bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive set‐point regulation of discrete‐time nonlinear systems
Authors: Hanba Shigeru
Published: August 2015

In this paper, adaptive set‐point regulation controllers for discrete‐time nonlinear systems are constructed. The system to be controlled is assumed to have a parametric uncertainty, and an excitation signal is used in order to obtain the parameter estimate. The proposed controller belongs to the category of indirect adaptive controllers, and its construction is based on the policy of calculating the control input rather than that of obtaining a control law. The proposed method solves the adaptive set‐point regulation problem under the assumption that the target state is reachable for each fixed parameter value. Additional feature of the proposed method is that Lyapunov‐like functions have not been used in the construction of the controllers. Copyright © 2015 John Wiley & Sons, Ltd.
Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid‐β Aggregates
Authors: Loynachan Colleen N. , Romero Gabriela , Christiansen Michael G. , Chen Ritchie , Ellison Rachel , O'Malley Tiernan T. , Froriep Ulrich P. , Walsh Dominic M. , Anikeeva Polina
Published: August 2015

Remotely triggered hysteretic heat dissipation by magnetic nanoparticles (MNPs) selectively attached to targeted proteins can be used to break up self‐assembled aggregates. This magnetothermal approach is applied to the amyloid‐β (Aβ) protein, which forms dense, insoluble plaques characteristic of Alzheimer's disease. Specific targeting of dilute MNPs to Aβ aggregates is confirmed via transmission electron microscopy (TEM) and is found to be consistent with a statistical model of MNP distribution on the Aβ substrates. MNP composition and size are selected to achieve efficient hysteretic power dissipation at physiologically safe alternating magnetic field (AMF) conditions. Dynamic light scattering, fluorescence spectroscopy, and TEM are used to characterize the morphology and size distribution of aggregates before and after exposure to AMF. A dramatic reduction in aggregate size from microns to tens of nanometers is observed, suggesting that exposure to an AMF effectively destabilizes Aβ deposits decorated with targeted MNPs. Experiments in primary hippocampal neuronal cultures indicate that the magnetothermal disruption of aggregates reduces Aβ cytotoxicity, which may enable future applications of this approach for studies of protein disaggregation in physiological environments.
Facile Fabrication of Robust Ice‐Phobic Polyurethane Sponges
Authors: Liu Fatang , Pan Qinmin
Published: August 2015

Bio‐inspired superhydrophobicity is a promising anti‐icing (or deicing) strategy, but a superhydrophobic surface may lose its anti‐icing capability once the deposited water freezes. Herein, it is shown that ice can be readily and repeatedly removed from the surface of superhydrophobic polyurethane sponges via a simple mechanical squeezing process. The sponges are fabricated through a mussel‐inspired process and subsequent deposition of Ag nanoparticles. The resulting sponges are able to shed off the ice layers formed on their surfaces up to 90 times, exhibiting robust icephobic properties among the reported superhydrophobic surfaces. The mechanism for the excellent icephobicity is investigated by a highly sensitive microelectrobalance and a fluorescent labeling method. It is revealed that the icephobicity is attributed to low ice adhesion of the superhydrophobic sponges, as well as mechanical durability of their surface textures. The present findings provide a facile strategy to fabricate robust icephobic surfaces for various technological applications.
Cationic Rhodium(III)‐Catalyzed Direct C‐2 Carboxamidation of Indoles with Isocyanates via CH Bond Functionalization
Authors: Xu Jun , Sharma Nandini , Sharma Upendra K. , Li Zhenghua , Song Gonghua , Van der Eycken Erik V.
Published: August 2015

A pentamethylcyclopentadienylrhodium(III)‐catalyzed regioselective synthesis of indole‐2‐carboxamides is described employing N‐pyrimidylindoles and isocyanates as coupling partners via CH functionalization. A wide variety of indole‐2‐carboxamides can be synthesized via this method under relatively mild conditions with broad functional group tolerance. The effect of various directing group on this transformation was also studied, unveiling the pyrimidyl group as an easily installable and removable directing group.

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Aluminium‐Catalysed Oxazolidinone Synthesis and their Conversion into Functional Non‐Symmetrical Ureas
Authors: Laserna Victor , Guo Wusheng , Kleij Arjan W.
Published: August 2015

An efficient and practical aluminium‐catalysed approach towards a range of functional oxazolidinones is reported. The method is based on cheap and readily available starting materials including terminal and internal (bicyclic) epoxides and phenyl carbamate. The oxazolidinones serve as highly useful synthons for the high yield preparation of non‐symmetrical ureas by nucleophilic ring‐opening affording the targeted urea compounds with excellent functional group diversity, high regioselectivity and isolated yields up to >99%.

