bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐ and multiple‐dose study to evaluate pharmacokinetics, safety and tolerability in healthy volunteers: A comparison of extended‐release oxycodone with sequestered naltrexone 40 mg twice daily to oxycontin 40 mg twice daily and extended‐release oxycodone with sequestered naltrexone 80 mg once daily
Authors: Gandelman Kuan , Lamson Michael , Bramson Candace , Matschke Kyle , Salageanu Joanne , Malhotra Bimal 
Published: November 2014

AbstractALO‐02 capsules (ALO‐02) contain pellets that consist of extended‐release oxycodone that surrounds sequestered naltrexone. The primary objective was to characterize the pharmacokinetics (PK) of oxycodone following single‐ and multiple‐dose oral administration of ALO‐02 40 mg BID in healthy volunteers. Secondary objectives were to characterize (1) the PK of oxycodone following single‐ and multiple‐dose administration of a comparator OxyContin (OXY‐ER) 40 mg BID as well as an alternate regimen of ALO‐02 80 mg QD, and (2) the safety and tolerability assessments. Healthy volunteers received three treatments on a background of oral naltrexone (50 mg). Noncompartmental PK parameters were calculated for oxycodone. All 12 subjects were male with a mean age (SD, range) of 44.6 years (7.6, 25–55). Single‐dose PK results for ALO‐02 indicate that median peak plasma oxycodone concentrations were reached by 12 hours compared to 4 hours for OXY‐ER. Compared to OXY‐ER, mean dose‐normalized, single‐dose Cmax values were approximately 27% and 23% lower for ALO‐02 40 mg BID and ALO‐02 80 mg QD treatments, respectively. Following multiple doses all treatments reached steady state by 3 days. At steady state, oxycodone peak‐to‐trough fluctuation was significantly lower for ALO‐02 BID versus OXY‐ER. Adverse events were consistent with opioid therapy. ALO‐02 40 mg BID treatment provided a PK profile appropriate for around‐the‐clock treatment of chronic pain.
Real‐Time Fluorescence Imaging of the DNA Damage Repair Response During Mitosis
Authors: Miwa Shinji , Yano Shuya , Yamamoto Mako , Matsumoto Yasunori , Uehara Fuminari , Hiroshima Yukihiko , Toneri Makoto , Murakami Takashi , Kimura Hiroaki , Hayashi Katsuhiro , Yamamoto Norio , Efimova Elena V. , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: November 2014

ABSTRACTThe response to DNA damage during mitosis was visualized using real‐time fluorescence imaging of focus formation by the DNA‐damage repair (DDR) response protein 53BP1 linked to green fluorescent protein (GFP) (53BP1‐GFP) in the MiaPaCa‐2Tet‐On pancreatic cancer cell line. To observe 53BP1‐GFP foci during mitosis, MiaPaCa‐2Tet‐On 53BP1‐GFP cells were imaged every 30 min by confocal microscopy. Time‐lapse imaging demonstrated that 11.4 ± 2.1% of the mitotic MiaPaCa‐2Tet‐On 53BP1‐GFP cells had increased focus formation over time. Non‐mitotic cells did not have an increase in 53BP1‐GFP focus formation over time. Some of the mitotic MiaPaCa‐2Tet‐On 53BP1‐GFP cells with focus formation became apoptotic. The results of the present report suggest that DNA strand breaks occur during mitosis and undergo repair, which may cause some of the mitotic cells to enter apoptosis in a phenomenon possibly related to mitotic catastrophe. J. Cell. Biochem. 116: 661–666, 2015. © 2014 Wiley Periodicals, Inc.
Pomelo enhances cyclosporine bioavailability in healthy male thai volunteers
Authors: Anlamlert Wirin , Sermsappasuk Pakawadee , Yokubol Dhirayudh , Jones Sirada 
Published: November 2014

