bluuebunny/crossref_metadata_2025 huggingface dataset:
Encapsulation and Polymerization of White Phosphorus Inside Single‐Wall Carbon Nanotubes
Authors: Hart Martin , White Edward R. , Chen Ji , McGilvery Catriona M. , Pickard Chris J. , Michaelides Angelos , Sella Andrea , Shaffer Milo S. P. , Salzmann Christoph G.
Published: May 2017

Elemental phosphorus displays an impressive number of allotropes with highly diverse chemical and physical properties. White phosphorus has now been filled into single‐wall carbon nanotubes (SWCNTs) from the liquid and thereby stabilized against the highly exothermic reaction with atmospheric oxygen. The encapsulated tetraphosphorus molecules were visualized with transmission electron microscopy, but found to convert readily into chain structures inside the SWCNT “nanoreactors”. The energies of the possible chain structures were determined computationally, highlighting a delicate balance between the extent of polymerization and the SWCNT diameter. Experimentally, a single‐stranded zig‐zag chain of phosphorus atoms was observed, which is the lowest energy structure at small confinement diameters. These one‐dimensional chains provide a glimpse into the very first steps of the transformation from white to red phosphorus.
Die Instandsetzung der Tonröhrenunterkünfte der Holocaustgedenkstätte in Landsberg am Lech
Authors: Rehm Jörg , Maus Helmut , Jagfeld Matthias
Published: May 2017

Das nahe der Stadt Landsberg am Lech gelegene ehemalige Konzentrationslager Kaufering VII wurde im Sommer 1944 als eines von elf Außenlagern des KZ Dachau errichtet. Mit Ausnahme von drei intakten und drei ruinösen Tonröhrenbauwerken sind keine oberflächig sichtbaren Baukörper des Lagers erhalten geblieben. Diese Bauwerke wurden als Unterkünfte für Zwangsarbeiter genutzt. Sie sind eine der letzten Zeugnisse für die menschenverachtende Internierung von Zivilisten während des Dritten Reichs.

Es ist dem engagierten Einsatz der Bürgerinitiative „Europäische Holocaustgedenkstätte Stiftung e. V.” zu verdanken, dass der vollständige Verfall der Bauwerke verhindert wurde. Ab 2009 wurden Maßnahmen zum dauerhaften Erhalt der baulichen Reste geplant und bis 2016 umgesetzt. Dabei sollten Schäden an noch intakten und bereits eingestürzten Bauwerken nur so weit bearbeitet und behoben werden, dass Gefährdungen für Besucher ausgeschlossen werden können und der weitere Verfall verzögert wird.

Die drei stehen gebliebenen, gewölbten und erdüberdeckten Tonröhrenbauwerke waren einsturzgefährdet. Die Gewölbeschalen, die Schildwände und die Sockel wiesen Risse und bereichsweise Durchfeuchtungen auf. Zahlreiche Tonröhren waren beschädigt oder fehlten komplett. Die denkmalpflegerische Vorgabe hatte die Bestandssicherung und den Erhalt des überkommenen Charakters der Baracken zum Inhalt. Eine substanzschonende, von der Außenseite durchgeführte Ertüchtigung besonders schadhafter Gewölbeabschnitte, kombiniert mit der Abdichtung der Raumschale gegen Niederschlagswasser, war für das Erreichen der Vorgaben zielführend.

Die durchgeführten Maßnahmen wurden 2016 mit dem Bayerischen Denkmalpflegepreis in Gold gewürdigt.
Synthesis and multi‐spectroscopic study on DNA‐binding, cleavage and biological properties of M(II) complexes based on N2O2 donor Schiff base ligand
Authors: Dhayabaran V. Violet , Prakash T. Daniel
Published: May 2017

A novel Schiff base, (S,Z)‐4‐(methylthio)‐2‐((3‐oxo‐2,3‐dihydro‐1H‐inden‐1‐ylidene)amino)butanoic acid (L) and four M(II) complexes (where M = Co, Cu, Ni and Zn) were synthesized and characterized. The DNA‐binding characteristics of the complexes were investigated using various spectroscopic methods and viscosity measurements. Analysis of the results suggests that all the complexes bind to calf thymus DNA via intercalation. Among the four, Cu(II) complex was found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm. These complexes also exhibit good antioxidant activities against 2,2‐diphenyl‐1‐picrylhydrazyl radical. In vitro antibacterial and antifungal assay indicates that these complexes are good antimicrobial agents.
Validity and reliability of the CatWalk system as a static and dynamic gait analysis tool for the assessment of functional nerve recovery in small animal models
Authors: Kappos Elisabeth A. , Sieber Patricia K. , Engels Patricia E. , Mariolo Alessio V. , D'Arpa Salvatore , Schaefer Dirk J. , Kalbermatten Daniel F.
Published: May 2017

Introduction

A range of behavioral testing paradigms have been developed for the research of central and peripheral nerve injuries with the help of small animal models. Following any nerve repair strategy, improved functional outcome may be the most important evidence of axon regeneration. A novel automated gait analysis system, the CatWalk™, can measure dynamic as well as static gait patterns of small animals. Of most interest in detecting functional recovery are in particular dynamic gait parameters, coordination measures, and the intensity of the animals paw prints. This article is designed to lead to a more efficient choice of CatWalk parameters in future studies concerning the functional evaluation of nerve regeneration and simultaneously add to better interstudy comparability.

Methods

The aims of the present paper are threefold: (1) to describe the functional method of CatWalk gait analysis, (2) to characterize different parameters acquired by CatWalk gait analysis, and to find the most frequently used parameters as well as (3) to compare their reliability and validity throughout the different studies.

Results

In the reviewed articles, the most frequently used parameters were Swing Duration (30), Print Size (27), Stride Length (26), and Max Contact Area (24). Swing Duration was not only frequently used but was also the most reliable and valid parameter. Therefore, we hypothesize that Swing Duration constitutes an important parameter to be chosen for future studies, as it has the highest level of reliability and validity.

Conclusion

In conclusion, CatWalk can be used as a complementary approach to other behavioral testing paradigms to assess clinically relevant behavioral benefits, with the main advantage that this system demonstrates both static and dynamic gait parameters at the same time. Due to limited reliability and validity of certain parameters, we recommend that only the most frequently assessed parameters should be used in the future.
A computational investigation of learning behaviors in MOOCs
Authors: Zhong Sheng‐Hua , Li Yanhong , Liu Yan , Wang Zhiqiang
Published: May 2017

Massive open online courses (MOOCs) are the latest e‐learning initiative to attain widespread popularity in the world. Thus, it is highly required to have a throughout analysis of learning in MOOCs, from theoretical to practical. Our primary goal is to take a detailed and comprehensive investigation into the learning behaviors in MOOCs, as well as to identify issues that have not yet to be adequately resolved. We employed commonly used educational data mining methodologies to analyze and interpret the behaviors in a computer science course based on the questionnaire survey data and daily activity data. We find most of the students could be divided into several groups that are coincident with their learning styles. Moreover, we can easily predict students’ learning styles based on their learning behaviors. This finding means the learning style could be a factor to indicate students’ learning behaviors, or even measure whether a student is appropriate to learn via MOOCs.
Metal‐free Hydroalkoxylation‐Formal [4+2] Cycloaddition Cascade for the Synthesis of Ketals
Authors: Gharpure Santosh J. , Nanda Santosh K. , Padmaja  , Shelke Yogesh G.
Published: May 2017

A transition metal free, acid promoted cascade hydroalkoxylation–formal [4+2] cycloaddition of various alkynols with salicylaldehyde is demonstrated for the synthesis of tetrahydrofurano/pyrano‐chromenes and spiroketals. In general, alkynols underwent hydroalkoxylations in an endo‐dig manner when internal alkynes were used to furnish the heteroannular ketals, whereas terminal alkynes proceeded in an exo‐dig fashion leading to spiroketals. The study revealed that intramolecular hydroalkoxylation of alkynols is a preferred path over a generation of oxonium ions when coupling partner is salicylaldehyde. This metal‐free transformation provides a new avenue for the stereoselective synthesis of tetrahydrofurano‐ and pyrano‐chromenes in an expeditious manner.
Identification of Breast Cancer Inhibitors Specific for G Protein‐Coupled Estrogen Receptor (GPER)‐Expressing Cells
Authors: Aiello Francesca , Carullo Gabriele , Giordano Francesca , Spina Elena , Nigro Alessandra , Garofalo Antonio , Tassini Sabrina , Costantino Gabriele , Vincetti Paolo , Bruno Agostino , Radi Marco
Published: May 2017

Together with estrogen receptors ERα and ERβ, the G protein‐coupled estrogen receptor (GPER) mediates important pathophysiological signaling pathways induced by estrogens and is currently regarded as a promising target for ER‐negative (ER−) and triple‐negative (TN) breast cancer. Only a few selective GPER modulators have been reported to date, and their use in cancer cell lines has often led to contradictory results. Herein we report the application of virtual screening and cell‐based studies for the identification of new chemical scaffolds with a specific antiproliferative effect against GPER‐expressing breast cancer cell lines. Out of the four different scaffolds identified, 8‐chloro‐4‐(4‐chlorophenyl)pyrrolo[1,2‐a]quinoxaline 14 c was found to be the most promising compound able to induce: 1) antiproliferative activity in GPER‐expressing cell lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained induction of cell‐cycle negative regulators p53 and p21.
Mixed Matrix Membranes with Excellent CO2 Capture Induced by Nano‐Carbon Hybrids
Authors: Pan Xinglong , Zhang Jianqiang , Xue Qingzhong , Li Xiaofang , Ding Degong , Zhu Lei , Guo Tianchao
Published: May 2017

1 D multi‐walled carbon nanotube/graphene oxide nanoribbon (MWCNT@GONRs) hybrids were prepared using a chemical method as fillers for Pebax‐based mixed matrix membranes (MMMs) with excellent CO2 separation performance. Herein, the GONRs shell provided a selective barrier and large gas adsorption area, which contributed to enhancement of gas selectivity, while MWCNTs core with smooth internal surface acted as a rapid transport channel, which improved the gas permeability. It is found that MMMs with 1 wt % loading showed the highest separation factor (80 for CO2/N2 and 23 for CO2/CH4) and high CO2 permeability, far surpassing the upper bound line. Therefore, the synergistic effect of the MWCNTs core and GONRs shell in MWCNT@GONRs nanohybrids can effectively enhance the gas‐separation performance of MMMs at low loading. The unique microstructures, ease of synthesis and low filled loading make MWCNT@GONRs promising candidates in post‐combustion and sustainable chemistry.
Thermophysical and Electrochemical Properties of Ethereal Functionalised Cyclic Alkylammonium‐based Ionic Liquids as Potential Electrolytes for Electrochemical Applications
Authors: Neale Alex R. , Murphy Sinead , Goodrich Peter , Hardacre Christopher , Jacquemin Johan
Published: May 2017

A series of hydrophobic room temperature ionic liquids (ILs) based on ethereal functionalised pyrrolidinium, piperidinium and azepanium cations bearing the bis[(trifluoromethyl)sulfonyl]imide, [TFSI]−, anion were synthesized and characterized. Their physicochemical properties such as density, viscosity and electrolytic conductivity, and thermal properties including phase transition behaviour and decomposition temperature have been measured. All of the ILs showed low melting point, low viscosity and good conductivity and the latter properties have been discussed in terms of the IL fragility, an important electrolyte feature of the transport properties of glass‐forming ILs. Furthermore, the studied [TFSI]−‐based ILs generally exhibit good electrochemical stabilities and, by coupling electrochemical experiments and DFT calculations, the effect of ether functionalisation at the IL cation on the electrochemical stability of the IL is discussed. Preliminary investigations into the Li‐redox chemistry at a Cu working electrode are also reported as a function of ether‐functionality within the pyrrolidinium‐based IL family. Overall, the results show that these ionic liquids are suitable for electrochemical devices such as battery systems, fuel cells or supercapacitors.
Industrial growth and characterization of Si‐doped GaAs crystal by a novel multi‐crucible Bridgman method
Authors: Jin Min , Shen Hui , Fan Shiji , He Qingbo , Xu Jiayue
Published: May 2017

In this wok, a novel multi‐crucible Bridgman method is developed to produce the Ø 2 inch Si‐doped GaAs crystals. Five placements are designed in the furnace means five ingots could be produced at the same time. Twinning and high dislocation density are the main growth defects that often take place in the crystals. After the solid‐liquid interface and crystal cooling rate are optimized, the Si‐doped GaAs crystals with favorable single crystalline yield are successfully obtained. The average etching pits density (EPD) of optimized GaAs crystals is <1500/cm2. Full width at half maximum (FWHM) are tested all less than 60″ that indicates GaAs crystals have high crystalline quality. The carrier concentration near the bottom and tail parts of ingots is in range of (4.5‐5.9) × 1017 /cm3 and (1.2‐2.1) × 1018 /cm3 due to segregation of Si element in GaAs crystals. Accordingly, the mobility is decreased from 2128–2651 cm2/v.s to 1581–1854 cm2/v.s. The result proves such multi‐crucible Bridgman method is a feasible way for industrial growth of Si‐doped GaAs crystals for opto‐electronic application.
Dopant‐Free Hole‐Transport Materials Based on Methoxytriphenylamine‐Substituted Indacenodithienothiophene for Solution‐Processed Perovskite Solar Cells
Authors: Liu Xiaoyuan , Zheng Xiaolu , Wang Yulong , Chen Zhiliang , Yao Fang , Zhang Qi , Fang Guojia , Chen Zhi‐Kuan , Huang Wei , Xu Zong‐Xiang
Published: May 2017

Solution‐processed hole transporting materials (HTMs) that are dopant‐free show promise for use in low‐cost, high‐performance perovskite solar cells (PSCs). The highest‐efficiency PSCs use organic HTMs, many of which have low mobilities and therefore require doping, which lowers the device stability. Additionally, these materials are not easily scaled because they often require complicated synthesis. Two new HTMs (IDT–TPA and IDTT–TPA) were synthesized, which contained either an extended fused‐ring indacenodithiophene (IDT) or indacenodithienothiophene (IDTT) core and strong electron‐donating methoxytriphenylamine (TPA) groups as the end‐capping units. The extended conjugation in the backbone of IDTT–TPA resulted in stronger π–π interactions (3.321 Å) and a higher hole mobility of 6.46×10−4 cm2 V−1 s−1 when compared with that of IDT–TPA (9.53×10−5 cm2 V−1 s−1). A dopant‐free, planar PSC that contained IDTT–TPA was fabricated and exhibited a high power conversion efficiency (PCE) of 15.7 %. This cell exhibited a higher PCE and less hysteresis than devices that contained IDT–TPA.
Host density increases parasite recruitment but decreases host risk in a snail–trematode system
Authors: Buck J. C. , Hechinger R. F. , Wood A. C. , Stewart T. E. , Kuris A. M. , Lafferty K. D.
Published: May 2017

Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail,Cerithideopsis californica(=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free‐swimming miracidia that hatch from trematode eggs deposited with final‐host (bird or mammal) feces. This complex life cycle decouples infective‐stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk at local scales. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail‐density–trematode‐prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (California,USA). At each site, we quantified snail density and used data on final‐host (bird and raccoon) distributions to control for between‐site variation in infective‐stage supply. After three months, overall trematode infections per cage increased with snail biomass density. For egg‐transmitted trematodes, per‐snail infection risk decreased with snail biomass density in the cage and surrounding area, whereas per‐snail infection risk did not decrease for miracidium‐transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective‐stage input, but this was significant only for miracidium‐transmitted species. A model parameterized with our experimental results and snail densities from 524 field transects estimated that safety in numbers, when combined with patchy host density, halved per capita infection risk in this snail population. We conclude that, depending on transmission mode, host density can enhance parasite recruitment and reduce per capita infection risk.
Impacts of an invasive plant are fundamentally altered by a co‐occurring forest disturbance
Authors: Sokol Noah W. , Kuebbing Sara E. , Bradford Mark A.
Published: May 2017

