Fiber Beam Analysis of Reinforced Concrete Members with Cyclic Constitutive and Material Laws

This paper presents a non-linear Timoshenko beam element with axial, bending, and shear force interaction for nonlinear analysis of reinforced concrete structures. The structural material tangent stiffness matrix, which relates the increments of load to corresponding increments of displacement, is properly formulated. Appropriate simplified cyclic uniaxial constitutive laws are developed for cracked concrete in compression and tension. The model also includes the softening effect of the concrete due to lateral tensile strain. To establish the validity of the proposed model, correlation studies with experimentally-tested concrete specimens have been conducted

The relevance of outsourcing and leagile strategies in performance optimization of an integrated process planning and scheduling

Over the past few years growing global competition has forced the manufacturing industries to upgrade their old production strategies with the modern day approaches. As a result, recent interest has been developed towards finding an appropriate policy that could enable them to compete with others, and facilitate them to emerge as a market winner. Keeping in mind the abovementioned facts, in this paper the authors have proposed an integrated process planning and scheduling model inheriting the salient features of outsourcing, and leagile principles to compete in the existing market scenario. The paper also proposes a model based on leagile principles, where the integrated planning management has been practiced. In the present work a scheduling problem has been considered and overall minimization of makespan has been aimed. The paper shows the relevance of both the strategies in performance enhancement of the industries, in terms of their reduced makespan. The authors have also proposed a new hybrid Enhanced Swift Converging Simulated Annealing (ESCSA) algorithm, to solve the complex real-time scheduling problems. The proposed algorithm inherits the prominent features of the Genetic Algorithm (GA), Simulated Annealing (SA), and the Fuzzy Logic Controller (FLC). The ESCSA algorithm reduces the makespan significantly in less computational time and number of iterations. The efficacy of the proposed algorithm has been shown by comparing the results with GA, SA, Tabu, and hybrid Tabu-SA optimization methods

Ndel1 and Reelin Maintain Postnatal CA1 Hippocampus Integrity

How the integrity of laminar structures in the postnatal brain is maintained impacts neuronal functions. Ndel1, the mammalian homolog of NuDE from the filamentous fungus Aspergillus nidulans, is an atypical microtubule (MT)-associated protein that was initially investigated in the contexts of neurogenesis and neuronal migration. Constitutive knock-out mice for Ndel1 are embryonic lethal, thereby necessitating the creation a conditional knock-out to probe the roles of Ndel1 in postnatal brains. Here we report that CA1 pyramidal neurons from mice postnatally lacking Ndel1 (Ndel1 conditional knock-out) exhibit fragmented MTs, dendritic/synaptic pathologies, are intrinsically hyperexcitable and undergo dispersion independently of neuronal migration defect. Secondary to the pyramidal cell changes is the decreased inhibitory drive onto pyramidal cells from interneurons. Levels of the glycoprotein Reelin that regulates MTs, neuronal plasticity, and cell compaction are significantly reduced in hippocampus of mutant mice. Strikingly, a single injection of Reelin into the hippocampus of Ndel1 conditional knock-out mice ameliorates ultrastructural, cellular, morphological, and anatomical CA1 defects. Thus, Ndel1 and Reelin contribute to maintain postnatal CA1 integrity.1112Ysciescopu

Coherent quantum state storage and transfer between two phase qubits via a resonant cavity

A network of quantum-mechanical systems showing long lived phase coherence of its quantum states could be used for processing quantum information. As with classical information processing, a quantum processor requires information bits (qubits) that can be independently addressed and read out, long-term memory elements to store arbitrary quantum states, and the ability to transfer quantum information through a coherent communication bus accessible to a large number of qubits. Superconducting qubits made with scalable microfabrication techniques are a promising candidate for the realization of a large scale quantum information processor. Although these systems have successfully passed tests of coherent coupling for up to four qubits, communication of individual quantum states between qubits via a quantum bus has not yet been demonstrated. Here, we perform an experiment demonstrating the ability to coherently transfer quantum states between two superconducting Josephson phase qubits through a rudimentary quantum bus formed by a single, on chip, superconducting transmission line resonant cavity of length 7 mm. After preparing an initial quantum state with the first qubit, this quantum information is transferred and stored as a nonclassical photon state of the resonant cavity, then retrieved at a later time by the second qubit connected to the opposite end of the cavity. Beyond simple communication, these results suggest that a high quality factor superconducting cavity could also function as a long term memory element. The basic architecture presented here is scalable, offering the possibility for the coherent communication between a large number of superconducting qubits.Comment: 17 pages, 4 figures (to appear in Nature

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Use of the internet for sexual health among sexually experienced persons aged 16 to 44 years: evidence from a nationally representative survey of the British population

BACKGROUND: Those who go online regarding their sexual health are potential users of new Internet-based sexual health interventions. Understanding the size and characteristics of this population is important in informing intervention design and delivery. OBJECTIVE: We aimed to estimate the prevalence in Britain of recent use of the Internet for key sexual health reasons (for chlamydia testing, human immunodeficiency virus [HIV] testing, sexually transmitted infection [STI] treatment, condoms/contraceptives, and help/advice with one's sex life) and to identify associated sociodemographic and behavioral factors. METHODS: Complex survey analysis of data from 8926 sexually experienced persons aged 16-44 years in a 2010-2012 probability survey of Britain's resident population. Prevalence of recent (past year) use of Internet sources for key sexual health reasons was estimated. Factors associated with use of information/support websites were identified using logistic regression to calculate age-adjusted odds ratios (AORs). RESULTS: Recent Internet use for chlamydia/HIV testing or STI treatment (combined) was very low (men: 0.31%; women: 0.16%), whereas 2.35% of men and 0.51% of women reported obtaining condoms/contraceptives online. Additionally, 4.49% of men and 4.57% of women reported recent use of information/support websites for advice/help with their sex lives. Prevalence declined with age (men 16-24 years: 7.7%; 35-44 years: 1.84%, P<.001; women 16-24 years: 7.8%; 35-44 years: 1.84%, P<.001). Use of information/support websites was strongly associated with men's higher socioeconomic status (managerial/professional vs semiroutine/routine: AOR 1.93, 95% CI 1.27-2.93, P<.001). Despite no overall association with area-level deprivation, those in densely populated urban areas were more likely to report use of information/support websites than those living in rural areas (men: AOR 3.38, 95% CI 1.68-6.77, P<.001; women: AOR 2.51, 95% CI 1.34-4.70, P<.001). No statistically significant association was observed with number of sex partners reported after age adjustment, but use was more common among men reporting same-sex partners (last 5 years: AOR 2.44, 95% CI 1.27-4.70), women reporting sex with multiple partners without condoms (last year: AOR 1.90, 95% CI 1.11-3.26), and, among both sexes, reporting seeking sex online (last year, men: AOR 1.80, 95% CI 1.16-2.79; women: AOR 3.00, 95% CI 1.76-5.13). No association was observed with reporting STI diagnosis/es (last 5 years) or (after age adjustment) recent use of any STI service or non-Internet sexual health seeking. CONCLUSIONS: A minority in Britain used the Internet for the sexual health reasons examined. Use of information/support websites was reported by those at greater STI risk, including younger people, indicating that demand for online STI services, and Internet-based sexual health interventions in general, may increase over time in this and subsequent cohorts. However, the impact on health inequalities needs addressing during design and evaluation of online sexual health interventions so that they maximize public health benefit

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand