gebhart/patrepeval huggingface dataset:
Chiral gadolinium complexes as potential contrast agents (1998)

The long electronic relaxation time and the high paramagnetism of the gadolinium(III) ion makes it ideal for use as a contrast agent in Magnetic Resonance Imaging. As a result of its toxicity, gadolinium must be administered in the form of a kinetically inert complex. By coupling a gadolinium(III) chelate to a macromolecule, substantial gains in relaxivity (the efficacy of a contrast agent) may be obtained. To this end the synthesis of three types of ligand, substituted with amino- or carboxylate bearing groups, was undertaken. A derivative of 1,4,7,10-tetraazacyclododecane with three amino bearing chains substituted at carbon was synthesised as a single enantiomer. An effective route to acetate substituted derivatives of D03A was developed. The lanthanide complexes of these ligands do not exhibit the expected properties of a q = 2 complex, and therefore do not represent useful chelates for application in a slowly tumbling system. A study of the lanthanide(in) complexes of all four stereoisomers of tetra(carboxyethyl) DOTA derivatives has been performed. The rate of water exchange has been found to be dependent upon the proportion of a complex adopting a twisted square antiprism in solution. This is ascribed to the steric crowding of the water binding site in this isomer. 2-D EXSY NMR experiments show that the [Ln.(RRRR-)] and [Ln.(RKRS-)] isomers do not undergo rapid arm rotation at room temperature, showing that ring motion is decoupled from arm rotation. This rigidity increases the stability of these complexes with respect to metal ion dissociation. A selective synthesis of the [Ln.(RRRR-)] diastereoisomeric complex is described. Crystal structures of the [Eu.(RRRR-)], [Gd.(RRRR-)] and [Tb.(RRRR-)] complexes each reveal a monocapped square antiprismatic co-ordination geometry at the metal centre in which there is one bound water molecule.
Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir (2007)

The complete genome sequence of Geobacillus thermodenitrificans NG80-2, a thermophilic bacillus isolated from a deep oil reservoir in Northern China, consists of a 3,550,319-bp chromosome and a 57,693-bp plasmid. The genome reveals that NG80-2 is well equipped for adaptation into a wide variety of environmental niches, including oil reservoirs, by possessing genes for utilization of a broad range of energy sources, genes encoding various transporters for efficient nutrient uptake and detoxification, and genes for a flexible respiration system including an aerobic branch comprising five terminal oxidases and an anaerobic branch comprising a complete denitrification pathway for quick response to dissolved oxygen fluctuation. The identification of a nitrous oxide reductase gene has not been previously described in Gram-positive bacteria. The proteome further reveals the presence of a long-chain alkane degradation pathway; and the function of the key enzyme in the pathway, the long-chain alkane monooxygenase LadA, is confirmed by in vivo and in vitro experiments. The thermophilic soluble monomeric LadA is an ideal candidate for treatment of environmental oil pollutions and biosynthesis of complex molecules.
BLT-humanized C57BL/6 Rag2−/−γc−/−CD47−/− mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection (2013)

The use of C57BL/6 Rag2(-/-)γc(-/-) mice as recipients for xenotransplantation with human immune systems (humanization) has been problematic because C57BL/6 SIRPα does not recognize human CD47, and such recognition is required to suppress macrophage-mediated phagocytosis of transplanted human hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47 on the C57BL/6 Rag2(-/-)γc(-/-) background negates the requirement for CD47-signal recognition protein α (SIRPα) signaling and induces tolerance to transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO-BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high levels of multilineage hematopoiesis. Importantly, these mice have an intact complement system and showed no signs of graft-versus-host disease (GVHD) out to 29 weeks after transplantation. Sustained, high-level HIV-1 infection was observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice exhibited hallmarks of human HIV infection including CD4(+) T-cell depletion, immune activation, and development of HIV-specific B- and T-cell responses. The lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term studies of pathogenesis, immune responses, therapeutics, and vaccines to human pathogens.
Association of Activated Vitamin D Treatment and Mortality in Chronic Kidney Disease (2008)

