bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and improvement of cross‐regulation effect in the primary side‐regulated multi‐output flyback converter
Authors: Guo Xifeng , Luan Fangjun , Liu Jian , Liu Meiju
Published: January 2017

In the multi‐output primary side‐regulated (PSR) flyback converters, cross‐regulation effect denotes the phenomenon that change of load current in either one of the outputs would lead to the output voltage variations in other output terminals. Because the PSR flyback converters are frequently used to provide power supplies in a power system, the steady operation of the power system may be affected. Based on an improved Cantilever model, this paper proposes a thorough analysis on the cross‐regulation effect in the PSR flyback converter. It has been found that the coupling between the output windings and the topology of the output terminal would have significant influence on the cross‐regulation effect. Moreover, a mathematical expression has been derived to calculate the relationship, in the time domain, between the voltages of the output windings in the PSR flyback converter. In the mathematical expression, the leakage inductances in the improved cantilever model are lumped into a matrix R′. Hence, the winding method and the geometry of the transformer can be optimized to improve the precision of the multi‐output voltages in the PSR flyback converter. A 10‐W PSR flyback prototype with three output terminals is built. Experimental results are given to validate the theoretical analysis. Copyright © 2017 John Wiley & Sons, Ltd.
Make faculty development accessible with short online lessons
Authors: Hope Joan
Published: January 2017

Faculty members appreciate high‐quality professional development opportunities. But getting them to show up for training sessions can be a challenge. And if your institution is like most, you don't have the funding to pay them extra to attend sessions.
Seek out innovative ways to educate your community
Authors: Sutton Halley
Published: January 2017

After graduating from Eastern Washington University, Keith Snow‐Flamer, president of the College of the Redwoods in California, thought his career would be in the Marines, not in higher education. However, after five years in the Marines, Snow‐Flamer left to work for Kraft Foods and Mobil Oil. While there, he started considering the legacy of his long‐term work.
Development of a new statewide eating disorder service: The role of evidence in a real world setting
Authors: Wade Tracey , Vall Eva , Kuek Angeline , Altman Emma , Long Randall , Mannion John
Published: January 2017

Objective

There are three aims of this report. First, to describe how research evidence informed a service development rationale for a new statewide eating disorder service (SEDS) for people aged 15 years and older. Second, to examine the profile of people accessing SEDS in the first 2 years of its operation with respect to the three broad dimensions: illness stage, illness severity, and previous history of treatment. Finally, to examine which patient characteristics resulted in the recommendation of ongoing treatment contact with SEDS.

Method

Over a 2‐year period (July 2014 to July 2016) 292 people were referred to the service, 171 (59%) who consented to have their data used in research.

Results

Half of the referrals related to anorexia nervosa (AN; 51.2%), with the remainder split between bulimia nervosa (25.3%) and other specified feeding and eating disorders (23.5%); 65.9% had previously received treatment for an eating disorder. The initial information about the service was typically provided by the general practitioner/primary care physician. Compared with any other eating disorder diagnosis, people with AN were three times more likely to be recommended to retain treatment contact with SEDS.

Discussion

Service development informed by research evidence, clinical expertise, and consideration of patients’ characteristics, values, and circumstances, allows for a flexible but accountable development strategy.
Combined effects of landscape composition and heterogeneity on farmland avian diversity
Authors: Santana Joana , Reino Luís , Stoate Chris , Moreira Francisco , Ribeiro Paulo F. , Santos José L. , Rotenberry John T. , Beja Pedro
Published: January 2017

Conserving biodiversity on farmland is an essential element of worldwide efforts for reversing the global biodiversity decline. Common approaches involve improving the natural component of the landscape by increasing the amount of natural and seminatural habitats (e.g., hedgerows, woodlots, and ponds) or improving the production component of the landscape by increasing the amount of biodiversity‐friendly crops. Because these approaches may negatively impact on economic output, it was suggested that an alternative might be to enhance the diversity (compositional heterogeneity) or the spatial complexity (configurational heterogeneity) of land cover types, without necessarily changing composition. Here, we develop a case study to evaluate these ideas, examining whether managing landscape composition or heterogeneity, or both, would be required to achieve conservation benefits on avian diversity in open Mediterranean farmland. We surveyed birds in farmland landscapes of southern Portugal, before (1995–1997) and after (2010–2012) the European Union's Common Agricultural Policy (CAP) reform of 2003, and related spatial and temporal variation in bird species richness to variables describing the composition, and the compositional and configurational heterogeneity, of the natural and production components of the landscape. We found that the composition of the production component had the strongest effects on avian diversity, with a particularly marked effect on the richness of farmland and steppe bird species. Composition of the natural component was also influential, mainly affecting the richness of woodland/shrubland species. Although there were some effects of compositional and configurational heterogeneity, these were much weaker and inconsistent than those of landscape composition. Overall, we suggest that conservation efforts in our area should focus primarily on the composition of the production component, by striving to maximize the prevalence of biodiversity‐friendly crops. This recommendation probably applies to other areas such as ours, where a range of species of conservation concern is strongly associated with crop habitats.
Contrasting effects of plant inter‐ and intraspecific variation on community trait responses to restoration of a sandy grassland ecosystem
Authors: Zuo Xiaoan , Yue Xiyuan , Lv Peng , Yu Qiang , Chen Min , Zhang Jing , Luo Yongqing , Wang Shaokun , Zhang Jing
Published: January 2017