Invasive species frequently co‐occur with other disturbances, which can impact the same ecosystem functions as the invader. Yet invasion studies rarely control for the presence of these other disturbances, although their overlapping effects may influence the direction and magnitude of impacts attributed to the invader alone. Here, we ask whether controlling for the presence of a co‐occurring disturbance, as well as the time since disturbance, yields different values of an invader's ecosystem effects than when these factors remain unaddressed. We used a chronosequence of six forest stands at a single site: five logged stands that each contained paired invaded‐uninvaded plots of the forest understory invasive grassMicrostegium vimineum, as well as one unlogged and uninvaded control stand. By controlling for the presence of both logging and invasion, we untangled the effects of each through time.We found that the co‐occurring disturbance of logging can dramatically alter the measured effects ofM. vimineumby amplifying, dampening, negating, or entirely reversing the direction of the invader's impacts. During its period of peak impact, logging amplified the invader's positive effect on the size of the soil microbial biomass pool by 24%, reduced the invader's positive effect on soil water holding capacity by 5%, negated the invader's positive effect on the particulate organic matter carbon pool (from a 9% increase to no significant effect), and reversed the direction of the invader's impact on net nitrogen mineralization rate from a 51% increase to a 52% decrease. Furthermore, the influence of logging on the invader's impacts was not static, but dynamic through time. The results from our site therefore demonstrate that failure to account for the impacts of a co‐occurring disturbance, as well as the time since disturbance, can result in flawed inference about the nature of an invader's effects. Future research should determine how widespread such flawed inference might be among other invasive species and across different environmental contexts. To help guide such research, we describe a general framework for disentangling the overlapping effects of invasions and co‐occurring disturbances through time.
Fatty acid metabolism and prospects for targeted therapy of cancer
Authors: Chen Tingting , Li Hua
Published: May 2017

Fatty acids are fundamental substrates required for energy storage, synthesis of membranes, generation of signaling molecules and lipid droplet formation in cancer cells. High levels of fatty acid metabolic activity are one of the most aberrant metabolic alterations in cancer cells. The de novo fatty acid synthesis pathway is the primary source of fatty acids in cancer cells, but cancer cells can also acquire fatty acids through the lipolytic pathway, which helps cells survive and maintain their invasiveness. Key enzymes, including ATP‐citrate lyase (ACLY), fatty acid synthase (FASN), acetyl‐coenzyme A (CoA) carboxylase (ACC), stearoyl‐CoA desaturase 1(SCD1) and monoacylglycerol lipase (MAGL), which are involved in fatty acid synthesis and degradation, are overexpressed in cancer cells. The alterations in fatty acid metabolomics in different cancers, at different stages of cancer, and in different tissues are clinically significant. This review focuses on current research into fatty acid metabolism to explore new targets against the fatty acid metabolic pathways for anticancer therapy.

Practical applications: High levels of fatty acid metabolic activity are one of the most aberrant metabolic alterations in cancer cells. Reprogramming in fatty acid metabolism plays an important role in energy storage, membrane proliferation, the generation of signaling molecules and lipid droplet formation in cancer cells. Understanding the mechanism of regulated the fatty acid metabolic pathways in cancer would reveal novel targeted therapy of cancer.

To maintain the balance of the free fatty acid composition and thus promote cancer cell growth, survival, and progression, the levels of de novo fatty acid synthesis and degradation are elevated. Therefore, the targeted inhibition of key enzymes involved in fatty acid metabolism, such as ACLY, ACC, FASN, MAGL, and SCD1, and the utilization of anticancer exogenous fatty acids might constitute effective cancer therapies. ATP, adenosine‐triphosphate; DAG, diacylglycerol; IHBTIS, inhibitors; MUFA, monounsaturated fatty acids; MAG, monoacylglycerol; TAG triacylglycerol.
Origin of the Base‐Dependent Facial Selectivity in Annulation Reactions of Nazarov‐Type Reagents with Unsaturated Indolo[2,3‐a]quinolizidine Lactams
Authors: Estarellas Carolina , Arioli Federica , Pérez Maria , Are Celeste , Hevia David , Molins Elies , Luque F. Javier , Bosch Joan , Amat Mercedes
Published: May 2017

Methyl‐substituted Nazarov reagent 4 reacts stereoselectively with Nind‐Boc indoloquinolizidine lactams to give the expected 3‐H/15‐H cis pentacyclic yohimbine‐type adducts when using 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as the base. However, a dramatic change of the facial selectivity was observed when the reaction was performed in the presence of Cs2CO3, leading to the corresponding trans adducts. This annulation is the key step of a stereocontrolled synthesis of the 17a‐carba analogue of the heteroyohimbine alkaloid akuammigine. Theoretical calculations were used to rationalize the facial selectivity of these double Michael addition reactions.
Application of the US EPA's risk‐screening indicators model and toxic release inventory database to study pollution prevention trends in paper manufacturing industry
Authors: Velagapudi Srikar , Kumar Ashok , Saripalli Meghadeep Varma
Published: May 2017

