bluuebunny/crossref_metadata_2025 huggingface dataset:
A Laser and Electric Pulse Modulated Nonvolatile Photoelectric Response in Nanoscale Copper Dusted Metal‐Oxide‐Semiconductor Structures
Authors: Gan Zhikai , Zhou Peiqi , Dong Anhua , Zheng Diyuan , Wang Hui
Published: July 2018

A novel photoelectric response observed in a nanoscale Cu‐dusted Cu–SiO2–Si structure is reported. By combining the application of a short voltage pulse with laser illumination, the photoelectric response of the structure can be permanently changed. Intriguingly, if a second voltage pulse of reverse polarity is applied under similar laser illumination, the photoelectric response of the structure can be restored to its initial state, showing that the photoelectric states of the structure can be switched back and forth in a nonvolatile manner. This phenomenon is attributed to a controllable change of height of the Schottky barrier formed between the Cu nanoparticles and the N‐type silicon substrate, indicating that tunneling of confined photoelectrons from the Si causes an adjustment of the Fermi level of the Cu particles. The work suggests a new switching approach for tailoring photoelectric sensors, nonvolatile memories, and even solar cells related materials.
Cerebellar atrophy and its contribution to cognition in frontotemporal dementias
Authors: Chen Yu , Kumfor Fiona , Landin‐Romero Ramon , Irish Muireann , Hodges John R. , Piguet Olivier
Published: July 2018

Objective

Increasing evidence suggests that cerebellar damage impacts on cognitive functions. Frontotemporal dementias (FTDs) are neurodegenerative brain conditions, primarily affecting the frontal and/or temporal lobe. Three main phenotypes are recognized, each with a distinct clinical and cognitive profile: behavioral‐variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The severity of cerebellar changes and their relation to cognition in FTD, however, remain unclear. This study aimed to establish cerebellar gray matter changes on magnetic resonance imaging (MRI) and their relation to profiles of cognitive deficits in FTD subtypes.

Methods

Ninety‐six FTD patients (45 bvFTD, 28 SD, and 23 PNFA), meeting current clinical diagnostic criteria, and 35 age‐, sex‐, and education‐matched controls underwent brain MRI and cognitive assessment. Cerebral and cerebellar gray matter integrity were investigated using voxel‐based morphometry.

Results

Compared with controls, widespread bilateral cerebellar changes were observed in all FTD subtypes, with the greatest atrophy present in bvFTD. Significant associations were found between cerebellar integrity and cognitive performance in attention and working memory in bvFTD, visuospatial function in SD, and language‐motor function in PNFA. Bilateral atrophy of crus and lobule VI were most commonly associated with cognitive deficits, irrespective of FTD phenotype.

Interpretation

This study is the first to identify distinct patterns of cerebellar atrophy across FTD syndromes, which in turn relate to discrete cognitive dysfunctions, after accounting for the effect of cerebral atrophy. These findings extend our understanding of the cerebellum and point to its involvement across an array of processes beyond the domain of motor function. Ann Neurol 2018;83:98–109
Haploinsufficiency of CUX1 Causes Nonsyndromic Global Developmental Delay With Possible Catch‐up Development
Authors: Platzer Konrad , Cogné Benjamin , Hague Jennifer , Marcelis Carlo L. , Mitter Diana , Oberndorff Katrin , Park Soo‐Mi , Ploos van Amstel Hans K. , Simonic Ingrid , van der Smagt Jasper J. , Stegmann Alexander P.A. , Stevens Servi J.C. , Stumpel Constance T.R.M. , Vincent Marie , Lemke Johannes R. , Jamra Rami
Published: July 2018

Objective

Developmental delay (DD) with favorable intellectual outcome and mild intellectual disability (ID) are mostly considered to be of complex genetic and environmental origin, but, in fact, often remain unclear. We aimed at proving our assumption that also mild cases of DD and ID may be of monogenic etiology.

Methods

We clinically evaluated 8 individuals and performed exome sequencing or array copy number analysis and identified variants in CUX1 as the likely cause. In addition, we included a case from the public database, DECIPHER.

Results

All 9 individuals harbored heterozygous null‐allele variants in CUX1, encoding the Cut‐homeobox 1 transcription factor that is involved in regulation of dendritogenesis and cortical synapse formation in layer II to IV cortical neurons. Six variants arose de novo, while in one family the variant segregated with ID. Of the 9 included individuals, 2 were diagnosed with moderate ID, 3 with mild ID, and 3 showed a normal age‐related intelligence at ages 4, 6, and 8 years after a previous history of significant DD.

Interpretation

Our results suggest that null‐allele variants, and thus haploinsufficiency of CUX1, cause an isolated phenotype of DD or ID with possible catch‐up development. This illustrates that such a developmental course is not necessarily genetic complex, but may also be attributed to a monogenic cause. Ann Neurol 2018;84:200–207
A Novel Autoantibody against Plexin D1 in Patients with Neuropathic Pain
Authors: Fujii Takayuki , Yamasaki Ryo , Iinuma Kyoko , Tsuchimoto Daisuke , Hayashi Yoshinori , Saitoh Ban‐yu , Matsushita Takuya , Kido Mizuho A. , Aishima Shinichi , Nakanishi Hiroshi , Nakabeppu Yusaku , Kira Jun‐ichi
Published: July 2018

Objective

To identify novel autoantibodies for neuropathic pain (NeP).

Methods

We screened autoantibodies that selectively bind to mouse unmyelinated C‐fiber type dorsal root ganglion (DRG) neurons using tissue‐based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and allergic neurologic diseases or other neuropathies, and 50 controls without NeP including 20 healthy subjects and 30 patients with neurodegenerative diseases or systemic inflammatory diseases. IgG purified from IFA‐positive patients' sera was subjected to Western blotting (WB) and immunoprecipitation (IP) using mouse DRG lysates. Immunoprecipitates were analyzed by liquid chromatography tandem mass spectrometry (LC‐MS/MS) to identify target autoantigens.

Results

Antiunmyelinated C‐fiber type DRG neuron antibodies were more frequent in patients with NeP than non‐NeP subjects (10% vs 0%; p < 0.05). These autoantibodies were all from the IgG2 subclass and colocalized mostly with isolectin B4‐ and P2X3‐positive pain‐conducting small neurons but not with S100β‐positive myelinated neurons. WB revealed a common immunoreactive band (approximately 220kDa). IP and LC‐MS/MS studies identified plexin D1 as a target autoantigen. Immunoadsorption tests with recombinant human plexin D1 in IFA revealed that all 11 anti–small DRG neuron antibody‐positive patients had anti–plexin D1 antibodies. Application of anti–plexin D1 antibody‐positive patient sera to cultured DRG neurons increased membrane permeability, leading to cellular swelling. NeP patients with anti–plexin D1 antibodies commonly developed burning pain and current perception threshold abnormalities for C‐fibers. Main comorbidities were atopy and collagen‐vascular disease. Immunotherapies ameliorated NeP in 7 treated cases.

Interpretation

Anti–plexin D1 antibodies are a novel biomarker for immunotherapy‐responsive NeP. Ann Neurol 2018;84:208–224
BRAF mutation leading to central nervous system rosai‐dorfman disease
Authors: Richardson Timothy E. , Wachsmann Megan , Oliver Dwight , Abedin Zahidur , Ye Diana , Burns Dennis K. , Raisanen Jack M. , Greenberg Benjamin M. , Hatanpaa Kimmo J.
Published: July 2018

Rosai–Dorfman disease (RDD) is an uncommon histiocytic proliferative disorder that can present in nodal, extranodal, or, extremely rarely, in central nervous system (CNS)‐restricted form. RDD is characterized histologically as a non‐Langerhans cell histiocytosis composed of atypical CD68+/S‐100+/CD1a– macrophages demonstrating prominent emperipolesis and effacement of the surrounding tissue. Previously thought to represent a reactive process, recent studies have raised the possibility that RDD and other histiocytic lesions, including Erdheim–Chester and Langerhans cell histiocytosis, are clonal processes linked to somatic mutations in the mitogen‐activated protein (MAP) kinase pathway. Herein, we present a fatal case of RDD isolated to the CNS and used a next‐generation targeted gene panel and Sanger sequencing to uncover a pathogenic deletion in the β3‐αC loop of the kinase domain in exon 12 of BRAF. This mutation, previously described in melanoma and Langerhans cell histiocytosis, represents the first BRAF mutation of this kind identified in RDD. These findings support the idea that RDD is a neoplastic condition and raise the possibility that inhibitors of the MAP kinase pathway may be effective in RDD. Ann Neurol 2018;83:147–152
Long‐range genomic regulators of THBS1 and LTBP4 modify disease severity in duchenne muscular dystrophy
Authors: Weiss Robert B. , Vieland Veronica J. , Dunn Diane M. , Kaminoh Yuuki , Flanigan Kevin M. ,   for the United Dystrophinopathy Project
Published: July 2018

Objective

Duchenne muscular dystrophy (DMD) is a severe X‐linked recessive disease caused by loss‐of‐function dystrophin (DMD) mutations in boys, who typically suffer loss of ambulation by age 12. Previously, we reported that coding variants in latent transforming growth factor beta (TGFβ)‐binding protein 4 (LTBP4) were associated with reduced TGFβ signaling and prolonged ambulation (p = 1.0 × 10−3) in DMD patients; this result was subsequently replicated by other groups. In this study, we evaluated whether additional DMD modifier genes are observed using whole‐genome association in the original cohort.

Methods

We performed a genome‐wide association study (GWAS) for single‐nucleotide polymorphisms (SNPs) influencing loss of ambulation (LOA) in the same cohort of 253 DMD patients used to detect the candidate association with LTBP4 coding variants. Gene expression and chromatin interaction databases were used to fine‐map association signals above the threshold for genome‐wide significance.

Results

Despite the small sample size, two loci associated with prolonged ambulation met genome‐wide significance and were tagged by rs2725797 (chr15, p = 6.6 × 10−9) and rs710160 (chr19, p = 4.7 × 10−8). Gene expression and chromatin interaction data indicated that the latter SNP tags regulatory variants of LTBP4, whereas the former SNP tags regulatory variants of thrombospondin‐1 (THBS1): an activator of TGFβ signaling by direct binding to LTBP4 and an inhibitor of proangiogenic nitric oxide signaling.

Interpretation

Together with previous evidence implicating LTBP4, the THBS1 modifier locus emphasizes the role that common regulatory variants in gene interaction networks can play in mitigating disease progression in muscular dystrophy. Ann Neurol 2018;84:234–245
Sustainable method for Alzheimer dementia prediction in mild cognitive impairment: Electroencephalographic connectivity and graph theory combined with apolipoprotein E
Authors: Vecchio Fabrizio , Miraglia Francesca , Iberite Francesco , Lacidogna Giordano , Guglielmi Valeria , Marra Camillo , Pasqualetti Patrizio , Tiziano Francesco Danilo , Rossini Paolo Maria
Published: July 2018

Objective

Mild cognitive impairment (MCI) is a condition intermediate between physiological brain aging and dementia. Amnesic‐MCI (aMCI) subjects progress to dementia (typically to Alzheimer‐Dementia = AD) at an annual rate which is 20 times higher than that of cognitively intact elderly. The present study aims to investigate whether EEG network Small World properties (SW) combined with Apo‐E genotyping, could reliably discriminate aMCI subjects who will convert to AD after approximately a year.

