Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms.

BACKGROUND: HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. METHODS AND RESULTS: Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups. CONCLUSIONS: Inno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation.

GENETIC INTERACTIONS OF FACTORS THAT REGULATE ALTERNATIVE RNA SPLICING IN THE MALE GERM LINE OF DROSOPHILA

Alternative RNA splicing is a critical process that contributes variety to protein functions, and further controls cell differentiation and normal development. Although it is known that most eukaryotic genes produce multiple transcripts in which splice site selection is regulated, how RNA binding proteins cooperate to activate and repress specific splice sites is still poorly understood. In addition how the regulation of alternative splicing affects germ cell development is also not well known. In this study, Drosophila Transformer 2 (Tra2) was used as a model to explore both the mechanism of its repressive function on its own pre-mRNA splicing, and the effect of the splicing regulation on spermatogenesis in testis. Half-pint (Hfp), a protein known as splicing activator, was identified in an S2 cell-based RNAi screen as a co-repressor that functions in combination with Tra2 in the splicing repression of the M1 intron. Its repressive splicing function is found to be sequence specific and is dependent on both the weak 3’ splice site and an intronic splicing silencer within the M1 intron. In addition we found that in vivo, two forms of Hfp are expressed in a cell type specific manner. These alternative forms differ at their amino terminus affecting the presence of a region with four RS dipeptides. Using assays in Drosophila S2 cells, we determined that the alternative N terminal domain is necessary in repression. This difference is probably due to differential localization of the two isoforms in the nucleus and cytoplasm. Our in vivo studies show that both Hfp and Tra2 are required for normal spermatogenesis and cooperate in repression of M1 splicing in spermatocytes. But interestingly, Tra2 and Hfp antagonize each other’s function in regulating germline specific alternative splicing of Taf1 (TBP associated factor 1). Genetic and cytological studies showed that mutants of Hfp and Taf1 both cause similar defects in meiosis and spermatogenesis. These results suggest Hfp regulates normal spermatogenesis partially through the regulation of taf1 splicing. These observations indicate that Hfp regulates tra2 and taf1 activity and play an important role in germ cell differentiation of male flies.

Table 5 Comparison of surface elevations by Seasat and optical survey along EGIG line

Surface elevation maps of the southern half of the Greenland subcontinent are produced from radar altimeter data acquired by the Seasat satellite. A summary of the processing procedure and examples of return waveform data are given. The elevation data are used to generate a regular grid which is then computer contoured to provide an elevation contour map. Ancillary maps show the statistical quality of the elevation data and various characteristics of the surface. The elevation map is used to define ice flow directions and delineate the major drainage basins. Regular maps of the Jakobshavns Glacier drainage basin and the ice divide in the vicinity of Crete Station are presented. Altimeter derived elevations are compared with elevations measured both by satellite geoceivers and optical surveying.

Synthesized grounding line and ice shelf mask for Antarctica

Iceberg calving has been assumed to be the dominant cause of mass loss for the Antarctic ice sheet, with previous estimates of the calving flux exceeding 2,000 gigatonnes per year. More recently, the importance of melting by the ocean has been demonstrated close to the grounding line and near the calving front. So far, however, no study has reliably quantified the calving flux and the basal mass balance (the balance between accretion and ablation at the ice-sheet base) for the whole of Antarctica. The distribution of fresh water in the Southern Ocean and its partitioning between the liquid and solid phases is therefore poorly constrained. Here we estimate the mass balance components for all ice shelves in Antarctica, using satellite measurements of calving flux and grounding-line flux, modelled ice-shelf snow accumulation rates and a regional scaling that accounts for unsurveyed areas. We obtain a total calving flux of 1,321 ± 144 gigatonnes per year and a total basal mass balance of -1,454 ± 174 gigatonnes per year. This means that about half of the ice-sheet surface mass gain is lost through oceanic erosion before reaching the ice front, and the calving flux is about 34 per cent less than previous estimates derived from iceberg tracking. In addition, the fraction of mass loss due to basal processes varies from about 10 to 90 per cent between ice shelves. We find a significant positive correlation between basal mass loss and surface elevation change for ice shelves experiencing surface lowering and enhanced discharge. We suggest that basal mass loss is a valuable metric for predicting future ice-shelf vulnerability to oceanic forcing.

