bluuebunny/crossref_metadata_2025 huggingface dataset:
Iridium‐ and Rhodium‐Catalyzed Carbocyclization between 2‐Phenylimidazo[1,2‐a]pyridine and α‐Diazo Esters
Authors: Li Yunyun , Wang Fen , Yu Songjie , Li Xingwei
Published: February 2016

Iridium(III) and rhodium(III) complexes can catalyze the carbocyclization between 2‐phenylimidazo[1,2‐a]pyridine and α‐diazo esters. The reaction occurs via CH activation and dialkylation of the arene followed by intramolecular nucleophilic substitution. Iridium(III) and rhodium(III) catalysis offer complementary scopes with respect to the α‐diazo esters.

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Non‐Heme Imine‐Based Iron Complexes as Catalysts for Oxidative Processes
Authors: Olivo Giorgio , Lanzalunga Osvaldo , Di Stefano Stefano
Published: February 2016

Non‐heme iron complexes are emerging as powerful and versatile catalysts in several oxidative transformations. The most investigated iron complex structures are based on aminopyridine ligands, but a number of imine‐based ligands have been also tested. In this review a collection of recent results obtained in oxidation catalysis with non‐heme imine‐based iron complexes is presented. Their catalytic performances in CH, CC and S oxidation are spread over a wide range of efficiency, going from very low to quite high. Such performances are discussed, whenever possible, in light of the operating reaction mechanisms and of catalyst stability. In order to facilitate the discussion, an initial survey of the most useful mechanistic tools widely applied to distinguish a metal‐based oxidation from a radical‐chain process is also reported. Imine‐based catalysts are divided into two classes: (i) salen‐Fe complexes, and (ii) imine‐Fe complexes. In some cases clues for free‐radical oxidation mechanisms have been reported while in other cases evidence for metal‐based mechanisms has been collected. The preferred mechanistic pathway is shown to be a function of catalyst structure and features. Interestingly, some imine‐based iron complexes are able to perform stereospecific oxidation reactions, demonstrating that the imine functionality can be incorporated in ligands designed for oxidation catalysis.

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Spiro‐Pyrrolidine‐Catalyzed Asymmetric Conjugate Addition of Hydroxylamine to Enals and 2,4‐Dienals
Authors: Dou Qing‐Yun , Tu Yong‐Qiang , Zhang Ye , Tian Jin‐Miao , Zhang Fu‐Min , Wang Shao‐Hua
Published: February 2016

A spiro‐pyrrolidine‐catalyzed tandem aza‐1,4‐addition/hemi‐acetalization reaction was developed with excellent enantioselectivity (12 examples of ≥99% ee), and several substrates proceeded with higher ee (up to 10% increase) compared with the literature data. Particularly, an interesting and unusual aza‐1,6‐/oxa‐1,4‐addition for some substrates was also observed.

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Designing of Epoxy Matrix by Chemically Modified Multiwalled Carbon Nanotubes
Authors: Gantayat Subhra , Sarkar Niladri , Prusty Gyanaranjan , Rout Dibyaranjan , Swain Sarat K.
Published: February 2016

A chemical treatment was applied to functionalize multiwalled carbon nanotubes (MWCNTs) to introduce –COOH and –OH groups on the surface for better interfacial interaction with an epoxy matrix. The functionalized MWCNT (f‐MWCNT) reinforced epoxy nanocomposites were prepared with varying compositions up to 1 wt% MWCNTs. The interaction between MWCNTs and epoxy matrix was evidenced by Fourier transform infrared spectroscopy. The structure and microstructure of f‐MWCNTs reinforced epoxy composite were studied by X‐ray diffraction, field emission scanning electron microscope, high‐resolution transmission electron microscope, and Raman spectroscope. The orientation of f‐MWCNT was investigated by an atomic force microscope. The incorporation of f‐MWCNTs enhanced the thermal stability and the conductivity of the epoxy matrix significantly. The results of tensile strength, tensile strain, extension, and load at break clearly revealed a substantial improvement in tensile properties of the epoxy matrix due to homogeneous dispersion of f‐MWCNTs in the epoxy matrix and strong interfacial adhesion between them as well. The improvement in thermal and mechanical properties in combination with an increase in electrical properties may make the material suitable for making electronic devices.
Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports
Authors: Brownstein Catherine A. , Kleiman Robin J. , Engle Elizabeth C. , Towne Meghan C. , D'Angelo Eugene J. , Yu Timothy W. , Beggs Alan H. , Picker Jonathan , Fogler Jason M. , Carroll Devon , Schmitt Rachel C. O. , Wolff Robert R. , Shen Yiping , Lip Va , Bilguvar Kaya , Kim April , Tembulkar Sahil , O'Donnell Kyle , Gonzalez‐Heydrich Joseph
Published: February 2016

Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention‐deficit hyperactivity disorder. Adolescent/adult‐ onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin‐proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis. © 2016 Wiley Periodicals, Inc.
The rare Costello variant HRAS c.173C>T (p.T58I) with severe neonatal hypertrophic cardiomyopathy
Authors: Hiippala Anita , Vasilescu Catalina , Tallila Jonna , Alastalo Tero‐Pekka , Paetau Anders , Tyni Tiina , Suomalainen Anu , Euro Liliya , Ojala Tiina
Published: February 2016

