bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Synthesis, and Evaluation of Novel Ferroquine and Phenylequine Analogues as Potential Antiplasmodial Agents
Authors: Jacobs Leon , de Kock Carmen , de Villiers Katherine A. , Smith Peter J. , Smith Vincent J. , van Otterlo Willem A. L. , Blackie Margaret A. L.
Published: October 2015

7‐Chloroquinoline‐based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine‐sensitive (CQS) NF54 (IC50: 4.2 nm) and chloroquine‐resistant (CQR) Dd2 (IC50: 33.7 nm) strains of P. falciparum. Several compounds were found to have good inhibitory activity against β‐hematin formation in an NP‐40 detergent assay, with IC50 values ranging between 10.4 and 19.2 μm.
Synthesis and Biological Evaluation of Novel Epothilone B Side Chain Analogues
Authors: Nicolaou K. C. , Rhoades Derek , Wang Yanping , Totokotsopoulos Sotirios , Bai Ruoli , Hamel Ernest
Published: October 2015

The design, synthesis, and biological evaluation of a series of epothilone analogues with novel side chains equipped with an amino group are described. Their design facilitates potential conjugation to selective drug delivery systems such as antibodies. Their synthesis proceeded efficiently via Stille coupling of a readily available vinyl iodide and heterocyclic stannanes. Cytotoxicity studies and tubulin binding assays revealed two of these analogues to be more potent than epothilones A–D and the anticancer agent ixabepilone, currently in clinical use.
Risk factors for refeeding hypophosphatemia in Japanese inpatients with anorexia nervosa
Authors: Kameoka Naomi , Iga Jun‐ichi , Tamaru Mai , Tominaga Takeo , Kubo Hiroko , Watanabe Shin‐Ya , Sumitani Satsuki , Tomotake Masahito , Ohmori Tetsuro
Published: October 2015

Objective

Refeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome, which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN.

Methods

We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years; range, 9 − 56 years).

Results

RH (phosphate < 2.3 mg/dL) occurred within 4.8 ± 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at Day 3 when her serum phosphate level was 1.6 mg/dL.

Conclusions

The significant risk factors for RH that we identified were lower body mass index, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for more than 5 days after admission. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:402–406).
Effects of fasting and nutritional restriction on the isotopic ratios of nitrogen and carbon: a meta‐analysis
Authors: Hertz Eric , Trudel Marc , Cox Marlin K. , Mazumder Asit
Published: October 2015

Many organisms experience fasting in their life time, and this physiological process has the potential to alter stable isotope values of organisms, and confound interpretation of food web studies. However, previous studies on the effects of fasting and starvation on stable isotopes show disparate results, and have never been quantitatively synthesized. We performed a laboratory experiment and meta‐analysis to determine how stable isotopes of δ15N and δ13C change with fasting, and we tested whether moderators such as taxa and tissue explain residual variation. We collected literature data from a wide variety of taxa and tissues. We surveyed over 2000 papers, and of these, 26 met our selection criteria, resulting in 51 data points for δ15N, and 43 data points for δ13C. We determine that fasting causes an average increase in the isotopic value of organisms of 0.5‰ for δ15N and that the only significant moderator is tissue type. We find that the overall effect size for δ13C is not significant, but when the significant moderator of tissue is considered, significant increases in blood and whole organisms are seen with fasting. Our results show that across tissues and taxa, the nutritional status of an organism must be considered when interpreting stable isotope data, as fasting can cause large differences in stable isotope values that would be otherwise attributed to other factors.
A comparative approach to testing hypotheses for the evolution of sex‐biased dispersal in bean beetles
Authors: Downey Michelle H. , Searle Rebecca , Bellur Sunil , Geiger Adam , Maitner Brian S. , Ohm Johanna R. , Tuda Midori , Miller Tom E. X.
Published: October 2015

Understanding the selective forces that shape dispersal strategies is a fundamental goal of evolutionary ecology and is increasingly important in changing, human‐altered environments. Sex‐biased dispersal (SBD) is common in dioecious taxa, and understanding variation in the direction and magnitude of SBD across taxa has been a persistent challenge. We took a comparative, laboratory‐based approach using 16 groups (species or strains) of bean beetles (genera Acanthoscelides, Callosobruchus, and Zabrotes, including 10 strains of one species) to test two predictions that emerge from dominant hypotheses for the evolution of SBD: (1) groups that suffer greater costs of inbreeding should exhibit greater SBD in favor of either sex (inbreeding avoidance hypothesis) and (2) groups with stronger local mate competition should exhibit greater male bias in dispersal (kin competition avoidance hypothesis). We used laboratory experiments to quantify SBD in crawling dispersal, the fitness effects of inbreeding, and the degree of polygyny (number of female mates per male), a proxy for local mate competition. While we found that both polygyny and male‐biased dispersal were common across bean beetle groups, consistent with the kin competition avoidance hypothesis, quantitative relationships between trait values did not support the predictions. Across groups, there was no significant association between SBD and effects of inbreeding nor SBD and degree of polygyny, using either raw values or phylogenetically independent contrasts. We discuss possible limitations of our experimental approach for detecting the predicted relationships, as well as reasons why single‐factor hypotheses may be too simplistic to explain the evolution of SBD.
Pattern recognition receptor mediated downregulation of microRNA‐650 fine‐tunes MxA expression in dendritic cells infected with influenza A virus
Authors: Pichulik Tica , Khatamzas Elham , Liu Xiao , Brain Oliver , Delmiro Garcia Magno , Leslie Alasdair , Danis Benedicte , Mayer Alice , Baban Dilair , Ragoussis Jiannis , Weber Alexander N. R. , Simmons Alison
Published: October 2015

