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High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees. © 2014 Nature America, Inc.

Background: Regulation of microRNA activity independent of processing and biogenesis has not been demonstrated. Results: The RNA-binding protein, TDP-43, interacts with mature miR-1/miR-206, limiting their RNA-induced silencing complex (RISC) association and activity. Conclusion: RNA-binding proteins can selectively control microRNA activity by disrupting RISC incorporation. Significance: This is the first known microRNA-protein interaction that controls microRNA activity independent of processing., MicroRNA (miRNA) maturation is regulated by interaction of particular miRNA precursors with specific RNA-binding proteins. Following their biogenesis, mature miRNAs are incorporated into the RNA-induced silencing complex (RISC) where they interact with mRNAs to negatively regulate protein production. However, little is known about how mature miRNAs are regulated at the level of their activity. To address this, we screened for proteins differentially bound to the mature form of the miR-1 or miR-133 miRNA families. These muscle-enriched, co-transcribed miRNA pairs cooperate to suppress smooth muscle gene expression in the heart. However, they also have opposing roles, with the miR-1 family, composed of miR-1 and miR-206, promoting myogenic differentiation, whereas miR-133 maintains the progenitor state. Here, we describe a physical interaction between TDP-43, an RNA-binding protein that forms aggregates in the neuromuscular disease, amyotrophic lateral sclerosis, and the miR-1, but not miR-133, family. Deficiency of the TDP-43 Drosophila ortholog enhanced dmiR-1 activity in vivo. In mammalian cells, TDP-43 limited the activity of both miR-1 and miR-206, but not the miR-133 family, by disrupting their RISC association. Consistent with TDP-43 dampening miR-1/206 activity, protein levels of the miR-1/206 targets, IGF-1 and HDAC4, were elevated in TDP-43 transgenic mouse muscle. This occurred without corresponding Igf-1 or Hdac4 mRNA increases and despite higher miR-1 and miR-206 expression. Our findings reveal that TDP-43 negatively regulates the activity of the miR-1 family of miRNAs by limiting their bioavailability for RISC loading and suggest a processing-independent mechanism for differential regulation of miRNA activity.

There is now a growing appreciation that estrogens are capable of rapidly activating a number of signaling cascades within the central nervous system. In addition, there are an increasing number of studies reporting that 17β-estradiol, the major biologically active estrogen, can modulate cognition within a rapid time frame. Here we review recent studies that have begun to uncover the molecular and cellular framework which contributes to estrogens ability to rapidly modulate cognition. We first describe the mechanisms by which estrogen receptors (ERs) can couple to intracellular signaling cascades, either directly, or via the transactivation of other receptors. Subsequently, we review the evidence that estrogen can rapidly modulate both neuronal function and structure in the hippocampus and the cortex. Finally, we will discuss how estrogens may influence cognitive function through the modulation of neuronal structure, and the implications this may have on the treatment of a range of brain disorders.

Use of automation, control and information technology for creating automated workflows and real-time assets management in the petroleum industry has rapidly grown in recent years. This integration of automation and communication produces large amounts of data, especially with optical fiber-based sensor systems and the need for providing real-time controls and optimization based on data-driven predictive analytics. The transition to the intelligent paradigm opens up new opportunities but also poses a number of challenges. Currently, most organizations are struggling to reduce their computing cost through the means of virtualization. This demand of reducing the computing cost has led to the innovation of cloud data management technologies. Cloud computing offers better computing through improved utilization, reduced infrastructure and maintenance costs, and increased flexibility to help meet changing business requirements. This paper gives a complete overview of cloud data management systems and their usefulness. In addition, it highlights some of the general cloud data management technologies available in the market and describes some of the development trends. It also examines the current challenges and risks facing the cloud data management technology deployments and provides highlights on the business opportunities.

The ability of a neuron to transduce extracellular signals into long lasting changes in neuronal morphology is central to its normal function. Increasing evidence shows that coordinated regulation of synaptic and nuclear signaling in response to NMDA receptor activation is crucial for long term memory, synaptic tagging, and epigenetic signaling. Although mechanisms have been proposed for synapse-to-nuclear communication, it is unclear how signaling is coordinated at both subcompartments. Here, we show that activation of NMDA receptors induces the bi-directional and concomitant shuttling of the scaffold protein afadin from the cytosol to the nucleus and synapses. Activity-dependent afadin nuclear translocation peaked 2 h post-stimulation, was independent of protein synthesis, and occurred concurrently with dendritic spine remodeling. Moreover, activity-dependent afadin nuclear translocation coincides with phosphorylation of histone H3 at serine 10 (H3S10p), a marker of epigenetic modification. Critically, blocking afadin nuclear accumulation attenuated activity-dependent dendritic spine remodeling and H3 phosphorylation. Collectively, these data support a novel model of neuronal nuclear signaling whereby dual-residency proteins undergo activity-dependent bi-directional shuttling from the cytosol to synapses and the nucleus, coordinately regulating dendritic spine remodeling and histone modifications.

Nkx2.5/Csx and dHAND/Hand2 are conserved transcription factors that are coexpressed in the precardiac mesoderm and early heart tube and control distinct developmental events during cardiogenesis. To understand whether Nkx2.5 and dHAND may function in overlapping genetic pathways, we generated mouse embryos lacking both Nkx2.5 and dHAND. Mice heterozygous for mutant alleles of Nkx2.5 and dHAND were viable. Although single Nkx2.5 or dHAND mutants have a morphological atrial and single ventricular chamber, Nkx2.5(-/-)dHAND(-/-) mutants had only a single cardiac chamber which was molecularly defined as the atrium. Complete ventricular dysgenesis was observed in Nkx2.5(-/-)dHAND(-/-) mutants; however, a precursor pool of ventricular cardiomyocytes was identified on the ventral surface of the heart tube. Because Nkx2.5 mutants failed to activate eHAND expression even in the early precardiac mesoderm, the Nkx2.5(-/-)dHAND(-/-) phenotype appears to reflect an effectively null state of dHAND and eHAND. Cell fate analysis in dHAND mutants suggests a role of HAND genes in survival and expansion of the ventricular segment, but not in specification of ventricular cardiomyocytes. Our molecular analyses also revealed the cooperative regulation of the homeodomain protein, Irx4, by Nkx2.5 and dHAND. These studies provide the first demonstration of gene mutations that result in ablation of the entire ventricular segment of the mammalian heart, and reveal essential transcriptional pathways for ventricular formation.

Two to three megabase deletions on chromosome 22q11 are the cytogenetic findings most commonly associated with cardiac and craniofacial defects in humans. The constellation of clinical findings associated with these deletions is termed the 22q11 deletion syndrome. We had earlier described a patient with the 22q11 deletion phenotype who was hemizygous for an atypical 20 kb microdeletion in this region. The deletion included coding regions of two genes organized head-to-head, UFD1L and CDC45L, along with an 884 bp CpG-rich intervening region. Based on this genomic organization, we hypothesized that both genes may be co-expressed and co-regulated by sequences within this region. We demonstrate that expression of both genes is enhanced in a similar pattern in precursors of structures affected by the deletion. The intergenic region is sufficient to direct transcription most strongly in the developing pharyngeal arches and limb buds of transgenic mice and can also direct bi-directional transcriptional activation in a neural crest-derived cell line. Deletion analyses revealed that a 404 bp fragment closest to UFD1L is necessary and sufficient to direct this bi-directional transcriptional activity. These results reveal the presence of a conserved regulatory region in the 22q11 deletion locus that can direct simultaneous transcription of genes involved in ubiquitin mediated protein processing (UFD1L) and cell cycle control (CDC45L).

The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND , are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are down-regulated in the adult. Their expression in specific chambers of healthy and diseased human hearts has not been studied previously. Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33, respectively, by fluorescent in situ hybridization. RNA from the four chambers of healthy human adult hearts, and from hearts of patients with several forms of cardiomyopathy, was obtained and assayed for dHAND and eHAND expression. Unlike in mice, dHAND expression was observed in all four chambers of the healthy human adult heart, but was diminished in the right atrium. In contrast, eHAND was expressed in the right and left ventricles, but was downregulated in both atrial chambers. We examined tissue from 15 human cardiomyopathic hearts obtained during cardiac transplantation or by endomyocardial biopsy for alterations in HAND gene expression. dHAND expression was unchanged in all forms of cardiomyopathy tested. However, cardiac expression of eHAND was severely down-regulated in six of six patients with ischemic cardiomyopathy and six of six patients with dilated cardiomyopathy. This study demonstrates that human dHAND and eHAND have unique spatial patterns of expression within human cardiac chambers. Downregulation of eHAND in ischemic and dilated cardiomyopathy suggests a correlation between eHAND dysregulation and the evolution of a subset of cardiomyopathies.

A conceptual framework to understand the chemical reactivity of fullerenes is developed as a design tool for nano-scale device applications. The internal and external chemical reactivity of fullerenes is found to depend strongly on the curvature and local atomic structure. As examples, we study C36, C60 and graphite, and use a hydrogen atom to probe chemical reactivity as a function of local atomic structure. The analysis shows that the balance of strain energy and chemical binding energy determines the local reactivity. This understanding provides an insight into the use of chemically doped endo-fullerenes as suitable target material for a recently proposed design of a solid-state quantum computer.

Appropriate interactions between the epithelium and adjacent neural crest-derived mesenchyme are necessary for normal pharyngeal arch development. Disruption of pharyngeal arch development in humans underlies many of the craniofacial defects observed in the 22q11.2 deletion syndrome (del22q11), but the genes responsible remain unknown. Tbx1 is a T-box transcription factor that lies in the 22q11.2 locus. Tbx1 transcripts were found to be localized to the pharyngeal endoderm and the mesodermal core of the pharyngeal arches, but were not present in the neural crest-derived mesenchyme of the pharyngeal arches. Sonic hedgehog (Shh) is also expressed in the pharyngeal arches and is necessary for normal craniofacial development. We found that Tbx1 expression was dependent upon Shh signaling in mouse embryos, consistent with their overlapping expression in the pharyngeal arches. Furthermore, Shh was sufficient to induce Tbx1 expression when misexpressed in selected regions of chick embryos. These studies reveal a Shh-mediated pathway that regulates Tbx1 during pharyngeal arch development.

Degradation of a low-density polyethylene (LDPE)/linear low-density polyethylene (LLDPE)/high-density polyethylene (HDPE) blend having different weight ratios of LLDPE (10–35 wt%) and HDPE (40–65 wt%) with fixed percentage of LDPE (25 wt%) was studied by aging the film samples at 55, 70, 85, and 100°C in air. Reactions involved in changing the molecular structure and formation of oxygenated and unsaturated groups during thermo-oxidative degradation are discussed. The molecular weight (M v) showed very little change in the initial hours of aging at different temperatures. Tensile strength was found to increase initially and then decrease with aging time. The increase in tensile strength suggests molecular enlargement, mainly by recombination of alkyl and alkoxy radicals, which produces nonradical products. The thermal stability decreases with increase in aging time and temperature.

Surface coatings based on ethyl silicate binders are categorised as inorganic coatings, whereas the conventional surface coatings which are mainly based on organic binders are referred to as organic coatings. Zinc-rich inorganic coatings based on ethyl silicate are quite successful for the protection of steel against corrosion under severe exposing conditions such as underground, marine atmosphere, industrial atmosphere, nuclear power plants, etc. These coatings provide unmatched corrosion protection to steel substrates exposed to high temperatures. Because of the formation of conductive matrix out of the binder after film curing, zinc-rich coatings based on ethyl silicate binder offer outstanding cathodic protection to steel structures. These coatings are mostly solvent-borne, but recently water-borne versions of the same have also been developed. However, the commercial success of water-borne systems is not yet well established. In the present article, the processes of hydrolysis of ethyl silicate in the presence of acidic and alkaline catalysts have been elaborated to produce ethyl silicate hydrolysates of desired degree of hydrolysis. Effect of various factors such as amount of catalysts, amount of water, type and amount of solvent, reaction temperature and reaction time has been discussed. Calculations to find out the amount of water and solvent required to yield the product of desired degree of hydrolysis have also been illustrated. Typical recipes useful for the preparation of ethyl silicate hydrolysates suitable for use as coating binders have also been presented. The chemistry and mechanism involved in the preparation of binder and the curing of film has also been discussed. This article also summarises the effect of various factors, viz. particle size and shape of zinc pigment, presence of extenders in the formulations, and the application technique on film performance. © 2001 Elsevier Science B.V. All rights reserved.

Blends of resole and epoxy were prepared by physical mixing, and cured with 30% polyamide based on blend resin and polyamide. Degradation of each sample was studied by dynamic thermogravimetric analysis in nitrogen atmosphere at a heating rate of 10°C min−1. The degradation of blends of epoxy and resole having 30 wt % polyamide proceeded with 0.50th order. This result was found with the Coats-Redfern equation using best-fit analysis, and further confirmed by linear regression analysis. The validity of data was checked by t test analysis. From this value of reaction order, activation energy (E) and pre-exponential factor (Z) were calculated. The values of activation energy increased, whereas the values of pre-exponential factor decreased as the resole content in the blend decreased from 100 to 0 wt %.

The thermal conductivity of several single-wall carbon nanotubes has been calculated over a temperature range of 100-500 K using molecular dynamics simulations with the Tersoff-Brenner potential for C-C interactions. In all cases, starting from similar values at 100 K, the thermal conductivities show a peaking behaviour before falling off at higher temperatures. The peak position shifts to higher temperatures for nanotubes with larger diameters and no significant dependence on the tube chirality is observed. It is shown that this phenomenon is due to the onset of Umklapp scattering, which shifts to higher temperatures for nanotubes with larger diameters.

The authors envision computational nanotechnology's role in developing the next generation of multifunctional materials and molecular-scale electronic and computing devices, sensors, actuators, and machines. They briefly review computational techniques and provide a few recent examples derived from computer simulations of carbon nanotube-based molecular nanotechnology. The four core areas are: molecular-scale, ultralightweight, extremely strong, functional or smart materials; molecular-scale or nanoscale electronics with possibilities for quantum computing; molecular-scale sensors or actuators; and molecular machines or motors with synthetic materials. The underlying molecular-scale building blocks in all four areas are fullerenes and carbon nanotube-based molecular materials. Only the different aspects of their physical, chemical, mechanical, and electronic properties create the many applications possible with these materials in vastly different areas.

Generalized anxiety disorder (GAD) is highly prevalent and incapacitating. Here we used the Carioca High-Conditioned Freezing (CHF) rats, a previously validated animal model for GAD, to identify biomarkers and structural changes in the hippocampus that could be part of the underlying mechanisms of their high-anxiety profile. Spatial and fear memory was assessed in the Morris water maze and passive avoidance test. Serum corticosterone levels, immunofluorescence for glucocorticoid receptors (GR) in the dentate gyrus (DG), and western blotting for hippocampal brain derived neurotrophic factor (BDNF) were performed. Immunohistochemistry for markers of cell proliferation (bromodeoxiuridine/Ki-67), neuroblasts (doublecortin), and cell survival were undertaken in the DG, along with spine staining (Golgi) and dendritic arborization tracing. Hippocampal GABA release was assessed by neurochemical assay.\ud \ud Fear memory was higher among CHF rats whilst spatial learning was preserved. Serum corticosterone levels were increased, with decreased GR expression. No differences were observed in hippocampal cell proliferation/survival, but the number of newborn neurons was decreased, along with their number and length of tertiary dendrites. Increased expression of proBDNF and dendritic spines was observed; lower ratio of GABA release in the hippocampus was also verified. These findings suggest that generalized anxiety/fear could be associated with different hippocampal biomarkers, such as increased spine density, possibly as a compensatory mechanism for the decreased hippocampal number of neuroblasts and dendritic arborization triggered by high corticosterone. Disruption of GABAergic signaling and BDNF impairment are also proposed as part of the hippocampal mechanisms possibly underlying the anxious phenotype of this model.

Abstract —Morphogenesis and developmental remodeling of cardiovascular tissues involve coordinated regulation of cell proliferation and apoptosis. In the heart, clear evidence points toward focal apoptosis as a contributor to development of the embryonic outflow tract, cardiac valves, conducting system, and the developing coronary vasculature. Apoptosis in the heart is likely regulated by survival and death signals that are also present in many other tissues. Cell type–specific regulation may be superimposed on general cell death/survival machinery through tissue-specific transcriptional pathways. In the vasculature, apoptosis almost certainly contributes to developmental vessel regression, and it is of proven importance in remodeling of arterial structure in response to local changes in hemodynamics. Physical forces, growth factors, and extracellular matrix drive vascular cell survival pathways, and considerable evidence points to local nitric oxide production as an important but complex regulator of vascular cell death. In both the heart and vasculature, progress has been impeded by inadequate information concerning the incidence of apoptosis, its relative importance compared with the diverse cell behaviors that remodel developing tissues, and by our primitive knowledge concerning regulation of cell death in these tissues. However, tools are now available to better understand apoptosis in normal and abnormal development of cardiovascular structures, and a framework has been established that should lead to considerable progress in the coming years.

Films of low-density (LD), high-density (HD) and linear low-density (LLD) polyethylenes have been prepared by melt blending in a single screw extruder (L/D ratio = 20 : 1). The film samples were aged at 50, 60, 70, 80, and 90°C for different time periods up to 750 h. A central composite rotatable design (CCRD) has been adopted to study the effect of blend composition, ageing time and ageing temperature on tensile strength using response surface methodology (RSM). Also, a linear second-order model has been developed to optimize and to study the interaction effects on tensile strength of the films. The optimized film sample had a maximum strength of 85.43 kg/cm2 when aged at 70°C for 333.5 h having 44.8, 27.7 and 27.7 wt.-% of LDPE, LLDPE and HDPE, respectively, in the blend system.

