bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Reaction of 2‐Substituted 5,5‐Dimethyl‐4‐oxo‐1‐pyrroline 1‐Oxides with Electrophilic Reagents.
Authors: REZNIKOV V. A. , VISHNIVETSKAYA L. A. , VOLODARSKII L. B.
Published: May 2016

The title compounds (I) react with the electrophilic reagents (II), N‐chlorosuccinimide, or (XV) either at the O‐atom of the nitrone group or at the CH2 group of the pyrroline ring to give the 1‐acyloxypyrrolines (III), the 3‐chloro derivatives (IV) or (VIII), or the oximes (XVI).
ChemInform Abstract: Synthesis of 4‐Aminocycloheptimidazoles.
Authors: ISHIDA N. , IMAFUKU K.
Published: May 2016

Treatment of (I) and (V) with hydrazoic acid, generated in situ from NaN3 in the presence of conc.
ChemInform Abstract: 1,3‐Dipolar Cycloadditions of Alkyl Azides with Picryl Isothiocyanate: Isolation of Stable Monoadducts.
Authors: L'ABBE G. , BREMS P. , ALBRECHT E.
Published: May 2016

The title adducts, e.g. (III), are exceptionally thermostable.
ChemInform Abstract: Synthesis of Piperidine Derivatives as Potential Analgetic Agents.
Authors: JILEK J. , RAJSNER M. , VALENTA V. , BOROVICKA M. , HOLUBEK J. , RYSKA M. , SVATEK E. , METYS J. , PROTIVA M.
Published: May 2016

A great variety of piperidine derivatives are synthesized including the compounds (II) and (V) related to fentanyl (I) as well as the cyclized compounds (VIII) and (X).
ChemInform Abstract: Synthesis of Thieno(3,2‐c)quinoline N‐Oxide and Thieno‐(3,2‐c)isoquinoline N‐Oxide. The NMR Spectra of the Six Isomeric Thieno‐Fused Quinoline and Isoquinoline N‐Oxides.
Authors: GRONOWITZ S. , TIMARI G.
Published: May 2016

Whereas the synthesis of the title compounds (VIII)‐(XI) had been already reported, the preparation of the missing members (IV) and (VII) is now given.
ChemInform Abstract: Synthesis of Pyrimido(4,5‐g)pyrimidine, Thieno(2,3‐d)pyrimidines, and 4‐Substituted Pyrimidines.
Authors: EL‐BAHAIE S. , ASSY M. G. , HEIKAL A. F.
Published: May 2016

The acetylmercaptopyrimidine (I) is converted to the chloride (II) which is coupled with the arylamines (III) or phenylhydrazine (VII) to give the substitution products (IV) or (VIII).
ChemInform Abstract: Benzo(g)(1,2,5)thiadiazolo(3,4‐b)quinoxaline‐5,10‐dione and Its Selenium Analogue. An Unusual Type of Quinones.
Authors: YAMASHITA Y. , TSUBATA Y. , SUZUKI T. , MIYASHI T. , MUKAI T. , TANAKA S.
Published: May 2016

The title compound (VIIIa) and its selenium analogue (VIIIb) are prepared applying previously described methods as outlined in the reaction scheme.
ChemInform Abstract: Chemistry of O,N‐ and S,N‐Containing Heterocycles. Part 12. Synthesis of Tricyclic 1,5‐Benzoxazepines.
Authors: BARTSCH H. , ERKER T.
Published: May 2016

Reaction of methylthiolactim (I) with strong basic nucleophiles (e.g.
ChemInform Abstract: Pentacoordinated Molecules. Part 81. Conformational Preferences of Spirocyclic Pentaoxyphosphoranes Varying in Ring Size.
Authors: SWAMY K. C. K. , DAY R. O. , HOLMES J. M. , HOLMES R. R.
Published: May 2016

The new bicyclic pentaoxyphosphoranes (III) (space group P21/c, Z=4), (V) and (VII) (for both P21/n, Z=4) containing ring sizes varying from five to seven membered are synthesized.
ChemInform Abstract: Models for Diferrous Forms of Iron‐Oxo Proteins. Structure and Properties of (Fe2BPMP(O2CR)2)BPh4 Complexes.
Authors: BOROVIK A. S. , HENDRICH M. P. , HOLMAN T. R. , MUENCK E. + , PAPAEFTHYMIOU V. , QUE L. JUN.
Published: May 2016

The Fe(II)Fe(II) complexes (IV) are synthesized to serve as models for the diferrous forms of iron‐oxo centers in proteins.
ChemInform Abstract: Intramolecular Metalation of C‐H Bonds with (cis,cis‐1,3,5‐Tris((diphenylphosphino)methyl)cyclohexane)rhodium(I) Chloride.
Authors: MAYER H. A. , KASKA W. C.
Published: May 2016

The novel tridentate ligand (II) is synthesized and treated with the Rh dimer (I).
ChemInform Abstract: Catalytic and Stoichiometric Carbonylation of β,γ‐Unsaturated Carboxylic Acids to Give Cyclic Anhydrides Through Intermediate Palladium‐Containing Cyclic Esters.
Authors: OSAKADA K. , DOH M.‐K. , OZAWA F. , YAMAMOTO A.
Published: May 2016

Palladium(0) complexes with tertiary phosphine ligands catalyze the carbonylative cyclization of the acid (I) to give, besides the isomerization product (III), the anhydrides (IV) and (V).
ChemInform Abstract: Total Syntheses of (‐)‐Histrionicotoxin and (‐)‐Histrionicotoxin 235 A.
Authors: STORK G. , ZHAO K.
Published: May 2016