MicroRNAs are important posttranscriptional regulators of gene expression, which have been shown to fine‐tune innate immune responses downstream of pattern recognition receptor (PRR) signaling. This study identifies miR‐650 as a novel PRR‐responsive microRNA that is downregulated upon stimulation of primary human monocyte‐derived dendritic cells (MDDCs) with a variety of different microbe‐associated molecular patterns. A comprehensive target search combining in silico analysis, transcriptional profiling, and reporter assays reveals that miR‐650 regulates several well‐known interferon‐stimulated genes, including IFIT2 and MXA. In particular, downregulation of miR‐650 in influenza A infected MDDCs enhances the expression of MxA and may therefore contribute to the establishment of an antiviral state. Together these findings reveal a novel link between miR‐650 and the innate immune response in human MDDCs.
1,2,4‐Triazole‐Based N‐Heterocyclic Carb­ene Nickel Complexes – Synthesis and Catalytic Application
Authors: Bheeter Linus P. , Wei Duo , Dorcet Vincent , Roisnel Thierry , Ghosh Prasenjit , Sortais Jean‐Baptiste , Darcel Christophe
Published: October 2015

Four nickel complexes bearing 1,2,4‐triazole‐based N‐heterocyclic carbene backbones and a cyclopentadienyl ligand were prepared from the corresponding 1,2,4‐triazolium salts and nickelocene in tetrahydrofuran (THF) under reflux. The obtained complexes were fully characterized, including by X‐ray diffraction analysis. They were then used as catalysts (5 mol‐%) for the borylation of aryl bromide derivatives with bis(pinacolato)diboron in the presence of Cs2CO3 as the base in THF at 70 °C for 20 h to form the corresponding borylated products in moderate yields.
Electronic Lability in a Dinuclear Cobalt–Bis(dioxolene) Complex
Authors: Madadi Azadeh , Itazaki Masumi , Gable Robert W. , Moubaraki Boujemaa , Murray Keith S. , Boskovic Colette
Published: October 2015

Remarkable electronic lability is evident from a preliminary study of a dinuclear cobalt complex with a bis(dioxolene) bridging ligand and tetraazamacrocylic ancillary ligands. Structural, magnetic, spectroscopic, and electrochemical data indicate coinciding metal‐ and ligand‐based mixed‐valence involving cobalt(II)/cobalt(III) and catecholate/semiquinonate couples. A thermally stimulated spin‐crossover or valence‐tautomeric transition is also observed above 200 K.
Easy Access to 1H‐Pyrrolo[3′,4′:5,6]pyrido[2,3‐d]pyrimidine‐2,4,6,8(3H,7H)‐tetraone and Selectively N7‐Substituted Analogues through Key Synthons
Authors: Tourteau Aurélien , Merlet Eric , Bontemps Alexis , Leland Mathilde , Helissey Philippe , Giorgi‐Renault Sylviane , Desbène‐Finck Stéphanie
Published: October 2015

To synthesize unsubstituted pyrrolo[3′,4′:5,6] pyrido[2,3‐d]pyrimidine‐2,4,6,8‐tetraone, we have developed new synthon 4‐formyl‐3‐hydroxy‐2,5‐dioxo‐2,5‐dihydro‐1H‐pyrrole, which was then treated under mild conditions with 6‐aminouracil. This new synthetic pathway could be extended to the preparation of N7‐selectively substituted heterocycles by starting either from this new synthon or from its N‐substituted analogues. Examples of N1,N7‐disubstituted and N1,N3,N7‐trisubstituted derivatives are also described. We have thus developed new synthons that lead to easy access to the unsubstituted pyrrolo[3′,4′:5,6]pyrido[2,3‐d]pyrimidine‐2,4,6,8‐tetraone skeleton and to selectively N7‐substituted analogues.
Regioselective [1N+2C+2C] Assembly of Fully Decorated Pyrroles from Primary Amines, 1,2‐Diaza‐1,3‐dienes, and 2,3‐­Allenoates
Authors: Perrulli Francesca R. , Favi Gianfranco , De Crescentini Lucia , Attanasi Orazio A. , Santeusanio Stefania , Mantellini Fabio
Published: October 2015

A mild, sequential multicomponent reaction strategy for the regioselective synthesis of functionalized pentasubstituted pyrroles from readily accessible primary amines, 1,2‐diaza‐1,3‐dienes, and 2,3‐allenoates, has been developed. The process allows a [1N+2C+2C] annulation to be achieved through two sequential hydroamination reactions followed by an enamine‐carbocyclization. Moreover, allenoates, as synthetic equivalents of monoactived alkynes, permit the specific preparation of multifunctionalized pyrroles.
Solvent‐Free Ball‐Milling Biginelli Reaction by Subcomponent Synthesis
Authors: Sahoo Prasit Kumar , Bose Anima , Mal Prasenjit
Published: October 2015