Methods

145 aMCI subjects were divided into two sub‐groups and, according to the clinical follow‐up, were classified as Converted to AD (C‐MCI, 71) or Stable (S‐MCI, 74).

Results

Results showed significant differences in SW in delta, alpha1, alpha2, beta2, gamma bands, with C‐MCI in the baseline similar to AD. Receiver Operating Characteristic(ROC) curve, based on a first‐order polynomial regression of SW, showed 57% sensitivity, 66% specificity and 61% accuracy(area under the curve: AUC=0.64). In 97 out of 145 MCI, Apo‐E allele testing was also available. Combining this genetic risk factor with Small Word EEG, results showed: 96.7% sensitivity, 86% specificity and 91.7% accuracy(AUC=0.97). Moreover, using only the Small World values in these 97 subjects, the ROC showed an AUC of 0.63; the resulting classifier presented 50% sensitivity, 69% specificity and 59.6% accuracy. When different types of EEG analysis (power density spectrum) were tested, the accuracy levels were lower (68.86%).

Interpretation

Concluding, this innovative EEG analysis, in combination with a genetic test (both low‐cost and widely available), could evaluate on an individual basis with great precision the risk of MCI progression. This evaluation could then be used to screen large populations and quickly identify aMCI in a prodromal stage of dementia. Ann Neurol 2018 Ann Neurol 2018;84:302–314
Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease
Authors: Kia Demis A. , Noyce Alastair J. , White Jon , Speed Doug , Nicolas Aude ,   IPDGC collaborators, Burgess Stephen , Lawlor Debbie A. , Davey Smith George , Singleton Andrew , Nalls Mike A. , Sofat Reecha , Wood Nicholas W.
Published: July 2018

Objective

Observational studies have shown that increased plasma urate is associated with lower risk of Parkinson's disease (PD), but these studies were not designed to test causality. If a causal relationship exists, then modulating plasma urate levels could be a potential preventive avenue for PD. We used a large two‐sample Mendelian randomization (MR) design to assess for a causal relationship between plasma urate and PD risk.

Methods

We used a genetic instrument consisting of 31 independent loci for plasma urate on a case‐control genome‐wide association study data set, which included 13,708 PD cases and 95,282 controls. Individual effect estimates for each SNP were combined using the inverse‐variance weighted (IVW) method. Two additional methods, MR‐Egger and a penalized weighted median (PWM)‐based approach, were used to assess potential bias attributed to pleiotropy or invalid instruments.

Results

We found no evidence for a causal relationship between urate and PD, with an effect estimate from the IVW method of odds ratio (OR) 1.03 (95% confidence interval [CI], 0.88–1.20) per 1‐standard‐deviation increase in plasma urate levels. MR Egger and PWM analyses yielded similar estimates (OR, 0.99 [95% CI, 0.83–1.17] and 0.99 [95% CI, 0.86−1.14], respectively).

Interpretation

We did not find evidence for a linear causal protective effect by urate on PD risk. The associations observed in previous observational studies may be, in part, attributed to confounding or reverse causality. In the context of the present findings, strategies to elevate circulating urate levels may not reduce overall PD risk. Ann Neurol 2018;84:191–199
Metal‐Free Synthetic Approach to 3‐Monosubstituted Unsymmetrical 1,2,4,5‐Tetrazines Useful for Bioorthogonal Reactions
Authors: Qu Yangyang , Sauvage François‐Xavier , Clavier Gilles , Miomandre Fabien , Audebert Pierre
Published: July 2018

A facile, efficient and metal‐free synthetic approach to 3‐monosubstituted unsymmetrical 1,2,4,5‐tetrazines is presented. Dichloromethane (DCM) is for the first time recognized as a novel reagent in the synthetic chemistry of tetrazines. Using this novel approach 11 3‐aryl/alkyl 1,2,4,5‐tetrazines were prepared in excellent yields (up to 75 %). The mechanism of this new reaction, including the role of DCM in the tetrazine ring formation, has been investigated by 13C labeling of DCM, and is also presented and discussed as well as the photophysical and electrochemical properties.
Highly Selective Mitochondrial Targeting by a Ruthenium(II) Peptide Conjugate: Imaging and Photoinduced Damage of Mitochondrial DNA
Authors: Burke Christopher S. , Byrne Aisling , Keyes Tia E.
Published: July 2018

Mitochondrial DNA (mtDNA) plays a crucial but incompletely understood role in cellular biochemistry and etiology of numerous disease states. Thus, there is an urgent need for targeted probes that can dynamically respond to changes to mtDNA such as copy number in live cells, but it is difficult to permeate the mitochondrial membrane of the living cell. Now, a ruthenium(II) light‐switching probe targeted by peptide vectorization selectively to mitochondrial nucleoids is presented. Evidence for DNA binding by the probe in live cells is derived from confocal fluorescence microscopy, resonance Raman, and luminescence lifetime imaging. While viable under imaging conditions, specific staining of mitochondrial DNA permitted efficient and selective photoinduced toxicity on a cell‐by‐cell basis under higher excitation intensities. This powerful combination of imaging and photocytotoxicity is an important step towards realizing phototheranostic application of such RuII probes.
A quantitative PCR‐based environmental DNA assay for detecting Atlantic salmon (Salmo salar L.)
Authors: Atkinson Siobhán , Carlsson Jeanette E.L. , Ball Bernard , Egan Damian , Kelly‐Quinn Mary , Whelan Ken , Carlsson Jens
Published: July 2018

The Atlantic salmon (Salmo salar L.) has worldwide ecological, cultural, and economic importance. The species has undergone extensive decline across its native range, yet concerns have been raised about its invasive potential in the Pacific. Knowledge on the distribution of this species is vital for addressing conservation goals.