(‐)‐Histrionicotoxin (‐)‐(XIII) and its simpler relative (‐)‐histrionicotoxin 235 A (‐)‐(VIII) are synthesized via the allylic epoxide cyclization method.
ChemInform Abstract: Asymmetric Total Synthesis of an A‐Ring Precursor to Hormonally Active 1α,25‐Dihydroxyvitamin D3.
Authors: POSNER G. H. , KINTER C. M.
Published: May 2016

Diels‐Alder reaction of the sulfonylpyrone (I) with the optically active vinyl ether (II) produces the bicyclic lactone (III) which is converted into the unsaturated ester (‐)‐(V) by consecutive methanolysis, desulfonylation, and double bond isomerization.
ChemInform Abstract: Synthesis of 9‐Deoxy‐8,9‐oxaprostaglandins.
Authors: KELLY M. J. , NEWTON R. F. , ROBERTS S. M. , WHITEHEAD J. F.
Published: May 2016

The title compounds (XII) and (XV) show no useful biological activity.
Bioelectricity Generation From Wastewater Sludge Using Microbial Fuel Cells: A Critical Review
Authors: Ömeroğlu Seçil , Sanin F. Dilek
Published: May 2016

Today, the majority of the world's energy is provided by fossil fuels. Natural energy resources soon will be consumed as a result of rising energy needs of the growing population, leading to a global energy crisis. The insecurity in the energy market also affects the global economy negatively and forces the governments to investigate renewable energy alternatives such as bioenergy. Bioenergy technologies can reduce greenhouse gas (GHG) emissions significantly and can serve to satisfy many forms of energy demand. Microbial fuel cells (MFCs) are one of the bioenergy technologies converting the chemical energy in the bonds of organic wastes into electricity through the biocatalytic reactions of microorganisms. Since the microorganisms present in MFCs utilize organic matter while producing electricity, the use of wastewater and sewage sludge as substrate (fuel) makes MFCs not only a renewable energy technology but also a treatment alternative. Especially, considering the energy consumption of conventional wastewater and sludge treatment systems, MFCs offer a sustainable solution that supply the energy required while achieving high levels of treatment. In addition to these, MFCs can be used in sensors, biohydrogen production and bioremediation. However, the technologic and economic problems with MFCs limit their large scale applications. The purpose of this study is to analyze the recent studies on MFCs and evaluate the outstanding operational parameters and investigate the energy production and efficiency in MFCs fed with different types of wastewater sludge.
Racial and ethnic differences in patient navigation: Results from the Patient Navigation Research Program
Authors: Ko Naomi Y. , Snyder Frederick R. , Raich Peter C. , Paskett Electra D. , Dudley Donald J. , Lee Ji‐Hyun , Levine Paul H. , Freund Karen M.
Published: May 2016

BACKGROUND

Patient navigation was developed to address barriers to timely care and reduce cancer disparities. The current study explored navigation and racial and ethnic differences in time to the diagnostic resolution of a cancer screening abnormality.

METHODS

The authors conducted an analysis of the multisite Patient Navigation Research Program. Participants with an abnormal cancer screening test were allocated to either navigation or control. The unadjusted median time to resolution was calculated for each racial and ethnic group by navigation and control. Multivariable Cox proportional hazards models were fit, adjusting for sex, age, cancer abnormality type, and health insurance and stratifying by center of care.

RESULTS

Among a sample of 7514 participants, 29% were non‐Hispanic white, 43% were Hispanic, and 28% were black. In the control group, black individuals were found to have a longer median time to diagnostic resolution (108 days) compared with non‐Hispanic white individuals (65 days) or Hispanic individuals (68 days) (P<.0001). In the navigated groups, black individuals had a reduction in the median time to diagnostic resolution (97 days) (P<.0001). In the multivariable models, among controls, black race was found to be associated with an increased delay to diagnostic resolution (hazard ratio, 0.77; 95% confidence interval, 0.69‐0.84) compared with non‐Hispanic white individuals, which was reduced in the navigated arm (hazard ratio, 0.85; 95% confidence interval, 0.77‐0.94).

CONCLUSIONS

Patient navigation appears to have the greatest impact among black patients, who had the greatest delays in care. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2715–2722. © 2016 American Cancer Society.
Synthesis of 2‐Butanol by Selective Hydrogenolysis of 1,4‐Anhydroerythritol over Molybdenum Oxide‐Modified Rhodium‐Supported Silica
Authors: Arai Takahiro , Tamura Masazumi , Nakagawa Yoshinao , Tomishige Keiichi
Published: May 2016

Rh‐MoOx/SiO2 (Mo/Rh=0.13) is an effective catalyst for the hydrogenolysis of 1,4‐anhydroerythritol (1,4‐AHERY) and provides 2‐BuOH in high yield of 51 %. This is the first report of the production of 2‐BuOH from 1,4‐AHERY by hydrogenolysis. 1,4‐AHERY was more suitable as a starting material than erythritol because the 2‐BuOH yield from erythritol was low (34 %). Based on the kinetics and comparison of reactivities of the related compounds using Rh‐MoOx/SiO2 and Rh/SiO2 catalysts, the modification of Rh/SiO2 with MoOx leads to the high activity and high selectivity to 2‐BuOH because of the generation of reactive hydride species and the strong adsorption of 1,4‐AHERY on MoOx species. The reaction proceeds by main two routes, (I) the combination of single C−O hydrogenolysis with the desorption of intermediates, a usual route in hydrogenolysis, and (II) multiple C−O hydrogenolysis without the desorption of intermediates from the active site, and the reaction mechanism for Route (II) is proposed.
The Sodium–Oxygen/Carbon Dioxide Electrochemical Cell
Authors: Xu Shaomao , Wei Shuya , Wang Hongsen , Abruña Hector D. , Archer Lynden A.
Published: May 2016