We report here an understanding of systems chemistry on small molecules through covalent mechanochemistry. As a proof‐of‐concept, the multicomponent Biginelli reaction by subcomponent synthesis was considered as a model system. Reactions were performed under solvent‐free, metal‐free, mechanochemical (ball milling) and ambient laboratory conditions. Br+‐catalyzed oxidation of benzyl alcohols led to the product benzaldehydes and byproduct H+ which were further promoted as component and catalyst, respectively, for a cascade transformation to dihydropyrimidones within the same reaction pot. Remarkably, in solution, the reaction system could not be reproduced at room temperature even after 24 h.
A Modular Synthesis of Multidentate S‐, N‐ and O‐Containing Meta‐ and Paracyclophanes
Authors: Rasheed Omer K. , Bailey Patrick D. , Lawrence Amy , Quayle Peter , Raftery James
Published: October 2015

The development of a modular approach to macrocycle assembly has enabled the synthesis of a library of pyridine‐based macrocycles possessing multiple donor sites where chirality was readily introduced from (R)‐ or (S)‐alanine, a representative amino acid. The facile, regioselective, nucleophilic ring opening of aziridines by dithiols enabled the synthesis of thioether‐based linkers which on subsequent alkylation provided access to optically pure macrocycles.
Anxiolytic and antidepressant‐like effects of Ferulago angulata essential oil in the scopolamine rat model of Alzheimer's disease
Authors: Bagci Eyup , Aydin Emel , Mihasan Marius , Maniu Calin , Hritcu Lucian
Published: October 2015

Ferulago angulata subsp. carduchorum (Apiaceae) is a shrub indigenous to western Iran, Turkey and Iraq. In traditional medicine, F. angulata is recommended for treating digestive pains, haemorrhoids, snake bites, ulcers and as a sedative. The present study analysed the possible anxiolytic, antidepressant and antioxidant properties of F. angulata essential oil in a scopolamine‐induced rat model of Alzheimer's disease. The anxiolytic and antidepressant‐like effects of F. angulata essential oil were studied using in vivo (elevated plus‐maze and forced swimming tests) approaches. Also, the antioxidant activity in the amygdala was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. The scopolamine‐treated rats exhibited the following: a decrease in the percentage of the time spent and the number of entries in the open arm within the elevated plus‐maze test and a decrease of swimming time and an increase of immobility time in the forced swimming test. Inhalation of F. angulata essential oil significantly exhibited anxiolytic and antidepressant‐like effects and also antioxidant potential. Furthermore, in silico studies carried out by employing molecular docking experiments pointed to the existence of strong interactions of monoterpenes from F. angulata essential oil with anxiolytic and antidepressant effects with GABAA receptor. Our results suggest that the F. angulata essential oil inhalation ameliorates scopolamine‐induced anxiety and depression by attenuation of the oxidative stress in the rat amygdala. Copyright © 2015 John Wiley & Sons, Ltd.
Bendamustine for relapsed blastic plasmacytoid dendritic cell leukaemia
Authors: Bétrian Sarah , Guenounou Sarah , Luquet Isabelle , Demur Cécile , Huynh Anne , Ysebaert Loïc , Recher Christian , Huguet Françoise
Published: October 2015

Optimal treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare entity of dismal prognosis previously described as CD4+/CD56+ hematodermic malignancies, is not defined. We report five cases of relapsed BPDCN treated with bendamustine hydrochloride, a well‐tolerated bifunctional drug acting as an alkylating and antimetabolite agent. All patients were above the age of 50 years and in advanced disease (early first relapse in two, subsequent relapse in three; multi‐organ involvement in four; previous intensive chemotherapy in five; and stem cell transplantation in four). Four patients were evaluable for response. Two failed therapy, one died from tumor lysis syndrome after rapid blast clearance from blood, and one reached and maintained complete remission for 7 months. Bendamustine should be further evaluated in BPDCN. Copyright © 2015 John Wiley & Sons, Ltd.
Seeing the forest and not the trees: When impact uncertainty heightens causal complexity
Authors: Au Evelyn W. M.
Published: October 2015

This study attempts to isolate the effects of experiencing uncertainty on people's cognitive processes. I argue that people can believe that their actions affect the outcome (i.e. outcome control), but still face uncertainty regarding the extent to which actions will make a difference (i.e. impact uncertainty). To this end, I introduce a novel experimental paradigm which isolates the effects of impact uncertainty from outcome control. The findings revealed that after experiencing impact uncertainty, participants demonstrated greater causal complexity (i.e. more likely to make situational attributions and judge outcomes as having a “ripple effect”), but did not make fewer effort attributions for the outcomes. These findings demonstrate how the experience of impact uncertainty can affect cognitive processing, without compromising outcome control. Implications of these findings for developing more nuanced theories on control and uncertainty are discussed.
Autophagy‐Mediated Degradation of IAPs and c‐FLIPL Potentiates Apoptosis Induced by Combination of TRAIL and Chal‐24
Authors: Xu Jennings , Xu Xiuling , Shi Shaoqing , Wang Qiong , Saxton Bryanna , He Weiyang , Gou Xin , Jang Jun‐Ho , Nyunoya Toru , Wang Xia , Xing Chengguo , Zhang Lin , Lin Yong
Published: October 2015