Changes in plant community traits along an environmental gradient are caused by interspecific and intraspecific trait variation. However, little is known about the role of interspecific and intraspecific trait variation in plant community responses to the restoration of a sandy grassland ecosystem. We measured five functional traits of 34 species along a restoration gradient of sandy grassland (mobile dune, semi‐fixed dune, fixed dune, and grassland) in Horqin Sand Land, northern China. We examined how community‐level traits varied with habitat changes and soil gradients using both abundance‐weighted and non‐weighted averages of trait values. We quantified the relative contribution of inter‐ and intraspecific trait variation in specific leaf area (SLA), leaf dry matter content (LDMC), leaf carbon content (LCC), leaf nitrogen content (LNC), and plant height to the community response to habitat changes in the restoration of sandy grassland. We found that five weighted community‐average traits varied significantly with habitat changes. Along the soil gradient in the restoration of sandy grassland, plant height, SLA, LDMC, and LCC increased, while LNC decreased. For all traits, there was a greater contribution of interspecific variation to community response in regard to habitat changes relative to that of intraspecific variation. The relative contribution of the interspecific variation effect of an abundance‐weighted trait was greater than that of a non‐weighted trait with regard to all traits except LDMC. A community‐level trait response to habitat changes was due largely to species turnover. Though the intraspecific shift plays a small role in community trait response to habitat changes, it has an effect on plant coexistence and the maintenance of herbaceous plants in sandy grassland habitats. The context dependency of positive and negative covariation between inter‐ and intraspecific variation further suggests that both effects of inter‐ and intraspecific variation on a community trait should be considered when understanding a plant community response to environmental changes in sandy grassland ecosystems.
Timing of nest vegetation measurement may obscure adaptive significance of nest‐site characteristics: A simulation study
Authors: McConnell Mark D. , Monroe Adrian P. , Burger Loren Wes , Martin James A.
Published: January 2017

Advances in understanding avian nesting ecology are hindered by a prevalent lack of agreement between nest‐site characteristics and fitness metrics such as nest success. We posit this is a result of inconsistent and improper timing of nest‐site vegetation measurements. Therefore, we evaluated how the timing of nest vegetation measurement influences the estimated effects of vegetation structure on nest survival. We simulated phenological changes in nest‐site vegetation growth over a typical nesting season and modeled how the timing of measuring that vegetation, relative to nest fate, creates bias in conclusions regarding its influence on nest survival. We modeled the bias associated with four methods of measuring nest‐site vegetation: Method 1—measuring at nest initiation, Method 2—measuring at nest termination regardless of fate, Method 3—measuring at nest termination for successful nests and at estimated completion for unsuccessful nests, and Method 4—measuring at nest termination regardless of fate while also accounting for initiation date. We quantified and compared bias for each method for varying simulated effects, ranked models for each method using AIC, and calculated the proportion of simulations in which each model (measurement method) was selected as the best model. Our results indicate that the risk of drawing an erroneous or spurious conclusion was present in all methods but greater with Method 2 which is the most common method reported in the literature. Methods 1 and 3 were similarly less biased. Method 4 provided no additional value as bias was similar to Method 2 for all scenarios. While Method 1 is seldom practical to collect in the field, Method 3 is logistically practical and minimizes inherent bias. Implementation of Method 3 will facilitate estimating the effect of nest‐site vegetation on survival, in the least biased way, and allow reliable conclusions to be drawn.
The long‐term legacy of geomorphic and riparian vegetation feedbacks on the dammed Bill Williams River, Arizona, USA
Authors: Kui Li , Stella John C. , Shafroth Patrick B. , House P. Kyle , Wilcox Andrew C.
Published: January 2017

On alluvial rivers, fluvial landforms and riparian vegetation communities codevelop as a result of feedbacks between plants and abiotic processes. The influence of vegetation on river channel and floodplain geomorphology can be particularly strong on dammed rivers with altered hydrology and reduced flood disturbance. We used a 56‐year series of aerial photos on the dammed Bill Williams River (Arizona, USA) to investigate how (a) different woody riparian vegetation types influence river channel planform and (b) how different fluvial landforms drive the composition of riparian plant communities over time. We mapped vegetation types and geomorphic surfaces and quantified how relations between fluvial and biotic processes covaried over time using linear mixed models. In the decades after the dam was built, woody plant cover within the river's bottomland nearly doubled, narrowing the active channel by 60% and transforming its planform from wide and braided to a single thread and more sinuous channel. Compared with native cottonwood–willow vegetation, nonnative tamarisk locally induced a twofold greater reduction in channel braiding. Vegetation expanded at different rates depending on the type of landform, with tamarisk cover on former high‐flow channels increasing 17% faster than cottonwood–willow. Former low‐flow channels with frequent inundation supported a greater increase in cottonwood–willow relative to tamarisk. These findings give insight into how feedbacks between abiotic and biotic processes in river channels accelerate and fortify changes triggered by dam construction, creating river systems increasingly distinct from predam ecological communities and landforms, and progressively more resistant to restoration of predam forms and processes.
Ruthenium(II)–Pyridylimidazole Complexes as Photoreductants and PCET Reagents
Authors: Pannwitz Andrea , Prescimone Alessandro , Wenger Oliver S.
Published: January 2017

