gebhart/patrepeval huggingface dataset:
Nanoparticles-induced vertical alignment in liquid crystal cell (2007)

This letter reports that adding nanoparticles in the negative dielectric anisotropic liquid crystal (LC) cell can exhibit the properties of vertical alignment without using alignment layers. The electro-optical properties of this nanoparticles-induced vertical alignment in the LC cell are very similar to the conventional homeotropic LC cell with alignment layers. This technique can be used to fabricate a flexible LC display requiring a low temperature process.
Structural Analysis of the Sulfotransferase (3-O-Sulfotransferase Isoform 3) Involved in the Biosynthesis of an Entry Receptor for Herpes Simplex Virus 1 (2004)

Heparan sulfate (HS) plays essential roles in assisting herpes simplex virus infection and other biological processes. The biosynthesis of HS includes numerous specialized sulfotransferases that generate a variety of sulfated saccharide sequences, conferring the selectivity of biological functions of HS. We report a structural study of human HS 3-O-sulfotransferase isoform 3 (3-OST-3), a key sulfotransferase that transfers a sulfuryl group to a specific glucosamine in HS generating an entry receptor for herpes simplex virus 1. We have obtained the crystal structure of 3-OST-3 at 1.95 A in a ternary complex with 3'-phosphoadenosine 5'-phosphate and a tetrasaccharide substrate. Mutational analyses were also performed on the residues involved in the binding of the substrate. Residues Gln255 and Lys368 are essential for the sulfotransferase activity and lie within hydrogen bonding distances to the carboxyl and sulfo groups of the uronic acid unit. These residues participate in the substrate recognition of 3-OST-3. This structure provides atomic level evidence for delineating the substrate recognition and catalytic mechanism for 3-OST-3.
Gadolinium-labeled liposomes: targeted MR contrast agents for the liver and spleen. (1987)

A contrast agent for use in magnetic resonance (MR) imaging of the liver and spleen has been designed in which gadolinium-DTPA is chemically incorporated into the lamellar phase of liposome particles. This agent has excellent in vivo stability and is taken up by liver and spleen of normal mice after intravenous administration. The T1 increased by 110% in liver and 66% in spleen at 4 degrees C. At 37 degrees, the relaxation rate in the liver increased by 180%. This method is an attractive concept for the development of various organ-specific liposomal contrast agents that may be used for either MR imaging or nuclear medicine.
The parathyroid-calcitriol axis in health and chronic renal failure. (1990)

Both PTH and calcitriol directly affect calcium homeostasis and each exercises important regulatory effects on the other
Design, Synthesis, and SAR of Potent and Selective Dipeptide-Derived Inhibitors for Dipeptidyl Peptidases (2003)

In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II inhibitors which can be characterized by their high selectivity for DPP II with regard to DPP IV. Dab-Pip and Dab-Pip-2-CN were selected as the most promising inhibitors (IC(50) nM range) and will enable us to study the physiological role of DPP II and to differentiate between DPP II and DPP IV in biological systems.
Identification and characterization of a membrane-bound cytotoxin of murine cytolytic lymphocytes that is related to tumor necrosis factor/cachectin. (1989)

Cytotoxic T lymphocytes (CTLs) kill their targets by a contact-dependent mechanism. We investigated the possibility that the CTL membranes themselves could exert direct cytotoxic activity. Murine CTLs that had been fixed with paraformaldehyde retained a slow cytotoxic activity toward various target cells that are also sensitive to another cytokine, tumor necrosis factor (TNF)/cachectin. This cytotoxic activity was neutralized by antibodies specific for TNF. Membrane fractions obtained from CTLs were cytotoxic to TNF-sensitive targets but not to several TNF-resistant cell lines. Immunoblot analysis revealed a membrane protein band of 50-60 kDa from CTLs that reacts with anti-TNF antibodies. The surface localization of this cytokine was further ascertained by flow cytometry, indirect immunofluorescence, and immunoelectron microscopy studies using TNF-specific antibodies. Radioiodination of CTL surface proteins followed by immunoprecipitation with anti-TNF antibodies confirmed the presence of a TNF-related cytokine in the plasma membranes of CTLs that migrated with an apparent molecular mass of 50-60 kDa under disulfide-reducing conditions. This cytokine can be removed from membranes by treatment with detergents but not with high-salt buffers, suggesting that it may be an integral membrane protein.
TECHNOLOGY UPDATE: Development of a gas-phase bioprocess for isoprene-monomer production using metabolic pathway engineering (2010)

