gebhart/patrepeval huggingface dataset:
Calnexin, Calreticulin, and Bip/Kar2p in Protein Folding (1995)

The generation of new proteins in the cell involves a series of processes that reach well beyond the end point implied by the so-called "central dogma" of molecular biology: DNA→RNA→polypeptide. It is not enough that the amino acids are linked correctly to form polypeptide chains. The chains have to be folded, often assembled into oligomeric complexes, and transported to the correct location within or outside the cell. Although the cellular mechanisms for dealing with the "folding problem" and the "sorting problem" remain incompletely understood, it is clear that the cellular machinery involved in folding and sorting is no less complex than that responsible for transcription and translation.
Up-regulation and Polarized Expression of the Sodium-Ascorbic Acid Transporter SVCT1 in Post-confluent Differentiated CaCo-2 Cells (2003)

Human cells acquire vitamin C using two different transporter systems, the sodium-ascorbic acid co-transporters with specificity for ascorbic acid, and the facilitative glucose transporters with specificity for dehydroascorbic acid. There is no information on the mechanism of vitamin C transport across the intestinal barrier, a step that determines the bioavailability of vitamin C in humans. We used the colon carcinoma cell line CaCo-2 as an in vitro model for vitamin C transport in enterocyte-like cells. The results of transport kinetics, sodium dependence, inhibition studies, and reverse transcriptase-PCR analysis indicated that CaCo-2 cells express the sodium-ascorbate co-transporters SVCT1 and SVCT2, the dehydroascorbic acid transporters GLUT1 and GLUT3, and a third dehydroascorbic acid transporter with properties expected for GLUT2. Analysis by real time quantitative PCR revealed that the post-confluent differentiation of CaCo-2 cells was accompanied by a marked increase (4-fold) in the steady-state level of SVCT1 mRNA, without changes in SVCT2 mRNA levels. Functional studies revealed that the differentiated cells expressed only one functional ascorbic acid transporter having properties expected for SVCT1, and transported ascorbic acid with a V(max) that was increased at least 2-fold compared with pre-confluent cells. Moreover, post-confluent Caco-2 cells growing as monolayers in permeable filter inserts showed selective sorting of SVCT1 to the apical membrane compartment, without functional evidence for the expression of SVCT2. The identification of SVCT1 as the transporter that allows vectorial uptake of ascorbic acid in differentiated CaCo-2 cells has a direct impact on our understanding of the mechanism for vitamin C transport across the intestinal barrier.
New Fully Homomorphic Encryption over the Integers. (2011)

We first present a fully homomorphic encryption scheme over the integers, which modifies the fully homomorphic encryption scheme in [vDGHV10]. The security of our scheme is merely based on the hardness of finding an approximate-GCD problem over the integers, which is given a list of integers perturbed by the small error noises, removing the assumption of the sparse subset sum problem in the origin scheme [vDGHV10]. Then, we construct a new fully homomorphic encryption scheme, which extends the above scheme from approximate GCD over the ring of integers to approximate principal ideal lattice over the polynomial integer ring. The security of our scheme depends on the hardness of the decisional approximate principle ideal lattice polynomial (APIP), given a list of approximate multiples of a principal ideal lattice. At the same time, we also provide APIP-based fully homomorphic encryption by introducing the sparse subset sum problem. Finally, we design a new fully homomorphic encryption scheme, whose security is based on the hardness assumption of approximate lattice problem and the decisional SSSP.
Protein Design of a Bacterially Expressed HIV-1 gp41 Fusion Inhibitor (2007)

Peptides derived from the carboxyl-terminal heptad repeat of the gp41 envelope glycoprotein ectodomain (C-peptides) can inhibit HIV-1 membrane fusion by binding to the amino-terminal trimeric coiled coil of the same protein. The fusion inhibitory peptide T-20 contains an additional tryptophan-rich sequence motif whose binding site extends beyond the gp41 coiled-coil region yet provides the key determinant of inhibitory activity in T-20. Here we report the design of a recombinant peptide inhibitor (called C52L) that includes both the C-peptide and tryptophan-rich regions. By calorimetry, C52L binds to a peptide mimic of the amino-terminal coiled coil with a Kd of 80 nM, reflecting the large degree of helicity in C52L as measured by circular dichroism spectroscopy. The C52L peptide potently inhibits in vitro infection of human T cells by diverse primary HIV-1 isolates irrespective of coreceptor preference, with nanomolar IC50 values. Significantly, C52L is fully active against T-20-resistant variants in a single-cycle HIV-1 infectivity assay. Moreover, because it can be expressed in bacteria, the C52L peptide might be more economical to manufacture on a large scale than T-20-like peptides produced by chemical synthesis. Hence the C52L fusion inhibitor may find a practical application, for example as a vaginal or rectal microbicide to prevent HIV-1 infection in the developing world.
Role of tyrosine kinase and membrane-spanning domains in signal transduction by the platelet-derived growth factor receptor. (1988)