Treatment with the activated vitamin D analogue calcitriol appears to be associated with significantly greater survival in patients with CKD not yet receiving dialysis. Randomized clinical trials are required to verify the causality of these associations and to examine whether similar associations are seen with different activated vitamin D analogues.
Cadmium-113 NMR studies of a 1:1 cadmium adduct with an 18-residue finger peptide from HIV-1 nucleic acid binding protein, p7 (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCadmium-113 NMR studies of a 1:1 cadmium adduct with an 18-residue finger peptide from HIV-1 nucleic acid binding protein, p7Terri L. South, Bo Kim, and Michael F. SummersCite this: J. Am. Chem. Soc. 1989, 111, 1, 395–396Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://pubs.acs.org/doi/10.1021/ja00183a074https://doi.org/10.1021/ja00183a074research-articleACS PublicationsRequest reuse permissionsArticle Views149Altmetric-Citations71LEARN 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
Phosphorylated Pak1 Level in the Cytoplasm Correlates with Shorter Survival Time in Patients with Glioblastoma (2007)

The presence of phosphorylated Pak1 in the cytoplasm of glioblastoma cells is associated with shorter survival, and Pak1 plays a role in the invasiveness of glioblastoma. These data suggest that Pak1 might be a potential target for the management of glioblastoma.
Increased expression of prostate‐specific G‐protein‐coupled receptor in human prostate intraepithelial neoplasia and prostate cancers (2004)

The G-protein-coupled receptors and signal transduction pathways represent important specific targets for a variety of human diseases, ranging from the control of blood pressure, allergic response, hormonal disorders and neurologic diseases to tumorigenesis. Most recently, we and others have identified a novel human prostate-specific G-protein coupled receptor (PSGR). To investigate the potential roles of PSGR in human normal prostate and prostate cancers, we examined the expression level of PSGR in 146 human prostate samples with real-time quantitative reverse transcription-PCR and in situ hybridization method. We significantly extended previous studies and demonstrated that PSGR is specifically expressed in human prostate tissues, not in any other normal and tumor samples tested. Compared to normal and benign prostatic hyperplasia tissues, the expression of PSGR increased significantly in human prostate intraepithelial neoplasia (PIN) and prostate tumors (approximately 10-fold), especially in early prostate tumors, suggesting PSGR may play an important role in early prostate cancer development and progression. The sensitivity and specificity estimates for PSGR expression were calculated as the area under the receiver-operating characteristics curve (0.902), indicating high-level sensitivity and specificity for discriminating benign prostate tissues from malignant prostate tissues. The association of PSGR expression with clinical parameters (clinical stages, Gleason scores, recurrent status and metastasis) was also investigated in this study. Our data suggest that overexpression of PSGR in human PIN and prostate cancers have the potential for early prostate cancer detection and diagnosis.
Indirect Health Effects of Relative Humidity in Indoor Environments (1986)

Anthony V. Arundel, Elia M. Sterling, Judith H. Biggin, Theodor D. Sterling, Indirect Health Effects of Relative Humidity in Indoor Environments, Environmental Health Perspectives, Vol. 65 (Mar., 1986), pp. 351-361
Targeted delivery of albumin bound paclitaxel in the treatment of advanced breast cancer (2009)

Taxanes are chemotherapeutic agents with a large spectrum of antitumor activity when used as monotherapy or in combination regimens. Paclitaxel and docetaxel have poor solubility and require a complex solvent system for their commercial formulation, Cremophor EL(R) (CrEL) and Tween 80(R) respectively. Both these biological surfactants have recently been implicated as contributing not only to the hypersensitivity reactions, but also to the degree of peripheral neurotoxicity and myelosuppression, and may antagonize the cytotoxicity. Nab-paclitaxel, or nanoparticle albumin-bound paclitaxel (ABI-007; Abraxane(R)), is a novel formulation of paclitaxel that does not employ the CrEL solvent system. Nab-paclitaxel demonstrates greater efficacy and a favorable safety profile compared with standard paclitaxel in patients with advanced disease (breast cancer, non-small cell lung cancer, melanoma, ovarian cancer). Clinical studies in breast cancer have shown that nab-paclitaxel is significantly more effective than standard paclitaxel in terms of overall objective response rate (ORR) and time to progression. Nab-paclitaxel in combination with gemcitabine, capecitabine or bevacizumab has been shown to be very active in patients with advanced breast cancer. An economic analysis showed that nab-paclitaxel would be an economically reasonable alternative to docetaxel or standard paclitaxel in metastatic breast cancer. Favorable tumor ORR and manageable toxicities have been reported for nab-paclitaxel as monotherapy or in combination treatment in advanced breast cancer.
Posttranslational N-Myristoylation Is Required for the Anti-apoptotic Activity of Human tGelsolin, the C-terminal Caspase Cleavage Product of Human Gelsolin (2006)

