Lipid profiles for antiretroviral-naive patients starting PI- and NNRTI-based therapy in the Swiss HIV cohort study

BACKGROUND: Blood lipid abnormalities in patients on highly active antiretroviral therapy (HAART) have been associated with exposure to protease inhibitors (PIs), particularly ritonavir. First therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) leads to relatively favourable lipid profiles. We report on medium-term lipid profiles (up to 5 years) for antiretroviral-naive patients starting NNRTI- and PI-based HAART in the Swiss HIV Cohort Study. METHODS: Since April 2000, blood samples taken at visits scheduled every 6 months have been analysed for cholesterol and triglyceride concentrations. For 1065 antiretroviral-naive patients starting HAART after April 2000, we estimated changes in concentration over time using multivariate linear regression with adjustment for baseline covariates, use of lipid-lowering drugs and whether the sample was taken in a fasting state. RESULTS: Non-high density lipoprotein (HDL) cholesterol levels increase with increasing exposure to either PI- or NNRTI-based therapy, HDL cholesterol levels increase and triglyceride levels decrease with increasing exposure to NNRTI-based therapy, whereas triglyceride levels increase with increasing exposure to PI-based therapy. Between NNRTI-based therapies, there is a slight difference in triglyceride levels, which tend to increase with increasing exposure to efavirenz and to decrease with increasing exposure to nevirapine. Of the three common PI-based therapies, nelfinavir appears to have a relatively favourable lipid profile, with little change with increasing exposure. Of the other two PI therapies, lopinavir with ritonavir has a more favourable profile than indinavir with ritonavir, with smaller increases in both non-HDL cholesterol and triglycerides and an increase in HDL cholesterol. Increasing exposure to abacavir is associated with a decrease in the level of triglycerides. CONCLUSION: In general, NNRTI-based therapy is associated with a more favourable lipid profile than PI-based therapy, but different PI-based therapies are associated with very different lipid profiles. Nelfinavir appears to have a relatively favourable lipid profile. Of the two boosted PI therapies, lopinavir appears to have a more favourable lipid profile than indinavir.

Body fat changes among antiretroviral-naive patients on PI- and NNRTI-based HAART in the Swiss HIV cohort study

BACKGROUND: Body fat changes are common in patients with HIV. For patients on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), these changes have been associated with increasing exposure to therapy in general and to stavudine in particular. Our objective is to show whether such associations are more or less likely for patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. METHODS: We included all antiretroviral-naive patients in the Swiss HIV Cohort Study starting HAART after April 2000 who had had body weight, CD4 cell count and plasma HIV RNA measured between 6 months before and 3 months after starting HAART, and at least one assessment of body fat changes after starting HAART. At visits scheduled every 6 months, fat loss or fat gain is reported by agreement between patient and physician. We estimate the association between reported body fat changes and both time on therapy and time on stavudine, using conditional logistical regression. RESULTS: Body fat changes were reported for 85 (9%) out of 925 patients at their first assessment; a further 165 had only one assessment. Of the remaining 675 patients, body fat changes were reported for 156 patients at a rate of 13.2 changes per 100 patient-years. Body fat changes are more likely with increasing age [odds ratio (OR) 1.18 (1.00-1.38) per 10 years], with increasing BMI [OR 1.06 (1.01-1.11)] and in those with a lower baseline CD4 cell count [OR 0.91 (0.83-1.01) per 100 cells/microl]. There is only weak evidence that body fat changes are more likely with increasing time on HAART [OR 1.16 (0.93-1.46)]. After adjusting for time on HAART, fat loss is more likely with increasing stavudine use [OR 1.70 (1.34-2.15)]. There is no evidence of an association between reported fat changes and time on NNRTI therapy relative to PI therapy in those patients who used either one therapy or the other [OR 0.98 (0.56-1.63)]. CONCLUSION: Fat loss is more likely to be reported with increasing exposure to stavudine. We find no evidence of major differences between PI and NNRTI therapy in the risk of reported body fat changes.

