bluuebunny/crossref_metadata_2025 huggingface dataset:
Ozone pretreatment of humid wheat straw for biofuel production
Authors: Al jibouri Ali Kamel H. , Turcotte Ginette , Wu Jiangning , Cheng Chil‐Hung
Published: September 2015

In an attempt to maximize the amount of ozone reacting with lignin inside humid wheat straw, some of the ozone‐reactive lignin degradation products were washed away before a second ozonolysis delignification stage. The total contact time for the two stages was kept the same as that for a one‐stage process for comparison. A significant decrease in the Acid Insoluble Lignin (AIL) content of the straw resulted: from 13.04 wt. % (after a 30‐min one‐stage ozonolysis) to 9.34 wt. % (after a 30‐min two‐stage ozonolysis, separated by a washing step). This significant improvement was accompanied by an increase in released fermentable sugars from an enzymatic hydrolysis. The yield increased from 60% theoretical sugars to 80%. A further improvement in AIL (down to 7.36 wt. %) and released sugars (up to 90% theoretical) occurred when the moisture content (MC) of the straw entering the second stage was adjusted to the optimum value of the straw entering first stage (45 wt. %, predicted from an experimental design). The authors believe this is the first time results are published for the introduction of a two‐stage process separated by a washing step.
Clean Power Plan—CO2 Regulations for Everyone
Authors: Campbell William
Published: September 2015

The Environmental Protection Agency (EPA) has taken on the complicated task of regulating carbon dioxide for existing electric‐generating units (EGUs).
Natural Gas Plays Central Role in Clean Power Plan
Authors: Wendaur Mark G.
Published: September 2015

President Obama and the Environmental Protection Agency (EPA) recently passed new regulations requiring America's electric power plants to reduce greenhouse gas emissions. These regulations come in the form of the Clean Power Plan (CPP). The purpose of the CPP is to reduce the amount of carbon dioxide emitted from existing and new electric power plants, also referred to as electric‐generating units (EGUs). In order to achieve the lower CO2 emission goals of the CPP, this nation will need to increase its use of natural gas for electricity generation.
Physical Security Becoming More Urgent
Authors: Hope Robert J.
Published: September 2015

I once heard the saying that “security is always too much until it is not enough.”
Electricity and Telecommunications Nexus Could Mean Increased Costs for Utilities
Authors: DeCotis Paul A.
Published: September 2015

[With this issue, we welcome Paul A. DeCotis as a columnist on electricity matters. As his biography shows, Paul has far‐reaching experience in electric regulation.—RW]
The Dynamics of Small Postglacial Lake Basins and the Nature of Their Archaeological Record: A Case Study of the Middle Palaeolithic Site Neumark‐Nord 2, Germany
Authors: Pop Eduard , Bakels Corrie , Kuijper Wim , Mücher Herman , van Dijk Madeleine
Published: September 2015

Due to favorable conditions of preservation, sedimentary basins provide rich records of human behavior and its environmental context. The conditions for the preservation of archaeological material however vary between basin types (large, river‐fed or small, closed basins), while conditions also differ within a particular basin environment. The goal of this paper is to understand how the dynamics of a small postglacial basin such as Neumark‐Nord 2, a context that dominates the Eemian archaeological record, affected the archaeology situated at its basin margin. The approach used here is to correlate the archaeological record with reconstructions of patterns of deposition and the water conditions within the basin, using lithology, micromorphology, pollen, and macroremains from a transect running from the basin center to the margin. The results show that (1) find levels were exposed to overland flow‐induced winnowing, which vertically concentrated finds but did not cause significant transport, (2) find levels correspond to phases of increased water presence in the basin, and (3) lateral shifts in hominin activity areas may reflect adjustments in the water level. The research shows the importance of large‐scale archaeological excavations and a multidisciplinary sampling strategy that covers both the basin center and the margins, when studying postglacial basin localities like Neumark‐Nord 2.
Yes‐associated protein 1 and transcriptional coactivator with PDZ‐binding motif activate the mammalian target of rapamycin complex 1 pathway by regulating amino acid transporters in hepatocellular carcinoma
Authors: Park Yun‐Yong , Sohn Bo Hwa , Johnson Randy L. , Kang Myoung‐Hee , Kim Sang Bae , Shim Jae‐Jun , Mangala Lingegowda S. , Kim Ji Hoon , Yoo Jeong Eun , Rodriguez‐Aguayo Cristian , Pradeep Sunila , Hwang Jun Eul , Jang Hee‐Jin , Lee Hyun‐Sung , Rupaimoole Rajesha , Lopez‐Berestein Gabriel , Jeong Woojin , Park Inn Sun , Park Young Nyun , Sood Anil K. , Mills Gordon B. , Lee Ju‐Seog
Published: September 2015