Protein N-myristoylation has been recognized as a cotranslational protein modification. Recently, it was demonstrated that protein N-myristoylation could occur posttranslationally, as in the case of the pro-apoptotic protein BID and cytoskeletal actin. Our previous study showed that the N-terminal nine residues of the C-terminal caspase cleavage product of human gelsolin, an actin-regulatory protein, efficiently direct the protein N-myristoylation. In this study, to analyze the posttranslational N-myristoylation of gelsolin during apoptosis, metabolic labeling of gelsolin and its caspase cleavage products expressed in COS-1 cells with [3H]myristic acid was performed. It was found that the C-terminal caspase cleavage product of human gelsolin (tGelsolin) was efficiently N-myristoylated. When COS-1 cells transiently transfected with gelsolin cDNA were treated with etoposide or staurosporine, apoptosis-inducing agents, N-myristoylated tGelsolin was generated, as demonstrated by in vivo metabolic labeling. The generation of posttranslationally N-myristoylated tGelsolin during apoptosis was also observed on endogenous gelsolin expressed in HeLa cells. Immunofluorescence staining and subcellular fractionation experiment revealed that exogenously expressed tGelsolin did not localize to mitochondria but rather was diffusely distributed in the cytoplasm. To study the role of this modification in the anti-apoptotic activity of tGelsolin, we constructed the bicistronic expression plasmid tGelsolin-IRES-EGFP capable of overexpressing tGelsolin concomitantly with EGFP. Overexpression of N-myristoylated tGelsolin in COS-1 cells using this plasmid significantly inhibited etoposide-induced apoptosis, whereas overexpression of the non-myristoylated tGelsolinG2A mutant did not cause resistance to apoptosis. These results indicate that posttranslational N-myristoylation of tGelsolin does not direct mitochondrial targeting, but this modification is involved in the anti-apoptotic activity of tGelsolin.
Modified-Release Solid Formulations for Colonic Delivery (2007)

Solid formulations intended for targeted drug release into the lower gastrointestinal (GI) tract are beneficial for the localized treatment of several diseases and conditions, mainly inflammatory bowel diseases, irritable bowel syndrome and colon cancer. Also, because of their inherent potential to delay or avoid systemic drug absorption from the small intestine, colonic formulations can be utilized for chronotherapy of diseases which are affected by circadian biorhythms (e.g., asthma, hypertension and arthritis), and to achieve clinically relevant bioavailability of drugs that are poorly absorbed from the upper parts of the GI tract because of their polar nature and/or susceptibility to chemical and enzymatic degradation in the small intestine (e.g., proteins and peptides). The purpose of this review is to summarize the recent patent literature concerning various modified-release (MR) formulation technologies that are claimed to provide colonic delivery for a wide array of therapeutic molecules. These technologies either utilize a single or a combination of two or more physiological characteristics of the colon, which includes pH, microflora (enterobacteria), transit time, and luminal pressure. Accordingly, these technologies may be grouped under four distinct classes: pH-controlled (or delayed-release) system, time-controlled (or time-dependent) system, microbially-controlled system, and pressure-controlled system. Among these, formulations that release drugs in response to colonic pH, enterobacteria, or both are most common and promising.
Triple Helix-Specific Ligands (1992)