Combination chemotherapy is an effective strategy for increasing anticancer efficacy, reducing side effects and alleviating drug resistance. Here we report that combination of the recently identified novel chalcone derivative, chalcone‐24 (Chal‐24), and TNF‐related apoptosis‐inducing ligand (TRAIL) significantly increases cytotoxicity in lung cancer cells. Chal‐24 treatment significantly enhanced TRAIL‐induced activation of caspase‐8 and caspase‐3, and the cytotoxicity induced by combination of these agents was effectively suppressed by the pan‐caspase inhibitor z‐VAD‐fmk. Chal‐24 and TRAIL combination suppressed expression of cellular FLICE (FADD‐like IL‐1β‐converting enzyme)‐inhibitory protein large (c‐FLIPL) and cellular inhibitor of apoptosis proteins (c‐IAPs), and ectopic expression of c‐FLIPL and c‐IAPs inhibited the potentiated cytotoxicity. In addition, TRAIL and Chal‐24 cooperatively activated autophagy. Suppression of autophagy effectively attenuated cytotoxicity induced by Chal‐24 and TRAIL combination, which was associated with attenuation of c‐FLIPL and c‐IAPs degradation. Altogether, these results suggest that Chal‐24 potentiates the anticancer activity of TRAIL through autophagy‐mediated degradation of c‐FLIPL and c‐IAPs, and that combination of Chal‐24 and TRAIL could be an effective approach in improving chemotherapy efficacy. J. Cell. Biochem. 117: 1136–1144, 2016. © 2015 Wiley Periodicals, Inc.
Indian hedgehog signaling and the role of graft tension in tendon‐to‐bone healing: Evaluation in a rat ACL reconstruction model
Authors: Carbone Andrew , Carballo Camila , Ma Richard , Wang Hongsheng , Deng Xianghua , Dahia Chitra , Rodeo Scott
Published: October 2015

The structure and composition of the native enthesis is not recapitulated following tendon‐to‐bone repair. Indian Hedgehog (IHH) signaling has recently been shown to be important in enthesis development in a mouse model but no studies have evaluated IHH signaling in a healing model. Fourteen adult male rats underwent ACL reconstruction using a flexor tendon graft. Rats were assigned to two groups based on whether or not they received 0N or 10N of pre‐tension of the graft. Specimens were evaluated at 3 and 6 weeks post‐operatively using immunohistochemistry for three different protein markers of IHH signaling. Quantitative analysis of staining area and intensity using custom software demonstrated that IHH signaling was active in interface tissue formed at the healing tendon‐bone interface. We also found increased staining area and intensity of IHH signaling proteins at 3 weeks in animals that received a pre‐tensioned tendon graft. No significant differences were seen between the 3‐week and 6‐week time points. Our data suggests that the IHH signaling pathway is active during the tendon‐bone healing process and appears to be mechanosensitive, as pre‐tensioning of the graft at the time of surgery resulted in increased IHH signaling at three weeks. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:641–649, 2016.
A meta‐analysis of American black duck winter habitat use along the Atlantic Coast
Authors: Ringelman Kevin M. , Williams Christopher K. , Devers Patrick K. , Coluccy John M. , Castelli Paul M. , Anderson Kurt A. , Bowman Jacob L. , Costanzo Gary R. , Cramer Dane M. , Dibona Matt T. , Eichholz Michael W. , Huang Min , Lewis Benjamin , Plattner Dawn M. , Yerkes Tina
Published: October 2015

American black duck (Anas rubripes) populations declined by more than 50% between the 1950s and 1990s, and the species serves as a flagship for conserving salt marsh habitats along the Atlantic Coast. Black ducks have generally been well studied throughout the annual cycle, but surprisingly, we lack a synthetic, quantitative understanding of their space use during the winter. This limits our ability to prioritize habitat acquisition and restoration efforts. We used >17,000 telemetry locations from 235 black ducks ranging from Connecticut to Virginia to study home range composition and space use during winter in relation to habitat quality, urbanization, and severe weather. Despite substantial environmental variation, home range sizes were similar among regions and years. Smaller home and core ranges contained a greater proportion of salt marsh habitat, and ducks experiencing more 4‐day freeze events had larger home and core ranges. Ducks exposed to prolonged periods of cold weather had smaller core ranges when those areas comprised more energy‐rich freshwater habitats. When we examined individual telemetry locations, we found that ducks used irregularly inundated high marsh more at night, presumably for foraging, and urban habitats more during the day and evening crepuscular periods. We found that black ducks used regularly inundated low marsh less on days where the temperature never rose above freezing, and instead used subtidal areas and forested wetlands more. Finally, we found ducks were marginally more likely to use freshwater habitats during high tides. Our study confirms that black ducks depend on salt marsh for wintering habitat, and points to an unexpectedly important role for forested wetlands during periods of cold weather. We found no evidence that black ducks avoided urban areas or roads, which supports the inclusion of all available habitats in carrying capacity modeling. We emphasize that new hypothesis‐driven, local telemetry studies are needed to further elucidate the relationships between black duck movements and environmental variation, especially cold weather. Further, given that most remaining coastal wetlands are currently protected via state and federal lands, we suggest black duck habitat management should strive to acquire and restore brackish and forested wetlands in close proximity to coastal marshes. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Stress corrosion cracking assessment of API X65 steel non‐conventionally heat treated
Authors: Natividad C. , García R. , López V. H. , Galván‐Martínez R. , Salazar M. , Contreras A.
Published: October 2015