Metabolic activation is a common feature of many cancer cells and is frequently associated with the clinical outcomes of various cancers, including hepatocellular carcinoma. Thus, aberrantly activated metabolic pathways in cancer cells are attractive targets for cancer therapy. Yes‐associated protein 1 (YAP1) and transcriptional coactivator with PDZ‐binding motif (TAZ) are oncogenic downstream effectors of the Hippo tumor suppressor pathway, which is frequently inactivated in many cancers. Our study revealed that YAP1/TAZ regulates amino acid metabolism by up‐regulating expression of the amino acid transporters solute carrier family 38 member 1 (SLC38A1) and solute carrier family 7 member 5 (SLC7A5). Subsequently, increased uptake of amino acids by the transporters (SLC38A1 and SLC7A5) activates mammalian target of rapamycin complex 1 (mTORC1), a master regulator of cell growth, and stimulates cell proliferation. We also show that high expression of SLC38A1 and SLC7A5 is significantly associated with shorter survival in hepatocellular carcinoma patients. Furthermore, inhibition of the transporters and mTORC1 significantly blocks YAP1/TAZ‐mediated tumorigenesis in the liver. These findings elucidate regulatory networks connecting the Hippo pathway to mTORC1 through amino acid metabolism and the mechanism's potential clinical implications for treating hepatocellular carcinoma. Conclusion: YAP1 and TAZ regulate cancer metabolism and mTORC1 through regulation of amino acid transportation, and two amino acid transporters, SLC38A1 and SLC7A5, might be important therapeutic targets. (Hepatology 2016;63:159–172)
Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining
Authors: Yoshimura Keito , Okanoue Takeshi , Ebise Hayao , Iwasaki Tsuyoshi , Mizuno Masayuki , Shima Toshihide , Ichihara Junji , Yamazaki Kazuto
Published: September 2015

It is important that patients with nonalcoholic steatohepatitis (NASH) are diagnosed and treated early to prevent serious complications, such as liver cirrhosis or hepatocellular carcinoma. However, current methods for NASH diagnosis are invasive given that they rely on liver biopsy, making early diagnosis difficult. In this study, we developed novel noninvasive markers for the diagnosis of NASH and NASH‐related fibrosis. A total of 132 Japanese patients with nonalcoholic fatty liver disease were included in this study. Blood samples were collected, and 261 biomolecules were quantified in serum. Using cluster and pathway analyses, we identified biomolecule modules connected to biological events that occur with disease progression to NASH. The modules were used as variables for diagnosis, leading to a NASH diagnostic marker associated with two biological events, that is, protective response to hepatic steatosis and hepatitis‐causing innate immune response. Regarding the NASH‐related fibrosis marker, immunological responses to hepatocyte injury were identified as a biological event. To develop diagnostic markers for NASH and NASH‐related fibrosis, specific biomolecules were selected from each biomolecule module. The former marker was obtained by averaging the levels of four biomolecules, whereas the latter was obtained by averaging the levels of two biomolecules. Both markers achieved a diagnostic accuracy of almost 0.9 of the area under the receiver operating characteristic curve, and the latter exhibited equivalent performance in an independent group of 62 prospectively recruited patients. Conclusion: We developed highly accurate markers for the diagnosis of both NASH and NASH‐related fibrosis (i.e., FM‐NASH index and FM‐fibro index, respectively). These markers may be used as an alternative diagnostic tool to liver biopsy. (Hepatology 2016;63:462–473)
To Reveal or Conceal? Managers' Disclosures of Private Information During Emotional Intelligence Training
Authors: Thory Kathryn
Published: September 2015

To date, emotional intelligence (EI) training interventions have been underresearched. This study responds to this paucity of scholarship by investigating the occurrence of private disclosures during managerial EI training. While an unorthodox practice, this article argues that trainers introduce opportunities to reveal private information to develop participants’ EI. The aims of this study are to explore the role of such disclosures and how emotion influences managers’ decisions to reveal or conceal private information. Data are drawn from participant observations and interviews with managers and trainers attending three externally provided, “popular” EI training courses. Applying Petronio's communication privacy management theory and Stiles's fever model of distress disclosure to analyze the data, a typology is presented that suggests managers reveal private information for “self‐awareness” and “catharsis” and conceal private information for “self‐protection” and “disengagement.” By applying Petronio's theory to a new work context of training and extending Stiles's model to a range of emotions, the article provides novel insights into managerial control over disclosures, privacy boundary turbulence, and how emotions serve as a resource and condition to disclosure practices. These findings have relevance for trainers and their strategies to develop EI.
Oxidative stress‐related DNA damage and homologous recombination repairing induced by N,N‐dimethylformamide
Authors: Wang Cui , Yang Jinhuan , Lu Dezhao , Fan Yongsheng , Zhao Meirong , Li Zhuoyu
Published: September 2015

The intensified anthropogenic release of N,N‐dimethylformamide (DMF) has been proven to have hepatotoxic effects. However, the potential mechanism for DMF‐induced toxicity has rarely been investigated. Our research implicated that DMF induced a significantly dose‐dependent increase in reactive oxygen species (ROS) in HL‐7702 human liver cells. Moreover, oxidative stress‐related DNA damage, marked as 8‐hydroxy‐2′‐deoxyguanosine, was increased 1.5‐fold at 100 mmol l–1. The most severe DNA lesion (double‐strand break, DSB), measured as the formation of γH2AX foci, was increased at/above 6.4 mmol l–1, and approximately 50% of cells underwent DSB at the peak induction. Subsequently, the DNA repair system triggered by molecules of RAD50 and MRE11A induced the homologous recombination (HR) pathway by upregulation of both gene and protein levels of RAD50, RAD51, XRCC2 and XRCC3 at 16 mmol l–1 and was attenuated at 40 mmol l–1. Consequently, cellular death observed at 40 mmol l–1 was exaggerated compared with exposure at 16 mmol l–1. Although the exact mechanism relying on the DMF‐induced hepatotoxicity needs further clarification, oxidative stress and DNA damage involved in DSBs partially explain the reason for DMF‐induced liver injury. Oxidative stress‐induced DNA damage should be first considered during risk assessment on liver‐targeted chemicals. Copyright © 2015 John Wiley & Sons, Ltd.
Influences of Quantum Mechanically Mixed Electronic and Vibrational Pigment States in 2D Electronic Spectra of Photosynthetic Systems: Strong Electronic Coupling Cases
Authors: Fujihashi Yuta , Fleming Graham R. , Ishizaki Akihito
Published: September 2015

