bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligand‐Induced Dimerization of a Truncated Parallel MYC G‐Quadruplex
Authors: Funke Andrea , Karg Beatrice , Dickerhoff Jonathan , Balke Darko , Müller Sabine , Weisz Klaus
Published: December 2017

Binding of an indoloquinoline derivative with an aminoalkyl side chain to a truncated sequence from the MYC promoter region was studied through isothermal titration calorimetry (ITC). The targeted MYC3 sequence lacks 3′‐flanking nucleotides and forms a monomeric parallel quadruplex (G4) with a blunt‐ended 3′‐outer tetrad under the solution conditions employed. Analysis of ITC isotherms reveals multiple binding equilibria with the initial formation of a 1:2 ligand/quadruplex complex. Evaluation of electrophoretic mobilities as well as NMR spectral data confirm ligand‐induced dimerization of MYC3 quadruplexes with the ligand sandwiched between the two 3′‐outer tetrads. Additional ligand molecules in excess bind to the 5′‐outer tetrads of the sandwich complex. Such a ligand‐promoted G4 dimerization may be exploited for the controlled assembly or disassembly of G4 aggregates to expand on present quadruplex‐based technologies.
Ready, set, pull, ow!
Authors: Butman Samuel M.
Published: December 2017

Key Points

The BADFORM technique is a novel technique in getting devices across otherwise uncrossable lesions

It is critical to perform the pulling parallel to the vessel

The technique and its success has only been described in the 10 cases reported so caution is advised
Nitroglycerin and the enduring principles of coronary procedures
Authors: Topaz On
Published: December 2017

Key Points

The benefits of nitroglycerin are numerous, from ensuring accurate interpretation of diagnostic angiograms to treatment of coronary spasm and support of PCIs in simple or complex lesion types.

The founders of the field were convinced that no coronary arteriography should be considered complete unless a vasodilator is used at some point during the study. This recommendation is valid.

The guidelines should change to include administration of intracoronary nitroglycerin.
Ischemia‐reperfusion injury and ischemic post‐conditioning in acute myocardial infarction: Lost in translation
Authors: Giustino Gennaro , Dangas George D.
Published: December 2017

Key Points

Ischemic post‐conditioning (IPoC) has been proposed as a strategy to mitigate the risk of ischemia‐reperfusion injury during primary percutaneous coronary intervention (PCI) for ST‐elevation myocardial infarction (STEMI).

In this comprehensive and updated meta‐analysis of randomized controlled trials, IPoC during primary PCI for STEMI had no significant effect on all‐cause mortality, re‐infarction, or new‐onset heart failure compared with no post‐conditioning.

Further strategies need to be prospectively evaluated to improve outcomes in patients with STEMI undergoing primary PCI.
The first antenatal diagnosis of KBG syndrome: a microdeletion at chromosome 16q24.2q24.3 containing multiple genes including ANKRD11 associated with the disorder
Authors: Hodgetts Morton Victoria , Quinlan‐Jones Elizabeth , Butts Natasha , Williams Denise , Hamilton Sue , Marton Tamas , Morris Katie
Published: December 2017

Key Clinical Message

The loss of ANKRD11 gene confirms the diagnosis of KBG syndrome but does not elucidate the pediatric phenotype providing a counseling challenge. With the expansion of prenatal diagnosis, and the potential to perform whole‐exome sequencing antenatally, we must describe the genetic abnormalities, antenatal ultrasound findings, and phenotype concurrently to facilitate counseling.
Understanding the Heterogeneous Electrocatalytic Reduction of Carbon Dioxide on Oxide‐Derived Catalysts
Authors: Pander James E. , Ren Dan , Huang Yun , Loo Nicholas Wei Xian , Hong Samantha Hui Lee , Yeo Boon Siang
Published: December 2017

Global climate change and energy concerns have led to a surge of interest in the electrochemical conversion of carbon dioxide (CO2) to fuels such as methane and ethanol. Metals such as copper, tin, gold, and others have proven effective as catalysts for reducing CO2 to a wide spectrum of products. Interestingly, it has recently been shown that oxidizing some of these metals further enhances their catalytic activities and selectivities. Oxidation seems to play a fundamental, but poorly understood, role in modulating the reactivity of these catalysts. In this Review, recent progress towards understanding the effect of oxygen, surface morphologies, and local pH gradients on the catalysis of CO2 reduction is discussed.
Ex Situ Evidence for the Role of a Fluoride‐Rich Layer Switching the Growth of Nanopores to Nanotubes: A Missing Piece of the Anodizing Puzzle
Authors: Shahzad Khurram , Kowalski Damian , Zhu Chunyu , Aoki Yoshitaka , Habazaki Hiroki
Published: December 2017

Anodizing involves a high‐voltage electrochemical conversion process that forms barrier‐type oxide layers or self‐organized nanoporous/nanotubular structures. So far, Al2O3‐like nanopores and TiO2‐like nanotubes could be successfully synthesized on many metals and alloys. The proposed models of anodic oxide nanotubes growth, however, sacrifice from lack of evidence of the transition from nanopores to nanotubes. The present study demonstrates a missing piece of this anodizing puzzle, which is responsible for the formation of nanotubes in fluoride‐containing organic electrolytes. For this purpose, we choose an anodic oxide formed on iron, as a model case, because both nanotubes and nanopores can be formed and slow kinetics of transition between those two forms allows us to observe, ex situ, a fluoride‐rich‐layer upon nanopores/nanotubes transition. The compositional fingerprints of this transition shed a light on the general mechanism of nanotubes growth in fluoride‐containing electrolytes.
Enhancing Van der Waals Interactions of Functionalized UiO‐66 with Non‐polar Adsorbates: The Unique Effect of para Hydroxyl Groups
Authors: Tovar Trenton M. , Iordanov Ivan , Sava Gallis Dorina F. , DeCoste Jared B.
Published: December 2017

