bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteriophage
T4
Authors: Mathews Christopher K
Published: August 2015

Bacteriophage
T4
and its host bacterium,
Escherichia coli
, can be considered among the earliest model organisms – biological systems that attract large numbers of investigators who, because of technical or conceptual advantages of the system, use the system to investigate processes and mechanisms of general significance in biology. Beginning in the mid‐twentieth century, studies focused on bacteriophage
T4
revealed essential features of the molecular nature of genes and genomes, mechanism and fidelity of
DNA
replication, genetic recombination,
DNA
repair, control of gene expression, genome organisation, assembly of complex macromolecular structures and pre‐emption of cell metabolism by virus infection. Although much of the molecular biology research community has moved on to eukaryotic model organisms, such as yeast, nematode worms, fruitflies, the plant
Arabidopsis
, zebrafish and mice, bacteriophage
T4
still presents the best opportunities for understanding at the molecular level
DNA
replication and recombination, and macromolecular assembly. In addition,
T4
and related phages are being used in investigations of bacteriophage therapy. Finally, recent analyses of
DNA
packaging and morphogenesis have suggested applications of
T4
as a gene delivery vehicle.

Key Concepts

Bacteriophage T4 presents numerous technical advantages as a model for studying virus reproduction or gene organisation and expression.

Bacteriophage T4 is representative of a large group of closely related phages found in varied environments worldwide.

Bacteriophage T4 is a virulent phage, which always lyses and kills its host bacterium.

The T4 virion has a complex multiprotein structure with a contractile tail that serves both for adsorption to host cells and for intracellular delivery of the viral genome.

Bacteriophage T4 contains a large, linear double‐stranded DNA genome, with chemical modifications of its cytosine residues.

The T4 genome is circularly permuted and terminally redundant with respect to base sequence; these features protect against information loss during replication of a linear DNA.

The T4 genome encodes numerous enzymes, used to support replication of the viral genome and to synthesise deoxyribonucleotides to support the enormous rate of DNA accumulation in infected cells.

T4 uses host cell RNA polymerase for transcription of its own genes, but it modifies the bacterial enzyme, both to prevent its transcription of bacterial genes after infection and to contribute towards a timed viral gene transcription program.

T4 morphogenesis involves separate subassembly pathways for viral heads, tails, tail baseplates and fibres, with the substructures assembling spontaneously.
T
‐Cell Receptors
Authors: Schoettle Louis N , Poindexter Morgan E , Blattman Joseph N
Published: August 2015

In order to combat a wide array of pathogens, the immune system must be able to generate cells with the ability to recognise virtually any pathogen while at the same time balancing this diversity with the maintenance of sufficient numbers of cells specific for each pathogen in order to mount an effective response. T cells, which are important for both the direct elimination of infected cells as well as providing support for other immune responses to pathogens, generate immunologic diversity by imprecise joining of gene segments to generate either α/β or γ/δ heterodimeric receptors during development. Although the potential diversity of rearranged T‐cell receptors (
TCR
) is many orders of magnitude greater than the number of T cells in any given individual, highly regulated steps in development, as well as restrictions in the specificity of
TCR
, facilitate the generation of sufficient numbers of T cells with each
TCR
to ensure efficacy in pathogen control.

Key Concepts

The T‐cell repertoire must balance diversity of antigen recognition with sufficient numbers of each specificity to elicit protection.

T cells may express either αβ or γδ T‐cell receptors, which have different roles in immunity.

T‐cell receptor diversity arises mainly through the process of somatic recombination.

Somatic recombination, the process of reorganisation of T‐cell receptor genes, is a highly ordered and regulated process.

T‐cell development includes checkpoints to ensure both self‐MHC restriction and negative selection to remove any autoreactive T cells.

T‐cell receptors recognise processed antigen displayed on self‐MHC complexes presented by antigen‐presenting cells.

T‐cell receptors signal intracellularly through the CD3 signalling complex.

TCR:pMHC activation with appropriate costimulation results in differentiation of effector T cells .
Hypersensitivity:TLymphocyte Mediated (TypeIV)
Authors: Hwang Shen‐An , Actor Jeffrey K
Published: August 2015

Five types of hypersensitivity reactions have been described: types I,II,IIIand V depend on antigen antibody interactions and have been termed ‘immediate’ and typeIVreactions depend on interaction of antigen with T lymphocytes and has been called ‘delayed‐type hypersensitivity’, orDTH. TheDTHreaction involves cellular activation of T helper cells (CD4+) and/or cytotoxic T cells (CD8+CTLs). Subsequent cytokine secretion gives rise to distinct pathologies. In many cases, sustained release of antigen and continued activation of sensitized T lymphocytes result in amplification of responses that provoke excessive immune activation. These events are the basis for development of a broad range of inflammatory pathologies that include erythema and oedema, granuloma formation, extended development of fibrosis, and tissue necrosis.

Key Concepts

Type IV hypersensitivity (also calleddelayed‐type hypersensitivity, DTH) represents immune reactivity where T lymphocytes have had prior encounter with antigen.

It is termed ‘delayed‐type’ hypersensitivity because the reaction usually manifests 12–24 h post antigen exposure.

DTH responses can manifest from contact with allergens or infectious agents, giving rise to localised inflammation, erythema and oedema.

