Regulation of vacuolar H+-ATPase activity by the Cdc42 effector Ste20 in Saccharomyces cerevisiae

In the budding yeast Saccharomyces cerevisiae, the Cdc42 effector Ste20 plays a crucial role in the regulation of filamentous growth, a response to nutrient limitation. Using the split-ubiquitin technique, we found that Ste20 forms a complex with Vma13, an important regulatory subunit of vacuolar H(+)-ATPase (V-ATPase). This protein-protein interaction was confirmed by a pulldown assay and coimmunoprecipitation. We also demonstrate that Ste20 associates with vacuolar membranes and that Ste20 stimulates V-ATPase activity in isolated vacuolar membranes. This activation requires Ste20 kinase activity and does not depend on increased assembly of the V1 and V0 sectors of the V-ATPase, which is a major regulatory mechanism. Furthermore, loss of V-ATPase activity leads to a strong increase in invasive growth, possibly because these cells fail to store and mobilize nutrients efficiently in the vacuole in the absence of the vacuolar proton gradient. In contrast to the wild type, which grows in rather small, isolated colonies on solid medium during filamentation, hyperinvasive vma mutants form much bigger aggregates in which a large number of cells are tightly clustered together. Genetic data suggest that Ste20 and the protein kinase A catalytic subunit Tpk2 are both activated in the vma13Δ strain. We propose that during filamentous growth, Ste20 stimulates V-ATPase activity. This would sustain nutrient mobilization from vacuolar stores, which is beneficial for filamentous growth.The project was supported by Deutsche Forschungsgemeinschaft grant HO 2098/3 to T.H. and NIH grant R01 GM50322 to P.M.K

Societal Change and Values in Arab Communities in Israel: Intergenerational and Rural–Urban Comparisons

This study tested and extended Greenfield’s theory of social change and human development to adolescent development in Arab communities in Israel undergoing rapid social change. The theory views sociodemographic changes—such as contact with an ethnically diverse urban setting and spread of technology—as driving changes in cultural values. In one research design, we compared three generations, high school girls, their mothers, and their grandmothers, in their responses to value-assessment scenarios. In a second research design, we compared girls going to high school in an ethnically diverse city with girls going to school in a village. As predicted by the theory, a t test and ANOVA revealed that both urban life and membership in the youngest generation were significantly related to more individualistic and gender-egalitarian values. Regression analysis and a bootstrapping mediation analysis showed that the mechanism of change in both cases was possession of mobile technologies

Performance evaluation of MPLS-enabled communications infrastructure for wide area monitoring systems

In order to obtain the transient power system measurement information, Wide Area Monitoring Systems (WAMS) should be able to collect Phasor Measurement Unit (PMU) data in a timely manner. Therefore along with the continual deployment of PMUs in Great Britain (GB) transmission system substations, a high performance communications infrastructure is becoming essential with regard to the establishment of reliable WAMS. This paper focuses mainly on evaluating the performance of the real-time WAMS communication infrastructure when Multi-Protocol Label Switching (MPLS) capability is added to a conventional IP network. Furthermore, PMU communications from geographically distributed substations to a Phasor Data Concentrator (PDC) are investigated over different transport protocols. Using OPNET Modeler, simulations are performed based on the existing WAMS infrastructure as installed on the GB transmission system. The simulation results are analyzed in detail in order to fully determine the different characteristics of communication delays between PMUs and PDC

Work domain analysis and intelligent transport systems: Implications for vehicle design

This article presents a Work Domain Analysis (WDA) of the road transport system in Victoria, Australia. A series of driver information requirements and tasks that could potentially be supported through the use of Intelligent Transport Systems (ITS) are then extracted from the WDA. The potential use of ITS technologies to circumvent these information gaps and provide additional support to drivers is discussed. It is concluded that driver information requirements are currently not entirely satisfied by contemporary vehicle design and also that there are a number of driving tasks that could be further supported through the provision of supplementary systems within vehicles

Parallel detrended fluctuation analysis for fast event detection on massive PMU data

("(c) 2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.")Phasor measurement units (PMUs) are being rapidly deployed in power grids due to their high sampling rates and synchronized measurements. The devices high data reporting rates present major computational challenges in the requirement to process potentially massive volumes of data, in addition to new issues surrounding data storage. Fast algorithms capable of processing massive volumes of data are now required in the field of power systems. This paper presents a novel parallel detrended fluctuation analysis (PDFA) approach for fast event detection on massive volumes of PMU data, taking advantage of a cluster computing platform. The PDFA algorithm is evaluated using data from installed PMUs on the transmission system of Great Britain from the aspects of speedup, scalability, and accuracy. The speedup of the PDFA in computation is initially analyzed through Amdahl's Law. A revision to the law is then proposed, suggesting enhancements to its capability to analyze the performance gain in computation when parallelizing data intensive applications in a cluster computing environment

Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines

We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC50 in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least equivalent pro-apoptotic effect than curcumin. The analysis of molecular mechanisms of action of the curcumin derivatives under study has highlighted that they decreased NF-κB transcriptional factor activity, and consequently the expression of some NF-κB targets. Our data confirmed once again that curcumin may represent a very good lead compound to design analogues with higher antitumor capacities and able to overcome drug resistance with respect to conventional ones, even in tumors difficult to treat as TNBC

Wheatering tight economic times: the sales evolution of consumer durables over the business cycle.