Electrochemical cells that utilize metals in the anode and an ambient gas as the active material in the cathode blur the lines between fuel cells and batteries. Such cells are under active consideration worldwide because they are considered among the most promising energy storage platforms for electrified transportation. Li–air batteries are among the most actively investigated cells in this class, but long‐term challenges, such as CO2 contamination of the cathode gas and electrolyte decomposition, are associated with loss of rechargeability owing to metal carbonate formation in the cathode. Remediation of the first of these problems adds significant infrastructure burdens to the Li–air cell that bring into question its commercial viability. Several recent studies offer contradictory evidence, namely, that the presence of substantial fractions of CO2 in the cathode gas stream can have significant benefits, including increasing the already high specific energy of a Li–O2 cell by as much as 200 %. In this report, we consider electrochemical processes in model Na–O2/CO2 cells and find that, provided the electrode/electrolyte interfaces are electrochemically stable, such cells are able to deliver both exceptional energy storage capacity and stable long‐term charge–discharge cycling behaviors at room temperature.
Mitochondrial DNA typing of laser‐captured single sperm cells to differentiate individuals in a mixed semen stain
Authors: Zhang Lu , Ding Mei , Pang Hao , Xing Jiaxin , Xuan Jinfeng , Wang Chunhong , Lin Ziqing , Han Song , Liang Kewei , Li Chunmei , Yao Jun , Wang Baojie
Published: May 2016

The identification of individuals in a mixture of two semen samples usually involves an analysis of autosomal and Y chromosomal short tandem repeats (STR) which can exclude unrelated individuals but cannot achieve the purpose of individual identification. In sperm cells, there are multiple copies of mitochondrial DNAs (mtDNA) which exhibit genetic polymorphisms in different matrilineal‐related individuals. Single‐cell capture technology can be applied to obtain some single sperm cells in a mixed semen sample, then polymerase chain reaction can be employed to amplify the mtDNA hypervariable region I (HVR I) from each cell. By pooling the cells with the same HVR I sequence, we can obtain the sufficient nuclear DNA for STR typing.
Shaking table testing for masonry infill walls: unreinforced versus reinforced solutions
Authors: Lourenço Paulo B. , Leite João M. , Paulo‐Pereira Manuel F. , Campos‐Costa A. , Candeias P. X. , Mendes Nuno
Published: May 2016

Several factors influence the behaviour of infilled frames, which have been a subject of research in the past with moderate success. The new generation of European design standards imposes the need to prevent brittle collapse of the infills and makes the structural engineer accountable for this requirement, yet it fails to provide sufficient information for masonry infills design. Therefore, the present work aims at understanding the seismic behaviour of masonry infill walls within reinforced concrete frames, using both unreinforced and reinforced solutions (bed joint reinforcement and reinforced plaster). For this purpose, three reinforced concrete buildings with different infill solutions were constructed at a scale of 1:1.5, all with the same geometry, and were tested on the shaking table of the National Laboratory for Civil Engineering, Portugal. All solutions performed adequately for the design earthquake, with no visible damage. Still, the experimental tests show that the double‐leaf‐unreinforced infill walls underperformed during a large earthquake, collapsing out of plane by rotating as rigid bodies with multiple configurations. Also the reinforced concrete buildings collapsed, because of the adverse interaction with the infill walls. The infill walls with bed joint reinforcement and reinforced plaster did not collapse out of plane, because of their connection to the concrete frame, which is an essential requirement. Copyright © 2016 John Wiley & Sons, Ltd.
A macro‐model with nonlinear springs for seismic analysis of URM buildings
Authors: Rinaldin Giovanni , Amadio Claudio , Macorini Lorenzo
Published: May 2016

Seismic assessment of existing unreinforced masonry buildings represents a current challenge in structural engineering. Many historical masonry buildings in earthquake regions were not designed to withstand seismic loading; thus, these structures often do not meet the basic safety requirements recommended by current seismic codes and need to be strengthened considering the results from realistic structural analysis. This paper presents an efficient modelling strategy for representing the nonlinear response of unreinforced masonry components under in‐plane cyclic loading, which can be used for practical and accurate seismic assessment of masonry buildings. According to the proposed strategy, generic masonry perforated walls are modelled using an equivalent frame approach, where each masonry component is described utilising multi‐spring nonlinear elements connected by rigid links. When modelling piers and spandrels, nonlinear springs are placed at the two ends of the masonry element for describing the flexural behaviour and in the middle for representing the response in shear. Specific hysteretic rules allowing for degradation of stiffness and strength are then used for modelling the member response under cyclic loading. The accuracy and the significant potential of the proposed modelling approach are shown in several numerical examples, including comparisons against experimental results and the nonlinear dynamic analysis of a building structure. Copyright © 2016 John Wiley & Sons, Ltd.
Seasonal changes in the sediment flux on steep hillslopes in a humid diurnal frost environment
Authors: Imaizumi Fumitoshi , Suzuki Osamu , Togari‐Ohta Asako
Published: May 2016

