Deficiency of Pkc1 activity affects glycerol metabolism in Saccharomyces cerevisiae

In pressProtein kinase C is apparently involved in the control of many cellular systems: the cell wall integrity pathway, the synthesis of ribosomes, the appropriated reallocation of transcription factors under specific stress conditions and also the regulation of N-glycosylation activity. All these observations suggest the existence of additional targets not yet identified. In the context of the control of carbon metabolism, previous data demonstrated that Pkc1 p might play a central role in the control of cellular growth and metabolism in yeast. In particular, it has been suggested that it might be involved in the derepression of genes under glucose-repression by driving an appropriated subcellular localization of transcriptional factors, such as Mig1 p. In this work, we show that pkc1∆ mutant is unable to grow on glycerol because it cannot perform the derepression of GUT1 gene that encodes for glycerol kinase. Additionally, active transport is also partially affected. Using this phenotype, we were able to isolate a new pkc1∆ revertant. We also isolated two transformants identified as the nuclear exportin Msn5 and the histone deacetylase Hos2 extragenic suppressors of this mutation. Based on these results, we postulate that Pkc1 p may be involved in the control of the cellular localization and/or regulation of the activity of nuclear proteins implicated in gene expression.Fundação Universidade Federal de Ouro Preto (FUFOP). Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) - CBS-1875/95. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - 300998/89-9 to R.L.B., 301255/01-6 to L.G.F

An interlaboratory comparison on the characterization of a sub-micrometer polydisperse particle dispersion

The measurement of polydisperse protein aggregates and particles in biotherapeutics remains a challenge, especially for particles with diameters of ≈ 1 µm and below (sub-micrometer). This paper describes an interlaboratory comparison with the goal of assessing the measurement variability for the characterization of a sub-micrometer polydisperse particle dispersion composed of five sub-populations of poly(methyl methacrylate) (PMMA) and silica beads. The study included 20 participating laboratories from industry, academia, and government, and a variety of state-of-the-art particle-counting instruments. The received datasets were organized by instrument class to enable comparison of intralaboratory and interlaboratory performance. The main findings included high variability between datasets from different laboratories, with coefficients of variation from 13 % to 189 %. Intralaboratory variability was, on average, 37 % of the interlaboratory variability for an instrument class and particle sub-population. Drop-offs at either end of the size range and poor agreement on maximum counts of particle sub-populations were noted. The mean distributions from an instrument class, however, showed the size-coverage range for that class. The study shows that a poly-disperse sample can be used to assess performance capabilities of an instrument set-up (including hardware, software, and user settings) and provides guidance for the development of polydisperse reference materials.Drug Delivery Technolog

Design and performance of profiled dielectric-loaded horns

Profiled dielectric loaded horns are investigated with the aim of obtaining low peak crosspolar level and high aperture efficiency. A number of nonlinear profiles are considered. The paper also looks into the influence of profiling on the bandwidth of the horn and the effect of nonuniformities in the dielectric material on horn performance

Antiretroviral therapy for HIV prevention: many concerns and challenges, but are there ways forward in sub-Saharan Africa?

Scientists from the WHO have presented a theoretical mathematical model of the potential impact of universal voluntary HIV testing and counselling followed by immediate antiretroviral therapy (ART). The results of the model suggests that, in a generalised epidemic as severe as that in sub-Saharan Africa (SSA), HIV incidence may be reduced by 95% in 10 years and that this approach may be cost effective in the medium term. This offers a 'ray of hope' to those who have thus far only dreamed of curbing the HIV/AIDS epidemic in SSA, as until now the glaring truth has been pessimistic. When it comes to ART, approximately 7 of 10 people who clinically need ART still do not receive it. From an epidemic point of view, for every person placed on ART an estimated four to six others acquire HIV. The likelihood of achieving the targets of the Millennium Development Goals for 2015 and universal ART access by 2010 are thus extremely low. A new window of opportunity may have now opened, but there are many unanswered feasibility and acceptability issues. In this paper, we highlight four key operational challenges linked to acceptability and feasibility and discuss possible ways forward to address them

Vital Registration in Rural Africa: Is There a Way Forward to Report on Health Targets of the Millennium Development Goals?