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Phosphoglucomutase‐1 deficiency: Intrafamilial clinical variability and common secondary adrenal insufficiency
Authors: Loewenthal Neta , Haim Alon , Parvari Ruti , Hershkovitz Eli
Published: August 2015

Phosphoglucomutase 1 (PGM1, EC 5.4.2.2) plays a critical role in glucose homeostasis and is also essential for protein N‐glycosylation. The main clinical manifestations of PGM1 deficiency (MIM 614921) reported in 19 patients from different ethnic backgrounds include the following: cleft uvula/palate, Pierre Robin sequence, muscle weakness, dilated cardiomyopathy, growth retardation, elevated serum transaminases, hypoglycemia, and various endocrine abnormalities. We report the variable clinical picture of seven patients with PGM1 deficiency from a consanguineous family. Medical records of the patients were reviewed for clinical details and endocrine evaluation. Whole exome sequencing (WES) was performed. Seven patients aged 2–29 years were included, one patient died at 13 years old when getting off the school bus. All patients have an abnormal palatine structure (cleft palate, bifid uvula) and elevated serum transaminases, 4/7 have short stature (<−2 SDS) and one was diagnosed with growth hormone deficiency. Recurrent episodes of ketotic hypoglycemia were present in 6/7 patients. In two patients, hypoglycemic episodes have spontaneously resolved later on. Four out of seven patients have deteriorating adrenal function with abnormally low cortisol and ACTH levels during hypoglycemia and subnormal response of cortisol to low dose ACTH test . Serum electrolytes were within normal range. Hydrocortisone replacement therapy improved, but not entirely eliminated hypoglycemic episodes. WES revealed a previously described homozygous mutation c.112A>T, p.Asn38Tyr in the PGM1 gene. The clinical picture of PGM1 deficiency is variable among patients with the same mutation and genetic background. ACTH deficiency should be considered in any PGM1 deficient patient with hypoglycemia. © 2015 Wiley Periodicals, Inc.
Co‐occurrence of hypertrophic cardiomyopathy and myeloproliferative disorder in a neonate with Noonan syndrome carrying Thr73Ile mutation in PTPN11
Authors: Yagasaki Hideaki , Nakane Takaya , Hasebe Youhei , Watanabe Atsushi , Kise Hiroaki , Toda Takako , Koizumi Keiichi , Hoshiai Minako , Sugita Kanji
Published: August 2015

Most cases of Noonan syndrome (NS) result from mutations in one of the RAS‐MAPK signaling genes, including PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 (MAP2K1), and CBL. Cardiovascular diseases of varying severity, such as pulmonary stenosis and hypertrophic cardiomyopathy (HCM), are common in NS patients. RAF1 mutations are most frequent in NS with HCM, while PTPN11 mutations are also well known. Thr73Ile is a gain‐of‐function mutation of PTPN11, which has been highly associated with juvenile myelomonocytic leukemia and NS/myeloproliferative disease (MPD), but has not previously been reported in HCM. Here, we report a Japanese female infant with NS carrying the PTPN11 T73I mutation with NS/MPD, complete atrio‐ventricular septal defect, and rapidly progressive HCM. No other HCM‐related mutations were detected in PTPN11, RAF1, KRAS, BRAF, and SHOC2. This patient provides additional information regarding the genotype–phenotype correlation for PTPN11 T73I mutation in NS. © 2015 Wiley Periodicals, Inc.
Genetic architecture for human aggression: A study of gene–phenotype relationship in OMIM
Authors: Zhang‐James Yanli , Faraone Stephen V.
Published: August 2015

Genetic studies of human aggression have mainly focused on known candidate genes and pathways regulating serotonin and dopamine signaling and hormonal functions. These studies have taught us much about the genetics of human aggression, but no genetic locus has yet achieved genome‐significance. We here present a review based on a paradoxical hypothesis that studies of rare, functional genetic variations can lead to a better understanding of the molecular mechanisms underlying complex multifactorial disorders such as aggression. We examined all aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM), an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human disorders that have documented aggressive symptoms in at least one individual with a well‐defined genetic variant. Altogether, we retrieved 86 causal genes. Although most of these genes had not been implicated in human aggression by previous studies, the most significantly enriched canonical pathways had been previously implicated in aggression (e.g., serotonin and dopamine signaling). Our findings provide strong evidence to support the causal role of these pathways in the pathogenesis of aggression. In addition, the novel genes and pathways we identified suggest additional mechanisms underlying the origins of human aggression. Genome‐wide association studies with very large samples will be needed to determine if common variants in these genes are risk factors for aggression. © 2015 Wiley Periodicals, Inc.
The Chemistry of Silacyclopropenes
Authors: Ishikawa Mitsuo , Naka Akinobu , Ohshita Joji
Published: August 2015

The synthesis and reactions of silacyclopropenes are summarized. Addition of silylenes to acetylenes and photochemical isomerization of alkynyldisilanes are known as two major routes for the synthesis of silacyclopropenes. Silacyclopropenes had been thought to be highly reactive and difficult to handle until the first crystal structure of a stable one was reported in 1980. Currently, however, it is commonly accepted that those molecules are stable under ambient conditions when sufficiently bulky substituents are introduced onto the strained three‐membered ring system to stabilize it kinetically. The reactivity of silacyclopropenes is interesting and depends on the nature of substituents. They, indeed, undergo a variety of reactions, such as photolysis, thermolysis, and transition‐metal‐catalyzed reactions, leading to the formation of reactive intermediates including silylenes and silapropadienes, and their transition‐metal complexes, through which numerous transformations into silicon‐containing cyclic and acyclic compounds are possible.
Niche partitioning and environmental factors affecting abundance of strepsirrhines in Angola
Authors: Bersacola Elena , Svensson Magdalena S. , Bearder Simon K.
Published: August 2015

The African nocturnal primates (galagos, pottos, and angwantibos: suborder Strepsirrhini) are the result of the first major primate radiation event in Africa, and are found in different primate communities spread across the entire sub‐Saharan Africa. Thus, they represent an interesting group of taxa to investigate community strategies to avoid interspecific competition. Here, we present the result of the first study on nocturnal primate communities in western Angola. We aimed to identify habitat factors influencing strepsirrhine abundance, collect evidence of spatial niche segregation, and discuss possible indications of competitive exclusion in this region. We conducted nocturnal surveys at four study sites: Kumbira, Bimbe, Northern Scarp, and Calandula. At each encounter we recorded species, group size, height of animals above ground, and GPS location. We sampled vegetation using the point‐centered quarter method and collected data on canopy cover, disturbance, and undergrowth density. We observed a total of five strepsirrhine species with varying community structures. We did not encounter Galagoides thomasi but we recorded a new species Galagoides sp. nov. 4. Levels of disturbance, canopy cover and undergrowth density were the habitat factors that most influenced variation in abundance of Galagoides demidovii and Perodicticus edwardsi, the latter also preferring the habitat with higher tree density. Vertical separation between sympatric strepsirrhines was strongest in Northern Scarp, where overall relative abundance was also highest. Competitive exclusion between G. thomasi and G. sp. nov. 4 may explain why the former was not present within the Angolan Escarpment sites. We observed coexistence between mainly allopatric Otolemur crassicaudatus and P. edwardsi in Kumbira, and of Galago moholi and G. demidovii in Calandula. Both unusual combinations showed some levels of spatial segregation. Habitat characteristics of the Escarpment region are likely to allow for unique nocturnal primate species assemblages. We urge immediate conservation interventions in the Angolan Escarpment. Am. J. Primatol. 77:1179–1192, 2015. © 2015 Wiley Periodicals, Inc.
Dendronisierte hochverzweigte Makromoleküle: weiche Materie mit einer neuartigen Segmentverteilung
Authors: Lederer Albena , Burchard Walther , Hartmann Tobias , Haataja Johannes S. , Houbenov Nikolay , Janke Andreas , Friedel Peter , Schweins Ralf , Lindner Peter
Published: August 2015

Die Dendronisierung von hochverzweigten Polyestern mit Dendronen unterschiedlicher Generationen führt zu pseudo‐dendritischen Strukturen. Der hochverzweigte Kern wurde durch divergente Kopplung von geschützten Monomereinheiten an die funktionellen Gruppen modifiziert. Verglichen mit Dendrimeren ist der präparative Aufwand hier deutlich geringer; die Eigenschaften sind Dendrimeren höherer Generationen jedoch sehr ähnlich. Die Anzahl der funktionellen Gruppen, die Molmasse und das rheologische Verhalten von Dendrimeren höherer Generationen (G5–G8) wird schon von Pseudo‐Dendrimeren niedrigerer Generationen (G1–G4) widergespiegelt. Der Vergleich mit perfekten Dendrimeren hinsichtlich ihrer Segment‐ und internen Struktur ist mittels SANS, dynamischer Lichtstreuung und Viskositätsanalysen, Mikroskopie und molekulardynamischer Simulationen gegeben. Die Interpretation der Ergebnisse zeigt einzigartige strukturelle Eigenschaften auf, die auf einer niedrigeren Segmentdichte im Kern beruhen, der schon in der ersten Generation zu einer weichen nanoskaligen Kugel mit glatter Oberfläche wird.
Structural Insights into the Incorporation of the Mo Cofactor into Sulfite Oxidase from Site‐Directed Spin Labeling
Authors: Hahn Aaron , Engelhard Christopher , Reschke Stefan , Teutloff Christian , Bittl Robert , Leimkühler Silke , Risse Thomas
Published: August 2015

Mononuclear molybdoenzymes catalyze a broad range of redox reactions and are highly conserved in all kingdoms of life. This study addresses the question of how the Mo cofactor (Moco) is incorporated into the apo form of human sulfite oxidase (hSO) by using site‐directed spin labeling to determine intramolecular distances in the nanometer range. Comparative measurements of the holo and apo forms of hSO enabled the localization of the corresponding structural changes, which are localized to a short loop (residues 263–273) of the Moco‐containing domain. A flap‐like movement of the loop provides access to the Moco binding‐pocket in the apo form of the protein and explains the earlier studies on the in vitro reconstitution of apo‐hSO with Moco. Remarkably, the loop motif can be found in a variety of structurally similar molybdoenzymes among various organisms, thus suggesting a common mechanism of Moco incorporation.
B‐Cell Lymphoma‐2 Localization in the Female Reproductive Tract of the Chinese Soft‐Shelled Turtle, Pelodiscus Sinensis and Its Relationship With Sperm Storage
Authors: Le Yuan , Chen Shaofan , Hu Lisi , Zhang Linli , Ullah Shakeeb , Liu Tengfei , Yang Ping , Liu Yi , Chen Qiusheng
Published: August 2015

The aim of the present study was to investigate the expression and localization of B‐cell lymphoma‐2 (Bcl‐2) in the oviduct of the Chinese soft‐shelled turtle, Pelodiscus sinensis, during the reproductive cycle to analyze the relationship between Bcl‐2 and sperm storage. Bcl‐2 expression was confirmed in the P. sinensis oviduct by western blot analysis. Hematoxylin‐eosin staining showed that female P. sinensis stored sperm from November to April of the following year. The oviduct showed positive immunostaining for Bcl‐2 of epithelial ciliated cells, gland ducts, and gland cells. Bcl‐2 expression in the oviduct was associated with sperm storage occurrence. This indicates that the survival factor Bcl‐2 may play a role in P. sinensis sperm storage. Anat Rec, 298:2011–2017, 2015. © 2015 Wiley Periodicals, Inc.
CSF N‐glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder
Authors: Barone Rita , Sturiale Luisella , Fiumara Agata , Palmigiano Angelo , Bua Rosaria O. , Rizzo Renata , Zappia Mario , Garozzo Domenico
Published: August 2015