Three types of mutations were introduced into the platelet-derived growth factor (PDGF) receptor to cause a loss of PDGF-stimulated tyrosine kinase activity: (i) a point mutation of the ATP-binding site, (ii) a deletion of the carboxyl-terminal region, and (iii) replacement of the membrane-spanning sequences by analogous transmembrane sequences of other receptors. Transfectants expressing mutated receptors bind, 125I-labeled PDGF with a high affinity but had no PDGF-sensitive tyrosine kinase activity, phosphatidylinositol turnover, increase in the intracellular calcium concentration, change in cellular pH, or stimulation of DNA synthesis. However, PDGF-induced receptor down regulation was normal in the mutant cells. These results indicate that the transmembrane sequence has a specific signal-transducing function other than merely serving as a membrane anchor and that the receptor kinase activity is necessary for most responses to PDGF but is not required for receptor down regulation.
Differentiation therapy of leukemia: 3 decades of development (2009)

Abstract A characteristic feature of leukemia cells is a blockade of differentiation at a distinct stage in cellular maturation. In the 1970s and 1980s, studies demonstrating the capabilities of certain chemicals to induce differentiation of hematopoietic cell lines fostered the concept of treating leukemia by forcing malignant cells to undergo terminal differentiation instead of killing them through cytotoxicity. The first promising reports on this notion prompted a review article on this subject by us 25 years ago. In this review, we revisit this interesting field of study and report the progress achieved in the course of nearly 3 decades. The best proof of principle for differentiation therapy has been the treatment of acute promyelocytic leukemia with all-trans retinoic acid. Attempts to emulate this success with other nuclear hormone ligands such as vitamin D compounds and PPARγ agonists or different classes of substances such as hematopoietic cytokines or compounds affecting the epigenetic landscape have not been successful on a broad scale. However, a multitude of studies demonstrating partial progress and improvements and, finally, the new powerful possibilities of forward and reverse engineering of differentiation pathways by manipulation of transcription factors support the continued enthusiasm for differentiation therapy of leukemia in the future.
Multiparametric analysis of waterline contamination in dental units (1996)

Microbial contamination of dental unit waterlines is thought to be the result of biofilm formation within the small-bore tubing used for these conduits. Systematic sampling of 121 dental units located at the dental school of Université de Montréal showed that none of the waterlines was spared from bacterial contamination. Multilevel statistical analyses showed significant differences between samples taken at the beginning of the day and samples taken after a 2-min purge. Differences were also found between water from the turbine and the air/water syringe. Random variation occurred mainly between measurements (80%) and to a lesser extent between dental units (20%). In other analyses, it was observed to take less than 5 days before initial bacterial counts reached a plateau of 2 x 10(5) CFU/ml in newly installed waterlines. Sphyngomonas paucimobilis, Acinetobacter calcoaceticus, Methylobacterium mesophilicum, and Pseudomonas aeruginosa were the predominant isolates. P. aeruginosa showed a nonrandom distribution in dental unit waterlines, since 89.5% of the all the isolates were located in only three of the nine clinics tested. Dental units contaminated by P. aeruginosa showed significantly higher total bacterial counts than the others. By comparison, P. aeruginosa was never isolated in tap water remote from or near the contaminated dental unit waterlines. In conclusion, dental unit waterlines should be considered an aquatic ecosystem in which opportunistic pathogens successfully colonize synthetic surfaces, increasing the concentration of the pathogens in water to potentially dangerous levels. The clinical significance of these findings in relation to routine dental procedures is discussed.
Recent Advancement in Application of Hydrophobic Interaction Chromatography for Aggregate Removal in Industrial Purification Process (2009)

Hydrophobic interaction chromatography (HIC) is a classic purification tool applied in protein and antibody, laboratory and industrial production process. It has been mainly used for the removal of both product-related impurities such as aggregates, as well as process contaminants such as host cell proteins. This review will focus on the recent development of HIC in its applications in the industrial purification processes. The process economy and requirements of high product purity and quality have driven much of the recent advancement in HIC chromatography in terms of increased throughput and enhanced selectivity or resolution. Meanwhile, high throughput screening (HTS), design of experiments (DoE) and platform approach for process development have been applied to shorten the development time. The throughput improvement has been achieved through new resins with increased binding capacity, using dual salts for load conditioning, and operating in the flow-through mode. In addition, hydrophobic interaction membrane filter chromatography technology reduces bed volumes and buffer usage and potentially improves process throughput by reducing cycle time. Selectivity and/or resolution enhancements have been achieved through optimization of operation parameters such as temperature and efforts such as application of solvent additives.
Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. (1989)