The classical manifestations of DTH are defined as cutaneous (contact), tuberculin or granulomatous hypersensitivity. Broader classification now includes subdivision based on dominant effector activity and defined elicited pathology.

DTH evolved as a protective host mechanism to combat pathogens; however, excessive DTH responses can lead to immunopathology, exhibited by granuloma formation, fibrosis or even tissue necrosis.

DTH reactions are prominent in autoimmune diseases, and have also been demonstrated to play a role in the response to transplantation of tissue from a genetically different donor (allogeneic transplantation).
Video Microscopy
Authors: Hinchcliffe Edward H
Published: August 2015

Video microscopy represents the first form of electronic imaging in light microscopy, and heralded the use of sophisticated fluorescence imaging techniques. However, today video microscopy – based on phase or differential interference optics – is considered to be an outdated technology. Rather than being yesterday's technology, a simple video microscope is a powerful tool for imaging cellular dynamics, and can easily be used to monitor cell cycle progression. Because the nonfluorescence imaging modes require significantly less light throughput, the video microscope is particularly suited for long‐term experiments, where photodamage can be a limiting factor. The video microscope is also an economical instrument that complements more sophisticated fluorescence‐based imaging systems, such as confocals, wide‐field deconvolution microscopes and super‐resolution microscopes. Here, I discuss a brief history of video microscopy, define some popular uses for the technology and discuss the selection of components for building a simple, yet functioning video microscopy system.

Key Concepts

Video microscopy represents the first electronic imaging system.

Simple video microscopes are an economical choice for live‐cell imaging.

System design requires selecting appropriate microscopes and illumination sources to allow long‐term imaging.

Live‐cell imaging requires control of temperature and pH.

Software selection to capture movies, control the imaging system and present the data is important.
Actin Reorganisation in Nerve Morphogenesis
Authors: Singh Ajeet P , Rodrigues Veronica , VijayRaghavan Krishnaswamy
Published: August 2015

Anatomists over centuries have described nerve cells which are notable for their diversity of architectures ranging from rather simple cells to highly complex and beautiful shapes. The soma of most neurons has two types of projections – dendrites, which receive inputs from the environment or other nerve cells, and axons, which specialise in information transfer. The correct shape of a neuron and its connectivity which forms the basis of a functional circuit is crucial for the normal physiology of an animal. Defects in neuronal morphogenesis have been shown to be the cause of several neurological diseases. In this article, we focus on a key molecule – actin, a component of the cytoskeleton – that forms the basis of cell shape and growth. We discuss how signals from within the cells and from its developmental milieu influence the organisation of actin which in turn impacts on the shape and function of a nerve cell.

Key Concepts

Actin is enriched in areas of neurons which undergo rapid changes in shape.

Actin dynamics is regulated by multiple upstream signals and intracellular effectors.

Local destabilisation of the actin cytoskeleton is a key downstream event during selection of an axon.

Actin dynamics in the growth cone regulates filopodial extension/retraction.

Actin cytoskeleton is highly dynamic in dendritic spines.

Neuronal activity‐dependent spine enlargement is correlated with a shift in F‐/G‐actin equilibrium towards F‐actin.

Rho GTPases are major intracellular regulators of actin dynamics.
Horizontal Gene Transfer in Evolution
Authors: Boto Luis
Published: August 2015

The concept of horizontal or lateral gene transfer (the non‐genealogical transmission of genetic material between organisms) was introduced in 1990s to explain the observed incongruence in phylogenetic reconstructions using different genes. Today, horizontal gene transfer is accepted as an important force modulating evolution of Bacteria, Archaea and unicellular eukaryotes, and evidence is rising for their role in the evolution of pluricellular eukaryotes (fungi, plants and animals). The realisation that horizontal gene transfer plays an important role in evolution of both, prokaryotes and eukaryotes, put in question the metaphor of the tree of life and the traditional view of evolution as a slow process. A more pluralistic approach to evolution is emerging that encompasses different evolutionary mechanisms operating at different levels of complexity.

Key Concepts

Horizontal gene transfer is the non‐genealogical transmission of genetic material between different organisms.

Horizontal gene transfer has become a part of evolutionary thinking over the past 25 years.

Horizontal gene transfer plays an important role in prokaryotic evolution.

Horizontal gene transfer also modulates evolution of unicellular eukaryotes.

Increasing evidence support the role of horizontal gene transfer in evolution of pluricellular eukaryotes.

Horizontal gene transfer challenges the tree of life metaphor.

Horizontal gene transfer challenges the traditional view of evolution as a slow process.

A pluralistic approach to evolution is needed.
Neurobiology of Itch (Pruritus)
Authors: Akiyama Tasuku , Mochizuki Hideki , Carstens E
Published: August 2015

Itch is often defined as an ‘unpleasant sensation that provokes the desire to scratch’. Recent studies have provided novel insights into the molecular mechanisms underlying itch‐selective signalling pathways from the periphery to the central nervous system. Chronic itch is often associated with inflammatory skin diseases such as atopic dermatitis, psoriasis or contact dermatitis, as well as systemic diseases such as renal, cholestatic, hematologic or endocrine pruritus or pruritus related to malignancy, and reduces quality of life. Chronic itch is thought to involve the sensitisation of itch‐signalling pathways, the molecular and cellular processes of which we are just starting to uncover. This review article describes recent findings regarding the basic mechanisms of itch transmission from the skin to the brain. We further describe the neuronal changes that occur both peripherally and centrally under conditions of chronic itch.