Mountain hillslopes are generally shaped by a combination of various types of sediment transport processes (e.g. surface erosion, soil creep, and dry ravel), which can occur simultaneously in the same area. Since sediment transport is generally affected by multiple microclimatic factors, such as heavy rainfall and changes in ground temperature, the types of predominant sediment transport processes vary by season. We conducted field observations in the southern Japanese Alps in the period from 2009 to 2013, using sediment traps and time lapse cameras, to investigate the seasonal changes in the type and flux of hillslope sediment transport on steep mountains in which both rainfall and diurnal freeze–thaw triggered sediment transport. In winter and early spring, sediment transport via diurnal freeze–thaw (soil creep and dry ravel) was highly active, whereas rainfall‐induced soil creep and selective transport by overland flow were active in summer and autumn when precipitation is abundant (average sediment flux of 0.033 and 0.074 kg m−1 day−1, respectively). Sediment flux was spatially variable and was affected by the form of the slope; sediment flux on the concave slope was higher than on the ridge‐shaped slope during both freeze–thaw and rainfall periods. Sediment flux on an old landslide exceeded that in second‐growth forest regardless of the slope shape. Temporal changes in the sediment flux were not completely synchronized among monitoring plots and were affected by slope shape, grain size, and episodic sediment supply events such as release of sediment from woody debris. Copyright © 2016 John Wiley & Sons, Ltd.
Properties of pumice aggregate concretes at elevated temperatures and comparison with ANN models
Authors: Türkmen İbrahim , Bingöl A. Ferhat , Tortum Ahmet , Demirboğa Ramazan , Gül Rüstem
Published: May 2016

The mechanical properties and thermal conductivity of concretes including pumice aggregate (PA) exposed to elevated temperature were analyzed by thermal conductivity, compressive strength, flexure strength, dynamic elasticity modulus (DEM) and dry unit weight tests. PA concrete specimens were cast by replacing a varying part of the normal aggregate (0–2 mm) with the PA. All concrete samples were prepared and cured at 23 ± 10C lime saturated water for 28 days. Compressive strength of concretes including PA decreased that reductions were 14, 19, 25 and 34% for 25, 50, 75 and 100% PA, respectively. The maximum thermal conductivity of 1.9382 W/mK was observed with the control samples containing normal aggregate. The tests were carried out by subjecting the samples to a temperature of 0, 100, 200, 300, 400 500, 600 and 700 °C for 3 h, then cooling by air cooling or in water method. The results indicated that all concretes exposed to a temperature of 500 and 700 °C occurred a significant decrease in thermal conductivity, compressive strength, flexure strength and DEM. An artificial neural network (ANN) approach was used to model the thermal and mechanical properties of PA concretes. The predicted values of the ANN were in accordance with the experimental data. The results indicate that the model can predict the concrete properties after elevated temperatures with adequate accuracy. Copyright © 2016 John Wiley & Sons, Ltd.
BRCA1‐2 diagnostic workflow from next‐generation sequencing technologies to variant identification and final report
Authors: Pilato Brunella , Pinto Rosamaria , De Summa Simona , Petriella Daniela , Lacalamita Rosanna , Danza Katia , Paradiso Angelo , Tommasi Stefania
Published: May 2016

The BRCA1‐BRCA2 genes predispose to hereditary breast and ovarian cancer, and the germline and mutational status of these genes defines a target population that can benefit from PARP inhibitor treatments. To respond to the increasing number of BRCA1‐BRCA2 tests, it is necessary to shift to high‐throughput technologies that are reliable and less time consuming. Different methodological platforms are dedicated to this purpose with different approaches and algorithms for analysis. Our aim was to set up a cost‐effective and low time‐consuming BRCA1‐BRCA2 mutation detection workflow using the Ion Torrent PGM technology. A retrospective cohort of 40 patients with familial breast/ovarian cancer previously tested by Sanger sequencing and a prospective cohort of 72 patients (validation set) were analyzed. The validation set included 64 patients affected by familial breast/ovarian cancer and eight sporadic ovarian cancer cases, who are potential candidates for PARPi treatments. A complete and standardized workflow easily usable and suitable in a certified laboratory has been proved and validated. This includes all steps from library preparation to the final report. The use of next‐generation sequencing will be of benefit for patients enrolled in the genetic counseling process and, moreover, will enhance the process of selecting patients eligible for personalized treatments. © 2016 Wiley Periodicals, Inc.
Adipocyte‐specific overexpression of retinol‐binding protein 4 causes hepatic steatosis in mice
Authors: Lee Seung‐Ah , Yuen Jason J. , Jiang Hongfeng , Kahn Barbara B. , Blaner William S.
Published: May 2016

There is considerable evidence that both retinoids and retinol‐binding protein 4 (RBP4) contribute to the development of liver disease. To understand the basis for this, we generated and studied transgenic mice that express human RBP4 (hRBP4) specifically in adipocytes. When fed a chow diet, these mice show an elevation in adipose total RBP4 (mouse RBP4 + hRBP4) protein levels. However, no significant differences in plasma RBP4 or retinol levels or in hepatic or adipose retinoid (retinol, retinyl ester, and all‐trans‐retinoic acid) levels were observed. Strikingly, male adipocyte‐specific hRBP4 mice fed a standard chow diet display significantly elevated hepatic triglyceride levels at 3‐4 months of age compared to matched littermate controls. When mice were fed a high‐fat diet, this hepatic phenotype, as well as other metabolic phenotypes (obesity and glucose intolerance), worsened. Because adipocyte‐specific hRBP4 mice have increased tumor necrosis factor‐α and leptin expression and crown‐like structures in adipose tissue, our data are consistent with the notion that adipose tissue is experiencing RBP4‐induced inflammation that stimulates increased lipolysis within adipocytes. Our data further establish that elevated hepatic triglyceride levels result from increased hepatic uptake of adipose‐derived circulating free fatty acids. We obtained no evidence that elevated hepatic triglyceride levels arise from increased hepatic de novo lipogenesis, decreased hepatic free fatty acid oxidation, or decreased very‐low‐density lipoprotein secretion. Conclusion: Our investigations establish that RBP4 expressed in adipocytes induces hepatic steatosis arising from primary effects occurring in adipose tissue. (Hepatology 2016;64:1534‐1546)
Circulating let‐7 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C
Authors: Matsuura Kentaro , De Giorgi Valeria , Schechterly Cathy , Wang Richard Y. , Farci Patrizia , Tanaka Yasuhito , Alter Harvey J.
Published: May 2016