This study presents an environmental DNA assay to detect S. salar in water samples, using quantitative polymerase chain reaction technology. Species‐specific primers and a minor groove binding probe were designed for the assay, based on the mitochondrial cytochrome oxidase I gene.

The results of this study indicate that environmental DNA is a highly effective tool for detecting S. salar in situ, and could provide an alternative, non‐invasive method for determining the distribution of this species.
Migration and feeding habits of juvenile Chinese sturgeon (Acipenser sinensis Gray 1835) in the Yangtze Estuary: Implications for conservation
Authors: Wang Sikai , Zhang Tao , Yang Gang , Wang Yu , Zhao Feng , Zhuang Ping
Published: July 2018

Spatial and temporal variation in migration and feeding ecology of juvenile Chinese sturgeon (Acipenser sinensis Gray 1835) is reported for waters around Chongming Island, Yangtze Estuary, between April and August 2015.

A migration survey showed that juvenile Chinese sturgeon remained within the Yangtze Estuary for a period of time preceding their onward migration to the sea; upper estuarine reaches were an important transition habitat during April and May, while nearshore coastal areas were foraging habitat during June to August.

Stable isotopic analysis revealed (1) significantly lower isotope values in smaller‐sized Chinese sturgeon (≤100 mm) than larger‐ sized fish (>100 mm), which indicated a dietary shift likely occurs at fork lengths greater than 100 mm; (2) the increase in values of δ13C and δ15N from May to August implied an ontogenetic dietary shift from lower to higher trophic‐level prey items; and (3) slight changes in distributional range among different coastal sites implied that individuals fed on similar food items.

Coastal shallows represent major foraging areas for juvenile Chinese sturgeon in the Yangtze Estuary. In addition to the conventional conservation measures at the nature reserve, we suggest additional conservation actions to better protect juvenile Chinese sturgeon residing in the estuary; namely: (1) expanding the protected area and adding a seasonal component, from April to August, to afford better protection of juvenile Chinese sturgeon in the whole estuary, but particularly just upstream of the estuary mouth and in nearshore waters; and (2) banning all fishing activities and extending protection to the food resources (such as zoobenthos and small‐sized fishes) of juvenile Chinese sturgeon in coastal shallows.
Decision making in the prisoner's dilemma game: The effect of exit on cooperation and social welfare
Authors: Haesevoets Tessa , Bostyn Dries H. , Reinders Folmer Chris , Roets Arne , Van Hiel Alain
Published: July 2018

The prisoner's dilemma game is a mixed‐motive game that offers two players the simultaneous choice between a cooperative and a defective alternative. An often neglected aspect of such a binary‐choice game, however, is that in many real‐life encounters, people can choose not only to cooperate or defect, but they also have a third option: to exit the social dilemma. Although in the literature a consensus has emerged that the addition of an exit opportunity benefits cooperation, there is only scant research into its effect on social welfare. In order to allow a direct comparison of cooperation rates and welfare levels across binary‐choice and trinary‐choice games, in this study, we used a design in which the same participants played similar games with and without an exit option (i.e., a within‐subjects design), and this in a range of structural variations. The findings of our study indicated that the aggregated outcome of both players is generally lower in games with an exit option than in games without an exit option. Moreover, our results showed that the efficiency of the exit option strongly depends on the specific outcome structure of the game (in terms of its endowment size, (a)symmetry, and level of noncorrespondence). In the discussion, it is argued that the implementation of an exit option as a strategy to increase social welfare should be critically assessed.
Superior protein titers in half the fermentation time: Promoter and process engineering for the glucose‐regulated GTH1 promoter of Pichia pastoris
Authors: Prielhofer Roland , Reichinger Michaela , Wagner Nina , Claes Katrien , Kiziak Christoph , Gasser Brigitte , Mattanovich Diethard
Published: July 2018

Protein production in Pichia pastoris is often based on the methanol‐inducible P
AOX1 promoter which drives the expression of the target gene. The use of methanol has major drawbacks, so there is a demand for alternative promoters with good induction properties such as the glucose‐regulated P
GTH1 promoter which we reported recently. To further increase its potential, we investigated its regulation in more details by the screening of promoter variants harboring deletions and mutations. Thereby we could identify the main regulatory region and important putative transcription factor binding sites of P
GTH1. Concluding from that, yeast metabolic regulators, monomeric Gal4‐class motifs, carbon source‐responsive elements, and yeast GC‐box proteins likely contribute to the regulation of the promoter. We engineered a P
GTH1 variant with greatly enhanced induction properties compared with that of the wild‐type promoter. Based on that, a model‐based bioprocess design for high volumetric productivity in a limited time was developed for the P
GTH1 variant, to employ a glucose fed‐batch strategy that clearly outperformed a classical methanol fed‐batch of a P
AOX1 strain in terms of titer and process performance.
Molecular Probes for Imaging Fibrosis and Fibrogenesis
Authors: Désogère Pauline , Montesi Sydney B. , Caravan Peter
Published: July 2018