Extraction of the s-wave pi N scattering lengths from data on pionic atoms

For many years a combined analysis of pionic hydrogen and deuterium atoms has been known as a good tool to extract information on the isovector and especially on the isoscalar s-wave pN scattering length. However, given the smallness of the isoscalar scattering length, the analysis becomes useful only if the pion–deuteron scattering length is controlled theoretically to a high accuracy comparable to the experimental precision. To achieve the required few-percent accuracy one needs theoretical control over all isospin-conserving three-body pNN !pNN operators up to one order before the contribution of the dominant unknown (N†N)2pp contact term. This term appears at next-to-next-to-leading order in Weinberg counting. In addition, one needs to include isospin-violating effects in both two-body (pN) and three-body (pNN) operators. In this talk we discuss the results of the recent analysis where these isospin-conserving and -violating effects have been carefully taken into account. Based on this analysis, we present the up-to-date values of the s-wave pN scattering lengths.

Photo-induced intramolecular charge transfer in an ambipolar field-effect transistor based on a pi-conjugated donor-acceptor dyad

A pi-conjugated tetrathiafulvalene-fused perylenediimide (TTF-PDI) molecular dyad is successfully used as a solution-processed active material for light sensitive ambipolar field-effect transistors with balanced hole and electron mobilities. The photo-response of the TTF-PDI dyad resembles its absorption profile. Wavelength-dependent photoconductivity measurements reveal an important photo-response at an energy corresponding to a PDI-localized electronic pi-pi* transition and also a more moderate effect due to an intramolecular charge transfer from the HOMO localized on the TTF unit to the LUMO localized on the PDI moiety. This work clearly elucidates the interplay between intra- and intermolecular electronic processes in organic devices.

Storia degli israeliti dai tempi più antichi sino al presente : ad uso scolastico e domestico

di Daniele Ehrmann. Prima versione ital. di S. R. Melli

Taking a New Look at Neo-Assyrian Gates

The Assyrian capitals are not only known for their magnificent temples and palaces, but also for their monumental city walls. The most impressive and at the same time most delicate features of all the town defenses were the city gates. As they interrupted the line of defense, they were al-ways a vulnerable spot of every system of fortifications. However, the walled cities’ economic needs demanded these gateways to be built, in order to ensure the steady flow of goods and pro-visions. Apart from that, they also had a significant ideological meaning, which is emphasized by many cuneiform texts. During the excavations of the Assyrian capitals of Ashur, Dūr Šarrūkīn, and Nineveh, a fairly large number of Assyrian city gates were brought to light. By re-examining the archaeological reports and employing remote sensing, many details of these structures can still be revealed. The paper aims at illuminating the different considerations that went into constructing these gates, as well as the development Assyrian city gates underwent and what may have influenced this process.

Sēfer Takšîtê nāšîm : senîf min-has-sēfer mûsār alef-vêt le-vānîm ; ḥeṣî mi-ḥelqat revîʿît ham-meyûḥedet le-vānôt ... (bi-lešôn aškenaz) be-loišn jidiš-daiṭš ... fir alle jidiše ṭechṭer ...

... Dawid Špiṭtzer

Rapid divergence in physiological and life-history traits between northern and southern populations of the British introduced neo-species, Senecio squalidus

Alien plants provide a unique opportunity to study evolution in novel environments, but relatively little is known about the extent to which they become locally adapted to different environments across their new range. Here, we compare northern and southern populations of the introduced species Senecio squalidus in Britain; S. squalidus has been in southern Britain for approximately 200 years and reached Scotland only about 50 years ago. We conducted common garden experiments at sites in the north and south of the species’ range in Britain. We also conducted glasshouse and growth chamber experiments to test the hypothesis that southern genotypes flower later, are more drought-tolerant, germinate and establish better at warmer temperatures, and are less sensitive to cold stress than their more northern counterparts. Results from the common garden experiments are largely consistent with the hypothesis of rapid adaptive divergence of populations of the species within the introduced range, with genotypes typically showing a home-site advantage. Results from the glasshouse and growth chamber experiments demonstrate adaptive divergence in ability to tolerate drought stress and high temperatures, as well as in phenology. In particular, southern genotypes were more tolerant of dry conditions and high temperatures and they flowered later than northern genotypes. Our results show that rapid local adaptation can occur in alien species, and they have implications for our understanding of the ecological genetics of range expansion of introduced weeds.

