gebhart/patrepeval huggingface dataset:
γ-Glutamyl carboxylation: An extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates (2002)

The posttranslational gamma-carboxylation of glutamate residues in secreted proteins to gamma-carboxyglutamate is carried out by the vitamin K-dependent enzyme gamma-glutamyl carboxylase. gamma-Carboxylation has long been thought to be a biochemical specialization of vertebrates, essential for blood clotting. Recently, a gamma-carboxylase was shown to be expressed in Drosophila, although its function remains undefined in this organism. We have characterized both cDNA and genomic clones for the gamma-glutamyl carboxylase from the marine mollusc, Conus, the only nonvertebrate organism for which gamma-carboxyglutamate-containing proteins have been biochemically and physiologically characterized. The predicted amino acid sequence has a high degree of sequence similarity to the Drosophila and vertebrate enzymes. Although gamma-carboxylases are highly conserved, the Conus and mammalian enzymes have divergent substrate specificity. There are striking parallels in the gene organization of Conus and human gamma-carboxylases. Of the 10 Conus introns identified, 8 are in precisely the same position as the corresponding introns in the human enzyme. This remarkable conservation of intron/exon boundaries reveals that an intron-rich gamma-carboxylase was present early in the evolution of the animal phyla; although specialized adaptations in mammals and molluscs that require this extracellular modification have been identified, the ancestral function(s) and wider biological roles of gamma-carboxylation still need to be defined. The data raise the possibility that most introns in the genes of both mammals and molluscs antedate the divergence of these phyla.
A novelβ‐sheet breaker, RS‐0406, reverses amyloidβ‐induced cytotoxicity and impairment of long‐term potentiationin vitro (2002)

Fibril formation of amyloid beta peptide (Abeta) is considered to be responsible for the pathology of Alzheimer's disease (AD). The Abeta fibril is formed by a protein misfolding process in which intermolecular beta-sheet interactions become stabilized abnormally. Thus, to develop potential anti-AD drugs, we screened an in-house library to find compounds which have a profile as a beta-sheet breaker. We searched for a beta-sheet breaker profile in an in-house library of approximately 113,000 compounds. From among the screening hits, we focused on N,N'-bis(3-hydroxyphenyl)pyridazine-3,6-diamine (named RS-0406), which had been newly synthesized in our laboratory. This compound (10-100 microg ml(-1)) was found to be capable of significantly inhibiting 25 microM Abeta(1-42) fibrillogenesis and, furthermore, disassembling preformed Abeta(1-42) fibrils in vitro. 3 We then investigated the effect of RS-0406 on 111 nM Abeta(1-42)-induced cytotoxicity in primary hippocampal neurons, and found that 0.3-3 microg ml(-1) RS-0406 ameliorates the cytotoxicity. Moreover, 3 microg ml(-1) RS-0406 reversed 1 micro M Abeta(1-42)-induced impairment of long-term potentiation in hippocampal slices. 4 In this study, we have succeeded in identifying RS-0406 which has potential to inhibit Abeta(1-42) fibrillogenesis, and to protect neurons against Abeta(1-42)-induced biological toxicity in vitro. These results suggest that RS-0406 or one of the derivatives could become a therapeutic agent for AD patients.
Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis. (2015)

Combining KL-6 with MMP7 may be a useful screening tool for patients at risk of ILD. SP-D may predict short-term decline in lung function.
General anesthetics. 3. Fluorinated methyl ethyl ethers as anesthetic agents (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGeneral anesthetics. 3. Fluorinated methyl ethyl ethers as anesthetic agentsRoss C. Terrell, Louise Speers, Alex J. Szur, Thomas Ucciardi, and James F. VitchaCite this: J. Med. Chem. 1972, 15, 6, 604–606Publication Date (Print):June 1, 1972Publication History Published online1 May 2002Published inissue 1 June 1972https://pubs.acs.org/doi/10.1021/jm00276a008https://doi.org/10.1021/jm00276a008research-articleACS PublicationsRequest reuse permissionsArticle Views252Altmetric-Citations40LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs) (2018)