A sustainable production system for isoprene is being developed based on microbial fermentation of renewable sugars (BioIsoprene™). Isoprene is an important commodity chemical used in a wide range of industrial applications, ranging from the production of synthetic rubber for tires and coatings, to use in adhesives and development of specialty elastomers. Current production of isoprene is derived entirely from petrochemical sources. There is an increasing global need for more isoprene and a simultaneous environmental imperative to reduce greenhouse gases, both of which can be achieved by a highefficiency fermentation-based process for polymer-grade isoprene production. The key to such a process is engineering a microbial cell factory that is streamlined in physiology to drive sugar conversion through engineered biosynthetic pathways, to produce isoprene at near theoretical yields. Two biosynthetic isoprenoid pathways being optimized towards this end, and processes delivering >60g/L of isoprene are described. The product produced in the gas-phase is recovered from the fermentation off-gas in a continuous process. Current state-of-the-art technology has resulted in production, recovery, polymerization, and manufacture of tires with the isoprene component produced via fermentation. Continued improvements in both the cell factory and the production process are being actively pursued.
Cryopreservation of Human Lymphocytes: A Brief Review and Evaluation of an Automated Liquid Nitrogen Freezer (1979)

Successful cryopreservation of human lymphocytes has been previously described. Cryopreserved lymphocytes are useful for a variety of in vitro immunologic studies. This study was performed to determine the applicability and/or advantages of using a programmable freezing system, and compares glycerol versus dimethyl sulfoxide (DMSO) at varying concentrations on post-thaw viability, E-rosetting and immunoglobulin fluorescence. Prefreeze T and B lymphocyte percentages were determined. Cells were then frozen in varying concentrations of glycerol and DMSO. Optimum cryoprotectant type and concentration was determined. Lymphocytes from seven individuals were frozen by the batch method in a mechanical freezer and with the automated liquid nitrogen injection system. Data on post-thaw T and B percentages and viability revealed 10% DMSO and liquid nitrogen control freezing method at 1 C/minute as the best conditions for lymphocyte preservation as reflected by post-thaw in vitro testing.
A New Splice Variant of the Major Subunit of Human Asialoglycoprotein Receptor Encodes a Secreted Form in Hepatocytes (2010)

We conclude that two naturally occurring ASGPR H1 splice variants are produced in human hepatocytes. A hetero-oligomeric complex sASGPR consists of the secreted form of H1 and H2 and may bind to free substrates in circulation and carry them to liver tissue for uptake by ASGPR-expressing hepatocytes.
Unusual Stability of Acetonitrile-Based Superconcentrated Electrolytes for Fast-Charging Lithium-Ion Batteries (2014)

The development of a stable, functional electrolyte is urgently required for fast-charging and high-voltage lithium-ion batteries as well as next-generation advanced batteries (e.g., Li-O2 systems). Acetonitrile (AN) solutions are one of the most promising electrolytes with remarkably high chemical and oxidative stability as well as high ionic conductivity, but its low stability against reduction is a critical problem that hinders its extensive applications. Herein, we report enhanced reductive stability of a superconcentrated AN solution (>4 mol dm(-3)). Applying it to a battery electrolyte, we demonstrate, for the first time, reversible lithium intercalation into a graphite electrode in a reduction-vulnerable AN solvent. Moreover, the reaction kinetics is much faster than in a currently used commercial electrolyte. First-principle calculations combined with spectroscopic analyses reveal that the peculiar reductive stability arises from modified frontier orbital characters unique to such superconcentrated solutions, in which all solvents and anions coordinate to Li(+) cations to form a fluid polymeric network of anions and Li(+) cations.
A systematic mutational analysis of hormone-binding determinants in the human growth hormone receptor. (1991)

