gebhart/patrepeval huggingface dataset:
Reversible-Deactivation Radical Polymerization in the Presence of Metallic Copper. Kinetic Simulation (2013)

Reversible-deactivation radical polymerization (RDRP) of methyl acrylate in DMSO in the presence of Cu0 was studied by kinetic simulations. Kinetic simulations give access to the rates and contributions of all reactions, including those of activation of alkyl halides by CuI and Cu0 species, disproportionation of CuI species, and comproportionation between CuII and Cu0. Every relevant reaction was quantified by experimentally measured rate coefficients. The rates and contributions allow the exact roles of Cu0 and CuI species to be evaluated. These simulations show that the control over the polymerization is due to the atom transfer radical polymerization (ATRP) dynamic equilibrium with CuI as the major activator and CuII as the major deactivator. The ATRP equilibrium is maintained throughout the entire process. The simulations confirmed earlier experimental findings that in dimethyl sulfoxide (DMSO) with tris[2-(dimethylamino)ethyl]amine (Me6TREN) ligand comproportionation between Cu0 and CuII species dominates disproportionation of CuI species, with both reactions being relatively slow. The contribution of Cu0 activation of alkyl halides to the overall reaction is very small, and plays only a supplemental role, since alkyl halides are predominantly activated by CuI species. The effect of Cu0 activity on polymerization rate and livingness were also studied by a series of simulations. In all cases, the rate of supplemental activation by Cu0 was similar to the rate of radical termination, with both being relatively low in order to preserve the livingness of the chains. Cu0 not only acts as a supplemental activator (SA), but also as a reducing agent (RA) and it is able to regenerate CuI from CuII, through comproportionation. Simulations based on experimentally measured rate coefficients showed that Cu0 acts as a supplemental activator and reducing agent (SARA) and the results of an RDRP in the presence of Cu0 are consistent with the SARA ATRP mechanism, and in direct conflict with the single electron transfer-living radical polymerization (SET-LRP) mechanism. The kinetic analysis also revealed that the contribution of disproportionation of CuI to the polymerization kinetics is negligible, and that the CuI species are predominantly involved in activation reactions. The effect of the surface area of Cu0, the effect of initially added CuII species, and other reaction parameters are discussed in light of SARA ATRP.
Human interferon-gamma has three domains associated with its antiviral function: a neutralizing epitope typing scheme for human interferon-gamma. (1993)

An antiviral activity-neutralizing monoclonal antibody (mAb), MIF3037, was developed by the immunization of BALB/c mice with recombinant human interferon-gamma (rhuIFN-gamma). Its neutralizing activity suggests that its epitope may be at or adjacent to a functional domain on the huIFN-gamma. MIF3037 was compared with representative mAb of previously identified epitope-specific groups in a competitive binding assay. In an attempt to determine if there are other functional epitopes recognized by mAb developed with different preparations of huIFN-gamma or different hybridoma screening methods, 14 additional mAb contributed by five other laboratories were similarly analysed. Based on their ability to bind to huIFN-gamma, all the neutralizing mAb except MIF3037 may be classified into three previously defined groups: E1, E2 and E1/E2. Monoclonal antibodies of the E1 group do not compete with those of the E2 group for huIFN-gamma binding, indicating that the E1 and E2 epitopes are distinct domains on the huIFN-gamma important for the antiviral function. Monoclonal antibodies of the E1/E2 group compete with some of the mAb of E1 and/or E2 groups and may bind to regions of the huIFN-gamma that partially overlap the E1 and E2 epitopes. MIF3037 demonstrated no competitive binding inhibition with mAb of the previously identified epitope specificity groups and, therefore, must represent a distinct functional epitope, E3. The huIFN-gamma, therefore, must have at least three distinct functional domains; none of these appeared to be responsible for cell surface receptor binding. Based on this finding, the epitope typing scheme must be extended to include the E3 epitope. The epitope specificity relationships of 13 neutralizing mAb developed by five other laboratories were established which allows correlation of results obtained with these mAb by different laboratories. The location of the epitopes of four widely studied mAb, 69B, 73A, 113B and 220A12, have been deduced based on their competition with the E1 mAb which have recently been mapped.
Control of the Selectivity of the Aquaporin Water Channel Family by Global Orientational Tuning (2002)

