gebhart/patrepeval huggingface dataset:
European and U.S. Perspectives on Civic Republicanism (1994)

It is always a great pleasure to learn from my distinguished friend and colleague Professor Jost Delbr?ck, but it is a special pleasure to learn that U.S. academic neorepublicanism offers a cure for Europe's problems. Such transatlantic confidence salves one's worry about purposelessness and revives one's hope of relevance. Nonetheless, from my U.S. perspective, I think that civic republicanism offers less guidance for the future than Professor Delbr?ck thinks it does from his European perspective. I will explain my reasons in a moment, but let me emphasize the very large area of agreement between Professor Delbr?ck and myself. First, though I am less optimistic about republicanism than is Professor Delbr?ck, I am fundamentally sympathetic with its ideals. Relatedly, the worlds that Professor Delbr?ck and I would like to see develop are, I believe, substantially similar. I just think that republicanism is too incomplete and too contradictory a collection of ideas to get us there. Indeed, the contrast between a European and a U.S. take on republicanism highlights this paradoxical quality. Because republicanism is so vague and contradictory, we can all find in it what we will; but for the same reason, it offers us limited guidance in coping with the problems of a diverse nation-state. Professor Delbr?ck's central concern is that ethnonationalism may be a bar to increased immigration and globalization. In his view, the problem with ethnonationalism is that as a public philosophy it is too culturally specific, too exclusionary, too orthodox: Germany for German persons and German ways, it insists.1 So Professor Delbr?ck seeks a countermodel that will allow many cultures to come together, and he finds one in U.S. civic republicanism, with its emphasis on constitutionalism and dialogic politics.2 In Professor Delbriick's projected Open Republic, national integration will occur simply through shared commitment to a clutch of general, tolerant
Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. (1997)

The direct application of a preconditioning stimulus in clinical practice has been shown, for the first time, to protect patients against irreversible myocyte injury.
Graph Twiddling in a MapReduce World (2009)

As the size of graphs for analysis continues to grow, methods of graph processing that scale well have become increasingly important. One way to handle large datasets is to disperse them across an array of networked computers, each of which implements simple sorting and accumulating, or MapReduce, operations. This cloud computing approach offers many attractive features. If decomposing useful graph operations in terms of MapReduce cycles is possible, it provides incentive for seriously considering cloud computing. Moreover, it offers a way to handle a large graph on a single machine that can't hold the entire graph as well as enables streaming graph processing. This article examines this possibility.
Study Of The Imaging Properties Of Retro-Reflective Materials Used In Head-Mounted Projective Displays (Hmpds) (2002)

The concept of head-mounted projective display (HMPD) has been recently proposed as an alternative to conventional eyepiece-type head-mounted displays (HMDs). An HMPD consists of a pair of miniature projection lenses and flat panel displays mounted on the head and retro-reflective sheeting material placed strategically in the environment. Recent efforts have been made to demonstrate the feasibility of the imaging concept and prototypes have been built. Our research indicates that the quality and properties of the retro-reflective material play critical roles in the overall imaging quality of HMPDs. The retro-reflective sheeting material is commonly used in traffic control and photonic lighting systems, rather than optimized for imaging purpose as in the HMPDs. The size and shape of the microstructures cause artifacts on images. In this paper, we will mainly focus on the evaluation of the various existing retro-reflective materials, and the examination of the impact of the material characteristics on imaging properties. The basic structures of the existing materials are briefly reviewed, the characteristic parameters used to quantify the material properties are defined, and a few samples are evaluated. The characteristics of interest include: the size and shape of the microstructure, the distribution pattern and density of the microstructure, retro-reflectivity, the profile of the reflected light, diffraction artifacts and ghost imaging. Finally, a comprehensive analysis are presented to examine how the material characteristics play their roles in an imaging system, such as the HMPD, and predict the imaging artifacts caused by these characteristics. © 2002 SPIE · 0277-786X/02/$15.00.
Good Manufacturing Practice Production of Self-Complementary Serotype 8 Adeno-Associated Viral Vector for a Hemophilia B Clinical Trial (2011)

To generate sufficient clinical-grade vector to support a phase I/II clinical trial of adeno-associated virus serotype 8 (AAV8)-mediated factor IX (FIX) gene transfer for hemophilia B, we have developed a large-scale, good manufacturing practice (GMP)-compatible method for vector production and purification. We used a 293T-based two-plasmid transient transfection system coupled with a three-column chromatography purification process to produce high-quality self-complementary AAV2/8 FIX clinical-grade vector. Two consecutive production campaigns using a total of 432 independent 10-stack culture chambers produced a total of ∼2 × 10(15) vector genomes (VG) by dot-blot hybridization. Benzonase-treated microfluidized lysates generated from pellets of transfected cells were purified by group separation on Sepharose beads followed by anion-exchange chromatography. The virus-containing fractions were further processed by gel filtration and ultrafiltration, using a 100-kDa membrane. The vector was formulated in phosphate-buffered saline plus 0.25% human serum albumin. Spectrophotometric analysis suggested ∼20% full particles, with only low quantities of nonviral proteins were visible on silver-stained sodium dodecyl sulfate-polyacrylamide gels. A sensitive assay for the detection of replication-competent AAV was developed, which did reveal trace quantities of such contaminants in the final product. Additional studies have confirmed the long-term stability of the vector at -80°C for at least 24 months and for at least 24 hr formulated in the clinical diluent and stored at room temperature within intravenous bags. This material has been approved for use in clinical trials in the United States and the United Kingdom.
APOBEC3G exerts tumor suppressive effects in human hepatocellular carcinoma (2014)

In this study, we collected 44 hepatitis B virus surface antigen positivity HBsAg (+) tumor and nontumor hepatocellular tissues from hepatocellular carcinoma (HCC) patients during hepatectomy, and quantified the APOBEC3G (A3G) mRNA by using a real-time PCR. Our results showed higher expression of A3G mRNA in the nontumor tissues than in the tumor tissues of the HBsAg (+) HCC patients. To further investigate this phenomenon, we constructed a pLV-A3G vector and transfected it into the human HCC cell line, Hep 3B. The results of an immunofluorescence analysis showed the overexpression of A3G in the cytoplasm. We then evaluated A3G cytotoxicity by using a cell viability assay (MTS assay), the results of which showed that Hep 3B cell viability was 88 and 58% after the transfection of pLV and pLV-A3G, respectively, indicating the growth inhibitory effects of A3G on Hep 3B cells. To further evaluate the tumor suppressive effects of A3G, we used a plastic pipette tip to scratch Hep 3B cells grown on a culture dish (to 70-80% confluence) after transfection with pLV-A3G. Our data indicated a ratio of wound closure of 100% in the control cells and in the pLV-expressing cells, compared with 43% in the pLV-A3G-overexpressing cells, 72 h after the wound scratch, as observed using phase-contrast microscopy. These results indicated that A3G inhibits wound healing in Hep 3B cells. Overall, our results suggest that A3G inhibits the growth of human hepatoma cells.
Dynamic shifts in occupancy by TAL1 are guided by GATA factors and drive large-scale reprogramming of gene expression during hematopoiesis (2014)

We used mouse ENCODE data along with complementary data from other laboratories to study the dynamics of occupancy and the role in gene regulation of the transcription factor TAL1, a critical regulator of hematopoiesis, at multiple stages of hematopoietic differentiation. We combined ChIP-seq and RNA-seq data in six mouse cell types representing a progression from multilineage precursors to differentiated erythroblasts and megakaryocytes. We found that sites of occupancy shift dramatically during commitment to the erythroid lineage, vary further during terminal maturation, and are strongly associated with changes in gene expression. In multilineage progenitors, the likely target genes are enriched for hematopoietic growth and functions associated with the mature cells of specific daughter lineages (such as megakaryocytes). In contrast, target genes in erythroblasts are specifically enriched for red cell functions. Furthermore, shifts in TAL1 occupancy during erythroid differentiation are associated with gene repression (dissociation) and induction (co-occupancy with GATA1). Based on both enrichment for transcription factor binding site motifs and co-occupancy determined by ChIP-seq, recruitment by GATA transcription factors appears to be a stronger determinant of TAL1 binding to chromatin than the canonical E-box binding site motif. Studies of additional proteins lead to the model that TAL1 regulates expression after being directed to a distinct subset of genomic binding sites in each cell type via its association with different complexes containing master regulators such as GATA2, ERG, and RUNX1 in multilineage cells and the lineage-specific master regulator GATA1 in erythroblasts.
A comprehensive sequence analysis program for the IBM personal computer (1984)

We have developed a versatile program for the analysis of nucleic acid and protein sequences on the IBM Personal Computer. The program is interactive and self-instructing. It contains all the features generally found in sequence analysis programs on large computers, including extensive homology routines, as well as new procedures for the entry of sequence data. The program contains facilities to store and utilize the entire Nucleic Acid Sequence Data Bank. We have devised a new algorithm to find restriction enzyme sites, which allows our microcomputer program to find all sites on a small plasmid for 100 different enzymes in 1 to 2 minutes.
HIV gag protein is efficiently cross‐presented when targeted with an antibody towards the DEC‐205 receptor in Flt3 ligand‐mobilized murine DC (2009)

DC present exogenous proteins to MHC class I-restricted CD8+ T cells. This function does not require endogenous antigen synthesis within DC, providing the potential to elicit CD8+ T-cell responses to immune complexes, inactivated microbes, dying cells, and proteins such as OVA. In mice, the CD8+ or DEC-205+ DC are specialized for cross-presentation, and this subset can be increased 10-fold in numbers following Fms-like tyrosine kinase 3 ligand (Flt3L) treatment in vivo. Therefore, we studied cross-presentation by abundant Flt3L DC using HIV gag protein. When enriched by positive selection with anti-CD11c beads, cells from Flt3L mice are not only more abundant but are also more highly enriched in CD11chigh DC, particularly the DEC-205+ subset. DC cross-present HIV gag to primed CD8+ T cells, but when the antigen is delivered within an antibody to DEC-205 receptor, cross-presentation becomes 100-fold more efficient than non-targeted antigen. This finding requires gag to be engineered into anti-DEC antibody, not just mixed with antibody. Flt3L DC are a valuable tool to study cross-presentation, since their use overcomes the obstacle posed by the low number of cross-presenting DC in the steady state. These findings support future experiments to use Flt3L to enhance presentation of DC-targeted vaccines.
The role of somatic mutation in determining the affinity of anti-DNA antibodies (2003)

Combinatorial antibody libraries were constructed from the spleen of a patient with concomitant systemic lupus erythematosus and idiopathic thrombocytopenia. Following selection of the libraries with DNA, a panel of 15 anti-DNA Fabs was isolated. Sequence analysis of these antibodies coupled with measurements of their affinities for ss- and dsDNA were used to investigate the role of somatic mutation in affinity maturation of the anti-DNA response. Examination of the germline genes used by these Fabs supports previous studies that suggest there is no restriction of the gene usage in the anti-DNA response. However, data are presented indicating that VH3 genes and the A27 V(kappa) paired with the J(kappa)1 may be over-expressed in the anti-DNA repertoire. Analysis of the role of somatic mutation in increasing affinity for DNA indicates that affinity maturation has occurred and suggests that the CDR1 and CDR2 of the heavy chain are of importance in this process.
Natural antibodies to factor VIII (anti-hemophilic factor) in healthy individuals. (1992)

Spontaneous inhibitors of factor VIII (FVIII) are pathogenic IgG autoantibodies of restricted isotypic heterogeneity found in the plasma of patients presenting with bleeding episodes and low levels of FVIII. We now report the presence of a natural FVIII-neutralizing activity in 85 of 500 plasma samples (17%) from healthy donors. FVIII-inhibitory activity was present in F(ab')2 fragments of purified IgG and was dose-dependent. The titer of anti-FVIII antibodies in normal plasma ranged between 0.4 (threshold of detection) and 2.0 Bethesda units. Anti-FVIII IgG was also detected in normal plasma by using an ELISA. Anti-FVIII antibodies from healthy individuals did not exhibit restricted isotypic heterogeneity. Mean levels of FVIII activity did not differ significantly between individuals with and without detectable anti-FVIII antibodies in plasma. Natural anti-FVIII IgG inhibited FVIII activity in pools of normal plasma and in plasma of certain donors in the pool but did not inhibit FVIII activity in autologous plasma. These observations demonstrate that polyclonal IgG antibodies against procoagulant FVIII are present in healthy individuals. The antibodies are natural IgG autoantibodies and/or antibodies directed against epitopes associated with a so far unidentified allotypic polymorphism of the human FVIII molecule.
Review—Practical Challenges Hindering the Development of Solid State Li Ion Batteries (2017)