Fibrosis, or the accumulation of extracellular matrix molecules that make up scar tissue, is a common result of chronic tissue injury. Advances in the clinical management of fibrotic diseases have been hampered by the low sensitivity and specificity of noninvasive early diagnostic options, lack of surrogate end points for use in clinical trials, and a paucity of noninvasive tools to assess fibrotic disease activity longitudinally. Hence, the development of new methods to image fibrosis and fibrogenesis is a large unmet clinical need. Herein, an overview of recent and selected molecular probes for imaging of fibrosis and fibrogenesis by magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography is provided.
The Dual‐State Luminescent Mechanism of 2,3,4,5‐Tetraphenyl‐1H‐pyrrole
Authors: Lei Yunxiang , Liu Qianwei , Dong Lichao , Cai Zhengxu , Shi Jianbing , Zhi Junge , Tong Bin , Dong Yuping
Published: July 2018

2,3,4,5‐Tetraphenyl‐1H‐pyrrole (TePP) was synthesized by a simple one‐step reaction. The compound showed a balanced emission in both the solution and solid state with the absolute quantum yield of ΦF/THF=65.6 % and ΦF/solid=74.3 %, respectively. Temperature and viscosity variation measurements demonstrated that the phenyl group at the 1‐position (N‐position) of the pyrrole core can act as a rotor in pyrrole‐based molecules, which can consume the excited energy and reduce the molecular emission in solution. TePP without the phenyl group at the 1‐position can effectively enhance the emission in solution. Single‐crystal analysis showed that the phenyl groups at the 2,5‐positions of pyrrole extend the molecular conjugation and lock the conformation. The phenyl groups at the 3,4‐positions with a twisted conformation prevent their molecules from close packing and are helpful for aggregated emission. A delicate balance between the twisting conformation and rigid conjugation takes advantage of both ACQ and AIE luminogens. The strategy can tune the AIE, ACQ, or solution and solid dual‐state emission properties of pyrrole‐based molecules by simply altering the position of phenyl groups, which provides a great opportunity to explore the luminescent mechanism in greater detail and to facilitate practical applications.
The distributed circuit within the piriform cortex makes odor discrimination robust
Authors: Srinivasan Shyam , Stevens Charles F.
Published: July 2018

Distributed circuits wherein connections between subcircuit components seem randomly distributed are common to the olfactory circuit, hippocampus, and cerebellum. In such circuits, activation patterns seem random too, showing no detectable spatial preference, and contrast with regions that have topographic connections between subcircuits and topographic activation patterns. Quantitative studies of topographic circuits in the neocortex have yielded common principles of organization. Whether distributed circuits share similar principles of organization is unknown because similar quantitative information is missing and understanding the way they encode information remains a challenge. We addressed these needs by providing a quantitative description of the mouse piriform cortex, a paleocortical distributed circuit that subserves olfaction. The quantitative information provided two insights. First, with a nearly parameter‐free model of the olfactory circuit, we show that the piriform cortex robustly maintains odor information and discrimination ability present in the olfactory bulb. Second, the paleocortex is quantitatively different from the neocortex: it has a lower surface area density, which decreases from the anterior to posterior paleocortex contrasting with the uniform neuronal density of the neocortex. These insights might also apply to other distributed circuits.
MHD Boundary Layers Theory in Sobolev Spaces Without Monotonicity I: Well‐Posedness Theory
Authors: Liu Cheng‐Jie , Xie Feng , Yang Tong
Published: July 2018

We study the well‐posedness theory for the MHD boundary layer. The boundary layer equations are governed by the Prandtl‐type equations that are derived from the incompressible MHD system with non‐slip boundary condition on the velocity and perfectly conducting condition on the magnetic field. Under the assumption that the initial tangential magnetic field is not zero, we establish the local‐i‐time existence, uniqueness of solutions for the nonlinear MHD boundary layer equations. Compared with the well‐posedness theory of the classical Prandtl equations for which the monotonicity condition of the tangential velocity plays a crucial role, this monotonicity condition is not needed for the MHD boundary layer. This justifies the physical understanding that the magnetic field has a stabilizing effect on MHD boundary layer in rigorous mathematics. © 2018 Wiley Periodicals, Inc.
Position adjustment–based location error–resilient geo‐opportunistic routing for void hole avoidance in underwater sensor networks
Authors: Shah Mehreen , Wadud Zahid , Sher Arshad , Ashraf Mahmood , Khan Zahoor Ali , Javaid Nadeem
Published: July 2018

This paper presents four routing protocols for Underwater Sensor Networks (USNs): Location Error–resilient Transmission Range adjustment–based protocol (LETR), Mobile Sink–based GEographic and Opportunistic Routing (MSGER), Mobile Sink–based LETR (MSLETR), and Modified MSLETR (MMS‐LETR). LETR considers transmission range levels for finding neighbor nodes. If a node fails to find any neighbor node within its defined maximum transmission range level, it recovers from communication void regions using depth adjustment technology. MSGER and MSLETR avoid depth and transmission range adjustment and overcome the problem of communication void regions using MSs, whereas MMS‐LETR takes into account noise attenuation at various depth levels, elimination of retransmissions using multi‐path communication and load balancing. The performance of our proposed protocols is evaluated through simulations using different parameters. The simulation results show that MSS‐LETR supersedes all counterpart schemes in terms of packet loss ratio. LETR significantly improves network performance in terms of energy consumption, packet loss ratio, fraction of void nodes, and the total amount of depth adjustment.
Organize projects for success
Authors: Felix Elliot
Published: July 2018

A team is a group of people working toward a common goal. A project committee is a kind of team, but too often these groups never become high‐performing teams, and projects suffer as a result: deadlines missed, budgets exceeded, people disengaged, and opportunities lost. This is because every day at colleges and universities, a new project committee is formed to work on renovating a space or rethinking a service or reorganizing a department. New groups of people are assembled to take on tasks that are new to them and to work with colleagues and consultants who are new to them as well.
Ruling may impact negligence liability for violence involving students
Authors: Rooksby Jacob H.
Published: July 2018