Complexes of the type [Ru(bpy)2pyimH]2+ [bpy = 2,2′‐bipyridine; pyimH = 2‐(2‐pyridyl)imidazole] with various substituents on the bpy ligands can act as photoreductants. Their reducing power in the ground state and in the long‐lived 3MLCT excited state is increased significantly upon deprotonation, and they can undergo proton‐coupled electron transfer (PCET) in the ground and excited state. PCET with both the proton and electron originating from a single donor resembles hydrogen atom transfer (HAT) and can be described thermodynamically by formal bond dissociation free energies (BDFEs). Whereas the class of complexes studied herein has long been known, their N–H BDFEs have not been determined even though this is important in view of assessing their reactivity. Our study demonstrates that the N–H BDFEs in the 3MLCT excited states are between 34 and 52 kcal mol–1 depending on the chemical substituents at the bpy spectator ligands. Specifically, we report on the electrochemistry and PCET thermochemistry of three heteroleptic complexes in 1:1 (v/v) CH3CN/H2O with CF3, tBu, and NMe2 substituents on the bpy ligands.
Au15Ag3(SPhMe2)14 Nanoclusters – Crystal Structure and Insights into Ligand‐Induced Variation
Authors: Kang Xi , Silalai Chantiem , Lv Ying , Sun Guodong , Chen Shuang , Yu Haizhu , Xu Fengqing , Zhu Manzhou
Published: January 2017

Understanding the ligand effects in the nanocluster (NC) range is crucial for tailoring the properties. We herein report on the crystal structure of the Au15Ag3(SPhMe2)14 nanocluster. Compared with the previously reported Au15Au3(SC6H11)14 nanocluster, Au15Ag3(SPhMe2)14 exhibits a different crystal and electronic structure, which further affects the optical spectra because of the ligand effect. In combination with density functional theory (DFT) calculations, the differences in the UV/Vis spectra were found to be caused by the distinct electronic components of the frontier orbitals. In addition, accompanied by many recrystallization steps on Au15Ag3(SPhMe2)14, mass spectrometry analysis revealed that the by‐products (i.e. Au14Ag4 and Ag13Ag5 nanoclusters) gradually decompose, and finally only the Au15Ag3 nanocluster exists. Our findings offer an extended insight into the ligand‐induced variation on a nanocluster level.
Hoveyda‐Type Quinone‐Containing Complexes – Catalysts to Prevent Migration of the Double Bond under Metathesis Conditions
Authors: Kajetanowicz Anna , Milewski Mariusz , Rogińska Joanna , Gajda Roman , Woźniak Krzysztof
Published: January 2017

Three new quinone‐containing Hoveyda‐type complexes have been synthesised and fully characterised. Their ability to suppress undesired double‐bond migration along the carbon chain during metathesis reactions was examined. It was proved that these catalysts decrease the amounts of undesired side‐products with a shifted double bond in the reaction mixture.
Solar Air Heating and Ventilation in Buildings: A Key Component in the Forthcoming Renewable Energy Mix
Authors: Ciriminna Rosaria , Meneguzzo Francesco , Pecoraino Mario , Pagliaro Mario
Published: January 2017

The achievements of the last two decades in using solar energy for naturally ventilating and heating buildings of any size and scope across the world are remarkable, though comprising a niche market and being generally poorly known to this point. Air quality, thermal and hygrometric comfort, and reduced energy costs are some of the benefits provided by solar ventilated spaces. We identify the remaining hurdles to be addressed prior to forthcoming widespread adoption of this technology in the building environment across the world, well beyond the cold‐climate countries.
Effect of temperature and aging on the adsorption and desorption of menadione in soil
Authors: Gao Minling , Lv Mengting , Gong Xiaolei , Song Wenhua , Qi Yun , Li Zhen
Published: January 2017

In this study, the effect of soil temperature and aging on the adsorption and desorption of menadione was investigated using the batch equilibrium method. The obtained isotherm data can be well fitted to the linearized form of the Freundlich equation, with R2 values ranging between 0.91 and 1.00. The adsorption and desorption of menadione in non‐aged (control) soil increased significantly when the temperature ranged between 15 and 37°C. Among soils that were amended with menadione and aged for 72 h, the sample with 2 μg·g−1 amendment showed significantly higher adsorption/desorption than those with 10 and 20 μg·g−1 amendments (P < 0.05). Thermodynamic and isotherm hysteresis analyses demonstrated that the sorption of menadione on the control and aged soils was a spontaneous and endothermic process. Physical sorption was the predominant mechanism, and there was negative hysteresis during desorption. Furthermore, thermodynamic calculation and infrared spectral analyses suggested that the main sorption force was hydrogen bonding in all the soil samples, and the entropy gain in the whole adsorbate‐adsorbent system was the main thermodynamic driving force. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 997–1004, 2017
Effects of cadmium, manganese, and lead on locomotor activity and neurexin 2a expression in zebrafish
Authors: Tu Hongwei , Fan Chengji , Chen Xiaohui , Liu Jiaxian , Wang Bin , Huang Zhibin , Zhang Yiyue , Meng Xiaojing , Zou Fei
Published: January 2017

