to be conformationally well-defined. Back-calculations of NOESY spectra were used to evaluate the quality of the structures. Our calculated structures resemble the ribbon diagram presentations that were recently reported by other groups. Several side-chain conformations appear to be well-defined as does the relative orientation of the C loop to the N-terminal half of the protein.
Insulin-Like Growth Factor I Correlates with Protein Intake Estimated from the Normalized Protein Catabolic Rate in Hemodialysis Patients (2000)

The s-IGF-I and the s-IGF-I/s-IGFBP-1 ratio were correlated with estimates of protein intake of the patients calculated from urea kinetics (PCRn) but not with direct estimates by the dietitian. The s-IGF-I SD score and the ratio s-IGF-I/s-IGFBP-1 might be a tool to monitor anabolic status and to select hemodialysis patients for therapeutic intervention with recombinant human IGF-I and/or recombinant human growth hormone to counteract catabolism.
High-Mobility Group Box-1 Isoforms as Potential Therapeutic Targets in Sepsis (2006)

High-mobility group box-1 (HMGB1) protein was originally described as a nuclear DNA-binding protein that functions as a structural cofactor critical for proper transcriptional regulation and gene expression. Recent studies indicate that damaged, necrotic cells liberate HMGB1 into the extracellular milieu where it functions as a proinflammatory cytokine. Indeed, HMGB1 represents a novel family of inflammatory cytokines composed of intracellular proteins that can be recognized by the innate immune system as a signal of tissue damage. Posttranslational modifications of HMGB 1 determine its interactions with other proteins and modulate its biological activity. However, very little is known about how these posttranslational modifications of HMGB1 affect its extracellular inflammatory activity and pathological potential. These studies can provide more efficient therapeutic strategies directed against specific HMGB1 isoforms. Therapeutic strategies against these specific HMGB1 isoforms can serve as models for more efficient therapeutic strategies against rheumatoid arthritis or sepsis. This article reviews the recent studies on HMGB1 regulation and their impact on the inflammatory activity and pathological contribution of HMGB 1 to infectious and inflammatory disorders.
Living radical polymerizations based on transition metal complexes (1996)

This review primarily discusses living radical polymerizations with transition metal comlexes of ruthenium, copper, etc., which involve the generation of the radical species from dormant carbon-halogen bonds via the redox reaction at the metal center. This new type of living radical polymerization can be applied around 60-130°C to most commercially available monomers such as styrene, methacrylates and acrylates, even in the presence of water and alcohols, to give polymers with controlled molecular weights and narrow MWD
New Developments in CRISPR Technology: Improvements in Specificity and Efficiency (2018)

In addition, the applications and novel breakthroughs in the field of CRISPR technology will be described.
Surface-enhanced Raman scattering of Langmuir-Blodgett monolayers of phthalocyanine by indium and silver island films (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface-enhanced Raman scattering of Langmuir-Blodgett monolayers of phthalocyanine by indium and silver island filmsRicardo Aroca, Carol Jennings, G. J. Kovac, Rafik O. Loutfy, and P. S. VincettCite this: J. Phys. Chem. 1985, 89, 19, 4051–4054Publication Date (Print):September 1, 1985Publication History Published online1 May 2002Published inissue 1 September 1985https://pubs.acs.org/doi/10.1021/j100265a025https://doi.org/10.1021/j100265a025research-articleACS PublicationsRequest reuse permissionsArticle Views295Altmetric-Citations59LEARN 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
Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis (2015)

These data show that hIFN-β produced by RA FLS transduced with ART-I02 is bioactive and that intra-articular delivery of rAAV5 drives expression of a therapeutic transgene in the joint, with only limited biodistribution of vector DNA to other tissues, supporting progress towards a phase 1 clinical trial for the local treatment of arthritis in patients with RA.
A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder (2012)