Key Concepts

There are a variety of endogenous pruritogens and external itch stimuli.

Itch transducing channels include TRPV1, TRPA1 and Nav1.7.

Spinal excitatory and inhibitory interneurons process itch information.

Descending noradrenergic and serotonergic systems modulate spinal itch transmission.

Sensitisation occurs in both peripheral and central nervous system under conditions of chronic itch.

NK1‐expressing spinal neurons play a major role in itch sensitisation.
LINC
Complexes and Their Role in Human Disease
Authors: Calvi Alessandra , Burke Brian
Published: August 2015

In most metazoan cell types, the nucleus occupies a clearly defined region of the cytoplasm. For instance in epithelial cells, it is commonly positioned close to the basal membrane, whereas in skeletal muscle fibres, the majority of nuclei are uniformly distributed adjacent to the plasma membrane. A few muscle cell nuclei, however, cluster beneath the postsynaptic membrane. In certain cell types, the nucleus may be repositioned according to cell cycle phase or cell activity. Each of these situations requires that nuclei be physically coupled to the cytoskeleton. This is accomplished in large part by
LINC
(linker of the nucleoskeleton and cytoskeleton) complexes. These structures consist of inner nuclear membrane
SUN
(Sad1p‐UNC‐84)‐domain proteins that function as transluminal tethers for outer nuclear membrane
KASH
‐domain proteins. Together,
SUN–KASH
pairs function as links in a molecular chain that couples cytoskeletal elements, including motor proteins, to nuclear components. In addition to having obligate roles in nuclear positioning and chromatin organisation,
LINC
complexes may also function in mechanotransduction. The fact that a number of human diseases have been associated with
LINC
complex defects indicates that in many cell types these represent essential structures at the interface between the nucleus and cytoplasm.

Key Concepts

The nuclear envelope forms the interface between the nucleus and cytoplasm. Its most prominent features are the inner and outer nuclear membranes (INM and ONM) separated by a narrow (∼50 nm) gap, the perinuclear space (PNS).

SUN domain proteins of the INM function as transluminal tethers for KASH domain proteins in the ONM.

The nucleoplasmic domain of SUN proteins provides binding sites for both chromatin proteins and components of the nuclear lamina.

KASH domain proteins represent attachment sites at the nuclear envelope for a variety of cytoskeletal elements, including motor proteins.

SUN–KASH pairs, which span both nuclear membranes, are known as LINC (linker of the nucleoskeleton and cytoskeleton) complexes and mechanically couple nuclear structures to the cytoskeleton.

LINC complexes have essential roles in nuclear migration and positioning in multiple cell types.

During meiosis, LINC complexes have an essential role in telomere‐led chromosome movement, a process that facilitates homologous chromosome pairing and synapsis.

LINC complexes are thought to mediate the transmission of mechanical signals to the nucleus: mechanotransduction.
Biocompatible and Flexible Chitosan‐Based Resistive Switching Memory with Magnesium Electrodes
Authors: Hosseini Niloufar Raeis , Lee Jang‐Sik
Published: August 2015

A flexible and transparent resistive switching memory based on a natural organic polymer for future flexible electronics is reported. The device has a coplanar structure of Mg/Ag‐doped chitosan/Mg on plastic substrate, which shows promising nonvolatile memory characteristics for flexible memory applications. It can be easily fabricated using solution processes on flexible substrates at room temperature and indicates reliable memory operations. The elucidated origin of the bipolar resistive switching behavior is attributed to trap‐related space‐charge‐limited conduction in high resistance state and filamentary conduction in low resistance state. The fabricated devices exhibit memory characteristics such as low power operation and long data retention. The proposed biocompatible memory device with transient electrodes is based on naturally abundant materials and is a promising candidate for low‐cost memory applications. Devices with natural substrates such as chitosan and rice paper are also fabricated for fully biodegradable resistive switching memory. This work provides an important step toward developing a flexible resistive switching memory with natural polymer films for application in flexible and biodegradable nanoelectronic devices.
Alkylations of Arylboronic Acids including Difluoroethylation/Trifluoroethylation via Nickel‐Catalyzed Suzuki Cross‐Coupling Reaction
Authors: Zhang Xiaofei , Yang Chunhao
Published: August 2015

An efficient alkylation method of functionalized alkyl halides under mild nickel‐catalyzed C(sp3)C(sp2) Suzuki cross‐coupling conditions is described. The features of this approach are excellent functional group compatibility, low cost nickel catalyst, and the use of a mild base. This is also the first successful example of the nickel‐catalyzed direct 2,2‐difluoroethylation or 2,2,2‐trifluoroethylation of aryl‐/heteroarylboronic acids.