The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular vesicles (EVs) were optimal for miRNA measurement and their correlation with hepatic miRNA expression, and the mechanistic plausibility of this association. We studied 130 CHC patients prospectively followed over several decades. A comprehensive miRNA profile in plasma using microarray with 2578 probe sets showed 323 miRNAs differentially expressed between healthy individuals and CHC patients, but only six that distinguished patients with mild versus severe chronic hepatitis. Eventually, let‐7a/7c/7d‐5p and miR‐122‐5p were identified as candidate predictors of disease progression. Cross‐sectional analyses at the time of initial liver biopsy showed that reduced levels of let‐7a/7c/7d‐5p (let‐7s) in plasma were correlated with advanced histological hepatic fibrosis stage and other fibrotic markers, whereas miR‐122‐5p levels in plasma were positively correlated with inflammatory activity, but not fibrosis. Measuring let‐7s levels in EVs was not superior to intact plasma for discriminating significant hepatic fibrosis. Longitudinal analyses in 60 patients with paired liver biopsies showed that let‐7s levels in plasma markedly declined over time in parallel with fibrosis progression. However, circulating let‐7s levels did not parallel those in the liver. Conclusion: Of all miRNAs screened, the let‐7 family showed the best correlation with hepatic fibrosis in CHC. A single determination of let‐7s levels in plasma did not have superior predictive value for significant hepatic fibrosis compared with that of fibrosis‐4 index, but the rate of let‐7s decline in paired longitudinal samples correlated well with fibrosis progression. Pathway analysis suggested that low levels of let‐7 may influence hepatic fibrogenesis through activation of transforming growth factor β signaling in hepatic stellate cells. (Hepatology 2016;64:732‐745)
Stem/progenitor cells in liver regeneration
Authors: Itoh Tohru
Published: May 2016

In severely or chronically injured livers where the proliferative capacity of hepatocytes is compromised, putative stem/progenitor cells are supposed to be activated. These cells are generally characterized as biliary epithelial cell marker‐positive cells that emerge ectopically in the parenchymal region of the liver, as determined by histopathological examination of various liver diseases in humans and animal models. Whereas the biliary system indeed harbors cells with stem/progenitor activity that can be defined ex vivo, genetic lineage tracing studies in mice have casted doubt on their exact contribution as the genuine stem/progenitor cell population that differentiates in situ into hepatocytes. Here, I briefly review recent advances in the characterization and certification of the stem/progenitor cells in the adult liver and discuss the ongoing and future challenges to further our understanding of the cellular basis of liver regeneration. (Hepatology 2016;64:663‐668)
Assessing the role of insulin‐like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels
Authors: Bonilla Carolina , Lewis Sarah J. , Rowlands Mari‐Anne , Gaunt Tom R. , Davey Smith George , Gunnell David , Palmer Tom , Donovan Jenny L. , Hamdy Freddie C. , Neal David E. , Eeles Rosalind , Easton Doug , Kote‐Jarai Zsofia , Al Olama Ali Amin , Benlloch Sara , Muir Kenneth , Giles Graham G. , Wiklund Fredrik , Grönberg Henrik , Haiman Christopher A. , Schleutker Johanna , Nordestgaard Børge G. , Travis Ruth C. , Pashayan Nora , Khaw Kay‐Tee , Stanford Janet L. , Blot William J. , Thibodeau Stephen , Maier Christiane , Kibel Adam S , Cybulski Cezary , Cannon‐Albright Lisa , Brenner Hermann , Park Jong , Kaneva Radka , Batra Jyotsna , Teixeira Manuel R. , Pandha Hardev ,   the PRACTICAL consortium, Lathrop Mark , Martin Richard M. , Holly Jeff M. P.
Published: May 2016

Circulating insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome‐wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF‐II and IGFBP‐3, less so for IGF‐I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF‐II/IGFBP‐3 level‐raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF‐II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.
Roughness gradients on zirconia for rapid screening of cell‐surface interactions: Fabrication, characterization and application
Authors: Flamant Quentin , Stanciuc Ana‐Maria , Pavailler Hugo , Sprecher Christoph Martin , Alini Mauro , Peroglio Marianna , Anglada Marc
Published: May 2016