The synaptic adhesion protein Neurexin 2a (Nrxn2a) plays a key role in neuronal development and is associated with cognitive functioning and locomotor behavior. Although low-level metal exposure poses a potential risk to the human nervous system, especially during the developmental stages, little is known about the effects of metal exposures on nrxn2a expression during embryonic development. We therefore exposed wild-type zebrafish embryos/larvae to cadmium (CdCl2), manganese (MnCl2), and lead ([CH3COO]2Pb), to determine their effect on mortality, malformation, and hatching rate. Concentrations of these metals in zebrafish were detected by inductively coupled plasma mass spectrometry analysis. Locomotor activity of zebrafish larvae was analyzed using a video-track tracking system. Expression of nrxn2a was assessed by in situ hybridization and quantitative polymerase chain reaction. The results showed that mortality, malformation, and bioaccumulation increased as the exposure dosages and duration increased. Developmental exposure to these metals significantly reduced larval swim distance and velocity. The nrxn2aa and nrxn2ab genes were expressed in the central nervous system and downregulated by almost all of the 3 metals, especially Pb. These data demonstrate that exposure to metals downregulates nrxn2a in the zebrafish model system, and this is likely linked to concurrent developmental processes. Environ Toxicol Chem 2017;36:2147–2154. © 2017 SETAC
Dynamic downlink resource allocation and access strategy for femtocell networks
Authors: Jiang Zhefeng , Mao Shiwen , Wang Xin
Published: January 2017

Femtocells are small, low‐power cellular base stations with high potential for coverage extension and offloading voice and wireless data. In this paper, we study the problem of joint access control and spectrum resource allocation in a 2‐tier femtocell network with 1 macro base station and multiple Femto access points (FAPs). The objective is to maximize the overall network capacity, while guaranteeing the quality of service requirement of all user equipments. We develop an access scheme for macro user equipments and a spectrum allocation mechanism for the FAPs. Spectrum allocation is used as an incentive mechanism to encourage FAPs to serve more macro user equipments. We also derive an upper bound of the network‐wide capacity through a reformulation of the problem. The proposed algorithms are validated, and the upper bound is shown to be quite accurate in the simulation study.
Sedimentary environment and geomorphic development of the uppermost Siwalik molasse in Kumaun Himalayan Foreland Basin, North India
Authors: Kotlia Bahadur Singh , Goswami Pradeep K. , Joshi Lalit Mohan , Singh Anoop Kumar , Sharma Arun Kumar
Published: January 2017

An area of about 250 sq. km. around Ramnagar and Garjiya within the Siwalik molasse in the Kumaun foothills was mapped for geomorphic evolution and sedimentation pattern. The area, bounded by Himalayan Frontal Thrust (HFT) in the south and Main Boundary Thrust (MBT) in the north, consists of the sediments of uppermost part of the Pinjor and overlying Boulder Conglomerate Formations. Sedimentologically, three facies associations (FAA–FAC) were recognized with their order of superposition as FAA → FAB, FAA → FAC, FAB → FAC and FAC → FAB with variability in depositional setting. Lithofacies FAA–FAC were seemingly deposited in sand‐dominated fluvial channel belt, gravelly braided channel belt and cut‐off channel settings, respectively. The sediment dispersal in the basin was influenced by active basinal tectonics that caused frequent avulsions during the Bounder Bed times. The compositions of the clasts of these lithofacies reveal a shift in the primary provenance from pre‐Tertiary Himalayan hinterlands during the emplacement of FAA (of the Pinjor Formation) to evolving frontal Siwalik highlands during the emplacement of FAB and FAC (of the Bouldder Conglomerate Formation). This temporal shift in the provenance indicates exhumation of the older Siwalik sequences during the later phases of Himalayan orogeny. A number of subordinate faults, oblique to above mentioned intracrustal boundary thrusts and formed after the sedimentation was seized, were likely responsible for displacement between the sediments of different associations. The neotectonic rejuvenation is also reflected by the upliftment of two sister basins in opposite direction, rapid uplift in V‐shaped valleys, fault escarpments, three levels of terrace development and displacement of rock types along the subordinate faults as well as deflection and entrenchment in the course of lower order streams. Copyright © 2017 John Wiley & Sons, Ltd.
The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis
Authors: Shimizu Yutaka , Peltzer Nieves , Sevko Alexandra , Lafont Elodie , Sarr Aida , Draberova Helena , Walczak Henning
Published: January 2017

Linear ubiquitination is a key posttranslational modification that regulates immune signaling and cell death pathways, notably tumor necrosis factor receptor 1 (TNFR1) signaling. The only known enzyme complex capable of forming linear ubiquitin chains under native conditions to date is the linear ubiquitin chain assembly complex, of which the catalytic core component is heme‐oxidized iron regulatory protein 2 ubiquitin ligase‐1–interacting protein (HOIP). To understand the underlying mechanisms of maintenance of liver homeostasis and the role of linear ubiquitination specifically in liver parenchymal cells, we investigated the physiological role of HOIP in the liver parenchyma. To do so, we created mice harboring liver parenchymal cell–specific deletion of HOIP (HoipΔhep
mice) by crossing Hoip‐floxed mice with albumin–Cre mice. HOIP deficiency in liver parenchymal cells triggered tumorigenesis at 18 months of age preceded by spontaneous hepatocyte apoptosis and liver inflammation within the first month of life. In line with the emergence of inflammation, HoipΔhep
mice displayed enhanced liver regeneration and DNA damage. In addition, consistent with increased apoptosis, HOIP‐deficient hepatocytes showed enhanced caspase activation and endogenous formation of a death‐inducing signaling complex which activated caspase‐8. Unexpectedly, exacerbated caspase activation and apoptosis were not dependent on TNFR1, whereas ensuing liver inflammation and tumorigenesis were promoted by TNFR1 signaling. Conclusion: The linear ubiquitin chain assembly complex serves as a previously undescribed tumor suppressor in the liver, restraining TNFR1‐independent apoptosis in hepatocytes which, in its absence, is causative of TNFR1‐mediated inflammation, resulting in hepatocarcinogenesis. (Hepatology 2017;65:1963‐1978).
Central role of the TIR‐domain‐containing adaptor‐inducing interferon‐β (TRIF) adaptor protein in murine sterile liver injury
Authors: Brempelis Katherine J. , Yuen Sebastian Y. , Schwarz Nicole , Mohar Isaac , Crispe Ian N.
Published: January 2017