Congenital heart disease is the leading non-infectious cause of death in children. It is becoming increasingly clear that many cardiac abnormalities once thought to have multifactorial aetiologies are attributable to mutations in developmental control genes. The consequences of these mutations can be manifest at birth as life-threatening cardiac malformations or later as more subtle cardiac abnormalities. Understanding the genetic underpinnings of cardiac development has important implications not only for understanding congenital heart disease, but also for the possibility of cardiac repair through genetic reprogramming of non-cardiac cells to a cardiogenic fate.

A classification of conjugate vein arrays is proposed on the basis of three angular parameters that can be readily measured at outcrops. Relationships amongst these parameters imply that geometry of conjugate vein arrays varies within a continuous spectrum limited by three end-members. A new triangular plot is devised for representation of conjugate vein arrays, and its application is substantiated by several published and new examples. Evidence from overprinting relationships and consistency in the orientations of principal stresses imply that different types of conjugate vein arrays can develop in a common stress system.

In this note, the problem of a sphere carrying a fluid source at its centre and rotating with slow uniform angular velocity about a diameter is studied. The analysis reveals that only the azimuthal component of velocity exists and is seen that the effect of the source is to decrease it. Also, the couple on the sphere is found to decrease on account of the source.

Proper morphogenesis and positioning of internal organs requires delivery and interpretation of precise signals along the anterior-posterior, dorsal-ventral, and left-right axes. An elegant signaling cascade determines left- versus right-sided identity in visceral organs in a concordant fashion, resulting in a predictable left-right (LR) organ asymmetry in all vertebrates. The complex morphogenesis of the heart and its connections to the vasculature are particularly dependent upon coordinated LR signaling pathways. Disorganization of LR signals can result in myriad congenital heart defects that are a consequence of abnormal looping and remodeling of the primitive heart tube into a multi-chambered organ. A framework for understanding how LR asymmetric signals contribute to normal organogenesis has emerged and begins to explain the basis of many human diseases of LR asymmetry. Here we review the impact of LR signaling pathways on cardiac development and congenital heart disease.

Congenital heart disease (CHD) is the most common human birth defect worldwide,1 taking a tremendous toll on affected families, caregivers, and healthcare systems. Approximately 40 000 children are born each year in the United States with a heart malformation, and at least another 40 000 are born annually with subclinical malformations that result in heart disease later in adulthood. Significant advances in cardiac care and surgery have lowered mortality, and there are now >1 million survivors of CHD in the United States. As a result, the economic effects of CHD are substantial, particularly when lifetime costs of management are considered. Article see p 295 As an increasing proportion of the CHD population reaches reproductive age, questions of the genetic contribution to disease and risk of transmission have become paramount. Such individuals also often suffer age-dependent complications in heart function that may be related to the initial developmental and/or genetic insult that resulted in the CHD. Although their causes remain generally unknown, most CHDs are thought to have a multifactorial origin with an interplay of genetic and environmental effects.2 However, the relative contributions of genes and the environment have been difficult to discern. In this issue of Circulation , Oyen et al3 use a uniquely sized and annotated population to estimate recurrence risk for specific CHDs in families and thereby indirectly assess the role of genetic inheritance in CHD. A number of studies have attempted to quantify the risks conferred by a family history of CHD, demographic qualities, or environmental exposures.4,5 Gestational insults such as rubella infection and gestational diabetes can predispose to CHD, as can exposure to ethanol and other teratogens like retinoic acid.4,6 Although the incidence of CHD is higher in the setting of these exposures, most fetuses remain unaffected, suggesting that only a …

Despite intense attention, the mechanisms regulating dendritic spine structure remain elusive. In this issue of Neuron, Jaworski and colleagues explore the morphological consequences of periodic spine incursions of dynamic microtubules and their associated protein, EB3. Microtubules, long thought to be absent from dendritic spines, are capable of controlling spine morphology, opening up a new line of investigation into mechanisms of spine plasticity and maintenance.

