gebhart/patrepeval huggingface dataset:
Mitotic recombination of yeast artificial chromosomes (1992)

Large regions of human DNA can be cloned and mapped in yeast artificial chromosomes (YACs). Overlapping YAC clones can be used in order to reconstruct genomic segments in vivo by meiotic recombination. This is of importance for reconstruction of a long gene or a gene complex. In this work we have taken advantage of yeast protoplast fusion to generate isosexual diploids followed by mitotic crossing-over, and show that it can be an alternative simple strategy for recombining YACs. Integrative transformation of one of the parent strains with the construct pRAN4 (containing the ADE2 gene) is used to disrupt the URA3 gene contained within the pYAC4 vector arm, providing the markers required for forcing fusion and detecting recombination. All steps can be carried out within the commonly used AB1380 host strain without the requirement for micromanipulation. The method was applied to YAC clones from the human MHC and resulted in the reconstruction of a 650 kb long single clone containing 18 known genes from the MHC class II region.
Presentation of antigen by B cells: functional dependence on radiation dose, interleukins, cellular activation, and differential glycosylation. (1985)

Whether resting B cells can present antigen to T cells is controversial. Several factors can influence the outcome of an assessment of the presenting function of resting B cells: the method of purifying resting B cells and maintaining them in culture without altering their resting state, the sensitivity of resting B cells to gamma-irradiation, the activation state of the T cells used to assess presenting function, and the requirement for exogenous interleukin 1. We have examined all of these variables and find that one adherent antigen-presenting cell is functionally equivalent to four LPS-activated B cells and to 1000 resting B cells. In addition, we have examined the potential functional relevance of the differential glycosylation of Ia molecules on resting B cells compared with adherent antigen-presenting cells. Altering the surface glycosylation of resting B cells by neuraminidase treatment results in a 25-fold increase in B cell antigen presentation without altering their resting state. More important, among antigen-presenting cells the effect of neuraminidase is limited to resting B cells. It also appears to involve a restricting element such as the Ia molecule rather than total cell surface charge, because neuraminidase treatment has no effect on the capacity of resting B cells to serve as accessory cells in the Con A response.
Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid-β Peptides (2005)

Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.
Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis (1992)

Human C fragment C5a is known to be a proinflammatory mediator and more recently shown to be a potent modulator of both humoral and cell-mediated immunity. We recently reported that natural and recombinant C5a induces the synthesis of IL-6-specific mRNA and secreted protein from human monocytes. Our studies using analogue peptides that are homologous to the carboxyl-terminal sequence of human C5a, indicate that the "effector" site for inducing IL-6 synthesis resides within the C-terminal region (C5a (70-74)) of the C5a molecule. C5a peptides containing the exact sequence of the natural factor were found to retain full agonist activity but exhibited low potency (0.01-0.1% of intact C5a). It was also shown that amino acid substitutions in the C5a peptides by aromatic/hydrophobic residues, outside the immediate effector site, resulted in analogue peptides with a substantial increase in potency relative to the most active natural peptide (C5a (56-74)). Moreover, these peptides approach the potency of natural C5a for induction of IL-6. Taken together, these results suggest that the inflammatory and immunoregulatory activities associated with C5a may, in part, be due to the synthesis of IL-6.
Molecular Identification of a Novel Protein That Regulates Biogenesis of Photosystem I, a Membrane Protein Complex (1997)

Photosystem I (PSI) is a multisubunit pigment-protein complex in the thylakoid membranes of cyanobacteria and chloroplasts. BP26, a random photosynthesis-deficient mutant strain of the cyanobacterium Synechocystis 6803 has a severely reduced PSI content, whereas its photosystem II is present in normal amount. The BP26 mutant is complemented by a novel gene, btpA, that encodes a 30-kDa protein. In this strain, a missense mutation in the btpA gene, resulting in the replacement of a valine by a glycine residue, significantly affects the accumulation of the PSI reaction center proteins, PsaA and PsaB. Northern blot analysis revealed that the steady-state levels of the transcripts from the psaAB operon, encoding these proteins, remain unaltered in the mutant strain. Hence the BtpA protein regulates a post-transcriptional process during the life cycle of the PSI protein complex such as 1) translation of the psaAB mRNA, 2) assembly of the PsaA/PsaB polypeptides and their associated cofactors into a functional complex, or 3) degradation of the protein complex. Close relatives of the BtpA protein have been found in nonphotosynthetic organisms, viz. the archaebacterium Methanococcus jannaschii, the eubacterium Escherichia coli, and the nematode, Caenorhabditis elegans, suggesting that these proteins may regulate biogenesis of other protein complexes in these evolutionarily distant organisms.
Enhanced efficiency of polymer light emitting diodes utilizing oxadiazole polymers (1995)