We report a 10‐year‐old girl presenting with severe neonatal hypertrophic cardiomyopathy (HCM), feeding difficulties, mildly abnormal facial features, and progressive skeletal muscle symptoms but with normal cognitive development. Targeted oligonucleotide‐selective sequencing of 101 cardiomyopathy genes revealed the genetic diagnosis, and the mutation was verified by Sanger sequencing in the patient and her parents. To offer insights into the potential mechanism of patient mutation, protein structural analysis was performed using the resolved structure of human activated HRAS protein with bound GTP analogue (PDB id 5P21) in Discovery Studio 4.5 (Dassault Systèmes Biovia, San Diego, CA). The patient with hypertrophic cardiomyopathy and normal cognitive development was diagnosed with an HRAS mutation c.173C>T (p.T58I), a milder variant of Costello syndrome affecting a highly conserved amino acid, threonine 58. Our analysis suggests that the p.G12 mutations slow GTP hydrolysis rendering HRAS unresponsive to GTPase activating proteins, and resulting in permanently active state. The p.T58I mutation likely affects binding of guanidine‐nucleotide‐exchange factors, thereby promoting the active state but also allowing for slow inactivation. Patients with the HRAS mutation c.173C>T (p.T58I) might go undiagnosed because of the milder phenotype compared with other mutations causing Costello syndrome. We expand the clinical and molecular picture of the rare HRAS mutation by reporting the first case in Europe and the fourth case in the literature. Our protein structure analysis offers insights into the mechanism of the mildly activating p.T58I mutation. © 2016 Wiley Periodicals, Inc.
Physical and verbal aggressive behavior and COMT genotype: Sensitivity to the environment
Authors: Tuvblad Catherine , Narusyte Jurgita , Comasco Erika , Andershed Henrik , Andershed Anna‐Karin , Colins Olivier F. , Fanti Kostas A. , Nilsson Kent W.
Published: February 2016

Catechol‐O‐methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population‐based cohort including 1,783 individuals, ages 20–24 years (47% males). A significant three‐way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent–child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent–child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples. © 2016 Wiley Periodicals, Inc.
Behavioral thermoregulation inLemur catta: The significance of sunning and huddling behaviors
Authors: Kelley Elizabeth A. , Jablonski Nina G. , Chaplin George , Sussman Robert W. , Kamilar Jason M.
Published: February 2016

Regulation of body temperature poses significant problems for organisms that inhabit environments with extreme and seasonally fluctuating ambient temperatures. To help alleviate the energetic costs of autonomic responses, these organisms often thermoregulate through behavioral mechanisms. Among primates, lemurs in Madagascar experience uncharacteristically seasonal and unpredictable climates relative to other primate‐rich regions. Malagasy primates are physiologically flexible, but different species use different mechanisms to influence their body temperatures.Lemur catta, the ring‐tailed lemur, experiences particularly acute diurnal temperature fluctuations in its mostly open‐canopy habitat in south and southwest Madagascar. Ring‐tailed lemurs are also atypical among lemurs in that they appear to use both sun basking postures and huddling to maintain body temperature when ambient temperatures are cold. To our knowledge, however, no one has systematically tested whether these behaviors function in thermoregulation. We present evidence that ring‐tailed lemurs use these postures as behavioral thermoregulation strategies, and that different environmental variables are associated with the use of each posture. Major predictors of sunning included ambient temperature, time of day, and season. Specifically,L. cattaconsistently assumed sunning postures early after daybreak when ambient temperatures were <13°C, and ceased sunning around 10:00a.m., after ambient temperatures approached 26°C. Sunning occurred more often during austral winter months. Huddling was associated with time of day, but not with ambient temperature or season. We conclude thatL. cattatend to sun, rather than huddle, under cold weather conditions when sunning is possible. However, both sunning and huddling are important behavioral adaptations ofL. cattathat augment chemical thermoregulation and the absence of a dynamic, insulating pelage. Sunning and huddling help to account for the great ecological flexibility of the species, but these adaptations may be insufficient in the face of future changes in protective vegetation and temperature. Am. J. Primatol. 78:745–754, 2016. © 2016 Wiley Periodicals, Inc.
Remarkable Charge Separation and Photocatalytic Efficiency Enhancement through Interconnection of TiO2 Nanoparticles by Hydrothermal Treatment
Authors: Ide Yusuke , Inami Nozomu , Hattori Hideya , Saito Kanji , Sohmiya Minoru , Tsunoji Nao , Komaguchi Kenji , Sano Tsuneji , Bando Yoshio , Golberg Dmitri , Sugahara Yoshiyuki
Published: February 2016