Sections of formalin-fixed, paraffin-embedded tissue from 185 primary breast carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining, which is known to correlate with gene amplification, was associated with earlier relapse, shorter postrelapse survival, and shorter overall survival. Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. Expression of the c-erbB-2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer.
Nucleotide sequence of the gene coding for Clostridium barati type F neurotoxin: Comparison with other clostridial neurotoxins (1993)

The neurotoxin gene from Clostridium barati ATCC43756 was cloned as a series of overlapping polymerase chain reaction (PCR) generated fragments using primers designed to conserve toxin sequences previously published. The toxin gene has an open reading frame (ORF) of 1268 amino acids giving a calculated molecular mass of 141049 Da. The sequence identity between the C. barati ATCC43756 and non-proteolytic C. botulinum 202F neurotoxins is 64.2% for the light chain and 73.6% for the heavy chain. This is much lower than reported identities for the type E neurotoxins from C. botulinum and C. butyricum (96% identity between light chains and 98.8% between the heavy chains). Previously identified conserved regions in other botulinal neurotoxins were also conserved in that of C. barati. An ORF upstream of the toxin coding region was revealed. This shows strong homology to the 3′ end of the gene coding for the nontoxic-nonhemagglutinin (NTNH) component of the progenitor toxin from C. botulinum type C neurotoxin.
Prevention and Treatment of Experimental Estrogen Receptor–Negative Mammary Carcinogenesis by the Synthetic Triterpenoid CDDO-Methyl Ester and the Rexinoid LG100268 (2008)

CDDO-Me and 268 are useful as individual drugs to prevent ER-negative mammary tumorigenesis and to treat established tumors. They synergize when used in combination for prevention.
Nanowire Arrays for Thermoelectric Devices (2003)

This study reports on the fabrication and characterization of two prototype thermoelectric devices constructed of either silicon (Si) or bismuth telluride (Bi2Te3) nanowire arrays. The growth mechanisms and fabrication procedures of the Si and Bi2Te3 devices are different as described in this paper. To characterize the thermoelectric device components, current-voltage (I-V) characteristics were first used to estimate their performance. For the Si device, the I-V characteristics suggest ohmic contacts at the metal-semiconductor junction. For the Bi2Te3 device, the I-V characteristics curve showed a rectifying contact. Either low doping of the Bi2Te3 or surface contamination, i.e. native oxide, may cause the rectifying contact. The reversible Peltier effects occurring within the Si device were analyzed using a micro-thermocouple. Results indicated possible limitations of using Si nanowire arrays for the thermoelectric device.
Review of Advanced Liquid−Liquid Extraction Systems for the Separation of Metal Ions by a Combination of Conversion of the Metal Species with Chemical Reaction (2001)

Recent developments in an advanced liquid−liquid extraction system for the separation of metal ions by combining a modification or chemical reaction of the metal species in the aqueous and organic phases demonstrate considerable potential. Possible techniques for the chemical conversion of aqueous-phase metal species include redox reactions for the metal ions, masking effects through the addition of water-soluble complexing agents, and complexing reactions with salting-out agents. For the conversion of organic-phase metal species, a synergistic effects through the addition of additional extractants and redox reactions for the extracted species are also useful. The separation of metal ions is effectively improved by the introduction of such chemical reactions to the extraction system.
Near Perfect Reconstruction Quadrature Mirror Filter (2008)

In this paper, various algorithms for designing quadrature mirror filter are reviewed and a new algorithm is presented for the design of near perfect reconstruction quadrature mirror filter bank. In the proposed algorithm, objective function is formulated using the perfect reconstruction condition or magnitude response condition of prototype filter at frequency (ω = 0.5π) in ideal condition. The cutoff frequency is iteratively changed to adjust the filters coefficients using optimization algorithm. The performances of the proposed algorithm are evaluated in term of computation time, reconstruction error and number of iterations. The design examples illustrate that the proposed algorithm is superior in term of peak reconstruction error, computation time, and number of iterations. The proposed algorithm is simple, easy to implement, and linear in nature.
Electroanalytical Detection of Glucose Using a Cyanometalate-Modified Electrode:  Requirements for the Oxidation of Buried Redox Sites in Glucose Oxidase (1996)