UiO‐66 is a highly stable metal‐organic framework (MOF) that has garnered interest for many adsorption applications. For small, nonpolar adsorbates, physisorption is dominated by weak Van der Waals interactions limiting the adsorption capacity. A common strategy to enhance the adsorption properties of isoreticular MOFs, such as UiO‐66, is to add functional groups to the organic linker. Low and high pressure O2 isotherms were measured on UiO‐66 MOFs functionalized with electron donating and withdrawing groups. It was found that the electron donating effects of ‐NH2, ‐OH, and ‐OCF3 groups enhance the uptake of O2. Interestingly, a significant enhancement in both the binding energy and adsorption capacity of O2 was observed for UiO‐66‐(OH)2‐p, which has two ‐OH groups para from one another. Density functional theory (DFT) simulations were used to calculate the binding energy of oxygen to each MOF, which trended with the adsorption capacity and agreed well with the heats of adsorption calculated from the Toth model fit to multi‐temperature isotherms. DFT simulations also determined the highest energy binding site to be on top of the electron π‐cloud of the aromatic ring of the ligand, with a direct trend of the binding energy with low pressure adsorption capacity. Uniquely, DFT found that oxygen molecules adsorbed to UiO‐66‐(OH)2‐p prefer to align parallel to the ‐OH groups on the aromatic ring. Similar effects for the electron donation of the functional groups were observed for the low pressure adsorption of N2, CH4, and CO2.
Silver(I)‐Mediated Base Pairs in DNA Sequences Containing 7‐Deazaguanine/Cytosine: towards DNA with Entirely Metallated Watson–Crick Base Pairs
Authors: Méndez‐Arriaga José M. , Maldonado Carmen R. , Dobado José A. , Galindo Miguel A.
Published: December 2017

DNA sequences comprising noncanonical 7‐deazaguanine (7CG) and canonical cytosine (C) are capable of forming Watson–Crick base pairs via hydrogen bonds as well as silver(I)‐mediated base pairs by coordination to central silver(I) ions. Duplexes I and II containing 7CG and C have been synthesized and characterized. The incorporation of silver(I) ions into these duplexes has been studied by means of temperature‐dependent UV spectroscopy, circular dichroism, and DFT calculations. The results suggest the formation of DNA molecules comprising contiguous metallated 7CG‐AgI‐C Watson–Crick base pairs that preserve the original B‐type conformation. Furthermore, additional studies performed on duplex III indicated that, in the presence of AgI ions, 7CG–C and 7CA–T Watson–Crick base pairs (7CA, 7‐deazadenine; T, thymine) can be converted to metallated 7CG‐AgI‐C and 7CA‐AgI‐T base pairs inside the same DNA molecule whilst maintaining its initial double helix conformation. These findings are very important for the development of customized silver–DNA nanostructures based on a Watson–Crick complementarity pattern.
Boron Nanowheels with Axles Containing Noble Gas Atoms: Viable Noble Gas Bound M©B10−Clusters (M=Nb, Ta)
Authors: Pan Sudip , Kar Susmita , Saha Ranajit , Osorio Edison , Zarate Ximena , Zhao Lili , Merino Gabriel , Chattaraj Pratim K.
Published: December 2017

The viability of noble gas axled boron nanowheels NgnM©B10−(Ng=Ar–Rn; M=Nb, Ta;n=1, 2) is explored by ab initio computations. In the resulting Ng2–M complexes, the Ng‐M‐Ng nanorod passes through the center of the B10−ring, providing them with an inverse sandwich‐like structure. While in the singly Ng bound analogue, the Ng binding enthalpyHbat 298 K ranges from 2.5 to 10.6 kcal mol−1, in doubly Ng bound cases it becomes very low for the Ng2M©B10−→Ng+NgM©B10−dissociation channel, except for the case of Rn, for which the correspondingHbvalues are 3.4 (Nb) and 4.0 kcal mol−1(Ta). For a given Ng, Ta has slightly higher Ng‐binding ability than Nb. The corresponding free‐energy changes indicate that these systems, particularly the Xe and Rn complexes, are good candidates for experimental realization in a low‐temperature matrix. The Ng−M bonds were found to be covalent in nature, as reflected in their large Wiberg bond indices, formation of a 2c–2e σ orbital between Ng and M centers in natural bond orbital and adaptive natural density partitioning (AdNDP) analyses, and the short Ng−M distances. Energy decomposition analysis and a study on the natural orbitals for chemical valence show that the Ng−M contact is supported mainly by the orbital and electrostatic interactions, with almost equal contributions. Although both the Ng→M σ donation and Ng←M π backdonation play roles in the origin of orbital interaction, the former is significantly dominant over the latter. Further, AdNDP analysis indicates that the doubly aromatic character (both σ and π) in MB10−clusters is not perturbed by the interaction with Ng atoms.
Population Pharmacokinetics of Desvenlafaxine: Pharmacokinetics in Korean Versus US Populations
Authors: Nichols Alice I. , Liao Sam , Abbas Richat
Published: December 2017