Despite its obvious importance, not much marketing research focuses on how business-cycle fluctuations affect individual companies and/or industries. Often, one only has aggregate information on the state of the national economy, even though cyclical contractions and expansions need not have an equal impact on every industry, nor on all firms in that industry. Using recent time-series developments, we introduce various measures to quantify the extent and nature of business-cycle fluctuations in sales. Specifically, we discuss the notions of cyclical volatility and cyclical comovement, and consider two types of cyclical asymmetry related, respectively, to the relative size of the peaks and troughs and the rate of change in upward versus downward parts of the cycle. In so doing, we examine how consumers adjust their purchasing behavior across different phases of the business cycle. We apply these concepts to a broad set (24) of consumer durables, for which we analyze the cyclical sensitivity in their sales evolution. In that way, we (i) derive a novel set of empirical generalizations, and (ii) test different marketing theory-based hypotheses on the underlying drivers of cyclical sensitivity. Consumer durables are found to be more sensitive to business-cycle fluctuations than the general economic activity, as expressed in an average cyclical volatility of more than four times the one in GNP, and an average comovement elasticity in excess of 2. This observation calls for an explicit consideration of cyclical variation in durable sales. Moreover, even though no evidence is found for depth asymmetry, the combined evidence across all durables suggests that asymmetry is present in the speed of up- and downward movements, as durables' sales falls much quicker during contractions than recover during economic expansions. Finally, key variables related to the industry's pricing activities, the nature of the durable (convenience vs. leisure), and the stage in a product's life cycle tend to moderate the extent of cyclical sensitivity in durable sales patterns.Business cycles; Companies; Consumer durables; Econometrics; Economy; Firms; Hypotheses; Industry; Information; Market; Marketing; Pricing; Product; Purchasing; Sales; Sales evolution; Sensitivity; Size; Time; Time-series econometrics; Time series; Variables; Volatility;

The essential signature of a massive starburst in a distant galaxy

Observations of carbon monoxide (CO) emission in high redshift (z>2) galaxies indicate the presence of large amounts of molecular gas. Many of these galaxies contain an active galactic nucleus (AGN) powered by accretion of gas onto a supermassive black hole, and a key question is whether their extremely high infrared luminosities result from the AGN, or from bursts of massive star formation (associated with the molecular gas), or both. In the Milky Way, high-mass stars form in the dense cores of interstellar molecular clouds; gas densities are n(H2)>105 cm-3 in the cores. Recent surveys show that virtually all galactic sites of high-mass star formation have similarly high densities. The bulk of the cloud material traced by CO observations is at a much lower density. In galaxies in the local Universe, the HCN(J=1-0) line is an effective tracer of the high-density molecular gas. Here we report observations of HCN emission in the early Universe from the infrared luminous 'Cloverleaf' quasar (at a redshift z=2.5579). The HCN line luminosity indicates the presence of 10 billion solar masses of very dense gas, an essential feature of an immense starburst that contributes, together with the AGN it harbors, to its high infrared luminosity.Comment: PDF pape

A semi-supervised approach to visualizing and manipulating overlapping communities

When evaluating a network topology, occasionally data structures cannot be segmented into absolute, heterogeneous groups. There may be a spectrum to the dataset that does not allow for this hard clustering approach and may need to segment using fuzzy/overlapping communities or cliques. Even to this degree, when group members can belong to multiple cliques, there leaves an ever present layer of doubt, noise, and outliers caused by the overlapping clustering algorithms. These imperfections can either be corrected by an expert user to enhance the clustering algorithm or to preserve their own mental models of the communities. Presented is a visualization that models overlapping community membership and provides an interactive interface to facilitate a quick and efficient means of both sorting through large network topologies and preserving the user's mental model of the structure. © 2013 IEEE

Assessing the short-term outcomes of a community-based intervention for overweight and obese children: The MEND 5-7 programme

Objective The aim of this study was to report outcomes of the UK service level delivery of MEND (Mind,Exercise,Nutrition...Do it!) 5-7, a multicomponent, community-based, healthy lifestyle intervention designed for overweight and obese children aged 5–7 years and their families. Design Repeated measures. Setting Community venues at 37 locations across the UK. Participants 440 overweight or obese children (42% boys; mean age 6.1 years; body mass index (BMI) z-score 2.86) and their parents/carers participated in the intervention. Intervention MEND 5-7 is a 10-week, family-based, child weight-management intervention consisting of weekly group sessions. It includes positive parenting, active play, nutrition education and behaviour change strategies. The intervention is designed to be scalable and delivered by a range of health and social care professionals. Primary and secondary outcome measures The primary outcome was BMI z-score. Secondary outcome measures included BMI, waist circumference, waist circumference z-score, children's psychological symptoms, parenting self-efficacy, physical activity and sedentary behaviours and the proportion of parents and children eating five or more portions of fruit and vegetables. Results 274 (62%) children were measured preintervention and post-intervention (baseline; 10-weeks). Post-intervention, mean BMI and waist circumference decreased by 0.5 kg/m2 and 0.9 cm, while z-scores decreased by 0.20 and 0.20, respectively (p<0.0001). Improvements were found in children's psychological symptoms (−1.6 units, p<0.0001), parent self-efficacy (p<0.0001), physical activity (+2.9 h/week, p<0.01), sedentary activities (−4.1 h/week, p<0.0001) and the proportion of parents and children eating five or more portions of fruit and vegetables per day (both p<0.0001). Attendance at the 10 sessions was 73% with a 70% retention rate. Conclusions Participation in the MEND 5-7 programme was associated with beneficial changes in physical, behavioural and psychological outcomes for children with complete sets of measurement data, when implemented in UK community settings under service level conditions. Further investigation is warranted to establish if these findings are replicable under controlled conditions