Although tremendous effort has been directed to synthesizing advanced TiO2, it remains difficult to obtain TiO2 exhibiting a photocatalytic efficiency higher than that of P25, a benchmark photocatalyst. P25 is composed of anatase, rutile, and amorphous TiO2 particles, and photoexcited electron transfer and subsequent charge separation at the anatase–rutile particle interfaces explain its high photocatalytic efficiency. Herein, we report on a facile and rational hydrothermal treatment of P25 to selectively convert the amorphous component into crystalline TiO2, which is deposited between the original anatase and rutile particles to increase the particle interfaces and thus enhance charge separation. This process produces a new TiO2 exhibiting a considerably enhanced photocatalytic efficiency. This method of synthesizing this TiO2, inspired by a recently burgeoning zeolite design, promises to make TiO2 applications more feasible and effective.
Intercellular Connections Related to Cell–Cell Crosstalk Specifically Recognized by an Aptamer
Authors: Zhang Nan , Bing Tao , Shen Luyao , Song Rusheng , Wang Linlin , Liu Xiangjun , Liu Meirong , Li Juan , Tan Weihong , Shangguan Dihua
Published: February 2016

Intercellular connections are an important pathway for cell–cell crosstalk. However, their formation mechanism and functions are far from being understood. The lack of molecular probes hampers the research in this area. Herein, we report a kind of intercellular connection that is specifically recognized by aptamer M17A2 generated by cell‐SELEX against MCF‐7R cells. These connections have different morphologies, but have the same skeleton composed of F‐actin. The long filamentous connections were identified to be tunneling nanotubes (TNTs), a recently discovered cell–cell communication route. These connections could be built not only between MCF‐7R cells, but also from MCF‐7R to other cells after co‐culture. Proteins could be transported between cells through these connections, suggesting their cell communication function. Aptamer M17A2 shows the potential to act as a new probe for investigating this kind of intercellular connection, as well as for studying cell–cell communication.
Iridium‐Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (−)‐Aspidophylline A
Authors: Jiang Shi‐Zhi , Zeng Xue‐Yi , Liang Xiao , Lei Ting , Wei Kun , Yang Yu‐Rong
Published: February 2016

The first enantioselective total synthesis of (−)‐aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3‐disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C−H activation conditions.
Bimetallic Au2Cu6 Nanoclusters: Strong Luminescence Induced by the Aggregation of Copper(I) Complexes with Gold(0) Species
Authors: Kang Xi , Wang Shuxin , Song Yongbo , Jin Shan , Sun Guodong , Yu Haizhu , Zhu Manzhou
Published: February 2016

The concept of aggregation‐induced emission (AIE) has been exploited to render non‐luminescent CuISR complexes strongly luminescent. The CuISR complexes underwent controlled aggregation with Au0. Unlike previous AIE methods, our strategy does not require insoluble solutions or cations. X‐ray crystallography validated the structure of this highly fluorescent nanocluster: Six thiolated Cu atoms are aggregated by two Au atoms (Au2Cu6 nanoclusters). The quantum yield of this nanocluster is 11.7 %. DFT calculations imply that the fluorescence originates from ligand (aryl groups on the phosphine) to metal (CuI) charge transfer (LMCT). Furthermore, the aggregation is affected by the restriction of intramolecular rotation (RIR), and the high rigidity of the outer ligands enhances the fluorescence of the Au2Cu6 nanoclusters. This study thus presents a novel strategy for enhancing the luminescence of metal nanoclusters (by the aggregation of active metal complexes with inert metal atoms), and also provides fundamental insights into the controllable synthesis of highly luminescent metal nanoclusters.
Hydride Reduction by a Sodium Hydride–Iodide Composite
Authors: Too Pei Chui , Chan Guo Hao , Tnay Ya Lin , Hirao Hajime , Chiba Shunsuke
Published: February 2016

Sodium hydride (NaH) is widely used as a Brønsted base in chemical synthesis and reacts with various Brønsted acids, whereas it rarely behaves as a reducing reagent through delivery of the hydride to polar π electrophiles. This study presents a series of reduction reactions of nitriles, amides, and imines as enabled by NaH in the presence of LiI or NaI. This remarkably simple protocol endows NaH with unprecedented and unique hydride‐donor chemical reactivity.
A Strategy for Configuration of an Integrated Flexible Sulfur Cathode for High‐Performance Lithium–Sulfur Batteries
Authors: Wang Hongqiang , Zhang Wenchao , Liu Huakun , Guo Zaiping
Published: February 2016

Lithium–sulfur batteries are regarded as promising candidates for energy storage devices owing to their high theoretical energy density. The practical application is hindered, however, by low sulfur utilization and unsatisfactory capacity retention. Herein, we present a strategy for configuration of the sulfur cathode, which is composed of an integrated carbon/sulfur/carbon sandwich structure on polypropylene separator that is produced using the simple doctor‐blade technique. The integrated electrode exhibits excellent flexibility and high mechanical strength. The upper and bottom carbon layers of the sandwich‐structured electrode not only work as double current collectors, which effectively improve the conductivity of the electrode, but also serve as good barriers to suppress the diffusion of the polysulfide and buffer the volume expansion of the active materials, leading to suppression of the shuttle effect and low self‐discharge behavior.
Glycation Reactivity of a Quorum‐Sensing Signaling Molecule
Authors: Tsuchikama Kyoji , Gooyit Major , Harris Tyler L. , Zhu Jie , Globisch Daniel , Kaufmann Gunnar F. , Janda Kim D.
Published: February 2016