The California Supreme Court issued a major decision in late March involving a public university's potential negligence liability for student‐on‐student injuries imparted during curricular activities.
Variation in context‐dependent foraging behavior across pollinators
Authors: Briggs Heather M. , Graham Stuart , Switzer Callin M. , Hopkins Robin
Published: July 2018

Pollinator foraging behavior has direct consequences for plant reproduction and has been implicated in driving floral trait evolution. Exploring the degree to which pollinators exhibit flexibility in foraging behavior will add to a mechanistic understanding of how pollinators can impose selection on plant traits. Although plants have evolved suites of floral traits to attract pollinators, flower color is a particularly important aspect of the floral display. Some pollinators show strong innate color preference, but many pollinators display flexibility in preference due to learning associations between rewards and color, or due to variable perception of color in different environments or plant communities. This study examines the flexibility in flower color preference of two groups of native butterfly pollinators under natural field conditions. We find that pipevine swallowtails (Battus philenor) and skippers (family Hesperiidae), the predominate pollinators of the two native Texas Phlox species, Phlox cuspidata and Phlox drummondii, display distinct patterns of color preferences across different contexts. Pipevine swallowtails exhibit highly flexible color preferences and likely utilize other floral traits to make foraging decisions. In contrast, skippers have consistent color preferences and likely use flower color as a primary cue for foraging. As a result of this variation in color preference flexibility, the two pollinator groups impose concordant selection on flower color in some contexts but discordant selection in other contexts. This variability could have profound implications for how flower traits respond to pollinator‐mediated selection. Our findings suggest that studying dynamics of behavior in natural field conditions is important for understanding plant–pollinator interactions.
Cattle selectivity by leopards suggests ways to mitigate human–leopard conflict
Authors: Khorozyan Igor , Ghoddousi Siavash , Soufi Mobin , Soofi Mahmood , Waltert Matthias
Published: July 2018

Addressing widespread livestock losses to carnivores requires information on which livestock categories are preferentially selected. We analyzed an individual‐based database of cattle grazing in forest (n = 932) and having been killed (n = 70) by leopards (Panthera pardus) in the Hyrcanian forest, Iran. We calculated Jacobs’ selectivity index for cattle age, sex, and coloration across four scales: the study area as a whole, three sites, nine villages, and 60 cattle owners. Naturally colored cattle were significantly preferred by leopards at all scales in comparison with black and black‐and‐white cattle, and there was also a preference for males and juveniles at the study area level. More research is needed to see whether cattle losses would decrease if the share of naturally colored individuals in local holdings was reduced and males and juveniles had limited access to forest. We conclude that phenotypic and biologic characteristics of livestock can affect depredation and appeal for more research in this direction, particularly within the predator–prey framework.
Total Synthesis of Estradiol Methyl Ether and Its Five‐Pot Synthesis with an Organocatalyst
Authors: Koshino Seitaro , Kwon Eunsang , Hayashi Yujiro
Published: July 2018

Enantioselective total synthesis of estradiol methyl ether has been accomplished in a highly diastereo‐ and enantioselective manner. The key reaction is diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives with A, C, and D rings of the steroids as a single isomer with excellent enantioselectivity. Each reaction was optimized, and the total synthesis could be accomplished in 12 pots with 10 purifications using silica gel, resulting in an overall yield of 6.8 %. The reaction sequence and reaction conditions were then optimized in terms of pot economy, whereupon estradiol methyl ether could be synthesized using five reaction vessels with four purifications in an overall yield of 15 %. Notably, six reactions, namely, oxidation, hydrogenation, formation of acid chloride, Friedel–Crafts reaction, deprotection, and reduction could be carried out in the last one‐pot sequence.
Quantifying wind‐driven firebrand production from roofing assembly combustion
Authors: Manzello Samuel L. , Suzuki Sayaka , Naruse Tomohiro
Published: July 2018

Large outdoor fires present a risk to the built environment. Examples often in the international media reports are wildfires that spread into communities, referred to as wildland‐urban interface (WUI) fires. Other examples are large urban fires including those that have occurred after earthquakes. Firebrands are a key mechanism on how rapidly fires spread in urban fires and WUI fires. An experimental protocol has been developed to ignite full‐scale roofing assemblies and quantify the degree of firebrand production during the combustion process. As wind is an important factor in firebrand generation, the experiments were conducted under a range of wind speeds at the Building Research Institute's Fire Research Wind Tunnel Facility. A further unique aspect of this work is that the experimental results are compared to firebrand size and mass distributions collected from an actual large‐scale urban fire in Japan. Results of these experiments demonstrate that when only oriented strand board is applied as sheathing, a significant number of firebrands collected from roofing assemblies were less than 1 g and 10 cm2. It was also observed that experiments on individual building component firebrand generation provided useful insights into actual urban fire firebrand generation.
A Transforming Growth Factor‐β and H19 Signaling Axis in Tumor‐Initiating Hepatocytes That Regulates Hepatic Carcinogenesis
Authors: Zhang Jinqiang , Han Chang , Ungerleider Nathan , Chen Weina , Song Kyoungsub , Wang Ying , Kwon Hyunjoo , Ma Wenbo , Wu Tong
Published: July 2018

