bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparative deracemization of unnatural amino acids
Authors: Fotheringham I. , Archer I. , Carr R. , Speight R. , Turner N.J.
Published: August 2015

Unnatural amino acids are a growing class of intermediates required for pharmaceuticals, agrochemicals and other industrial products. However, no single method has proven sufficiently versatile to prepare these compounds broadly at scale. To address this need, we have developed a general chemoenzymatic process to prepare enantiomerically pure L- and D-amino acids in high yield by deracemization of racemic starting materials. This method involves the concerted action of an enantioselective oxidase biocatalyst and a non-selective chemical reducing agent to effect the stereoinversion of one enantiomer and can result in an enantiomeric excess of >99% from the starting racemate, and product yields of over 90%. This approach compares very favourably with resolution processes, which have a maximum single-pass yield of 50%. We have developed efficient methods to adapt the process towards new target compounds and to optimize key factors that influence process efficiency and offer competitive economics at scale.
S-Adenosylmethionine: jack of all trades and master of everything?
Authors: Loenen W.A.M.
Published: August 2015

SAM (S-adenosylmethionine, also known as AdoMet) is well known as the methyl donor for the majority of methyltransferases that modify DNA, RNA, histones and other proteins, dictating replicational, transcriptional and translational fidelity, mismatch repair, chromatin modelling, epigenetic modifications and imprinting, which are all topics of great interest and importance in cancer research and aging. In total, 15 superfamilies of SAM-binding proteins have been identified, with many additional functions varying from methylation of phospholipids and small molecules such as arsenic to synthesis of polyamines or radical formation. SAM is regenerated from demethylated SAM via the methionine cycle, which involves folate. Imbalance of this cycle in humans, e.g. through folate shortage via dietary insufficiency, alcohol abuse, arsenic poisoning or hereditary factors, leads to depletion of SAM and human disease. In addition to its role as a methyl donor to modification enzymes that protect bacterial DNA against cognate restriction, SAM also serves as a co-factor for nucleases such as the type I restriction enzyme EcoKI, which is unable to restrict DNA in the absence of SAM. Finally, on a completely different tack, SAM can bind to certain RNA structures called riboswitches that control transcription or translation. In this way, expression of multiple genes can be regulated in a SAM-dependent manner, an unexpected finding that opens up new avenues into gene control. This minireview discusses some of these diverse and amazing roles of this small metabolite.
Requirements for a successful defence reaction by the CRISPR–Cas subtype I-B system
Authors: Stoll Britta , Maier Lisa-Katharina , Lange Sita J. , Brendel Jutta , Fischer Susan , Backofen Rolf , Marchfelder Anita
Published: August 2015

Uptake of foreign mobile genetic elements is often detrimental and can result in cell death. For protection against invasion, prokaryotes have developed several defence mechanisms, which take effect at all stages of infection; an example is the recently discovered CRISPR (clustered regularly interspaced short palindromic repeats)–Cas (CRISPR-associated) immune system. This defence system directly degrades invading genetic material and is present in almost all archaea and many bacteria. Current data indicate a large variety of mechanistic molecular approaches. Although almost all archaea carry this defence weapon, only a few archaeal systems have been fully characterized. In the present paper, we summarize the prerequisites for the detection and degradation of invaders in the halophilic archaeon Haloferax volcanii. H. volcanii encodes a subtype I-B CRISPR–Cas system and the defence can be triggered by a plasmid-based invader. Six different target-interference motifs are recognized by the Haloferax defence and a 9-nt non-contiguous seed sequence is essential. The repeat sequence has the potential to fold into a minimal stem–loop structure, which is conserved in haloarchaea and might be recognized by the Cas6 endoribonuclease during the processing of CRISPR loci into mature crRNA (CRISPR RNA). Individual crRNA species were present in very different concentrations according to an RNA-Seq analysis and many were unable to trigger a successful defence reaction. Recognition of the plasmid invader does not depend on its copy number, but instead results indicate a dependency on the type of origin present on the plasmid.
Endocannabinoid signalling in Alzheimer's disease
Authors: Maroof Nazia , Pardon Marie Christine , Kendall David A.
Published: August 2015

The ECs (endocannabinoids) AEA (anandamide) and 2-AG (2-arachidonoylglycerol) and their lipid congeners OEA (N-oleoylethanolamide) and PEA (N-palmitoylethanolamide) are multifunctional lipophilic signalling molecules. The ECs, OEA and PEA have multiple physiological roles including involvement in learning and memory, neuroinflammation, oxidative stress, neuroprotection and neurogenesis. They have also been implicated in the pathology of, or perhaps protective responses to, neurodegenerative diseases. This is particularly the case with Alzheimer's disease, the most common age-related dementia associated with impairments in learning and memory accompanied by neuroinflammation, oxidative stress and neurodegeneration. The present mini-review examines the evidence supporting the roles that ECs appear to play in Alzheimer's disease and the potential for beneficial therapeutic manipulation of the EC signalling system.
The CINs of the centromere
Authors: Forsburg Susan L.
Published: August 2015