Stress corrosion cracking (SCC) susceptibility of API X65 steel non‐conventionally heat‐treated was evaluated through slow strain rate tests (SSRTs) using the synthetic soil solution NS4 at 20, 40 and 60 °C. Polarization curves (PCs) and corrosion potential (Ecorr) measurements were also performed. The non‐conventional heat treatment (HT) was made by heating plates at 1050 °C for 30 min followed by water quenching. The tensile strength of the heat‐treated plates increased to values similar to API X80 steel. The SCC index obtained by ratios of mechanical properties indicated that X65 steel without HT is not susceptible to SCC whereas with HT is slightly susceptible to SCC. The SCC mechanism in the soil solution in the heat‐treated plates was influenced by hydrogen diffusion as confirmed by the internal cracks and the brittle fracture observed in the specimens. The electrochemical study suggests that the corrosion process of X65 steel with and without HT occurs via a mix mechanism where the charge transfer resistance is influenced by a mass transfer process. Crevice corrosion features were found in the surface of the steel. It is likely that this type of corrosion could have sensitized the X65 steel and induced cracks when the steel was under tensile stress.
Effect of low temperature sensitization on the susceptibility to intergranular corrosion in AA5083 aluminum alloy
Authors: Wei W. , González S. , Hashimoto T. , Prasath Babu R. , Thompson G. E. , Zhou X.
Published: October 2015

The effect of thermal exposure at 70 and 100 °C on intergranular corrosion (IGC) susceptibility of AA5083 alloy has been studied. At both temperatures, metastable β′ phase has been detected at grain boundaries. The thermal exposure resulted in sensitized microstructure in the alloy and, consequently, increased mass loss values during the nitric acid mass loss test (NAMLT). The sensitization of the alloy is related to the formation of the β′ phase. The as‐received O temper alloy showed relatively high resistance to IGC and exhibited a discontinuous distribution of the β′ phase precipitates at grain boundaries. After exposure at 70 °C for 480 h, the size of β′ phase precipitate at the grain boundaries slightly increased, resulting in an increased mass loss. After exposure at 100 °C for 240 h, the alloy became severely sensitized due to the more continuous distribution of β′ phase precipitate along the grain boundaries.
The effect of conversion bath convection on the formation of Zr‐based thin‐film coatings on multi‐metal surfaces
Authors: Cerezo J. , Posner R. , Vandendael I. , de Wit J. H. W. , Terryn H. , Mol J. M. C.
Published: October 2015

The present study investigates the effect of different conversion bath agitation and stirring conditions on the generation of Zr‐based thin film conversion coatings for steel, zinc galvanized steel, and aluminum substrates. Therefore, samples were immersed in a copper containing fluoric acid of zirconium. Film formation was monitored in situ via open circuit potential (OCP) measurements recorded during the pre‐treatment of the samples in solution. The resulting thickness and elemental distribution of the obtained Zr‐based coatings formed with and without stirring were analyzed ex situ by means of high‐resolution Auger electron spectroscopy (AES) depth profiles. Under the studied conditions, the conversion film thickness on AA6014 and cold rolled steel increased three and two times as a result of stirring. For hot dip galvanized steel, a thickness increase of 400% was achieved. The data point at mass transfer as the dominant factor for film formation. In this context, specific relations for each metal substrate type were detected.
The influence of the tempering temperature on hydrogen embrittlement in carbonitrided modified SAE 10B22 steel
Authors: Brandolt C. S. , Gonçalves F. V. , Savaris I. D. , Schroeder R. M. , Malfatti C. F.
Published: October 2015

The modified SAE 10B22 steel has high hardenability, which provides its use in special engineering applications, such as in self‐drilling screws, with carbonitrided layer, quenched and tempered. However, these components are susceptible to hydrogen embrittlement, which can cause damage to structural components. In addition, the study of the behavior regarding to hydrogen embrittlement of components with carbonitrided layer has not been done hitherto. In this work the tempering temperature influence on hydrogen embrittlement of modified SAE 10B22 steel, was evaluated after a carbonitriding process. Standard samples and M4 × 50 screws were tested. A galvanostatic circuit was used for hydrogen charging of the samples, which were characterized by low‐strain tensile test and the samples fracture were analyzed by SEM. The obtained results demonstrate that by lowering tempering temperatures, the hydrogen‐loaded samples presented a greater loss of mechanical properties and greater changes of the micromechanics of fracture. In addition, the geometry of the screw was more prone to the deleterious effects of the hydrogen charging than the conventional specimens.
Functional calculus on real interpolation spaces for generators of C0‐groups
Authors: Haase Markus , Rozendaal Jan
Published: October 2015

We study functional calculus properties of C0‐groups on real interpolation spaces using transference principles. We obtain interpolation versions of the classical transference principle for bounded groups and of a recent transference principle for unbounded groups. Then we show that each group generator on a Banach space has a bounded ‐calculus on real interpolation spaces. Additional results are derived from this.
Review of the Effectiveness of a Consultant Physiotherapy‐Led Musculoskeletal Interface Team: A Welsh Experience
Authors: Candy Elizabeth , Haworth‐Booth Sam , Knight‐Davis Mark
Published: October 2015

Objective

The present service evaluation aimed to assess patients’ experience of the musculoskeletal interface (MSKI) team, evaluate the outcomes of referrals to secondary care and determine if patients returned to secondary musculoskeletal (MSK) care following discharge from the MSKI team.