In 2D electronic spectroscopy studies, long‐lived quantum beats have recently been observed in photosynthetic systems, and several theoretical studies have suggested that the beats are produced by quantum mechanically mixed electronic and vibrational states. Concerning the electronic‐vibrational quantum mixtures, the impact of protein‐induced fluctuations was examined by calculating the 2D electronic spectra of a weakly coupled dimer with the Franck‐Condon active vibrational modes in the resonant condition [Fujihashi et al., J. Chem. Phys.­ 2015, 142, 212403.]. This analysis demonstrated that quantum mixtures of the vibronic resonance are rather robust under the influence of the fluctuations at cryogenic temperatures, whereas the mixtures are eradicated by the fluctuations at physiological temperatures. However, this conclusion cannot be generalized because the magnitude of the coupling inducing the quantum mixtures is proportional to the inter‐pigment electronic coupling. In this study, we explore the impact of the fluctuations on electronic‐vibrational quantum mixtures in a strongly coupled dimer with an off‐resonant vibrational mode. Toward this end, we calculate energy transfer dynamics and 2D electronic spectra of a model dimer that corresponds to the most strongly coupled bacteriochlorophyll molecules in the Fenna‐Matthews‐Olson complex in a numerically accurate manner. The quantum mixtures are found to be robust under the exposure of protein‐induced fluctuations at cryogenic temperatures, irrespective of the resonance. At 300 K, however, the quantum mixing is disturbed more strongly by the fluctuations, and therefore, the beats in the 2D spectra become obscure even in a strongly coupled dimer with a resonant vibrational mode. Further, the overall behaviors of the energy transfer dynamics are demonstrated to be dominated by the environment and coupling between the 0 0 vibronic transitions as long as the Huang‐Rhys factor of the vibrational mode is small. The electronic‐vibrational quantum mixtures do not necessarily play a significant role in electronic energy transfer dynamics despite contributing to the enhancement of long‐lived quantum beating in the 2D spectra.
Stepping Into Retirement: A Postcard From the Threshold
Authors: Hoyt Michael F.
Published: September 2015

As I begin a postclinical career transition, I pause and describe various early retirement personal, familial, and professional reverberations, as well as some aging‐related “long‐view” observations about conducting therapy.
A New Energetic Material and its Risk Research
Authors: Han Zhiyue , Zhang Yinghao , Yao Qian , Du Zhiming , He Chunlin , Zhang Jingchang
Published: September 2015

Bis (1, 5‐diamino‐4‐methyl‐tetrazolium) azotetrazolate (BMDATZT) was synthesized with high yield in this work. The yield is 97.46%. The structure was characterized by IR, 1H NMR, and MS. The single crystal of BMDATZT•2H2O was first cultivated. The heat of formation, detonation pressure, and detonation velocity were first calculated. The crystalline density of BMDATZT•2H2O is 1.573 g/cm3. BMDATZT has high detonation pressure and detonation velocity (P =25.06 GPa, D = 7.805 km s−1), which are higher than those of 2,4,6‐Trinitrotoluene (TNT). Its thermal and mechanical sensitivities are moderate. Therefore, it is a kind of insensitive nitrogen‐rich energetic ionic salt with good performance, and it has potential application prospect in gas generating agent, explosive and solid propellant.
Epidemiology of gastroenteritis viruses in Japan: Prevalence, seasonality, and outbreak
Authors: Thongprachum Aksara , Khamrin Pattara , Maneekarn Niwat , Hayakawa Satoshi , Ushijima Hiroshi
Published: September 2015

Acute gastroenteritis has been recognized as one of the most common diseases in humans and continues to be a major public health problem worldwide. Several groups of viruses have been reported as the causative agents of acute gastroenteritis, including rotavirus, norovirus, sapovirus, human astrovirus, adenovirus, and an increasing number of others which have been reported more recently. The epidemiology, prevalence, seasonality, and outbreaks of these viruses have been reviewed in a number of studies conducted in Japan over three decades. Rotavirus and norovirus were the two most common viruses detected almost equally in children under 5 years of age who were suffering from acute gastroenteritis. Like many other countries, the main rotavirus strains circulating in pediatric patients in Japan are G1P[8], G2P[4], G3P[8], and G9P[8]. Norovirus GII.4 was involved in most outbreaks in Japan and found to be associated with the emergence of new variants Sydney_2012. The classic human astrovirus, MLB, and VA clades astroviruses were also commonly found in pediatric patients with acute diarrhea. The sapovirus and adenovirus have been identified as the minor viral causative agents for acute gastroenteritis in Japan.J. Med. Virol. 88:551–570, 2016.© 2015 Wiley Periodicals, Inc.
Robotic rectal surgery
Authors: Rencuzogullari Ahmet , Gorgun Emre
Published: September 2015