Aquaporins are transmembrane channels found in cell membranes of all life forms. We examine their apparently paradoxical property, facilitation of efficient permeation of water while excluding protons, which is of critical importance to preserving the electrochemical potential across the cell membrane. We have determined the structure of the Escherichia coli aquaglyceroporin GlpF with bound water, in native (2.7 angstroms) and in W48F/F200T mutant (2.1 angstroms) forms, and carried out 12-nanosecond molecular dynamics simulations that define the spatial and temporal probability distribution and orientation of a single file of seven to nine water molecules inside the channel. Two conserved asparagines force a central water molecule to serve strictly as a hydrogen bond donor to its neighboring water molecules. Assisted by the electrostatic potential generated by two half-membrane spanning loops, this dictates opposite orientations of water molecules in the two halves of the channel, and thus prevents the formation of a "proton wire," while permitting rapid water diffusion. Both simulations and observations revealed a more regular distribution of channel water and an increased water permeability for the W48F/F200T mutant.
The millimeter wave gunn oscillator and self-oscillating mixer using the nonradiative dielectric waveguide (2005)

A new and promising millimeter wave active device is presented in this paper. n kc- nonradlative dielectric waveguide (NRD-guide) Gunn oscillator and seir-oscillating mixer have many advantages, such as simple structure, easy to fabricate and adjust, low-cost and light- weight. The operative properties of NRD-guide Gunn oscillator and self-oscillating mixer at 35 (Nz are investigated.
Oral Administration of Lactoferrin Inhibits Inflammation and Nociception in Rat Adjuvant-Induced Arthritis (2004)

Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced micro-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inflammatory effects, and also whether it modulates LPS-induced TNF-alpha and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injected paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-alpha production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the development of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-alpha and up-regulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.
Composition and search with a video algebra (1995)

A new data model called algebraic video provides operations for composing, searching, navigating,and playing back digital video presentations. A prototype system helps find video segments of interest from existing collections and create new video presentations with algebraic combinations of these segments.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk (2004)

The risk for cardiovascular disease and total mortality associated with hemoglobin A1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes.
Recombinant Holotoxoid Vaccine against Botulism (2007)

The botulinum neurotoxins (BoNT) are the most toxic proteins for humans and designated "Category A Select Agents." The current vaccine against botulism is in limited supply, and there is a need to develop new vaccine strategies. A recombinant BoNT/A toxoid was produced in Clostridium botulinum that contained a double amino acid substitution, R363A Y365F (termed BoNT/A(RYM)). BoNT/A(RYM) was noncatalytic for SNAP25 and nontoxic for mice. Immunization with BoNT/A(RYM) protected mice from challenge at levels that were similar to chemically inactivated BoNT/A toxoid. BoNT/A(RYM) elicited an immune response against the light-chain and heavy-chain components of the toxin. Neutralizing anti-BoNT/A(RYM) sera blocked BoNT toxicity in primary cortical neurons and blocked ganglioside binding by the heavy chain. BoNT/A(RYM) represents a viable vaccine candidate for a holotoxoid against botulism.
DNA Damage Induced by Red Food Dyes Orally Administered to Pregnant and Male Mice (2001)