Replication stress is a significant contributor to genome instability. Recent studies suggest that the centromere is particularly susceptible to replication stress and prone to rearrangements and genome damage, as well as chromosome loss. This effect is enhanced by loss of heterochromatin. The resulting changes in genetic organization, including chromosome loss, increased mutation and loss of heterozygosity, are important contributors to malignant growth.
The subtype I-F CRISPR–Cas system influences pathogenicity island retention in Pectobacterium atrosepticum via crRNA generation and Csy complex formation
Authors: Richter Corinna , Fineran Peter C.
Published: August 2015

CRISPR (clustered regularly interspaced short palindromic repeats) arrays and Cas (CRISPR-associated) proteins confer acquired resistance against mobile genetic elements in a wide range of bacteria and archaea. The phytopathogen Pectobacterium atrosepticum SCRI1043 encodes a single subtype I-F CRISPR system, which is composed of three CRISPR arrays and the cas operon encoding Cas1, Cas3 (a Cas2–Cas3 fusion), Csy1, Csy2, Csy3 and Cas6f (Csy4). The CRISPR arrays are transcribed into pre-crRNA (CRISPR RNA) and then processed by Cas6f to generate crRNAs. Furthermore, the formation of Cas protein complexes has been implicated in both the interference and acquisition stages of defence. In the present paper, we discuss the development of tightly controlled ‘programmable’ CRISPR arrays as tools to investigate CRISPR–Cas function and the effects of chromosomal targeting. Finally, we address how chromosomal targeting by CRISPR–Cas can cause large-scale genome deletions, which can ultimately influence bacterial evolution and pathogenicity.
Interplay between mitotic kinesins and the Aurora kinase–PP1 (protein phosphatase 1) axis
Authors: Meadows John C.
Published: August 2015

Correct transmission of genetic information from mother to daughter cells is necessary for development and survival. Accurate segregation is achieved by bipolar attachment of sister kinetochores in each chromatid pair to spindle microtubules emanating from opposite spindle poles, a process known as chromosome bi-orientation. Achieving this requires dynamic interplay between kinetochore proteins, kinesin motor proteins and cell cycle regulators. Chromosome bi-orientation is monitored by a surveillance mechanism known as the SAC (spindle assembly checkpoint). The Aurora B kinase, which is bound to the inner centromere during early mitosis, plays a central role in both chromosome bi-orientation and the spindle checkpoint. The application of tension across centromeres establishes a spatial gradient of high phosphorylation activity at the inner centromere and low phosphorylation activity at the outer kinetochore. This gradient is further refined by the association of PP1 (protein phosphatase 1) to the outer kinetochore, which stabilizes kinetochore–microtubule interactions and silences the spindle checkpoint by dephosphorylating Aurora B kinase targets when chromosome bi-orientation is achieved. In the present review, I discuss emerging evidence that bidirectional cross-talk between mitotic kinesins and the Aurora kinase–PP1 axis is crucial for co-ordinating chromosome bi-orientation and spindle checkpoint signalling in eukaryotes.
Systematic genetic analysis of transcription factors to map the fission yeast transcription-regulatory network
Authors: Chua Gordon
Published: August 2015

Mapping transcriptional-regulatory networks requires the identification of target genes, binding specificities and signalling pathways of transcription factors. However, the characterization of each transcription factor sufficiently for deciphering such networks remains laborious. The recent availability of overexpression and deletion strains for almost all of the transcription factor genes in the fission yeast Schizosaccharomyces pombe provides a valuable resource to better investigate transcription factors using systematic genetics. In the present paper, I review and discuss the utility of these strain collections combined with transcriptome profiling and genome-wide chromatin immunoprecipitation to identify the target genes of transcription factors.
Membrane bound O-acyltransferases and their inhibitors
Authors: Masumoto Naoko , Lanyon-Hogg Thomas , Rodgers Ursula R. , Konitsiotis Antonios D. , Magee Anthony I , Tate Edward W.
Published: August 2015

Since the identification of the membrane-bound O-acyltransferase (MBOATs) protein family in the early 2000s, three distinct members [porcupine (PORCN), hedgehog (Hh) acyltransferase (HHAT) and ghrelin O-acyltransferase (GOAT)] have been shown to acylate specific proteins or peptides. In this review, topology determination, development of assays to measure enzymatic activities and discovery of small molecule inhibitors are compared and discussed for each of these enzymes.
Molecular mechanisms of Nrf2 regulation and how these influence chemical modulation for disease intervention
Authors: Harder Bryan , Jiang Tao , Wu Tongde , Tao Shasha , de la Vega Montserrat Rojo , Tian Wang , Chapman Eli , Zhang Donna D.
Published: August 2015