A mutational strategy is presented that allowed us to identify hormone-binding determinants in the extracellular portion of the human growth hormone receptor (hGHbp), a 238-residue protein with sequence homology to a number of cytokine receptors. By systematically replacing side chains with alanine we probed the importance of charged residues (49 total, typically located on the surface), aromatic residues (9 total), and neighbors of these (26 total). The alanine substitutions that were most disruptive to hormone binding are located predominantly in four segments of a cysteine-rich domain in the hGHbp, and collectively they form a patch when mapped upon a structural model proposed for cytokine receptors. Control experiments with monoclonal antibodies confirmed that most of these alanine substitutions do not disrupt the overall antigenic structure of the hGHbp. This high-resolution functional analysis will complement structural studies and provides a powerful basis for evaluating and engineering the energetics of hormone-receptor interactions. Moreover, the hormone-binding determinants identified here may be similarly located in other, homologous, receptors.
Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro (1992)

We have probed the structural organization of the human immunodeficiency virus type 1 integrase protein by limited proteolysis and the functional organization by site-directed mutagenesis of selected amino acid residues. A central region of the protein was relatively resistant to proteolysis. Proteins with altered amino acids in this region, or in the N-terminal part of the protein that includes a putative zinc-binding motif, were purified and assayed for 3' processing, DNA strand transfer, and disintegration activities in vitro. In general, these mutations had parallel effects on 3' processing and DNA strand transfer, suggesting that integrase may utilize a single active site for both reactions. The only proteins that were completely inactive in all three assays contained mutations at conserved amino acids in the central region, suggesting that this part of the protein may be involved in catalysis. In contrast, none of the mutations in the N-terminal region resulted in a protein that was inactive in all three assays, suggesting that this part of integrase may not be essential for catalysis. The disintegration reaction was particularly insensitive to these amino acid substitutions, indicating that some function that is important for 3' processing and DNA strand transfer may be dispensable for disintegration.
Doxorubicin-Induced Cardiomyopathy (1998)

Doxorubicin (Adriamycin) has been used in oncologic practice since the late 1960s. It held promise as a powerful drug in the fight against cancer. The tumors most commonly responding to doxorubicin when it is given as a single agent or in combination with other antitumor agents include breast and esophageal carcinomas; osteosarcoma, Kaposi's sarcoma, and soft-tissue sarcomas; and Hodgkin's and non-Hodgkin's lymphomas. Other cancers that are less responsive to doxorubicin but that are still treated with the drug because of its overall benefits include gastric, liver, bile-duct, pancreatic, and endometrial carcinomas. However, reports of fatal cardiotoxic effects of doxorubicin have . . .
hrcA, the first gene of the Bacillus subtilis dnaK operon encodes a negative regulator of class I heat shock genes (1996)

Whereas in Escherichia coli only one heat shock regulon is transiently induced by mild heat stress, for Bacillus subtilis three classes of heat shock genes regulated by different mechanisms have been described. Regulation of class I heat shock genes (dnaK and groE operons) involves an inverted repeat (CIRCE element) which most probably serves as an operator for a repressor. Here, we report on the analyses of an hrcA null mutant (delta hrcA), in which hrcA, the first gene of the dnaK operon, was deleted from the B. subtilis chromosome. This strain was perfectly viable at low and high temperatures. Transcriptional analysis of the deletion mutant revealed a high level of constitutive expression of both the dnaK and groE operons even at a low temperature. A further increase in the amount of groE transcript was observed after temperature upshift, suggesting a second induction mechanism for this operon. Overproduction of HrcA protein from a second copy of hrcA derived from a plasmid (phrcA+) in B. subtilis wild-type and delta hrcA strains prevented heat shock induction of the dnaK and groE operons at the level of transcription almost completely and strongly reduced the amounts of mRNA at a low temperature as well. Whereas the wild-type strain needed 4 h to resume growth after temperature upshift, the delta hrcA strain stopped growth only for about 1 h. Overproduction of HrcA protein prior to a heat shock almost completely prevented growth at a high temperature. These data clearly demonstrate that the hrcA product serves as a negative regulator of class I heat shock genes.
Real-Time PCR Assay for Detection of Quinolone-Resistant Neisseria gonorrhoeae in Urine Samples (2007)