Protein N‐glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N‐glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late‐onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2‐ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co‐occurrence of psychiatric disturbances. We studied the N‐glycome profile of the cerebrospinal fluid (CSF) in a 14 year‐old patient with GM2‐gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work‐up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N‐glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo‐core fucosylated bisected N‐glycans. No changes of total plasma N‐glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N‐glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2‐gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. Autism Res 2016, 9: 423–428. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
RNA structure: Merging chemistry and genomics for a holistic perspective
Authors: Kubota Miles , Chan Dalen , Spitale Robert C.
Published: August 2015

The advent of deep sequencing technology has unexpectedly advanced our structural understanding of molecules composed of nucleic acids. A significant amount of progress has been made recently extrapolating the chemical methods to probe RNA structure into sequencing methods. Herein we review some of the canonical methods to analyze RNA structure, and then we outline how these have been used to probe the structure of many RNAs in parallel. The key is the transformation of structural biology problems into sequencing problems, whereby sequencing power can be interpreted to understand nucleic acid proximity, nucleic acid conformation, or nucleic acid‐protein interactions. Utilizing such technologies in this way has the promise to provide novel structural insights into the mechanisms that control normal cellular physiology and provide insight into how structure could be perturbed in disease.
Fluorescence resonance energy transfer between bovine serum albumin and fluoresceinamine
Authors: Bai Zhijun , Liu Yushuang , Zhang Ping , Guo Jun , Ma Yuxing , Yun Xiaoling , Zhao Xinmin , Zhong Ruibo , Zhang Feng
Published: August 2015

Physical binding‐mediated organic dye direct‐labelling of proteins could be a promising technology for bio‐nanomedical applications. Upon binding, it was found that fluorescence resonance energy transfer (FRET) occurred between donor bovine serum albumin (BSA; an amphiphilic protein) and acceptor fluoresceinamine (FA; a hydrophobic fluorophore), which could explain fluorescence quenching found for BSA. FRET efficiency and the distance between FA and BSA tryptophan residues were determined to 17% and 2.29 nm, respectively. Using a spectroscopic superimposition method, the saturated number of FAs that bound to BSA was determined as eight to give a complex formula of FA8–BSA. Finally, molecular docking between BSA and FA was conducted, and conformational change that occurred in BSA upon binding to FA molecules was also studied by three‐dimensional fluorescence microscopy. Copyright © 2015 John Wiley & Sons, Ltd.
Adsorptive removal of dyes from synthetic and real textile wastewater using magnetic iron oxide nanoparticles: Thermodynamic and mechanistic insights
Authors: Nassar Nashaat N. , Marei Nedal N. , Vitale Gerardo , Arar Laith A.
Published: August 2015

Magnetic iron‐oxide nanoparticles exhibit high efficiency in wastewater treatment for many important reasons, including that they can remove contaminants from wastewater rapidly owing to their high external surface area/unit mass and interstice reactivity. Additionally, this type of iron oxide can easily be separated using a magnet after finishing the treatment process, can be used as a catalyst for the decomposition of adsorbed contaminants and thus reduce sludge formation, and can cost‐effectively meet the environmental regulations for wastewater treatment since it can be prepared in situ where treatment is needed via various techniques. In this study, we use magnetic iron oxide nanoparticles for dye removal from synthetic and real textile wastewater for the first time. The effects of different experimental parameters on dye removal, such as contact time, initial concentration, solution pH, and coexisting ions, were investigated. Computational modelling of the interaction of different dye molecules with different surfaces of γ‐Fe2O3 nanoparticles is performed to obtain more mechanistic insights on the adsorption behaviour. The results showed that dye adsorption was fast, as external adsorption was dominated. The adsorption equilibrium data fit very closely to the Langmuir adsorption isotherm model, confirming monolayer adsorption, which is supported by the adsorption computational calculations. The adsorption was spontaneous, endothermic, and physical in nature.
Comprehensive experimental study and numerical simulation of vapour extraction (VAPEX) process in heavy oil systems
Authors: Mohammadpoor Mehdi , Torabi Farshid
Published: August 2015

There are significant heavy oil and bitumen resources in Canada. Global energy demand is rising while environmental constraints make heavy oil recovery more challenging. Therefore, looking for an economically viable and environmentally‐friendly heavy oil recovery technique is essential. Recently, solvent‐based heavy oil recovery techniques (i.e., VAPEX) have attracted attention due to their economic and environmental advantages over thermal methods. In this research, an extensive experimental and numerical simulation study on the VAPEX technique was carried out to provide more in‐depth information about key parameters which affect the ultimate performance of the VAPEX process. For this purpose, VAPEX experiments were conducted in two large‐scale physical models and various solvents were utilized. PVT experiments were also carried out, and CMG's STARSTM was used for numerical simulation studies and to history‐match the experimental results. Image analysis of the VAPEX chamber evolution showed that the highest sweep efficiency was observed after injecting propane, followed by butane, a propane/carbon dioxide mixture, a propane/methane mixture, carbon dioxide, and methane. The experiments were simulated numerically, and satisfactory history‐matching results were achieved. The major difference between the experimental and simulation results was observed after the first breakthrough of the solvent. In addition, the results showed that injection and production well configurations significantly affected the recovery performance of the process. A longer distance between the injection and production wells alongside the drainage height will increase the production rate in VAPEX.
Identification of Chlorophene in a Backwater Stream in Kerala (India) and its Sonochemical Degradation Studies
Authors: Rayaroth Manoj P. , Khalid Nejumal K. , Sasi Subha , Aravind Usha K. , Aravindakumar Charuvila T.
Published: August 2015