Roughness is one of the key parameters for successful osseointegration of dental implants. The understanding of how roughness affects cell response is thus crucial to improve implant performance. Surface gradients, which allow rapid and systematic investigations of cell‐surface interactions, have the potential to facilitate this task. In this study, a novel method aiming to produce roughness gradients at the surface of zirconia using hydrofluoric acid etching was implemented. The topography was exhaustively characterized at the microscale and nanoscale by white light interferometry and atomic force microscopy, including the analysis of amplitude, spatial, hybrid, functional, and fractal parameters. A rapid screening of the influence of roughness on human mesenchymal stem cell morphology was conducted and potential correlations between roughness parameters and cell morphology were investigated. The roughness gradient induced significant changes in cell area (p < 0.001), aspect ratio (p = 0.01), and solidity (p = 0.026). Nanoroughness parameters were linearly correlated to cell solidity (p < 0.005), while microroughness parameters appeared nonlinearly correlated to cell area, highlighting the importance of multiscale optimization of implant topography to induce the desired cell response. The gradient method proposed here drastically reduces the efforts and resources necessary to study cell‐surface interactions and provides results directly transferable to industry. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2502–2514, 2016.
Pharmacokinetics and Pharmacodynamics of Omarigliptin, a Once‐Weekly Dipeptidyl Peptidase‐4 (DPP‐4) Inhibitor, After Single and Multiple Doses in Healthy Subjects
Authors: Krishna Rajesh , Addy Carol , Tatosian Daniel , Glasgow Xiaoli S. , Gendrano III Isaias Noel , Robberechts Martine , Haazen Wouter , de Hoon J.N. , Depré Marleen , Martucci Ashley , Peng Joanna Z. , Johnson‐Levonas Amy O. , Wagner John A. , Stoch S. Aubrey
Published: May 2016

The pharmacokinetics (PK) and pharmacodynamics (PD) of omarigliptin, a novel once‐weekly DPP‐4 inhibitor, were assessed following single and multiple doses in healthy subjects. Absorption was rapid, and food did not influence single‐dose PK. Accumulation was minimal, and steady state was reached after 2 to 3 weeks. Weekly (area under the curve) AUC and Cmax displayed dose proportionality within the dose range studied at steady state. The average renal clearance of omarigliptin was ∼2 L/h. DPP‐4 inhibition ranged from ∼77% to 89% at 168 hours following the last of 3 once‐weekly doses over the dose range studied. Omarigliptin resulted in ∼2‐fold increases in weighted average postprandial active GLP‐1. Omarigliptin acts by stabilizing active GLP‐1, which is consistent with its mechanism of action as a DPP‐4 inhibitor. Administration of omarigliptin was generally well tolerated in healthy subjects, and both the PK and PD profiles support once‐weekly dosing. A model‐based assessment of QTc interval risk from the single ascending dose study predicted a low risk of QTc prolongation within the likely clinical dose range, a finding later confirmed in a thorough QT trial.
Mild cognitive impairment is prevalent in persons with severe obesity
Authors: Rochette Amber D. , Spitznagel Mary Beth , Strain Gladys , Devlin Michael , Crosby Ross D. , Mitchell James E. , Courcoulas Anita , Gunstad John
Published: May 2016

Objective

This study examines the prevalence of mild cognitive impairment (MCI) in a sample of adults with severe obesity and whether undergoing bariatric surgery reduces the frequency of MCI.

Methods

A total of 171 participants with severe obesity (mean age = 43.07 ± 11.21) completed computerized cognitive testing. A subset of participants underwent bariatric surgery as part of the Longitudinal Assessment of Bariatric Surgery project. MCI was operationalized using commonly used criteria to establish prevalence in the overall sample and to examine possible changes after bariatric surgery.

Results

More than half of the overall sample met criteria for MCI at baseline (53.8%), and MCI was prevalent even in young and middle‐aged adults with severe obesity. Within the subset of participants who underwent bariatric surgery, the prevalence of MCI was reduced by 48.9% at 12‐month follow‐up (from 53.4% to 27.3%).

Conclusions: Findings suggest that many individuals with severe obesity meet criteria for MCI and that prevalence rates decline after bariatric surgery. A better understanding of the mechanisms linking severe obesity to adverse neurological outcomes is much needed.
Double‐Gloving Impairs the Quality of Surgical Knot Tying: A Randomised Controlled Trial
Authors: Battersby Christopher L. F. , Battersby Nicholas J. , Hollyman Marianne , Hunt John A.
Published: May 2016

Background

Double‐gloving is endorsed by a number of healthcare authorities worldwide, on the basis that it promotes patient and surgeon safety; adoption of this practice amongst surgeons remains limited, based upon anecdotal reporting that double‐gloving may compromise surgical technique due to impaired dexterity and sensation. The aim of this study is to formally investigate and demonstrate the effect of double‐gloving upon the quality of knot tying, an essential surgical skill.

Methods

An international cohort of practising general surgeons hand tied surgical knots, under both single‐gloved and double‐gloved conditions, using monofilament and braided sutures, at two different gauges. Half of the participants tied single‐gloved first. The mechanical strength of the knots was determined by tensile testing, and each knot was given a knot quality score (KQS), a validated assessment of knot quality.

Results and conclusions

1466 knots were tested. Double‐gloving was shown to reduce KQS for all suture types, compared to knots tied under single‐gloved conditions (p = 0.001). There was no difference in the KQS of the double‐gloved ties between those who routinely double‐gloved and those who did not (p = 0.640). The OR showed that double‐gloving reduced the KQS by 24 % overall, with the effect being much more prominent when the finer 4.0 suture was used, as knot quality was reduced by almost 50 % (95 % CI 13–93 %). Double‐gloving impairs the quality of knot tying, and therefore, surgeons should consider other precautions to ensure patient and surgeon safety. These findings also question the validity of recommendations that surgeons should double‐glove as a routine.
The Impact of Angelina Jolie (AJ)'s Story on Genetic Referral and Testing at an Academic Cancer Centre in Canada
Authors: Raphael Jacques , Verma Sunil , Hewitt Paul , Eisen Andrea
Published: May 2016