AbstractThe aim of this study was to investigate the effect of pomelo pulp on the pharmacokinetics of cyclosporine in healthy male Thai volunteers.The study design was an open‐label, randomized, single dose, crossover study with a 2‐week washout period. A single oral dose of 2 × 100 mg cyclosporine was administered with 200 mL of water. Each subject received 250 g of pomelo pulp or 250 mL of water 1 hour before drug administration and once again 10 minutes following drug administration. Blood samples were collected over a 24 hour period. The point estimates (90% confidence intervals) of the test/control ratio using logarithmic transformed data for the area under the curve (AUC) for blood concentration from time 0 to infinity (AUC0–∞) and the observed maximum concentration (Cmax) were 128.8% (120.6–137.6) and 136.1% (126.0–146.8), respectively. These 90% confidence intervals were higher than the accepted bioequivalence range defined by the European Medicines Agency guidelines for narrow therapeutic index drugs (90%–111% for AUC and 80%–125% for Cmax). However, the apparent terminal half‐life (t1/2) was not significantly different. In conclusion, co‐administration of cyclosporine and pomelo pulp increased the relative bioavailability of cyclosporine.
Safety and tolerability of serelaxin, a recombinant human relaxin‐2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populations
Authors: Dahlke Marion , Ng Dik , Yamaguchi Masayuki , Machineni Surendra , Berger Sergej , Canadi Jasna , Rajman Iris , Lloyd Peter , Pang Yinuo 
Published: November 2014

AbstractSerelaxin, a recombinant form of the human relaxin‐2 hormone, is currently under clinical investigation for treatment of acute heart failure. This double‐blind, placebo‐controlled, dose‐ranging study investigated the effect of Japanese ethnicity on the pharmacokinetics (PK), pharmacodynamics (PD), and safety and tolerability of serelaxin. Japanese healthy subjects (n = 32) received 10, 30, or 100 µg/kg/day of serelaxin, or placebo, administered as a 48‐hour intravenous infusion. A Caucasian cohort (n = 8) receiving 30 µg/kg/day open‐label serelaxin was included for comparison. In all subjects, serum serelaxin concentrations increased rapidly after the start of infusion, approached steady state as early as 4 hours, and declined rapidly upon treatment cessation. Serum exposure to serelaxin increased with increasing doses. Statistical dose proportionality was shown for AUCinf over the entire dose range. A significant increase in estimated glomerular filtration rate from baseline to Day 2 (30 and 100 µg/kg/day) and to Day 3 (10 and 100 µg/kg/day) was observed compared with placebo. Serelaxin was well tolerated by all subjects. In conclusion, PK, PD, and safety profiles of serelaxin were generally comparable between Japanese and Caucasian subjects, suggesting that no dose adjustment will be required in Japanese subjects during routine clinical use of this agent.
The fungal laccase‐catalyzed oxidation of EGCG and the characterization of its products
Authors: Lee Yeonhee , Lin Zhi , Du Guocheng , Deng Zhuangmei , Yang Haiquan , Bai Wenxiang 
Published: November 2014

AbstractBACKGROUNDFungal laccase (EC 1.10.3.2) is an important enzyme for catalyzing the oxidation of tea polyphenols during the fermentation of tea. (−)‐Epigallocatechin gallate (EGCG) is the main ingredient of tea polyphenols. To a certain extent, the oxidation degree of EGCG reflects the fermentation degree of tea. This study preliminarily optimized the conditions for catalytically oxidizing EGCG by Aspergillus sp. trijbl1112 laccase and systematically analyzed the components and contents of the EGCG oxidation products.RESULTSAspergillus sp. trijbl1112 laccase oxidized EGCG into free catechins, ester catechins, gallic acid and tea pigments. The reaction conditions had a significant impact on the oxidation rate, types and concentrations of the products. At natural pH, 69.29% of EGCG was oxidized when 1 mL of EGCG (1 mmol L−1) was catalyzed by 10 µg of fungal laccase for 150 min at 70 °C. When the EGCG oxidation rate was 69.27%, free catechins ((+)‐catechin and (−)‐epigallocatechin) and tea pigments (mainly thearubigin and theabrownin) constituted 48.42 and 38.87% of the oxidation products respectively.CONCLUSIONThe results may provide a theoretical basis for the application of EGCG oxidation using laccase and provide a novel technique for obtaining high production of tea pigments. © 2014 Society of Chemical Industry
A synergistic effect of pretreatment on cell wall structural changes in barley straw (Hordeum vulgare L.) for efficient bioethanol production
Authors: Sheikh Md Mominul Islam , Kim Chul‐Hwan , Park Hyeong‐Hun , Nam Hye‐Gyeong , Lee Gyeong Sun , Jo Hu Seung , Lee Ji‐Young , Kim Jae Won 
Published: November 2014