Evaluación del dispositivo Raspberry Pi como elemento de despliegue de servicios en el marco de las Smart Grids

La tendencia actual de las redes de telecomunicaciones conduce a pensar en un futuro basado en el concepto emergente de las Smart Cities¸ que tienen como objetivo el desarrollo urbano basado en un modelo de sostenibilidad que responda a las necesidades crecientes de las ciudades. Dentro de las Smart Cities podemos incluir el concepto de Smart Grid, el cual está referido a sistemas de administración y producción de energía eficientes, que permitan un sistema energético sostenible, y que den cabida a las fuentes de energía renovables. Sistemas de este tipo se muestran a los usuarios como un conjunto de servicios con los que interactuar sin ser tan sólo un mero cliente, sino un agente más del entorno energético. Por otro lado, los sistemas de software distribuidos son cada vez más comunes en una infraestructura de telecomunicaciones cada vez más extensa y con más capacidades. Dentro de este ámbito tecnológico, las arquitecturas orientadas a servicios han crecido exponencialmente sobre todo en el sector empresarial. Con sistemas basados en estas arquitecturas, se pueden ofrecer a empresas y usuarios sistemas software basados en el concepto de servicio. Con la progresión del hardware actual, la miniaturización de los equipos es cada vez mayor, sin renunciar por ello a la potencia que podemos encontrar en sistemas de mayor tamaño. Un ejemplo es el dispositivo Raspberry Pi, que contiene un ordenador plenamente funcional contenido en el tamaño de una cajetilla de tabaco, y con un coste muy reducido. En este proyecto se pretenden aunar los tres conceptos expuestos. De esta forma, se busca utilizar el dispositivo Raspberry Pi como elemento de despliegue integrado en una arquitectura de Smart Grid orientada a servicios. En los trabajos realizados se ha utilizado la propuesta definida por el proyecto de I+D europeo e-GOTHAM, con cuya infraestructura se ha tenido ocasión de realizar diferentes pruebas de las descritas en esta memoria. Aunque esta arquitectura está orientada a la creación de una Smart Grid, lo experimentado en este PFG podría encajar en otro tipo de aplicaciones. Dentro del estudio sobre las soluciones software actuales, se ha trabajado en la evaluación de la posibilidad de instalar un Enterprise Service Bus en el Raspberry Pi y en la optimización de la citada instalación. Una vez conseguida una instalación operativa, se ha desarrollado un controlador de un dispositivo físico (sensor/actuador), denominado Dispositivo Lógico, a modo de prueba de la viabilidad del uso del Raspberry Pi para actuar como elemento en el que instalar aplicaciones en entornos de Smart Grid o Smart Home. El éxito logrado con esta experimentación refuerza la idea de considerar al Raspberry Pi, como un importante elemento a tener en cuenta para el despliegue de servicios de Smart Cities o incluso en otros ámbitos tecnológicos. ABSTRACT. The current trend of telecommunication networks lead to think in a future based on the emerging concept of Smart Cities, whose objective is to ensure the urban development based on a sustainable model to respond the new necessities of the cities. Within the Smart cites we can include the concept of Smart Grid, which is based on management systems and efficient energy production, allowing a sustainable energy producing system, and that includes renewable energy sources. Systems of this type are shown to users as a set of services that allow users to interact with the system not only as a single customer, but also as other energy environment agent. Furthermore, distributed software systems are increasingly common in a telecommunications infrastructure more extensive and with more capabilities. Within this area of technology, service-oriented architectures have grown exponentially especially in the business sector. With systems based on these architectures, can be offered to businesses and users software systems based on the concept of service. With the progression of the actual hardware, the miniaturization of computers is increasing, without sacrificing the power of larger systems. An example is the Raspberry Pi, which contains a fully functional computer contained in the size of a pack of cigarettes, and with a very low cost. This PFG (Proyecto Fin de Grado) tries to combine the three concepts presented. Thus, it is intended to use the Raspberry Pi device as a deployment element integrated into a service oriented Smart Grid architecture. In this PFG, the one proposed in the European R&D e-GOTHAM project has been observed. In addition several tests described herein have been carried out using the infrastructure of that project. Although this architecture is oriented to the creation of a Smart Grid, the experiences reported in this document could fit into other applications. Within the study on current software solutions, it have been working on assessing the possibility of installing an Enterprise Service Bus in the Raspberry Pi and optimizing that facility. Having achieved an operating installation, it has been developed a driver for a physical device (sensor / actuator), called logical device, for testing the feasibility of using the Raspberry Pi to act as an element in which to install applications in Smart Grid and Smart Home Environments. The success of this experiment reinforces the idea of considering the Raspberry Pi as an important element to take into account in the deployment of Smart Cities services or even in other technological fields.

Mari-Pi [ [Material gráfico]: Manuel Nicola : Cullera- Valencia.