The efficacy and tolerability of Lu AA21004 at 5 mg/day, a novel multimodal antidepressant, were assessed in elderly patients with recurrent major depressive disorder. Patients were randomly assigned (1:1:1) to Lu AA21004 5 mg/day, duloxetine 60 mg/day (reference) or to placebo in an 8-week double-blind study. The primary efficacy measure was the 24-item Hamilton Depression Scale (HAM-D(24)) total score (analysis of covariance, last observation carried forward). Patients (mean age 70.6 years) had a mean baseline HAM-D(24) score of 29.0. Lu AA21004 showed significantly (P = 0.0011) greater improvement on the primary efficacy endpoint compared with placebo at week 8 (3.3 points). Duloxetine also showed superiority to placebo at week 8, thereby validating the study. HAM-D(24) response (53.2 vs. 35.2%) and HAM-D(17) remission (29.2 vs. 19.3%) rates at endpoint were higher for Lu AA21004 than for placebo. Lu AA21004 showed superiority to placebo in cognition tests of speed of processing, verbal learning and memory. The withdrawal rate due to adverse events was 5.8% (Lu AA21004), 9.9% (duloxetine) and 2.8% (placebo). Whereas nausea was the only adverse event with a significantly higher incidence on treatment with Lu AA21004 (21.8%) compared with placebo (8.3%), the incidence of nausea, constipation, dry mouth, hyperhidrosis and somnolence was higher for duloxetine. In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder.
Email-based identification and authentication: an alternative to PKI? (2003)

E-mail-based identification and authentication is an emerging alternative to public-key infrastructure. It overcomes many problems inherent with traditional authentication techniques, such as social security numbers, and. provides functional security when used within a limited context.
Effects of Coenzyme Q10 in Early Parkinson Disease (2002)

Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.
Cyclosporin A inhibits CD40 ligand expression in T lymphocytes. (1994)

The ligand for CD40 is expressed on activated T lymphocytes and delivers contact-dependent activation signals to B lymphocytes. The mechanisms regulating CD40 ligand gene expression are largely unknown. Optimal expression of CD40 ligand required activation of protein kinase C and a rise in intracellular calcium concentration. CD40 ligand expression was inhibited by pretreatment of T cells with cyclosporin A. Cyclosporin A analogues inhibited CD40 ligand expression with a potency mirroring the ability of each compound to inhibit calcineurin activity, indicating that calcineurin plays a key role in CD40 ligand gene expression. Cyclosporin A inhibited IL-4-driven CD40 ligand-dependent IgE isotype switching in PBMC but did not inhibit IgE synthesis induced by CD40 mAb plus IL-4. PBMC derived from transplant patients receiving cyclosporin A failed to express CD40 ligand upon stimulation. These results suggest that patients receiving cyclosporin A may be deficient in CD40 ligand-dependent T cell help.
The Microevolution of Mathematical Knowledge: The Case of Randomness (2002)

Abstract In this article, we explore the growth of mathematical knowledge and in particular, seek to clarify the relation between abstraction and context. Our method is to gain a deeper appreciation of the process by which mathematical abstraction is achieved and the nature of abstraction itself, by connecting our analysis at the level of observation with a corresponding theoretical analysis at an appropriate grain size. In this article, we build on previous work to take a further step toward constructing a viable model of the microevolution of mathematical knowledge in context. The theoretical model elaborated here is grounded in data drawn from a study of 10 to 11 year olds' construction of meanings for randomness in the context of a carefully designed computational microworld, whose central feature was the visibility of its mechanisms-how the random behavior of objects actually "worked." In this article, we illustrate the theory by reference to a single case study chosen to illuminate the relation between the situation (including, crucially, its tools and tasks) and the emergence of new knowledge. Our explanation will employ the notion of situated abstraction as an explanatory device that attempts to synthesize existing micro- and macrolevel descriptions of knowledge construction. One implication will be that the apparent dichotomy between mathematical knowledge as decontextualized or highly situated can be usefully resolved as affording different perspectives on a broadening of contextual neighborhood over which a network of knowledge elements applies.
IC–P–045: Using partial–least squares to demonstrate a correlation between combined PET/MRI scores and apolipoprotein E ϵ4 gene dose (2006)

We have recently developed a voxel–based multimodal multivariate image analysis technique using partial least squares (PLS) to characterize the relationship between the patterns in a person's functional and structural brain images. For instance, we have shown how the PLS could compute a combined “PET/MRI score” to characterize the relationship between a person's PET image of regional cerebral glucose metabolism and his or her MRI image of regional gray matter density. To characterize the relationship between PLS–derived PET/MRI scores and three levels of genetic risk for Alzheimer's disease (AD). A “multi–block” version of the PLS was used to analyze FDG PET and volumetric MRI images from 91 cognitively normal persons, 57±4 years of age, including 26 apolipoprotein E (APOE) ϵ4 homozygotes, 25 ϵ4 heterozygotes, and 40 ϵ4 non–carriers. Using this version of the PLS, FDG PET and MRI gray matter density data were treated as independent blocks, APOEϵ4 gene dose was treated as the dependent block, and a super–score deflation scheme was used to prevent mixing of the voxel–based PET and MRI datasets; a combined PET/MRI score was computed from the complementary images in each subject. There was a highly significant correlation between subjects' PLS–derived PET/MRI scores and their APOE ϵ4 gene dose (R=0.65, p=3.2e–12). PLS–derived PET and MRI spatial profiles implicated several brain regions found to be preferentially affected in imaging studies of AD. Our multi–modal PLS algorithm found highly significant correlations between PET/MRI scores and three levels of genetic risk for AD. This study illustrates the potential to capitalize on complementary datasets from the same person to characterize his or her biologically relevant features in a new and more powerful way. Additional studies are needed to determine the extent to which these findings can be confirmed in an independent group of subjects, assist in the unusually early detection, tracking, and diagnosis of AD, used in the cost–effective evaluation of putative disease–slowing and prevention therapies, and extended to the analysis of other complementary complex datasets from the same individual.
In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents (1996)

Oxazolidinones make up a relatively new class of antimicrobial agents which possess a unique mechanism of bacterial protein synthesis inhibition. U-100592 (S)-N-[[3-[3-fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide and U-100766 (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]- 2-oxo-5-oxazolidinyl]methyl]-acetamide are novel oxazolidinone analogs from a directed chemical modification program. MICs were determined for a variety of bacterial clinical isolates; the respective MICs of U-100592 and U-100766 at which 90% of isolates are inhibited were as follows: methicillin-susceptible Staphylococcus aureus, 4 and 4 micrograms/ml; methicillin-resistant S. aureus, 4 and 4 micrograms/ml; methicillin-susceptible Staphylococcus epidermidis, 2 and 2 micrograms/ml; methicillin-resistant S. epidermidis, 1 and 2 micrograms/ml; Enterococcus faecalis, 2 and 4 micrograms/ml; Enterococcus faecium, 2 and 4 micrograms/ml; Streptococcus pyogenes, 1 and 2 micrograms/ml; Streptococcus pneumoniae, 0.50 and 1 microgram/ml; Corynebacterium spp., 0.50 and 0.50 micrograms/ml; Moraxella catarrhalis, 4 and 4 micrograms/ml; Listeria monocytogenes, 8 and 2 micrograms/ml; and Bacteroides fragilis, 16 and 4 micrograms/ml. Most strains of Mycobacterium tuberculosis and the gram-positive anaerobes were inhibited in the range of 0.50 to 2 micrograms/ml. Enterococcal strains resistant to vancomycin (VanA, VanB, and VanC resistance phenotypes), pneumococcal strains resistant to penicillin, and M. tuberculosis strains resistant to common antitubercular agents (isoniazid, streptomycin, rifampin, ethionamide, and ethambutol) were not cross-resistant to the oxazolidinones. The presence of 10, 20, and 40% pooled human serum did not affect the antibacterial activities of the oxazolidinones. Time-kill studies demonstrated a bacteriostatic effect of the analogs against staphylococci and enterococci but a bactericidal effect against streptococci. The spontaneous mutation frequencies of S. aureus ATCC 29213 were <3.8 x 10(-10) and <8 x 10(-11) for U-100592 and U-100766, respectively. Serial transfer of three staphylococcal and two enterococcal strains on drug gradient plates produced no evidence of rapid resistance development. Thus, these new oxazolidinone analogs demonstrated in vitro antibacterial activities against a variety of clinically important human pathogens.
Acyclic stereoselection. 40. Steric effects, as well as .sigma.*-orbital energies, are important in diastereoface differentiation in additions to chiral aldehydes (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcyclic stereoselection. 40. Steric effects, as well as .sigma.*-orbital energies, are important in diastereoface differentiation in additions to chiral aldehydesEric P. Lodge and Clayton H. HeathcockCite this: J. Am. Chem. Soc. 1987, 109, 11, 3353–3361Publication Date (Print):May 1, 1987Publication History Published online1 May 2002Published inissue 1 May 1987https://pubs.acs.org/doi/10.1021/ja00245a027https://doi.org/10.1021/ja00245a027research-articleACS PublicationsRequest reuse permissionsArticle Views1755Altmetric-Citations139LEARN 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
亚洲金融危机和菲律宾的反应：长期的见解（上） (2000)