Nrf2 (nuclear factor erytheroid-derived-2-like 2) transcriptional programmes are activated by a variety of cellular stress conditions to maintain cellular homoeostasis. Under non-stress conditions, Nrf2 is under tight regulation by the ubiquitin proteasome system (UPS). Detailed mechanistic investigations have shown the Kelch-like ECH-associated protein 1 (Keap1)–cullin3 (Cul3)–ring-box1 (Rbx1) E3-ligase to be the primary Nrf2 regulatory system. Recently, both beta-transducin repeat-containing E3 ubiquitin protein ligase (β-TrCP) and E3 ubiquitin-protein ligase synoviolin (Hrd1) have been identified as novel E3 ubiquitin ligases that negatively regulate Nrf2 through Keap1-independent mechanisms. In addition to UPS-mediated regulation of Nrf2, investigations have revealed a cross-talk between Nrf2 and the autophagic pathway resulting in activation of Nrf2 in a non-canonical manner. In addition to regulation at the protein level, Nrf2 was recently shown to be regulated at the transcriptional level by oncogenic K-rat sarcoma (Ras). A consequence of these differential regulatory mechanisms is the dual role of Nrf2 in cancer: the canonical, protective role and the non-canonical ‘dark-side’ of Nrf2. Based on the protective role of Nrf2, a vast effort has been dedicated towards identifying novel chemical inducers of Nrf2 for the purpose of chemoprevention. On the other hand, upon malignant transformation, some cancer cells have a constitutively high level of Nrf2 offering a growth advantage, as well as rendering cancer cells resistant to chemotherapeutics. This discovery has led to a new paradigm in cancer treatment; the initially counterintuitive use of Nrf2 inhibitors as adjuvants in chemotherapy. Herein, we will discuss the mechanisms of Nrf2 regulation and how this detailed molecular understanding can be leveraged to develop Nrf2 modulators to prevent diseases, mitigate disease progression or overcome chemoresistance.
Targeting the 18-kDa translocator protein: recent perspectives for neuroprotection
Authors: Da Pozzo Eleonora , Giacomelli Chiara , Barresi Elisabetta , Costa Barbara , Taliani Sabrina , Passetti Federico Da Settimo , Martini Claudia
Published: August 2015

The translocator protein (TSPO, 18 kDa), mainly localized in the outer mitochondrial membrane of steroidogenic tissues, is involved in several cellular functions. TSPO level alterations have been reported in a number of human disorders, particularly in cancer, psychiatric and neurological diseases. In the central nervous system (CNS), TSPO is usually expressed in glial cells, but also in some neuronal cell types. Interestingly, the expression of TSPO on glial cells rises after brain injury and increased TSPO expression is often observed in neurological disorders, gliomas, encephalitis and traumatic injury. Since TSPO is up-regulated in brain diseases, several structurally different classes of ligands targeting TSPO have been described as potential diagnostic or therapeutic agents. Recent researches have reported that TSPO ligands might be valuable in the treatment of brain diseases. This review focuses on currently available TSPO ligands, as useful tools for the treatment of neurodegeneration, neuro-inflammation and neurotrauma.
Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress
Authors: Mutter Fiona E. , Park B. Kevin , Copple Ian M.
Published: August 2015

Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre-clinical identification of chemicals and drugs with toxic liability in humans.
Dysregulation of the Keap1–Nrf2 pathway in cancer
Authors: Leinonen Hanna M. , Kansanen Emilia , Pölönen Petri , Heinäniemi Merja , Levonen Anna-Liisa
Published: August 2015

Accumulating evidence suggests that dysregulation of the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor E2-related factor 2 (Nrf2) pathway resulting in constitutively active Nrf2 and increased expression of cytoprotective Nrf2 target genes, has a pivotal role in cancer. Cancer cells are able to hijack the Keap1–Nrf2 system via multiple mechanisms leading to enhanced chemo- and radio-resistance and proliferation via metabolic reprogramming as well as inhibition of apoptosis. In this mini-review, we will describe the mechanisms leading to increased Nrf2 activity in cancer with a focus on the information achieved from large-scale multi-omics projects across various cancer types.
Nrf2 as a master regulator of tissue damage control and disease tolerance to infection
Authors: Soares Miguel P. , Ribeiro Ana M.
Published: August 2015

Damage control refers to those actions made towards minimizing damage or loss. Depending on the context, these can range from emergency procedures dealing with the sinking of a ship or to a surgery dealing with severe trauma or even to an imaginary company in Marvel comics, which repairs damaged property arising from conflicts between super heroes and villains. In the context of host microbe interactions, tissue damage control refers to an adaptive response that limits the extent of tissue damage associated with infection. Tissue damage control can limit the severity of infectious diseases without interfering with pathogen burden, conferring disease tolerance to infection. This contrasts with immune-driven resistance mechanisms, which although essential to protect the host from infection, can impose tissue damage to host parenchyma tissues. This damaging effect is countered by stress responses that confer tissue damage control and disease tolerance to infection. Here we discuss how the stress response regulated by the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) acts in such a manner.
The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic
Authors: O’Connell Maria A. , Hayes John D.
Published: August 2015