New oxadiazole polymers for use in LEDs are reported that have high thermal stability and excellent film‐forming properties. The characteristics of the polymers themselves and of heterolayer LEDs based on poly(phenylenevinylene) that incorporate the polymers as efficient elecron transport and injection layers are discussed. The stability, operating time and quantum efficiency are shown to be improved compared to monolayer devices.
Reversal of Integration and DNA Splicing Mediated by Integrase of Human Immunodeficiency Virus (1992)

In retroviral integration, the viral integration protein (integrase) mediates a concerted DNA cleavage-ligation reaction in which the target DNA is cleaved and the resulting 5' ends of target DNA are joined to the 3' ends of viral DNA. Through an oligonucleotide substrate that mimics the recombination intermediate formed by this initial cleavage-ligation reaction, the purified integrase of human immunodeficiency virus was shown to promote the same reaction in reverse, a process called disintegration. Analysis of a set of structurally related substrates showed that integrase could promote a range of DNA cleavage-ligation reactions. When the viral DNA component of the disintegration substrate was single-stranded, integrase could mediate a DNA splicing reaction analogous to RNA splicing.
Preparation and derivatives of poly-(6-O-methacryloyl-D-galactose) and poly-(6-O-acryloyl-D-galactose) (1966)

The 6-methacryloyl and 6-acryloyl esters of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose have been synthesised and polymerised to polymers of high molecular weight. The isopropylidene blocking groups have been removed by treatment with formic acid–water at 20°, to give poly-(6-O-methacryloyl-D-galactose) and poly-(6-O-acryloyl-D-galactose); which are linear, water-soluble, and reducing polymers with novel properties not possessed by natural polysaccharides. Various derivatives of these polymers are described. Chlorous acid at pH 3 oxidises the reducing group at C-1 of these polymers to give poly-(6-O-methacryloyl-D-galactonic acid) and poly-(6-O-acryloyl-D-galactonic acid), which exist in solution only; isolation and drying leads to loss of water from each galactonic acid residue with formation of the poly-1,4-lactones. The sodium salts of these polyacids are viscous polyelectrolytes which precipitate in the presence of many metal ions.
Highly Mismatched Molecules Resembling Recombination Intermediates Efficiently Transform Mismatch Repair Proficient Escherichia coli (1997)

The ability of related DNAs to undergo recombination decreases with increased sequence divergence. Mismatch repair has been proposed to be a key factor in preventing homeologous recombination; however, the contribution of mismatch repair is not universal. Although mismatch repair has been proposed to act by preventing strand exchange and/or inactivating multiply mismatched heteroduplexes, there has been no systematic study to determine at what step(s) in recombination mismatch repair acts in vivo. Since heteroduplex is a commonly proposed intermediate in many models of recombination, we have investigated the consequences of mismatch repair on plasmids that are multiply mismatched in heteroduplex structures that are similar to those that might arise during recombination. Plasmids containing multiply mismatched regions were transformed into wild-type and Mut+ Escherichia coli mutants. There was only a 30-40% reduction in transformation of Mut+ as compared to mutS and mutL strains for DNAs containing an 18% mismatched heteroduplex. The products obtained from mutS hosts differed from those obtained from Mut+ hosts in that there were many more colonies containing mixtures of two plasmids, due to survival of both strands of the heteroduplex. There were nearly 10 times more recombinants obtained from the mutS as compared to the wild-type host. Based on these results and those from other studies with E. coli and yeast, we propose that the prevention of recombination between highly diverged DNAs may be at a step earlier than heteroduplex formation.
Localization of an immunologically functional region of the streptococcal superantigen pepsin-extracted fragment of type 5 M protein. (1993)