Desvenlafaxine exposure in Korean and US populations was compared using population pharmacokinetic (PK) analysis. Data from a single‐ and multiple‐dose study of desvenlafaxine (50, 100, and 200 mg) in 30 healthy Korean subjects were added to a population PK model previously developed using sparse PK samples from patients with major depressive disorder, including 140 Korean patients, combined with rich PK data from healthy volunteers. The structural PK model was an open 1‐compartment linear disposition model with parallel first‐order and 0‐order inputs. The effects of Korean status on apparent oral clearance (CL/F) and apparent volume of distribution (V/F) were tested against the base model separately. External validation results indicated good agreement between the model predictions and observed desvenlafaxine concentrations for Korean subjects. The geometric mean CL/F and V/F of Korean subjects were 9.1% and 16.7% lower, respectively, than those of US subjects, who had a 20% higher mean body weight. Results for patients with major depressive disorder were similar. There were no meaningful differences for weight‐normalized CL/F and V/F values between Korean and US subjects or patients. The minor differences in CL/F and V/F observed between Korean and US populations appear to be solely due to lower body weights in the Korean population.
A coarse‐grained page cache aware multivariate analytical model for the storage performance of a parallel file system
Authors: Inacio Eduardo C. , Dantas Mario A. R.
Published: December 2017

Huge requirements of emerging Big Data applications combined with the performance impairment of current I/O subsystems pose a great challenge on data storage, management, and access performance. In order to design efficient storage systems, a clear understanding about how factors in the I/O path affect the performance of a data‐intensive application is of utmost importance. This paper reports our ongoing research toward addressing this issue, presenting a coarse‐grained page cache aware multivariate analytical model for the performance of write operations in a parallel file system. The proposed model was developed to reflect the performance behavior observed in an extensive experimental effort, in which the impact of 14 parameters in the response time and throughput of the OrangeFS was investigated. More than one million experiments were carried out using four distinct computing infrastructures, providing a detailed performance characterization. Additionally, a thorough evaluation of the proposed model, covering more than 14 000 scenarios, is reported, discussing both qualitative and quantitative aspects. Evaluation results indicate that the model succeeded in representing the behavior of the parallel file system performance, achieving a Mean Absolute Percentage Error of 39.94%.
Integration of Central and Peripheral Regulation of the Circulation during Exercise: Acute and Chronic Adaptations
Authors: Mueller Patrick J. , Clifford Philip S. , Crandall Craig G. , Smith Scott A. , Fadel Paul J.
Published: December 2017

Physical movement lasting any more than a few seconds (e.g., exercise), requires coordination of motor control with concomitant changes in the cardiovascular and respiratory support necessary to respond to the rapid increases in metabolic demand. Without such coordination, delivery of oxygen and removal of waste products become rate limiting and will restrict the duration, speed, and quality of movement. Fortunately, under healthy conditions, the central and peripheral nervous systems contribute importantly to this remarkable level of coordination via complex mechanisms that remain to be fully elucidated. The purposes of this review are to present the current state of knowledge regarding: (i) mechanisms by which the body maintains appropriate perfusion pressure to all organs during acute bouts of exercise, and (ii) alterations occurring in these mechanisms via central nervous system adaptations when exercise is performed or not performed on a regular basis (e.g., physically active versus sedentary lifestyle, respectively). Results from studies performed in humans and laboratory animals provide the reader a well‐rounded knowledge base. They are intended to instill an appreciation of what is known, and not known, about how the brain regulates the cardiovascular system during acute bouts of exercise, and the adaptations that occur when individuals exercise regularly versus when chronically sedentary. Discussion of the latter is intended to provide novel mechanisms for the increased incidence of cardiovascular disease in sedentary individuals versus a reduced incidence in individuals who are regularly active. © 2018 American Physiological Society.Compr Physiol8:103‐151, 2018.
Molecular Regulation of Sprouting Angiogenesis
Authors: Duran Camille L. , Howell David W. , Dave Jui M. , Smith Rebecca L. , Torrie Melanie E. , Essner Jeffrey J. , Bayless Kayla J.
Published: December 2017

The term angiogenesis arose in the 18th century. Several studies over the next 100 years laid the groundwork for initial studies performed by the Folkman laboratory, which were at first met with some opposition. Once overcome, the angiogenesis field has flourished due to studies on tumor angiogenesis and various developmental models that can be genetically manipulated, including mice and zebrafish. In addition, new discoveries have been aided by the ability to isolate primary endothelial cells, which has allowed dissection of various steps within angiogenesis. This review will summarize the molecular events that control angiogenesis downstream of biochemical factors such as growth factors, cytokines, chemokines, hypoxia‐inducible factors (HIFs), and lipids. These and other stimuli have been linked to regulation of junctional molecules and cell surface receptors. In addition, the contribution of cytoskeletal elements and regulatory proteins has revealed an intricate role for mobilization of actin, microtubules, and intermediate filaments in response to cues that activate the endothelium. Activating stimuli also affect various focal adhesion proteins, scaffold proteins, intracellular kinases, and second messengers. Finally, metalloproteinases, which facilitate matrix degradation and the formation of new blood vessels, are discussed, along with our knowledge of crosstalk between the various subclasses of these molecules throughout the text.Compr Physiol8:153‐235, 2018.
Strategies toward Long‐Life Light‐Emitting Electrochemical Cells
Authors: Gao Jun
Published: December 2017