The United States Environmental Protection Agency (EPA) developed Toxic Release Inventory (TRI) using information submitted by different industries in the United States. This research examines the contaminants released by paper manufacturing industry in the United States and Ohio over time and what paper manufacturers are doing to diminish the quantities of chemical wastes generated, released to the environment, or managed by other means. It is understood that there is a reduction in the Risk‐Screening Environmental Indicators (RSEI) scores from 2002 to 2014 in all the states, which can be related to the adaptation of recycling or reusing of the chemicals in various other manufacturing processes. The other significant observation inferred from the analysis is that the facilities in the states such as Wisconsin, Louisiana, South Carolina, Connecticut, and Pennsylvania based on the economic feasibility or recycling prospects, they are generating higher quantities of the selected chemical resulting in the higher RSEI scores respectively for the above‐mentioned states. This article demonstrates the application of the risk‐screening indicators model to a large database to analyze pollution data. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 808–814, 2017
Effects of different spatial distributions of physical soil crusts on runoff and erosion on the Loess Plateau in China
Authors: Lu Pei , Xie Xinli , Wang Linhua , Wu Faqi
Published: May 2017

The response of runoff and erosion to soil crusts has been extensively investigated in recent decades. However, there have been few attempts to look at the effects of spatial configuration of different soil crusts on erosion processes. Here we investigated the effects of different spatial distributions of physical soil crusts on runoff and erosion in the semi‐arid Loess Plateau region. Soil boxes (1.5 m long × 0.2 m wide) were set to a slope of 17.6% (10°) and simulated rainfall of 120 mm h−1 (60 minutes). The runoff generation and erosion rates were determined for three crust area ratios (depositional crust for 20%, 33%, and 50% of the total slope) and five spatial distribution patterns (depositional crust on the lower, lower‐middle, middle, mid‐upper, and upper slope) of soil crusts. The reduction in sediment loss (‘sediment reduction’) was calculated to evaluate the effects of different spatial distributions of soil crusts on erosion. Sediment yield was influenced by the area ratio and spatial position of different soil crusts. The runoff rate reached a steady state after an initial trend of unsteadily increasing with increasing rainfall duration. Sediment yield was controlled by detachment limitation and then transport limitation under rainfall. The shifting time of erosion from a transport to detachment‐limiting regime decreased with increasing area of depositional crust. No significant differences were observed in the total runoff among treatments, while the total sediment yield varied under different spatial distributions. At the same area ratio, total sediment yield was the largest when the depositional crust was on the upper slope, and it was smallest when the crust was deposited on the lower slope. The sediment reduction of structural crust (42.5–66.5%) was greater than that of depositional crust (16.7–34.3%). These results provide a mechanistic understanding of how different spatial distributions of soil crusts affect runoff and sediment production. Copyright © 2017 John Wiley & Sons, Ltd.
Acute oligodendrocyte loss with persistent white matter injury in a third trimester equivalent mouse model of fetal alcohol spectrum disorder
Authors: Newville Jessie , Valenzuela Carlos Fernando , Li Lu , Jantzie Lauren L. , Cunningham Lee Anna
Published: May 2017

Alcohol exposure during central nervous system (CNS) development can lead to fetal alcohol spectrum disorder (FASD). Human imaging studies have revealed significant white matter (WM) abnormalities linked to cognitive impairment in children with FASD; however, the underlying mechanisms remain unknown. Here, we evaluated both the acute and long‐term impacts of alcohol exposure on oligodendrocyte number and WM integrity in a third trimester‐equivalent mouse model of FASD, in which mouse pups were exposed to alcohol during the first 2 weeks of postnatal development. Our results demonstrate a 58% decrease in the number of mature oligodendrocytes (OLs) and a 75% decrease in the number of proliferating oligodendrocyte progenitor cells (OPCs) within the corpus callosum of alcohol‐exposed mice at postnatal day 16 (P16). Interestingly, neither mature OLs nor OPCs derived from the postnatal subventricular zone (SVZ) were numerically affected by alcohol exposure, indicating heterogeneity in susceptibility based on OL ontogenetic origin. Although mature OL and proliferating OPC numbers recovered by postnatal day 50 (P50), abnormalities in myelin protein expression and microstructure within the corpus callosum of alcohol‐exposed subjects persisted, as assessed by western immunoblotting of myelin basic protein (MBP; decreased expression) and MRI diffusion tensor imaging (DTI; decreased fractional anisotropy). These results indicate that third trimester‐equivalent alcohol exposure leads to an acute, albeit recoverable, decrease in OL lineage cell numbers, accompanied by enduring WM injury. Additionally, our finding of heterogeneity in alcohol susceptibility based on the developmental origin of OLs may have therapeutic implications in FASD and other disorders of WM development.
Biases in the reporting of hepatocellular carcinoma tumor sizes on the liver transplant waiting list
Authors: Samoylova Mariya L. , Nigrini Mark J. , Dodge Jennifer L. , Roberts John P.
Published: May 2017