Reported herein is that (4S)‐4,5‐dihydroxy‐2,3‐pentanedione (DPD) can undergo a previously undocumented non‐enzymatic glycation reaction. Incubation of DPD with viral DNA or the antibiotic gramicidin S resulted in significant biochemical alterations. A protein‐labeling method was consequently developed that facilitated the identification of unrecognized glycation targets of DPD in a prokaryotic system. These results open new avenues toward tracking and understanding the fate and function of the elusive quorum‐sensing signaling molecule.
Oxygen‐binding Protein Fiber and Microgel: Supramolecular Myoglobin–Poly(acrylate) Conjugates
Authors: Ono Toshikazu , Hisaoka Yasushi , Onoda Akira , Oohora Koji , Hayashi Takashi
Published: February 2016

A supramolecular conjugate of myoglobin (Mb) and water‐soluble poly(acrylate), (PA5k and PA25k, where 5k and 25k represent the molecular weight of the polymers, respectively), is constructed on the basis of a noncovalent heme‐heme pocket interaction. The modified heme with an amino group linked to the terminus of one of the heme‐propionates is coupled to the side‐chain carboxyl groups of poly(acrylate) activated by N‐hydroxysuccinimide. The ratios of the heme‐modified monomer unit and the unmodified monomer unit (m:n) in the polymer chains of Heme‐PA5k and Heme‐PA25k were determined to be 4.5:95.5 and 3.1:96.9, respectively. Subsequent addition of apoMb to the conjugated polymers provides Mb‐connected fibrous nanostructures confirmed by atomic force microscopy. A mixture of the heme‐modified polymer and dimeric apomyoglobin as a cross‐linker forms a microgel in which the reconstituted myoglobin retains its native exogenous ligand binding activity.
Water needs and productivity of Jatropha curcas in India: myths and facts
Authors: Wani Suhas P. , Garg Kaushal K. , Chander Girish
Published: February 2016

Jatropha curcas referred as a ‘wonder plant’ with low water requirement, which can be cultivated on wastelands in dry tropical conditions to provide oil seeds for biodiesel without competing for prime cropland. However, results from experiments and case studies in semi‐arid tropical locations in India indicated that evapotranspiration (ET) demand for Jatropha ranges between 750 and 1000 mm under optimal conditions. Jatropha extracted water from soil layer 150 cm below with transpiration requirements of 600–800 mm with increasing age. The yield potential of current genotypes is low (2–3 ton/ha) for realizing the potential of Jatropha cultivation on wastelands subject to limited availability of nutrients and water. Jatropha curcas is drought tolerant, but contrary to belief, it is not a crop that requires less water: in fact, it requires 750–1000 mm water to achieve economic production. However, Jatropha curcas demonstrated good potential for enhancing green water use efficiency without adversely affecting the blue water component, and for promoting crop management options facilitating carbon sequestration and nutrient recycling when grown on degraded lands. Improved cultivars of Jatropha curcas with synchronized flowering to enable mechanical harvesting, along with improved land and water management, are needed for harnessing the potential of Jatropha as a commercially viable biofuel crop. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Accountability Systems and Group Norms: Balancing the Risks of Mindless Conformity and Reckless Deviation
Authors: Patil Shefali V. , Tetlock Philip E. , Mellers Barbara A.
Published: February 2016

In dynamic task environments, decision makers are vulnerable to two types of errors: sticking too closely to the rules (excessive conformity) or straying too far from them (excessive deviation). We explore the effects of process and outcome accountability on the susceptibility to these errors. Using a multiple‐cue probability‐learning task, we show that process accountability encourages conformity errors and outcome accountability promotes deviation errors. Two additional studies explore the moderating effects of self‐focused and other‐focused group norms. Self‐focused norms reduce the effect of process accountability on excessive conformity. Other‐focused norms reduce the effect of outcome accountability on excessive deviation. Our results qualify prevailing claims about the benefits of process over outcome accountability and show that those benefits hinge on prevailing group norms, on the effectiveness of prescribed decision rules, and on the amount of irreducible uncertainty in the prediction task. Copyright © 2016 John Wiley & Sons, Ltd.
Nodule Detection with Eye Movements
Authors: Wedel Michel , Yan Jin , Siegel Eliot L. , Li Hongshuang ( Alice)
Published: February 2016

Radiologists often miss nodules that may represent lung cancer on chest radiographs. We investigated whether eye movements collected during the search for lung nodules by large samples of laypeople may provide information that could assist radiologists in their detection. For that purpose, we developed a partially invisible Markov model with partially unobserved states and analyzed eye tracking data of over 100 laypeople who reviewed 14 chest X‐ray images, of which seven contained a potentially cancerous nodule. We used the luminance value of the pixels in the X‐ray images as prior information on the possible location of a nodule and identified six regions of interest on each image that may contain a nodule. Our study demonstrated that the eye movements recorded from laypersons contained information that may assist radiologists in the detection of nodules in chest X‐rays, which has important implications for crowdsourcing of search for pulmonary nodules, which are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Descriptive analysis of high birth prevalence rate geographical clusters of congenital anomalies in South America
Authors: Gili Juan Antonio , Poletta Fernando Adrián , Giménez Lucas Gabriel , Pawluk Mariela Soledad , Campaña Hebe , Castilla Eduardo Enrique , López‐Camelo Jorge Santiago
Published: February 2016

Background

The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA.