In this paper a new approach to evaluate the drag force in a simple way on a restricted axially symmetric body placed in a uniform stream (i) parallel to its axis, (ii) transverse to its axis, is advanced when the flow is governed by the Stokes equations. The method exploits the well-known integral for evaluating the drag on a sphere. The method not only provides the value of the drag on prolate and oblate spheroids and a deformed sphere in axial flow which already exists in literature but also new results for a cycloidal body, an egg shaped body and a deformed sphere in transverse flow. The salient results are exhibited graphically. The limitations imposed on the analysis because of the lack of fore and aft symmetry in the case of an eggshaped body is also indicated. It is also seen that the analysis can be extended to calculate the couple on a body rotating about its axis of symmetry.

Nano-plasticity of thin single-wall carbon nanotubes under uniaxial compression is investigated through generalized tight-binding molecular dynamics (GTBMD) and ab-initio electronic structure methods. A novel mechanism of nano-plasticity of carbon nanotubes under uniaxial compression is observed in which bonding geometry collapses from a graphitic (sp(sup 2)) to a localized diamond like (sp(sup 3)) reconstruction. The computed critical stress (approximately equals 153 G Pa) and the shape of the resulting plastic deformation is in good agreement with recent experimental observation of collapse and fracture of compressed carbon nanotubes in polymer composites.

Several factors influence the tensile strength during the degradation of nylon-6 films viz. antioxidant concentration, aging time and aging temperature. A 3×5 experimental design has been adopted to study the effect of these factors using Response Surface Methodology. A linear second-order model has been developed to optimize and to study the interaction effects on tensile strength of the nylon-6 films.

Simulation calculations were carried out to investigate the energetics of adsorption and desorption processes taking place during etching of the Si(100) surface by Cl atoms. Clean and fully chlorinated surfaces with step edges were taken into consideration. Attachment energies of Cl atoms at step edge sites and subsequent detachment (etching) energies of SiClx species were calculated. Configurational characteristics of Cl bonded regions were also investigated. Results provide a systematic description of Cl adsorption and etching processes.

The possibility of nanoscale etching and indentation of Si(001)(2x1) surface by (8,0) and (10,10) carbon nanotube tips is demonstrated, for the first time, by classical molecular dynamics simulations employing Tersoff's many-body potential for a mixed C/Si/Ge system. In the nanotube tip barely touching the surface scenario atomistic etching is observed, where as in the nanoindentation scenario nanotube tip penetrates the surface without much hindrance. The results are explained in terms of the relative strength of C-C, C-Si, and Si-Si bonds.

The structure of boron nitride nanotubes is investigated using a generalized tight-binding molecular dynamics method. It is shown that dynamic relaxation results in a wavelike or "rippled" surface in which the B atoms rotate inward and the N atoms move outward, reminiscent of the surface relaxation of the III-V semiconductors. More importantly, the three different morphologies of the tube closing with flat, conical and amorphous ends, as observed in experiments, are shown to be directly related to the tube chiralities. The abundance of flat end tubes observed in experiments is, thus, shown to be an indication of the greater stability of "zig-zag" BN tubes over the "arm-chair" tubes under experimental conditions.

Simulations that model the effects of conformational strain on the chemical reactivity of single-walled carbon nanotubes suggest a method for significantly enhancing their reactivity locally by controlled deformations. The chemisorption of hydrogen atoms is predicted to be enhanced by as much as 1.6 eV at regions of high conformational deformation, suggesting that local reactivity will be significantly enhanced. Analysis of the local electronic density of states suggests the introduction of radical p orbital character to the sites that are locally deformed, consistent with the heightened reactivity and large pyramidalization angles at these sites. Preliminary experimental data consistent with this predicted heightened reactivity is also presented.

Fluorination of a dimerized Si(001)-2×1 surface near single-layer high step edges has been studied with molecular statics and dynamics simulations using the Stillinger–Weber potential for Si–Si, Si–F, and F–F interactions. Binding energies for up to three F atoms on Si atoms at the step edges have been investigated for fully relaxed systems. We find that F-bonded Si atoms relax away from the surface with increasing fluorination which lowers the desorption/etching energies of SiFx(x=1,3) species. Room temperature molecular dynamics simulations then show direct etching of SiF3 from Si atoms bonded to step edges. The calculations predict an anisotropy in the step edge induced etching of the Si(001)-2×1 surface. This is in qualitative agreement with an experimental observation on the same surface though using Cl instead of F atoms.

Optimal and nonoptimal methods of fault‐slip analysis are tested on the simple type of kink bands by treating these structures as if they were striated faults. Results from different graphical and numerical techniques are mutually consistent and all imply development of these kink bands in a thrust regime as a consequence of NNW‐SSE‐oriented maximum compression ( \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackage[OT2,OT1]{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cyr} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} \landscape $\sigma _{\mathrm{l}\,}$ \end{document} ‐axis). These results are confirmed independently by comparing the geome...