Chlorophene, a chlorinated phenolic compound and a well‐known emerging pollutant due to its extensive use as an antimicrobial agent, has been identified in a local backwater stream using liquid chromatography quadrupole time of flight MS (LC‐Q‐TOF‐MS). The concentration of chlorophene has been calculated as 6 × 10−7 mol L−1 (0.132 ppm). In order to develop a suitable treatment protocol, ultrasound mediated oxidative degradation has been carried out. Prior to the investigation of chlorophene in the backwater sample, the degradation in pure water has been investigated at 620 kHz and 40.25 W mL−1. Complete disappearance of chlorophene was observed within 40 min of sonication. The presence of various inorganic ions had no significant influence on the degradation. A complete chemical oxygen demand removal in the local backwater samples was achieved within 3 h of sonication. Three major intermediate products have been identified by LC‐Q‐TOF‐MS and a plausible mechanism of the degradation is proposed. The same method was applied for the backwater sample containing chlorophene with a concentration of 6 × 10−7 mol L−1. Complete disappearance of chlorophene and nearly 85.7% COD removal was observed in this system as well.
Restoration of cytoskeletal and membrane tethering defects but not defects in membrane trafficking in the intestinal brush border of mice lacking both myosin Ia and myosin VI
Authors: Hegan Peter S. , Kravtsov Dmitri V. , Caputo Christina , Egan Marie E. , Ameen Nadia A. , Mooseker Mark S.
Published: August 2015

Myosin Ia (Myo1a), the most prominent plus‐end directed motor and myosin VI (Myo6) the sole minus‐end directed motor, together exert opposing tension between the microvillar (MV) actin core and the apical brush border (BB) membrane of the intestinal epithelial cell (IEC). Mice lacking Myo1a or Myo6 each exhibit a variety of defects in the tethering of the BB membrane to the actin cytoskeleton. Double mutant (DM) mice lacking both myosins revealed that all the defects observed in either the Myo1a KO or Snell's waltzer (sv/sv) Myo6 mutant mouse are absent. In isolated DM BBs, Myo1a crosslinks between MV membrane and MV actin core are absent but the gap (which is lost in Myo1a KO) between the MV core and membrane is maintained. Several myosins including Myo1c, d, and e and Myo5a are ectopically recruited to the BB. Consistent with the restoration of membrane tethering defects by one or more of these myosins, upward ATP‐driven shedding of the BB membrane, which is blocked in the Myo1a KO, is restored in the DM BB. However, Myo1a or Myo6 dependent defects in expression of membrane proteins that traffic between the BB membrane and endosome (NaPi2b, NHE3, CFTR) are not restored. Compared to controls, Myo1a KO, sv/sv mice exhibit moderate and DM high levels of hypersensitivity to dextran sulfate sodium‐induced colitis. Consistent with Myo1a and Myo6 playing critical roles in maintaining IEC integrity and response to injury, DM IECs exhibit increased numbers of apoptotic nuclei, above that reported for Myo1a KO. © 2015 Wiley Periodicals, Inc.
Prostate cancer imaging of FSHR antagonist modified with a hydrophilic linker
Authors: Zhu Chen , Xu Qing , Pan Donghui , Xu Yuping , Liu Ping , Yang Runlin , Wang Lizhen , Sun Xinchen , Luo Shineng , Yang Min
Published: August 2015

Follicle‐stimulating hormone receptor (FSHR) is selectively expressed in endothelial cells of prostate cancer (PCa) and becomes a potential target for tumor diagnosis and therapy. 18F‐Al‐NOTA‐MAL‐FSH1 is a promising PET imaging probe for targeting FSHR; however, the unfavorable abdominal backgrounds may hamper clinical translation. GGGRDN is a new hydrophilic linker, which can improve the imaging quality of radiolabeled peptides. In this study, GGGRDN‐FSH1 (denoted as FSH2) was designed and conjugated with NOTA‐MAL for 18F‐Al radiolabeling. NOTA‐MAL‐FSH2 was obtained with about 50% yield and labeled using 18F‐Al in a one‐step method within 20 min with a yield of 41.46 ± 10.36% (non‐decay‐corrected). The radiochemical purity was more than 95% and the specific activity was more than 50 GBq/µmol. The in vitro stability studies were determined in PBS and human serum. 18F‐Al‐NOTA‐MAL‐FSH2 remained stable in PBS and human serum. Balb/c nude mice bearing PC‐3 human PCa were used for in vivo study. PC‐3 tumors were clearly visualized with good contrast to background through microPET. ROI analysis showed the tumor uptake values were 2.68 ± 0.52 and 1.97 ± 0.61%ID/g at 30 and 60 min post injection (p.i.), respectively. Biodistribution studies showed that the accumulations of 18F‐Al‐NOTA‐MAL‐FSH2 in liver and intestine were 0.47 ± 0.11 and 0.12 ± 0.03%ID/g respectively at 60 min p.i. FSHR‐binding specificity was also demonstrated by reduced tumor uptake after coinjection of excessive unlabeled FSH2. In conclusion, 18F‐Al‐NOTA‐MAL‐FSH2 was successfully prepared in a one‐step method and showed better pharmacokinetics than 18F‐Al‐NOTA‐MAL‐FSH1. Favorable preclinical study revealed that 18F‐Al‐NOTA‐MAL‐FSH2 appears to be a promising candidate for FSHR‐positive tumor imaging. Copyright © 2015 John Wiley & Sons, Ltd.
Changes in body mass index in long‐term childhood cancer survivors
Authors: van Santen Hanneke M. , Geskus Ronald B. , Raemaekers Steven , van Trotsenburg A. S. Paul , Vulsma Thomas , van der Pal Helena J. H. , Caron Hubert N. , Kremer Leontien C. M.
Published: August 2015