Robotic technology is increasingly used in colorectal surgery during last decade. Whether this technology will translate into clinical efficiency and value of care remains to be determined. This review aims to discuss current data in robotic rectal surgery with emphasize on ergonomics, cost, and learning curve aspects. All relevant articles are reviewed in addition to published and unpublished work from the authors’ own experience. J. Surg. Oncol. 2015; 112:326–331. © 2015 Wiley Periodicals, Inc.
The Strongest Correlates of PTSD for Firefighters: Number, Recency, Frequency, or Perceived Threat of Traumatic Events?
Authors: Pinto Ricardo J. , Henriques Sandra P. , Jongenelen Inês , Carvalho Cláudia , Maia Ângela C.
Published: September 2015

Firefighters experience a wide range of traumatic events while on duty and are at risk to develop psychopathology and posttraumatic stress disorder (PTSD). According to cognitive models, the person's interpretation of the traumatic event is responsible for the development of PTSD rather than the traumatic event itself. This cross‐sectional study aimed to explore the contribution of perceived threat to explain PTSD symptoms in Portuguese firefighters, after adjusting for potential confounding factors. A sample of 397 firefighters completed self‐report measures of exposure to traumatic events, psychopathology, and PTSD. Perceived threat explained unique variance in PTSD symptoms, R2 = .40, ΔR2 = .02, F(10, 367) = 24.55, p < .001, Cohen's f2 =.03, after adjusting for psychopathology, number, recency, and frequency of the events, and other potential confounding variables. The association between psychopathology and PTSD was also moderated by perceived threat, R2 = .43, ΔR2 = .03, F(11, 366) = 25.33, p < .001, Cohen's f2 =.05. Firefighters may benefit from interventions that focus on perceived threat to prevent PTSD symptoms.
Deposit‐free Cutting of Polycarbonate
Authors: Holl Kai , Seidel Eva , Seul Thomas
Published: September 2015

Until now, it has not been possible to cut polycarbonate free from visible deposits using laser radiation. Through a smart process control it has been possible to produce cut edges which show no visible deposits or degraded material. The polymer, its additives, the process parameters and the process equipment determine the quality. Only their correct combination leads to good results.
Process Monitoring at Laser Welding of Thermoplastics
Authors: Schmailzl Anton , Steger Sebastian , Hierl Stefan
Published: September 2015

A pyrometer, integrated into a 3D‐scanner, offers the possibility to measure the weld seam temperature at quasi‐simultaneous laser transmission welding. Experimental studies have shown that gaps located in the joining zone can be identified by a temperature rise even at a high scanning velocity. This enables the implementation of algorithms for observation and control strategies.
Patterns and controls of reef‐scale production of dissolved organic carbon by giant kelp Macrocystis pyrifera
Authors: Reed Daniel C. , Carlson Craig A. , Halewood Elisa R. , Nelson J. Clinton , Harrer Shannon L. , Rassweiler Andrew , Miller Robert J.
Published: September 2015

We investigated the patterns and controls of dissolved organic carbon (DOC) production by the giant kelp (Macrocystis pyrifera) using data from short‐term in situ incubations of entire blades and portions of stipes. These data were incorporated into an empirical model of reef‐scale net primary production (NPP) at Mohawk Reef in southern California, U.S.A. for an 8‐yr period. Rates of DOC release of incubated blades varied unpredictably with time of year, but were significantly related to the irradiance at the sea surface during the incubations. The growth stage, C/N ratio, and epiphyte load of the blades and the temperature of the ocean during the incubations had no discernable effect on rates of DOC release. Blades produced on average 2–3 times more DOC than stipes, and stipes and blades produced on average 30% and 80% more DOC respectively during the day compared to the night. Modeled DOC NPP at the reef scale was on average highest in summer and spring (∼0.5 g C m−2 d−1) and lowest in winter and autumn (∼0.31 g C m−2 d−1), but it varied greatly among years for any given season as large oscillations in standing biomass led to corresponding fluctuations in reef‐scale DOC NPP. The fraction of NPP released as DOC was highly variable when examined at the monthly time scale, but became much more stable at seasonal and annual time scales averaging 14% of total NPP.
Fundamental limits on the losses of phase and amplitude optical actuators
Authors: Zanotto Simone , Morichetti Francesco , Melloni Andrea
Published: September 2015

Amplitude and phase are the basic properties of all wave phenomena; as far as optical waves are concerned, the ability to act on these variables is at the root of a wealth of switching devices. To quantify the performance of an optical switching device, an essential aspect is to determine the tradeoff between the insertion loss and the amplitude or phase modulation depth. Here it is shown that every optical switching device is subject to such a tradeoff, intrinsically connected to the dielectric response of the materials employed inside the switching element itself. This limit finds its roots in fundamental physics, as it directly derives from Maxwell's equations for linear dielectrics, and is hence applicable to a wide class of optical components. Furthermore, a result is that concepts such as filtering, resonance, and critical coupling could be of advantage in approaching the limit.