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Generalized Mechanochemical Synthesis of Biomass‐Derived Sustainable Carbons for High Performance CO2 Storage
Authors: Balahmar Norah , Mitchell Andrew C. , Mokaya Robert
Published: August 2015

Novel mechanochemical activation generates biomass‐derived carbons with unprecedented CO2 storage capacity due to higher porosity than analogous conventionally activated carbons but similar pore size. The mechanochemical activation, or so‐called compactivation, process involves compression, at 740 MPa, of mixtures of activating agent (KOH) and biomass hydrochar into pellets/disks prior to thermal activation. Despite the increase in surface area and pore volume of between 25% and 75% compared to conventionally activated carbons, virtually all of the porosity of the biomass (sawdust and lignin) derived mechanochemically activated carbons is from small micropores (5.8–6.5 Å), which results in a dramatic increase in CO2 storage capacity at 25 °C and low pressure (≤1 bar). The ambient temperature CO2 uptake for a carbon derived from sawdust at 600 °C and a KOH/carbon ratio of 2, rises from 1.3 to 2.0 mmol g−1 at 0.15 bar, and from 4.3 to 5.8 mmol g−1 at 1 bar, which is the highest ever reported for carbonaceous materials. The mechanochemically activated carbons have a superior CO2 working capacity for pressure swing adsorption and vacuum swing adsorption processes and, due to a high packing density, they exhibit excellent volumetric CO2 uptake that is higher than for any material reported to date.
Marfan syndrome patient experiences as ascertained through postings on social media sites
Authors: Kelleher Erin , Giampietro Philip F. , Moreno Megan A.
Published: August 2015

Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents [Population Reference Bureau, 2013]. Some adolescent patients with MS may use social media to express their experiences and emotions, but little is known about what patients choose to share online. To investigate social media content related to Marfan syndrome we used search terms “Marfan syndrome” and “Marfans” on six different social media sites. The top five recent and popular posts for each site were collected and coded weekly for five weeks. Posts were excluded if they were reshared content or not in English. A codebook was developed using an iterative process to categorize posts and comments. Out of 300 posts collected 147 posts (49.0%) were included for evaluation. Categories of displayed content included personal pictures, memes and pictures featuring symptoms of MS (41.5%) and personal MS experiences (27.1% of posts). One quarter of the posts specifically mentioned a positive experience or how thankful the profile owner was for their life. A unique category of posts (13.7%) referenced Austin Carlile, a celebrity singer with MS, as a role model. Physicians and healthcare providers may consider using social media to understand common MS concerns and to place future health education materials. © 2015 Wiley Periodicals, Inc.
Stereocontrolled Synthesis of Difunctionalized Azetidinones and β2, 3‐Amino Acid Derivatives from Cyclodienes by Ring‐Opening and Cross‐Metathesis Reactions
Authors: Kardos Márton , Kiss Loránd , Fülöp Ferenc
Published: August 2015

A stereocontrolled approach to highly functionalized 3,4‐disubstituted azetidin‐2‐ones and β2, 3‐amino acid derivatives from readily available cycloalkadienes was achieved. The syntheses involved 1,3‐dipolar cycloaddition of chlorosulfonyl isocyanate, followed by ring‐opening metathesis of the unsaturated bi‐ or tricyclic β‐lactams, and cross‐metathesis of the resulting divinyl‐substituted azetidinones. The substituted lactams were subsequently transformed by heteroring‐opening into the corresponding functionalized acyclic β2, 3‐amino acid derivatives.
A framework to assess the value of application of formal criteria to check clinical relevance in RCTs as part of a benefit assessment strategy
Authors: Vach Werner , Gladstone Beryl Primrose
Published: August 2015

Recently, the topic of assessing clinical relevance on top of statistical significance in the analysis of randomized control trials (RCTs) has got increasing attention, in particular as part of benefit assessments. Several formal criteria to serve this purpose have been published. In this paper, we present a framework to assess the value of the application of such criteria. We propose to quantify the need for the assessment of clinical relevance by the actual risk of having accepted a benefit for a treatment with an irrelevant effect in a successful RCT. We then study how this risk can be controlled by two popular criteria based on comparing the effect estimate or the lower bound of the confidence interval with a given threshold. We further propose to quantify the impact of using formal criteria by considering the expected costs when specifying error‐specific costs for each of the three possible types of errors: A benefit may be accepted for a treatment, which is actually inferior, or which is not inferior, but only implies an irrelevant improvement, or a benefit may be rejected for a treatment implying a relevant improvement. This way we can demonstrate that the impact depends on parameters which are typically not explicitly defined in the frame of benefit assessments. Depending on the values of these parameters, formal checks of clinical relevance may imply better decisions on average, but they may also imply more harm than good on average.
Macrocyclic Weakly Coordinating Anions
Authors: Landskron Kai
Published: August 2015

Herein, the concept of macrocyclic weakly coordinating anions (M‐WCAs) is introduced. Synthetic methodologies are described how to access M‐WCAs by thermodynamically controlled self‐assembly in high yields, in particular through condensation and alkyne metathesis reactions. The anticipated properties and applications of M‐WCAs in solid state and in solution are discussed, specifically for gas storage and separation, homogeneous and heterogeneous catalysis, and as liquid and solid electrolytes.
Engineering of Energy Levels for Fully Conjugated D‐A Block CopolymersviaTuning the Ratios of Donor P3HT and Acceptor PNDIT
Authors: Wang Shifan , Guo Yan , Yang Jie , Tao Youtian , Huang Wei
Published: August 2015