In May 2013, Angelina Jolie revealed to the media that she had undergone preventive double mastectomy after testing positive for a BRCA1 gene mutation. Media coverage has been extensive, but it is not clear how such a personal story affected the public and cancer genetics clinics. We conducted a retrospective review using data from the clinical database of the Familial Cancer Program at our centre. The impact of Ms. Jolie's story on genetic counseling referrals and the appropriateness of such referrals were assessed and reported. The number of women referred for genetic counseling increased by 90 % after 6 months and remained high one year after AJ's story with an increase of 88 % from baseline. The number of women who qualified for genetic testing increased by 105 % after 6 months; this increase persisted but was somewhat lower after one year with an increase of 68 % from baseline. Furthermore the number of BRCA1/2 carriers identified increased by 110 % after 6 months and by 42 % after one year.

The effect of Mrs. Jolie's story persisted one year after its release; however in the latter half of the year, the hereditary cancer risk of referred women was significantly lower than initially observed. The next challenge for our health care system will not only be to meet the increased demand for cancer genetic services in our region, but also to ensure that referrals and hence use of genetic counseling resources are appropriate.
Hepatitis C virus treatment update — A new era of all‐oral HCV treatment
Authors: Chayama Kazuaki , Imamura Michio , Hayes C. Nelson
Published: May 2016

There are estimated to be more than a hundred million hepatitis C virus (HCV) carriers worldwide. About 30% of carriers develop serious liver diseases, such as liver cirrhosis and hepatocellular carcinoma. HCV Genotype 1 is the most common genotype worldwide and the most difficult to treat with interferon‐based therapy. Therapy for patients with chronic HCV infection is complicated by poor tolerability and inadequate rates of sustained virological response (SVR). Although the addition of a protease inhibitor in combination with peg‐interferon alpha plus ribavirin improved SVR rates and shortened the treatment period, many patients could not tolerate this therapy because of advanced age and clinical conditions such as anemia and low platelet count. Interferon‐free therapies that combine two or more direct‐acting antiviral (DAA) agents can improve both efficacy and tolerability. Phase III trials of daclatasvir plus asunaprevir, ombitasvir plus parataprevir/r, and sofosbuvir plus ledipasvir all showed high overall SVR rates with few adverse events. However, development of antiviral resistance is a concern with DAA therapies, and it is important to avoid treating patients with existing NS5A Y93H mutations with daclatasvir plus asunaprevir or ombitasvir plus parataprevir/r therapy to prevent viral breakthrough. Fortunately, sofosbuvir plus ledipasvir therapy seems to be less affected by NS5A Y93H variants. An important goal of HCV therapy is to expand treatment to all patients. The current study aims to show the efficacy and safety of these therapies both in clinical trial and real world settings based on our own clinical experiences.
Platinum-group minerals in dolerites from Alexandra Land Island (Franz Josef Land Archipelago)
Authors: Sklyarov E.V. , Karyakin Yu.V. , Karmanov N.S. , Tolstykh N.D.
Published: May 2016

Lavas in Alexandra Land Island of the Franz Josef Land Archipelago bear Au-Cu-Pd-type mineralization. The found mineral species belong to the Cu–Au–Pd and Pd–Cu–(Te + Sb + S + As) systems being, respectively, (i) cuproauride (Au(Cu, Pd)) and auricupride (Au(Cu,Pd)3) and (ii) phases similar to skaergaardite (PdCu), nielsenite (PdCu3), and numerous S–Te–Sb–Pd–Cu phases of various compositions. The morphology of PGM existing as tiny grains and films along the boundaries of plagioclase and clinopyroxene and in cracks, their crystallization at low temperatures predicted by experimental data, and the presence of native copper with sulfur impurity are signatures of postmagmatic origin. The Alexandra Land tholeiitic basalts and dolerites were, most likely, produced by the hotspot which may be the source of PGE-bearing intrusions in eastern Greenland that contain PGM similar to those discussed in the paper.
Innovative Regulation through Competition: A Response to Rapidly Evolving Markets
Authors: Baum Ido
Published: May 2016

How can regulators keep up with sea changes in dynamic markets? This article proposes the use of competitive forces to generate innovative regulation. In markets where national, social, cultural, economic or other interests must be maintained in the face of evolving risks, heightened uncertainties and dynamic technological developments, regulators have to learn by doing.

This article proposes the novel concept of intra-regulatory competition (IRC), a powerful method for developing innovative regulatory solutions by staging a contest between different regulatory regimes imposed simultaneously on market participants in a given jurisdiction. The article describes the principles of and justifications for IRC, conditions for its effective implementation, its potential benefits and drawbacks. IRC is analysed against the backdrop of similar concepts such as randomised law, experimental law and inter-jurisdictional competition. Finally, the article argues that the regulation of media content in order to promote cultural pluralism and the regulation of computerised trading in securities and futures markets are fields that are ripe for and compatible with the application of IRC.
Taxonomic survivorship curves and Van Valen's Law
Authors: Raup David M.
Published: May 2016

As Van Valen has demonstrated, the taxonomic survivorship curve is a valuable means of investigating extinction rates in the fossil record. He suggested that within an adaptive zone, related taxa display stochastically constant and equal extinction rates. Such a condition is evidenced by straight survivorship curves for species and higher taxa. Van Valen's methods of survivorship analysis can be improved upon and several suggestions are presented. With proper manipulation of data, it is possible to pool the information from extinct and living taxa to produce a single survivorship curve and therefore a single estimate of extinction rate. If extinction rate is constant at the species level (producing a straight survivorship curve), higher taxa in the same group should be expected to have convex survivorship curves. The constancy of extinction rates (here termed Van Valen's Law) can and should be tested rigorously. Several methods are available, of which the Total Life method of Epstein is particularly effective.
A review of fighting adaptations in dinocephalians (Reptilia, Therapsida)
Authors: Barghusen Herbert R.
Published: May 2016