AbstractBACKGROUNDBarley straw (Hordeum vulgare L.) is an attractive lignocellulosic material and one of the most abundant renewable resources for fuel ethanol production. Although it has high cellulose and hemicellulose contents, there are several challenges and limitations in the process of converting it to fuel ethanol. High ash, silica and lignin contents in barley straw make it an inferior feedstock for enzymatic hydrolysis. Therefore pretreatment of barley straw could play an important role in inducing structural and compositional changes that increase the efficiency of enzymatic hydrolysis and make the whole process economically viable.RESULTSSaccharification was enhanced using various concentrations (0.0, 0.5, 1.0, 2.0 and 3.0% v/v) of a solution of sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2) and various reaction times (15, 30 and 45 min) during pretreatment at 121 °C. The highest yield of glucose (447 mg g−1) was achieved by pretreatment with 2.0% NaClO+H2O2 solution for 30 min, representing an increase of 65.99% compared with untreated barley straw (152 mg g−1). During fermentation, the highest amount of ethanol (207 mg g−1) was obtained under anaerobic plus 0.4 mmol L−1 benzoic acid conditions, representing an increase of 57.49, 38.16 and 10.14% compared with untreated sample (88 mg g−1), aerobic (128 mg g−1) and anaerobic (186 mg g−1) conditions respectively.CONCLUSIONThe results suggest that pretreatment with 2.0% NaClO+H2O2 solution disrupted the recalcitrant structure of barley straw and enhanced the glucose yield and subsequent bioethanol production. © 2014 Society of Chemical Industry
Arrest of progression of pre‐induced abdominal aortic aneurysm in apolipoprotein E‐deficient mice by low level laser phototherapy
Authors: Gavish Lilach , Beeri Ronen , Gilon Dan , Rubinstein Chen , Berlatzky Yacov , Bulut Atilla , Reissman Petachia , Gavish Leah Y. , Gertz S. David 
Published: November 2014

Background and ObjectivesUsing non‐invasive, high‐frequency ultrasonography (HF‐u/s), we showed that low‐level laser phototherapy (LLL) inhibits de‐novo formation of abdominal aortic aneurysms (AAA) in apolipoprotein‐E‐deficient (Apo‐E‐/‐) mice. The current study tests the effect of LLL on the progression of pre‐induced AAA.Study Design/Material and MethodsAAA was induced in Apo‐E‐/‐ mice (age16–20 weeks) by subcutaneous infusion of angiotensin‐II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF‐u/s (40 MHz, 0.01 mm resolution, Vevo‐770, VisualSonics) was used to measure the maximum cross‐sectional‐diameter (MCD) of the suprarenal abdominal aorta, the anterior wall displacement (AWD), and radial wall velocity (RWV). The aortas of mice that developed >35% dilatation at 2 weeks over baseline were exposed retroperitoneally and treated with LLL (780 nm, 2.2 J/cm2, 9 minutes) or sham‐operated. HF‐u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology.ResultsOf all mice with >35% MCD expansion of the suprarenal aorta at 2 weeks, 7(58%) of 12 non‐treated, but only 1(7%) of 14 LLL, had increased MCD(> 1 SD) at 4 weeks (P < 0.009 by Fisher's Exact Test [FET]). The mean change in MCD from 2–4 weeks was also markedly reduced in the LLL‐treated mice (control vs. LLL, 0.24 ± 0.25 vs. −0.06 ± 0.39mm, P = 0.029 by unpaired t‐test). Similar results were obtained when limiting the analysis to animals with ≥50% expansion at 2 weeks. The deterioration in AWD from 2–4 weeks in non‐treated controls was not observed in LLL‐treated animals (ΔAWD: control, 0.03 ± 0.05 mm, P < 0.036 vs. LLL, 0.00 ± 0.05, P = 0.91 by paired t‐test). By the modified Daugherty classification, we found significantly fewer severe aneurysms at 4 weeks in the LLL‐treated animals versus control (3 of 10 vs. 9 of 11, P = 0.03 by FET).ConclusionsLLL not only prevents de novo development of AAA, but, from this study, also arrests further progression of pre‐induced AAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo‐E‐/‐ mice. Lasers Surg. Med. 46:781–790, 2014. © 2014 Wiley Periodicals, Inc.
Increased activity of MMP‐2 in hypertensive obese children is associated with hypoadiponectinemia
Authors: Belo Vanessa A. , Lacchini Riccardo , Miranda Josiane A. , Lanna Carla M.M. , Souza‐Costa Debora C. , Tanus‐Santos Jose E. 
Published: November 2014