Methods

Excel spreadsheets were designed for data capture. The survey was undertaken in June 2012. Patients were invited to complete and return the questionnaire. Data were collated and reported. Clinicians were given a list of patient identification numbers for those they had referred to secondary care. Using the patient electronic record system, they checked the outcome as recorded and entered data onto the spreadsheet. Patients who had been discharged between December 2011 and November 2012 were identified, their cases were reviewed and data were entered onto the spreadsheet. The information was then collated and reported.

Results

In June 2012, 415 patients attended clinics, of whom 231 (56%) responded to the patient experience survey. On average, 206 (89%) patients agreed that they were satisfied or highly satisfied with their clinic experience. A total of 2,362 (89%) discharges were reviewed; 1,565 patients (61%) were discharged to their general practitioner (GP) and not referred back to a secondary care surgical or medical service, of these 21% were referred to secondary care by the MSKI team. By 2014, a total of 286 patients had been referred to secondary care by their GP following discharge but only 54 (2%) of whom returned for secondary care assessment for the same condition. Between December 2011 and November 2012, 620 (26%) patients seen in clinic were referred to secondary care; 462 (75%) were referred to orthopaedic surgeons, 66 (11%) to the orthopaedic physician, 44 (8%) to the pain clinic and 48 (1%) to ‘other‘, including neurology, rheumatology, etc.

Conclusion

Physiotherapy‐led multi‐professional teams provide effective management of MSK conditions, and the majority of patients are satisfied with their care. A year to 18 months year following discharge, only 2% of patients returned for secondary care assessment for the same condition. Copyright © 2015 John Wiley & Sons, Ltd.
Genetically modified pig models for neurodegenerative disorders
Authors: Holm Ida E , Alstrup Aage Kristian Olsen , Luo Yonglun
Published: October 2015

Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia–telangiectasia. We also highlight how non‐invasive bioimaging technologies such as positron emission tomography (PET), computer tomography (CT), and magnetic resonance imaging (MRI), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (MAP) approach by using the rapid growth of the ground‐breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). With this approach, we hope to shorten the temporal requirement in generating multiple transgenic pigs, increase the survival rate of founder pigs, and generate genetically modified pigs that will more closely resemble the disease‐causing mutations and recapitulate pathological features of human conditions. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Characteristics of biodegradable poly(butylene succinate) nanocomposites with thermally reduced graphene nanosheets
Authors: Kumari Pallathadka Pramoda , Koh Xue Qi , Khatta Akhila , Luckachan Gisha E. , Mittal Vikas
Published: October 2015

Poly(butylene succinate) (PBS) is a biodegradable aliphatic polyester and is semicrystalline in nature. It has a wide range of engineering applications owing to its attractive combination of good processability and mechanical properties. PBS nanocomposites with graphene nanosheets were prepared by melt compounding. We report on their structure and their thermal, electrical, and mechanical properties. The thermal stability of the nanocomposite increased by 35°C compared with that of neat PBS. The crystallization and melting behavior of the PBS matrix in the presence of dispersed graphene nanosheets were studied by differential scanning calorimetry and polarised optical microscope. We also observed an interesting phenomenon in the PBS/graphene nanocomposites from our FTIR investigation. β‐form of PBS crystals are formed in the composite samples with 5 wt% graphene loading, which otherwise forms in pure PBS only under stress. We observed ∼12% modulus enhancement for 2 wt% PBS/graphene nanocomposites. The electrical conductivity increased to ∼105‐fold for 5 wt% PBS/graphene nanocomposites. POLYM. COMPOS., 38:E42–E48, 2017. © 2015 Society of Plastics Engineers
Postpartum depression, a direct and mediating risk factor for preschool wheeze in girls
Authors: Alton Megan E. , Zeng Yiye , Tough Suzanne C. , Mandhane Piushkumar J. , Kozyrskyj Anita L.
Published: October 2015

Background

Postpartum depression affects over 1 in 10 child‐bearing women. A growing body of evidence links maternal distress during the key developmental stages of infants with poor health outcomes, including wheeze and asthma.

Objective

We sought to investigate whether postpartum depression had an independent association with the development of wheeze in preschool‐aged children. A second a priori objective was to ascertain whether postpartum depression functioned as a mediating factor for associations between wheeze, and prenatal distress and nutrition.

Methods

Data from the Community Perinatal Care Trial on maternal postpartum depression (Edinburgh Postnatal Depression Scale), the dependent variable, wheeze at age 3, and possible confounding factors were obtained for 791 women and their children in Calgary, Canada. Adjusted gender‐specific logistic regression analyses were performed to test the association between postpartum depression and child wheeze, which was independent of maternal distress and vitamin use during pregnancy, pre/postnatal smoking, preterm birth, exclusive breastfeeding duration, daycare attendance, and maternal education. The potential mediating effects of postpartum depression were investigated in a path analysis.