Impreso en el ángulo superior izquierdo: "R. de E. nº 9.048" y en el superior derecho:"Importado de España"

Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: Implications for AIDS pathology

The small HIV-1 accessory protein Vpr (virus protein R) is a multifunctional protein that is present in the serum and cerebrospinal fluid of AIDS patients. We previously showed that Vpr can form cation-selective ion channels across planar lipid bilayers, introducing the possibility that, if incorporated into the membranes of living cells, Vpr might form ion channels and consequently perturb the maintained ionic gradient. In this study, we demonstrate, by a variety of approaches, that Vpr added extracellularly to intact cells does indeed form ion channels. We use confocal laser scanning microscopy to examine the subcellular localization of fluorescently labeled Vpr. Plasmalemma depolarization and damage are examined using the anionic potential-sensitive dye bis(1,3-dibutylbarbituric acid) trimethine oxonol and propidium iodide (PI), respectively, and the effect of Vpr on whole-cell current is demonstrated directly by using the patch-clamp technique. We show that recombinant purified extracellular Vpr associates with the plasmalemma of hippocampal neurons to cause a large inward cation current and depolarization of the plasmalemma, eventually resulting in cell death. Thus, we demonstrate a physiological action of extracellular Vpr and present its mechanistic basis. These findings may have important implications for neuropathologies in AIDS patients who possess significant amounts of Vpr in the cerebrospinal fluid.

In vivo suppression of the renal Na+/Pi cotransporter by antisense oligonucleotides.

A 20-mer phosphorothioate oligonucleotide (AS1) was designed to hybridize to the message for the rat kidney sodium phosphate cotransporter NaPi-2 close to the translation initiation site. Single intravenous doses of this oligonucleotide were given to rats maintained on a low phosphorus diet to increase NaPi-2 expression. At 3 days after oligonucleotide infusion, rats receiving 2.5 micromol of AS1 exhibited a reduction in renal NaPi-2 to cyclophilin mRNA ratio by 40% +/- 17%, and rats receiving 7.5 micromol of AS1 exhibited a reduction in NaPi-2 to cyclophilin mRNA ratio by 46% +/- 21%. Reversed-sequence AS1 was without effect. The higher dose of 7.5 micromol of AS1 also reduced the rate of phosphate uptake into renal brush border membrane vesicles and the expression of NaPi-2 protein detected by Western blotting in these vesicles. Reversed sequence AS1 was again without effect on these parameters. These results suggest that systemically infused oligonucleotides can exert antisense effects in the renal proximal tubule.

Analisi e riprogettazione dei processi aziendali in un’azienda di Global Service. Il caso A.C.R. S.p.A.

La tesi tratta dell'analisi e della riprogettazione dei processi in un'azienda di global service. Vengono pertanto illustrati le principali metodologie e teorie riguardanti il process management e gli strumenti di supporto più utilizzati per la modellazione dei processi. Viene inoltre presentato il caso riguardante l'azienda ACR SpA, in cui si è eseguita la riprogettazione dei processi critici al fine di migliorare sensibilmente i principali parametri di performance del sistema. Tale riprogettazione è stata finalizzata all'introduzione di un sistema di document management all'interno delle principali funzioni aziendali, grazie a cui si è potuto razionalizzare e automatizzare i processi ritenuti critici ottenendo una sensibile riduzione dei relativi lead time e costi di processo, quantificata attraverso KPI definiti ad hoc. In conclusione la tesi ha permesso di illustrare con un caso pratico l'applicazione degli strumenti di business process reengineering, evidenziandone i pregi e ribadendo l'importanza della continua ricerca di efficienza all'interno dei processi di business aziendali.

Importante scoperta per conservare freschissime delle migliaja d'uova per l'inverno ed anche per più anni con un soldo di spesa e nessuna fatica : dettugliamante esposta a vantaggio d'ogni privata famiglia, degli osti, offellaj, confetturieri, bottegai, contadini, ed in generale di chiunque consumi uova one faccia provvigione per la vendita od altri usi /

Treatise on preservation of eggs; refers to various methods of preserving eggs dating back to the Roman Empire and Renaissance; describes in detail methods in use in England and France during late 1700-early 1800; includes citations from numerous experts (i.e. Reaumur, Parmentier, European agricultural journals, etc.). Footnote on p. 55 from R.D. Peschier of Geneva, doctor of chemistry and medicine, cites an example of eggs preserved for six years in lime-water.