Methods

This observational descriptive study is based on clinical epidemiological data registered by the Latin‐American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters.

Results

We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters.

Conclusion

The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions. Birth Defects Research (Part A) 106:257–266, 2016. © 2016 Wiley Periodicals, Inc.
Photoluminescence and electron paramagnetic resonance properties of a potential phototherapic agent: MMgF4:Gd3+ (M = Ba, Sr) sub‐microphosphors
Authors: Tamboli Sumedha , Kadam R. M. , Dhoble S. J.
Published: February 2016

Novel narrow band UVB‐emitting phosphors, BaMgF4:Gd3+ and SrMgF4:Gd3+ phosphors, were synthesized using a co‐precipitation synthesis method. X‐Ray diffraction analysis was carried out to confirm compound formation, phase purity and crystallinity of the phosphor. At 274 nm excitation, phosphors show a sharp narrow band emission at 313 nm that can be assigned to 6P7/2 → 8S7/2 transition of the Gd3+ ion. With increasing dopant concentration, intensity enhances and then decreases after a certain concentration, which is an indication of concentration quenching taking place in the phosphor. Scanning electron microscopy images of the phosphor show agglomerated particles in the sub‐micron range. Particles range in size from 600 to 800 nm. Electron paramagnetic resonance studies of the phosphors were carried out to detect radicals present in the prepared phosphor. With narrow band UVB emission, phosphor seems to be a good candidate for UV phototherapy application. Copyright © 2016 John Wiley & Sons, Ltd.
CHO cells knocked out for TSC2 display an improved productivity of antibodies under fed batch conditions
Authors: McVey Duncan , Aronov Michael , Rizzi Giovanni , Cowan Alexis , Scott Charo , Megill John , Russell Reb , Tirosh Boaz
Published: February 2016

The kinase mTOR operates in two cellular complexes, mTORC1 and mTORC2. mTORC1 adjusts metabolic activity according to external growth conditions and nutrients availability. When conditions are prosperous, mTOR facilitates protein and lipid biosyntheses and inhibits autophagy, while under metabolic constraints, however, its attenuation induces a catabolic program, energy preservation and autophagy. CHO is a key cell line for manufacturing of biologics owing to its remarkable ability to grow to high densities and maintain protein production and secretion for extended times. While high mTOR activity has been associated with high productivity in CHO cells, its inhibition by rapamycin has also been documented to augment productivity via promotion of viability. Here using CRISPR/Cas9 editing we engineered CHO cells to enforce high mTORC1 activity by knocking‐out TSC2, a major mTOR inhibitory protein, or PTEN, a phosphatase that attenuates the PI3K/AKT/mTOR pathway. Only TSC2‐deleted cells exhibited a constitutive activation of mTORC1 under fed batch conditions. Cells grew larger in size, synthesized more proteins and displayed an over twofold elevation in their specific productivity. While peak viable cell density was compromised, overall titers increased to an extent dependent upon the parental clone. Our data underscore manipulation of TSC as a strategy to improve performance of CHO cell in bioreactors. Biotechnol. Bioeng. 2016;113: 1942–1952. © 2016 Wiley Periodicals, Inc.
Influence of process dynamics on the microbial diversity in a nitrifying biofilm reactor: Correlation analysis and simulation study
Authors: Vannecke Thomas P. W. , Bernet Nicolas , Winkler Mari K. H. , Santa‐Catalina Gaelle , Steyer Jean‐Philippe , Volcke Eveline I. P.
Published: February 2016

For engineers, it is interesting to gain insight in the effect of control strategies on microbial communities, on their turn influencing the process behavior and its stability. This contribution assesses the influence of process dynamics on the microbial community in a biofilm reactor for nitrogen removal, which was controlled according to several strategies aiming at nitrite accumulation. The process dataset, combining conventional chemical and physical data with molecular information, was analyzed through a correlation analysis and in a simulation study. During nitrate formation, an increased nitrogen loading rate (NLR) resulted in a drop of the bulk liquid oxygen concentration without resulting in nitrite accumulation. A biofilm model was able to reproduce the bulk liquid nitrogen concentrations in two periods before and after this increased NLR. As the microbial parameters calibrated for the ammonia‐oxidizing bacteria (AOB) and nitrite‐oxidizing bacteria (NOB) in both periods were different, it was concluded that the increased NLR governed an AOB and NOB population shift. Based on the molecular data, it was assumed that each period was typified by one dominant AOB and probably several subdominant NOB populations. The control strategies for nitrite accumulation influenced the bulk liquid composition by controlling the competition between AOB and NOB. Biotechnol. Bioeng. 2016;113: 1962–1974. © 2016 Wiley Periodicals, Inc.
Decompressive laparotomy for abdominal compartment syndrome
Authors: De Waele J J , Kimball E , Malbrain M , Nesbitt I , Cohen J , Kaloiani V , Ivatury R , Mone M , Debergh D , Björck M
Published: February 2016

Background

The effect of decompressive laparotomy on outcomes in patients with abdominal compartment syndrome has been poorly investigated. The aim of this prospective cohort study was to describe the effect of decompressive laparotomy for abdominal compartment syndrome on organ function and outcomes.