Fully conjugated donor‐acceptor (D‐A) block copolymers, P3HT‐b‐PNDIT, containing p‐type poly(3‐hexylthiophene) (P3HT) and n‐type poly(naphthalene bismide) (PNDIT) segments are synthesized in a one‐pot reaction via Stille coupling polycondensation. Various D‐A block copolymers with low polydispersities (1.42–1.56) are obtained through further separation via preparative GPC. The structural and molecular features of block copolymers are verified by1H NMR, FTIR spectra, UV‐Vis absorption, differential scanning calorimetry (DSC) and cyclic voltammetry (CV). It is found that optical and electrochemical properties of D‐A block copolymers are strongly dependent on the combination ratio of the donor P3HT and acceptor PNDIT segment. By reducing the acceptor block lengths, the highest occupied molecular orbital (HOMO) energy levels of D‐A block copolymers sequentially rise, leading to the sequential decrease of energy gaps. To the best of our knowledge, this is the first report on engineering the energy levels of fully conjugated D‐A block copolymers by tuning donor and acceptor chain lengths. More?over, compared to D/A polymer blends, the all‐conjugated D‐A block copolymer films show significant fine structures and much smoother film morphologies.
Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease
Authors: Mathur Pankaj , Ding Zufeng , Saldeen Tom , Mehta Jawahar L.
Published: August 2015

Oxidants/antioxidants play an important role in cellular homeostasis. The human body has endogenous molecules that work as antioxidants, such as glutathione, superoxide dismutase, peroxidases, and catalase. Exogenous substances in the diet, such as β‐carotene, ascorbate, and vitamin E, are vital antioxidants. Of these, vitamin E is likely the most important antioxidant in the human diet, and many studies have been performed to elucidate its role in health and disease. Vitamin E is a family of several compounds, of which α‐tocopherol is the most widely known analog. α‐Tocopherol exhibits antioxidative property in vitro and inhibits oxidation of low‐density lipoprotein cholesterol. In addition, α‐tocopherol shows anti‐inflammatory activity and modulates expression of proteins involved in the uptake, transport, and degradation of atherogenic lipids. Though α‐tocopherol exhibits important antioxidant, anti‐inflammatory, and antiatherogenic features in vitro, α‐tocopherol supplements have failed to consistently reduce atherosclerosis‐related events in human trials. The conflicting results have led to reconsideration of the importance previously given to α‐tocopherol and led to interest in other members of vitamin E family, especially γ‐tocopherol, which exerts a much more potent antioxidant, anti‐inflammatory, and cardioprotective effect than α‐tocopherol. This reconsideration has been backed by solid laboratory and clinical research. We suggest that the absence of γ‐tocopherol in traditional preparations may be one reason for the lack of consistent salutary effects of vitamin E preparations in clinical trials. This review summarizes our current understanding of tocopherols as antioxidant molecules and emerging evidence of an important role of γ‐tocopherol in the pathophysiology of atherosclerosis‐related cardiovascular disease.
The expression of tubb2b undergoes a developmental transition in murine cortical neurons
Authors: Breuss Martin , Morandell Jasmin , Nimpf Simon , Gstrein Thomas , Lauwers Mattias , Hochstoeger Tobias , Braun Andreas , Chan Kelvin , Sánchez Guajardo Edmundo R. , Zhang Lijuan , Suplata Marek , Heinze Katrin G. , Elsayad Kareem , Keays David A.
Published: August 2015

The development of the mammalian brain requires the generation, migration, and differentiation of neurons, cellular processes that are dependent on a dynamic microtubule cytoskeleton. Mutations in tubulin genes, which encode for the structural subunits of microtubules, cause detrimental neurological disorders known as the tubulinopathies. The disease spectra associated with different tubulin genes are overlapping but distinct, an observation believed to reflect functional specification of this multigene family. Perturbation of the β‐tubulin TUBB2B is known to cause polymicrogyria, pachygyria, microcephaly, and axon guidance defects. Here we provide a detailed analysis of the expression pattern of its murine homolog Tubb2b. The generation and characterization of BAC‐transgenic eGFP reporter mouse lines has revealed that it is highly expressed in progenitors and postmitotic neurons during cortical development. This contrasts with the 8‐week‐old cortex, in which Tubb2b expression is restricted to macroglia, and expression is almost completely absent in mature neurons. This developmental transition in neurons is mirrored in the adult hippocampus and the cerebellum but is not a universal feature of Tubb2b; its expression persists in a population of postmitotic neurons in the 8‐week‐old retina. We propose that the dynamic spatial and temporal expression of Tubb2b reflects specific functional requirements of the microtubule cytoskeleton. J. Comp. Neurol. 523:2161–2186, 2015. © 2015 Wiley Periodicals, Inc.
SymS: a symmetrical scheduler to improve multi‐threaded program performance on NUMA systems
Authors: Zhu Liang , Jin Hai , Liao Xiaofei
Published: August 2015

The nonuniform memory access (NUMA) architecture has been used extensively in data centers. Most of the previous works used single‐threaded multiprogrammed workloads to study the performance of NUMA systems, which mainly focus on two classes of problems: resource contention and data locality. However, when running multi‐threaded programs on NUMA systems, the critical thread of these programs significantly influences the system performance and brings new challenges that are different from those in a single‐threaded situation. In particular, an additional scheduling scheme is desired to avoid the performance degradation caused by the critical thread of multi‐threaded programs running on NUMA systems. This work presents a scheduler, Symmetrical Scheduler, which successfully solves the lagging problem by balancing the number of the costly remote shared data accesses for threads on NUMA systems. To the best of our knowledge, little work has been conducted to examine the performance impacted by the critical thread of multi‐threaded programs on NUMA systems. By running the PARSEC benchmark on such systems, our methodology can improve the program performance by a factor of 6% on average and achieve maximally 25.3% improvement compared with Linux kernel scheduling mechanism. Copyright © 2015 John Wiley & Sons, Ltd.
A model‐based longitudinal meta‐analysis of FEV1 in randomized COPD trials
Authors: Korell J , Martin SW , Karlsson MO , Ribbing J
Published: August 2015

A model‐based, longitudinal meta‐analysis of the efficacy on morning trough forced expiratory volume in 1 second (FEV1) in chronic obstructive pulmonary disease (COPD) is presented. Literature data from 142 randomized maintenance trials were included, comprising 106,422 patients who received 19 compounds. 1982 morning trough FEV1 observations were available, each representing the mean FEV1 for a study arm at a specific timepoint. The final model for absolute FEV1 included baseline, disease progression, placebo effect, and drug effect estimates for all compounds, with interstudy variability on all model components and additional interarm variability on baseline. A dose–response relationship was identifiable for 10 of the 19 compounds. Drug–drug interactions among direct bronchodilators and the effect of concomitant background COPD treatment were included. Covariates were identified on baseline. Disease progression was proportional to the baseline FEV1, and a mean baseline of <1.2 L resulted in a lower efficacy, in particular for antiinflammatory treatments.
Mapping cell populations in flow cytometry data for cross‐sample comparison using the Friedman–Rafsky test statistic as a distance measure
Authors: Hsiao Chiaowen , Liu Mengya , Stanton Rick , McGee Monnie , Qian Yu , Scheuermann Richard H.
Published: August 2015

Flow cytometry (FCM) is a fluorescence‐based single‐cell experimental technology that is routinely applied in biomedical research for identifying cellular biomarkers of normal physiological responses and abnormal disease states. While many computational methods have been developed that focus on identifying cell populations in individual FCM samples, very few have addressed how the identified cell populations can be matched across samples for comparative analysis. This article presents FlowMap‐FR, a novel method for cell population mapping across FCM samples. FlowMap‐FR is based on the Friedman–Rafsky nonparametric test statistic (FR statistic), which quantifies the equivalence of multivariate distributions. As applied to FCM data by FlowMap‐FR, the FR statistic objectively quantifies the similarity between cell populations based on the shapes, sizes, and positions of fluorescence data distributions in the multidimensional feature space. To test and evaluate the performance of FlowMap‐FR, we simulated the kinds of biological and technical sample variations that are commonly observed in FCM data. The results show that FlowMap‐FR is able to effectively identify equivalent cell populations between samples under scenarios of proportion differences and modest position shifts. As a statistical test, FlowMap‐FR can be used to determine whether the expression of a cellular marker is statistically different between two cell populations, suggesting candidates for new cellular phenotypes by providing an objective statistical measure. In addition, FlowMap‐FR can indicate situations in which inappropriate splitting or merging of cell populations has occurred during gating procedures. We compared the FR statistic with the symmetric version of Kullback–Leibler divergence measure used in a previous population matching method with both simulated and real data. The FR statistic outperforms the symmetric version of KL‐distance in distinguishing equivalent from nonequivalent cell populations. FlowMap‐FR was also employed as a distance metric to match cell populations delineated by manual gating across 30 FCM samples from a benchmark FlowCAP data set. An F‐measure of 0.88 was obtained, indicating high precision and recall of the FR‐based population matching results. FlowMap‐FR has been implemented as a standalone R/Bioconductor package so that it can be easily incorporated into current FCM data analytical workflows. © 2015 International Society for Advancement of Cytometry
The federal government/higher education: Working together to provide employment support for individuals with ASD
Authors: Meeks Lisa M. , Rigler Michelle , Butler Pamela A.
Published: August 2015

Research on employment and individuals with autism spectrum disorder demonstrates that gainful employment leads to improved outcomes, including improved emotional state, greater financial gain, decreased anxiety, greater self‐esteem and greater independence. That's according to Karen Hurlbutt and Lynn Chalmers in “Employment and Adults with Asperger Syndrome” in the journal Focus on Autism and Other Developmental Disabilities. Individuals with ASD possess a valuable set of skills (e.g., attention to detail, persistence, intense focus, and the ability to think creatively and efficiently when solving problems). Unfortunately, poor interviewing skills, lack of social awareness and savvy, and deficits in the “art of conversation” often present roadblocks during the interview, hiring and promotion processes.
Take steps to make your campus deaf‐friendly
Authors: Hope Joan
Published: August 2015

Cheryl Fielitz, interpreter; Maria Holloway, interpreter; and Dann Trainer, access consultant explained some of their strategies for making the University of Minnesota campus deaf‐friendly.
Support college students with disabilities who do not identify and self‐advocate
Authors: Gaddy Stephanie
Published: August 2015

One major goal as a disability service provider is to promote success for all students with disabilities. Thus, you probably provide a lot of encouragement to students with disabilities to self‐advocate and to request accommodations to succeed in their courses.
Tracking changes in life‐history traits related to unnecessary virulence in a plant‐parasitic nematode
Authors: Castagnone‐Sereno Philippe , Mulet Karine , Iachia Cathy
Published: August 2015

Evaluating trade‐offs in life‐history traits of plant pathogens is essential to understand the evolution and epidemiology of diseases. In particular, virulence costs when the corresponding host resistance gene is lacking play a major role in the adaptive biology of pathogens and contribute to the maintenance of their genetic diversity. Here, we investigated whether life‐history traits directly linked to the establishment of plant–nematode interactions, that is, ability to locate and move toward the roots of the host plant, and to invade roots and develop into mature females, are affected in Meloidogyne incognita lines virulent against the tomato Mi‐1.2 resistance gene. Virulent and avirulent near‐isogenic lines only differing in their capacity to reproduce or not on resistant tomatoes were compared in single inoculation or pairwise competition experiments. Data highlighted (1) a global lack of trade‐off in traits associated with unnecessary virulence with respect to the nematode ability to successfully infest plant roots and (2) variability in these traits when the genetic background of the nematode is considered irrespective of its (a)virulence status. These data suggest that the variation detected here is independent from the adaptation of M. incognita to host resistance, but rather reflects some genetic polymorphism in this asexual organism.
Levosimendan improves exercise performance in patients with advanced chronic heart failure
Authors: Mushtaq Saima , Andreini Daniele , Farina Stefania , Salvioni Elisabetta , Pontone Gianluca , Sciomer Susanna , Volpato Valentina , Agostoni Piergiuseppe
Published: August 2015

Aims

Cardiopulmonary exercise test (CPET) provides parameters such as peak VO2 and ventilation/CO2 production (VE/VCO2) slope, which are strong prognostic predictors in patients with stable advanced chronic heart failure (ADHF). The study aim was to evaluate the effects of the inodilator levosimendan on CPET in patients with ADHF under stable clinical conditions.

Methods and results

We enrolled patients with ADHF (peak VO2 < 12 mL/min/kg) in a double‐blind, placebo‐controlled protocol. Patients were randomly assigned to i.v. infusion of placebo (500 mL 5% glucose; n = 19) or levosimendan (in 500 mL 5% glucose; n = 23). Before and 24 h after the end of the infusion, patients underwent determination of New York Heart Association class, B‐type natriuretic peptide (BNP), haemoglobin, serum creatinine, and blood urea nitrogen levels, as well as CPET, standard spirometry, and alveolar capillary gas diffusion. BNP showed no change with placebo (1042 ± 811 to 1043 ± 867 pg/mL), but it was decreased with levosimendan (1163 ± 897 to 509 ± 543 pg/mL, P < 0.001). No changes were observed for haemoglobin, creatinine, and blood urea nitrogen in either group. With levosimendan, a minor improvement was observed in spirometry measurements, but not in alveolar capillary gas diffusion. Peak VO2 showed a small, non‐significant increase with placebo (9.5 ± 1.7 to 10.0 ± 2.1 mL/kg/min, P = 0.12), and a greater increase with levosimendan (9.8 ± 1.7 to 11.0 ± 1.9 mL/kg/min, P < 0.005). The VE/VCO2 slope showed no change (44.0 ± 11 vs. 43.4 ± 10.3, P = 0.44), and a decrease (41.9 ± 10 vs. 36.6 ± 6.4, P < 0.001) in the placebo and in the levosimendan group, respectively.

Conclusion

Levosimendan treatment significantly improves peak VO2 and reduces VE/VCO2 slope and BNP in patients with ADHF.
Extended Threefold‐Symmetric Second‐Harmonic‐Generation Chromophores Based on 1,3,5‐Trisubstituted Benzene Complexes
Authors: Ziemann Elisabeth A. , Mietner J. Benedikt , Deffner Michael , Van Steerteghem Nick , Clays Koen , Herrmann Carmen , Heck Jürgen
Published: August 2015

The elongation of the π system of a donor–π–acceptor (D–π–A) chromophore has often proven to be beneficial for its nonlinear optical (NLO) activity. Against this background, different alkynyl protecting groups such as organosilyl and dicobalt hexacarbonyl functions were investigated with respect to their ability to enable the coordination of an electron‐withdrawing CpRu+ fragment (Cp = cyclopentadienyl) to a threefold ethynyl‐substituted benzene ring, acting as a potential 2D NLOphore, without undesired side reactions. In addition, the influence of the perpendicularly coordinated CpRu+ unit on the NLO properties was examined. The obtained organometallic triisopropylsilyl‐substituted benzene ruthenium complex and the multinuclear dicobalt hexacarbonyl protected ferrocene complex were fully characterized. Owing to the problems during the purification of the trimethylsilyl‐protected benzene ruthenium complex and the subsequent deprotection to the free alkyne complex, it was not possible to fully characterize those complexes. The introduction of the CpRu+ fragment was sensitive to the steric demands of the benzene substituents but beneficial for the generation of NLO activity. The first hyperpolarizabilities of the triisopropyl and dicobalt hexacarbonyl complexes were investigated by hyper‐Rayleigh scattering. The molecular structures were characterized by X‐ray crystallography and infrared (IR) spectroscopy. The structures and IR spectra were compared with Kohn–Sham density functional theory calculations.
Base‐Induced Cyclization of Propargyl ­Alkenylsulfones: A High‐Yielding Synthesis of 4,5‐Disubstituted 2H‐Thiopyran 1,1‐Dioxides
Authors: Hatial Ishita , Das Joyee , Ghosh Ananta K. , Basak Amit
Published: August 2015