Multiple pathways drive the sterile injury response in the liver; however, it is unclear how the type of cells injured or the mechanism of injury activates these pathways. Here, we use a model of selective hepatocyte death to investigate sterile liver injury. In this model, the TIR‐domain‐containing adaptor‐inducing interferon‐β (TRIF) was a central mediator of the resulting intrahepatic inflammatory response that was independent of both upstream Toll‐like receptor (TLR) 4 signaling and downstream type I interferon (IFN) signaling. TRIF was required for induction of interleukin (IL)‐10, IL‐6, and IL‐1β cytokines. Conversely, although induction of C‐C motif chemokine ligand (CCL) 2 and C‐X‐C motif chemokine ligand (CXCL) 1 chemokines and up‐regulation of chemokine (Ccl2, Ccl7, Cxcl1, Cxcl2, and Cxcl10) and cell‐adhesion (intracellular adhesion molecule 1 and vascular cell adhesion molecule 1) genes involved in myeloid cell recruitment was reduced in a majority of TRIF–/– mice, a subset of TRIF–/– mice showed breakthrough inflammation and the ability to induce these genes and proteins, indicating that redundant pathways exist to respond to hepatocyte death. Furthermore, we found that hepatocytes themselves were the main responders to hepatocyte death, increasing transcription of genes involved in myeloid cell recruitment more than either liver sinusoidal endothelial cells or Kupffer cells. Conclusion: Our studies define a TRIF‐dependent, TLR4‐ and type I IFN‐independent pathway of sterile liver injury in which hepatocytes are both the targets of damage and the principal responding cell type. (Hepatology 2017;65:1336‐1351).
A prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis
Authors: Bissonnette Julien , Altamirano José , Devue Cécile , Roux Olivier , Payancé Audrey , Lebrec Didier , Bedossa Pierre , Valla Dominique , Durand François , Ait‐Oufella Hafid , Sancho‐Bru Pau , Caballeria Joan , Ginès Pere , Boulanger Chantal M. , Bataller Ramon , Rautou Pierre‐Emmanuel
Published: January 2017

The diagnosis of alcoholic hepatitis (AH) often requires a transjugular liver biopsy (TJLB), a procedure that is not always readily accessible. We analyzed plasma biomarkers to estimate the presence of histological features of AH among patients with clinical suspicion of AH. Using enzyme‐linked immunosorbent assay, we tested M65 and M30 (circulating fragments of cytokeratin‐18) and their respective fraction carried by microvesicles (MVs), CCL20 and TREM1. Leukocyte, platelet, and endothelial‐derived MVs were quantified by way of flow cytometry. Test and validation cohorts prospectively included patients with clinical features of AH undergoing TJLB. In the test cohort, 46 of 83 (55%) patients showed histological features of AH. Age, bilirubin, INR, and creatinine (ABIC) score was B or C in 83%. Patients with histologically proven AH had higher levels of total and MV‐bound M65 and total and MV‐bound M30 and CCL20 than those without (P < 0.001 for all tests). Levels of TREM‐1 and of subpopulations of MVs were not different between groups. M65 and M30 both had an area under the receiver operating characteristics curve of 0.84 to estimate the presence of AH. For M65, a cutoff of 2000 IU/L had a positive predictive value of 91%, whereas a cutoff of 641 IU/L had a negative predictive value of 88%. In the validation cohort, AH was histologically confirmed in 48 of 68 (71%) patients. ABIC score was B or C in 69% of patients. For M65, the above cutoffs had a diagnostic accuracy of 81%. Even better results were obtained in patients with suspicion of severe AH (ABIC B or C) in both cohorts. Conclusion: Plasma levels of cytokeratin‐18 fragments are reliable noninvasive markers of AH. Using the proposed cutoffs for M65, two thirds of TJLB can be avoided, which can be useful in centers where this technique is not readily available. (Hepatology 2017;66:555–563).
Ventral hippocampal neurons inhibit postprandial energy intake
Authors: Hannapel Reilly C. , Henderson Yoko H. , Nalloor Rebecca , Vazdarjanova Almira , Parent Marise B.
Published: January 2017