Methods

This was a prospective cohort study in adult patients who underwent decompressive laparotomy for abdominal compartment syndrome. The primary endpoints were 28-day and 1-year all-cause mortality. Changes in intra-abdominal pressure (IAP) and organ function, and laparotomy-related morbidity were secondary endpoints.

Results

Thirty-three patients were included in the study (20 men). Twenty-seven patients were surgical admissions treated for abdominal conditions. The median (i.q.r.) Acute Physiology And Chronic Health Evaluation (APACHE) II score was 26 (20–32). Median IAP was 23 (21–27) mmHg before decompressive laparotomy, decreasing to 12 (9–15), 13 (8–17), 12 (9–15) and 12 (9–14) mmHg after 2, 6, 24 and 72 h. Decompressive laparotomy significantly improved oxygenation and urinary output. Survivors showed improvement in organ function scores, but non-survivors did not. Fourteen complications related to the procedure developed in eight of the 33 patients. The abdomen could be closed primarily in 18 patients. The overall 28-day mortality rate was 36 per cent (12 of 33), which increased to 55 per cent (18 patients) at 1 year. Non-survivors were no different from survivors, except that they tended to be older and on mechanical ventilation.

Conclusion

Decompressive laparotomy reduced IAP and had an immediate effect on organ function. It should be considered in patients with abdominal compartment syndrome.
Consider legal parameters, practical concerns of public debates, protests and demonstrations on campus
Authors: Porter Michael
Published: February 2016

Many campuses have seen a significant uptick in vigorous verbal exchanges, protests and demonstrations, particularly related to race relations. This activity tests colleges' desire to create open dialogue while also fulfilling their obligations to provide a campus environment focused on learning and the safe exchange of ideas.
Comparison of outcome of patients with CLL who are referred or nonreferred to a specialized CLL clinic: a Canadian population‐based study
Authors: Beiggi Sara , Banerji Versha , Deneka Angela , Griffith Jane , Gibson Spencer B. , Johnston James B.
Published: February 2016

Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) patients in Manitoba are either referred to the CLL Clinic at CancerCare Manitoba (CCMB) or are followed by other hematologists and general practitioners. However, it has been unclear whether referral to the CLL clinic influences patient outcome. Overall survival (OS) was assessed for all CLL/SLL patients diagnosed in Manitoba between 2007 and 2011. Of 555 patients, 281 (51%) were referred to the CLL clinic. Patients seen in this clinic had a twofold increased OS compared to patients who were managed by other hematologists and general practitioners (HR 2.375, P 0.0002) when adjusted for age, gender, presence of pre‐ or post‐CLL cancer, treatment and urban/rural location. In the nonreferred population there was a striking correlation between advancing age and decreasing OS. However, this correlation was almost eliminated in the referred population who were more likely to receive chemotherapy. Patients referred and seen in the CLL clinic have an improved OS compared to nonreferred patients and this appears to be primarily related to improved OS in the elderly. Possible explanations for this finding are discussed.
Be proactive, collaborate to address mental health threats
Authors: Hope Joan
Published: February 2016

Since the mass shootings at Virginia Polytechnic Institute and State University, campus safety officials across the country have given a lot of thought to preventing similar tragedies. The Virginia Tech shooter had clear mental health issues. Officials missed the warning signs because people on campus weren't talking to each other, said Cheryl Newman‐Tarwater, captain of the Community College Bureau for the Los Angeles County Sheriff's Department. Her unit provides public safety services for the Los Angeles Community College District.
Study finds significant increase in reported rapes on football game days
Authors: Sutton Halley
Published: February 2016

Does a college or university campus with a significant sports presence create a heightened risk of sexual assault for college‐aged women? A recent study found there was a 28 percent increase in reported rapes of college‐aged women (defined by the study as 17–24 years old) on those days on which Division I‐A football games were played versus reported rapes on non‐game days.
Influence of epidermal growth factor (EGF) and hydrocortisone on the co‐culture of mature adipocytes and endothelial cells for vascularized adipose tissue engineering
Authors: Huber Birgit , Czaja Alina Maria , Kluger Petra Juliane
Published: February 2016