A convenient synthesis of 4,5‐disubstituted 2H‐thiopyran 1,1‐dioxides is reported through a base induced process starting from eneyne sulfones. Except for strongly electron‐withdrawing groups, the reaction tolerated a wide variety of substituents in the two aryl rings. This finding represents a major departure from the behaviour of the corresponding ethers. The reaction most probably proceeds through a 6π‐electrocyclization from an in‐situ‐generated 1,3,5‐trienyl sulfinate.
A Rapid Entry to Diverse γ‐Ylidenetetronate Derivatives through Regioselective ­Bromination of Tetronic Acid Derived γ‐Lactones and Metal‐Catalyzed Postfunctionalization
Authors: Chopin Nicolas , Yanai Hikaru , Iikawa Shinya , Pilet Guillaume , Bouillon Jean‐Philippe , Médebielle Maurice
Published: August 2015

The synthesis of a series of diverse methyl and benzyl γ‐ylidenetetronate derivatives was accomplished through the condensation of methyl and benzyl tetronates with (hetero)aryl aldehydes in a new two‐ or three‐step aldolisation/dehydration sequence. The bromination of methyl and benzyl γ‐ylidenetetronates occurred under mild conditions to provide the corresponding C‐3‐brominated γ‐unsaturated lactones. Di‐ and tribrominated γ‐lactones were prepared under slightly different conditions. Some brominated materials were employed in representative Stille, Suzuki–Miyaura, and Sonogashira cross‐coupling reactions to yield functionalized methyl and benzyl γ‐ylidenetetronate derivatives. Compounds that resulted from the Sonogashira cross‐coupling reactions were desilylated and converted into 1,2,3‐triazole derivatives through a copper(I)‐catalyzed 1,3‐dipolar cycloaddition reaction with benzyl azide.
Molecular screening of microbial communities for candidate indicators of multiple metal impacts in marine sediments from northern Australia
Authors: Cornall Alyssa , Rose Alea , Streten Claire , McGuinness Keith , Parry David , Gibb Karen
Published: August 2015

Coastal sediments accumulate metals from anthropogenic sources and as a consequence industry is required to monitor sediment health. The total concentration of a metal does not necessarily reflect its potential toxicity or biological impact, so biological assessment tools are useful for monitoring. Rapid biological assessment tools sensitive enough to detect relatively small increases in metal concentrations would provide early warning of future ecosystem impact. The authors investigated in situ populations of Archaea and Bacteria as potential tools for rapid biological assessment in sediment at 4 northern Australian coastal locations over 2 yr, in both wet and dry seasons. The 1 M HCl-extractable concentrations of metals in sediment were measured, and Archaeal and Bacterial community profiles were obtained by next-generation sequencing of sediment deoxyribonucleic acid (DNA). Species response curves were used to identify several taxonomic groups with potential as biological indicators of metal impact. Spatial variation, sediment grain size, water depth, and dissolved oxygen also correlated with microbial population shifts. Seasonal variation was less important than geographic location. Metal-challenge culture trials supported the identification of metal-resistant and -sensitive taxa. In situ Archaea and Bacteria are potentially sensitive indicators for changes in bioavailable concentrations of metals; however, the complexity of the system suggests it is important to identify metal-specific functional genes that may be informed by these sequencing surveys, and thus provide a useful addition to identity-based assays. Environ Toxicol Chem 2016;35:468–484. © 2015 SETAC
Simultaneous exposure to chronic hypoxia and dissolved polycyclic aromatic hydrocarbons results in reduced egg production and larval survival in the sheepshead minnow (Cyprinodon variegatus)
Authors: Hedgpeth Bryan M. , Griffitt Robert J.
Published: August 2015

Estuarine fish in the northern Gulf of Mexico are exposed annually to hypoxic conditions. In addition to hypoxia, fish located throughout the northern Gulf of Mexico were potentially exposed to oil released during the Deepwater Horizon incident. Therefore, the interaction between oil exposure and hypoxia is worth investigating. To examine this interaction, the authors exposed adult and larval sheepshead minnow (Cyprinodon variegatus) to crude or dispersed oil under both normoxic and hypoxic conditions. The authors examined total egg production, egg hatching success, and larval survival post hatch. The authors' results indicate that co-exposure to crude or dispersed oil and hypoxia resulted in a significant decrease in egg production, as well as a significant decrease in both egg hatch success and larval survival post hatch. The significant impact on reproductive success following crude or dispersed oil and hypoxia exposure indicates the importance of including environmental parameters such as hypoxia when evaluating the impact of an oil spill. Environ Toxicol Chem 2016;35:645–651. © 2015 SETAC