This Minireview examines the operational lifetime of light‐emitting electrochemical cells (LECs). Under continuous operation, both polymer‐based LECs (PLECs) and ionic transition‐metal complex (iTMC)‐based LECs (iTMC‐LECs) now exhibit a luminance half‐life exceeding 1000 h. This improved performance was accomplished with several effective strategies aimed at optimizing the operating scheme, the material composition, and the device architecture. These strategies are presented in detail with PLECs as an example. iTMC‐LECs are also highlighted owing to their excellent stress stability with regards to both luminance and operating voltage. The survey of literature data points to clear trends, as well as some unexpected results in LECs stressed for an extended period. Major challenges still exist, but long‐lasting LECs are possible when the proven strategies are combined with innovative materials and device design.
Metacognitive beliefs as a predictor of health anxiety in a self‐reporting Italian clinical sample
Authors: Melli Gabriele , Bailey Robin , Carraresi Claudia , Poli Andrea
Published: December 2017

Research has supported the specific role that anxiety sensitivity, health‐related dysfunctional beliefs, and metacognitive beliefs may play in the development and maintenance of health anxiety symptoms. However, the role of metacognitive beliefs in health anxiety has only been explored in analogue samples. The aim of this study was to explore for the first time the association between metacognitive beliefs and health anxiety symptoms in a sample of participants who reported having received a diagnosis of severe health anxiety (hypochondriasis) or illness anxiety disorder and test whether these beliefs are significant predictors of health anxiety after controlling for anxiety, depression, anxiety sensitivity, and dysfunctional beliefs. A series of dimensional self‐report measures were administered to a large Italian sample (N = 458). At a bivariate level, Beliefs that Thoughts are Uncontrollable had a stronger association with health anxiety than any of the dysfunctional beliefs and anxiety sensitivity subscales. Results from hierarchical multiple regression analysis indicated that Beliefs that Thoughts are Uncontrollable predicted health anxiety symptoms over‐and‐above depression, general anxiety, anxiety sensitivity, and health‐related dysfunctional beliefs. Despite many important limitations, this study supported the hypothesis that metacognition may have an important role in health anxiety in clinical samples.
How does routinely delivered cognitive–behavioural therapy for gambling disorder compare to “gold standard” clinical trial?
Authors: Smith David P. , Fairweather‐Schmidt A. Kate , Harvey Peter W. , Battersby Malcolm W.
Published: December 2017

Currently, it is unknown whether treatment outcomes derived from randomized controlled trials (RCTs) of cognitive–behavioural therapy (CBT) for problem gamblers still hold when applied to patients seen in routine practice. Thus, data from an RCT of cognitive therapy versus exposure therapy for problem gambling versus patients of a gambling help service were compared. Assessments of problem gambling severity, psychosocial impairment, and alcohol use were undertaken at baseline and post‐treatment and evaluated within a counterfactual framework. Findings showed that the contrast between routine CBT for pokies and horse betting had a significant effect, indicative of a 62% lower gambling urge score if routine CBT recipients had all been horse/track betters opposed to gambling with “pokies.” However, the majority of contrasts indicated therapeutic outcomes achieved in routine CBT treatments were of equivalent robustness relative to RCT conditions. The present findings infer routine practice treatment outcomes are as efficacious as those generated in RCT contexts.
Pediatric Development of Molecularly Targeted Oncology Drugs
Authors: Patel Shivam Kamlesh , Leong Ruby , Zhao Hong , Barone Amy , Casey Denise , Liu Qi , Burckart Gilbert J. , Reaman Gregory
Published: December 2017

Oncology products developed for adult cancers often receive full waivers of pediatric studies. This analysis retrospectively identified products with potential pediatric development opportunities despite a full waiver. Initial pediatric study plans submitted to the US Food and Drug Administration from 2012 to 2016 for oncology products with plans to request full waivers of pediatric studies were reviewed to determine if a scientific rationale existed for pediatric evaluation based on the molecular mechanism of action (MOA), clinical experience, nonclinical evidence, or published genome sequencing data. Of the 98 oncology products reviewed, pediatric studies were eventually conducted in 55 (56%) despite having a waiver, 33 additional (34%) products were considered to have a rationale for pediatric evaluation but were not studied, and 10 (10%) products had no current evidence to support pediatric development. Conducting pediatric studies based on molecular MOA, rather than indication, provides opportunities to evaluate products earlier and accelerate pediatric oncology drug development.
Designing In and Around Tolerability Considerations for Immunotherapy Combinations
Authors: Stroh Mark
Published: December 2017

Over a century ago, paths diverged in the treatment of cancer: the well‐traveled path employed cytotoxic chemotherapy drugs, while one of the roads less traveled included immunotherapies. Cancer immunotherapy is now a path to durable responses, however not all patients benefit. Immunotherapy combinations promise responses for a larger proportion of patients, but tolerability can prove to be a barrier. Providing deep, durable responses to more patients requires us to successfully navigate emerging combination tolerability issues.
Model‐Based Assessments of CYP‐Mediated Drug–Drug Interaction Risk of Alectinib: Physiologically Based Pharmacokinetic Modeling Supported Clinical Development
Authors: Cleary Yumi , Gertz Michael , Morcos Peter N. , Yu Li , Youdim Kuresh , Phipps Alex , Fowler Stephen , Parrott Neil
Published: December 2017

Alectinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK‐positive non‐small cell lung cancer. Alectinib and its major active metabolite M4 exhibited drug–drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C8 in vitro. Clinical relevance of the DDI risk was investigated as part of a rapid development program to fulfill the breakthrough therapy designation. Therefore, a strategy with a combination of physiologically based pharmacokinetic (PBPK) modeling and limited clinical trials focused on generating informative data for modeling was made to ensure extrapolation ability of DDI risk. The PBPK modeling has provided mechanistic insight into the low victim DDI risk of alectinib through CYP3A4 by a novel two‐dimensional analysis for fmCYP3A4 and FG, and demonstrated negligible CYPs 2C8 and 3A4 enzyme‐modulating effects at clinically relevant exposure. This work supports that alectinib can be prescribed without dose adjustment for CYP‐mediated DDI liabilities.
Cryptanalysis of an identity‐based authenticated key exchange protocol
Authors: Hatri Younes , Otmani Ayoub , Guenda Kenza
Published: December 2017

Authenticated key exchange protocols represent an important cryptographic mechanism that enables several parties to communicate securely over an open network. Elashry, Mu, and Susilo proposed an identity‐based authenticated key exchange (IBAKE) protocol where different parties establish secure communication by means of their public identities.The authors also introduced a new security notion for IBAKE protocols called resiliency, that is, if the secret shared key is compromised, the entities can generate another shared secret key without establishing a new session between them. They then claimed that their IBAKE protocol satisfies this security notion.

We analyze the security of their protocol and prove that it has a major security flaw, which renders it insecure against an impersonation attack. We also disprove the resiliency property of their scheme by proposing an attack where an adversary can compute any shared secret key if just one secret bit is leaked.
Network condition and application‐based data adaptive intelligent message routing in vehicular network
Authors: Purkait Rajesh , Tripathi Sachin
Published: December 2017

Recent advances in intelligent transportation systems enable a broad range of potential applications that significantly improve the vehicle and road safety and facilitate the efficient dissemination of information among the vehicles. To assist the vehicle traffic, message broadcasting is a widely adopted technique for road safety. But efficient message broadcasting is a significant issue, especially in a high network density due to the broadcast storm problem. To solve this issue, several methods are proposed to eliminate the redundant transmission of safety packets. However, they lack in restricting the broadcasting region of safety messages, and the transmissions of safety packets outside the dangerous region, and force the vehicles to unnecessary detours. This paper proposes an adaptive multimode routing protocol, network condition, and application‐based data adaptive intelligent message routing in vehicular network (NetCLEVER) that supports 2 modes of operation such as message broadcasting and intelligent routing. In message broadcasting mode, the NetCLEVER decides the dangerous region of the network by considering the changes of neighbor vehicles velocity, instead of current vehicle velocity, because a vehicle decision in velocity is interdependent with the preceding vehicles. In intelligent routing mode, the NetCLEVER exploits the cuckoo search optimization in routing by taking into account multiple routing factors such as the road topology of intersections and traffic signals and their impact on link stability, which improves the reliability of routing packets significantly. The performance evaluation illustrates that the proposed NetCLEVER improves reliable wireless communication as well as road safety in vehicular ad hoc networks.
Utility of core biopsy with concurrent ROSE FNA in the diagnosis of pancreatic tumor‐does the biopsy add any diagnostic benefit?
Authors: Yan Lei , Ikemura Kenji , Park Ji‐Weon
Published: December 2017

Background

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) and endoscopic ultrasound‐guided core‐needle biopsy (EUS‐CNB) are widely used for diagnosis of pancreatic tumors. The aim of our study was to compare the diagnostic performance of ROSE EUS‐FNA and EUS‐CNB for diagnosis of pancreatic malignancy during the same EUS.

Methods

Patients who underwent both FNA and CNB during the same EUS for pancreatic solid lesion were reviewed retrospectively. Sample adequacy, diagnostic yield (defined as percentage of definitive diagnosis), sensitivity and specificity for malignancy were compared between FNA and CNB.

Results

A total of 48 patients with solid pancreatic lesions were evaluated. The proportions of adequate samples were 48/48 (100%) for FNA and 45/48 (93.7%) for core biopsy (P = .24). The diagnostic yield was 42/48 (87.5%) and 33/48 (68.7%) for FNA and CNB respectively (P = .046). The incremental increase in diagnostic yield by combining both methods was 2/48 (4%). The diagnostic yield for malignancy was 30/32 (93.7%) for FNA and 23/32 (71.8%) for CNB (P = .043). The sensitivity for the diagnosis of malignancy for FNA and CNB were 90.6% and 69%, respectively (P = .045). The specificity was 100% for both methods. The sensitivity for diagnosing malignancy increased to 93.8% when the two methods were combined. The difference in diagnostic yield was not associated with lesion size or location.