Solid state electrolyte systems boasting Li+ conductivity of >10 mS cm<sup>-1</sup> at room temperature have opened the potential for developing a solid state battery with power and energy densities that are competitive with conventional liquid electrolyte systems. The primary focus of this review is twofold. First, differences in Li penetration resistance in solid state systems are discussed, and kinetic limitations of the solid state interface are highlighted. Second, technological challenges associated with processing such systems in relevant form factors are elucidated, and architectures needed for cell level devices in the context of product development are reviewed. Specific research vectors that provide high value to advancing solid state batteries are outlined and discussed.
Reputation Measurement and Malicious Feedback Rating Prevention in Web Service Recommendation Systems (2014)

Web service recommendation systems can help service users to locate the right service from the large number of available web services. Avoiding recommending dishonest or unsatisfactory services is a fundamental research problem in the design of web service recommendation systems. Reputation of web services is a widely-employed metric that determines whether the service should be recommended to a user. The service reputation score is usually calculated using feedback ratings provided by users. Although the reputation measurement of web service has been studied in the recent literature, existing malicious and subjective user feedback ratings often lead to a bias that degrades the performance of the service recommendation system. In this paper, we propose a novel reputation measurement approach for web service recommendations. We first detect malicious feedback ratings by adopting the cumulative sum control chart, and then we reduce the effect of subjective user feedback preferences employing the Pearson Correlation Coefficient. Moreover, in order to defend malicious feedback ratings, we propose a malicious feedback rating prevention scheme employing Bloom filtering to enhance the recommendation performance. Extensive experiments are conducted by employing a real feedback rating data set with 1.5 million web service invocation records. The experimental results show that our proposed measurement approach can reduce the deviation of the reputation measurement and enhance the success ratio of the web service recommendation.
Interactions of very long-chain saturated fatty acids with serum albumin (2002)

The remarkable binding properties of serum albumin have been investigated extensively, but little is known about an important class of fatty acids, the very long-chain saturated fatty acids (VLCFA; >18 carbons). Although VLCFA are metabolized efficiently in normal individuals, they are markers for and possibly causative agents of several peroxisomal disorders. We studied the binding of [(13)C]carboxyl-enriched arachidic (C20:0), behenic (C22:0), lignoceric (C24:0), and hexacosanoic (C26:0) acids to bovine serum albumin (BSA) by (13)C-NMR spectroscopy. For each VLCFA, the NMR spectra showed multiple signals at chemical shifts previously identified for long-chain fatty acids (12-18 carbons), suggesting stabilization of binding by similar, if not identical, interactions of the fatty acid carboxyl anion with basic amino acid residues. The maximal binding (mol of VLCFA/mol of BSA) and the number of observed binding sites decreased with increasing chain length, from 4-5 for C20:0, 3-4 for C22:0, and 2 for C24:0; we validated our previous conclusion that BSA has only one site for C26:0 (Ho, J. K., H. Moser, Y. Kishimoto, and J. A. Hamilton. 1995. J. Clin. Invest. 96: 1455-1463). Analysis of chemical shifts suggested that the highest affinity sites for VLCFA are low affinity sites for long-chain fatty acids. In competition experiments with (13)C-labeled C22:0 (3 mol/mol of BSA) and unlabeled oleic acid, C22:0 bound to BSA in the presence of up to 4 mol of oleic acid/mol of BSA, but 1 mol was shifted into a different site. Our studies suggest that albumin has adequate binding capacity for the low plasma levels of VLCFA with 20 to 26 carbons, but the protein may not be able to bind longer chain VLCFA.
Hydrophilic Cyanine Dyes as Contrast Agents for Near-infrared Tumor Imaging: Synthesis, Photophysical Properties and Spectroscopic In vivo Characterization ¶ (2000)

We have synthesized a group of glucamine and gluosamine-substituted cyanine dyes structurally related to indocyanine green (ICG) and have characterized these compounds with regard to their potential as contrast agents for biomedical optical imaging. The compounds reported herein exhibit increased hydrophilicity and less plasma protein binding (< 50%), and are thus expected to have different pharmacokinetic properties compared with ICG. Furthermore, we measured enhanced fluorescence quantum yields (7-15%) in a physiological environment with respect to ICG. For the derivative with the highest hydrophilicity (5a) the efflux from tumor and normal tissue was monitored by intensity-modulated diffuse optical spectroscopy after intravenous injection into tumor-bearing rats. In comparison with ICG, 5a exhibited a considerably enhanced tissue-efflux half-life (73 min versus less than 10 min for ICG in tumor tissue), a two-fold higher initial tissue absorption coefficient compared to ICG, and finally, it generated an elevated tumor-to-tissue concentration gradient up to 1 h after injection. In conclusion, compounds such as 5a are promising contrast agents for optical imaging, and could facilitate highly sensitive and specific detection of breast cancer or other malignancies by utilizing mechanisms similar to contrast-enhanced magnetic resonance imaging or computerized tomography.
Bone marrow or peripheral blood as a source of stem cells for allogeneic transplantation. (2002)

The general feeling is that PB grafts are indicated for patients with advanced disease, whereas for early phase patients the two sources may give comparable results.
Effects of recombinant human interferons on rheumatoid arthritis B lymphocytes activated by Epstein-Barr virus. (1987)

We evaluated the effects of all 3 classes of recombinant human interferon (IFN) on Epstein-Barr virus (EBV) infection of purified B lymphocytes from patients with rheumatoid arthritis (RA). After EBV infection, RA B cells secreted more IgM and significantly more IgM rheumatoid factor (RF) than normals. Spontaneous (no EBV) proliferation, IgM, and IgM RF were also higher in RA. All 3 types of IFN inhibited dose dependently EBV induced B cell activation. In RA, however, higher doses of each class of IFN were necessary to obtain 50% inhibition. IFN gamma was most potent in normals and RA. Four IgM RF production IFN gamma was significantly more potent than IFN alpha and IFN beta in reducing the spontaneous activation of RA B cells, and a similar trend was seen in B cell proliferation. These findings are discussed in the context of ongoing clinical trials with IFN gamma in RA.
The Binding between the Stem Regions of Human Growth Hormone (GH) Receptor Compensates for the Weaker Site 1 Binding of 20-kDa Human GH (hGH) than That of 22-kDa hGH (2000)

Despite the lower site 1 affinity of the 20-kDa human growth hormone (20K-hGH) for the hGH receptor (hGHR), 20K-hGH has the same hGHR-mediated activity as 22-kDa human GH (22K-hGH) at low hGH concentration and even higher activity at high hGH concentration. This study was performed to elucidate the reason why 20K-hGH can activate hGHR to the same level as 22K-hGH. To answer the question, we hypothesized that the binding between the stem regions of hGHR could compensate for the weaker site 1 binding of 20K-hGH than that of 22K-hGH in the sequential binding with hGHR. To demonstrate it, we prepared 15 types of alanine-substituted hGHR gene at the stem region and stably transfected them into Ba/F3 cells. Using these cells, we measured and compared the cell proliferation activities between 20K- and 22K-hGH. As a result, the activity of 20K-hGH was markedly reduced than that of 22K-hGH in three types of mutant hGHR (T147A, H150A, and Y200A). Regarding these mutants, the dissociation constant of hGH at the first and second step (KD1 and KD2) in the sequential binding with two hGHRs was predicted based on the mathematical cell proliferation model and computational simulation. Consequently, it was revealed that the reduction of the activity in 20K-hGH was attributed to the change of not KD1 but KD2. In conclusion, these findings support our hypothesis, which can account for the same potencies for activating hGHR between 20K- and 22K-hGH, although the site 1 affinity of 20K-hGH is lower than that of 22K-hGH.