Safe and effective DNA delivery systems are required to enable or enhance clinical strategies and research involving gene therapy and DNA vaccinations. To address this delivery problem, a series of charge-altering releasable transporters (CARTs) with varied lipid content were prepared and evaluated for plasmid DNA (pDNA) delivery into cultured cells. These lipid-modified CART co-oligomers were synthesized in only two steps via sequential organocatalytic ring-opening polymerization of lipid-containing cyclic carbonate monomers and morpholinone monomers. Lipid variations of the CARTs substantially impacted the delivery efficiency of pDNA, with oleyl- and linoleyl-based CARTs showing enhanced performance relative to the commercial transfection agent Lipofectamine 2000 (L2000). The best-performing oleyl CART was carried forward to study stable luciferase transfection with a Sleeping Beauty ( SB) transposon system. The oleyl CART outperformed the L2000 positive control with respect to stable transfection efficiency. CART-pDNA complexes represent a new DNA delivery system for research and clinical applications.
Photochemical Sensing of NO2 with SnO2 Nanoribbon Nanosensors at Room Temperature This work was supported by the Camille and Henry Dreyfus Foundation, 3M Corporation, the National Science Foundation, and the University of California, Berkeley. P.Y. is an Alfred P. Sloan Research Fellow. Work at the Lawrence Berkeley National Laboratory was supported by the Office of Science, Basic Energy Sciences, Division of Materials Science of the US Department of Energy. We thank the National Center for Electron Microscopy for the use of their facilities. (2002)

Good candidates for miniaturized, ultrasensitive gas sensors in many applications are individual single-crystalline SnO2 nanoribbons. Here it is shown that they can be used to detect ppm-level concentrations of NO2 at room temperature under UV illumination. The picture illustrates that they work reliably even near their resolution limit under 365-nm light.
Inhibition of Synovial Plasma Extravasation by Preemptive Administration of an Antiinflammatory Irrigation Solution in the Rat Knee (2001)

Preemptive, intraarticular irrigation of a combination of multiple antiinflammatory drugs is a novel and potentially effective method for reducing the synovial inflammatory response, such as that during arthroscopy. In this study, a three-drug combination infusion was statistically superior to one- or two-drug infusions in a rat model.
The Original Pathologische Anatomie Leiden-Endothelium Monoclonal Antibody Recognizes a Vascular Endothelial Growth Factor–Binding Site within Neuropilin-1 (2007)

For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the original PAL-E antibody. We found that a subset of the selected panel of peptides had motifs with strong homology to an exposed site within the b1 domain of human neuropilin-1 (NRP-1). We confirmed peptide binding by ELISA and by surface plasmon resonance. We also showed that the PAL-E antigen colocalizes with NRP-1 staining in endothelial cells. Crystal structure of the b1 domain in NRP-1 suggests that the PAL-E binding site overlaps with a vascular endothelial growth factor (VEGF) binding site. Taken together, these results indicate that NRP-1 is an endothelial cell antigen recognized by the true PAL-E antibody. The consistent biochemical, morphologic, and functional features between the PAL-E antigen and NRP-1 support our interpretation. Given that NRP-1 is a VEGF receptor, these results explain the attributes of the PAL-E antibody as a marker of vascular permeability and angiogenesis.
Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline (1997)

All patients with cutaneous rosacea had some degree of ocular involvement. Tear break-up time is abnormal in patients with rosacea. Ocular erythema and telangiectasia, meibomian gland dysfunction, and short tear break-up time in patients with cutaneous rosacea are indicators of ocular rosacea. Doxycycline, 100 mg daily, will improve ocular disease and increase the tear break-up time.
Effect of Ni2+ Content on Lithium/Nickel Disorder for Ni-Rich Cathode Materials (2015)

Li excess LiNi0.8Co0.1Mn0.1O2 was produced by sintering the Ni0.8Co0.1Mn0.1(OH)2 precursor with different amounts of a lithium source. X-ray photoelectron spectroscopy confirmed that a greater excess of Li(+) leads to an increase in the number of Ni(2+) ions. Interestingly, the level of Li(+)/Ni(2+) disordering decreases with an increase in Ni(2+) content determined by the I003/I104 ratio in the X-ray diffraction patterns. The electrochemical measurement shows that the cycling stability and rate capability improve with an increase in Ni(2+) content. After cycling, electrochemical impedance spectroscopy shows decreased charge transfer resistance, and the XRD patterns exhibit an increased I003/I104 ratio with an increase in Ni(2+) content, reflecting the decrease in the level of Li(+)/Ni(2+) disorder during cycling.
Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads (2003)

Multipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the tissue-engineered cartilage and bone using in vitro techniques and by placing cells into the hind legs of five severe combined immunodeficient mice. After six weeks, radiological and histological analysis indicated that the PLA cells induced into the chondrogenic phenotype had the histological appearance of hyaline cartilage. Cells transfected with the BMP-2 gene media produced abundant bone, which was beginning to establish a marrow cavity. Tissue-engineered cartilage and bone from infrapatellar fat pads may prove to be useful for the treatment of osteochondral defects.
Effects of buffer pH on electroosmotic flow control by an applied radial voltage for capillary zone electrophoresis (1993)

Electroosmotic flow has been shown to be controlled via an applied radial voltage. Many factors determine the effectiveness of this control, and one major factor is buffer pH. In this study the effectiveness of the applied radial voltage for controlling electroosmotic flow while varying buffer pH is examined. Previously developed theory is applied and compared to experimental results for a pH range from 1.4 to 6.32. Analysis time is dramatically reduced by applying a radial voltage for separation of a peptide mixture at pH 1.4. Theory predicts laminar flow profiles under some conditions when applying this technique. However, experimental evidence at pH 6.32 and 1.4 shows no evidence of band broadening from a laminar flow profile. Theoretical and experimental results indicate the largest range of effective electroosmotic flow control via an applied radial voltage occurs at low ph. Furthermore, a sigmoidal relationship between electroosmotic flow and applied radial voltage is clearly apparent under these conditions. In contrast, at high buffer pH ( > 6) the relationship appears to be linear and is only over a limited range of flow velocities.
Chemical Characterization of a CommercialCommiphora wightiiResin Sample and Chemical Profiling to Assess for Authenticity (2011)

The gum resin of Commiphora wightii [(Hook. ex Stocks) Engl.] is an ayurvedic medicine for the treatment of arthritis, inflammation, obesity, lipid disorders, and cardiovascular diseases and is known as guggul. Morphologically, it is not easy to distinguish guggul from closely related gum resins of other plants. Reliability of the commercially available guggul is critical due to the high risk of adulteration. To check authenticity, a commercial guggul sample was investigated for its chemical markers and 17 metabolites were identified, including three new, 20(S),21-epoxy-3-oxocholest-4-ene (1), 8 β-hydroxy-3,20-dioxopregn-4,6-diene (2), and 5-(13' Z-nonadecenyl)resorcinol (17) from the ethyl acetate soluble part. During the current study, compounds 14- 17 were identified as constituents of Mangifera indica gum, as an adulterant in the commercial guggul sample. This discovery highlighted the common malpractices in the trade of medicinal raw material in the developing world. The structures of the compounds were deduced by the spectroscopic technique and chemical methods, as well as by comparison with the reported data. The structure of 20(S),21-epoxy-3-oxocholest-4-ene (1) was also unambiguously deduced by single-crystal X-ray diffraction technique.
Transgenic rice lines expressing maize C1 and R‐S regulatory genes produce various flavonoids in the endosperm (2006)

Flavonoids, compounds that possess diverse health-promoting benefits, are lacking in the endosperm of rice. Therefore, to develop transgenic lines that produce flavonoids, we transformed a white rice cultivar, Oryza sativa japonica cv. Hwa-Young, with maize C1 and R-S regulatory genes. Expression of these transgenes was restricted to the endosperm using the promoter of a rice prolamin gene. The pericarp of the C1/R-S homozygous lines became dark brown in accordance with their maternal genotype, whereas the endosperm turned chalky, similar to the opaque kernel phenotype. Analysis via high-performance liquid chromatography (HPLC) revealed that numerous kinds of flavonoids were produced in these transgenic kernels. To identify individual flavonoids, the number of HPLC peaks was reduced through moderate acid hydrolysis, followed by ethyl acetate partitioning. Amongst the major flavonoids, dihydroquercetin (taxifolin), dihydroisorhamnetin (3'-O-methyl taxifolin) and 3'-O-methyl quercetin were identified through liquid chromatography/mass spectrometry/mass spectrometry and nuclear magnetic resonance analyses. Fluorescence labelling with diphenylboric acid showed that the flavonoids were highly concentrated in the cells of four to five outer endosperm layers. More importantly, a high fluorescence signal was present in the cytosol of the inner endosperm layers. However, the overall signal in the inner layers was significantly lower because starch granules and protein bodies occupied most of the cytosolic space. Our estimate of the total flavonoid content in the transgenic kernels suggests that C1/R-S rice has the potential to be developed further as a novel variety that can produce various flavonoids in its endosperm.
β-Hairpin nucleation by Pro-Gly β-turns. Comparison of D-Pro-Gly and L-Pro-Gly sequences in an apolar octapeptide (1998)

The solution conformation of the synthetic octapeptide Boc-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe 1 and Boc-Leu-Val-Val-Pro-Gly-Leu-Val-Val-OMe 2 have been investigated in organic solvents by NMR spectroscopy. Peptide 1 adopts well-defined β-hairpin conformations in CDCl3, C6D6 and (CD3)2SO, nucleated by a D-Pro-Gly Type II′ β-turn, as demonstrated by the observation of characteristic nuclear Overhauser effects (NOEs) between backbone protons and solvent shielding of NH groups involved in cross-strand hydrogen bonding. Chemical shifts and coupling constants provide further support for the β-hairpin conformation, which is consistent with the observation of a single negative circular dichroism band at 216 nm in methanol. In peptide 2, there is no characteristic interstrand NOE observed in (CD3)2SO, while in CDCl3 pronounced aggregation results in line broadening. The observation of a low temperature coefficient for the Leu(6)NH proton favours a population of Pro-Gly Type II β-turn conformations. These results suggest that in short peptide sequences, the precise nature of the β-turn is critical for hairpin formation, with Type II′ β-turns being particularly effective.
Energy Systems for ATP Regeneration in Cell-Free Protein Synthesis Reactions (2007)

Supplying energy for cell-free protein synthesis reactions is one of the biggest challenges to the success of these systems. Oftentimes, short reaction duration is attributed to an unstable energy source. Traditional cell-free reactions use a compound with a high-energy phosphate bond, such as phosphoenolpyruvate, to generate the ATP required to drive transcription and translation. However, recent work has led to better understanding and activation of the complex metabolism that can occur during cell-free reactions. We are now able to generate ATP using energy sources that are less expensive and more stable. These energy sources generally involve multistep enzymatic reactions or recreate entire energy-generating pathways, such as glycolysis and oxidative phosphorylation. We describe the various types of energy sources used in cell-free reactions, give examples of the major classes, and demonstrate protocols for successful use of three recently developed energy systems: PANOxSP, cytomim, and glucose.
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes (2007)

Achieving efficient in vivo delivery of siRNA to the appropriate target cell would be a major advance in the use of RNAi in gene function studies and as a therapeutic modality. Hepatocytes, the key parenchymal cells of the liver, are a particularly attractive target cell type for siRNA delivery given their central role in several infectious and metabolic disorders. We have developed a vehicle for the delivery of siRNA to hepatocytes both in vitro and in vivo, which we have named siRNA Dynamic PolyConjugates. Key features of the Dynamic PolyConjugate technology include a membrane-active polymer, the ability to reversibly mask the activity of this polymer until it reaches the acidic environment of endosomes, and the ability to target this modified polymer and its siRNA cargo specifically to hepatocytes in vivo after simple, low-pressure i.v. injection. Using this delivery technology, we demonstrate effective knockdown of two endogenous genes in mouse liver: apolipoprotein B (apoB) and peroxisome proliferator-activated receptor alpha (ppara). Knockdown of apoB resulted in clear phenotypic changes that included a significant reduction in serum cholesterol and increased fat accumulation in the liver, consistent with the known functions of apoB. Knockdown of ppara also resulted in a phenotype consistent with its known function, although with less penetrance than observed in apoB knockdown mice. Analyses of serum liver enzyme and cytokine levels in treated mice indicated that the siRNA Dynamic PolyConjugate was nontoxic and well tolerated.
Adiponectin and the mediation of HDL-cholesterol change with improved lifestyle: the Look AHEAD Study (2012)

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI.
A Protein Kinase C Translocation Inhibitor as an Isozyme-selective Antagonist of Cardiac Function (1996)

Protein kinase C (PKC) isozymes translocate to unique subcellular sites following activation. We previously suggested that translocation of activated isozymes is required for their function and that in addition to binding to lipids, translocation involves binding of the activated isozymes to specific anchoring proteins (receptors for activated protein kinase C. Using cultured cardiomyocytes we identified inhibitors, the V1 fragment of epsilonPKC (epsilonV1), and an 8-amino acid peptide derived from it that selectively inhibited the translocation of epsilonPKC. Inhibition of epsilonPKC translocation but not inhibition of delta or betaPKC translocation specifically blocked phorbol ester- or norepinephrine-mediated regulation of contraction. These isozyme-selective translocation inhibitors provide novel tools to determine the function of individual PKC isozymes in intact cells.
H NMR Analysis of Chain Unsaturations in Ethene/1-Octene Copolymers Prepared with Metallocene Catalysts at High Temperature (2005)

In this paper, we report the full resonance assignments in the olefinic region of the 600 MHz 1H NMR spectra of a typical ethene/1-octene copolymer (4.0 mol % of octene units) produced with a metallocene catalyst at high temperature, and of an ethene homopolymer prepared under similar conditions for comparison. The assignments were based on a thorough analysis of 1D (1H, 1H{1H}, 13C) spectra and of 2D 1H−1H (COSY, TOCSY) and 1H−13C (HSQC, DEPT-HSQC) maps. Thirteen different olefinic structures were identified, and their formation explained in terms of plausible mechanistic paths associated with the high polymerization temperature. The fraction of internal chain unsaturations traceable to allylic activation turned out to be comparable to that of terminal ones in both samples. Despite its complexity, the said spectral region is now amenable to deconvolution and full simulation in terms of known and recognizable patterns, and usable for fast (possibly on-line) measurements of chain unsaturation degree, as well as for catalyst “fingerprinting” studies.