A triple helix is formed upon binding of an oligodeoxynucleotide to the major groove of duplex DNA. A benzo[e]pyridoindole derivative (BePI) strongly stabilized this structure and showed preferential binding to a triplex rather than to a duplex. Energy transfer experiments suggest that BePI intercalates within the triple helix. Sequence-specific inhibition of transcription initiation of a specific gene by Escherichia coli RNA polymerase by a triplex-forming oligodeoxynucleotide is strongly enhanced when the triplex is stabilized by BePI. Upon irradiation with ultraviolet light, BePI induces covalent modifications of the target within the triple helix structure.
A human anti-insulin IgG autoantibody apparently arises through clonal selection from an insulin-specific "germ-line" natural antibody template. Analysis by V gene segment reassortment and site-directed mutagenesis. (1995)

We analyzed the structural correlates underlying the insulin-dependent selection of the specific anti-insulin IgG1 kappa mAb13-producing cell clone, derived from a patient with insulin-dependent diabetes mellitus treated with recombinant human insulin. First, we cloned the germ-line genes that putatively gave rise to the expressed VH and V kappa segments and used them to generate the full (unmutated) "germ-line revertant" of the "wild-type" (somatically mutated) mAb13, using recombinant PCR methods and an in vitro human C gamma 1 and C kappa expression system. The full "germ-line revertant" bound insulin specifically and in a dose-saturable fashion, but with a relative avidity (AVrel) more than three-fold lower than that of its wild-type counterpart (Avrel, 1.69 x 10(-8) vs 4.91 x 10(-9) g/microliters). Second, we established, by reassorting wild-type and germ-line revertant forms of the mAb13 VH and V kappa segments, that the increased Avrel for insulin of mAb13 when compared with its full "germ-line revertant" counterpart was entirely dependent on the mutations in the VH not those in the V kappa chain. Third, we determined, by site-directed mutagenesis experiments, that of the three mutations in the mAb13 VH segment (Ser-->Gly, Ser-->Thr, and Ser-->Arg at positions 31, 56, and 58, respectively), only Arg58 was crucial in increasing the mAb13 Avrel (from 1.44 x 10(-8) to 5.14 x 10(-9) g/microliters) and affinity (Kd, from 189 to 59 nM) for insulin. The affinity enhancement mediated by the VH segment Arg58 residue reflected about a threefold decrease in dissociation rate constant (Koff, from 4.92 x 10(-3) to 1.54 x 10(-3) s-1) but not an increase in association rate constant (Kon, from 2.60 x 10(4) to 2.61 x 10(4) M-1 s-1), and it contrasted with the complete loss of insulin binding resulting from the substitution of the VH segment Asn52 by Lys. The present findings suggest that human insulin, a self Ag, has the potential to recruit a natural autoantibody-producing cell precursor expressing a specific surface receptor for Ag in unmutated configuration, and drive it through affinity maturation. They also show that binding of insulin by such a receptor can be enhanced or completely abrogated by a single amino acid change.
Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance (2017)

Increased plasma AA concentrations were observed mainly in subjects with obesity and NAFLD, likely as a consequence of increased IR and protein catabolism. The GSG-index is a possible marker of severity of liver disease independent of body mass index. (Hepatology 2018;67:145-158).
STRUCTURE, FUNCTION, AND EVOLUTION OF MICROBIAL PHYTOCHROMES (2006)