A need exists for the development of applicable surveillance tools to detect fluoroquinolone-resistant Neisseria gonorrhoeae (QRNG) in urine samples. We describe here a real-time PCR assay for detecting mutations in the Ser91 codon of the gyrA gene of N. gonorrhoeae in urine specimens. We tested 96 urine samples collected along with Gonorrhea Isolate Surveillance Project (GISP) urethral swab samples and compared the results with matched MICs of ciprofloxacin, as reported by the regional GISP laboratory. We then tested 100 urine specimens, known to be gonorrhea positive by nucleic acid amplification testing, provided by females to challenge the real-time PCR assay with urine specimens containing potentially less target DNA content than specimens from symptomatic males. With an MIC threshold of 0.125 mug of ciprofloxacin/ml, our assay correctly identified resistance in 41 of 44 (93.2%; 95% confidence interval [CI] = 81.3 to 98.6%) corresponding resistant culture specimens and correctly identified 51 of 51 (100%; 95% CI = 93.0 to 100%) susceptible specimens. One specimen did not amplify. The assay successfully amplified the gyrA amplicon and determined a susceptibility genotype in 72 of 100 (72%) urine specimens collected from female patients. We developed an assay for detecting QRNG in urine specimens that correlated well with MIC results of cultured specimens and had moderate sensitivity with urine specimens. This methodology might fulfill the need for a QRNG detection system for urine specimens, a useful characteristic in the age of nucleic acid amplification testing for gonococcal infection.
Prion Diseases and Neurodegeneration (1994)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Neutralizing Antibodies Against HIV-1 BRU and SF2 Isolates Generated in Mice Immunized with Recombinant Vaccinia Virus Expressing HIV-1 (BRU) Envelope Glycoproteins and Boosted with Homologous gp160 (1991)

Anti-human immunodeficiency virus type 1 (Anti-HIV-1) antibody response was compared in four groups of mice following inoculation with HIV-1 gp160, with live recombinant vaccinia virus expressing HIV-1 envelope glycoproteins, or with both immunogens in alternate orders for primary or secondary immunizations. Both subunit and recombinant virus immunogens induced similar levels of antibody response following primary immunization. However, after secondary immunization, mice primed with live recombinant virus and then boosted with subunit gp160 immunogen showed significantly higher antibody response than those in the other three groups. Neutralizing antibodies were generated only in this group of mice and were shown to neutralize both the homologous virus (BRU) and a divergent isolate (SF2) of HIV-1. On the other hand, their reactivities to peptide sequences from the principal neutralizing determinant (PND) of gp120 were limited to the BRU isolate, not SF2 or MN, indicating that the cross-neutralizing activities were directed against determinants other than the linear epitope(s) within the PND. These results also indicate that combined immunization by priming with liver recombinant virus and boosting with subunit immunogen may be more effective than immunization by either immunogen alone.
Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. (1994)