ObjectiveTo compare the circulating levels of MMP‐2 and TIMP‐2 and the MMP‐2/TIMP‐2 ratio in control, obese, and obese hypertensive children and adolescents and to assess whether hypoadiponectinemia is associated with MMP‐2 and TIMP‐2 levels and MMP‐2/TIMP‐2 ratios.MethodsStudies were carried out with 53 control, 73 obese, and 29 obese hypertensive children and adolescents in this cross‐sectional study. Adiponectin and TIMP‐2 concentrations were measured by ELISA. MMP‐2 concentrations were measured by gelatin zymography. Multiple linear regression analysis was carried out to assess the effects of adiponectin on MMP‐2 and TIMP‐2 levels and MMP‐2/TIMP‐2 ratios.ResultsThe obese hypertensive group had the lowest adiponectin levels among groups (P < 0.05) while obese subjects had lower adiponectin levels than control subjects (P < 0.05). Obese hypertensive subjects also had higher circulating MMP‐2 concentrations than obese subjects (P < 0.05) and had the highest MMP‐2/TIMP‐2 ratios among groups (P < 0.05). Moreover, obese/hypertensive subjects had the lowest TIMP‐2 levels among groups (P < 0.05). A multiple linear regression analysis showed that MMP‐2 levels and MMP‐2/TIMP‐2 ratios are negatively associated with adiponectin levels (P = 0.034 and P = 0.011, respectively) while TIMP‐2 levels is positively associated with adiponectin levels (P = 0.013).ConclusionsIncreased activity of MMP‐2 (MMP‐2/TIMP‐2 ratio) and reduced TIMP‐2 levels may play an important role in clinical hypertension of childhood obesity. Additionally, hypoadiponectinemia may contribute to increased activity of MMP‐2 in obese/hypertensive children and adolescents.
Secondhand smoke and traffic exhaust confer opposing risks for asthma in normal and overweight children
Authors: LeMasters Grace , Levin Linda , Bernstein David I. , Lockey Stephen D. , Lockey James E. , Burkle Jeff , Khurana Hershey Gurjit K. , Brunst Kelly , Ryan Patrick H. 
Published: November 2014