Evidence suggests that the memory of a recently ingested meal limits subsequent intake. Given that ventral hippocampal (vHC) neurons are involved in memory and energy intake, the present experiment tested the hypothesis that vHC neurons contribute to the formation of a memory of a meal and inhibit energy intake during the postprandial period. We tested (1) whether pharmacological inactivation of vHC neurons during the period following a sucrose meal, when the memory of the meal would be undergoing consolidation, accelerates the onset of the next sucrose meal and increases intake and (2) whether sucrose intake increases vHC expression of the synaptic plasticity marker activity‐regulated cytoskeletal‐associated protein (Arc). Adult male Sprague‐Dawley rats were trained to consume a 32% sucrose solution daily at the same time and location. On the experimental day, the rats were given intra‐vHC infusions of the GABAA receptor agonist muscimol or vehicle after they finished their first sucrose meal. Compared to vehicle infusions, postmeal intra‐vHC muscimol infusions decreased the latency to the next sucrose meal, increased the amount of sucrose consumed during that meal, increased the total number of sucrose meals and the total amount of sucrose ingested. In addition, rats that consumed sucrose had higher levels of Arc expression in both vHC CA1 and CA3 subfields than cage control rats. Collectively, these findings are the first to show that vHC neurons inhibit energy intake during the postprandial period and support the hypothesis that vHC neurons form a memory of a meal and inhibit subsequent intake. © 2016 Wiley Periodicals, Inc.
A phase I, randomized, proof‐of‐clinical‐mechanism study assessing the pharmacokinetics and pharmacodynamics of the oral PDE9A inhibitor BI 409306 in healthy male volunteers
Authors: Boland Katja , Moschetti Viktoria , Dansirikul Chantaratsamon , Pichereau Solen , Gheyle Lien , Runge Frank , Zimdahl‐Gelling Heike , Sand Michael
Published: January 2017

Objective

Cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE) inhibitors are hypothesized to improve cognition in schizophrenia and Alzheimer disease by increasing cGMP levels in certain brain regions. This phase I, randomized, parallel‐group, double‐blind, placebo‐controlled study provides proof‐of‐mechanism evidence for BI 409306, a novel, oral PDE9A inhibitor.

Methods

In healthy males, exposure of BI 409306 (25‐, 50‐, 100‐, and 200‐mg single dose) and placebo was assessed in plasma and cerebrospinal fluid (CSF). Effect of BI 409306 on CSF cGMP levels was evaluated, and adverse events (AEs) were monitored.

Results

In all enrolled subjects (N = 20), plasma BI 409306 concentration increased rapidly (median tmax: 0.75–1.25 hr) followed by rapid increases in CSF (median tmax: 1.5–2.0 hr). Maximum CSF cGMP concentrations were achieved within 2 to 5 hr, declining to baseline levels 10 to 14 hr after dosing. Dose‐dependent increases in plasma and CSF exposure and CSF cGMP were shown. BI 409306 was safe and well tolerated. Most AEs were mild to moderate in intensity and study procedure–related.

Conclusions

BI 409306 increased rapidly in plasma and was subsequently detected in CSF, resulting in dose‐dependent increases in cGMP levels in CSF. Results indicate BI 409306 efficiently crosses the blood‐CSF barrier, with an acceptable level of AEs.
Cervical cancer incidence after screening with HPV, cytology, and visual methods: 18‐Year follow‐up of the Guanacaste cohort
Authors: Rodríguez Ana Cecilia , Ávila Carlos , Herrero Rolando , Hildesheim Allan , Sherman Mark E. , Burk Robert D. , Morales Jorge , Alfaro Mario , Guillén Diego , Trejos María Ethel , Vargas Rosa María , Torres Guillermo , Schiffman Mark
Published: January 2017

Testing negative for human papillomavirus (HPV) predicts long‐term reassurance against invasive cervical cancer (ICC). To provide realistic estimates of effectiveness for new screening programs, we studied ICC risk after a 7‐year repeated multimethod screening effort. In 1993–1994, 10,049 women aged 18–97 years were enrolled into a population‐based cohort study of cervical HPV in Guanacaste, Costa Rica. Women were screened at different intervals according to enrollment results. Each visit (mean 3.2, 90% attendance) included split‐sample conventional, automated, and liquid‐based cytology, visual inspection, cervicography, and PCR‐based HPV testing. Abnormal screening led to colposcopy and excisional treatment as appropriate during the study. Referral to colposcopy for HPV in the absence of other findings was introduced only at the last visit. Population‐based Costa Rica Cancer Registry linkage identified cohort women diagnosed with ICC in the 18 years following cohort enrollment. The ICC cumulative risk was 0.4% (n = 38); 18 were diagnosed with ICC after study participation. Of these, 9 were missed at the screening step (negative screening or below the referral threshold, refused screening or colposcopy), 5 attended colposcopy but were not diagnosed as CIN2+, and 4 were treated for CIN2/3 but progressed to ICC nonetheless. Decreasing age‐standardized ICC rates for the 1993–2011 period were observed in Guanacaste; cohort women showed additional 31% ICC incidence reduction with apparent downstaging of cancers that occurred. ICC risk following negative HPV testing in the optimal age range 30–50 years was extremely low. Real‐life screening effectiveness following introduction is lower than the potential near‐complete efficacy predicted by HPV natural history.
Fabrication and characterization of shape memory polyurethane porous scaffold for bone tissue engineering
Authors: Yu Juhong , Xia Hong , Teramoto Akira , Ni Qing‐Qing
Published: January 2017

Tissue engineering is a promising alternative for treating bone defects. However, improvements in scaffold design are needed to precisely match the irregular boundaries of bone defects as well as facilitate clinical application. In this study, a shape memory polyurethane scaffold was fabricated using a salt‐leaching‐phase inverse technique. Different sizes of salts were used to obtain scaffolds with different pore sizes. Scanning electron microscope, X‐ray photoelectron spectroscopy, and X‐ray micro‐computed tomography analysis confirmed that three‐dimensional porous polyurethane scaffolds were obtained. The mechanical properties and biocompatibility of the scaffolds were analyzed by compression testing, thermal mechanical analysis, and cell experiments with osteosarcoma MG‐63 cells. The results revealed that the scaffolds had good mechanical properties and shape memory properties for bone repair, and also had the ability to promote cell proliferation. Thus, this scaffold design has good prospects for application to bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1132–1137, 2017.
Cytokine networks and their association with Helicobacter pylori infection in gastric carcinoma
Authors: Bagheri Vahid , Memar Bahram , Momtazi Amir Abbas , Sahebkar Amirhossein , Gholamin Mehran , Abbaszadegan Mohammad Reza
Published: January 2017