We investigated the possibility that patients with hepatocellular carcinoma (HCC) listed for liver transplant with tumors just outside stage T2 size criteria may be inaccurately reported as just meeting the tumor size criteria for transplant. The United Network for Organ Sharing/Standard Transplant Analysis and Research database identified 12,958 patients listed for liver transplants with HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor. A logistic power peak function was fitted to the single‐tumor size histogram, with the fitted values representing unbiased expected values. The difference between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238 (22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients with tumors outside of transplant criteria had their measurements recorded at the margins of eligibility. A risk‐adjusted Poisson model evaluated the ratio of observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences among 6,049 transplants. Only 2.0‐cm tumors had observed to expected recurrence differing from 1 (ratio 0.73, 95% confidence interval 0.57‐0.94), indicating a 27% lower than expected rate of recurrence. Conclusion: Higher than expected observed tumor counts at the lower transplant criteria margin were corroborated by lower than expected HCC recurrence, suggesting that tumor sizes at the margins of HCC transplant criteria may be subject to inaccurate reporting. (Hepatology 2017;66:1144‐1150)
The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on lipid droplets by evading ubiquitylation
Authors: BasuRay Soumik , Smagris Eriks , Cohen Jonathan C. , Hobbs Helen H.
Published: May 2017

A sequence variation (I148M) in patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) is strongly associated with fatty liver disease, but the underlying mechanism remains obscure. In this study, we used knock‐in (KI) mice (Pnpla3148M/M
) to examine the mechanism responsible for accumulation of triglyceride (TG) and PNPLA3 in hepatic lipid droplets (LDs). No differences were found between Pnpla3148M/M
and Pnpla3+/+
mice in hepatic TG synthesis, utilization, or secretion. These results are consistent with TG accumulation in the Pnpla3148M/M
mice being caused by impaired TG mobilization from LDs. Sucrose feeding, which is required to elicit fatty liver in KI mice, led to a much larger and more persistent increase in PNPLA3 protein in the KI mice than in wild‐type (WT) mice. Inhibition of the proteasome (bortezomib), but not macroautophagy (3‐methyladenine), markedly increased PNPLA3 levels in WT mice, coincident with the appearance of ubiquitylated forms of the protein. Bortezomib did not increase PNPLA3 levels in Pnpla3148M/M
mice, and only trace amounts of ubiquitylated PNPLA3 were seen in these animals. Conclusion: These results are consistent with the notion that the 148M variant disrupts ubiquitylation and proteasomal degradation of PNPLA3, resulting in accumulation of PNPLA3‐148M and impaired mobilization of TG from LDs. (Hepatology 2017;66:1111‐1124).
Current guidelines for chemoembolization for hepatocellular carcinoma: Room for improvement?
Authors: White Jared A. , Gray Stephen H. , Li Peng , Simpson Heather N. , McGuire Brendan M. , Eckhoff Devin E. , Abdel Aal Ahmed Mohamed Kamel , Saddekni Souheil , Dubay Derek A.
Published: May 2017

Transarterial chemoembolization (TACE) is the most common oncologic therapy used according to the American Association for the Study of Liver Diseases (AASLD) guidelines established in 2005, revised in 2011. The purpose of this study was to determine how AASLD criteria for the management of hepatocellular carcinoma (HCC) have impacted TACE practice in the community. Clinical, demographic, and cause of death information were collected for patients diagnosed with HCC in the 2012 linkage of the Surveillance, Epidemiology, and End Results Medicare database. Propensity score survival analysis was used to compare survival outcomes in patients whose HCC tumor characteristics were less than, met, or were beyond AASLD criteria. The proportion of patients with HCC receiving TACE who met the AASLD‐recommended criteria increased after the 2005 guidelines were published. Up to 17% of patients treated with TACE had tumor characteristics less than the AASLD criteria and were not offered potentially curative therapies. Propensity score matching demonstrated the largest survival advantage in patients with HCC whose tumor characteristics met the AASLD criteria (hazard ratio, 0.42; 95% confidence interval, 0.38‐0.47). A significant survival advantage was also observed in patients with HCC whose tumor characteristics exceeded the AASLD criteria. Conclusion: The AASLD criteria successfully identify a population of patients with HCC that maximally benefit from TACE therapy. However, patients with HCC with tumor characteristics beyond the AASLD criteria also appear to receive a significant survival advantage with TACE. Further studies are necessary to improve referral patterns and appropriate use of chemoembolization in the management of unresectable HCC. (Hepatology Communications 2017;1:338–346)
New psychoactive substances: Purchasing and supply patterns in Australia
Authors: Sutherland Rachel , Bruno Raimondo , Peacock Amy , Dietze Paul , Breen Courtney , Burns Lucinda , Barratt Monica J.
Published: May 2017

Objective

To examine the purchasing and supply patterns of new psychoactive substance (NPS) consumers in Australia.

Method

Data were obtained from a self‐selected sample of 296 past‐year NPS consumers, with comparisons made across dimethyltryptamine (n = 104), 2C‐x (n = 59), NBOMe (n = 27), and synthetic cannabinoid (n = 22) users.

Results

Most consumers (58%) nominated a friend as their main NPS source, and almost half (46%) reported that they had supplied NPS to others in the past year (predominantly “social supply”). However, when comparisons were made across NPS, NBOMe users were more likely to nominate a dealer (30%) or online marketplace (22%) as their main source and to report: supplying NPS to others (63%); supplying to strangers (29%) and acquaintances (24%); and supplying NPS for cash profit (29%).

Similarly, NPS consumers who nominated online markets as their main NPS source (9%; n = 26) were more likely to have supplied NPS to others (risk ratio [RR] 1.57); supplied to strangers (RR 6.05) and acquaintances (RR 12.11); sold NPS for cash profit (RR 4.36); and to have exchanged NPS for something else (RR 3.27) than those who reported alternative primary sources.