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Subnormothermic ex vivo liver perfusion is a safe alternative to cold static storage for preserving standard criteria grafts
Authors: Spetzler Vinzent N. , Goldaracena Nicolas , Echiverri Juan , Kaths J. Moritz , Louis Kristine S. , Adeyi Oyedele A. , Yip Paul M. , Grant David R. , Selzner Nazia , Selzner Markus
Published: September 2015

We developed a novel technique of subnormothermic ex vivo liver perfusion (SNEVLP) for the storage of liver grafts before transplantation. To test the safety of SNEVLP for the nonextended criteria grafts (standard grafts), we compared it to a control group with minimal cold static storage (CS) time. Heart‐beating pig liver retrieval was performed. Grafts were either stored in cold unmodified University of Wisconsin solution (CS‐1), in cold University of Wisconsin solution with ex vivo perfusion additives (CS‐2), or preserved with a sequence of 3 hours CS and 3 hours SNEVLP (33°C), followed by orthotopic liver transplantation. Liver function tests and histology were investigated. Aspartate aminotransferase (AST) levels during SNEVLP remained stable (54.3 ± 12.6 U/L at 1 hour to 47.0 ± 31.9 U/L at 3 hours). Posttransplantation, SNEVLP versus CS‐1 livers had decreased AST levels (peak at day 1, 1081.9 ± 788.5 versus 1546.7 ± 509.3 U/L; P = 0.14; at day 2, 316.7 ± 188.1 versus 948.2 ± 740.9 U/L; P = 0.04) and alkaline phosphatase levels (peak at day 1, 150.4 ± 19.3 versus 203.7 ± 33.6 U/L; P = 0.003). Bilirubin levels were constantly within the physiological range in the SNEVLP group, whereas the CS‐1 group presented a large standard deviation, including pathologically increased values. Hyaluronic acid as a marker of endothelial cell (EC) function was markedly improved by SNEVLP during the early posttransplant phase (5 hours posttransplant, 1172.75 ± 598.5 versus 5540.5 ± 2755.4 ng/mL). Peak international normalized ratio was similar between SNEVLP and CS‐1 groups after transplantation. Immunohistochemistry for cleaved caspase 3 demonstrated more apoptotic sinusoidal cells in the CS‐1 group when compared to SNEVLP grafts 2 hours after reperfusion (19.4 ± 19.5 versus 133.2 ± 48.8 cells/high‐power field; P = 0.002). Adding normothermic CS‐2 had no impact on liver injury or function after transplantation when compared to CS‐1. In conclusion, SNEVLP is safe to use for standard donor grafts and is associated with improved EC and bile duct injury even in grafts with minimal CS time. Liver Transpl 22:111‐119, 2016. © 2015 AASLD.
Outflow reconstruction for right liver allograft with multiple hepatic veins: “V‐plasty” of hepatic veins to form a common outflow channel versus 2 or more hepatic vein–to–inferior vena cava anastomoses in limited retrohepatic space
Authors: Thorat Ashok , Jeng Long‐Bin , Yang Horng‐Ren , Li Ping‐Chun , Li Ming‐Li , Yeh Chun‐Chieh , Chen Te‐Hung , Hsu Shih‐Chao , Poon Kin‐Shing
Published: September 2015

Outflow reconstruction in living donor liver transplantation (LDLT) is certainly difficult in limited retrohepatic space with using right liver grafts with venous anomalies. Venoplasty of the inferior right hepatic veins (IRHVs) and middle hepatic vein (MHV) reconstruction using synthetic grafts to form a common outflow channel or a second venocaval anastomosis are available options. We aim to compare outcomes of LDLT recipients who underwent outflow reconstruction with a “V‐Plasty” technique and outcomes of patients who underwent a second venocaval anastomosis. Out of 325 recipients who underwent LDLT from March 2011 to September 2014, 45 received right liver allografts that were devoid of MHV with multiple draining IRHVs (2 or more). Group A (n = 16) comprised the recipients with outflow reconstruction with a V‐Plasty, and group B (n = 29) included the recipients with a second venocaval anastomosis. Group A recipients (male:female, 10:6; median age, 50.5 years) had a mean Model for End‐Stage Liver Disease score of 14.7, whereas for group B recipients (male:female, 20:9; median age, 52.0 years) it was 17.2. The mean IRHV diameter for group A and B grafts was 8.3 mm each. Mean warm ischemia time for group A was significantly lower (25.2 minutes) as compared to group B recipients (34.6 minutes) with P < 0.001. The 2‐month patency rates of vascular grafts were 100% for group A recipients with no evidence of thrombosis. In conclusion, the V‐Plasty technique of MHV and IRHV reconstruction to form a common outflow is a new concept that proves to be a safe and feasible alternative for second venocaval anastomosis. Liver Transpl 22:192‐200, 2016. © 2015 AASLD.
Delayed‐onset Friedreich's ataxia revisited
Authors: Lecocq Claire , Charles Perrine , Azulay Jean‐Philippe , Meissner Wassilios , Rai Myriam , N'Guyen Karine , Péréon Yann , Fabre Nelly , Robin Elsa , Courtois Sylvie , Guyant‐Maréchal Lucie , Zagnoli Fabien , Rudolf Gabrielle , Renaud Mathilde , Sévin‐Allouet Mathieu , Lesne Fabien , Alaerts Nick , Goizet Cyril , Calvas Patrick , Eusebio Alexandre , Guissart Claire , Derkinderen Pascal , Tison Francois , Brice Alexis , Koenig Michel , Pandolfo Massimo , Tranchant Christine , Dürr Alexandra , Anheim Mathieu
Published: September 2015

Background

Friedreich's ataxia usually occurs before the age of 25. Rare variants have been described, such as late‐onset Friedreich's ataxia and very‐late‐onset Friedreich's ataxia, occurring after 25 and 40 years, respectively. We describe the clinical, functional, and molecular findings from a large series of late‐onset Friedreich's ataxia and very‐late‐onset Friedreich's ataxia and compare them with typical‐onset Friedreich's ataxia.