Cytokine networks as dynamic networks are pivotal aspects of tumor immunology, especially in gastric cancer (GC), in which infection, inflammation, and antitumor immunity are key elements of disease progression. In this review, we describe functional roles of well‐known GC‐modulatory cytokines, highlight the functions of cytokines with more recently described roles in GC, and emphasize the therapeutic potential of targeting the complex cytokine milieu. We also focus on the role of Helicobacter pylori (HP)‐induced inflammation in GC and discuss how HP‐induced chronic inflammation can lead to the induction of stem cell hyperplasia, morphological changes in gastric mucosa and GC development.
Nanotubes impregnated human olfactory bulb neural stem cells promote neuronal differentiation in Trimethyltin‐induced neurodegeneration rat model
Authors: Marei Hany E. , Elnegiry Ahmed A. , Zaghloul Adel , Althani Asma , Afifi Nahla , Abd‐Elmaksoud Ahmed , Farag Amany , Lashen Samah , Rezk Shymaa , Shouman Zeinab , Cenciarelli Carlo , Hasan Anwarul
Published: January 2017

Neural stem cells (NSCs) are multipotent self‐renewing cells that could be used in cellular‐based therapy for a wide variety of neurodegenerative diseases including Alzheimer's diseases (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Being multipotent in nature, they are practically capable of giving rise to major cell types of the nervous tissue including neurons, astrocytes, and oligodendrocytes. This is in marked contrast to neural progenitor cells which are committed to a specific lineage fate. In previous studies, we have demonstrated the ability of NSCs isolated from human olfactory bulb (OB) to survive, proliferate, differentiate, and restore cognitive and motor deficits associated with AD, and PD rat models, respectively. The use of carbon nanotubes (CNTs) to enhance the survivability and differentiation potential of NSCs following their in vivo engraftment have been recently suggested. Here, in order to assess the ability of CNTs to enhance the therapeutic potential of human OBNSCs for restoring cognitive deficits and neurodegenerative lesions, we co‐engrafted CNTs and human OBNSCs in TMT‐neurodegeneration rat model. The present study revealed that engrafted human OBNSCS‐CNTs restored cognitive deficits, and neurodegenerative changes associated with TMT‐induced rat neurodegeneration model. Moreover, the CNTs seemed to provide a support for engrafted OBNSCs, with increasing their tendency to differentiate into neurons rather than into glia cells. The present study indicate the marked ability of CNTs to enhance the therapeutic potential of human OBNSCs which qualify this novel therapeutic paradigm as a promising candidate for cell‐based therapy of different neurodegenerative diseases.
Quantitative determination of nine water‐soluble vitamins in the complex matrix of corn steep liquor for raw material quality assessment
Authors: Hofer Alexandra , Herwig Christoph
Published: January 2017

BACKGROUND

Although raw materials such as corn steep liquor (CSL) are commonly used as supplements in media for biotechnological production of valuable products such as antibiotics, however, determination of the composition of CSL is still a scarcely explored field of research. Especially for some B‐vitamins, which are badly soluble and compose just a small fraction in CSL, no adequate analytical method has been published yet.

RESULTS

In this study we adopted a RP‐HPLC‐UV method for the simultaneous determination of nine water‐soluble vitamins (biotin, cyanocobalamin, folic acid, niacin amide, nicotinic acid, pantothenic acid, pyridoxine, riboflavin, thiamine) and evaluated six different methods for the extraction of vitamins from CSL (two liquid–liquid extractions and four enzymatic extractions). The proposed method showed relative errors of about 2%; LOD and LOQ were ranged between 0.07 and 0.875 µg mL−1 and 0.2 and 2.5 µg mL−1, respectively, deviating just for the low absorbing pantothenic acid. The method was successfully applied to eight CSL samples which differed in manufacturer and corn quality (dried or wet corn). Seven out of nine vitamins could be identified in CSL and correlations between some vitamins and manufacturer (i.e. nicotinic acid, pantothenic acid and biotin) and quality (i.e. thiamine, pyridoxine and cyanocobalamin), respectively, could be observed.