Conclusion

EUS‐guided FNA is a superior method of assessing solid pancreatic lesion and pancreatic malignancy with better diagnostic yield and higher sensitivity than EUS‐CNB.
Axon guidance pathways and the control of gene expression
Authors: Russell Samantha A. , Bashaw Greg J.
Published: December 2017

Axons need to be properly guided to their targets to form synaptic connections, and this requires interactions between highly conserved extracellular and transmembrane ligands and their cell surface receptors. The majority of studies on axon guidance signaling pathways have focused on the role of these pathways in rearranging the local cytoskeleton and plasma membrane in growth cones and axons. However, a smaller body of work has demonstrated that axon guidance signaling pathways also control gene expression via local translation and transcription. Recent studies on axon guidance ligands and receptors have begun to uncover the requirements for these alternative mechanisms in processes required for neural circuit formation: axon guidance, synaptogenesis, and cell migration. Understanding the mechanisms by which axon guidance signaling regulates local translation and transcription will create a more complete picture of neural circuit formation, and they may be applied more broadly to other tissues where axon guidance ligands and receptors are required for morphogenesis. Developmental Dynamics 247:571–580, 2018. © 2017 Wiley Periodicals, Inc.
Molecular mechanisms underlying monosynaptic sensory‐motor circuit development in the spinal cord
Authors: Imai Fumiyasu , Yoshida Yutaka
Published: December 2017

Motor behaviors are precisely controlled by the integration of sensory and motor systems in the central nervous system (CNS). Proprioceptive sensory neurons, key components of the sensory system, are located in the dorsal root ganglia and project axons both centrally to the spinal cord and peripherally to muscles and tendons, communicating peripheral information about the body to the CNS. Changes in muscle length detected by muscle spindles, and tension variations in tendons conveyed by Golgi tendon organs, are communicated to the CNS through group Ia /II, and Ib proprioceptive sensory afferents, respectively. Group Ib proprioceptive sensory neurons connect with motor neurons indirectly through spinal interneurons, whereas group Ia/II axons form both direct (monosynaptic) and indirect connections with motor neurons. Although monosynaptic sensory‐motor circuits between spindle proprioceptive sensory neurons and motor neurons have been extensively studied since 1950s, the molecular mechanisms underlying their formation and upkeep have only recently begun to be understood. We will discuss our current understanding of the molecular foundation of monosynaptic circuit development and maintenance involving proprioceptive sensory neurons and motor neurons in the mammalian spinal cord. Developmental Dynamics 247:581–587, 2018. © 2017 Wiley Periodicals, Inc.
Modeling and Analysis of Traffic Flow Considering Automatic Gap Control
Authors: HOSHINO TAKAHIRO , YOSHIDA SATOSHI , HAMAMATSU YOSHIO
Published: December 2017

In recent years, the number of vehicles with automatic gap control (AGC) (e.g., adaptive cruise control) has increased with the development of vehicle control technology. AGC mainly helps to ease driver fatigue on highways. Vehicles equipped with AGC can maintain an appropriate distance between two vehicles. Therefore, the traffic flow can be improved by AGC‐equipped vehicles. In this research, we develop a traffic flow model that considers AGC‐equipped vehicles, and is based on the Nagel–Schreckenberg model, which is a probabilistic cellular automaton model. The Nagel–Schreckenberg model can reproduce the basic features of traffic flow. On analyzing the mathematical model for the traffic including AGC‐equipped vehicles, we can obtain analytical solutions of the traffic flow and the average velocity.
Not all toxic butterflies are toxic: high intra‐ and interspecific variation in sequestration in subtropical swallowtails
Authors: Dimarco Romina D. , Fordyce James A.
Published: December 2017

Many herbivorous insects make use of plant secondary metabolites by consuming and storing these toxic compounds in their body tissue or integument, thereby obtaining chemical defense against their natural enemies. Swallowtail butterflies in the tribe Troidini (Papilionidae) sequester toxic alkaloids (aristolochic acids, AAs) from their host plants in the genusAristolochia. Troidine butterflies have been a model group for development of theory on host plant chemical sequestration, but most studies on this group have been limited to a single species in North America. These studies have led, in part, to the paradigm that troidine butterflies are toxic, thereby explaining the numerous mimicry relationships that exist throughout most of their range. Herein, we present one of the first comparative studies in a single location of a community of troidine butterflies. We examined the AA content of five co‐occurring troidine butterfly species and their twoAristolochiahost plants. We found that oneAristolochiaspecies,A. triangularis, was preferred in choice assays and did not possess quantifiable levels of AA. We also found that most troidine butterflies did not possess quantifiable levels of AAs, but larvae have the ability to sequester AAs when it is present in their diet. A larval preference experiment showed that host plant AA concentration did not influence larval feeding choice. A performance experiment showed that higher levels of AAs in the diet increased larval mortality, which might indicate a cost associated with sequestration of the chemical defense and also might shed some light on why so many troidine butterflies in this community have little or no AAs. We propose that automimicry might be operating in this system and many putative models of this paradigmatic system might not possess plant‐derived defensive chemistry.
Nuclear magnetic resonance‐based metabolomics identifies phenylalanine as a novel predictor of incident heart failure hospitalisation: results from PROSPER and FINRISK 1997
Authors: Delles Christian , Rankin Naomi J. , Boachie Charles , McConnachie Alex , Ford Ian , Kangas Antti , Soininen Pasi , Trompet Stella , Mooijaart Simon P. , Jukema J. Wouter , Zannad Faiez , Ala‐Korpela Mika , Salomaa Veikko , Havulinna Aki S. , Welsh Paul , Würtz Peter , Sattar Naveed
Published: December 2017

Aims

We investigated the association between quantified metabolite, lipid and lipoprotein measures and incident heart failure hospitalisation (HFH) in the elderly, and examined whether circulating metabolic measures improve HFH prediction.

Methods and results

Overall, 80 metabolic measures from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial were measured by proton nuclear magnetic resonance spectroscopy (n = 5341; 182 HFH events during 2.7‐year follow‐up). We repeated the work in FINRISK 1997 (n = 7330; 133 HFH events during 5‐year follow‐up). In PROSPER, the circulating concentrations of 13 metabolic measures were found to be significantly different in those who were later hospitalised for heart failure after correction for multiple comparisons. These included creatinine, phenylalanine, glycoprotein acetyls, 3‐hydroxybutyrate, and various high‐density lipoprotein measures. In Cox models, two metabolites were associated with risk of HFH after adjustment for clinical risk factors and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP): phenylalanine [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.10–1.53; P = 0.002] and acetate (HR 0.81, 95% CI 0.68–0.98; P = 0.026). Both were retained in the final model after backward elimination. Compared to a model with established risk factors and NT‐proBNP, this model did not improve the C‐index but did improve the overall continuous net reclassification index (NRI 0.21; 95% CI 0.06–0.35; P = 0.007) due to improvement in classification of non‐cases (NRI 0.14; 95% CI 0.12–0.17; P < 0.001). Phenylalanine was replicated as a predictor of HFH in FINRISK 1997 (HR 1.23, 95% CI 1.03–1.48; P = 0.023).

Conclusion

Our findings identify phenylalanine as a novel predictor of incident HFH, although prediction gains are low. Further mechanistic studies appear warranted.
Stereoselective Synthesis and Biological Evaluation of ent‐Asperolide C and its Analogues
Authors: Xin Zhengyuan , Song Yunlong Lu, Zhiqiang , He Yuchen , Li Jiabin , Lin Kejiang , Xue Xiaowen
Published: December 2017

A stereoselective synthesis of ent‐asperolide C and its analogues is described. A chiral‐pool approach was used with a linear sequence of 10 steps, starting from readily available and inexpensive andrographolide. The approach features the construction of a five‐membered lactone skeleton with suitable chiral centres from andrographolide through diastereoselective epoxidation of the exocyclic double bond, and tandem oxidative cleavage of the C‐14=C‐15 double bond and subsequent epoxide ring opening. The stereochemistry of 8 was established by X‐ray crystallographic analysis. Four analogues of ent‐asperolide C were synthesized, and their biological activities were evaluated against A539 and HeLa cell lines. Compound 12 was found to show a weak to moderate antiproliferation effect against both cell lines.
Fabrication of Cu−CeO2 Coated Multiwall Carbon Nanotube Composite Electrode for Simultaneous Determination of Guanine and Adenine
Authors: Aktürk Merve , Karabiberoğlu Şükriye Ulubay , Dursun Zekerya
Published: December 2017

A copper nano particles and cerium (IV) oxide modified carbon nanotube based composite on glassy carbon electrode (Cu−CeO2/MWCNT/GCE) was fabricated for simultaneous determination of guanine and adenine. The surface morphology, chemistry and conductance of the prepared electrodes were characterized by scanning electron microscopy (SEM), energy dispersion X‐ray (EDX), X‐Ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). The Cu−CeO2/MWCNT/GCE improved electrochemical behaviour of guanine and adenine compared to other electrodes. The modified electrode was also used for individual and simultaneous determination of guanine and adenine. Under optimized conditions, the calibration curves were obtained linearly in the range of 0.20 to 6.00 μM for the guanine and 0.10 to 8.0 μM for the adenine by differential pulse voltammetry. The limits of detection of guanine and adenine were calculated as 0.128 and 0.062 μM, respectively. Interferences studies were also performed in the presence of inorganic and organic compounds. Moreover, the determination of guanine and adenine contents were carried out in a calf thymus DNA sample by the developed method with satisfactory results.
Enhanced Catalytic Activity of Iron‐Promoted Nickel on γ‐Al2O3 Nanosheets for Carbon Dioxide Methanation
Authors: Mebrahtu Chalachew , Abate Salvatore , Chen Shiming , Sierra Salazar Andrés Felipe , Perathoner Siglinda , Krebs Florian , Palkovits Regina , Centi Gabriele
Published: December 2017

Iron‐promoted nickel on γ‐Al2O3 nanosheets shows enhanced catalytic activity, selectivity, and stability for carbon dioxide methanation, a relevant process for energy storage and transportation (power‐to‐gas) for the future low‐carbon economy. Nanosheet‐type catalysts were synthesized by a two‐step hydrothermal method and characterized by several physicochemical methods. The catalytic activity for CO2 methanation was investigated in the 300–350 °C temperature range at a pressure of 5 bar. A high activity at 300 °C (≈860 molCH4 molNi−1 h−1) and 99 % CH4 selectivity with a stable catalytic performance for more than 50 h were observed for the nanosheets‐based sample promoted with iron. With respect to a commercial methanation catalyst, the Fe‐promoted nanosheets‐based catalyst showed an integral rate of CO2 conversion to methane more than three times higher, with a rate of deactivation 5 times lower at 300 °C. With respect to nanosheets catalysts without the use of Fe as promoter, the rate of CO2 conversion is approximately 5 times higher, and with respect to a catalyst with the same composition, but prepared using a bulk‐type alumina, the activity is approximately 2.5 times higher. There is thus a synergistic role of the unique nanostructure and Fe promotion. The nanosheets structure promotes Ni dispersion, forming small Ni nanoparticles (≈11–13 nm) upon reduction, which are very stable with time on stream and against oxidation. Fe forms an alloy with Ni upon reduction and improves the dispersion and reduction degree. No relation is observed between the quantitative number of basic sites and turnover frequency (TOF) values, but data suggest that the mobility of adsorbed CO2 towards the Ni particles, favored by the weakening of medium‐strong basic sites related to Fe promotion and nanosheets structure, determines the reaction rate and TOF.
Effect of nano silica and fine silica sand on compressive strength of sodium and potassium activators synthesised fly ash geopolymer at elevated temperatures
Authors: Shaikh Faiz , Haque Sharany
Published: December 2017