Light is the dominant environmental signal for almost all cellular organisms, providing both the energy (either direct or indirect) necessary for growth and metabolism and the sensory information helpful for adaptation. Like plants, microorganisms are profoundly influenced by their surrounding light environment (Hader, 1987; Armitage, 1997; Loros and Dunlap, 2001; Braatsch and Klug, 2004). For photosynthetic species, various photosensory systems provide positional information to optimise light capture and to help minimize damage inflicted by excess solar radiation. In the short term, these sensory systems help these microbes move/grow toward more favourable light fluences. In the long term, they help the organism adjust to the spectral quality of the light (sun versus shade) by modulating the complement of photosynthetic accessory pigments, and/or entrain their growth and development to the diurnal and possibly seasonal cycles. For non-photosynthetic microorganisms, light is also an important environmental cue. Here, light directs preference/avoidance and adaptive strategies similar to those used by photosynthetic species, which in turn enhances their survival or assists them in locating more favourable ecological niches. Whereas the architectures of the microbial photoreceptor systems used for energy capture are known in exquisite detail, we have begun to appreciate only recently the repertoire of photoreceptors employed for sensory information. Much of this new understanding has emerged from the exponentially expanding number of completely sequenced genomes that can now be easily searched for signature photoreceptor motifs by the BLAST algorithm. Recent examples include the discovery of retinal-based bacteriorhodopsin, p-hydroxycinnamic acid-based xantopsin, and flavin-based LOV-type and cryptochrome-type photoreceptors in a variety of bacterial, fungal and animal species (van der Horst and Hellingwerf, 2004; Venter et al., 2004; see Chapters 11, 13). Phytochromes (Phys) are one of the best examples where genome analyses have greatly enhanced our understanding of light perception in the microbial world. This class of photoreceptors is defined by the use of a bilin (or linear tetrapyrrole) chromophore (Smith, 2000; Quail, 2002). Once bound to the apoprotein, the bilin
Secretion of Active Recombinant Human Tissue Plasminogen Activator Derivatives in Escherichia coli (2001)

The DNA fragment coding for kringle 2 plus serine protease domains (K2S) of tissue plasminogen activator (tPA) was inserted into a phagemid vector, pComb3HSS. In the recombinant vector, pComb3H-K2S, the K2S gene was fused to gpIII of PhiM13 and linked to the OmpA signal sequence. The resulting gene, rK2S-gpIII, was inducibly expressed in Escherichia coli XL-1 Blue. The protein was presented on the phage particle. To stop the expression of gpIII, a stop codon between K2S and the gpIII gene was inserted by site-directed mutagenesis. This mutated vector, MpComb3H-K2S, was transformed in XL-1 Blue. After induction with IPTG (isopropyl-beta-D-thiogalactopyranoside), rK2S was found both in the periplasm as an inactive form of approximately 32% and in the culture supernatant as an active form of approximately 68%. The secreted form of rK2S was partially purified by ammonium sulfate (55%) precipitation. The periplasmic form was isolated from whole cells by chloroform extraction. The fibrin binding site of kringle 2 was demonstrated in all expressed versions (phage-bound, periplasmic, and secreted forms) using the monoclonal anti-kringle 2 antibody (16/B). Only the secreted form of rK2S revealed a fibrinogen-dependent amidolytic activity with the specific activity of 236 IU/microg. No amidolytic activity of rK2S was observed in either the periplasmic or the phage-bound form. The secretion of rK2S as an active enzyme offers a novel approach for the production of the active-domain deletion mutant tPA, rK2S, without any requirements for bacterial compartment preparation and in vitro refolding processes. This finding is an important technological advance in the development of large-scale, bacterium-based tPA production systems.
Detection of Listeria species and Listeria monocytogenes using polymerase chain reaction (1990)

Five oligonucleotide sequences are described that were used as primers in the polymerase chain reaction (PCR) to amplify specific sequences from Listeria DNA. When all five primers were used in combination, three PCR products were possible; a Listeria specific product that occurs with DNA from any Listeria sp., a Listeria monocytogenes specific product that occurs only in the presence of DNA from this organism and a universal product that is found using DNA from any bacterial source. The occurrence of these PCR products was used as a diagnostic test on bacteria isolated from various food samples to detect Listeria sp. and L. monocytogenes.
Pulsatile Myocardial Tubes Fabricated With Cell Sheet Engineering (2006)

Functional myocardial tubes that have the potential for circulatory support can be created with cell sheet engineering. These results also suggest that pulsation due to host blood flow within the lumen of the myocardial tubes has a profound effect on stimulating cardiomyocyte hypertrophy and growth. These results demonstrate a novel approach for the future development of engineered cardiac tissues with the ability for independent cardiac assistance.