在亚洲金融危机爆发了一年多以后，人们对于其大致的原因以及应该采取什么措施来防止危机的复发，似乎仍然没有取得一致的看法。尽管有关的论文、讨论会、出版物和官方会议日益增多，人们还是没能对该危机的突然发生、其严重性及其在亚洲和世界其余地区的广泛蔓延作出一致的解释。有一种极端的思想流派认为，该危机的起因是受害国经济基础的弱点，这体现在宏观经济不平衡、过度借贷、货币高估和投资不足等方。
Autoantibody to Human c-myc Oncogene Product in Autoimmune Patient’s Sera (1988)

Sera from autoimmune diseases including systemic lupus erythematosus, dermatomyositis, progressive systemic sclerosis and Sjögren's disease, were examined for reactivity against human c-myc oncogene product. We first found the presence of the autoantibody to human c-myc oncogene product in sera from autoimmune diseases. No significant correlation between the presence of the anti-c-myc product antibody and disease activity, clinical disease types and other autoantibodies such as antinuclear factor, anti-DNA antibody, anti-RNP antibody and anti-Sm antibody were shown in this study.
Site-Directed Mutagenesis and Use of Bile Acid−MTS Conjugates to Probe the Role of Cysteines in the Human Apical Sodium-Dependent Bile Acid Transporter (SLC10A2) (2005)

The residues involved in substrate interaction of the human apical sodium-dependent bile acid transporter (hASBT, SLC10A2) remain undefined. Biochemical modification of conserved cysteine residues has suggested their direct involvement in hASBT function. In the present study, we developed novel methanethiosulfonyl (MTS)−bile salt derivatives and describe their reactivity toward hASBT and its mutants. Endogenous Cys residues were subjected to Ala/Thr scanning mutagenesis and subsequent exposure to affinity inactivators. We show that C51A/T, C105A/T, C144A, and C255A/T are loss-of-function mutations. Additionally, C74A/T cell surface expression was abolished suggesting a role in protein folding and/or trafficking. C270A remained largely unaffected in the presence of 1.0 mM polar and charged MTS reagents (MTSEA, MTSES, and MTSET) and retained function similar to wt-hASBT control. However, in the presence of synthetic cholyl− and chenodeoxycholyl−MTS analogues, C270A displayed a significant decrease in KT and Jmax. Our findings demonstrate that Cys270 is a highly accessible extracellular residue susceptible to thiol modification in its native form that remains largely unaffected upon mutation to Ala. Consequently, C270A provides an ideal scaffold for cysteine scanning mutagenesis studies. Furthermore, the substantial decrease in ligand affinity and maximal transport capacity of C270A suggest that C270 may potentially impact, although not critically, a putative substrate binding domain of hASBT. Overall, bile acid−MTS conjugates can serve as novel and powerful tools to probe the role of endogenous as well as engineered Cys residues and, ultimately, aid in defining their role in the bile acid binding region(s) of hASBT.
Yarrowia lipolytica as a potential producer of citric acid from raw glycerol (2002)

Raw glycerol is an industrial feedstock appearing in increasing quantities as the main by-product of bio-diesel production facilities. The present study describes an alternative way of glycerol valorization, with the production of remarkable amounts of citric acid, in addition to its main valorization way (production of 1,3-propanediol by bacteria).
Alternating current electrokinetic separation and detection of DNA nanoparticles in high‐conductance solutions (2008)

In biomedical research and diagnostics, it is a significant challenge to directly isolate and identify rare cells and potential biomarkers in blood, plasma and other clinical samples. Additionally, the advent of bionanotechnology is leading to numerous drug delivery approaches that involve encapsulation of drugs and imaging agents within nanoparticles, which now will also have to be identified and separated from blood and plasma. Alternating current (AC) electrokinetic techniques such as dielectrophoresis (DEP) offer a particularly attractive mechanism for the separation of cells and nanoparticles. Unfortunately, present DEP techniques require the dilution of blood/plasma, thus making the technology less suitable for clinical sample preparation. Using array devices with microelectrodes over-coated with porous hydrogel layers, AC electric field conditions have been found which allow the separation of DNA nanoparticles to be achieved under high-conductance (ionic strength) conditions. At AC frequencies in the 3000 Hz to 10,000 Hz range and 10 volts peak-to-peak, the separation of 10-microm polystyrene particles into low field regions, and 60-nm DNA-derivatized nanoparticles and 200-nm nanoparticles into high-field regions was carried out in 149 mM 1xPBS buffer (1.68 S/m). These results may allow AC electrokinetic systems to be developed that can be used with clinically relevant samples under physiological conditions.