Ten overlapping synthetic peptides, spanning the entire amino acid sequence of pepsin-extracted type 5 M protein, (pep M5), were used to delineate regions within this molecule that are important for the mitogenic activity of this streptococcal superantigen. Two of the overlapping peptides, SM5-8 and SM5-10, blocked the response of T cells to pep M5 in a dose-dependent manner. Neither peptide was toxic to T cells, but SM5-8 exhibited nonspecific inhibition of the T-cell response to either superantigen or polyclonal mitogens. In contrast, the inhibition by SM5-10 was pep M5-specific. Analysis of TCR V beta gene usage of the pep M5 response in the presence and absence of SM5-10 revealed that this peptide preferentially blocks the expansion of pep M5-specific V beta elements. The degree of inhibition of V beta expansion varied from one individual to the other, reflecting their TCR repertoire. SM5-10 did not significantly inhibit the response of T cells to other streptococcal superantigens. The data suggest that the region represented by SM5-10 of the pep M5 is important for superantigenic activity. In addition, the ability of this synthetic peptide to inhibit the response to pep M5 provides evidence that the mitogenic response is indeed mediated by this superantigen and is not a result of contamination with other streptococcal superantigens.
Somatic Activation of ras K Gene in a Human Ovarian Carcinoma (1984)

A tumor isolate from a patient with serous cystadenocarcinoma of the ovary contained an activated rasK gene detected hy transfection of NIH/3T3 cells. In contrast, DNA from normal cells of the same patient lacked transforming activity, indicating that activation of this transforming gene was the consequence of somatic mutation in the neoplastic cells. The transforming gene product displayed an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels that differed from the mobilities of rasK transforming proteins in other tumors, indicating that a previously undescribed mutation was responsible for activation of rasK in this ovarian carcinoma.
Development of autoimmunity after skin graft rejection via an indirect alloresponse1 (2002)

Autoreactivity can develop after transplant rejection via the indirect pathway. Although the direct alloresponse is likely to be the driving force in acute graft rejection, posttransplantation induced autoimmune responses may be important elements of delayed or chronic rejection.
COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer (2006)

Increased expression of COX-2 or VEGF-C has been correlated with progressive disease in certain cancers. Present study utilized several human breast cancer cell lines (MCF-7, T-47D, Hs578T and MDA-MB-231, varying in COX-2 expression) as well as 10 human breast cancer specimens to examine the roles of COX-2 and prostaglandin E (EP) receptors in VEGF-C expression or secretion, and the relationship of COX-2 or VEGF-C expression to lymphangiogenesis. We found a strong correlation between COX-2 mRNA expression and VEGF-C expression or secretion levels in breast cancer cell lines and VEGF-C expression in breast cancer tissues. Expression of LYVE-1, a selective marker for lymphatic endothelium, was also positively correlated with COX-2 or VEGF-C expression in breast cancer tissues. Inhibition of VEGF-C expression and secretion in the presence of COX-1/2 or COX-2 inhibitors or following downregulation of COX-2 with COX-2 siRNA established a stimulatory role COX-2 in VEGF-C synthesis by breast cancer cells. EP1 as well as EP4 receptor antagonists inhibited VEGF-C production indicating the roles of EP1 and EP4 in VEGF-C upregulation by endogenous PGE2. Finally, VEGF-C secretion by MDA-MB-231 cells was inhibited in the presence of kinase inhibitors for Her-2/neu, Src and p38 MAPK, indicating a requirement of these kinases for VEGF-C synthesis. These results, for the first time, demonstrate a regulatory role of COX-2 in VEGF-C synthesis (and thereby lymphangiogenesis) in human breast cancer, which is mediated at least in part by EP1/EP4 receptors.
Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. (1996)

We have evaluated the effect of dehydroepiandrosterone (DHEA) replacement therapy in 60- to 70-year-old women (n = 15) who received a single daily percutaneous application of a 10% DHEA cream for 12 months. While anthropometric measurements showed no change in body weight, we observed a 9.8% decrease in subcutaneous skinfold thickness at 12 months (P < 0.05). This was confirmed by measurements of midthigh fat and muscle areas by computed tomography where a 3.8% decrease (P < 0.05) in femoral fat and a 3.5% increase (P < 0.05) in femoral muscular areas were observed at 12 months. There was no significant change in abdominal fat measurements but the waist-to-hip ratio was only 0.83 at the onset of treatment. These changes in body fat and muscular mass were associated with a 11% decrease (P < 0.05) in fasting plasma glucose and a 17% decrease (P < 0.05) in fasting insulin levels. Treatment with DHEA had no adverse effect on the lipid or lipoprotein profile. In fact, an overall trend towards a decrease in total cholesterol and its lipoprotein fractions was observed. Plasma triglycerides were not affected. Plasma high-density lipoprotein (HDL) cholesterol decreased by 8% but the ratio HDL/cholesterol was unchanged by DHEA treatment because of a parallel decrease in total cholesterol. The index of sebum secretion showed a 73% increase (P < 0.05) during the 12 months of DHEA therapy followed by a return to pretreatment values 3 months after cessation of therapy. At the same time, sex hormone-binding globulin levels decreased (P < 0.05) during treatment and returned to pretreatment values 3 months after the end of therapy. Serum gonadotropins were not changed by DHEA treatment. Although not significant, we observed a tendency towards an elevation in serum GH levels. Values of serum IGF-I remained unchanged while plasma IGF-binding protein-3 levels significantly decreased (P < 0.05) during treatment and returned to pretreatment values after cessation of DHEA therapy. The present data clearly indicate the beneficial effects of DHEA therapy in postmenopausal women through its transformation into androgens and/or estrogens in specific intracrine tissues without any significant side effects.
Retinal Imaging Techniques in Diabetes (2000)