BACKGROUND

Previous studies have reported changes in the body mass index (BMI) with time in childhood cancer survivors (CCSs) during follow‐up. The limitations of these studies include that they described only a subgroup of survivors or used questionnaires with self‐reported heights and weights. The goal of this study was to examine BMI in a large cohort of long‐term CCSs and relate this to the BMI at diagnosis, age, sex, tumor type, treatment, and endocrine defects.

METHODS

All patients treated for childhood cancer at the Emma Children's Hospital/Academic Medical Center between 1966 and 1996 who had survived for at least 5 years were eligible for inclusion. For 893 CCSs with a mean follow‐up of 14.9 years, the BMI at the late effects outpatient clinic was compared with the BMI for the general Dutch population.

RESULTS

For girls, an increased prevalence of obesity was found. Risk factors for developing a high BMI at follow‐up were a younger age and a high BMI at diagnosis and treatment with cranial radiotherapy. A significantly increased prevalence of severe underweight was found in all adult subgroups except for females aged 26 to 45 years. An association was found between a low BMI at diagnosis and a low BMI at follow‐up. No treatment‐related variables could be related to changes in BMI.

CONCLUSIONS

The BMI at diagnosis is one of the most important predictors for the BMI at follow‐up, and this suggests an important genetic or environmental cause. Adult CCSs are at high risk for developing severe underweight at follow‐up. Future studies should focus on the causes and clinical consequences of underweight. Cancer 2015;121:4197–4204. © 2015 American Cancer Society.
Preanalytic parameters in epidermal growth factor receptor mutation testing for non–small cell lung carcinoma: A review of cytologic series
Authors: da Cunha Santos Gilda , Saieg Mauro Ajaj
Published: August 2015

The results from molecular assays can be affected significantly by the preanalytic condition of cytologic samples. The authors review current knowledge on the use of cytologic samples for epidermal growth factor receptor (EGFR) mutation testing in non–small cell lung cancer with a focus on preanalytic parameters. A systematic electronic search of the MEDLINE database was performed to identify original articles that reported the use of cytologic samples for EGFR molecular analysis and included a minimum of 100 samples. The information collected included author(s), journal, and year of publication; number of patients and samples; sampling method; type of preparation; type of fixative; staining techniques; mutation analysis techniques; tumor cellularity; the percentage of tumor cells; data on DNA quantity, quality, and concentration; failed assays; and the mutation rate. EGFR mutation analysis was conducted on 4999 cytologic samples from 22 studies that fulfilled the inclusion criteria. Fine‐needle aspirates and pleural effusions were the most common types of specimens used. DNA was mainly extracted from cell blocks and smears, and the most commonly reported fixatives included formalin, ethanol, and CytoLyt. Cellularity assessments and DNA yields were available from 5 studies each. The average success rate for the assays that used cytologic specimens was 95.87% (range, 85.2%‐100%). The mutation rate ranged from 6% to 50.46%, and a higher mutation detection rate and lower numbers of insufficient cases were reported for pleural effusions and lymph node samples from endobronchial ultrasound‐guided transbronchial needle aspiration compared with histologic specimens. Low cellularity and a low percentage of tumor cells were associated with higher test failure rates. Future guidelines should consider the current data for specific recommendations regarding cytologic samples. Cancer (Cancer Cytopathol) 2015;123:633–643. © 2015 American Cancer Society.
Second tectofugal pathway in a songbird (Taeniopygia guttata) revisited: Tectal and lateral pontine projections to the posterior thalamus, thence to the intermediate nidopallium
Authors: Wild J. Martin , Gaede Andrea H.
Published: August 2015

Birds are almost always said to have two visual pathways from the retina to the telencephalon: thalamofugal terminating in the Wulst, and tectofugal terminating in the entopallium. Often ignored is a second tectofugal pathway that terminates in the nidopallium medial to and separate from the entopallium (e.g., Gamlin and Cohen [1986] J Comp Neurol 250:296–310). Using standard tract‐tracing and electroanatomical techniques, we extend earlier evidence of a second tectofugal pathway in songbirds (Wild [1994] J Comp Neurol 349:512–535), by showing that visual projections to nucleus uvaeformis (Uva) of the posterior thalamus in zebra finches extend farther rostrally than to Uva, as generally recognized in the context of the song control system. Projections to “rUva” resulted from injections of biotinylated dextran amine into the lateral pontine nucleus (PL), and led to extensive retrograde labeling of tectal neurons, predominantly in layer 13. Injections in rUva also resulted in extensive retrograde labeling of predominantly layer 13 tectal neurons, retrograde labeling of PL neurons, and anterograde labeling of PL. It thus appears that some tectal neurons could project to rUva and PL via branched axons. Ascending projections of rUva terminated throughout a visually responsive region of the intermediate nidopallium (NI) lying between the nucleus interface medially and the entopallium laterally. Lastly, as shown by Clarke in pigeons ([1977] J Comp Neurol 174:535–552), we found that PL projects to caudal cerebellar folia. J. Comp. Neurol. 524:963–985, 2016. © 2015 Wiley Periodicals, Inc.
Compiler transformation of nested loops for general purpose GPUs
Authors: Tian Xiaonan , Xu Rengan , Yan Yonghong , Chandrasekaran Sunita , Eachempati Deepak , Chapman Barbara
Published: August 2015

Manycore accelerators have the potential to significantly improve performance of scientific applications when offloading computationally intensive program portions to accelerators. Directive‐based high‐level programming models, such as OpenACC and OpenMP, are used to create applications for accelerators through annotating regions of code meant for offloading. OpenACC is an emerging directive‐based programming model for programming accelerators that typically enable inexperienced programmers to achieve portable and productive performance within applications. In this paper, we present our research in developing challenges and solutions when creating an open‐source OpenACC compiler in an industrial framework (OpenUH as a branch of Open64). We then discuss in detail techniques we developed for loop scheduling reduction operations on general purpose GPUs. The compiler is evaluated with benchmarks from the NAS Parallel Benchmarks suite and self‐written micro‐benchmarks for reduction operations. This implementation has been designed to serve as a compiler infrastructure for researchers to explore advanced compiler techniques, extend OpenACC to other programming models, and build performance tools used in conjunction with OpenACC programs. Copyright © 2015 John Wiley & Sons, Ltd.
The Transition States for CO2 Capture by Substituted Ethanolamines
Authors: Gangarapu Satesh , Marcelis Antonius T. M. , Alhamed Yahia A. , Zuilhof Han
Published: August 2015

Quantum chemical studies are used to understand the electronic and steric effects on the mechanisms of the reaction of substituted ethanolamines with CO2. SCS‐MP2/6‐311+G(2d,2p) calculations are used to obtain the activation energy barriers and reaction energies for both the carbamate and bicarbonate formation. Implicit solvent effects are included with the universal solvation model SMD. Carbamate formation is more favorable than bicarbonate formation for monoethanolamine (MEA) both kinetically and thermodynamically. Increase of the steric hindrance on the C atoms around the N atom in substituted ethanolamines favors bicarbonate formation over carbamate formation with lower activation barriers and thereby higher reaction rates. In contrast, substitution by an N‐methyl or N‐ethyl group on MEA leads to a lower activation barrier for both carbamate formation and bicarbonate formation. As a result, higher reaction rates are expected as compared to MEA, and therefore these compounds have significant potential as industrial CO2 capturing solvents.
Growth of LaBGeO5 crystal fibers by the micro‐pulling down technique
Authors: Assi F. , Ferriol M. , Cochez M. , Aillerie M.
Published: August 2015

The LaBGeO5 compound (LBGO) was prepared by solid state reaction at 1050°C and characterized by XRD and DTA analysis. The direct growth of LBGO fibers from the melt using micro‐pulling down technique was unsuccessful because of its high viscosity. The study of the LBGO‐LiF phase diagram showed that LiF could be considered as a convenient flux to reduce viscosity of the melt during the growth process. Several crystal fibers were then grown and characterized by Raman spectroscopy. To decrease the high volatility of LiF, B2O3 was added to the melt. A white cloudy fiber was obtained from LiF‐B2O3 flux and checked by Raman spectroscopy and scanning electron microscopy.
Validated MicroRNA Target Databases: An Evaluation
Authors: Ji (Diana) Lee Yun , Kim Veronica , Muth Dillon C. , Witwer Kenneth W.
Published: August 2015

Preclinical Research

Positive findings from preclinical and clinical studies involving depletion or supplementation of microRNA (miRNA) engender optimism about miRNA‐based therapeutics. However, off‐target effects must be considered. Predicting these effects is complicated. Each miRNA may target many gene transcripts, and the rules governing imperfectly complementary miRNA: target interactions are incompletely understood. Several databases provide lists of the relatively small number of experimentally confirmed miRNA: target pairs. Although incomplete, this information might allow assessment of at least some of the off‐target effects. We evaluated the performance of four databases of experimentally validated miRNA: target interactions (miRWalk 2.0, miRTarBase, miRecords, and TarBase 7.0) using a list of 50 alphabetically consecutive genes. We examined the provided citations to determine the degree to which each interaction was experimentally supported. To assess stability, we tested at the beginning and end of a five‐month period. Results varied widely by database. Two of the databases changed significantly over the course of 5 months. Most reported evidence for miRNA: target interactions were indirect or otherwise weak, and relatively few interactions were supported by more than one publication. Some returned results appear to arise from simplistic text searches that offer no insight into the relationship of the search terms, may not even include the reported gene or miRNA, and may thus, be invalid. We conclude that validation databases provide important information, but not all information in all extant databases is up‐to‐date or accurate. Nevertheless, the more comprehensive validation databases may provide useful starting points for investigation of off‐target effects of proposed small RNA therapies. Drug Dev Res 76 : 389–396, 2015. © 2015 Wiley Periodicals, Inc.
Synthesis of CaTiO3 Nanofibers with Controllable Drug‐Release Kinetics
Authors: Zhang Qiuhong , Li Xiang , Ren Zhaohui , Han Gaorong , Mao Chuanbin
Published: August 2015