The interaction of a carbon nanotube tip with two chemically modified caps with a single-height-stepped C diamond surface is studied by performing molecular dynamics simulations. The and radicals are attached to the end cap of a nanotube. The forces for solving the classical equations of motion are derived from Brenner's many-body reactive potential. Depending on the surface impact site, the nanotube initial velocity towards the diamond surface, and the nanotube withdrawal rate a variety of mechano-chemical reactions have been observed. The strong tip-surface interaction results in creation of chemically different nanostructures on the diamond surface for tip, while the tip with allows us to remove a dimer of carbon atoms from the upper terrace of diamond. The possibility of using a nanotube with chemically modified caps for selective etching and nanolithography on different semiconductor surfaces is discussed.

A kink-band can be graphically represented as a point on an equilateral triangle whose vertices define the angles between external foliation and kink plane, between internal foliation and kink plane, and between internal- and external-foliations. Four typical deformation paths that correspond to the four modes of kink-band growth can be discerned on this triangle. The three linear relationships between each of the kink-band angles and the inclination of the σ1-axis with respect to the unrotated layering can be transformed into a straight line on the triangular plot. Application of this plot in paleostress analysis is demonstrated by several examples. The method, however, yields best results when a large number of data on the kink-band angles are plotted and contoured on the triangular graph.

Deepak Srivastava is a Director at the Gladstone Institute of Cardiovascular Disease and a Distinguished Professor in Paediatric Developmental Cardiology at the University of California, San Francisco. As well as caring for sick children as a physician at the Benioff Children's Hospital in San Francisco, he runs an active research group that studies the biology of heart development and regeneration. In March 2015, we met up with Deepak and asked him about his career.

Recent advances in fullerene science and technology suggest that it may be possible, in the distant future, to design and build atomically precise programmable machines composed largely of functionalized fullerenes. Large numbers of such machines with appropriate interconnections could conceivably create a material able to react to the environment and repair itself. This paper reviews some of the experimental and theoretical work relating to these materials, sometimes called machine phase, including the fullerene gears and high-density memory recently designed and simulated in our laboratory.

Complex three-point junctions of single-walled carbon nanotubes are proposed as building blocks of nanoscale electronic devices. Both T- and Y-junctions, made up of tubes with differing diameters and chiralities, are studied as prototypes. All the proposed complex junctions have been found to be local minima of the total energy on relaxation with a generalized tight-binding molecular dynamics scheme.

Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived branchial arches and branchial arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the branchial arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second arches are hypoplastic secondary to programmed cell death and the third and fourth arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the branchial arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null branchial arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal branchial arch. Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome.

The carbon nanotube junctions have recently emerged as excellent candidates for use as the building blocks in the formation of nanoscale electronic devices. While the simple joint of two dissimilar tubes can be generated by the introduction of a pair of heptagon-pentagon defects in an otherwise perfect hexagonal graphene sheet, more complex joints require other mechanisms. In this work we explore structural and electronic properties of complex three-point junctions of carbon nanotubes using a generalized tight-binding molecular-dynamics scheme.

The carbon nanotube junctions have recently emerged as excellent candidates for use as the building blocks in the formation of nanoscale molecular electronic networks. While the simple joint of two dissimilar tubes can be generated by the introduction of a pair of heptagon-pentagon defects in an otherwise perfect hexagonal graphene sheet, more complex joints require other mechanisms. In this work we explore structural characteristics of complex 3-g38 point junctions of carbon nanotubes using a generalized tight-binding molecular-dynamics scheme. The study of pi-electron local densities of states (LDOS) of these junctions reveal many interesting features, most prominent among them being the defect-induced states in the gap.

DNA polymerase beta is required in mammalian cells for the predominant pathway of base excision repair involving single nucleotide gap filling DNA synthesis. Here we examine the relationship between oxidative stress, cellular levels of DNA polymerase beta and base excision repair capacity in vitro , using mouse monocytes and either wild-type mouse fibroblasts or those deleted of the DNA polymerase beta gene. Treatment with an oxidative stress-inducing agent such as hydrogen peroxide, 3-morpholinosydnonimine, xanthine/xanthine oxidase or lipopolysaccharide was found to increase the level of DNA polymerase beta in both monocytes and fibroblasts. Base excision repair capacity in vitro , as measured in crude cell extracts, was also increased by lipopolysaccharide treatment in both cell types. In monocytes lipopolysaccharide-mediated up-regulation of the base excision repair system correlated with increased resistance to the monofunctional DNA alkylating agent methyl methanesulfonate. By making use of a quantitative PCR assay to detect lesions in genomic DNA we show that lipopolysaccharide treatment of fibroblast cells reduces the incidence of spontaneous DNA lesions. This effect may be due to the enhanced DNA polymerase beta-dependent base excision repair capacity of the cells, because a similar decrease in DNA lesions was not observed in cells deficient in base excision repair by virtue of DNA polymerase beta gene deletion. Similarly, fibroblasts treated with lipopolysaccharide were more resistant to methyl methanesulfonate than untreated cells. This effect was not observed in cells deleted of the DNA polymerase beta gene. These results suggest that the DNA polymerase beta-dependent base excision repair pathway can be up-regulated by oxidative stress-inducing agents in mouse cell lines.

The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Hand2 is expressed in the deciduum. Previous studies have demonstrated that Hand2 is required for formation of the right ventricle of the heart and the aortic arch arteries. We have generated a germline mutation in the mouse Hand1 gene by replacing the first coding exon with a beta-galactosidase reporter gene. Embryos homozygous for the Hand1 null allele died between embryonic days 8.5 and 9.5 and exhibited yolk sac abnormalities due to a deficiency in extraembryonic mesoderm. Heart development was also perturbed and did not progress beyond the cardiac-looping stage. Our results demonstrate important roles for Hand1 in extraembryonic mesodermal and heart development.

A phenomenological model for the rotational dynamics of a single laser-powered molecular motor is discussed and tested through molecular dynamics simulations. The motor is used to power carbon nanotube-based gears. For a given laser power density and arrangement of free charges in the body of the gear we have defined an intrinsic frequency of the gear oscillatory rotations. The nanotube rotations are not of an oscillatory nature if the laser field frequency is of the same order of magnitude as the intrinsic frequency of the tube and there is an additional phase match between the two. For the laser-powered gear motor dynamics, the rotational angular momentum of the driven gear tend to stabilize the rotational dynamics of the system, and unidirectional rotations for the entire duration of the simulations are observed.

During heart formation in all vertebrate species, the linear heart tube undergoes rightward looping followed by the formation of the atrial and ventricular chambers. The direction of cardiac looping is determined in part by the asymmetric expression of members of the transforming growth factor beta family across the left-right axis of the embryo. The basic helix-loop-helix (bHLH) transcription factors dHAND and eHAND are expressed in the heart tube within specific cardiogenic precursors destined to form the right and left ventricular regions, respectively, and loss-of-function experiments have demonstrated the importance of these factors for looping morphogenesis and ventricular development. We propose a model in which the HAND gene products interpret asymmetric positional information in the developing heart and participate in transcriptional programmes that control development of the right and left ventricular compartments of the heart.

The vibrational dynamics of hydrogen on low-index diamond surfaces is studied by the molecular dynamics method using an empirical Molecular Mechanics (MM3) potential. We find that the CH stretching peak positions in the vibrational spectra of hydrogen are sensitive to the surface structure and can be used for the experimental in situ analysis of the growing CVD diamond phase. The differences in the spectral features corresponding to the CH bending vibrations have been correlated with the results of the vibrational energy relaxation rate estimates. We find that the major contributions to the lifetimes of the excited CH stretching states come from the anharmonic coupling between the CH stretching and CCH bending vibration modes. The latter is highly coupled with the substrate phonons which leads to the formation of broad spectral regions associated with CCH bending vibrations. The dynamic analysis of the motion induced by the symmetric and antisymmetric stretching excitation on C {100} (2 × 1) H surface have been performed and the reasons for the unstability of the pure antisymmetric vibrations are discussed.

Blends of resole with epoxy resin (General Purpose) having different weight ratios (0/100, 25/75, 50/50, 75/25, and 100/0) based on physical mixing have been prepared. These blends were cured by adding polyamide in a 60:40 ratio based on blend resins and polyamide. The degradation kinetics of these resins was studied by dynamic thermogravimetric analysis in nitrogen atmosphere at a heating rate of 15°C/min by using the Coats-Redfern equation. It is concluded that the degradation of each sample follows first-order (n = 1) degradation kinetics. This is obtained on the basis of best fit analysis, and all the parameters are confirmed by regression analysis. From the reaction order value, activation energy (E) and preexponential factor (Z) were calculated by the slope and intercept of the plot between X and Y, respectively.