Fas/APO-1 is a cell surface protein known to trigger apoptosis in a variety of cell types upon specific antibody binding. Although extensively studied on normal and malignant hematopoietic cells, little is known about Fas/APO-1 on nonhematopoietic cells. In the study presented here, we have examined Fas/APO-1 expression and function on 11 human tumors of nonhematopoietic origin. By flow cytometric analysis, Fas/APO-1 was expressed on 10 of the 11 tumors at levels comparable to those previously reported for lymphoid cells sensitive to the cytolytic effects of anti-Fas. Despite abundant cell surface expression, only 4 of the 10 Fas-positive tumors were sensitive to the cell-killing effects of anti-Fas. Moreover, anti-Fas enhanced the growth of 2 of 10 Fas-positive tumors. Additional studies using cycloheximide demonstrated that de novo protein synthesis was required for anti-Fas-triggered growth stimulation and, at least in one case, was responsible for the resistance to antibody-induced apoptosis. The biological effects initiated by anti-Fas engagement, however, were not correlated with endogenous bcl-2 expression. This report documents that: (a) Fas/APO-1 is widely expressed on cultured nonhematopoietic tumors; (b) the inherent susceptibility to anti-Fas-induced apoptosis is not correlated with expression of the Fas/APO-1 protein; (c) Fas/APO-1 engagement can result in growth enhancement; and (d) protective/growth-promoting proteins other than bcl-2 may contribute to the diverse spectrum of biological effects induced by anti-Fas engagement of the Fas/APO-1 protein.
Induction of antibodies to the envelope protein of the human immunodeficiency virus by immunization with monoclonal anti-idiotypes. (1991)

Anti-idiotypes that possess the internal image of antigen can induce protective humoral immunity toward microbes. Herein we demonstrate antigen mimicry by monoclonal anti-idiotypes of a distinct epitope of the human immunodeficiency virus (HIV) envelope protein that is defined by a synthetic peptide. This peptide, corresponding to amino acid residues 503-535 (peptide 503-535) of HIV-1 IIIB gp160, induced antibodies in three mammalian species that interacted with HIV-1 gp120 and inhibited in vitro syncytium formation caused by HIV-1, IIIB and MN isolates. Three monoclonal anti-idiotypes were generated against rabbit anti-gp120 antibodies specific for peptide 503-535. These anti-idiotypes recognize an interspecies cross-reactive idiotype expressed on mouse, chimpanzee, baboon, rabbit, and human anti-gp120 antibodies specific for peptide 503-535. The interaction with the cross-reactive idiotype is inhibited by synthetic peptide and HIV-1 gp160. Furthermore, rabbits immunized with the monoclonal anti-idiotypes produced antibodies that also bind HIV-1 gp120 and gp160 and recognized the epitope defined by peptide 503-535.
Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation (2008)

Neural precursor cells (NPCs) differentiate into neurons, astrocytes, and oligodendrocytes in response to intrinsic and extrinsic changes. Notch signals maintain undifferentiated NPCs, but the mechanisms underlying the neuronal differentiation are largely unknown. We show that SIRT1, an NAD(+)-dependent histone deacetylase, modulates neuronal differentiation. SIRT1 was found in the cytoplasm of embryonic and adult NPCs and was transiently localized in the nucleus in response to differentiation stimulus. SIRT1 started to translocate into the nucleus within 10 min after the transfer of NPCs into differentiation conditions, stayed in the nucleus, and then gradually retranslocated to the cytoplasm after several hours. The number of neurospheres that generated Tuj1(+) neurons was significantly decreased by pharmacological inhibitors of SIRT1, dominant-negative SIRT1 and SIRT1-siRNA, whereas overexpression of SIRT1, but not that of cytoplasm-localized mutant SIRT1, enhanced neuronal differentiation and decreased Hes1 expression. Expression of SIRT1-siRNA impaired neuronal differentiation and migration of NPCs into the cortical plate in the embryonic brain. Nuclear receptor corepressor (N-CoR), which has been reported to bind SIRT1, promoted neuronal differentiation and synergistically increased the number of Tuj1(+) neurons with SIRT1, and both bound the Hes1 promoter region in differentiating NPCs. Hes1 transactivation by Notch1 was inhibited by SIRT1 and/or N-CoR. Our study indicated that SIRT1 is a player of repressing Notch1-Hes1 signaling pathway, and its transient translocation into the nucleus may have a role in the differentiation of NPCs.