We determined the genotoxicity of synthetic red tar dyes currently used as food color additives in many countries, including JAPAN: For the preliminary assessment, we treated groups of 4 pregnant mice (gestational day 11) once orally at the limit dose (2000 mg/kg) of amaranth (food red No. 2), allura red (food red No. 40), or acid red (food red No. 106), and we sampled brain, lung, liver, kidney, glandular stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after treatment. We used the comet (alkaline single cell gel electrophoresis) assay to measure DNA damage. The assay was positive in the colon 3 h after the administration of amaranth and allura red and weakly positive in the lung 6 h after the administration of amaranth. Acid red did not induce DNA damage in any sample at any sampling time. None of the dyes damaged DNA in other organs or the embryo. We then tested male mice with amaranth, allura red, and a related color additive, new coccine (food red No. 18). The 3 dyes induced DNA damage in the colon starting at 10 mg/kg. Twenty ml/kg of soaking liquid from commercial red ginger pickles, which contained 6.5 mg/10 ml of new coccine, induced DNA damage in colon, glandular stomach, and bladder. The potencies were compared to those of other rodent carcinogens. The rodent hepatocarcinogen p-dimethylaminoazobenzene induced colon DNA damage at 1 mg/kg, whereas it damaged liver DNA only at 500 mg/kg. Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver and bladder, it did not induce colon DNA damage. N-nitrosodiethylamine at 14 mg/kg did not induce DNA damage in any organs examined. Because the 3 azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted.
New biotinylating reagent utilizing carbodiimide function. (1995)

A biotin derivative having a carbodiimide function (fig.1 Carbo-biotin) was synthesized and reacted with DNAs. This compound was used to label biotin to DNAs, by reaction of carbodiimide group and nucleotides as they form stable adducts. Our experiments showed that it is able to bind to both single and double stranded DNAs. The DNA oligomer labeled with this reagent was shown to hybridize to complementary DNA chain. From our results, this compound is expected to be a useful biotinylating reagent for non-radioactive detection.
Heat Treatment of Turkey Litter for Reuse as Bedding (2003)

Local and national laws regulating poultry litter (PL) land application may require that PL be applied based on crop needs and PL nutrient content such as N and P. In addition, some may require monitoring of soil metals such as Cu and Zn. Even with efforts to decrease fecal nutrient excretion, there is also a need to extend the useful life of current bedding materials and to develop alternative uses of spent PL. Heat treatment of PL may extend bedding life and offer alternative uses of PL. The objective of this study was to determine if heat processed turkey litter (TL) can be reused as bedding for turkeys. Pine shavings (PS) which had been used as bedding to rear Large White male turkeys from hatch to 20 weeks of age was processed at 95 and 220 C in an enclosed auger system. Four litter treatments (LT) were used: 1) control - new PS (T ), o 1 2) TL processed at 95 C (T ), 3) a 70:30 (w/w) mixture of TL processed at 95 or 220 C (T ) and 4) a 95:5 o o 2 3 (w/w) mixture of TL processed at 95 or 220 C (T ). These bedding mixtures were placed in 36 floor pens in o 4 a randomized block design to provide 9 replicate pens per LT. Thirty Large White turkey hen poults were placed in each pen on day of hatch. The birds were reared to 14 wk. Mortality and feed consumption were monitored. Period and cumulative feed conversion (FC) ratios were calculated. Regression analysis of SAS, Inc. was used for data analysis. The LS Means procedure was used to separate treatment means (P<0.05). At 6 wks, T hens were heavier than T (1.78 kg), T (1.80 kg) or T (1.81 kg) hens. There were no differences 3 1 2 4 in BW at 10 (5.42 kg) or 14 wk (8.67 kg) among treatments. There were no differences in FC. The LT did not affect bird mortality. Litter treated by the heat process used for this study produces a bedding material suitable for rearing market turkeys.
Post-translational activation introduces a free radical into pyruvate formate-lyase. (1984)

Pyruvate formate-lyase (formate acetyltransferase; EC 2.3.1.54) of Escherichia coli cells is post-translationally interconverted between inactive and active forms. Conversion of the inactive to the active form is catalyzed by an Fe2+-dependent activating enzyme and requires adenosylmethionine and dihydroflavodoxin. This process is shown here to introduce a paramagnetic moiety into the structure of pyruvate formate-lyase. It displays an EPR signal at g = 2 with a doublet splitting of 1.5 mT and could comprise an organic free radical located on an amino acid residue of the polypeptide chain. Hypophosphite was discovered as a specific reagent that destroys both the enzyme radical and the enzyme activity; it becomes covalently bound to the protein. The enzymatic generation of the radical, which is linked to adenosylmethionine cleavage into 5'-deoxyadenosine and methionine, possibly occurs through an Fe-adenosyl complex. These results suggest a radical mechanism for the catalytic cycle of pyruvate formate-lyase.
Treatment of Streptococcal Pharyngitis With Once-Daily Compared With Twice-Daily Amoxicillin (2006)