Modification of a nickel electrode with a mixture of iron and ruthenium cyanometalates allows one to efficiently turn over glucose oxidase in the presence of its substrate. A limit of detection for glucose of 25 μM can be obtained with an observed saturation concentration of 10 mM. Glucose detection is found to be very sensitive to the cationic environment of the electrolyte. The largest currents for glucose oxidation are observed in the presence of nonelectroactive multiply charged cations. The solid state nature of the surface-confined cyanometalate redox mediator argues against the widely held mechanism for enzyme oxidation in which the redox mediator is required to enter the enzyme active site.
15-deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats (2000)

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-gamma agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-gamma in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-gamma in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2) were more potent than troglitazone. These findings suggest that PPAR-gamma may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2), may be useful in the treatment of RA.
Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. (1988)

We have constructed a set of packaging cell lines useful for the generation of helper-free recombinant retroviruses with amphotropic and ecotropic host ranges. To eliminate the problems of transfer of packaging functions and helper virus formation encountered with the previously available packaging systems, two mutant Moloney murine leukemia virus-derived proviral genomes carrying complementary mutations in the gag-pol or env regions were sequentially introduced into NIH 3T3 cells by cotransformation. Both genomes contained a deletion of the psi sequence necessary for the efficient encapsidation of retroviral genomes into virus particles and additional alterations at the 3' end of the provirus. We show that the resulting packaging cell lines psi CRIP and psi CRE can be used to isolate clones that stably produce high titers (10(6) colony-forming units/ml) of recombinant retroviruses with amphotropic and ecotropic host ranges, respectively. More importantly, we demonstrate that viral producers derived from the packaging cell lines do not transfer the packaging functions, or yield helper virus, even under conditions where existing packaging cell lines can be shown to yield transfer of packaging functions and/or helper virus. These properties of the psi CRIP and psi CRE packaging lines make them particularly valuable reagents for in vivo gene transfer studies aimed at cell lineage analysis and the development of human gene replacement therapies.
Adenovirus DNA polymerase is recognized by human CD8+ T cells (2008)

Donor lymphocytes have potential as a treatment for adenovirus (Ad) disease in haematopoietic stem cell transplant (SCT) recipients, but better understanding of Ad-specific T-cell responses is required. Most healthy adults exhibit memory T-cell responses to hexon, a capsid protein synthesized late after infection. However, since the Ad E3-19k downregulates major histocompatibility complex (MHC) class I molecules, cytotoxic T cells (CTLs) targeted to early viral proteins may be more effective in eliminating Ad-infected cells in vivo. Here we show that Ad-specific CTLs recognize the early region 2 proteins DNA polymerase (Pol) and DNA-binding protein (DBP). Firstly, memory Ad-specific CD8(+) T cells were amplified from healthy donors by in vitro stimulation with Ad-infected dendritic cells and found to exhibit MHC-restricted cytotoxicity to targets expressing Pol and DBP. Secondly, gamma interferon responses to HLA A2-binding motif peptides from Pol and DBP were directly detected in peripheral blood mononuclear cells (PBMCs) from a recently infected normal donor. Peptide-specific CTLs generated to Pol and DBP epitopes were confirmed to exhibit HLA A2-restricted killing of targets expressing Pol or DBP. Lastly, Pol-epitope-specific T cells were detected at similar or higher frequencies than hexon and DBP in three of three SCT recipients recovering from invasive Ad disease. Pol epitopes were well conserved among different Ad serotypes. Therefore, Pol is a promising target for immunotherapy of Ad disease.
Design and Synthesis of New PotentC2-Symmetric HIV-1 Protease Inhibitors. Use ofl-Mannaric Acid as a Peptidomimetic Scaffold (1998)

A study on the use of derivatized carbohydrates as C2-symmetric HIV-1 protease inhibitors has been undertaken. L-Mannaric acid (6) was bis-O-benzylated at C-2 and C-5 and subsequently coupled with amino acids and amines to give C2-symmetric products based on C-terminal duplication. Potent HIV protease inhibitors, 28 Ki = 0.4 nM and 43 Ki = 0.2 nM, have been discovered, and two synthetic methodologies have been developed, one whereby these inhibitors can be prepared in just three chemical steps from commercially available materials. A remarkable increase in potency going from IC50 = 5000 nM (23) to IC50 = 15 nM (28) was observed upon exchanging -COOMe for -CONHMe in the inhibitor, resulting in the net addition of one hydrogen bond interaction between each of the two -NH- groups and the HIV protease backbone (Gly 48/148). The X-ray crystal structures of 43 and of 48 have been determined (Figures 5 and 6), revealing the binding mode of these inhibitors which will aid further design.