Methods

Phenotypic and genotypic comparison of 44 late‐onset Friedreich's ataxia, 30 very late‐onset Friedreich's ataxia, and 180 typical Friedreich's ataxia was undertaken.

Results

Delayed‐onset Friedreich's ataxia (late‐onset Friedreich's ataxia and very‐late‐onset Friedreich's ataxia) had less frequently dysarthria, abolished tendon reflexes, extensor plantar reflexes, weakness, amyotrophy, ganglionopathy, cerebellar atrophy, scoliosis, and cardiomyopathy than typical‐onset Friedreich's ataxia, along with less severe functional disability and shorter GAA expansion on the smaller allele (P < 0.001). Delayed‐onset Friedreich's ataxia had lower scale for the assessment and rating of ataxia and spinocerebellar degeneration functional scores and longer disease duration before wheelchair confinement (P < 0.001). Both GAA expansions were negatively correlated to age at disease onset (P < 0.001), but the smaller GAA expansion accounted for 62.9% of age at onset variation and the larger GAA expansion for 15.6%. In this comparative study of late‐onset Friedreich's ataxia and very‐late‐onset Friedreich's ataxia, no differences between these phenotypes were demonstrated.

Conclusion

Typical‐ and delayed‐onset Friedreich's ataxia are different and Friedreich's ataxia is heterogeneous. Late‐onset Friedreich's ataxia and very‐late‐onset Friedreich's ataxia appear to belong to the same clinical and molecular continuum and should be considered together as “delayed‐onset Friedreich's ataxia.” As the most frequently inherited ataxia, Friedreich's ataxia should be considered facing compatible pictures, including atypical phenotypes (spastic ataxia, retained reflexes, lack of dysarthria, and lack of extraneurological signs), delayed disease onset (even after 60 years of age), and/or slow disease progression.
An in vitro gastrulation model recapitulates the morphogenetic impact of pharmacological inhibitors of developmental signaling pathways
Authors: Li Aileen S. W. , Marikawa Yusuke
Published: September 2015

Certain chemical agents act as teratogens, causing birth defects and fetal deaths when pregnant women are exposed to them. The establishment of in vitro models that recapitulate crucial embryonic events is therefore vital to facilitate screening of potential teratogens. Previously, we created a three‐dimensional culture method for mouse P19C5 embryonal carcinoma stem cells that, when cultured as embryoid bodies, display elongation morphogenesis resembling gastrulation, which is the critical event resulting in the germ layers and major body axes. Determination of how well this in vitro morphogenesis represents in vivo gastrulation is essential to assess its applicability as well as to identify limitations of the model for detecting teratogenic agents. Here, we investigated the morphological and molecular characteristics of P19C5 morphogenesis using pharmacological agents that are known to cause abnormal patterning in the embryo in vivo by inhibiting major developmental signaling—e.g., involving Wnt, Nodal, Bone morphogenic protein (Bmp), Fibroblast growth factor (Fgf), Retinoic acid, Notch, and Hedgehog pathways. Inhibitors of Wnt, Nodal, Bmp, Fgf, and Retinoic acid signaling caused distinct changes in P19C5 morphogenesis that were quantifiable using morphometric parameters. These five inhibitors, plus the Notch inhibitor, also altered temporal expression profiles of developmental regulator genes in a manner consistent with the in vivo roles of the corresponding signaling pathways. In contrast, the Hedgehog inhibitor did not have any impact on the process, suggesting an absence of active Hedgehog signaling in these embryoid bodies. These results indicate that the P19C5 in vitro gastrulation model is a promising tool to screen for teratogenic agents that interfere with many of the key developmental signals. Mol. Reprod. Dev. 82: 1015–1036, 2015. © 2015 Wiley Periodicals, Inc.
RF peak power reduction in CAIPIRINHA excitation by interslice phase optimization
Authors: Sbrizzi Alessandro , Poser Benedikt A. , Tse Desmond H. Y. , Hoogduin Hans , Luijten Peter R. , van den Berg Cornelis A. T.
Published: September 2015

The purpose of this work was to show that the overall peak power of RF pulses for CAIPIRINHA excitation can be substantially reduced by applying interslice phase relaxation. The optimal phases are scan dependent and can be quickly calculated by the proposed method.

The multi‐band RF pulse design is implemented as the minimization of a linear objective function with quadratic constraints. The interslice phase is considered to be a variable for optimization. In the case of a phase cycling scheme (CAIPIRINHA), the peak power is considered over all pulses.

The computation time (about 1 s) is compatible with online RF pulse design. It is shown that the optimal interslice phases depend on the CAIPIRINHA scheme used and that RF peak power is reduced when the CAIPIRINHA phase cycling is taken into account in the optimization.