The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, with gene called NFE2L2) is a master regulator of the antioxidant response. In the last decade, interest has intensified in this research area as its importance in several physiological and pathological processes has become widely recognized; these include redox signalling and redox homoeostasis, drug metabolism and disposition, intermediary metabolism, cellular adaptation to stress, chemoprevention and chemoresistance, toxicity, inflammation, neurodegeneration, lipogenesis and aging. Regulation of Nrf2 is complex and although much attention has focussed on its repression by Kelch-like ECH-associated protein-1 (Keap1), recently it has become increasingly apparent that it is also controlled by cross-talk with other signalling pathways including the glycogen synthase kinase-3 (GSK-3)−β-transducin repeat-containing protein (β-TrCP) axis, ERAD (endoplasmic reticulum-associated degradation)-associated E3 ubiquitin-protein ligase (Hrd1, also called synoviolin), nuclear factor-kappa B (NF-κB), Notch and AMP kinase. Due to its beneficial role in several diseases, Nrf2 has become a major therapeutic target, with novel natural, synthetic and targeted small molecules currently under investigation to modulate the pathway and in clinical trials.
Manipulating membrane lipid profiles to restore T-cell function in autoimmunity
Authors: Waddington Kirsty E. , Jury Elizabeth C.
Published: August 2015

Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T-cells from patients with the autoimmune disease systemic lupus erythematosus (SLE).
Developing Brain Injury Interventions on Both Ends of the Treatment Continuum Depends Upon Early Research Partnerships and Feasibility Studies
Authors: Sohlberg McKay Moore , Kucheria Priya , Fickas Stephen , Wade Shari L.
Published: August 2015

Purpose

The purpose of this research article is to describe two very different lines of brain injury treatment research, both of which illuminate the benefits of implementation science.

Method

The article first describes the development and pilot of a computerized cognitive intervention and highlights how adherence to implementation science principles improved the design of the intervention. Second, the article describes the application of implementation science to the development of assistive technology for cognition.

Results

The Consolidated Framework for Implementation Research (CFIR; Damschroder et al., 2009) and the menu of implementation research strategies by Powell et al. (2012) provide a roadmap for cognitive rehabilitation researchers to attend to factors in the implementation climate that can improve the development, usability, and adoptability of new treatment methods.

Conclusion

Attention to implementation science research principles has increased the feasibility and efficacy of both impairment-based cognitive rehabilitation programs and assistive technology for cognition.
Performance optimisation for bit‐interleaved coded modulation with iterative demapping with max‐log‐ maximum a posterior detection
Authors: Qian Chen , Xie Qiuliang , Zhao Peiyao , Wang Zhaocheng
Published: August 2015

Max‐log‐maximum a posterior (MAP) detection is preferred in practical systems rather than log‐MAP because of its lower complexity, but also suffers from a considerable performance loss. In this study, the authors focus on the performance optimisation for (doped) bit‐interleaved coded modulation with iterative demapping schemes where max‐log‐MAP detection is employed. First, they study the effects of max‐log‐MAP detection to the extrinsic information transfer curves of the (doped) demapper and decoder, and reselect the constellation labelling. Second, they find that the small difference between max‐log‐MAP and log‐MAP detection in each iteration would be accumulated during the whole iterative procedure referred to as error accumulation, which causes a large performance loss, and consequently they propose some methods to control the error accumulation. Owing to the labelling reselection and error‐accumulation control, the proposed scheme exhibits several tenths to 1 dB gains, compared with the conventional schemes, while maintaining low complexity.
Error mitigation using RaptorQ codes in an experimental indoor free space optical link under the influence of turbulence
Authors: Pernice Riccardo , Parisi Antonino , Andò Andrea , Mangione Stefano , Garbo Giovanni , Busacca Alessandro C. , Perez Joaquin , Ghassemlooy Zabih
Published: August 2015

In free space optical (FSO) communications, several factors can strongly affect the link quality. Among them, one of the most important impairments that can degrade the FSO link quality and its reliability – even under the clear sky conditions – consists of optical turbulence. In this work, the authors investigate the generation of both weak and moderate turbulence regimes in an indoor environment to assess the FSO link quality. In particular, they show that, due to the presence of the turbulence, the link experiences both erasure errors and packet losses during transmission, and also compare the experimental statistical distribution of samples with the predicted Gamma–Gamma model. Furthermore, the authors demonstrate that the application of the RaptorQ codes noticeably improves the link quality decreasing the packet error rate (PER) by about an order of magnitude, also offering – in certain cases – an error‐free transmission with a PER of ∼10−2 at Rytov variance value of 0.5. The results show that the recovery rate increases with the redundancy, the packet length and the number of source packets, and it decreases with increasing data rates.
Improved approach to delay‐dependent stability and stabilisation of two‐dimensional discrete‐time systems with interval time‐varying delays
Authors: Peng Dan , Hua Changchun
Published: August 2015