Results

Wheeze at age 3 was almost 5 times more likely in girls of mothers who experienced postpartum depression. Results from a path analysis suggested that postpartum depression has a direct effect on wheeze (beta‐coefficient=0.135, P < 0.05), and also mediates the effects of prenatal distress and vitamin use on wheeze in preschool girls. In boys, only prenatal smoking was a statistically significant predictor of wheeze, mainly through the effects of postnatal smoking.

Conclusions & Clinical Relevance

Postpartum depression may be a risk factor for preschool wheeze among girls in a low risk population, directly and indirectly through prenatal distress and vitamin use. Interventions which target postpartum depression and promote a healthy pregnancy may also reduce the risk of wheeze in children. Pediatr Pulmonol. 2016;51:349–357. © 2015 Wiley Periodicals, Inc.
Investigation of Nitramine‐Based Amorphous Energetics
Authors: Stepanov Victor , Patel Rajen B. , Mudryy Ruslan , Qiu Hongwei
Published: October 2015

To date, the use of high explosives (HEs) has been largely limited to their crystalline forms. The glassy forms of these materials have not received much attention. While the highest density and stability of HEs is only attainable in the crystalline state, the unique properties exhibited by glasses may offer significant practical advantages. In this work, the production and properties of glassy molecular dispersions based on CL‐20 with HMX and polyvinyl acetate additives were investigated. The glassy form was achieved by rapid precipitation of the composite ingredients using spray drying. The role of the additives on glass formation was examined. Characterization revealed multiple novel properties in comparison to the traditional crystalline HE‐based compositions. Differential scanning calorimetry (DSC) analysis showed that in the glassy state the materials have a higher configurational enthalpy, by as much as 42 J g−1. Thermomechanical analysis (TMA) results indicate that the glassy materials undergo a glass transition at around 50 °C, during which a transformation from a rigid to a liquid‐like state occurs. The glasses showed a tendency to crystallize, as was observed with TMA and DSC analysis. It was observed that the stability of the amorphous phase with respect to crystallization improved with increasing pellet density. These findings serve to highlight the unique opportunity presented by glassy energetics to achieve improvements beyond those attainable with traditional crystalline materials.
Pioneer 10 and 11 Spacecraft Anomalous Acceleration in the light of the Nonsymmetric Kaluza–Klein (Jordan–Thiry) Theory
Authors: Kalinowski M. W.
Published: October 2015

The Nonsymmetric Kaluza–Klein (Jordan–Thiry) Theory leads to a model of a modified acceleration that can fit an anomalous acceleration experienced by the Pioneer 10 and 11 spacecraft. The future positions of those spacecrafts are predicted using distorted hyperbolic orbit. A connection between an anomalous acceleration and a Hubble constant is solved in the theory together with a relation to a cosmological constant in CDMΛ model. In the paper we consider an exact solution of a point mass motion in the Solar System under an influence of an anomalous acceleration. We find two types of orbits: periodic and chaotic. Both orbits are bounded. This means there is no possibility to escape from the Solar System. Some possibilities to avoid this conclusion are considered. We resolve also a coincidence between an anomalous acceleration and the cosmological constant using a paradigm of modern cosmology. Relativistic effects and a cosmological drifting of a gravitational constant are considered. The model of an anomalous acceleration does not cause any contradiction with Solar System observations. We give a full statistical analysis of the model. We consider also a full formalism of the Nonsymmetric Jordan–Thiry Theory for the problem and present a relativistic model of an anomalous acceleration. We consider the model for General Relativity approximation, i.e.(). In this model there are no contradictions with General Relativity tests in the Solar System. Pioneer 10/11 spacecrafts will come back in 106years (a time scale of our periodic solutions is 106years). Moreover, almost relativistic or relativistic spacecrafts can escape from the Solar System. We consider also a model of a relativistic acceleration which is more complicated, withtaken into account.
Population Pharmacokinetics and Pharmacodynamics of Lampalizumab Administered Intravitreally to Patients With Geographic Atrophy
Authors: Le KN , Gibiansky L , van Lookeren Campagne M , Good J , Davancaze T , Loyet KM , Morimoto A , Strauss EC , Jin JY
Published: October 2015

Intravitreally administered lampalizumab is an investigational complement inhibitor directed against complement factor D (CFD) for the treatment of geographic atrophy (GA) secondary to age‐related macular degeneration. We sought to develop an integrated ocular and systemic pharmacokinetic/pharmacodynamic model for lampalizumab in patients with GA using the data from the clinical phase I and II studies. The kinetics of lampalizumab and CFD disposition were well described by the combined ocular/serum target‐mediated drug disposition model using a quasi‐steady‐state approximation. This model takes into account the drug, target, and drug–target complex clearance, their transfer rates between ocular and serum compartments, and turnover kinetics of CFD. The constructed model provided a prediction of target occupancy in ocular tissues and supported that the two dosing regimens (10 mg q4w and 10 mg q6w) selected for the phase III studies are expected to be efficacious and able to achieve near‐complete target engagement in the vitreous humor.
Quantitative measurements of internal electric fields with differential phase contrast microscopy on InGaN/GaN quantum well structures
Authors: Lohr Matthias , Schregle Ralph , Jetter Michael , Wächter Clemens , Müller‐Caspary Knut , Mehrtens Thorsten , Rosenauer Andreas , Pietzonka Ines , Strassburg Martin , Zweck Josef
Published: October 2015