The composition of vascularized adipose tissue is still an ongoing challenge as no culture medium is available to supply adipocytes and endothelial cells appropriately. Endothelial cell medium is typically supplemented with epidermal growth factor (EGF) as well as hydrocortisone (HC). The effect of EGF on adipocytes is discussed controversially. Some studies say it inhibits adipocyte differentiation while others reported of improved adipocyte lipogenesis. HC is known to have lipolytic activities, which might result in mature adipocyte dedifferentiation. In this study, we evaluated the influence of EGF and HC on the co‐culture of endothelial cells and mature adipocytes regarding their cell morphology and functionality. We showed in mono‐culture that high levels of HC promoted dedifferentiation and proliferation of mature adipocytes, whereas EGF seemed to have no negative influence. Endothelial cells kept their typical cobblestone morphology and showed a proliferation rate comparable to the control independent of EGF and HC concentration. In co‐culture, HC promoted dedifferentiation of mature adipocytes, which was shown by a higher glycerol release. EGF had no negative impact on adipocyte morphology. No negative impact on endothelial cell morphology and functionality could be seen with reduced EGF and HC supplementation in co‐culture with mature adipocytes. Taken together, our results demonstrate that reduced levels of HC are needed for co‐culturing mature adipocytes and endothelial cells. In co‐culture, EGF had no influence on mature adipocytes. Therefore, for the composition of vascularized adipose tissue constructs, the media with low levels of HC and high or low levels of EGF can be used.
Covalent Modification of MoS2 with Poly(N‐vinylcarbazole) for Solid‐State Broadband Optical Limiters
Authors: Cheng Hongxia , Dong Ningning , Bai Ting , Song Yi , Wang Jun , Qin Yuanhao , Zhang Bin , Chen Yu
Published: February 2016

New soluble MoS2 nanosheets covalently functionalized with poly(N‐vinylcarbazole) (MoS2–PVK) were in situ synthesized for the first time. In contrast to MoS2 and MoS2/PVK blends, both the solution of MoS2–PVK in DMF and MoS2–PVK/poly(methyl methacrylate) (PMMA) film show superior nonlinear optical and optical limiting responses. The MoS2–PVK/PMMA film shows the largest nonlinear coefficients (βeff) of about 917 cm GW−1 at λ=532 nm (cf. 100.69 cm GW−1 for MoS2/PMMA and 125.12 cm GW−1 for MoS2/PVK/PMMA) and about 461 cm GW−1 at λ=1064 nm (cf. −48.92 cm GW−1 for MoS2/PMMA and 147.56 cm GW−1 for MoS2/PVK/PMMA). A larger optical limiting effect, with thresholds of about 0.3 GW cm−2 at λ=532 nm and about 0.5 GW cm−2 at λ=1064 nm, was also achieved from the MoS2–PVK/PMMA film. These values are among the highest reported for MoS2‐based nonlinear optical materials. These results show that covalent functionalization of MoS2 with polymers is an effective way to improve nonlinear optical responses for efficient optical limiting devices.
The Palladium Way to N‐Heteroacenes
Authors: Bunz Uwe H. F. , Engelhart Jens U.
Published: February 2016

Novel synthetic methodologies allow increasingly efficient access to known organic materials, as well as the preparation of otherwise inaccessible species. Pd‐catalyzed coupling of aromatic dihalides to ortho‐diaminoarenes furnishes embedded stable N,N′‐dihydropyrazines expediently and in often excellent yields. The embedded N,N′‐dihydropyrazines can then be oxidized by MnO2 to give substituted azatetracenes, azapentacenes, azahexacenes, and azaheptacenes, which are soluble, processable, and stable. This powerful Pd‐catalyzed methodology allows the preparation of azaacenes, including diaza‐, tetraaza‐ and hexaazaacenes. In combination with a suitable Pd precursor, Buchwald‐type biarylphosphines have been shown to give excellent results. Activated dihalides such as 2,3‐dihaloquinoxalines are coupled easily under simplified conditions, whereas 2,3‐dibromoacenes require more stringent conditions and advanced catalyst precursors. Pd catalysts effect the assembly of azaacenes with otherwise difficult to obtain substitution patterns. High yields and flexibility make this method most attractive.
Transmission Sources of Waterborne Viruses in South Sudan Refugee Camps
Authors: Guerrero‐Latorre Laura , Hundesa Ayalkibet , Girones Rosina
Published: February 2016

Outbreaks of hepatitis E virus (HEV) are typically associated with contaminated drinking water. A recent HEV outbreak (2012–14) in South Sudan affected ≥10 000 people. This study evaluated different water matrices and food during the last phase of the outbreak by analyzing HEV and human adenovirus (HAdV) as viral indicator of human contamination. The results revealed that the water sources analyzed were negative and that only household samples presented HAdV contamination, identifying a possible route of viral transmission within the population.
Transcriptome analysis reveals a diverse family of kinesins essential for spermatogenesis in the fern Marsilea
Authors: Tomei Erika J. , Wolniak Stephen M.
Published: February 2016

