gebhart/patrepeval huggingface dataset:
B cells help CD8+ T-cell responses (2016)

In this issue of Blood , Guo et al used an anti-CD20 monoclonal antibody (mAb) in a murine model of immune thrombocytopenia (ITP) to show for the first time that B-cell depletion therapy inhibits splenic CD8 + T-cell proliferation and rescues T-cell–mediated ITP. 1
Diurnal, Weekly, and Long-Time Variation in Serum Concentrations of YKL-40 in Healthy Subjects (2008)

Serum YKL-40 is a potential biomarker of prognosis in cancer patients, but assessment of serum YKL-40 requires knowledge of its normal variation. In this study, we evaluated diurnal, weekly, and long-term variation in serum YKL-40 in healthy subjects using a commercial ELISA. The intra-assay coefficient of variation was <or=5.0% and interassay <or=10.2%. Systematic changes in diurnal measurements of serum YKL-40 could not be shown. Physical exercise for 20 min had no effect on serum YKL-40. The within-subject coefficient of variation, including variation over time and interassay, was 28.8% and 30.2% over a period of 2 and 3 years, and the intraclass correlation coefficients were 72.4% and 72.2%, indicating reasonable reliability of serum YKL-40 measurements. The 95% confidence limits for the difference between two measurements (same subject), including interassay variation, were a 52% reduction and a 109% increase in serum YKL-40. These studies show that relatively small variation is found in serum YKL-40 in healthy subjects. However, a single measurement of serum YKL-40 from an individual may not have a prognostic value, and serum YKL-40 alone cannot be a good biomarker for cancer because serum YKL-40 can be elevated in patients with other diseases characterized by inflammation and tissue remodeling.
고객 성격유형별 효과적인 미용 상담시간에 관한 연구 (2012)

This study is aiming to support the beauty industry by researching on the most effective beauty consultation period for a beauty customer by categorizing the customer upon behavior types based on the DiSC behavior type theory. For the study, female and male customers to beauty salons located in Seoul and Gyeonggi-do were surveyed with a short answer survey, and it is composed with general demographic features and effective consultation period per DiSC behavior type. The collected data was analyzed with SPSS 16.0 with a frequency analysis and a cross frequency. As for general demographical features of the surveyed, the number of females was about 3 times more than of males and into the age ranges of 20s and 30s, they were predominantly fell. Single 4 year college-graduate females were taking the largest percentage, and for the occupation, an office worker taking the largest portion and followed by a student. The most answered average income range was a 2 million won range. The study shows that the D-Type is irrelevant with the beauty consultation period, but as for the i-type and c-type, 16 minutes or longer finds to be the most likely answered and 11 to 15 minutes for the S-type. From this study, it is reasonable to believe that the effective beauty consultation period is varied upon DiSC behavior types. I believe that since this study suggests the proper beauty consultation type for each type of customers, it can help improve satisfaction degrees of customers in the beauty industry in general.
Subjective Improvement in Proprioception in 2 Patients With Atypical Friedreich Ataxia Treated With Varenicline (Chantix) (2009)

Two patients with atypical Friedreich ataxia (heterozygotes for a GAA expansion and a G130V point mutation) experienced modest proprioceptive improvements in their extremities within a month of taking varenicline (Chantix), a drug approved for smoking cessation.
Clinical Utility of Measurement of Anti-Müllerian Hormone in Reproductive Endocrinology (2010)

Development of novel antibodies directed against anti-Müllerian hormone (AMH) has allowed measurement in serum and immunohistochemical assessment in tissues. AMH is secreted by granulosa cells in late preantral and small antral follicles and appears in serum in detectable and stable amounts throughout the menstrual cycle. AMH measurement allows an assessment of ovarian reserve with several advantages over other biochemical and biophysical markers. Recent research has highlighted utility in cases of premature ovarian failure, either iatrogenic after treatment for cancer, or naturally occurring, in polycystic ovary syndrome and in the management of superovulation in assisted reproduction. A surge in research activity has taken place over the last 5 yr, and the true place of AMH in reproductive medicine remains to be fully elucidated, but the rapid and widespread adoption of AMH assay into clinical practice demonstrates the degree of interest in this new marker amongst reproductive endocrinologists.
X-ray structures of a hydrolytic antibody and of complexes elucidate catalytic pathway from substrate binding and transition state stabilization through water attack and product release (1997)

The x-ray structures of the unliganded esterase-like catalytic antibody D2.3 and its complexes with a substrate analogue and with one of the reaction products are analyzed. Together with the structure of the phosphonate transition state analogue hapten complex, these crystal structures provide a complete description of the reaction pathway. At alkaline pH, D2.3 acts by preferential stabilization of the negatively charged oxyanion intermediate of the reaction that results from hydroxide attack on the substrate. A tyrosine residue plays a crucial role in catalysis: it activates the ester substrate and, together with an asparagine, it stabilizes the oxyanion intermediate. A canal allows facile diffusion of water molecules to the reaction center that is deeply buried in the structure. Residues bordering this canal provide targets for mutagenesis to introduce a general base in the vicinity of the reaction center.
Shallow-depth 3d interaction (2007)

On traditional tables, people frequently use the third dimension to pile, sort and store objects. However, while effective and informative for organization, this use of the third dimension does not usually extend far above the table. To enrich interaction with digital tables, we present the concept of shallow-depth 3D -- 3D interaction with limited depth. Within this shallow-depth 3D environment several common interaction methods need to be reconsidered. Starting from any of one, two and three touch points, we present interaction techniques that provide control of all types of 3D rotation coupled with translation (6DOF) on a direct-touch tabletop display. The different techniques exemplify a wide range of interaction possibilities: from the one-touch technique, which is designed to be simple and natural, but inherits a degree of imprecision from its simplicity; through to three-touch interaction, which allows precise bimanual simultaneous control of multiple degrees of freedom, but at the cost of simplicity. To understand how these techniques support interaction in shallow-depth 3D, we present a user study that examines the efficiency of, and preferences for, the techniques developed. Results show that users are fastest and most accurate when using the three-touch technique and that their preferences were also strongly in favour of the expressive power available from three-touch.
Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. (1993)

In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of their volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smooth muscle cells in the cap.
Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition (2017)

Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions. Both preventative and therapeutic Ad-HER3-FL immunization delayed tumor growth but were associated with both intratumoral PD-1 expressing CD8<sup>+</sup> T cells and regulatory CD4<sup>+</sup> T cell infiltrates. Immune checkpoint inhibition with either anti-PD-1 or anti-PD-L1 antibodies increased intratumoral CD8<sup>+</sup> T cell infiltration and eliminated tumor following preventive vaccination with Ad-HER3-FL vaccine. The combination of dual PD-1/PD-L1 and CTLA4 blockade slowed the growth of tumor in response to Ad-HER3-FL in the therapeutic model. We conclude that HER3-targeting vaccines activate HER3-specific T cells and induce anti-HER3 specific antibodies, which alters the intratumoral T cell infiltrate and responses to immune checkpoint inhibition.
Click Chemistry, A Powerful Tool for Pharmaceutical Sciences (2008)

Click chemistry refers to a group of reactions that are fast, simple to use, easy to purify, versatile, regiospecific, and give high product yields. While there are a number of reactions that fulfill the criteria, the Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes has emerged as the frontrunner. It has found applications in a wide variety of research areas, including materials sciences, polymer chemistry, and pharmaceutical sciences. In this manuscript, important aspects of the Huisgen cycloaddition will be reviewed, along with some of its many pharmaceutical applications. Bioconjugation, nanoparticle surface modification, and pharmaceutical-related polymer chemistry will all be covered. Limitations of the reaction will also be discussed.
Blocking the Initiation of Coagulation by RNA Aptamers to Factor VIIa (2000)