We conclude that amoxicillin given once daily is not inferior to amoxicillin given twice daily. Gastrointestinal and other events did not occur significantly more often in the once-daily treatment group. From the data in this large, investigator-blinded, controlled study, once-daily amoxicillin appears to be a suitable regimen for treatment of GAS pharyngitis.
[Sensory neuropathy in HIV infection: pathogenesis and therapy]. (2001)

An axonal sensory neuropathy is a frequent complication in the course of HIV infection; more than 30% of all HIV-infected individuals will develop a polyneuropathy. Low CD4 cell counts and high HIV RNA loads increase the risk. This neuropathy causes pain, paresthesias and burning sensations and/or numbness in the feet, which sometimes occurs in the hands as well. Neurological examination reveals sensory deficits in a stocking and glove distribution and depressed or absent ankle reflexes, without severe paresis. The cause of the sensory neuropathy is unknown. Either the HIV infection or certain other infections, for example cytomegalovirus, may play a role in the pathogenesis; vasculitis may be a process associated with this. Some antiretroviral drugs within the nucleoside analogue group cause a neuropathy but the pathogenesis of this remains unclear. Amitriptyline, tramadol and carbamazepine can be used for symptomatic treatment. The efficacy of lamotrigine and gabapentin has yet to be confirmed.
Poly(ethylene glycol) Conjugated Drugs and Prodrugs: A Comprehensive Review (2000)

Low molecular weight Polyethylene glycol) (PEG) (< 20,000)-drug conjugates, prepared over a 20-year period, have been scrutinized and their properties and efficacy reviewed. No commercial products have thus far been reported for these types of compounds. However, during the past 5 years a renaissance in the field of PEG-(anticancer) drug conjugates has taken place, initiated by the use of higher molecular weight PEGs (> 20,000), especially 40,000, which is estimated to have a plasma circulating half-life of approximately 8-9 h. This recent resuscitation of small organic molecule delivery by high molecular weight PEG conjugates was founded on meaningful in vivo testing using established tumor models and has led to a clinical candidate. Recent applications of high molecular weight PEG prodrug strategies to amino-containing drugs are also detailed.
Preferential increase in chylomicron levels of the xanthophylls lutein and zeaxanthin compared to beta-carotene in the human. (1996)

The time-course of appearance of five carotenoids in chylomicrons and their distribution pattern were studied following ingestion of a single dose of Betatene, a natural carotenoid source composed of 0.5% lutein, 0.75% zeaxanthin, 3.6% alpha-carotene, 70.3% all-trans beta-carotene, 22.7% beta-carotene cis isomers, 2.1% unidentified carotenoids and no lycopene. Lutein, zeaxanthin, alpha-carotene and all-trans beta-carotene but not lycopene levels in chylomicrons increased after Betatene ingestion with a maximum at 9 h and a distinct decline from 9 to 12 h. However, the carotenoid pattern in the chylomicron fraction did not match the pattern in Betatene, with a 14-fold and 4-fold higher level of lutein and zeaxanthin, respectively, compared to their content in Betatene. The contribution of alpha-carotene to the carotenoid composition in chylomicrons reflected its content in Betatene, whereas the relative amount of all-trans beta-carotene was substantially lower than in Betatene. Thus, in the presence of high amounts of beta-carotene, there is a preferential uptake of the xanthophylls lutein and zeaxanthin as compared to all-trans beta-carotene from the intestinal lumen into chylomicrons.
Effect of deletion mutation on the recombination activity of Cre recombinase. (2005)