The male gametophyte of the semi‐aquatic fern, Marsilea vestita, produces multiciliated spermatozoids in a rapid developmental sequence that is controlled post‐transcriptionally when dry microspores are placed in water. Development can be divided into two phases, mitosis and differentiation. During the mitotic phase, a series of nine successive division cycles produce 7 sterile cells and 32 spermatids in 4.5–5 h. During the next 5–6 h, each spermatid differentiates into a corkscrew‐shaped motile spermatozoid with ∼140 cilia. In order to study the mechanisms that regulate spermatogenesis, we used RNAseq to generate a reference transcriptome that allowed us to assess abundance of transcripts at different stages of development. Here, we characterize transcripts present in the kinesin motor family. Over 120 kinesin‐like sequences were identified in our transcriptome that represent 56 unique kinesin transcripts. Members of the kinesin‐2, −4, −5, −7, −8, −9, −12, −13, and −14 families, in addition to several plant specific and ‘orphan’ kinesins are present. Most (91%) of these kinesin transcripts change in abundance throughout gametophyte development, with 52% of kinesin mRNAs enriched during the mitotic phase and 39% enriched during differentiation. Functional analyses of six kinesins with different patterns of transcript abundance show that the temporal regulation of these transcripts during gametogenesis correlates directly with kinesin protein function. © 2016 Wiley Periodicals, Inc.
α‐Ketobenzothiazole Serine Protease Inhibitors of Aberrant HGF/c‐MET and MSP/RON Kinase Pathway Signaling in Cancer
Authors: Han Zhenfu , Harris Peter K. W. , Karmakar Partha , Kim Tommy , Owusu Ben Y. , Wildman Scott A. , Klampfer Lidija , Janetka James W.
Published: February 2016

Upregulation of the HGF and MSP growth‐factor processing serine endopeptidases HGFA, matriptase and hepsin is correlated with increased metastasis in multiple tumor types driven by c‐MET or RON kinase signaling. We rationally designed P1’ α‐ketobenzothiazole mechanism‐based inhibitors of these proteases. Structure–activity studies are presented, which resulted in the identification of potent inhibitors with differential selectivity. The tetrapeptide inhibitors span the P1–P1’ substrate cleavage site via a P1’ amide linker off the benzothiazole, occupying the S3’ pocket. Optimized inhibitors display sub‐nanomolar enzyme inhibition against one, two, or all three of HGFA, matriptase, and hepsin. Several compounds also have good selectivity against the related trypsin‐like proteases, thrombin and Factor Xa. Finally, we show that inhibitors block the fibroblast (HGF)‐mediated migration of invasive DU145 prostate cancer cells. In addition to prostate cancer, breast, colon, lung, pancreas, gliomas, and multiple myeloma tumors all depend on HGF and MSP for tumor survival and progression. Therefore, these unique inhibitors have potential as new therapeutics for a diverse set of tumor types.
Antineoplastic Isoflavonoids Derived from Intermediate ortho‐Quinone Methides Generated from Mannich Bases
Authors: Frasinyuk Mykhaylo S. , Mrug Galyna P. , Bondarenko Svitlana P. , Khilya Volodymyr P. , Sviripa Vitaliy M. , Syrotchuk Oleksandr A. , Zhang Wen , Cai Xianfeng , Fiandalo Michael V. , Mohler James L. , Liu Chunming , Watt David S.
Published: February 2016

The regioselective condensations of various 7‐hydroxyisoflavonoids with bis(N,N‐dimethylamino)methane in a Mannich reaction provided C‐8 N,N‐dimethylaminomethyl‐substituted isoflavonoids in good yield. Similar condensations of 7‐hydroxy‐8‐methylisoflavonoids led to the C‐6‐substituted analogs. Thermal eliminations of dimethylamine from these C‐6 or C‐8 N,N‐dimethylaminomethyl‐substituted isoflavonoids generated ortho‐quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho‐quinone methide intermediates trapped dienophiles including 2,3‐dihydrofuran, 3,4‐dihydro‐2H‐pyran, 3‐(N,N‐dimethylamino)‐5,5‐dimethyl‐2‐cyclohexen‐1‐one, 1‐morpholinocyclopentene, and 1‐morpholinocyclohexene to give various inverse electron‐demand Diels–Alder adducts. Several adducts derived from 8‐N,N‐dimethylaminomethyl‐substituted isoflavonoids displayed good activity in the 1–10 μm concentration range in an in vitro proliferation assay using the PC‐3 prostate cancer cell line.
Finite element models of the human shoulder complex: a review of their clinical implications and modelling techniques
Authors: Zheng Manxu , Zou Zhenmin , Bartolo Paulo jorge Da silva , Peach Chris , Ren Lei
Published: February 2016

The human shoulder is a complicated musculoskeletal structure and is a perfect compromise between mobility and stability. The objective of this paper is to provide a thorough review of previous finite element (FE) studies in biomechanics of the human shoulder complex. Those FE studies to investigate shoulder biomechanics have been reviewed according to the physiological and clinical problems addressed: glenohumeral joint stability, rotator cuff tears, joint capsular and labral defects and shoulder arthroplasty. The major findings, limitations, potential clinical applications and modelling techniques of those FE studies are critically discussed. The main challenges faced in order to accurately represent the realistic physiological functions of the shoulder mechanism in FE simulations involve (1) subject‐specific representation of the anisotropic nonhomogeneous material properties of the shoulder tissues in both healthy and pathological conditions; (2) definition of boundary and loading conditions based on individualised physiological data; (3) more comprehensive modelling describing the whole shoulder complex including appropriate three‐dimensional (3D) representation of all major shoulder hard tissues and soft tissues and their delicate interactions; (4) rigorous in vivo experimental validation of FE simulation results. Fully validated shoulder FE models would greatly enhance our understanding of the aetiology of shoulder disorders, and hence facilitate the development of more efficient clinical diagnoses, non‐surgical and surgical treatments, as well as shoulder orthotics and prosthetics. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.