The tissue factor/factor VIIa complex is thought to be the primary initiator of most physiologic blood coagulation events. Because of its proximal role in this process, we sought to generate new inhibitors of tissue factor/factor VIIa activity by targeting factor VIIa. We employed a combinatorial RNA library and in vitro selection methods to isolate a high affinity, nuclease-resistant RNA ligand that binds specifically to coagulation factor VII/VIIa. This RNA inhibits the tissue factor-dependent activation of factor X by factor VIIa. Kinetic analyses of the mechanism of action of this RNA suggest that it antagonizes factor VIIa activity by preventing formation of a functional factor VII/tissue factor complex. Furthermore, this RNA significantly prolongs the prothrombin time of human plasma in a dose dependent manner, and has an in vitro half-life of approximately 15 h in human plasma. Thus, this RNA ligand represents a novel class of anticoagulant agents directed against factor VIIa.
Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis. (2003)

Physiologically, angiogenesis is tightly regulated, or otherwise it leads to pathological processes, such as tumors, inflammatory diseases, gynecological diseases and diabetic retinopathy. The vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis. The VEGF gene expression is regulated by a variety of stimuli. Hypoxia is one of the most potent inducers of the VEGF expression. The hypoxia inducible factor 1 (HIF-1) plays as a key transcription factor in hypoxia-mediated VEGF gene upregulation. Nitric oxide (NO) as well as hypoxia is reported to upregulate the VEGF gene by enhancing HIF-1 activity. The Akt/protein kinase B (PKB) pathway may be involved in NO-mediated HIF-1 activation in limited cell lines. There are some reports of negative effects of NO on HIF-1 and VEGF activity. These conflicting data of NO effects may be attributed mainly to the amount of released NO. Indeed, NO can be a positive or negative modulator of the VEGF gene under the same conditions simply by changing its amounts. The VEGF-mediated angiogenesis requires NO production from activated endothelial NO synthase (eNOS). Activation of eNOS by VEGF involves several pathways including Akt/PKB, Ca(2+)/calmodulin, and protein kinase C. The NO-mediated VEGF expression can be regulated by HIF-1 and heme oxygenase 1 (HO-1) activity, and the VEGF-mediated NO production by eNOS can be also modulated by HIF-1 and HO-1 activity, depending upon the amount of produced NO. These reciprocal relations between NO and VEGF may contribute to regulated angiogenesis in normal tissues.
Aminolevulinic Acid Derivatives and Liposome Delivery as Strategies for Improving 5-Aminolevulinic Acid- Mediated Photodynamic Therapy (2006)

Photodynamic Therapy employing 5-aminolevulinic acid (ALA) as a precursor of the photosensitizer Protoporphyrin IX has become a promising approach to treat superficial cancers. However, the hydrophilic nature of the ALA molecule somewhat limits the penetration through the skin as well as all cell membranes. Different attempts are currently under investigation to enhance ALA penetration, such as the development of new synthetic and more lipophilic molecules derived from ALA and the incorporation of ALA into lipophilic vehicles such as liposomes. Among the new synthesized molecules, we can find ALA esters, ALA aminoacid derivatives and ALA dendrimers. In general, there is consensus that the promising results obtained in vitro with ALA esters cannot be reproduced in vivo. However, ALA methyl ester (1) has been widely used for treatment of skin malignancies and ALA hexyl ester (15) proved to be more powerful than ALA in bladder imaging. ALA aminoacid derivatives have been designed to use specific cellular aminopeptidases to targeting tumors, and it was shown that they can be metabolized to ALA with some specificity.
In vivo compatibility and degradation of crosslinked gelatin gels incorporated in knitted Dacron (2000)

Gelatin gels were applied to porous Dacron meshes with the aim of using these gels for local drug delivery. In this article, the biocompatibility and degradation of gelatin gels with different crosslink densities applied in Dacron were studied in vivo by subcutaneous implantation in rats. Dacron discs were treated with carbon dioxide gas plasma to improve hydrophilicity, and subsequently impregnated with gelatin type B. The gelatin samples were crosslinked to different extents using various amounts of water-soluble carbodiimide (EDC) and N-hydroxysuccinimide (NHS). After 6 h, 2, 5, and 10 days, and 3, 6, and 10 weeks of postimplantation, the tissue reactions and biodegradation were studied by light microscopy. The early reaction of macrophages and polymorphonuclear cells to crosslinked gelatin was similar to or milder than Dacron. Giant cell formation was predominantly aimed at Dacron fibers and was markedly reduced in the presence of a crosslinked gelatin coating. At week 10 of implantation, the crosslinked gelatin gels were still present in the Dacron matrix. The gelatin degradation was less for samples with the highest crosslink density. The gelatin gel with the lowest crosslink density showed clear cellular ingrowth, starting after 6 weeks of implantation. The intermediate and high crosslinked gelatin gels showed little or no ingrowth. In these gels, giant cells were involved in the phagocytosis of gelatin parts at week 10. Application of carbodiimide crosslinked gelatin gels in Dacron is suitable for medical applications because of the good biocompatibility of the gels and the possibility of adapting the degradation rate of gelatin to a specific application.
Tissue factor contributes to microvascular defects after focal cerebral ischemia. (1993)

These results indicate that tissue factor-mediated events may also contribute to no-reflow in noncapillary microvessels after focal cerebral ischemia.
Increasing cAMP Attenuates Induction of Inducible Nitric-oxide Synthase in Rat Primary Astrocytes (1997)

Nitric oxide produced by inducible nitric-oxide synthase (iNOS) in different brain cells in response to various cytokines plays an important role in the pathophysiology of stroke and other neurodegenerative diseases. This study underlines the importance of cAMP in inhibiting the induction of NO production by lipopolysaccharide (LPS) and cytokines in rat primary astrocytes. Compounds (forskolin, 8-bromo-cAMP, and (Sp)-cAMP) that increase cAMP and activate protein kinase A (PKA) were found to inhibit LPS- and cytokine-mediated production of NO as well as the expression of iNOS, whereas compounds (H-89 and (Rp)-cAMP) that decrease cAMP and PKA activity stimulated the production of NO and the expression of iNOS in rat primary astrocytes. Forskolin, but not the inactive analogue 1,9-dideoxyforskolin, inhibited NO production and iNOS expression in a dose-dependent manner in astrocytes. The inhibition of LPS- and/or cytokine-induced NO production in rat C6 glial cells by forskolin suggest that similar to astrocytes, iNOS expression in C6 cells is also regulated by similar mechanisms. In contrast, in rat peritoneal macrophages the cAMP analogues stimulated the LPS- and cytokine-induced production of NO. In vitro, the PKA had no effect on iNOS activity in LPS-treated astrocytes or macrophages, suggesting that PKA modulates the intracellular signaling events associated with the induction of iNOS biogenesis rather than the post-translational modification of iNOS. The compounds which activate PKA activity, blocked the activation of NF-kappabeta in astrocytes but stimulated the activation of NF-kappabeta in macrophages. This differential regulation of NF-kappabeta activation in two different cell types (astrocytes and macrophages) by the same second messenger (cAMP) indicates that intracellular events or pathways in the activation of NF-kappabeta may be different. Moreover, this inhibition of iNOS expression in LPS- and cytokine-treated astrocytes by cAMP may be of therapeutic potential in NO-mediated cytotoxicity in neurodegenerative diseases.
Association of Cerebrospinal Fluid Deficiency of 5-Methyltetrahydrofolate, but Not S-Adenosylmethionine, with Reduced Concentrations of the Acid Metabolites of 5-Hydroxytryptamine and Dopamine (1994)

1. Folate deficiency, or inborn errors of folate metabolism, cause reduced turnover of 5-hydroxytryptamine (serotonin), and perhaps dopamine, in the central nervous system. The mechanism by which this occurs are not known. One possibility is that this is mediated by deficiency of the methyl-donor S-adenosylmethionine. 2. To test this in humans, we have measured cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid and homovanillic acid, metabolites of 5-hydroxytryptamine and dopamine, respectively, in children with inborn errors of the methyl-transfer pathway. These children are naturally deficient in 5-methyltetrahydrofolate, S-adenosylmethionine or both before treatment, and replete with S-adenosylmethionine, but not necessarily with 5-methyltetrahydrofolate, during treatment. 3. Children with subnormal cerebrospinal fluid concentrations of 5-methyltetrahydrofolate had significantly reduced concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. Children with subnormal cerebrospinal fluid concentrations of S-adenosylmethionine did not have significantly reduced concentrations of these metabolites. 4. We conclude that the mechanism by which deficiency of 5-methyltetrahydrofolate causes reduced 5-hydroxytryptamine and dopamine turnover is unlikely to be mediated by S-adenosylmethionine.
Design of a Compact Disk-like Microfluidic Platform for Enzyme-Linked Immunosorbent Assay (2004)