Two recent Lyapunov‐based methods: free weighting matrix approach and Jensen inequality approach, have reduced the conservatism and the complexity of the stability result for one‐dimensional (1D) time‐delay systems, respectively. In this study, the authors further concern the analysis of delay‐dependent stability and stabilisation for two‐dimensional (2D) discrete systems with interval time‐varying delays. By applying a new Lyapunov functional combining with the approaches of 2D Jensen inequalities and free weighting matrices, a new delay‐dependent stability criterion is derived in terms of linear matrix inequalities (LMIs). Compared with the existing result, less decision variables are involved in the stability condition, so the burden of numerical computation is reduced greatly. It is also rigorously proved that the author's result is less conservative than some recent ones. On the basis of the stability criterion, state feedback is considered to realise the stability control and the state feedback gain can be solved by LMIs. Numerical examples show the effectiveness and advantage of their results.
Direction‐cosine‐matrix‐based attitude control subject to actuator saturation
Authors: Forbes James Richard
Published: August 2015

Set‐point attitude control of a rigid body explicitly preventing actuator saturation is considered. The attitude control approach developed does not employ any sort of direction‐cosine‐matrix (DCM) parameterisation, such as Euler angles or quaternions. Rather, the DCM is used directly within the feedback control algorithm. Together a proportional control term and an angular velocity control term make up the attitude controller. The angular velocity control is composed of a strictly positive real system subject to a special input non‐linearity. The specific form of the proportional control and angular velocity control ensure control torques are below the saturation level of the on‐board actuators. Two controller synthesis methods are considered. The first uses the linearised system, the solution to the linear quadratic regulator problem, and the Kalman–Yakubovich–Popov lemma to design the controller. The second employs a simple low‐pass filter that is guaranteed to stabilise the closed‐loop system; tuning the low‐pass filter is also considered. Numerical simulation results demonstrate effective closed‐loop control in the presence of plant disturbances and sensor noise.
Induction machines sensors‐less wind generator with integrated intelligent maximum power point tracking and electric losses minimisation technique
Authors: Pucci Marcello
Published: August 2015

This study presents a high‐performance wind generation system with induction machine (IM), specifically devised with the target of maximising the efficiency of the electromechanical conversion, and contemporary minimising the number of the system sensors and their cost. To this aim, the control system has been integrated, from one side, with an intelligent maximum power point tracking (MPPT) technique, so to make the generator track the power available in the wind, from the other side with techniques for the minimisation of the electrical losses (ELMT). Particularly, the power converters’ switching losses have been reduced adopting a discontinuous pulsewidth modulation, while the IM overall losses have been reduced by a suitable electric losses minimisation technique. Contemporary, to reduce costs and increase the reliability of the system, the system has been devised as a fully sensors‐less generation unit, meaning that both the wind speed and the machine speed sensors are not present. The anemometer has been substituted by the wind speed estimator integrated in the MPPT, based on the growing neural gas (GNG) network. The encoder has been substituted with an intelligent IM speed estimator, the so called MCA EXIN + reduced order observer (ROO). The performance of the adopted technique has been verified experimentally on a suitably devised test set‐up.
Using weakly conditionally stable‐body of revolution‐finite‐difference time‐domain method to simulate dielectric film‐coated circular waveguide
Authors: Chen Juan , Wang Jianguo , Tian Chunming
Published: August 2015

In this study, a weakly conditionally stable‐body of revolution‐finite‐difference time‐domain (BOR‐FDTD) method is presented to simulate a dielectric film‐coated circular waveguide. The time‐step size for this method only depends on the spatial cell size Δz. The formulas of the method are presented and its time stable condition is demonstrated. Numerical results show that when this method is applied to simulate the dielectric film‐coated circular waveguide, it is more efficient than the conventional BOR‐FDTD method in terms of computation time.
Class of miniaturised/arbitrary power division ratio couplers with improved design flexibility
Authors: Honari Mohammad Mahdi , Mirzavand Rashid , Mousavi Pedram , Abdipour Abdolali
Published: August 2015

This study describes a new class of couplers using single‐layer microstrip lines that reduce the occupied area, suppress the harmonic components and provide arbitrary power division ratios. It consists of lumped reactances between transmission lines to reach realisable impedances and shorten line lengths. To provide a design guideline, closed‐form formulas are derived and five different designs are produced and built to investigate the couplers performance and design accuracy. The simulation results prove to be in good agreement with measurements. More than 70% size reduction with respect to the conventional structures, 12 dB harmonic suppression and high power division ratios (9:1) achieved in various presented branch line, rat race and multi‐section Wilkinson dividers. This proposed class of coupler structures can effectively be used in miniaturised and/or arbitrary power division ratio couplers with harmonic suppression.
Distributed FlowVisor: a distributed FlowVisor platform for quality of service aware cloud network virtualisation
Authors: Liao Lingxia , Shami Abdallah , Leung Victor C.M.
Published: August 2015

Cloud‐based virtual networking environments are required to provide fine‐grained quality of service (QoS) control without sacrificing scalability. However, no single approach can currently achieve these two goals simultaneously. FlowVisor is a building block to virtualise networks with fine‐grained QoS support; however, scalability issues caused by the OpenFlow protocol and the centralised control model are a major concern. This study introduces a distributed FlowVisor (DFVisor) platform to address these scalability issues. The proposed DFVisor uses a layered overlay mechanism to improve network addressing space and switch capacity. DFVisor uses a distributed synchronised two‐level database system with a synchronisation mechanism to enable the centralised control functions in the current FlowVisor platform in distributed control modules within the virtual network controllers. Therefore it removes a single point of failure in the network and reduces the flow setup latency without sacrificing the centralised network configuration and management capabilities. More importantly, the proposed DFVisor platform enables an advanced push‐based flow setup and statistics collection mechanism to address scalability issues caused by the current pull‐based flow setup and statistics collection method. A DFVisor prototype and an evaluation of this distributed synchronised two‐level database are presented, and key issues for future research are discussed.
High resolution three-dimensional photoacoustic imaging of human finger joints in vivo
Authors: Xi Lei , Jiang Huabei
Published: August 2015

We present a method for noninvasively imaging the hand joints using a three-dimensional (3D) photoacoustic imaging (PAI) system. This 3D PAI system utilizes cylindrical scanning in data collection and virtual-detector concept in image reconstruction. The maximum lateral and axial resolutions of the PAI system are 70 μm and 240 μm. The cross-sectional photoacoustic images of a healthy joint clearly exhibited major internal structures including phalanx and tendons, which are not available from the current photoacoustic imaging methods. The in vivo PAI results obtained are comparable with the corresponding 3.0 T MRI images of the finger joint. This study suggests that the proposed method has the potential to be used in early detection of joint diseases such as osteoarthritis.
A first-principles study of cementite (Fe3C) and its alloyed counterparts: Elastic constants, elastic anisotropies, and isotropic elastic moduli
Authors: Ghosh G.
Published: August 2015

A comprehensive computational study of elastic properties of cementite (Fe3C) and its alloyed counterparts (M3C (M = Al, Co, Cr, Cu, Fe, Hf, Mn, Mo, Nb, Ni, Si, Ta, Ti, V, W, Zr, Cr2FeC and CrFe2C) having the crystal structure of Fe3C is carried out employing electronic density-functional theory (DFT), all-electron PAW pseudopotentials and the generalized gradient approximation for the exchange-correlation energy (GGA). Specifically, as a part of our systematic study of cohesive properties of solids and in the spirit of materials genome, following properties are calculated: (i) single-crystal elastic constants, Cij, of above M3Cs; (ii) anisotropies of bulk, Young’s and shear moduli, and Poisson’s ratio based on calculated Cijs, demonstrating their extreme anisotropies; (iii) isotropic (polycrystalline) elastic moduli (bulk, shear, Young’s moduli and Poisson’s ratio) of M3Cs by homogenization of calculated Cijs; and (iv) acoustic Debye temperature, θD, of M3Cs based on calculated Cijs. We provide a critical appraisal of available data of polycrystalline elastic properties of alloyed cementite. Calculated single crystal properties may be incorporated in anisotropic constitutive models to develop and test microstructure-processing-property-performance links in multi-phase materials where cementite is a constituent phase.
Accelerating low-carbon development in Portland, Oregon and Kunming, Yunnan
Authors: Armstrong A. Michael , Wang B. Xuehai , Tang C. Chong
Published: August 2015

As urbanization continues across the globe, cities face significant challenges and opportunities to grow in ways that reduce carbon emissions while providing high quality of life. An EcoPartnership between the cities of Portland, Oregon, USA and Kunming, China is designed to accelerate the exchange of policies and strategies for low-carbon development. Kunming successfully implemented China's first bus-rapid transit system (BRT); Portland is currently analyzing the feasibility of BRT. Portland relies on an urban growth boundary (UGB) as a key policy to guide growth management; Kunming is evaluating the feasibility of a UGB. Both cities are investing in infrastructure for bicycle networks. Key characteristics of successful collaboration include shared substantive priorities; familiarity with the institutional context and roles of the individuals involved; a good match in the responsibilities of the participating agencies and individuals; interpersonal rapport and trust; and the persistence of the collaboration over time.
Numerical simulation of MHD pulsatile flow of a biofluid in a channel
Authors: Ali Kashif , Ahmad Shahzad , Ashraf Muhammad
Published: August 2015