Conclusion

NBOMe consumers and those who nominated online markets as their main NPS source reported greater engagement with for‐profit supply; it is unclear if these individuals have “drifted” into dealing or if they were already engaged in such activities.
Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter‐observational study
Authors: Acciavatti Tiziano , Lupi Matteo , Santacroce Rita , Aguglia Andrea , Attademo Luigi , Bandini Laura , Ciambrone Paola , Lisi Giulia , Migliarese Giovanni , Pinna Federica , Quattrone Diego , Ribolsi Michele , Signorelli Maria Salvina , Calò Salvatore , Schifano Fabrizio , di Giannantonio Massimo , Martinotti Giovanni
Published: May 2017

Objective

Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this multicentre survey is to investigate the consumption of a number of psychoactive substances in a young psychiatric sample.

Methods

Between December 2013 and September 2015, a questionnaire was administered in 10 Italian psychiatric care facilities to a sample of 671 patients, aged 18–26 (mean age 22.24; SD 2.87).

Results

About 8.2% of the sample declared to have used NPS at least once, and 2.2% had consumed NPS in the previous 3 months. The three psychiatric diagnoses most frequently associated with NPS use were bipolar disorder (23.1%), personality disorders (11.8%), and schizophrenia and related disorders (11.6%). In univariate regression analysis, bipolar disorder was positively associated with NPS consumption, an association that did not reach statistical significance in the multivariate analysis.

Conclusions

The use of NPS in a young psychiatric population appears to be frequent, and probably still underestimated. Bipolar disorder shows an association with NPS use. Careful and constant monitoring and an accurate evaluation of possible clinical effects related to NPS use are necessary.
CANFIS based glioma brain tumor classification and retrieval system for tumor diagnosis
Authors: Sivakumar P. , Ganeshkumar P.
Published: May 2017

Brain tumor classification and retrieval system plays an important role in medical field. In this paper, an efficient Glioma Brain Tumor detection and its retrieval system is proposed. The proposed methodology consists of two modules as classification and retrieval. The classification modules are designed using preprocessing, feature extraction and tumor detection techniques using Co‐Active Adaptive Neuro Fuzzy Inference System (CANFIS) classifier. The image enhancement can be achieved using Heuristic histogram equalization technique as preprocessing and further texture features as Local Ternary Pattern (LTP) features and Grey Level Co‐occurrence Matrix (GLCM) features are extracted from the enhanced image. These features are used to classify the brain image into normal and abnormal using CANFIS classifier. The tumor region in abnormal brain image is segmented using normalized graph cut segmentation algorithm. The retrieval module is used to retrieve the similar segmented tumor regions from the dataset for diagnosing the tumor region using Euclidean algorithm. The proposed Glioma Brain tumor classification methodology achieves 97.28% sensitivity, 98.16% specificity and 99.14% accuracy. The proposed retrieval system achieves 97.29% precision and 98.16% recall rate with respect to ground truth images.
Brightness preserving bi‐level fuzzy histogram equalization for MRI brain image contrast enhancement
Authors: Magudeeswaran V. , Ravichandran C. G. , Thirumurugan P.
Published: May 2017

In this article, brightness preserving bi‐level fuzzy histogram equalization (BPFHE) is proposed for the contrast enhancement of MRI brain images. Histogram equalization (HE) is widely used for improving the contrast in digital images. As a result, such image creates side‐effects such as washed‐out appearance and false contouring due to the significant change in brightness. In order to overcome these problems, mean brightness preserving HE based techniques have been proposed. Generally, these methods partition the histogram of the original image into sub histograms and then independently equalize each sub‐histogram. The BPFHE consists of two stages. First, fuzzy histogram is computed based on fuzzy set theory to handle the inexactness of gray level values in a better way compared to classical crisp histograms. In the second stage, the fuzzy histogram is divided into two sub‐histograms based on the mean intensities of the multi‐peaks in the original image and then equalizes them independently to preserve image brightness. The quantitative and subjective enhancement of proposed BPBFHE algorithm is evaluated using two well known parameters like entropy or average information contents (AIC) and Feature Similarity Index Matrix (FSIM) for different gray scale images. The proposed method have been tested using several images and gives better visual quality as compared to the conventional methods. The simulation results show that the proposed method has better performance than the existing methods, and preserve the original brightness quite well, so that it is possible to be utilized in medical image diagnosis.
Intrinsic fluorescence and mechanical testing of articular cartilage in human patients with osteoarthritis
Authors: Padilla‐Martinez Juan Pablo , Lewis William , Ortega‐Martinez Antonio , Franco Walfre
Published: May 2017

The degeneration of articular cartilage is the main cause of osteoarthritis (OA), a common cause of disability among elderly patients. The aim of this study is to understand the correlation between intrinsic fluorescence of articular cartilage and its biomechanical properties in patients with osteoarthritis. Cylindrical samples of articular cartilage 6 mm in diameter were extracted via biopsy punch from the femoral condyles of 6 patients with advanced OA undergoing knee replacement surgery. The mechanical stiffness and fluorescence of each cartilage plug were measured by indentation test and spectrofluorometry. Maps of fluorescence intensity, at excitation/emission wavelengths of 240–520/290‐530 nm, were used to identify wavelengths of interest. The mechanical stiffness and fluorescence intensity were correlated using a Spearman analysis. The excitation/emission maps demonstrated three fluorescence peaks at excitation/emission wavelength pairs 330/390, 350/430 and 370/460 nm. The best correlation between the fluorescence intensity and stiffness of cartilage was obtained for the 330 nm excitation band [R=0.82, p=0.04]. The intrinsic fluorescence of articular cartilage may have application in optically assessing the state of cartilage in patients with osteoarthritis.