Functions of transforming growth factor‐β (TGF‐β) in the liver vary depending on specific cell types and their temporal response to TGF‐β during different stages of hepatocarcinogenesis (HCG). Through analysis of tumor tissues from hepatocellular carcinoma (HCC) patients, we were able to cluster hepatic epithelial cell‐derived TGF‐β gene signatures in association with distinct clinical prognoses. To delineate the role of hepatic epithelial TGF‐β signaling in HCC development, we used an experimental system in which tumor‐initiating hepatocytes (TICs) were isolated from TGF‐β receptor II floxed mice (Tgfbr2fl/fl
) and transplanted into syngeneic C57BL/6J mice by splenic injection. Recipient mice were then administered Cre‐expressing adenovirus (Ad‐Cre) to inactivate Tgfbr2 in transplanted TICs. After latency, Tgfbr2‐inactivated TICs formed larger and more tumor nodules in recipient livers compared to TICs without Tgfbr2 inactivation. In vitro analyses revealed that treatment of cultured TICs with TGF‐β inhibited expression of progenitor cell factors (including SRY (sex determining region Y)‐box 2 [Sox2]). RNA sequencing (RNA‐seq) analysis identified H19 as one of the most up‐regulated long noncoding RNA (lncRNA) in association with Tgfbr2 inactivation in TICs. Tgfbr2 inactivation by Ad‐Cre led to a 5‐fold increase of H19 expression in TICs. Accordingly, TGF‐β treatment reduced H19 expression. We observed that forced overexpression of Sox2 in TICs increased transcription of H19, whereas knockdown of Sox2 decreased it. Furthermore, depletion of H19 reduced the progenitor property of TICs in vitro and decreased their tumorigenic potential in vivo. Finally, we observed a low level of H19 mRNA expression in human HCC tissues from patients with the epithelial TGF‐β gene signature in association with favorable prognosis. Conclusion: Our findings describe a TGF‐β and H19 signaling axis by Sox2 in TICs that importantly regulates HCG.
ADAPT: An Algorithm Incorporating PRO‐C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis
Authors: Daniels Samuel J. , Leeming Diana J. , Eslam Mohammed , Hashem Ahmed M. , Nielsen Mette J. , Krag Aleksander , Karsdal Morten A. , Grove Jane I. , Neil Guha Indra , Kawaguchi Takumi , Torimura Takuji , McLeod Duncan , Akiba Jun , Kaye Philip , de Boer Bastiaan , Aithal Guruprasad P. , Adams Leon A. , George Jacob
Published: July 2018

Given the high global prevalence of nonalcoholic fatty liver disease (NAFLD), the need for relevant noninvasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis (≥ F3) is the most crucial, as these individuals have the greatest risk of adverse, long‐term, liver‐related outcomes. We aimed to investigate the role of PRO‐C3 (a marker of type III collagen formation) as a biomarker for advanced fibrosis in NAFLD. We measured PRO‐C3 by enzyme‐linked immunosorbent assay in two large independent cohorts with extensive clinical phenotyping and liver biopsy: 150 in the derivation and 281 in the validation cohort. A PRO‐C3‐based fibrosis algorithm that included age, presence of diabetes, PRO‐C3, and platelet count (ADAPT) was developed. PRO‐C3 increased with fibrosis stage (Rho 0.50; P < 0.0001) and was independently associated with advanced fibrosis (odds ratio = 1.05; 95% confidence interval [CI] 1.02‐1.08; P = 0.003). ADAPT showed areas under the receiver operating characteristics curve of 0.86 (95% CI 0.79‐0.91) in the derivation and 0.87 in the validation cohort (95% CI 0.83‐0.91) for advanced fibrosis. This was superior to the existing fibrosis scores, aspartate aminotransferase to platelet ratio index (APRI), FIB‐4, and NAFLD fibrosis score (NFS) in most comparisons. Conclusion: PRO‐C3 is an independent predictor of fibrosis stage in NAFLD. A PRO‐C3‐based score (ADAPT) accurately identifies patients with NAFLD and advanced fibrosis and is superior to APRI, FIB‐4, and NFS.
Liver Stiffness Measurements in Patients with Noncirrhotic Portal Hypertension—The Devil Is in the Details
Authors: Vuppalanchi Raj , Mathur Karan , Pyko Maximillian , Samala Niharika , Chalasani Naga
Published: July 2018

Noncirrhotic portal hypertension (NCPH) is often a diagnostic challenge due to signs and symptoms of portal hypertension that overlap with cirrhosis. The etiology of NCPH is broadly classified as prehepatic, hepatic (presinusoidal and sinusoidal) and posthepatic.1 Some common etiologies of NCPH encountered in clinical practice include portal vein thrombosis (prehepatic) and nodular regenerative hyperplasia (hepatic). Liver histology, although considered gold standard to exclude cirrhosis in individuals with suspected NCPH, is often limited by subtle histologic features or inadequate sampling. Liver stiffness measurements (LSMs) by vibration‐controlled transient elastography may provide clinically important information to distinguish NCPH from cirrhosis by revealing normal LSM in prehepatic and presinusoidal NCPH.
Dual Targeting of Histone Methyltransferase G9a and DNA‐Methyltransferase 1 for the Treatment of Experimental Hepatocellular Carcinoma
Authors: Bárcena‐Varela Marina , Caruso Stefano , Llerena Susana , Álvarez‐Sola Gloria , Uriarte Iker , Latasa M. Ujue , Urtasun Raquel , Rebouissou Sandra , Alvarez Laura , Jimenez Maddalen , Santamaría Eva , Rodriguez‐Ortigosa Carlos , Mazza Giuseppe , Rombouts Krista , San José‐Eneriz Edurne , Rabal Obdulia , Agirre Xabier , Iraburu Maria , Santos‐Laso Alvaro , Banales Jesus M. , Zucman‐Rossi Jessica , Prósper Felipe , Oyarzabal Julen , Berasain Carmen , Ávila Matías A. , Fernández‐Barrena Maite G.
Published: July 2018