The purpose of this paper is to numerically study the interaction of an external magnetic field with the flow of a biofluid through a Darcy-Forchhmeir porous channel, due to an oscillatory pressure gradient, in the presence of wall transpiration as well as chemical reaction considerations. We have noticed that if the Reynolds number of the wall transpiration flow is increased, the average (or maximum) velocity of the main flow direction is raised. Similar effect has also been observed for the rheological parameter and the Darcy parameter, whereas an opposite trend has been noted for both the Forchheimer quadratic drag parameter and the magnetic parameter. Further, an increase in the Reynolds number results in straightening the concentration profile, thus making it an almost linear function of the dimensionless spatial variable.
Observations on Si-based micro-clusters embedded in TaN thin film deposited by co-sputtering with oxygen contamination
Authors: Lee Young Mi , Jung Min-Sang , Choi Duck-Kyun , Jung Min-Cherl
Published: August 2015

Using scanning electron microscopy (SEM) and high-resolution x-ray photoelectron spectroscopy with the synchrotron radiation we investigated Si-based micro-clusters embedded in TaSiN thin films having oxygen contamination. TaSiN thin films were deposited by co-sputtering on fixed or rotated substrates and with various power conditions of TaN and Si targets. Three types of embedded micro-clusters with the chemical states of pure Si, SiOx-capped Si, and SiO2-capped Si were observed and analyzed using SEM and Si 2p and Ta 4f core-level spectra were derived. Their different resistivities are presumably due to the different chemical states and densities of Si-based micro-clusters.
Predicting genome variations between passages of Clostridium difficle by ribotypes
Authors: Gürtler Volker
Published: August 2015

Ribotyping is the most widely used method for differentiating strains of Clostridium difficile for epidemiological studies and infection control. Recently there have been calls for standardisation of the technique to which sophisticated technical solutions have been offered. This note offers a solution for standardisation based on conserved rrn operon Type-specific flanking genes. Furthermore, this technique can be used to detect Type-specific rrn operon deletions in passages from a single strain of C. difficile
The opportunistic marine pathogen
Vibrio parahaemolyticus
becomes virulent by acquiring a plasmid that expresses a deadly toxin
Authors: Lee Chung-Te , Chen I-Tung , Yang Yi-Ting , Ko Tzu-Ping , Huang Yun-Tzu , Huang Jiun-Yan , Huang Ming-Fen , Lin Shin-Jen , Chen Chien-Yu , Lin Shih-Shun , Lightner Donald V. , Wang Han-Ching , Wang Andrew H.-J. , Wang Hao-Ching , Hor Lien-I , Lo Chu-Fang
Published: August 2015

Significance

Since 2009, an emergent shrimp disease, acute hepatopancreatic necrosis disease (AHPND), has been causing global losses to the shrimp farming industry. The causative agent of AHPND is a specific strain of
Vibrio parahaemolyticus
. We present evidence here that the opportunistic
V. parahaemolyticus
becomes highly virulent by acquiring a unique AHPND-associated plasmid. This virulence plasmid, which encodes a binary toxin [
V. parahaemolyticus Photorhabdus
insect-related toxins (PirA

vp

and PirB

vp

)] that induces cell death, is stably inherited via a postsegregational killing system and disseminated by conjugative transfer. The cytotoxicity of the PirA

vp

/PirB

vp

system is analogous to the structurally similar insecticidal pore-forming Cry toxin. These findings will significantly increase our understanding of this emerging disease, which is essential for developing anti-AHPND measures.
Risk and Outcomes of Substance Use Disorder among Anesthesiology Residents
Authors: Warner David O. , Berge Keith , Sun Huaping , Harman Ann , Hanson Andrew , Schroeder Darrell R.
Published: August 2015

AbstractAbstract

In a nested, matched case-cohort design of 384 anesthesia residents who developed substance use disorder (SUD) and 768 controls who did not, receiving medical education in the United States, but not anesthesia knowledge early in residency, was associated with risk of developing SUD. By the end of follow-up, 54 anesthesiology residents (14.1%) with SUD and 10 controls (1.3%) were dead. Those with SUD were 15-, 10-, and 7-fold more likely to not complete residency, to not become board certified, or have adverse medical licensure actions, respectively.

Background:

The goal of this work is to evaluate selected risk factors and outcomes for substance use disorder (SUD) in physicians enrolled in anesthesiology residencies approved by the Accreditation Council for Graduate Medical Education.

Methods:

For each of 384 individuals with evidence of SUD while in primary residency training in anesthesiology from 1975 to 2009, two controls (n = 768) who did not develop SUD were identified and matched for sex, age, primary residency program, and program start date. Risk factors evaluated included location of medical school training (United States vs. other) and anesthesia knowledge as assessed by In-Training Examination performance. Outcomes (assessed to December 31, 2013, with a median follow-up time of 12.2 and 15.1 yr for cases and controls, respectively) included mortality and profession-related outcomes.

Results:

Receiving medical education within the United States, but not performance on the first in-training examination, was associated with an increased risk of developing SUD as a resident. Cases demonstrated a marked increase in the risk of death after training (hazard ratio, 7.9; 95% CI, 3.1 to 20.5), adverse training outcomes including failure to complete residency (odds ratio, 14.9; 95% CI, 9.0 to 24.6) or become board certified (odds ratio, 10.4; 95% CI, 7.0 to 15.5), and adverse medical licensure actions subsequent to residency (hazard ratio, 6.8; 95% CI, 3.8 to 12.2). As of the end of follow-up, 54 cases (14.1%) were deceased compared with 10 controls (1.3%); 28 cases and no controls died during residency.