Cre recombinase from bacteriophage P1 is widely used in both in vitro and in vivo DNA manipulations. Based on a structural and functional analysis, three deleted cre mutants were constructed and expressed in Escherichia coli. Mutated recombinases were purified and their recombination activities were determined in vitro. Our results revealed that the mutant with amino-terminal deletion retains the recombination activity as high as wild type Cre; however, the carboxy-terminal deletion and the middle region deletion both lead to a complete loss of the recombinase function.
Effects of FTY720 in MRL-lpr/lpr mice: therapeutic potential in systemic lupus erythematosus. (2002)

FTY720 suppressed the development of autoimmunity and prolonged the lifespan of female MRL/lpr mice. Suppression of autoimmunity, at least in part, may have resulted from an apoptogenic potential of FTY720. Hence, it could be useful for primary or adjunctive therapy of human SLE.
Novel small molecule alpha v integrin antagonists: comparative anti-cancer efficacy with known angiogenesis inhibitors. (1999)

Recent evidence supports the involvement of integrins in angiogenesis: blockade of alpha v beta 3 and alpha v beta 5 integrins disrupts angiogenesis leading to decreased blood vessel formation and hence decreased tumor growth. We hypothesized that av antagonists could inhibit tumor growth in tumor cells devoid of alpha v beta 3 integrins. We evaluated SM256 and SD983, novel small molecules that are specific av antagonists in mouse models of angiogenesis and tumorigenesis, and compared them with standards: TNP470, a fumagillin analog in the clinic, and flavopiridol, a cell cycle kinase inhibitor. In vitro SM256 was a selective alpha v beta 3 inhibitor with an IC50 = 4nM, and the affinity of SD983 against the mouse endothelial alpha v beta 3 integrin yielded an IC50 = 2nM and an IC50 = 54nM against alpha v beta 5. In the mouse Matrigel model of angiogenesis SM256 decreased blood vessel formation (hemoglobin content) with an ED50 = 0.055 ug/kg/day, tenfold more potent than TNP470. SG545, an ester of SD983, decreased blood vessel formation with an ED50 = 6 ug/kg/day, while flavopiridol ED50 = 18 ug/kg/day. In the mouse xenograft model, using human colon carcinoma RKO cells that do not express alpha v beta 3 but express alpha v beta 5, tumor growth was inhibited by SG545 (10 mg/kg/day) and flavopiridol (5 mg/kg/every other day) 40% and 70%, respectively (p < 0.05). Although the proliferative index (measured by BrdU incorporation) was not significantly changed with SM256, SG545 or flavopiridol (29-32%), the apoptotic index increased significantly (p < 0.05) in the SM256 and SG545-treated groups (2.3-2.7%) compared with controls (1.1%), suggesting increased cell death contributed to decreased tumor volumes. Neovascularization decreased with SM256 and SG545 treatment. The data demonstrate that potent selective av antagonist can target endothelial cells, tumor cells, inhibit angiogenesis and inhibit tumor growth.
The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases β-cell mass in diabetic mice (2002)

NN2211 is a long-acting, metabolically stable glucagon-like peptide-1 (GLP-1) derivative designed for once daily administration in humans. NN2211 dose dependently reduced the glycemic levels in ob/ob mice, with antihyperglycemic activity still evident 24 h postdose. Apart from an initial reduction in food intake, there were no significant differences between NN2211 and vehicle treatment, and body weight was not affected. Histological examination revealed that beta-cell proliferation and mass were not increased significantly in ob/ob mice with NN2211, although there was a strong tendency for increased proliferation. In db/db mice, exendin-4 and NN2211 decreased blood glucose compared with vehicle, but NN2211 had a longer duration of action. Food intake was lowered only on day 1 with both compounds, and body weight was unaffected. beta-Cell proliferation rate and mass were significantly increased with NN2211, but with exendin-4, only the beta-cell proliferation rate was significantly increased. In conclusion, NN2211 reduced blood glucose after acute and chronic treatment in ob/ob and db/db mice and was associated with increased beta-cell mass and proliferation in db/db mice. NN2211 is currently in phase 2 clinical development.