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Withdrawn: Interaction of lincRNA ROR and p53/miR‐145 correlates with lung cancer stem cell signatures
Authors: Xia Fan , Xiong Ye , Li Qiang
Published: May 2017

The above article, published online as accepted article, prior to the version of record, on 18 May 2017 in Wiley Online Library (https://doi.org/10.1002/jcb.25960) has been withdrawn by agreement between the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC.
Plasminogen Activator Inhibitor Type‐1 as a Regulator of Fibrosis
Authors: Rabieian Reyhaneh , Boshtam Maryam , Zareei Mahshid , Kouhpayeh Shirin , Masoudifar Aria , Mirzaei Hamed
Published: May 2017

Fibrosis is known as a frequent and irreversible pathological condition which is associated with organ failure. Tissue fibrosis is a central process in a variety of chronic progressive diseases such as diabetes, hypertension, and persistent inflammation. This state could contribute to chronic injury and the initiation of tissue repair. Fibrotic disorders represent abnormal wound healing with defective matrix turnover and clearance that lead to excessive accumulation of extracellular matrix components. A variety of identified growth factors, cytokines, and persistently activated myofibroblasts have critical roles in the pathogenesis of fibrosis. Irrespective of etiology, the transforming growth factor‐β pathway is the major driver of fibrotic response. Plasminogen activator inhibitor‐1 (PAI‐1) is a crucial downstream target of this pathway. Transforming growth factor‐β positively regulates PAI‐1 gene expression via two main pathways including Smad‐mediated canonical and non‐canonical pathways. Overexpression of PAI‐1 reduces extracellular matrix degradation via perturbing the plasminogen activation system. Indeed, elevated PAI‐1 levels inhibit proteolytic activity of tissue plasminogen activator and urokinase plasminogen activator which could contribute to a variety of inflammatory elements in the injury site and to excessive matrix deposition. This review summarizes the current knowledge of critical pathways that regulate PAI‐1 gene expression and suggests effective approaches for the treatment of fibrotic disease. J. Cell. Biochem. 119: 17–27, 2018. © 2017 Wiley Periodicals, Inc.
Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway
Authors: Chao Yuelin , Ye Peng , Zhu Linlin , Kong Xiangquan , Qu Xinliang , Zhang Junxia , Luo Jie , Yang Hongfeng , Chen Shaoliang
Published: May 2017

Reactive oxygen species (ROS) contribute to many aspects of physiological and pathological cardiovascular processes. However, the underlying mechanism of ROS induction by low shear stress (LSS) remains unclear. Accumulating evidence has shown that the angiotensin II type 1 receptor (AT1R) is involved in inflammation, apoptosis, and ROS production. Our aim was to explore the role of AT1R in LSS‐mediated ROS induction. We exposed human umbilical vein endothelial cells (HUVECs) to LSS (3 dyn/cm2) for different periods of time. Western blotting and immunofluorescence showed that LSS significantly induced AT1R expression in a time‐dependent manner. Using immunohistochemistry, we also noted a similar increase in AT1R expression in the inner curvature of the aortic arch compared to the descending aorta in C57BL/6 mice. Additionally, HUVECs were cultured with a fluorescent probe, either DCFH, DHE or DAF, after being subjected to LSS. Cell chemiluminescence and flow cytometry results revealed that LSS stimulated ROS levels and suppressed nitric oxide (NO) generation in a time‐dependent manner, which was reversed by the AT1R antagonist Losartan. We also found that Losartan markedly increased endothelial NO synthase (eNOS) phosphorylation at Ser(633,1177) and dephosphorylation at Thr(495), which involved AKT and ERK. Moreover, the ROS level was significantly reduced by endogenous and exogenous NO donors (L‐arginine, SNP) and increased by the eNOS inhibitor L‐NAME. Overall, we conclude that LSS induces ROS via AT1R/eNOS/NO.
Choice among two and three alternatives
Authors: Beeby Emma , Alsop Brent
Published: May 2017

Although choice between two alternatives has been widely researched, fewer studies have examined choice across multiple (more than two) alternatives. Past models of choice behavior predict that the number of alternatives should not affect relative response allocation, but more recent research has found violations of this principle. Five pigeons were presented with three concurrently scheduled alternatives. Relative reinforcement rates across these alternatives were assigned 9:3:1. In some conditions three keys were available; in others, only two keys were available. The number of available alternatives did not affect relative response rates for pairs of alternatives; there were no significant differences in behavior between the two and three key conditions. For two birds in the three‐alternative conditions and three birds in the two‐alternative conditions, preference was more extreme for the pair of alternatives with the lower overall pairwise reinforcer rate (3:1) than the pair with higher overall reinforcer rate (9:3). However, when responding during the changeover was removed three birds showed the opposite pattern in the three‐alternative conditions; preference was more extreme for the pair of alternatives with the higher overall reinforcer rate. These findings differ from past research and do not support established theories of choice behavior.