Calcium titanate (CaTiO3) nanofibers with controlled microstructure were fabricated by a combination of sol–gel and electrospinning approaches. The fiber morphology has been found to rely significantly on the precursor composition. Altering the volume ratio of ethanol to acetic acid from 3.5 to 1.25 enables the morphology of the CaTiO3 nanofibers to be transformed from fibers with a circular cross section to curved ribbon‐like structures. Ibuprofen (IBU) was used as a model drug to investigate the drug‐loading capacity and drug‐release profile of the nanofibers. It was found that the BET surface area and the pore volume decrease markedly with the utilization of F127 surfactant. The nanofibers synthesized without F127 surfactant present the highest drug‐loading capacity and the most sustained release kinetics. This study suggests that calcium titanate nanofibers can offer a promising platform for localized drug delivery.
Postfunctionalization of the BODIPY Core: Synthesis and Spectroscopy
Authors: Boens Noël , Verbelen Bram , Dehaen Wim
Published: August 2015

In this review we describe the various new methodologies for synthetic postmodification of the BODIPY core designed and developed by our research groups, as well as their electronic spectroscopic properties. We discuss the different strategies created for functionalization of the BODIPY framework at the pyrrole C‐ring positions and the meso‐position. Halogenated boron dipyrrins are substrates for nucleophilic substitution or Pd‐catalyzed cross‐coupling reactions. α‐Unsubstituted BODIPYs can be functionalized with N and C nucleophiles through oxidative or vicarious nucleophilic substitution (VNS) of the α‐hydrogen atoms. Combining this methodology with reversible Michael addition onto nitrostyrenes provides a route to 3‐styrylated BODIPYs. Furthermore, the one‐step, Pd‐catalyzed C–H arylation of 3,5‐unsubstituted BODIPYs leads to 3‐ and 3,5‐arylated dyes. Finally, radical C–H arylation at the 3,5‐positions of α‐unsubstituted BODIPYs provides an additional synthesis route to arylated dyes.
Access to Indene Derivatives by a Sequence of Intermolecular anti‐Carbopalladation, Heck Reaction, and Electrophilic Attack
Authors: Pawliczek Martin , Jones Peter G. , Werz Daniel B.
Published: August 2015

Enynes substituted with a tertiary hydroxyl group attached to one of the alkyne units react with iodobenzenes in a Pd‐catalyzed domino reaction. The cascade consists of an intermolecular anti‐carbopalladation and a terminating Heck reaction. This process leads to arene‐substituted dienes. One tetrasubstituted double bond is embedded in a six‐membered ring system, and the other trisubstituted alkene is located in an exocyclic position. On treatment with acid, the emerging tertiary carbocation is attacked by the arene to give a five‐membered ring, and thus results in the formation of alkylated indenes.
Improving the Conversion and Energy Efficiency of Carbon Dioxide Splitting in a Zirconia‐Packed Dielectric Barrier Discharge Reactor
Authors: Van Laer Koen , Bogaerts Annemie
Published: August 2015

The use of plasma technology for CO2 splitting is gaining increasing interest, but one of the major obstacles to date for industrial implementation is the considerable energy cost. We demonstrate that the introduction of a packing of dielectric zirconia (ZrO2) beads into a dielectric barrier discharge (DBD) plasma reactor can enhance the CO2 conversion and energy efficiency up to a factor 1.9 and 2.2, respectively, compared to that in a normal (unpacked) DBD reactor. We obtained a maximum conversion of 42 % and a maximum energy efficiency of 9.6 %. However, it is the ability of the packing to almost double both the conversion and the energy efficiency simultaneously at certain input parameters that makes it very promising. The improved conversion and energy efficiency can be explained by the higher values of the local electric field and electron energy near the contact points of the beads and the lower breakdown voltage, demonstrated by 2 D fluid modeling.
Altered prefrontal activity and connectivity predict different cognitive deficits in schizophrenia
Authors: Ferrarelli Fabio , Riedner Brady A. , Peterson Michael J. , Tononi Giulio
Published: August 2015

Background

Cognitive dysfunction is considered a core feature of schizophrenia, and impaired performances in episodic memory (EM) and executive function (EF) tasks are consistently reported in schizophrenia patients. Traditional fMRI and EEG studies have helped identifying brain areas, including the prefrontal cortex (PFC), involved in these tasks. However, it is unclear whether intrinsic defects in prefrontal function per se contribute to poor performance in schizophrenia, given the presence of confounds like reduced motivation and psychotic symptoms. TMS/hd‐EEG measurements are obtained without cognitive effort, and can be calculated in any cortical area.

Methods

We performed TMS/hd‐EEG recordings in parietal, motor, premotor, and PFC in healthy individuals (N = 20) and schizophrenia patients (N = 20). Source modeling of TMS‐evoked responses was performed, and measures of cortical activity (significant current density, SCD) and connectivity (significant current scattering, SCS) were computed. Patients with schizophrenia also performed Penn Word memory delayed (CPWd) and Penn Conditional Exclusion Test (PCET). CPWd evaluates EM and involves primarily PFC, whereas PCET reflects EF and implicates PFC with other brain regions.

Findings

We found no difference in SCD and SCS after TMS of parietal/motor cortices, whereas those parameters were reduced in premotor/prefrontal areas in schizophrenia patients. In PFC, where these measures were most defective, SCD was negatively correlated with performance in CPWd whereas higher SCS values were associated with more errors in PCET.

Conclusion

These findings indicate that schizophrenia patients have intrinsic defects in both activity and connectivity of PFC, and that these defects are specifically associated with impairments in cognitive abilities. Hum Brain Mapp 36:4539–4552, 2015. © 2015 Wiley Periodicals, Inc.