Vital registration - the systematic recording of births and deaths - has both legal and health significance. In particular, accurate recording and reporting of vital statistics are public goods to enable the monitoring of progress towards achieving health related targets of the 2015 United Nations Millennium Development Goals (MDG). The reality in Africa is that most births and deaths cannot be traced in legal records or official statistics and as such, there is currently no way of assessing progress towards achieving MDG targets and this applies particularly to rural settings in Africa. From the context of a rural district in Malawi, we describe an informal traditional system for the reporting of deaths at village level, and discuss the potential opportunities, challenges and ways forward in the wider implementation and interpretation of vital data generated by such a system. Such a system might provide an interim solution for accelerating the production and use of district level vital statistics for legal, administrative, statistical purposes and to report on the MDG in rural Africa while waiting for more comprehensive national systems to become a reality

Task shifting in HIV/AIDS: opportunities, challenges and proposed actions for sub-Saharan Africa.

Sub-Saharan Africa is facing a crisis in human health resources due to a critical shortage of health workers. The shortage is compounded by a high burden of infectious diseases; emigration of trained professionals; difficult working conditions and low motivation. In particular, the burden of HIV/AIDS has led to the concept of task shifting being increasingly promoted as a way of rapidly expanding human resource capacity. This refers to the delegation of medical and health service responsibilities from higher to lower cadres of health staff, in some cases non-professionals. This paper, drawing on Médecins Sans Frontières' experience of scaling-up antiretroviral treatment in three sub-Saharan African countries (Malawi, South Africa and Lesotho) and supplemented by a review of the literature, highlights the main opportunities and challenges posed by task shifting and proposes specific actions to tackle the challenges. The opportunities include: increasing access to life-saving treatment; improving the workforce skills mix and health-system efficiency; enhancing the role of the community; cost advantages and reducing attrition and international 'brain drain'. The challenges include: maintaining quality and safety; addressing professional and institutional resistance; sustaining motivation and performance and preventing deaths of health workers from HIV/AIDS. Task shifting should not undermine the primary objective of improving patient benefits and public health outcomes

Tageslichtnutzung in Gebaeuden, Nutzakzeptanz von Lichtsystemen Abschlussbericht

During the planning process of buildings the energy consciousness and the visual comfort is getting more and more important. Since there are new daylighting systems on the market which promise to increase both - energy savings and visual comfort - there was no possibility to check these promises or to plan these systems. For that reason new procedures to assess performance and user acceptance have been developed. New innovative systems have been selected and investigated. A suitable testing procedure has been developed to get the necessary optical and thermal data. The systems have been tested in scaled models, 1:1 rooms and in optical laboratories. A fully turnable 1:1 twin test room at Fraunhofer ISE has been built during the project. With that facility, comparable system data are collected. Actually it is used to evaluate new blind systems for industrial partners. At BLL new test rooms for performing the objective testing and for measuring the illuminance distribution have been set up. Together with the new developed objective testing procedure, these rooms are used for getting performance values. In the Philips rooms different controls for artificial lighting are investigated and user assessments are performed. Computer models for some of the new systems have been developed out of the laboratory measurements. The validation of the models with the 1:1 system measurements has been successful. Due to general restrictions of the simulation programs, it is impossible to model all types of system now. Further developments on the simulation programs are necessary. For the energy savings prediction a combined thermal and lighting simulation procedure has been developed, based on well defined optical and thermal models. A new procedure to investigate acceptance has been developed, based on photorealistic representation of computer-simulated scenes (SVR), which creates the impression of 3-D-virtual reality for the observer. A lot of calibration measurements were needed to get the correct luminance and color distribution. User assessments in real offices and in SVR have been performed. The results show a good correspondence for the SVR results, especially for glare and brightness issues. One of the main results is the non-existence of a glare or comfort index, because the range of answers is extremely broad. For a lot of the available systems it is now possible to evaluate the important issues user acceptance and energy savings. (orig.)SIGLEAvailable from TIB Hannover: F00B1174 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman