gebhart/patrepeval huggingface dataset:
Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160. (1993)

SCID mice reconstituted with adult human peripheral blood leukocytes (hu-PBL-SCID mice) make antigen-specific human antibody responses following secondary immunization and can be infected with human immunodeficiency virus 1 (HIV-1), suggesting that they might prove useful for evaluating protective immunity to HIV-1 following vaccination of PBL donors. HIV-seronegative volunteers were immunized with vaccinia expressing HIV-1LAV-1/Bru 160-kDa envelope glycoprotein (vaccinia gp160) and subsequently given booster injections of recombinant gp160 protein (rgp160). Their PBLs were used at intervals of 4-72 weeks after booster injections to construct hu-PBL-SCID mice, which were then challenged with 10(2)-10(3) minimal animal infectious doses of highly homologous HIV-1IIIB. Control hu-PBL-SCID mice were constructed from donors receiving vaccinia, alum, or hepatitis B vaccine. Protection against virus infection was defined as the absence of HIV-1 by culture and no detection of proviral genomes following PCR amplification. Control animals were highly susceptible to HIV infection. By contrast, hu-PBL-SCID mice reconstituted with cells from three of four donors immunized with vaccinia gp160 and recently injected with rgp160 showed no evidence of HIV-1 infection by culture or PCR assays. With increasing time after rgp160 injection, the ability of vaccine-derived hu-PBL-SCID mice to resist HIV-1 infection diminished. These results demonstrate that a potentially protective human immune response was stimulated by this HIV gp160 immunization protocol and show the utility of the hu-PBL-SCID model in the rapid evaluation of candidate vaccines.
Binding Kinetics of Thrombin and Antithrombin III with Immobilized Heparin Using a Spacer (1992)

The immobilization of heparin onto polymeric surfaces using a hydrophilic spacer was effective in curtailing surface induced thrombus formation. In this study, the binding kinetics of immobilized heparin with antithrombin III (ATIII) and thrombin were investigated. Low molecular weight heparin (molecular weight, 6,000 daltons) was fractionated on an ATIII affinity column, and it was immobilized onto a styrene/p-amino styrene random co-polymer surface via hydrophilic spacer groups. This polymer substrate was coated onto glass beads (diameter range, 0.088-0.105 mm). PEO (molecular weight 3,400), modified by tolylene diisocyanate, was covalently coupled as a spacer group, followed by heparin. The bioactivity of immobilized heparin was approximately 16.2%, relative to free heparin, and nearly 1:1 binding between heparin and PEO was calculated. The binding constants of immobilized heparin and ATIII, and immobilized heparin and thrombin, were 0.958 x 10(7) M-1 and 1.76 x 10(8) M-1, respectively. The immobilized heparin bound with both ATIII and thrombin, and the binding mechanism was similar to that of free heparin.
Experimental evolution of resistance to an antimicrobial peptide (2005)

A novel class of antibiotics based on the antimicrobial properties of immune peptides of multicellular organisms is attracting increasing interest as a major weapon against resistant microbes. It has been claimed that cationic antimicrobial peptides exploit fundamental features of the bacterial cell so that resistance is much less likely to evolve than in the case of conventional antibiotics. Population models of the evolutionary genetics of resistance have cast doubt on this claim. We document the experimental evolution of resistance to a cationic antimicrobial peptide through continued selection in the laboratory. In this selection experiment, 22/24 lineages of Escherichia coli and Pseudomonas fluorescens independently evolved heritable mechanisms of resistance to pexiganan, an analogue of magainin, when propagated in medium supplemented with this antimicrobial peptide for 600–700 generations.
Two outer membrane transport systems for vitamin B12 in Salmonella typhimurium (1989)

The involvement of an outer membrane transport component for vitamin B12 uptake in Salmonella typhimurium, analogous to the btuB product in Escherichia coli, was investigated. Mutants of S. typhimurium selected for resistance to bacteriophage BF23 carried mutations at the btuB locus (butBS) (formerly called bfe, at the analogous map position as the E. coli homolog) and were defective in high-affinity vitamin B12 uptake. The cloned E. coli btuB gene (btuBE) hybridized to S. typhimurium genomic DNA and restored vitamin B12 transport activity to S. typhimurium btuBS mutants. An Mr-60,000 protein in the S. typhimurium outer membrane was repressed by growth with vitamin B12 and was eliminated in a btuBS mutant. The btuBS product thus appears to play the same role in vitamin B12 transport by S. typhimurium as does the E. coli btuBE product. A second vitamin B12 transport system that is not present in E. coli was found by cloning a fragment of S. typhimurium DNA that complemented btuB mutants for vitamin B12 utilization. In addition to this plasmid with a 6-kilobase insert of S. typhimurium DNA, vitamin B12 utilization by E. coli btuB strains required the btuC and btuD products, necessary for transport across the cytoplasmic membrane, but not the btuE or tonB product. The plasmid conferred low levels of vitamin B12-binding and energy-dependent transport activity but not susceptibility to phage BF23 or utilization of dicyanocobinamide. The cloned S. typhimurium DNA encoding this new transport system did not hybridize to the btuBE gene or to E. coli chromosomal DNA and therefore does not carry the S. typhimurium btuBS locus. Increased production of an Mr -84,000 polypeptide associated with the outer membrane was seen. The new locus appears to be carried on the large plasmid in most S. typhimurium strains. Thus S. typhimurium possesses both high- and low-affinity systems for uptake of cobalamins across the outer membrane.
Demonstration of the involvement of interleukin 2 in the differentiation of Staphylococcus aureus Cowan I-stimulated B cells. (1984)

The effect of IL 2 on Staphylococcus aureus Cowan I (SAC)-driven IgG production of human B cells was examined by utilizing chromatographically purified IL 2 (R-IL 2) and the transcription product of the cloned cDNA for human IL 2 purified from recombinant E. coli (G-IL 2). Both preparations of IL 2 by themselves were not enough to induce optimal IgG-production in the SAC-stimulated tonsillar B cell fraction, which was highly enriched for B cells, but effectively induced IgG production in the presence of a subeffective number of T cells or a late-acting B cell differentiation factor (BCDF). In addition, the activity that induced IgG production in the presence of a subeffective number of T cells was absorbed with an IL 2-dependent mouse T cell line. These results clearly indicate that IL 2 has a definite effect on B cell differentiation in this system. Although the mechanisms of this effect remain to be elucidated, a direct effect of IL 2 on B cells may be involved, because the addition of IL 2 along with SAC induced a limited but significant increase of 3H-TdR incorporation in the highly enriched B cell population, which showed very little response to PHA and Con A even in the presence of IL 2, and, as mentioned above, IL 2 induced IgG production in the B cell preparation without any supplement of T cells provided the late-acting BCDF fraction was present in the culture.
Prevalence of Human Papillomavirus Genomes in Tissues from the Lower Genital Tract as Detected by Molecular In Situ Hybridization (1991)

Incidence cases of human papillomavirus (HPV)-related disease of the lower anogenital tract were prospectively collected and submitted to RNA-DNA in situ hybridization, which allows a direct correlation between morphology and the presence of viral DNA. The overall HPV detection rate in condylomata and intraepithelial or invasive neoplasia varied for the different genital areas: cervix (64%), vagina (56%), vestibule (59%), vulva (50%), and penis (42%). HPVs 6/11 were associated with condylomata, whereas HPV 16 was associated with intraepithelial and invasive neoplasia. Not a single case of intraepithelial or invasive neoplasia contained HPV 6/11, which supports the notion of the oncogenic potential of HPV 16. Condylomata were positive for HPV 16 only when adjacent to HPV 16-positive cervical intraepithelial neoplasias (CINs). The amount of viral DNA (copy number) was low in invasive cancers, intermediate in intraepithelial neoplasia, and conspicuously high in condylomata. In biopsies (n = 142) taken from lesions suggestive of subclinical papillomavirus infection on the basis of minor colposcopic and histologic abnormalities, HPV DNA was not detectable. Histologically normal tissue (n = 210) adjacent to condyloma, CIN, or cancer, and thus potential carrier of latent HPV infection, also proved negative for HPV DNA by in situ hybridization. The inability to detect viral DNA by in situ hybridization in tissues diagnosed as subclinically or latently infected may have been due to limited sensitivity of the hybridization method applied in this study.
Low temperature and light regulate delta 12 fatty acid desaturases (FAD2) at a transcriptional level in cotton (Gossypium hirsutum) (2008)

Lipid modifying enzymes play a key role in the development of cold stress tolerance in cold-resistant plants such as cereals. However, little is known about the role of the endogenous enzymes in cold-sensitive species such as cotton. Delta 12 fatty acid desaturases (FAD2), known to participate in adaptation to low temperatures through acyl chain modifications were used in gene expression studies in order to identify parameters of plant response to low temperatures. The induction of microsomal delta 12 fatty acid desaturases at an mRNA level under cold stress in plants is shown here for first time. Quantitative PCR showed that though both delta 12 omega 6 fatty acid desaturase genes FAD2-3 and FAD2-4 identified in cotton are induced under cold stress, FAD2-4 induction is significantly higher than FAD2-3. The induction of both isoforms was light regulated, in contrast a third isoform FAD2-2 was not affected by cold or light. Stress tolerance and light regulatory elements were identified in the predicted promoters of both FAD2-3 and FAD2-4 genes. Di-unsaturated fatty acid species rapidly increased in the microsomal fraction isolated from cotton leaves, following cold stress. Expression analysis patterns were correlated with the observed increase in both total and microsomal fatty acid unsaturation levels suggesting the direct role of the FAD2 genes in membrane adaptation to cold stress.
Pharmacokinetic study on the utilisation of 5‐methyltetrahydrofolate and folic acid in patients with coronary artery disease (2004)

1. Methylenetetrahydrofolate reductase (MTHFR) is a regulating enzyme in folate-dependant homocysteine remethylation, because it catalyses the reduction of 5,10 methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-MTHF). 2. Subjects homozygous for the 677C --> T mutation in the MTHFR enzyme suffer from an increased cardiovascular risk. It can be speculated that the direct administration of 5-MTHF instead of folic acid can facilitate the remethylation of homocysteine in methionine. 3. The aim of this study was to determine the pharmacokinetic properties of orally administered 6[R,S] 5-MTHF versus folic acid in cardiovascular patients with homozygosity for 677C --> T MTHFR. 4. This is an open-controlled, two-way, two-period randomised crossover study. Patients received a single oral dose of either 5 mg folic acid or 5 mg 5-MTHF in each period. The concentrations of the 6[S] 5-MTHF and 6[R] 5-MTHF diastereoisomers were determined in venous blood samples. 5. All pharmacokinetic parameters demonstrate that the bioavailability of 5-MTHF is higher compared to folic acid. The peak concentration of both isomers following the administration of 6[R,S] 5-MTHF is almost seven times higher compared to folic acid, irrespective of the patient's genotype. However, at 1 week after the administration of a single dosage 6[R,S] 5-MTHF, we detected 6[R] 5-MTHF following the administration of folic acid, indicating storage of this isomer in the body. 6. Our results demonstrate that oral 5-MTHF has a different pharmacokinetic profile with a higher bioavailability compared to folic acid, irrespective of the patient's genotype. Detrimental effects of the storage of high levels of the non-natural isomer 6[R] 5-MTHF cannot be excluded.
Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array (2005)

Whole genome association studies of complex human diseases represent a new paradigm in the postgenomic era. In this study, we report application of the Affymetrix, Inc. (Santa Clara, CA) high-density single nucleotide polymorphism (SNP) array containing 11,555 SNPs in a pilot case-control study of esophageal squamous cell carcinoma (ESCC) that included the analysis of germ line samples from 50 ESCC patients and 50 matched controls. The average genotyping call rate for the 100 samples analyzed was 96%. Using the generalized linear model (GLM) with adjustment for potential confounders and multiple comparisons, we identified 37 SNPs associated with disease, assuming a recessive mode of transmission; similarly, 48 SNPs were identified assuming a dominant mode and 53 SNPs in a continuous mode. When the 37 SNPs identified from the GLM recessive mode were used in a principal components analysis, the first principal component correctly predicted 46 of 50 cases and 47 of 50 controls. Among all the SNPs selected from GLMs for the three modes of transmission, 39 could be mapped to 1 of 33 genes. Many of these genes are involved in various cancers, including GASC1, shown previously to be amplified in ESCCs, and EPHB1 and PIK3C3. In conclusion, we have shown the feasibility of the Affymetrix 10K SNP array in genome-wide association studies of common cancers and identified new candidate loci to study in ESCC.
Intracellular Delivery of Proteins via Fusion Peptides in Intact Plants (2016)

In current plant biotechnology, the introduction of exogenous DNA encoding desired traits is the most common approach used to modify plants. However, general plant transformation methods can cause random integration of exogenous DNA into the plant genome. To avoid these events, alternative methods, such as a direct protein delivery system, are needed to modify the plant. Although there have been reports of the delivery of proteins into cultured plant cells, there are currently no methods for the direct delivery of proteins into intact plants, owing to their hierarchical structures. Here, we demonstrate the efficient fusion-peptide-based delivery of proteins into intact Arabidopsis thaliana. Bovine serum albumin (BSA, 66 kDa) was selected as a model protein to optimize conditions for delivery into the cytosol. The general applicability of our method to large protein cargo was also demonstrated by the delivery of alcohol dehydrogenase (ADH, 150 kDa) into the cytosol. The compatibility of the fusion peptide system with the delivery of proteins to specific cellular organelles was also demonstrated using the fluorescent protein Citrine (27 kDa) conjugated to either a nuclear localization signal (NLS) or a peroxisomal targeting signal (PTS). In conclusion, our designed fusion peptide system can deliver proteins with a wide range of molecular weights (27 to 150 kDa) into the cells of intact A. thaliana without interfering with the organelle-targeting peptide conjugated to the protein. We expect that this efficient protein delivery system will be a powerful tool in plant biotechnology.
Self-ligating appliances: evolution or revolution? (2008)

Self-ligating brackets are here to stay and continue to be refined and enhanced. Further prospective studies investigating their clinical application and performance would be welcome.
Metal thiolate clusters in cobalt(II)-metallothionein. (1981)

Rabbit liver metallothionein-1 in which all seven metal-binding sites are occupied by cobalt(II) exhibits spectral features typical of tetrathiolate coordination with approximate Td microsymmetry [Vasák, M. (1980) J. Am. Chem. Soc. 102, 3953-3955]. With a total of 20 cysteine residues per molecule, this mode of metal binding implies that some of the thiolate ligands are shared by neighboring Co(II) ions, resulting in clustered structures. In this study, evidence for the existence of thiolate-linked Co(II) clusters is presented and their mode of formation is explored by comparing the optical and magnetic properties of forms of Co(II)-metallothionein containing 1-7 equivalents of Co(II). Preparations with up to 4 Co(II) equivalents display electronic spectra in the d-d and charge-transfer regions that resemble those of isolated tetrahedral Co(II)-tetrathiolate complexes. Upon binding of more than four Co(II) ions, however, the spectrum changes progressively and approaches in the fully saturated Co(II)-metallothionein an absorption profile similar to that of crystallographically defined model (Co)II-tetrathiolate clusters [Dance, I. G. (1979) J. Am. Chem. Soc. 101, 6264-6273]. These effects are closely paralleled by changes in the ESR spectrum. Above 4 Co(II) equivalents per thionein, the ESR signal at gx approximately 5.9 measured at 4 K decreases progressively in intensity, until in the fully occupied protein the complex is nearly diamagnetic. These changes, which were confirmed by measurements of paramagnetic susceptibility, establish the existence of Co(II) thiolate clusters in Co(II)-metallothionein. The loss of paramagnetism reflects most likely antiferromagnetic coupling of neighboring Co(II) ions brought about by a superexchange mechanism via the thiolate bridging ligands.
Relationship of C-Reactive Protein With Clinical Response After Therapy With Ustekinumab in Crohn's Disease (2009)

The potential benefit of ustekinumab in CD is supported by serum CRP reductions. Evidence suggests that increased systemic inflammation as manifested by higher baseline CRP values leads to larger treatment effects with ustekinumab, especially in infliximab-experienced patients.
Exploring the use of three level guides in elementary and middle school classrooms (2000)

Collaborative classroom research among a group of elementary and middle school teachers provides insight into the effective use of the Three Level Guide. Building lessons around content area materials, teachers employed the Three Level Guide regularly, coming together to share successes and frustrations and to offer suggestions. Their reflective analyses of the use of the Three Level Guide offer insight into its impact on teacher effectiveness as well as its impact on students' academic achievement, critical thinking ability, and academic esteem.
The Activating Dual Phosphorylation of MAPK by MEK Is Nonprocessive (1997)

Activation of mitogen-activated protein kinases (MAPKs), also known as extracellular-signal-regulated kinases (ERKs), by MAPK/extracellular protein kinase kinases (MEKs) requires phosphorylation at two sites. The first step in MAPK activation by MEK must be the formation of a MEK x MAPK enzyme-substrate complex, followed by phosphorylation producing monophosphorylated MAPK (pMAPK). Subsequently, one of two events may occur. (1) MEK catalyzes the second and fully activating phosphorylation of MAPK, producing ppMAPK (a processive mechanism). (2) The complex of MEK x pMAPK dissociates before the second phosphorylation occurs, full activation requiring a reassociation of pMAPK with MEK (a nonprocessive or distributive mechanism). Simulations indicate that these two mechanisms predict different kinetics of MAPK activation. Specifically, the nonprocessive mechanism predicts that there will be a paradoxical decrease in the rate of MAPK activation as the MAPK concentration is increased. The present study uses p42 MAPK, also known as ERK2, and MEK1 as representatives of their respective classes of enzymes. We find that increasing the ERK2 concentration decreases the rate of activation by a mechanism which does not involve inhibition of MEK1 function. The accumulation of the active, doubly phosphorylated ERK2 (ppERK2) was directly assessed using a phosphorylation-state-specific antibody. The rate of accumulation of ppERK2 is decreased by increasing the ERK2 concentration. Therefore, the mechanism of ERK2 activation by MEK1 in vitro is nonprocessive.
Interaction of Mycoplasma gallisepticum with sialyl glycoproteins (1980)

The binding of several glycoproteins to freshly grown and harvested cells of Mycoplasma gallisepticum was examined. Only human glycophorin, the major sialoglycoprotein of the erythrocyte membrane, bound tightly as judged by direct binding assays with 125I-labeled glycoproteins. Neuraminidase-treated glycophorin did not bind, suggesting that binding is mediated through sialic acid groups. Although other sialoglycoproteins did not appear to bind M. gallisepticum by direct binding assays, some inhibited the binding of glycophorin. The best inhibitors had a mucin-like structure, with high molecular weights and high sialic acid contents. N-acetylneuraminic acid appeared to be the favored sialic acid structure for binding, but there was no strict specificity for its anomeric linkage. Neuraminidase activity could not be detected on the surface of M. gallisepticum, suggesting that this enzyme is not involved in the mechanism of adherence of sialoglycoproteins. Binding of sialoglycoproteins was time dependent, however, and markedly diminished with increasing ionic strength, but was largely unaffected between pH 4 and 9.
MED-SuMoLig:  A New Ligand-Based Screening Tool for Efficient Scaffold Hopping (2007)

The identification of small molecules with selective bioactivity, whether intended as potential therapeutics or as tools for experimental research, is central to progress in medicine and in the life sciences. To facilitate such study, we have developed a ligand-based program well-suited for effective screening of large compound collections. This package, MED-SuMoLig, combines a SMARTS-driven substructure search aiming at 3D pharmacophore profiling and computation of the local atomic density of the compared molecules. The screening utility was then investigated using 52 diverse active molecules (against CDK2, Factor Xa, HIV-1 protease, neuraminidase, ribonuclease A, and thymidine kinase) merged to a library of about 40,000 putative inactive (druglike) compounds. In all cases, the program recovered more than half of the actives in the top 3% of the screened library. We also compared the performance of MED-SuMoLig with that of ChemMine or of ROCS and found that MED-SuMoLig outperformed both methods for CDK2 and Factor Xa in terms of enrichment rates or performed equally well for the other targets.
Complex translocation in a boy with trichorhinophalangeal syndrome. (1985)

We report a boy with a trichorhinophalangeal syndrome (TRP syndrome), severe mental retardation, and transient megacephaly, whose karyotype showed complex, apparently balanced, translocations with breakpoints in bands 3q13, 8p22, 8q13, 11p12, and 11q21. The fact that cases presenting with phenotypes corresponding to the TRP II syndrome and deletions of the long arm of chromosome 8 have been recently reported prompted us to report this case to help in the clarification of the possible relation between 8q chromosomal mutation and the aetiology of TRP syndromes.
<title>Photosensitizer for PDT based on phosphonate phthalocyanine derivative</title> (1996)

It is very important to develop new sensitizer which could be efficiently excited at wavelengths exceeding 685 nm where own tissue absorption can be neglected. We have synthesize water soluble phthalocyanine derivative having phosphonate groups as substituents in macrocycle. New sensitizer efficiently absorbs in spectral range 685 - 710 nm. It exhibits intense fluorescence in range 690 -720 nm. The photodynamic activity of new sensitizer is higher than in the case of sulfonated aluminum phthalocyanine.