The proposed method is extremely fast and results in RF pulses with low peak power for CAIPIRINHA excitation. The MATLAB implementation is given in the appendix; it allows for online determination of scan‐dependent phase parameters. Furthermore, the method can be easily extended to pTx shimming systems in the context of multi‐slice excitations, and this possibility is included in the software. Copyright © 2015 John Wiley & Sons, Ltd.
Genetically engineered mouse models for studying inflammatory bowel disease
Authors: Mizoguchi Atsushi , Takeuchi Takahito , Himuro Hidetomo , Okada Toshiyuki , Mizoguchi Emiko
Published: September 2015

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting‐edge technologies such as cell‐specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Animal modelling for inherited central vision loss
Authors: Kostic Corinne , Arsenijevic Yvan
Published: September 2015

Disease‐causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale‐up of new therapies. Examples of innovative approaches will be presented such as lentiviral‐based transgenesis in pigs and adeno‐associated virus (AAV)‐gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Rheological properties and fracture toughness of epoxy resin/multi‐walled carbon nanotube composites
Authors: Park Soo‐Jin , Heo Gun‐Young , Jin Fan‐Long
Published: September 2015

Multi‐walled carbon nanotubes (MWCNTs), surface‐treated via chemical functionalization, i.e., oxidation and amidation, were used to reinforce diglycidylether of bisphenol F (DGEBF) epoxy resin. The effects of the functionalization on the dispersion stability, rheological properties, and fracture toughness of DGEBF/MWCNT composites were investigated. The dispersion homogeneity of the MWCNTs in the epoxy matrix improved after functionalization. In addition, isothermal rheology measurements revealed that the DGEBF/dodecyl amine‐functionalized MWCNT (D‐MWCNT) composite had a longer gel time and higher activation energy of cross‐linking than the DGEBF/acid‐treated MWCNT (A‐MWCNT) composite. The fracture toughness of the former was also significantly higher than that of the latter; this resulted from the relatively high dispersion stability of the D‐MWCNTs in the epoxy matrix, owing to the presence of alkyl groups on the D‐MWCNT surface. POLYM. ENG. SCI., 55:2676–2682, 2015. © 2015 Society of Plastics Engineers
The Rayleigh law in silicon doped hafnium oxide ferroelectric thin films
Authors: Guan Yan , Zhou Dayu , Xu Jin , Liu Xiaohua , Cao Fei , Dong Xianlin , Müller Johannes , Schenk Tony , Schroeder Uwe
Published: September 2015

A wealth of studies have confirmed that the low‐field hysteresis behaviour of ferroelectric bulk ceramics and thin films can be described using Rayleigh relations, and irreversible domain wall motion across the array of pining defects has been commonly accepted as the underlying micro‐mechanism. Recently, HfO2 thin films incorporated with various dopants were reported to show pronounced ferroelectricity, however, their microscopic domain structure remains unclear till now. In this work, the effects of the applied electric field amplitude, frequency and temperature on the sub‐coercive polarization reversal properties were investigated for 10 nm thick Si‐doped HfO2 thin films. The applicability of the Rayleigh law to ultra‐thin ferroelectric films was first confirmed, indicating the existence of a multi‐domain structure. Since the grain size is about 20–30 nm, a direct observation of domain walls within the grains is rather challenging and this indirect method is a feasible approach to resolve the domain structure. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Static anti‐windup design for a class of Markovian jump systems with partial information on transition rates
Authors: Wei Yunliang , Zheng Wei Xing , Xu Shengyuan
Published: September 2015

This paper investigates the problem of static anti‐windup design for uncertain continuous‐time Markovian jump systems with partially unknown transition rates in the face of actuator saturation. The underlying system is subject to time‐varying and norm‐bounded parameter uncertainties in both the state and input matrices. It is assumed that a set of stabilizing dynamic output‐feedback controllers have been designed for the system in the absence of control saturation. The objective is to design anti‐windup compensation gains for the given controllers such that the system can still be stabilized, irrespective of whether actuator saturation appears or not. To obtain a maximum estimation of the domain of attraction of the resulting closed‐loop system, a convex optimization problem in the linear matrix inequality framework is formulated. Furthermore, the results are extended to the cases of the systems with completely known transition rates and with completely unknown transition rates. Finally, the usefulness of the developed method is demonstrated through simulation examples. Copyright © 2015 John Wiley & Sons, Ltd.
Hire, Fire, or Train: Innovation and Human Capital Responses to Recessions
Authors: Knudsen Eirik Sjåholm , Lien Lasse B.
Published: September 2015

Research summary

We examine how firms' relative emphasis on exploration and exploitation influence their human capital responses to recessions. We hypothesize and find that the higher the focus on exploration, the more firms invest in training, the more likely they are to hire, and the more likely they are to lay off employees during a recession. Finally, we also find that exploration‐oriented firms are more likely to combine the accumulation of human capital through training, with both hiring and firing. This indicates that firms focusing on exploration more actively pursue the opportunities created by increased labor market imperfections during recessions. These results contribute to the literature by highlighting how recessions affect firms' flow of human capital investments, and subsequently stocks, depending on their strategic orientations.

