gebhart/patrepeval huggingface dataset:
Current status of liver disease in Korea: Nonalcoholic fatty liver disease (2009)

Recently, obesity (BMI>or=25 kg/m2) and type II diabetes mellitus have reached epidemic proportions in Korea, and rates of nonalcoholic fatty liver disease (NAFLD) are between 10% and 25% of the general population. NAFLD in Korea is as closely associated with several components of metabolic syndrome including, obesity, hypertension, diabetes and dyslipidemia as it is in Western countries. Insulin resistance and hyperinsulinemia may play a role in the pathogenesis of fatty liver in patients with normal body weight as well as in patients with obesity. And, obesity induced accumulation of fat in the adipose tissue leads to an imbalance in the regulation of adipokines, such as downregulation of adiponectin and upregulation of retinol-binding protein 4 (RBP4) and ghrelin. High BMI, the AST/ALT ratio, and ALT levels could be used to distinguish NASH from simple steatosis in Korean patients. In large number of NAFLD patients who underwent a voluntary medical checkup, even a small weight reduction was associated with improvements in their hepatic steatosis grade on ultrasonography, serum aminotransferase levels, and related metabolic abnormalities. Subjects with fatty liver disease should be advised to lose weight through lifestyle modifications. Small animal and human studies of treatment with PPAR agonists and betaine have been reported in the Korean literature. It is now acknowledged that NAFLD is the most common liver disease in Korea, largely due to the considerable increase in metabolic abnormalities such as obesity and diabetes. Future studies should continue to focus both on the pathogenesis and the treatment of NAFLD in order to accumulate more of our own data.
Instability of delayed-type hypersensitivity skin test anergy in human immunodeficiency virus infection (1995)

<h3>Objective:</h3> To evaluate stability of delayed-type hypersensitivity (DTH) skin test over time in human immunodeficiency virus (HIV)—seropositive and HIV-seronegative injecting drug users. <h3>Method:</h3> A community-based cohort of injecting drug users who had serial skin testing with purified protein derivative tuberculin, mumps, and<i>Candida albicans</i>antigen. Delayed-type hypersensitivity anergy was defined as a skin test result of less than 3 mm for all three antigens; DTH positivity was a skin test result of 3 mm or greater for at least one antigen (Centers for Disease Control and Prevention, Atlanta, Ga, 1993). <h3>Results:</h3> At baseline, 36% of HIV-seropositive subjects (n=401) were anergic as compared with 14% of HIV-seronegative subjects (n=552;<i>P</i>&lt;.001). During follow-up, fewer HIV-seropositive subjects remained DTH positive (42%) and more remained anergic (19%) than of HIV-seronegative subjects (67% and 7%, respectively). Twenty-four percent of HIV-seropositive subjects who were initially DTH positive became anergic as compared with 15.3% of the HIV-seronegative subjects. However, the proportion changing from anergy to DTH positivity was greater among HIV-seropositive subjects (15%) than HIV-seronegative subjects (12%). In comparison to those who remained DTH positive, HIV-seropositive subjects with CD4 cell counts of less than 0.50×10<sup>9</sup>/L (odds ratio=6.4) and less than 0.35×10<sup>9</sup>/L (odds ratio=11.2) were more likely to remain anergic than those who had CD4 cell counts above 0.50×10<sup>9</sup>/L or were HIV seronegative. <h3>Conclusions:</h3> Although the prevalence and incidence of DTH anergy were higher in HIV-seropositive subjects, high rates of change in DTH status occurred in both directions. This suggests that instability of DTH skin testing is substantial and only partially dependent on HIV status. Although a single test may be an unreliable indicator of HIV-induced immunosuppression, two consecutive anergic readings were strongly associated with a CD4 cell count below 0.50×10<sup>9</sup>/L and particularly below 0.35×10<sup>9</sup>/L. For determining false negativity of tuberculin tests, persistent DTH anergy is more reliable than a single test among HIV-seropositive injecting drug users. Anergy testing appears to be unnecessary with CD4 cell counts greater than 0.50×10<sup>9</sup>/L. (Arch Intern Med. 1995;155:2111-2117)
The effect of Intravenous Sodium Cromoglycate on the Bronchoconstriction Induced by Sulphur Dioxide Inhalation in Man (1985)

Ten healthy subjects received, on separate occasions, intravenous infusions of 0.9% NaCl solution (saline) and of sodium cromoglycate given in a double-blind cross-over fashion. After 20 min of infusion the specific airway conductance (sGaw) of each subject was measured in a body plethysmograph. The subject then breathed first a low (1-20 p.p.m.) and then a higher (4-40 p.p.m.) concentration of sulphur dioxide (SO2) for 2 min while the infusion continued. Measurements of sGaw were repeated after each inhalation of SO2. Sodium cromoglycate infusion did not affect the sGaw measured before challenge with SO2. During the infusion of sodium cromoglycate, the falls in sGaw in response to both concentrations of SO2 were significantly less than those which occurred during saline infusion. Plasma concentrations of sodium cromoglycate were found to be 209 +/- 22 nmol/l at the end of the drug infusion. This is about one-hundredth of lowest dose required to stabilize mast cells in vitro. We conclude that sodium cromoglycate acted by a mechanism which did not involve mast cells. Other possible modes of action are discussed.
Somatostatin Receptor Scintigraphy: Its Sensitivity Compared with That of Other Imaging Methods in Detecting Primary and Metastatic Gastrinomas: A Prospective Study (1996)

Somatostatin receptor scintigraphy is the single most sensitive method for imaging either primary or metastatic liver lesions in patients with the Zollinger-Ellison syndrome. Because of its sensitivity, simplicity, and cost-effectiveness, it should be the first imaging method used in these patients. For patients with negative results on somatostatin receptor scintigraphy, guidelines about the use of other imaging studies are proposed.
The potential of extrachromosomal replicating vectors for gene therapy (1996)

Persistence of DNA vectors in target cells is advantageous in most applications of gene therapy. Particularly when target cells are undergoing proliferation, vector longevity will depend on either the integration of the vector into the chromosomes or the ability of the vector to replicate and be retained extrachromosomally. Vectors that efficiently integrate in a nonrandom fashion are currently unavailable, and those that can replicate extrachromosomally provide a major alternative strategy. Several classes of such vectors are under development, carrying mechanisms for prolonging DNA retention in mammalian nuclei that extend vector lifetime in non-proliferating cells as well. The vectors utilize either chromosomal or viral elements to mediate replication and retention, and have a large size capacity for insertion of genes of interest. I discuss the state of the art for these vectors, including the assets and limitations of their future use in gene therapy.
Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis (2011)

Inactivation of the p53 tumor suppressor is a frequent event in tumorigenesis. In most cases, the p53 gene is mutated, giving rise to a stable mutant protein whose accumulation is regarded as a hallmark of cancer cells. Mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions that endow cells with growth and survival advantages. Interestingly, mutations in the p53 gene were shown to occur at different phases of the multistep process of malignant transformation, thus contributing differentially to tumor initiation, promotion, aggressiveness, and metastasis. Here, the authors review the different studies on the involvement of p53 inactivation at various stages of tumorigenesis and highlight the specific contribution of p53 mutations at each phase of cancer progression.
Characterization of Invasive Group B Streptococcus Strains from the Greater Toronto Area, Canada (2014)

We determined the capsular polysaccharide (CPS) type of 600 group B Streptococcus (GBS) (also known as Streptococcus agalactiae) strains recovered from patients with invasive infections in the greater Toronto area, Canada, between 2009 and 2012. GBS strains of CPS type III were the most prevalent among infants (44% in those with early-onset disease, 75% in those with late-onset disease), while type V strains were most frequently isolated from adult patients (26% in patients≥19 years old). We next investigated the presence in our collection of GBS strains belonging to the hypervirulent multilocus sequence typing clonal complex 17 (CC17). We used a PCR test described as specific for the detection of CC17 strains, which targets the gene encoding the major virulence factor HvgA. We identified 91 hvgA-positive strains; of these, 88 were CPS type III, 2 were CPS type IV, and 1 was CPS type V. Using whole-genome sequencing, we showed that the two hvgA-positive CPS type IV strains are CC17 strains which underwent capsular switching. However, sequence analysis revealed that the hvgA-positive CPS type V strain does not belong to CC17 but instead is a bona fide CC1 strain which acquired hvgA, probably by recombination from a CC17 donor. Our findings underline the importance of recombination in GBS pathogenesis and caution against the use of single-gene-based PCR tests to detect CC17 GBS strains.
Use of synthetic peptides as tracer antigens in fluorescence polarization immunoassays of high molecular weight analytes (1993)

This paper describes a homogeneous immunoassay based on fluorescence polarization that enables subnanomolar detection of high molecular weight analytes. A monoclonal antibody (Mab) to human chorionic gonadotrophin (hCG) was screened against a panel of 221 synthetic peptides using the method of Geysen et al. (Geysen, H. M.; et al. J. Immunol. Methods 1987, 102, 259-274. Geysen, H. M.; et al. J. Mol. Immunol. 1986, 23, 709-715). One of these peptides, which was located near the C-terminus of the hCG beta chain, bound to the Mab with high affinity. It was labeled with tetramethylrhodamine (TMR) and used as the tracer antigen in a competitive fluorescence polarization immunoassay (FPIA) for hCG. The peptide-TMR conjugate binds specifically to the anti-hCG Mab with an antigen-binding affinity (Ka) of 1.5 x 10(7) M-1 at 6 degrees C. Its fluorescence intensity was enhanced by approximately 20% upon binding as a result of a prolonged excited-state lifetime. In a typical embodiment, hCG was determined at a level of 1 x 10(-9) M (95% confidence limit)--a 100-fold improvement over similar systems reported in the literature. This is mainly attributed to the large difference in hydrodynamic volume between the tracer and the antibody, which resulted in large changes in polarization of the peptide tracer upon binding. Issues related to sensitivity, specificity, and reversibility were also investigated. This method is believed to be of significant importance to rapid and economical measurements of high molecular weight antigens of clinical interest.
Automated Wireless Carpooling System for an eco-friendly travel (2011)

In this paper we discuss about the Design of an Automated Wireless Carpooling System (AWCS), which can curtail the over usage of on road vehicles to a considerable amount. This system is designed for private vehicle owners who commute individually from the workplace to home. The system makes use of pre registration method, by which only identified people get into the carpool vehicles so that crime can be reduced. The Central Monitoring system (CMS) used here intelligently handles carpool requests and switches them efficiently. The user can acquire details of his/her travel by sending a SMS from their mobile phone. Waiting centers are allocated at each part of the city and the users can enter the carpooled vehicles only from these waiting centers. A person is assigned at each waiting center to check the identity of the people entering. Thus the proposed AWCS can be implemented in a city efficiently.
Crystal structure, folding, and operator binding of the hyperstable Arc repressor mutant PL8 (1995)

Arc repressor is a small, dimeric DNA-binding protein that belongs to the ribbon-helix-helix family of transcription factors. Replacing Pro8 at the N-terminal end of the beta-sheet with leucine increases the stability of the mutant protein by 2.5 kcal/mol of dimer. However, this enhanced stability is achieved at the expense of significantly reduced DNA binding affinity. The structure of the PL8 mutant dimer has been determined to 2.4-A resolution by X-ray crystallography. The overall structure of the mutant is very similar to wild type, but Leu8 makes an additional interstrand hydrogen bond at each end of the beta-sheet of the mutant, increasing the total number of beta-sheet hydrogen bonds from six to eight. Comparison of the refolding and unfolding kinetics of the PL8 mutant and wild-type Arc shows that the enhanced stability of the mutant is accounted for by a decrease in the rate of protein unfolding, suggesting that the mutation acts to stabilize the native state and that the beta-sheet forms after the rate-limiting step in folding. The reduced operator affinity of the PL8 dimer appears to arise because the mutant cannot make the new interstrand hydrogen bonds and simultaneously make the wild-type set of contacts with operator DNA.
The native structure of intercellular adhesion molecule-1 (ICAM-1) is a dimer. Correlation with binding to LFA-1 (1995)

In solution, intercellular adhesion molecule-1 (ICAM-1) exhibits extremely low affinity for its receptor, LFA-1, as direct binding to LFA-1 has not been reported. Furthermore, there are conflicting reports on the ability of ICAM-1 in solution to inhibit cell adhesion events. These differences could be due to the valency or an oligomeric native biochemical form of membrane-bound and soluble ICAM-1, which may correlate with its ability to bind to integrins. To test this, stimulated adenocarcinoma (A549) cells or HUVEC were labeled with 35S-methionine/cysteine and treated with a chemical cross-linker. A high m.w. form (200 kDa) of ICAM-1 but not ICAM-2 was specifically immunoprecipitated from cross-linked cell lysates and supernatants. Affinity purification of crosslinked supernatants revealed that the majority of ICAM-1 was dimeric as opposed to recombinant soluble ICAM-1, which contains a minor fraction of dimer. Gel filtration chromatography was used to isolate monomeric and dimer-rich fractions of recombinant soluble ICAM-1, and tested for direct binding to affinity-purified LFA-1. Dimer-rich fractions demonstrated an enhanced ability and estimated affinity, compared with monomeric protein, to bind to purified LFA-1. These data suggest that ICAM-1 exists in its native membrane-bound and shed form as a non-covalent dimer, and that dimerization directly correlates with enhanced binding to LFA-1.
Large Amplitude Twisting Motions of an Interdomain Hinge: A Disulfide Trapping Study of the Galactose-Glucose Binding Protein (1995)

The galactose--glucose binding protein possesses two structural domains bordering a ligand binding cleft, with three polypeptide strands serving as a flexible hinge connecting the two domains. The hinge is known to bend, enabling the cleft to open by an angle of at least 18 degrees. Here the twisting motions of the hinge were examined by placing pairs of engineered cysteines on the perimeter of the cleft to generate six stable di-cysteine proteins. Each cysteine pair introduced reactive sulfhydryls into both rims of the cleft, one in the N-terminal domain and the other in the C-terminal domain. Collisions between sulfhydryls in different domains were trapped by disulfide formation, yielding sensitive detection of large amplitude domain rotations. When the cleft was occupied by the ligand D-glucose, counterclockwise hinge twist rotations were detected with amplitudes up to 36 degrees, and frequencies ranging from 10(1) to 10(3) collisions s-1. Removal of ligand from the cleft increased the range of twist angles 3-fold and the frequency of motions up to 10(2)-fold. Thus, in this representative hinged cleft protein, large amplitude hinge twist motions occur on biologically relevant timescales. The functional implications of such motions are discussed.
Skin colour and skin cancer –MC1R, the genetic link (2002)

Pigmentary traits such as red hair, fair skin, lack of tanning ability and propensity to freckle (the RHC phenotype) have been identified as genetic risk factors for both melanoma and non-melanocytic skin cancers when combined with the environmental risk factor of high ultraviolet light exposure. The human melanocortin-1 receptor (MC1R) is a key determinant of the pigmentation process and can account in large part for the diverse range of variation in human pigmentation phenotypes and skin phototypes. The coding sequence is highly polymorphic in human populations, with several of these variant forms of the receptor now known to be associated with the RHC phenotype. We have examined variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins with defined pigmentation characteristics. Variant allele frequencies have also been determined in several case-control studies of sporadic melanoma, basal cell carcinoma and squamous cell carcinoma, and in familial melanoma kindreds collected within Australia. These studies have shown that three RHC alleles - Arg151Cys, Arg160Trp and Asp294His - were associated with increased risk in all forms of skin cancer and with penetrance and age of onset in familial melanoma in mutation carriers. There is a significant RHC allele heterozygote carrier effect on skin phototype and skin cancer risk, which indicates that variant alleles do not behave in a strictly recessive manner. Ultimately, the genetic and chemical assessment of melanin synthesis rather than skin colour will be the best indicator for skin cancer risk, and such genetic association studies combined with functional analysis of variant alleles should provide the link to understanding skin phototypes.
LIVER TARGETING OF HEPATITIS-B ANTIVIRAL LAMIVUDINE USING THE HEPDIRECT™ PRODRUG TECHNOLOGY (2005)

A new class of phosphate and phosphonate prodrugs, called HepDirect prodrugs, has been developed to deliver drugs to the liver while simultaneously diminishing drug exposure to extra-hepatic tissues. The technology combines liver-selective cleavage and kinase by pass with high plasma and tissue stability to achieve increased drug levels in the liver. Lamivudine (LMV), a nucleoside analogue, is a currently approved treatment for hepatitis B infection, but shows modest efficacy and significant drug resistance due to inefficient phosphorylation. LMV is inadequately phosphorylated to the corresponding nucleoside triphosphate in rat and human hepatocytes. A HepDirect prodrug of LMV monophosphate generated 34-fold higher levels of the triphosphate in rat hepatocytes and 320-fold higher triphosphate levels in the liver of treated rats relative to LMV.
Pharmaceutical approaches to colon targeted drug delivery systems. (2003)

Improved drug delivery systems are required for drugs currently in use to treat localized diseases of the colon. The advantages of targeting drugs specifically to the diseased colon are reduced incidence of systemic side effects, lower dose of drug, supply of the drug to the biophase only when it is required and maintenance of the drug in its intact form as close as possible to the target site.
Phase I Clinical Trial and Pharmacokinetics of Intravesical Mitomycin C in Dogs with Localized Transitional Cell Carcinoma of the Urinary Bladder (2010)

Intravesical MMC has antitumor activity in dogs with invasive TCC. Further study is needed to determine the cause of the myelosuppression associated with MMC administration, and to develop strategies to minimize this risk.
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Heteropolyflavan-3-ols and Glucosylated Heteropolyflavans in Sorghum [Sorghum bicolor (L.) Moench] (2002)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to characterize the structural diversity of polyflavans in Ruby Red sorghum [Sorghum bicolor (L.) Moench]. Deionization of the polyflavan fractions with Dowex 50 x 8-400 cation-exchange resin and subsequent addition of cesium trifluoroacetate ((133)Cs) allowed the detection of exclusively [M + Cs](+) ions. MALDI-TOF MS of the polyflavans that eluate from Sephadex LH-20 columns with methanol and acetone detected a series of masses corresponding to heteropolyflavan-3-ols differing in degree of hydroxylation and nature of the interflavan bond (A-type and B-type). MALDI-TOF MS of the Sephadex-ethanol/methanol (v/v) eluate revealed a series of masses corresponding to heteropolyflavan-5-O-beta-glucosides that vary in the extent of hydroxylation and contain a flavanone (eriodictyol or eriodictyol-5-O-beta-glucoside) as the terminal unit. The combination of liquid chromatographic separation and MALDI-TOF MS to characterize sorghum polyflavans indicates that the structural heterogeneity is much greater than previously described.
Analysis of membranes photolabeled with lipid analogues. Reaction of phospholipids containing a disulfide group and a nitrene or carbene precursor with lipids and with gramicidin A. (1980)

Analogues of fatty acids have been synthesized which contain an S-S bridge in the aliphatic chain and at the @-carbon the photoactivatable p-(3-trifluoromethyldiazirino)phenyl or p-azidophenyl group as a carbene and nitrene precursor, respectively.These acids were used to acylate 1-palmitoyl phosphatidylcholine by the procedure described by Gupta et al. (
Plaque Rupture Complications in Murine Atherosclerotic Vein Grafts Can Be Prevented by TIMP-1 Overexpression (2012)

The current study describes the incidence and phenotype of plaque rupture complications in murine vein grafts. Since matrix metalloproteinases (MMPs) are highly involved in atherosclerotic plaque vulnerability and plaque rupture, we hypothesized that this model can be validated by overexpression of the MMP inhibitor TIMP-1. First we studied 47 vein grafts in hypercholesterolemic ApoE3*Leiden mice for the incidence of plaque complications. In 79% of these grafts, extensive lesions with plaque rupture complications like dissections, intraplaque hemorrhages or erosions with intramural thrombi were found. Next, in vivo Near-InfraRed-Fluorescence imaging demonstrated that electroporation mediated TIMP-1-overexpression reduced local MMP activity in vein grafts by 73% (p<0.01). This led to a 40% reduction in lesion-size after 28d (p = 0.01) and a more stable lesion phenotype with significant more smooth muscle cells (135%), collagen (47%) and significant less macrophages (44%) and fibrin (55%) than controls. More importantly, lesions in the TIMP-1 group showed a 90% reduction of plaque complications (10/18 of control mice showed plaque complications versus 1/18 in TIMP-1 treated mice). Murine vein grafts are a relevant spontaneous model to study plaque stability and subsequent hemorrhagic complications, resulting in plaque instability. Moreover, inhibition of MMPs by TIMP-1-overexpression resulted in decreased plaque progression, increased stabilization and decreased plaque rupture complications in murine vein grafts.
The soybean-Phytophthora resistance locus Rps1-k encompasses coiled coil-nucleotide binding-leucine rich repeat-like genes and repetitive sequences (2008)

These data indicate that the Rps1 locus is located in a gene-poor region. The abundance of repetitive sequences in the Rps1-k region suggested that the location of this locus is in or near a heterochromatic region. Poor recombination frequencies combined with presence of two functional Rps genes at this locus has been providing stable Phytophthora resistance in soybean.