ObjectiveExposure to ultrafine particles (UFP) in secondhand smoke (SHS) and traffic‐related air pollution (TRAP) may elicit chronic inflammation. It was hypothesized that the association between these exposures would be potentiated in overweight versus normal‐weight children.MethodsAverage lifetime exposure to TRAP and SHS and objective, physician‐diagnosed asthma were determined for 575 children at age 7. Overweight was defined as having a body mass index (BMI) >85th percentile for age and gender. The association between TRAP and SHS exposure and asthma was examined by logistic regression stratified by BMI.ResultsA total of 131 children were overweight; the prevalence of asthma was 24.4% and 14.2% among overweight and normal‐weight children, respectively. Exposure to SHS was significantly associated with asthma among overweight (adjusted odds ratio [adjOR] = 3.0; 95% confidence interval [CI] = 1.2, 7.4) but not normal‐weight children (adjOR = 1.1; 95% CI = 0.4, 2.7). In contrast, TRAP was significantly associated with asthma among normal‐weight (adjOR = 1.8; 95% CI = 1.0, 3.4) but not overweight children (adjOR = 0.7; 95% CI = 0.4, 2.7).ConclusionsThe association between SHS and TRAP exposure and asthma is modified by children's weight. Children's time‐activity patterns, including time spent indoors or outdoors, may vary by weight and play an important role in these UFP exposures.
Nationwide demonstration project of next‐generation sequencing of cell‐free DNA in maternal plasma in Japan: 1‐year experience
Authors: Sago Haruhiko , Sekizawa Akihiko ,   Japan NIPT consortium
Published: November 2014

AbstractObjectiveTo report the 1‐year experience of a nationwide demonstration project to introduce noninvasive prenatal testing of aneuploidy from maternal plasma and discuss how to implement this program in Japan.MethodsThe test was conducted to detect aneuploidy in high‐risk pregnant women with adequate genetic counseling. The clinical data, test results, and pregnancy outcomes were recorded.ResultsOf the 7740 women tested, 142 (1.8%) had positive results, 7594 (98.1%) had negative results, and four (0.1%) had results that were not reportable. Of the 142 women who tested positive, 13 cases resulted in intrauterine fetal death, and three cases refused to undergo the invasive procedure. Of the 126 positive cases confirmed on karyotyping, a normal karyotype was observed for trisomy 21 in three cases, trisomy 18 in eight cases, and trisomy 13 in two cases. In the follow‐up study of the negative cases (n = 1638), only one false‐negative case of trisomy 18 was detected.ConclusionsWe described our nationwide 1‐year experience with noninvasive prenatal genetic testing. It is expected that the present data will stimulate a debate regarding prenatal genetic testing and hopefully lead to improvements in the perinatal care system with respect to genetic counseling in Japan. © 2014 John Wiley & Sons, Ltd.
FLATCON® CPV module with 36.7% efficiency equipped with four‐junction solar cells
Authors: Steiner Marc , Bösch Armin , Dilger Alexander , Dimroth Frank , Dörsam Tobias , Muller Matt , Hornung Thorsten , Siefer Gerald , Wiesenfarth Maike , Bett Andreas W. 
Published: November 2014

AbstractIn this paper we present the application of high efficiency four‐junction solar cells using SOITEC bonding technology under a Fresnel lens optic and in a FLATCON®‐type CPV module. We demonstrate very high performance. The measurement of a sub‐module, consisting of a four‐junction solar cell adjusted under a single Fresnel lens, showed an efficiency of 38.9%. An 829.6 cm2 sized FLATCON®‐type CPV module yielded in an efficiency of 35.0% and 36.7% at CSOC and CSTC, respectively. Thus, both, the sub‐module and the CPV module showed record values, which prove the usefulness of high efficiency four‐junction solar cells in CPV applications. Copyright © 2014 John Wiley & Sons, Ltd.
Charge transfer in and conductivity of molecularly doped thiophene‐based copolymers
Authors: Ghani Fatemeh , Opitz Andreas , Pingel Patrick , Heimel Georg , Salzmann Ingo , Frisch Johannes , Neher Dieter , Tsami Argiri , Scherf Ullrich , Koch Norbert 
Published: November 2014