Diabetic retinopathy is progressive, and detection early is essential for the prevention of blindness. Doppler flowmetry, retinal photography, scanning laser ophthalmoscopy, and retinal oximetry measurements may identify proliferative disease early. Drawbacks of these methods include lack of compliance, failure to refer, and failure to identify disease early. As a result, diabetic retinopathy is a leading cause of blindness. Our retinal oximeter measures the blood oxygen saturation in the large vessels of the retina near the optic disc. Retinal vessel oxygen saturations measured with our instrument are sensitive indicators of blood loss and hypoxia in swine. We are generating scientific data that suggests that retinal vessel oxygen saturations may be used to identify retinal hypoxia prior to changes in retinal vessel architecture. We expect to study humans within the next two years, and a clinically useful eye oximeter should be available in the near future.
Specificity determinants in the attachment sites of bacteriophages HK022 and lambda (1990)

The Int proteins of bacteriophages HK022 and lambda promote recombination between phage and bacterial attachment sites. Although the proteins and attachment sites of the two phages are similar, neither protein promotes efficient recombination between the pair of attachment sites used by the other phage. To analyze this difference in specificity, we constructed and characterized chimeric attachment sites in which segments of one site were replaced with corresponding segments of the other. Most such chimeras recombined with appropriate partner sites in vivo and in vitro, and their differential responses to the Int proteins of the two phages allowed us to locate determinants of the specificity difference in the bacterial attachment sites and a central segment of the phage attachment sites. The location of these determinants encompasses three of the four core-type binding sites for lambda Int: C, B, and most importantly, B'. The regions corresponding to the C' core binding site and the arm-type binding sites of lambda Int play no role in the specificity difference and, indeed, are well conserved in the two phages. We found, unexpectedly, that the effect of replacement of an Int-binding region on the recombinational potency of one chimeric site was reversed by a change of partner. This novel context effect suggests that postsynaptic interactions affect the specificity of recognition of attachment sites by Int.
Bridging the Processor-Memory Performance Gapwith 3D IC Technology (2005)

Microprocessor performance has been improving at roughly 60% per year. Memory access times, however, have improved by less than 10% per year. The resulting gap between logic and memory performance has forced microprocessor designs toward complex and power-hungry architectures that support out-of-order and speculative execution. Moreover, processors have been designed with increasingly large cache hierarchies to hide main memory latency. This article examines how 3D IC technology can improve interactions between the processor and memory. Our work examines the performance of a single-core, single-threaded processor under representative work loads. We have shown that reducing memory latency by bringing main memory on chip gives us near-perfect performance. Three-dimensional IC technology can provide the much needed bandwidth without the cost, design complexity, and power issues associated with a large number of off-chip pins. The principal challenge remains the demonstration of a highly manufacturable 3D IC technology with high yield and low cost.
Chemical approaches to artificial photosynthesis (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical approaches to artificial photosynthesisThomas J. MeyerCite this: Acc. Chem. Res. 1989, 22, 5, 163–170Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://doi.org/10.1021/ar00161a001Request reuse permissionsArticle Views8248Altmetric-Citations1182LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-Alertsclose Get e-Alerts
Organ Preservation Solutions Increase Endothelial Permeability and Promote Loss of Junctional Proteins (1999)

The changes in occludin, VE-cadherin, and F-actin content and organization and increased permeability associated with cold storage demonstrate that alterations of the tight and adherens junctions may underlie organ edema associated with cold organ preservation. These data also suggest that novel strategies to maintain the content and integrity of endothelial junctional proteins may provide an important therapeutic avenue for organ preservation.