Managerial summary

We examine how firms' strategic orientations influence how they respond to recessions in terms of their human capital. We find that the higher the strategic focus on exploration of new opportunities, the more firms invest in training, the more likely they are to hire, and the more likely they are to lay off employees during a recession. The opposite is the case for firms with a higher focus on exploiting existing (cost) advantages. Finally, we find that exploration‐oriented firms are more likely to combine the three human capital responses. In sum, our findings indicate that firms emphasizing innovation and exploration of new opportunities more actively pursue the opportunities created in labor markets during recessions.
Srebp-1 Interacts with c-Myc to Enhance Somatic Cell Reprogramming
Authors: Wu Yi , Chen Keshi , Liu Xiyin , Huang Lili , Zhao Danyun , Li Linpeng , Gao Mi , Pei Duanqing , Wang Chenguang , Liu Xingguo
Published: September 2015

Somatic cell reprogramming is accompanied by changes in lipid metabolism. While attempting to dissect the molecular mechanisms of the lipid metabolic switch during reprogramming, we found that overexpression of sterol regulatory element binding protein-1 (Srebp-1), a transcriptional factor required for lipid homeostasis, enhances reprogramming efficiency, while knockdown or pharmaceutical inhibition of Srebp-1 is inhibitory. Srebp-1 overexpression blocks the formation of partially reprogrammed cells, and functions in the early phase of reprogramming. Furthermore, Srebp-1 functions in nucleus and depends on its transcriptional activity but not its ability to bind the E-box motif and regulation of canonical targets. Mechanistically, Srebp-1 interacts with c-Myc, facilitates its binding to downstream pluripotent targets, strengthens the function of c-Myc in enhancing other Yamanaka factors' binding, and thereby promotes the expression of pluripotent genes. These results elucidate a novel role for Srebp-1 in somatic cell reprogramming and provide insights into understanding the metabolic switch during reprogramming.

Video Highlight: https://youtu.be/DfC5vz8q-ts
Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase
Authors: Okada Motoi , Kim Ha Won , Matsu-ura Kaoru , Wang Yi-Gang , Xu Meifeng , Ashraf Muhammad
Published: September 2015

Previously, we reported that a novel subpopulation of young mesenchymal stem cells (YMSCs) existed in old bone marrow, which possessed high antiaging properties as well as excellent efficacy for cardiac repair. MicroRNAs (miRNAs) have emerged as key regulators in post-transcriptional gene expression programs, and however, it is unknown whether miRNAs directly control stem cell senescence. Here we present the first evidence that miR-195 overexpressed in old MSCs (OMSCs) induces stem cell senescence deteriorating their regenerative ability by directly deactivating telomerase reverse transcriptase (Tert), and abrogation of miR-195 can reverse stem cell aging. MiRNAs profiling analysis in YMSCs and OMSCs by microarray showed that miR-140, miR-146a/b, and miR-195 were significantly upregulated in OMSCs, which led us to hypothesize that these are age-induced miRNAs involved in stem cell senescence. Of these miRNAs, we found miR-195 directly targeted 3′-untranslated region of Tert gene by computational target prediction analysis and luciferase assay, and knockdown of miR-195 significantly increased Tert expression in OMSCs. Strikingly, miR-195 inhibition significantly induced telomere relengthening in OMSCs along with reduced expression of senescence-associated β-galactosidase. Moreover, silencing miR-195 in OMSCs by transfection of miR-195 inhibitor significantly restored antiaging factors expression including Tert and Sirt1 as well as phosphorylation of Akt and FOXO1. Notably, abrogation of miR-195 markedly restored proliferative abilities in OMSCs. Transplantation of OMSCs with knocked out miR-195 reduced infarction size and improved LV function. In conclusion, rejuvenation of aged stem cells by miR-195 inhibition would be a promising autologous therapeutic strategy for cardiac repair in the elderly patients.
IONA test for first‐trimester detection of trisomies 21, 18 and 13
Authors: Poon L. C. , Dumidrascu‐Diris D. , Francisco C. , Fantasia I. , Nicolaides K. H.
Published: September 2015

Objective

To assess the potential performance of screening for fetal trisomies 21, 18 and 13 by cell‐free DNA (cfDNA) analysis of maternal blood using the IONA® test.

Methods

This was a nested case–control study of cfDNA analysis of maternal plasma using the IONA test. Samples were obtained at 11–13 weeks' gestation, before chorionic villus sampling, from 201 euploid pregnancies, 35 with trisomy 21, four with trisomy 18 and two with trisomy 13. Laboratory personnel were blinded to the fetal karyotype.

Results

Probability scores for trisomies 21, 18 and 13 were given for 241/242 samples analyzed. No probability score was provided for one (0.5%) euploid pregnancy because of low fetal fraction. In all 35 cases of trisomy 21 the probability score for trisomy 21 was > 95% and the scores for trisomies 18 and 13 were ≤ 0.0001%. In all four cases of trisomy 18, the probability score for trisomy 18 was > 77% and the scores for trisomies 21 and 13 were ≤ 0.0001%. In the two cases of trisomy 13, the probability score for trisomy 13 was > 59% and the scores for trisomies 21 and 18 were ≤ 0.0001%. In the 200 euploid pregnancies with a test result, the probability score was < 0.08% for trisomy 21, < 0.001% for trisomy 18 and < 0.002% for trisomy 13. Therefore, the IONA test detected 100% of all three trisomies, with a false‐positive rate of 0%.

Conclusion

The IONA test successfully differentiated all cases of trisomies 21, 18 and 13 from euploid pregnancies. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.