The cranial structure of anteosaurid and many tapinocephalid dinocephalians became modified in a manner consistent with Geist's hypothesis that they used their heads for pushing and ramming during intraspecific combat. These modifications are most pronounced in certain tapinocephalids by the evolution of a strong dorsal head shield supported by a massive arch network suitable for receiving and supporting blows delivered to the dorsal surface of the head. The position of the occipital condyle reduced the torque created by such blows at the craniocervical joint. Evidence also indicates that the head was reoriented into a position suitable for butting. The cranial architecture displayed by dinocephalians suspected of headbutting differs from that of living mammalian rammers. The differences can be directly attributed to the modification, in the former, of a reptilian skull with its relatively unexpanded braincase into a ramming instrument.
Levoatriocardinal vein in D-transposition of the great arteries
Authors: Moodley Shreya , Duncan Walter , Gandhi Sanjiv
Published: May 2016

The levoatriocardinal vein is the embryological remnant of the connection between the pulmonary and systemic venous systems. It is a rare lesion that usually occurs in the presence of left-sided obstruction, developing as a pathway for decompression of the pulmonary veins. We report the first case of a levoatriocardinal vein in a patient with D-transposition of the great arteries.
Bringing Objectification into Social Relationships Research: Is Self-Objectification Harmful for Authenticity?
Authors: Rollero Chiara
Published: May 2016

Self-objectification is a pervasive process in contemporary Western societies and psychological literature has largely shown its negative consequences in terms of body shame, appearance anxiety, mental health and performance. Mass media play a key role in promoting such process through the extensive sexualization of individuals’ body and the separation of sexualized body parts from the rest of the body. The purpose of the present study was to extend past research by examining the effects of self-objectification in the context of social relationships among young adults. Participants were 235 undergraduates (55.7% females). A three-step model was successfully tested: results showed that internalization of media standards is related to increased self-objectification (β = .33, SE = .08, p = .01), which in turn is associated with authenticity, being high self-objectifiers less devoted to authentic living (β = –.21, SE = .09, p = .01) and more self-alienated (β = .14, SE = .08, p = .04) and dependent on others’ influence (β = .50, SE = .01, p = .01). The pattern of these relationships did not significantly vary across gender (χ2 = 6.29; p = .18). Implications concerning the impact of self-objectification in the domain of social relationships are discussed.
Stereotype Threat in der Grundschule
Authors: Hermann Johanna Maria , Vollmeyer Regina
Published: May 2016

Zusammenfassung. Das Ziel der Studie war es zu untersuchen, ob bereits Grundschulkinder von Stereotype-Threat- beziehungsweise Lift-Effekten in ihrer Mathematikleistung beeinflusst werden. Dazu wurde auf eine implizite Manipulation zurückgegriffen, um Geschlechtsstereotype zu aktivieren, bevor ein Mathematiktest absolviert wurde. Bei Mädchen sollte die Aktivierung zu einer schlechteren Leistung führen, während für Jungen ein Leistungsvorsprung erwartet wurde. An der Untersuchung nahmen 120 Viertklässler teil (66 männlich, 54 weiblich, Alter M = 9.24, SD = 0.61). Hypothesenkonform ergab sich eine signifikante Interaktion zwischen Geschlecht und Stereotypaktivierung bei schwierigen Aufgaben. Während Mädchen in der Stereotypgruppe schlechter abschnitten als Mädchen in der Kontrollgruppe, konnte bei den Jungen kein Leistungsunterschied beobachtet werden. Die Ergebnisse bestätigen, dass Geschlechtsstereotype implizit bereits in der Grundschule die Mathematikleistung von Mädchen beeinträchtigen können.
Storms Cause Infrequent Turbulence for Aircraft, New Study Finds
Authors: Deatrick Elizabeth
Published: May 2016

Scientists using lightning sensors to automate air-turbulence detection have found evidence that storms jostle aircraft much less than previously thought.
Generating giant and tunable nonlinearity in a macroscopic mechanical resonator from a single chemical bond
Authors: Huang Pu , Zhou Jingwei , Zhang Liang , Hou Dong , Lin Shaochun , Deng Wen , Meng Chao , Duan Changkui , Ju Chenyong , Zheng Xiao , Xue Fei , Du Jiangfeng
Published: May 2016

Nonlinearity in macroscopic mechanical systems may lead to abundant phenomena for fundamental studies and potential applications. However, it is difficult to generate nonlinearity due to the fact that macroscopic mechanical systems follow Hooke’s law and respond linearly to external force, unless strong drive is used. Here we propose and experimentally realize high cubic nonlinear response in a macroscopic mechanical system by exploring the anharmonicity in chemical bonding interactions. We demonstrate the high tunability of nonlinear response by precisely controlling the chemical bonding interaction, and realize, at the single-bond limit, a cubic elastic constant of 1 × 1020 N m−3. This enables us to observe the resonator’s vibrational bi-states transitions driven by the weak Brownian thermal noise at 6 K. This method can be flexibly applied to a variety of mechanical systems to improve nonlinear responses, and can be used, with further improvements, to explore macroscopic quantum mechanics.