Epigenetic modifications such as DNA and histone methylation functionally cooperate in fostering tumor growth, including that of hepatocellular carcinoma (HCC). Pharmacological targeting of these mechanisms may open new therapeutic avenues. We aimed to determine the therapeutic efficacy and potential mechanism of action of our dual G9a histone‐methyltransferase and DNA‐methyltransferase 1 (DNMT1) inhibitor in human HCC cells and their crosstalk with fibrogenic cells. The expression of G9a and DNMT1, along with that of their molecular adaptor ubiquitin‐like with PHD and RING finger domains‐1 (UHRF1), was measured in human HCCs (n = 268), peritumoral tissues (n = 154), and HCC cell lines (n = 32). We evaluated the effect of individual and combined inhibition of G9a and DNMT1 on HCC cell growth by pharmacological and genetic approaches. The activity of our lead compound, CM‐272, was examined in HCC cells under normoxia and hypoxia, human hepatic stellate cells and LX2 cells, and xenograft tumors formed by HCC or combined HCC+LX2 cells. We found a significant and correlative overexpression of G9a, DNMT1, and UHRF1 in HCCs in association with poor prognosis. Independent G9a and DNMT1 pharmacological targeting synergistically inhibited HCC cell growth. CM‐272 potently reduced HCC and LX2 cells proliferation and quelled tumor growth, particularly in HCC+LX2 xenografts. Mechanistically, CM‐272 inhibited the metabolic adaptation of HCC cells to hypoxia and induced a differentiated phenotype in HCC and fibrogenic cells. The expression of the metabolic tumor suppressor gene fructose‐1,6‐bisphosphatase (FBP1), epigenetically repressed in HCC, was restored by CM‐272. Conclusion: Combined targeting of G9a/DNMT1 with compounds such as CM‐272 is a promising strategy for HCC treatment. Our findings also underscore the potential of differentiation therapy in HCC.
What Drives Engineering Students To Be Entrepreneurs? Evidence of Validity for an Entrepreneurial Motivation Scale
Authors: Yi Soohyun , Duval‐Couetil Nathalie
Published: July 2018

Background

Educators and policymakers are increasingly interested in making entrepreneurship education accessible to engineering students given engineers' potential contributions to innovation and the economy. However, what motivates engineering students to choose entrepreneurial careers and how this could be influenced through education have not been fully explored in the literature.

Purpose

The study develops and tests an entrepreneurial motivation scale for engineering students. It required providing initial evidence of validity for the scale based on guidelines for developing educational and psychological tests.

Design/Method

Following a comprehensive literature review, we chose to modify an existing scale and administer it to engineering students. Here we present two sources of evidence of validity for examining how entrepreneurial motivation relates to variables commonly used to measure the impact of entrepreneurship education. They were developed by examining factor structure and psychometric properties as well as conducting mediation analysis.

Results

Data obtained from 460 engineering students supported three factors underlying the construct of entrepreneurial motivation:Motivation for Creation and Solution(MCS),Motivation for Personal Interests(MPS), andManagerial Motivation(MM). MCS and MM effectively explained intention to become an entrepreneur with mediation effects of venturing and technology self‐efficacy.

Conclusion

These findings resulted in a more parsimonious categorization of factors underlying the construct of entrepreneurial motivation than identified in prior studies, providing a foundational understanding of entrepreneurial motivation among engineering students. The results can be useful in assessment, research, and/or policy decisions related to delivering entrepreneurship education to engineering students.
Antioxidant activity and phenolic composition in pomegranate (Punica granatum L.) genotypes from south Italy by UHPLC–Orbitrap‐MS approach
Authors: Di Stefano Vita , Pitonzo Rosa , Novara Maria Eugenia , Bongiorno David , Indelicato Serena , Gentile Carla , Avellone Giuseppe , Bognanni Rosaria , Scandurra Salvatore , Melilli Maria Grazia
Published: July 2018

Background

Pomegranate fruits are a rich source of polyphenols with numerous health‐promoting effects. Pomegranate juices of five genotypes (‘Mollar’, ‘Kingdom’, ‘Dente di Cavallo’, and two old populations ‘Francofonte’ and ‘Santa Tecla’) were evaluated regarding anthocyanin and non‐anthocyanin phenolic contents using ultrahigh performance liquid chromatography (UHPLC)–Orbitrap‐mass spectrometry (MS). Moreover, total antioxidant activity (TAA) was evaluated using a 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS) assay.

Results

Twenty‐three phenolic compounds were identified. Cyanidin‐3,5‐O‐diglucoside and pelargonidin‐3,5‐O‐diglucoside were the most representative anthocyanins in all genotypes; the Santa Tecla population had the highest content of these anthocyanins, 97.64 mg L−1 and 40.29 mg L−1 respectively. In the Francofonte population, ferulic acid hexoside was the most abundant compound (391.18 mg L−1). TAA values ranged between 221.5 and 36.73 µmol Trolox equivalents/100 mL of juice. A high TAA value was recorded for the Santa Tecla pomegranate population.

Conclusion

The UHPLC–Orbitrap‐MS approach was employed for the first time to identify the phenolic compound profiling in five pomegranate genotypes. TAA was analysed using an ABTS assay, and the results showed a significant variability in nutraceutical potential of the pomegranate genotypes studied. The inclusion of phenolic information in the linear discriminant analysis allowed very good discriminations among genotypes to be obtained. © 2018 Society of Chemical Industry