Conclusion:

The attributable risk of SUD to several adverse outcomes during and after residency training, including death and adverse medical license actions, is substantial.
Concurrence of Intraoperative Hypotension, Low Minimum Alveolar Concentration, and Low Bispectral Index Is Associated with Postoperative Death
Authors: Willingham Mark D. , Karren Elliott , Shanks Amy M. , O’Connor Michael F. , Jacobsohn Eric , Kheterpal Sachin , Avidan Michael S.
Published: August 2015

AbstractAbstract

In a retrospective study of nearly 14,000 patients from three clinical trials, the likelihood of 30- and 90-day mortality was increased approximately 10% for every 15 cumulative minutes in the triple low state, after controlling for known confounders for perioperative death.

Background:

An intraoperative concurrence of mean arterial pressure less than 75 mmHg, minimum alveolar concentration less than 0.8, and bispectral index less than 45 has been termed a “triple low” state. An association between triple low and postoperative mortality has been reported but was not replicated in a subsequent study. The authors pooled existing data from clinical trials to further evaluate the purported association in an observational study.

Methods:

This retrospective observational study included 13,198 patients from three clinical trials: B-Unaware, BAG-RECALL, and Michigan Awareness Control Study. Patients with greater than 15 not necessarily consecutive minutes of triple low were propensity matched to controls with similar characteristics and comorbidities. A multivariable Cox proportional hazards model was used to evaluate the association between triple low duration and postoperative mortality.

Results:

Thirty-day mortality was 0.8% overall, 1.9% in the triple low cohort, and 0.4% in the nontriple low cohort (odds ratio, 5.16; 95% CI, 4.21 to 6.34). After matching and adjusting for comorbidities, cumulative duration of triple low was significantly associated with an increased risk of mortality at 30 days (hazard ratio, 1.09; 95% CI, 1.07 to 1.11, per 15 min) and 90 days (hazard ratio, 1.09; 95% CI, 1.08 to 1.11, per 15 min).

Conclusion:

There is a weak independent association between the triple low state and postoperative mortality, and the propensity-matched analysis does not suggest that this is an epiphenomenon.
A blueprint for vocal learning: auditory predispositions from brains to genomes
Authors: Wheatcroft David , Qvarnström Anna
Published: August 2015

Memorizing and producing complex strings of sound are requirements for spoken human language. We share these behaviours with likely more than 4000 species of songbirds, making birds our primary model for studying the cognitive basis of vocal learning and, more generally, an important model for how memories are encoded in the brain. In songbirds, as in humans, the sounds that a juvenile learns later in life depend on auditory memories formed early in development. Experiments on a wide variety of songbird species suggest that the formation and lability of these auditory memories, in turn, depend on auditory predispositions that stimulate learning when a juvenile hears relevant, species-typical sounds. We review evidence that variation in key features of these auditory predispositions are determined by variation in genes underlying the development of the auditory system. We argue that increased investigation of the neuronal basis of auditory predispositions expressed early in life in combination with modern comparative genomic approaches may provide insights into the evolution of vocal learning.
A call for full annual cycle research in animal ecology
Authors: Marra Peter P. , Cohen Emily B. , Loss Scott R. , Rutter Jordan E. , Tonra Christopher M.
Published: August 2015

For vertebrates, annual cycles are organized into a series of breeding and non-breeding periods that vary in duration and location but are inextricably linked biologically. Here, we show that our understanding of the fundamental ecology of four vertebrate classes has been limited by a severe breeding season research bias and that studies of individual and population-level responses to natural and anthropogenic change would benefit from a full annual cycle perspective. Recent emergence of new analytical and technological tools for studying individual and population-level animal movement could help reverse this bias. To improve understanding of species biology and reverse the population declines of many vertebrate species, a concerted effort to move beyond single season research is vital.
Predicting global community properties from uncertain estimates of interaction strengths
Authors: Barabás György , Allesina Stefano
Published: August 2015

The community matrix measures the direct effect of species on each other in an ecological community. It can be used to determine whether a system is stable (returns to equilibrium after small perturbations of the population abundances), reactive (perturbations are initially amplified before damping out), and to determine the response of any individual species to perturbations of environmental parameters. However, several studies show that small errors in estimating the entries of the community matrix translate into large errors in predicting individual species responses. Here, we ask whether there are properties of complex communities one can still predict using only a crude, order-of-magnitude estimate of the community matrix entries. Using empirical data, randomly generated community matrices, and those generated by the Allometric Trophic Network model, we show that the stability and reactivity properties of systems can be predicted with good accuracy. We also provide theoretical insight into when and why our crude approximations are expected to yield an accurate description of communities. Our results indicate that even rough estimates of interaction strengths can be useful for assessing global properties of large systems.