gebhart/patrepeval huggingface dataset:
X-ray structure of human relaxin at 1.5 A. Comparison to insulin and implications for receptor binding determinants. (1991)

The X-ray crystal structure of relaxin at 1.5 A resolution is reported for the physiologically active form of the human hormone. Relaxin is a small, two-chain polypeptide that is a member of the protein hormone family that also includes insulin and the insulin-like growth factors IGF-I and IGF-II. These hormones have biologically diverse activities but are structurally similar, sharing a distinctive pattern of cysteine and glycine residues. The predicted structural homology of relaxin to insulin is confirmed by this structural analysis; however, there are significant differences in the terminal regions of the b-chain. Although relaxin, like insulin, crystallizes as a dimer, the orientation of the molecules in the respective dimers is completely different. The region of the relaxin molecule proposed to be involved in receptor binding is part of the dimer interface, suggesting that some of the other residues contained in the dimer contact surface might be receptor binding determinants as well. The proposed receptor binding determinants for insulin likewise include residues at its dimer interface. However, because the dimer contacts of relaxin and insulin are quite different, it appears that these two structurally related hormones have evolved somewhat dissimilar mechanisms for receptor binding.
Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children (2016)

A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1-11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2 % of bleeding episodes were successfully treated with one or two injections of rIX-FP (95 % CI: 92 % to 99 %), 88.7 % with one injection, and 96 % of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531).
In vitro toxicology and pharmacokinetics of antisense oligonucleotides. (1991)

The ability to rationally design antisense drugs and the theoretical selectivity of these compounds for specific genomic and viral mRNA targets make their use as therapeutic agents extremely attractive. Pharmacologic data emerging from our and other laboratories indicate that some unmodified and backbone modified oligonucleotides may be cytotoxic. In general, cytotoxicity was usually seen at concentrations higher than those required for specific antisense effects. Factors that may modulate the toxicity of phosphorothioates include cell type, various media components including serum, length and method of preparation. Pharmacokinetic experiments using phosphodiester, phosphorothioate and methylphosphonate oligonucleotides suggest that these compounds may be taken up and distributed within some cells. Uptake was generally time, temperature, concentration dependent, and required cellular energy. The mechanism of uptake varied according to oligonucleotide type. The in vitro data as well as preliminary in vivo studies demonstrating the safety, antiviral activity and bioavailability of a number of oligonucleotides suggest that these compounds represent a novel therapeutic modality.
External Quantum Efficiency Above 100% in a Singlet-Exciton-Fission–Based Organic Photovoltaic Cell (2013)

Singlet exciton fission transforms a molecular singlet excited state into two triplet states, each with half the energy of the original singlet. In solar cells, it could potentially double the photocurrent from high-energy photons. We demonstrate organic solar cells that exploit singlet exciton fission in pentacene to generate more than one electron per incident photon in a portion of the visible spectrum. Using a fullerene acceptor, a poly(3-hexylthiophene) exciton confinement layer, and a conventional optical trapping scheme, we show a peak external quantum efficiency of (109 ± 1)% at wavelength λ = 670 nanometers for a 15-nanometer-thick pentacene film. The corresponding internal quantum efficiency is (160 ± 10)%. Analysis of the magnetic field effect on photocurrent suggests that the triplet yield approaches 200% for pentacene films thicker than 5 nanometers.
Abstract 5320: Deletion of TGFß signaling in Gr-1+CD11b+ myeloid cells attenuates breast adenocarcinoma progression (2010)

Abstract TGFß is a very important mediator in tumor progression. However, the contribution of TGFß signaling in tumor-infiltrating inflammatory cells in this process is unclear. Gr-1+CD11b+ myeloid cells are overproduced in tumor host. They infiltrate into tumor tissues and contribute to immune suppression, tumor angiogenesis and metastasis. Data from our studies demonstrate that Gr-1+CD11b+ myeloid cells are recruited into the invasive front of breast adenocarcinomas. Tumor-infiltrating Gr-1+CD11b+ cells exhibit a significantly elevated TGFß signaling, including increased expression of TGFß type I and type II receptor, TGFß1 and TGFß3 ligands, as well as latent TGFß binding protein. They also produce a high level of multiple matrix metalloproteinases (MMPs) such as MMP13, MMP14, MMP2 and MMP9. Interestingly, genetic deletion of the gene encoding TGFß type II receptor (Tgfbr2) in Gr-1+CD11b+ cells significantly attenuates the production of MMP14 and MMP2. These in vitro studies were conducted by transduction of Gr-1+CD11b+ cells from Tgfbr2flox/flox mice (loxP-flanked Tgfbr2) with adenovirus expressing DNA recombinase. To further investigate if TGFß signaling plays an important role in Gr-1+CD11b+ myeloid cells mediated breast tumor progression, mice with conditional knockout of Tgfbr2 in Gr-1+CD11b+ cells are generated through cross breeding of Tgfbr2flox/flox mice with LysM-Cre mice expressing Cre in myeloid cells. These mutant mice are viable and appear to be normal. Southern blotting showed that Tgfbr2 deletion is restricted to bone marrow, spleen and lymph node but not other organs. Sorted Gr-1+CD11b+ myeloid cells but not T or B lymphoid cells exhibited over 85% of Tgfbr2 deletion. This specific TGF-ß inactivation in Gr-1+CD11b+ cells allows us to investigate its effect on tumor growth and angiogenesis, as well as metastasis. We observed a significantly attenuated 4T1 tumor growth in these knockout mice compared with the control littermates. We postulate that TGFß signaling in host derived Gr-1+CD11b+ cells is an important part of TGFß effect in tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5320.
Cloning vectors for the expression of green fluorescent protein fusion proteins in transgenic plants (1998)

A series of versatile cloning vectors has been constructed that facilitate the expression of protein fusions to the Aequorea victoria green fluorescent protein (GFP) in plant cells. Amino-terminal- and carboxy-terminal protein fusions have been created and visualized by epifluorescence microscopy, both in transgenic Arabidopsis thaliana and after transient expression in onion epidermal cells. Using tandem dimers and other protein fusions to GFP, we found that the previously described localization of wild-type GFP to the cell nucleus is most likely due to diffusion of GFP across the nuclear envelope rather than to a cryptic nuclear localization signal. A fluorescence-based, quantitative assay for nuclear localization signals is described. In addition, we have employed the previously characterized mutants GFP-S65T and GFP-Y66H in order to allow for the expression of red-shifted and blue fluorescent proteins, respectively, which are suitable for double-labeling studies. Expression of GFP-fusions was controlled by a cauliflower mosaic virus 35S promoter. Using the Arabidopsis COP1 protein as a model, we confirmed a close similarity in the subcellular localization of native COP1 and the GFP-tagged COP1 protein. We demonstrated that COP1 was localized to discrete subnuclear particles and further confirmed that fusion to GFP did not compromise the activity of the wild-type COP1 protein.
Syntheses of 4‘-C-Ethynyl-β-d-arabino- and 4‘-C-Ethynyl-2‘-deoxy-β-d-ribo-pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity (2000)

4'-C-Ethynyl-beta-D-arabino- and 4'-C-ethynyl-2'-deoxy-beta-D-ribo-pentofuranosylpyrimidine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabinopyrimidine derivatives were prepared from the corresponding ribo derivatives via O(2),2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC(50) values ranging from 0.0003 to 0. 03 microM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC(50) values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2, 6-diamino-2'-deoxypurine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2'-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.
Polarization mechanism for bremsstrahlung and radiative recombination in a plasma with heavy ions (2002)

The role of the polarization mechanism in bremsstrahlung and radiative recombination in a plasma with heavy ions is investigated. A study is made of a hot plasma with the electron temperature T e=0.5 keV, containing Fe, Mo, W, and U ions, a relatively cold plasma with a temperature of 0.1–10 eV, and a storage-ring plasma with relatively low-energy electrons. The spectral characteristics, as well as the total cross sections and rate constants for electron-ion recombination, are calculated with allowance for real ionization equilibrium in a plasma. The calculations are carried out using the quasiclassical approximation for electron scattering and the statistical model for the ions, which provides a universal description of the spectra of various chemical elements over a wide temperature range. It is shown that the polarization mechanism contributes to both the effective radiation intensity and the total radiative recombination rate. The temperature range is found where the polarization recombination of electrons in collisions with FeIII ions plays an important role, which indicates the collective behavior of the electron core of an iron ion in this temperature range. Taking into account polarization effects increases the calculated total continuum intensity. As a consequence, the effective plasma charge Z eff determined from this intensity without allowance for polarization effects turns out to be overestimated.
Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. (2002)

A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement.
Removal Of Pesticides By Use Of Ozone Or Hydrogen Peroxide/Ozone (1995)

Abstract This article deals with the efficiency of an ozonation step in drinking water treatment plants remove pesticides. These tests are carried out with a laboratory technique, the "OZOTEST" method, which simulates operating conditions on site and allows a complete oxidation assessment. Efficiency of the two oxidant systems – ozone and ozone coupled with hydrogen peroxide – is evaluated for 11 pesticides commonly analyzed in control laboratories. Comparison of the two systems is made in terms of pesticide removal, but also in terms of ozone consumption. Matrix effects and contact time are also taken into account, and an order of reactivity for each system considered is suggested. Key Words: OzoneHydrogen PeroxideAdvanced Oxidation"OZOTEST" MethodPesticidesOzone Contact TimeCarbonatesAtrazineTerbutrynIsoproturonMalathionHCBAldrinAldicarbα-EndosulfanLindaneM-ParathionLinuron
Fabrication and nanostructure of oriented FePt particles (2000)

Thin films of oriented tetragonal FePt particles separated by amorphous alumina have been fabricated by electron beam evaporation. The ordering of the FePt particles without coarsening can be tailored by annealing conditions. The value of coercivity of the annealed film reached as high as 4.4 kOe. The perpendicular magnetic coercivity of the annealed film was slightly larger than in-plane coercivity. Some of the tetragonal FePt particles were found to have {111} twins and stacking faults. From our high-resolution electron microscopy observations, it was determined that central region of the ordered FePt particles tended to have c-axis perpendicular to the film plane.
Does Fibrin Glue Cause Foreign Body Reactions? (1992)

The study was performed in 20 Wistar rats. Approximately 4 mm perforations were created in the left colon of ten rats to which fibrin glue was applied (Group D). The control group had the same injury without any therapeutic or surgical measures (Group K). Of the 20 rats in both groups none died during the postoperative period. All animals sacrificed on the 11th postoperative day. All ten rats of Group D displayed inflammatory foreign body reactions. The control group showed no such reaction.
Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (γ‐hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies inAldh5a1−/−mice and characterization of γ‐hydroxybutyric acid pharmacology (2007)

We overview the pathophysiological bases, clinical approaches and potential therapeutic options for succinate semialdehyde dehydrogenase (SSADH; EC1.2.1.24) deficiency (gamma-hydroxybutyric aciduria, OMIM 271980, 610045) in relation to studies on SSADH gene-deleted mice, outcome data developed from 25 years of patient evaluation, and characterization of gamma-hydroxybutyric acid (GHB) pharmacology in different species. The clinical picture of this disorder encompasses a wide spectrum of neurological and psychiatric dysfunction, such as psychomotor retardation, delayed speech development, epileptic seizures and behavioural disturbances, emphasizing the multifactorial pathophysiology of SSADH deficiency. The murine SSADH-/- (e.g. Aldh5a1-/-) mouse model suffers from epileptic seizures and succumbs to early lethality. Aldh5a1-/- mice accumulate GHB and gamma-aminobutyric acid (GABA) in the central nervous system, exhibit alterations of amino acids such as glutamine (Gln), alanine (Ala) and arginine (Arg), and manifest disturbances in other systems including dopamine, neurosteroids and antioxidant status. Therapeutic concepts in patients with SSADH deficiency and preclinical therapeutic experiments are discussed in light of data collected from research in Aldh5a1-/- mice and animal studies of GHB pharmacology; these studies are the foundation for novel working approaches, including pharmacological and dietary trials, which are presented for future evaluation in this disease.
Induction of anti‐carbohydrate antibodies by phage library‐selected peptide mimics (1997)

One of the prerequisites for the development of polysaccharide subunit vaccines is the induction of an efficient immune response to carbohydrate antigens like lipopolysaccharide (LPS) or capsular polysaccharide antigens of pathogens. In an attempt to overcome the problems that arise from the T-independent immune response induced by such antigens, selecting peptide sequences that mimic protective carbohydrate epitopes has been proposed. In this study, we investigate a new selection strategy for immunogenic peptide mimics using the phage-displayed peptide library technology. Two monoclonal antibodies (mAb) of the A isotype (mIgA), mIgA C5 and mIgA I3, specific for the O-antigen (O-Ag) part of the human pathogen Shigella flexneri serotype 5a LPS and protective against homologous infection were used to screen two phage-displayed nonapeptide libraries in pVIII. Using mIgA C5, 13 different specific clones were selected, and 6 using mIgA I3; 5 of the latter also interacted in enzyme-linked immunosorbent assay with the first mAb. All of the 19 clones selected were separately used to immunize mice, but only 2 of them, p100c (mIgA I3-specific) and p115 (interacting with both mIgA) were able to induce anti-O-Ag antibodies. The immune response was specific for the O-Ag of the S. flexneri serotype 5a, and also selectively recognized the corresponding bacterial strain. The amino acid sequences of p100c and p115 immunogenic peptide mimics were YKPLGALTH (flanked by two Cys residues) and KVPPWARTA, respectively. These results are the first example of immunogenic mimicry of carbohydrates by phage-displayed peptides, and indicate a new strategy of selection of immunogens for the development of anti-polysaccharide vaccines.
Genome-Wide Analyses of Escherichia coli Gene Expression Responsive to the BaeSR Two-Component Regulatory System (2005)

The BaeSR two-component regulatory system controls expression of exporter genes conferring drug resistance in Escherichia coli (S. Nagakubo, K. Nishino, T. Hirata, and A. Yamaguchi, J. Bacteriol. 184:4161-4167, 2002; N. Baranova and H. Nikaido, J. Bacteriol. 184:4168-4176, 2002). To understand the whole picture of BaeSR regulation, a DNA microarray analysis of the effect of BaeR overproduction was performed. BaeR overproduction activated 59 genes related to two-component signal transduction, chemotactic responses, flagellar biosynthesis, maltose transport, and multidrug transport, and BaeR overproduction also repressed the expression of the ibpA and ibpB genes. All of the changes in the expression levels were also observed by quantitative real-time reverse transcription-PCR analysis. The expression levels of 15 of the 59 BaeR-activated genes were decreased by deletion of baeSR. Of 11 genes induced by indole (a putative inducer of the BaeSR system), 10 required the BaeSR system for induction. Combination of the expression data sets revealed a BaeR-binding site sequence motif, 5'-TTTTTCTCCATDATTGGC-3' (where D is G, A, or T). Several genes up-regulated by BaeR overproduction, including genes for maltose transport, chemotactic responses, and flagellar biosynthesis, required an intact PhoBR or CreBC two-component regulatory system for up-regulation. These data indicate that there is cross-regulation among the BaeSR, PhoBR, and CreBC two-component regulatory systems. Such a global analysis should reveal the regulatory network of the BaeSR system.
Leakage of fluid around low‐pressure tracheal tube cuffs (1997)

The aim of the study was to evaluate leakage of liquid past the low-pressure cuffs of tracheal tubes. Ten samples of each of nine different types of tubes were tested in a PVC mock trachea, using intracuff pressures of 20, 30, 40 and 50 cmH2O. In five types of tubes, 6-10 cuffs allowed profuse leakage (> 20 ml water in 5 min) even at the highest intracuff pressure, i.e. 50 cmH2O. In the most efficient tube, all the cuffs were leak-proof (leakage < 5 ml in 5 min) at 40 cmH2O and in the second best type the cuffs were leak-proof at 50 cmH2O. The leakage of fluid past the tracheal tube remains an unresolved problem with low-pressure cuffs.