This paper presents an integrated microfluidic device on a compact disk (CD) that performs an enzyme-linked immunosorbent assay (ELISA) for rat IgG from a hybridoma cell culture. Centrifugal and capillary forces were used to control the flow sequence of different solutions involved in the ELISA process. The microfluidic device was fabricated on a plastic CD. Each step of the ELISA process was carried out automatically by controlling the rotation speed of the CD. The work on analysis of rat IgG from hybridoma culture showed that the microchip-based ELISA has the same detection range as the conventional method on the 96-well microtiter plate but has advantages such as less reagent consumption and shorter assay time over the conventional method.
Pyruvate Kinase M2: A Potential Target for Regulating Inflammation (2016)

Pyruvate kinase (PK) is the enzyme responsible for catalyzing the last step of glycolysis. Of the four PK isoforms expressed in mammalian cells, PKM2 has generated the most interest due to its impact on changes in cellular metabolism observed in cancer as well as in activated immune cells. As our understanding of dysregulated metabolism in cancer develops, and in light of the growing field of immunometabolism, intense efforts are in place to define the mechanism by which PKM2 regulates the metabolic profile of cancer as well as of immune cells. The enzymatic activity of PKM2 is heavily regulated by endogenous allosteric effectors as well as by intracellular signaling pathways, affecting both the enzymatic activity of PKM2 as a PK and the regulation of the recently described non-canonical nuclear functions of PKM2. We here review the current literature on PKM2 and its regulation, and discuss the potential for this protein as a therapeutic target in inflammatory disorders.
Examination of bilayer lipid membranes for ‘pin-hole’ character (2004)

BLM prepared on electrode substrates by supporting or tethering were tested for 'pin-hole' character, comparing data from cyclic voltammetry (CV), surface plasmon resonance (SPR) and rotating disc electrodes (RDE). 1-hexadecylamine tethered BLMs on SAM modified gold electrodes were compared with BLMs assembled on modified polyHEMA or sol-gel layers. BLM formation followed by SPR showed that the initial phase of the assembly was complete in 5-20 minutes and produced layers of thickness >5 nm, compared with the expected final BLM thickness of approximately 3 nm. The CVs of the K(3)[Fe(CN)(6)] couple were significantly suppressed irrespective of the method of BLM assembly, without major differences emerging for the different methods. However, data from the RDE distinguished the 'pin-hole' character of the different preparations. The data were consistent with incomplete initial (<1 h, SPR estimated BLM thickness >5 nm) vesicle fusion leaving 'pin-holes' of approximately 2 microm (HDA-11-mercaptoundecanoic acid (MUA) tethered BLM) to approximately 3 microm (tetraethylorthosilicate sol-gel supported BLM) followed by a slow maturation (>15 h; impedance spectroscopy estimated thickness approximately 3 nm) and lateral spreading and fusion, resulting in loss of 'pin-hole' character (<1 microm). The BLM could be used in conjunction with potentiometric measurement to observe the incorporation of nystatin into the BLM and the rate of incorporation adjusted according to original permeability of the BLM. The 'pin-hole-free' BLM construction with lowest permeability (TEOS supported, 4 x 10(-10) cm s(-1) compared with HDA-MUA, 3 x 10(-9) cm s(-1)) gave a potentiometric signal independent of bulk ion-concentration across 5 decades change in concentration. Formed on an ion-selective electrode, nystatin incorporation could be followed as a change in potential, over >2 h, whereas the TEOS supported BLM with permeability 1 x 10(-9) cm s(-1) shows nystatin incorporation within 1 h. In this instance, addition of ConA reduced the potential to the same value as prior to nystatin incorporation, consistent with nystatin channel closure.