Environment friendly geopolymer is a new binder which gained increased popularity due to its better mechanical properties, durability, chemical resistance, and fire resistance. This paper presents the effect of nano silica and fine silica sand on residual compressive strength of sodium and potassium based activators synthesised fly ash geopolymer at elevated temperatures. Six different series of both sodium and potassium activators synthesised geopolymer were cast using partial replacement of fly ash with 1%, 2%, and 4% nano silica and 5%, 10%, and 20% fine silica sand. The samples were heated at 200°C, 400°C, 600°C, and 800°C at a heating rate 5°C per minute, and the residual compressive strength, volumetric shrinkage, mass loss, and cracking behaviour of each series of samples are also measured in this paper. Results show that, among 3 different NS contents, the 2% nano silica by wt. exhibited the highest residual compressive strength at all temperatures in both sodium and potassium‐based activators synthetised geopolymer. The measured mass loss and volumetric shrinkage are also lowest in both geopolymers containing 2% nano silica among all nano silica contents. Results also show that although the unexposed compressive strength of potassium‐based geopolymer containing nano silica is lower than its sodium‐based counterpart, the rate of increase of residual compressive strength exposed to elevated temperatures up to 400°C of potassium‐based geopolymer containing nano silica is much higher. It is also observed that the measured residual compressive strengths of potassium based geopolymer containing nano silica exposed at all temperatures up to 800°C are higher than unexposed compressive strength, which was not the case in its sodium‐based counterpart. However, in the case of geopolymer containing fine silica sand, an opposite phenomenon is observed, and 10% fine silica sand is found to be the optimum content with some deviations. Quantitative X‐ray diffraction analysis also shows higher amorphous content in both geopolymers containing nano silica at elevated temperatures than those containing fine silica sand.
A method to assess downward flame spread and dripping characteristics of fire‐retardant polymer composites
Authors: Wen Chuchu , Zhang Jiyue , Levendis Yiannis A. , Delichatsios Michael A.
Published: December 2017

A method is described to assess the flame retardancy of polyethylene composites by measuring both their downward flame spread rates as well as their combined melting and dripping rates on rectangular rods, ignited at their top. The composite materials were produced by mixing pulverized polymer with organic additives of differing particle sizes, shapes, and mass fractions. The resulting mix was melted in a mold, and then it was solidified into rods. The additives were carbonaceous solids with particle sizes spanning from tens of nanometers to tens of micrometers. The mass fraction of the additives in the polymer matrix varied from 1 to 5 wt%. Upon ignition of the upper tips of the polymer composite rods, the downward flame spread rate and the melting and dripping rate were separately assessed by measuring their mass loss and their heights. The addition to polyethylene of finely sized carbonaceous additives at mass fractions of 4 to 5 wt% proved effective at significantly slowing down its downward flame spread by drastically hindering its dripping tendency. The effectiveness of the additives increased with increasing their mass fraction and decreasing their particle size. High mass fractions of carbon additives resulted in wicking, which can enhance radiatively the heat transfer.
SOFC Operation with Real Biogas
Authors: Hagen A. , Winiwarter A. , Langnickel H. , Johnson G.
Published: December 2017

Biogas is a valuable energy source and will be available in future in systems relying on renewables. It is an attractive fuel for solid oxide fuel cells (SOFC), which are able to utilize the carbon contained in the biogas and which produce electricity with high efficiency. In the current paper, state‐of‐the‐art SOFCs were studied regarding performance and durability in relation to biogas as fuel and considering important contaminants, specifically sulfur. First, the catalytic behavior in relevant synthetic biogas mixtures was studied and the potential of dry reforming was demonstrated. Successful long term operation of an SOFC under both, conditions of steam and dry reforming, i.e., addition of steam or CO2 to avoid carbon formation was shown. For the steam reforming case a remarkable period of 3,500 h, hereof 3,000 h in the presence of H2S was achieved. Finally, a real biogas from a landfill gas unit was used as fuel. The concept of dry reforming was realized. The SOFC was successfully operated with and in one case even without a specific gas cleaning unit.
Synoptic monthly gridded global and regional four‐dimensional World Ocean Database and Global Temperature and Salinity Profile Programme (T, S, u, v) fields with the optimal spectral decomposition and P‐vector methods
Authors: Chu Peter C. , Fan Chenwu
Published: December 2017

Synoptic monthly gridded (SMG) world ocean temperature (T) and salinity (S) fields with (1° × 1°) horizontal resolution and 28 standard vertical levels from the ocean surface to 3000 m deep have been established from the observational (T, S) profiles from the NOAA National Centers for Environmental Information (NCEI) World Ocean Database (WOD) from January 1945 to December 2014 and the Global Temperature and Salinity Profile Programme (GTSPP) from January 1990 to December 2009 using the optimal spectral decomposition (OSD) method. The world ocean abstract geostrophic currents (u, v) are calculated from the 4D SMG‐WOD and SMG‐GTSPP (T, S) data using the P‐vector inverse method. The SMG‐WOD (T, S, u, v) and SMG‐GTSPP (T, S, u, v) fields with a higher horizontal resolution (0.25° × 0.25°) have also been produced for the Mediterranean Sea, the Japan/East Sea, and the Gulf of Mexico.