Piezoelectric and spontaneous polarization play an essential role in GaN‐based devices. InGaN quantum wells (QWs) in GaN host material, especially grown along the polar c‐direction, exhibit strong internal fields in the QW region due to the indium‐induced strain. An exact knowledge of the electric fields is essential, since they are one of the factors limiting the performance of green LDs and LEDs. Differential phase contrast in a scanning transmission electron microscope enables direct, local, and quantitative measurements of these electric fields. For a multi‐QW sample, it was possible to determine the piezoelectric field in the range of 43–67 MV m−1 with a resolution of 10 MV m−1 ( 10 mV nm−1).
Prediction of large‐for‐gestational‐age neonates: screening by maternal factors and biomarkers in the three trimesters of pregnancy
Authors: Frick A. P. , Syngelaki A. , Zheng M. , Poon L. C. , Nicolaides K. H.
Published: October 2015

Objective

To develop a model based on maternal characteristics and medical history (maternal factors) for the prediction of delivery of large‐for‐gestational‐age (LGA) neonates, and to examine the potential value of first‐, second‐ and third‐trimester fetal biometry and biomarkers in improving such a model.

Methods

This was a screening study in 76 300, 54 999, 25 727 and 6181 singleton pregnancies at 11–13, 19–24, 30–34 and 35–37 weeks' gestation, respectively. The a‐priori risk for LGA with birth weight > 95th percentile (LGA > 95th) was calculated using multivariable logistic regression analysis to determine which of the maternal factors had a significant contribution. Regression analysis was then used to determine whether screening by a combination of maternal factors, fetal biometry and various biophysical and biochemical markers had significant contribution in predicting delivery of LGA neonates.

Results

The likelihood of LGA > 95th increased with increasing maternal weight and height and was lower in women of Afro‐Caribbean and South Asian racial origins, in cigarette smokers and in nulliparous women. The risk was higher in women with pre‐existing diabetes mellitus Type I and lower in those with chronic hypertension. In parous women, the risk increased with birth‐weight Z‐score in previous pregnancy and prior history of gestational diabetes and decreased with interpregnancy interval. Screening by maternal factors at 11–13 weeks predicted 32%, 44% and 60% of LGA > 95th at false‐positive rates (FPRs) of 5%, 10% and 20%, respectively. With the addition of fetal biometry, the detection rates improved to 37%, 51% and 68% at 19–24 weeks, 50%, 65% and 81% at 30–34 weeks and 60%, 73% and 85% at 35–37 weeks at FPRs of 5%, 10% and 20%, respectively. The addition of biomarkers did not improve the detection rates achieved when screening by a combination of maternal factors and fetal biometry.

Conclusion

Combined screening by maternal factors and fetal biometry can predict a high proportion of pregnancies that will deliver LGA neonates. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Genome engineering: Drosophila melanogaster and beyond
Authors: Venken Koen J. T. , Sarrion‐Perdigones Alejandro , Vandeventer Paul J. , Abel Nicholas S. , Christiansen Audrey E. , Hoffman Kristi L.
Published: October 2015

A central challenge in investigating biological phenomena is the development of techniques to modify genomic DNA with nucleotide precision that can be transmitted through the germ line. Recent years have brought a boon in these technologies, now collectively known as genome engineering. Defined genomic manipulations at the nucleotide level enable a variety of reverse engineering paradigms, providing new opportunities to interrogate diverse biological functions. These genetic modifications include controlled removal, insertion, and substitution of genetic fragments, both small and large. Small fragments up to a few kilobases (e.g., single nucleotide mutations, small deletions, or gene tagging at single or multiple gene loci) to large fragments up to megabase resolution can be manipulated at single loci to create deletions, duplications, inversions, or translocations of substantial sections of whole chromosome arms. A specialized substitution of chromosomal portions that presumably are functionally orthologous between different organisms through syntenic replacement, can provide proof of evolutionary conservation between regulatory sequences. Large transgenes containing endogenous or synthetic DNA can be integrated at defined genomic locations, permitting an alternative proof of evolutionary conservation, and sophisticated transgenes can be used to interrogate biological phenomena. Precision engineering can additionally be used to manipulate the genomes of organelles (e.g., mitochondria). Novel genome engineering paradigms are often accelerated in existing, easily genetically tractable model organisms, primarily because these paradigms can be integrated in a rigorous, existing technology foundation. The Drosophila melanogaster fly model is ideal for these types of studies. Due to its small genome size, having just four chromosomes, the vast amount of cutting‐edge genetic technologies, and its short life‐cycle and inexpensive maintenance requirements, the fly is exceptionally amenable to complex genetic analysis using advanced genome engineering. Thus, highly sophisticated methods developed in the fly model can be used in nearly any sequenced organism. Here, we summarize different ways to perform precise inheritable genome engineering using integrases, recombinases, and DNA nucleases in the D. melanogaster. WIREs Dev Biol 2016, 5:233–267. doi: 10.1002/wdev.214

This article is categorized under:

Technologies > Perturbing Genes and Generating Modified Animals