ABSTRACTThe electrical conductivity of organic semiconductors can be enhanced by orders of magnitude via doping with strong molecular electron acceptors or donors. Ground‐state integer charge transfer and charge‐transfer complex formation between organic semiconductors and molecular dopants have been suggested as the microscopic mechanisms causing these profound changes in electrical materials properties. Here, we study charge‐transfer interactions between the common molecular p‐dopant 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane and a systematic series of thiophene‐based copolymers by a combination of spectroscopic techniques and electrical measurements. Subtle variations in chemical structure are seen to significantly impact the nature of the charge‐transfer species and the efficiency of the doping process, underlining the need for a more detailed understanding of the microscopic doping mechanism in organic semiconductors to reliably guide targeted chemical design. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 58–63
Above, below, and in‐between the two glass transitions of ultrathin free‐standing polystyrene films: Thermal expansion coefficient and physical aging
Authors: Pye Justin E. , Roth Connie B. 
Published: November 2014

ABSTRACTIn previous work we observed two simultaneous transitions in high molecular weight (MW) free‐standing polystyrene films that were interpreted as two thickness‐dependent reduced glass transition temperatures (Tgs). The weaker lower transition agreed well with the MW‐dependent Tg(h) previously reported, while the much stronger upper transition matched the MW‐independent Tg(h) previously observed in low‐MW free‐standing films. Here, we investigate the nature of these two transitions by inspecting the temperature dependence of the films' thermal coefficient of expansion (TCE) and present physical aging measurements using ellipsometry both below and in‐between the two transitions. TCE values indicate approximately 80 to 90% of the film solidifies at the upper transition, while only 10 to 20% remains mobile to lower temperatures, freezing out at the lower transition. Physical aging is observed at a temperature below the upper transition, but above the lower transition, indicative of the upper transition being an actual glass transition associated with the α‐relaxation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 64–75
Features of titanium oxide memristor fabrication by pulsed laser deposition
Authors: Maslova Natalia , Khrapovitskaya Yulia , Sokolov Ivan , Grishchenko Yulia , Mamichev Dmitry , Zanaveskin Maxim 
Published: November 2014

AbstractThe structural and electrophysical properties of titanium oxide based memristor obtained by pulsed laser deposition were analysed. The experimental results found the possibility of fine tuning of memristor active layers stoichiometry during deposition. In addition, the atomic force microscopy analysis of the surface of titanium oxide films revealed its high morphological homogeneity and continuity. The obtained memristors with gold contacts have been possessed bipolar switching mechanism and high endurance. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effect of TiOx/TiO2 layer thickness on the properties of the pulsed laser deposited memristive device
Authors: Tselikov G. I. , Emelyanov A. V. , Antropov I. M. , Demin V. A. , Kashkarov P. K. 
Published: November 2014

AbstractMemristive properties of the pulsed laser deposited Pt/TiOx/TiO2/Pt heterostructures with different layer thicknesses are studied. It was found that the memristor device provides nonmonotonic dependence of the ratio of its resistance in low and high conductive states Roff/Ron on layers thickness. The maximum value of the ratio Roff/Ron = 200 is obtained when the thickness of both TiOx and TiO2 layers is 30 nm. The dependence of the stoichiometry index of deposited layers from their thicknesses is studied by means of Auger spectroscopy measurements. The nonmonotonic behaviour of the ratio Roff/Ron on layer thickness is discussed in terms of wide stoichiometry distribution through the amorphous TiOx/TiO2 structure. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ion current rectification effect of porous graphene membrane
Authors: Zeng Jian , Yao Huijun , Mo Dan , Duan Jinglai , Liu Jiande , Cao Dianliang , Zhai Pengfei , Liu Jie , Sun Youmei 
Published: November 2014

AbstractGraphene, as an important ideal two‐dimensional material, is driving more and more attention because of its unique mechanical strength and chemical stability. In this work, the rectification effect of nanopores in graphene/PET structure at different KCl concentration is investigated. Porous graphene membrane is obtained by using heavy ion irradiation technology. During investigating the ion current rectification effect, PET membrane with conical pores acts as porous graphene's substrate. The rectification coefficient of nanopores in graphene/PET is deduced from the current‐voltage curves at KCl solution with different concentrations. The porous graphene/PET shows a relative higher rectification ratio and is more resistive to pH value while comparing the nanopores in PET. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)