CONCLUSION

The variation in vitamin composition found in the different CSL samples points out the importance of an incoming inspection of CSL to reduce variations in bioprocesses which are caused by raw material variability. This contribution provides a valuable quantitative tool for this task. © 2017 Society of Chemical Industry
Tibial Nerve Block Using an Ultrasound‐Guided Inframalleolar Medial Plantar Nerve Perineural Injection: A Technical Note
Authors: Burke Christopher J. , Adler Ronald S.
Published: January 2017

Sonographic‐guided tibial nerve block allows for rapid anesthetization of the heel and plantar regions of the foot. We describe a variant technique for tibial nerve regional anesthesia utilizing perineural injection of the medial plantar nerve proximal to the sustentaculum tali where the nerve is superficial and readily accessed, with resultant retrograde flow of local anesthetic proximally. Perineural injection of the medial plantar nerve at the inframalleolar level provides a simple, safe, and effective alternative method to achieve tibial nerve block for regional anesthesia in a variety of procedures. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:134–137, 2017
Comparative binding to DR4 and DR5 receptors of TRAIL and BNNTs/PAHE/mPEG‐DSPE/TRAIL nanoparticles
Authors: Guillaume Yves Claude , André Claire
Published: January 2017

TRAIL is a member of the tumor necrosis factor family of cytokines, which induces apoptosis of cancer cells, thanks to its binding to its cognate receptors DR5 and DR4. We have recently demonstrated that nanovectorization of TRAIL with single‐walled carbon nanotubes enhanced TRAIL affinity to DR5. In this paper, 1‐pyrenebutyric acid N‐hydroxysuccinimide ester functionalized boron nitride nanotubes (BNNTs) were used to anchor the TRAIL protein. The resulting BNNT/1‐pyrenebutyric acid N‐hydroxysuccinimide ester nanotubes were mixed with methoxy‐poly(ethylene glycol)‐1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐conjugates so as to allow a good dispersion of these nanoparticle TRAIL (NPT) in aqueous solution. The difference of binding between NPT and soluble TRAIL to DR4 and DR5 receptors was then studied by the use of affinity chromatography. DR4 and DR5 receptors were thus immobilized on a chromatographic support, and the binding of the 2 ligands TRAIL and NPT to DR4 and DR5 was studied in the temperature range 30°C to 50°C. Negative enthalpy (ΔH) values indicated that van der Waals interactions and hydrogen bonding are engaged favorably at the ligand‐receptor interface. It was shown that their rank‐ordered affinities were strongly different in the sequence TRAILDR4 < NPTDR4 < TRAILDR5 < NPTDR5, and the highest affinity for NPT to DR4 and DR5 receptors observed at low pHs was due to the less accessibility of the His molecular switch to be protonated when TRAIL was immobilized on BNNTs. Taken together, our results demonstrated that nanovectorization of TRAIL with BNNTs enhanced its binding to both DR4 and DR5 receptors at 37°C. Our novel nanovector could potentially be used for delivering TRAIL to cells for cancer treatment.
In silico characterization of enantioselective molecularly imprinted binding sites
Authors: Terracina Jacob J. , Sharfstein Susan T. , Bergkvist Magnus
Published: January 2017

A 2‐step molecular mechanical and quantum mechanical geometry optimization scheme (MM ➔ QM) was used to “computationally imprint” chiral molecules. Using a docking technique, we show the imprinted binding sites to exhibit an enantioselective preference for the imprinted molecule over its enantiomer. Docking of structurally similar chiral molecules showed that the sites computationally imprinted with R‐ or S‐tBOC‐tyrosine were able to differentiate between R‐ and S‐forms of other tyrosine derivatives. The cross‐enantioselectivity did not hold for chiral molecules that did not share the tyrosine H‐bonding functional group orientations. Further analysis of the individual monomer‐target interactions within the binding site lead us to conclude that H‐bonding functional groups that are located immediately next to the chiral center and therefore spatially fixed relative to the chiral center will have a stronger contribution to the enantioselectivity of the site than those groups separated from the chiral center by 2 or more rotatable bonds. Here, we present our novel approach for computationally imprinting and characterizing enantioselective binding sites. All modeling schemes were designed to minimize the computational expense. In silico analysis of the properties of molecularly imprinted polymer systems will ultimately allow for the fabrication of more sensitive and selective materials.
Functional MRI of human pancreas using BOLD contrast: Responses following glucose ingestion
Authors: Chen Bozhu , Chen Weibo , Chan Queenie , Zhou Nan , He Jian , Zhou Zhengyang
Published: January 2017

Purpose

To evaluate the response of the pancreas to glucose ingestion in healthy volunteers by blood oxygenation level‐dependent (BOLD) magnetic resonance imaging (MRI).

Materials and Methods

This study was approved by the local Ethics Committee, and informed consent was obtained from all subjects. A multiple gradient recalled echo (mGRE) sequence was performed on a 3.0T MR scanner in 12 healthy volunteers before and after glucose or water ingestion. Pancreatic
values were calculated from it at each timepoint, and changes following stimulation were analyzed using summary measures. The valley values and times were compared between the glucose and water ingestion by paired samples t‐test. The repeatability of the pancreatic
measurements was assessed by calculating the intraclass correlation coefficient (ICC) and coefficient of variation (CV).

Results

Pancreatic
measurements showed good repeatability (all ICC >0.75). CV for the six baseline acquisitions was 2.74 ± 0.97%, indicating a 5.37% measurement error. A transient but significant decrease (–6.88 ± 1.01%, P value, 0.0005–0.0467) in the pancreatic
values was observed within 5 minutes after glucose ingestion, rather than water consumption. Compared to water, glucose ingestion induced earlier (valley times: 3.46 ± 3.22 vs. 7.75 ± 4.09 min, P = 0.0006) and remarkable pancreatic
decrease (valley values: –15.33 ± 5.90% vs. –6.88 ± 3.11%, P = 0.0006).

Conclusion

BOLD MRI enabled noninvasive quantification of pancreatic
changes during glucose stimulation. Glucose ingestion resulted in a rapid and significant pancreatic
decrease in healthy young volunteers.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. MAGN. RESON. IMAGING 2017;46:831–836