Estudio acústico del estadio "La Peineta" utilizando line arrays

El proyecto fin de carrera consiste en un estudio acústico del Estadio de la Peineta (estadio de fútbol perteneciente al club Atlético de Madrid el cual se encuentra en construcción). Se realizará el diseño por completo de una maqueta del estadio utilizando el programa EASE. Esta maqueta se hará a escala real, exactamente como se está construyendo el estadio. A dicha maqueta se le incorporarán los diferentes materiales absorbentes específicos a cada una de las superficies que compongan el estadio. Se crearán tantas zonas de audiencia como superficies se obtenga en cada grada sobre donde se realizarán dos estudios acústicos diferentes. El primer estudio se realizará con un total de 24 clústeres de altavoces los cuales están compuestos por 10 altavoces Aero 50. La colocación estratégica de cada uno de estos altavoces se estudiará con la herramienta EASE Focus 2. Una vez obtenidas las posiciones se importarán cada uno de estos clústeres de altavoces su respectiva configuración. El otro estudio se realizará con la mitad de arrays de altavoces con la intención de tener una comparativa de recubrimiento entre un estudio y otro. Las pruebas de simulación serán analizando el nivel de presión sonora que provoca cada uno de estos estudios cuando tienen sus altavoces en funcionamiento. Se utilizará el módulo de “Area mapping” para estudiar el mapeo en cada una de las zonas de audiencia definidas, así como cada una de las distribuciones por área que predominan. Se irán anotando cada uno de los problemas e ideas que van surgiendo a lo largo de dicho proyecto para proponer una continuación y mejora del mismo. Se planteará una serie de pasos e pruebas al final de la memoria ya que se trata de un proyecto sin cerrar y puede ser continuado por otra persona. ABSTRACT. The final project is an acoustic studio Peineta Stadium (soccer stadium belongs to the club Atletico Madrid which is under construction). The design is made entirely of a model of the stadium using the EASE program. This model will be full scale, exactly as is building the stadium. A model that should be incorporated into the various specific absorbent material to each of the surfaces that make up the stadium. Hearing so many areas as surfaces is obtained in each tier on which two different acoustic studies will be conducted will be created. The first study was conducted with a total of 24 speaker clusters which are composed of 10 speakers Aero 50. The strategic placement of each of these speakers will be studied with the EASE Focus 2. Once obtained tool positions are imported each these clusters of the respective speaker configuration. The other study was conducted with half speaker arrays with the intention of having a comparative study between a coating and another. Simulation tests will be analyzing the sound pressure level which causes each of these studies have their speakers when in operation. Module "mapping area" will be used to study the mapping in each of the areas defined audience, and each of the area distributions predominate. They will be written down each of the issues and ideas that arise throughout the project to propose a continuation and improvement. a series of steps and tests at the end of the memory will be raised because it is a project without closing and may be continued for another person.

Development of a safe live Leishmania vaccine line by gene replacement.

Vaccination with live Leishmania major has been shown to yield effective immunization in humans; however, this has been discontinued because of problems associated with virulence of the available vaccine lines. To circumvent this, we tested the ability of a dhfr-ts- null mutant of L. major, obtained by gene targeting, to infect and then to vaccinate mice against challenge with virulent L. major. Survival and replication of dhfr-ts- in macrophages in vitro were dependent upon thymidine, with parasites differentiating into amastigotes prior to destruction. dhfr-ts- parasites persisted in BALB/c mice for up to 2 months, declining with a half-life of 2-3 days. Nonetheless, dhfr-ts- was incapable of causing disease in both susceptible and immunodeficient (nu/nu) BALB/c mice. Animal infectivity could be partially restored by thymidine supplementation. When inoculated by the i.v., s.c., or i.m. routes into mice, dhfr-ts- could elicit substantial resistance to a subsequent challenge with virulent L. major. Thus, Leishmania bearing auxotrophic gene knockouts can be safe and induce protective immunity. Potentially, dhfr-ts- could be used as a platform for delivery of immunogens relevant to other diseases.

Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to rescue developing motoneurons in vivo and in vitro from both naturally occurring and axotomy-induced cell death. To test whether GDNF has trophic effects on adult motoneurons, we used a mouse model of injury-induced adult motoneuron degeneration. Injuring adult motoneuron axons at the exit point of the nerve from the spinal cord (avulsion) resulted in a 70% loss of motoneurons by 3 weeks following surgery and a complete loss by 6 weeks. Half of the loss was prevented by GDNF treatment. GDNF also induced an increase (hypertrophy) in the size of surviving motoneurons. These data provide strong evidence that the survival of injured adult mammalian motoneurons can be promoted by a known neurotrophic factor, suggesting the potential use of GDNF in therapeutic approaches to adult-onset motoneuron diseases such as amyotrophic lateral sclerosis.

Report of Commissioners appointed to settle the line between New-Hampshire and Maine.

Half-title.

Parallel photographs of the spectra of the sun, of iron, and of iridium, from the line (H) to near the line (D), in six sections. Also separate photographs of the spectrum of titanic iron ore, in six sections.

Half-title. Reprinted from the Monthly notices of the Royal astronomical society, vol.XLIX, no.7.

All-fiber-integrated soliton-similariton laser with in-line fiber filter

We demonstrate an all-fiber-integrated Er-doped fiber laser operating in the soliton-similariton mode-locking regime. In the similariton part of the cavity, a self-similarly evolving parabolic pulse with highly linear chirp propagates in the presence of normal dispersion. Following an in-line fiber-based birefringent filter, the pulse evolves into a soliton in the part of the cavity with anomalous dispersion. The similariton and the soliton pulses are dechirped to 75.5 and 167.2 fs, respectively, outside of the cavity. Mode-locked operation is very robust, owing to the influence of the two similariton and soliton attractors that predominate each half of the laser cavity. The experimental results are supported with numerical simulations, which provide good agreement.

On the numerical solution of a Cauchy problem in an elastostatic half-plane with a bounded inclusion

We propose an iterative procedure for the inverse problem of determining the displacement vector on the boundary of a bounded planar inclusion given the displacement and stress fields on an infinite (planar) line-segment. At each iteration step mixed boundary value problems in an elastostatic half-plane containing the bounded inclusion are solved. For efficient numerical implementation of the procedure these mixed problems are reduced to integral equations over the bounded inclusion. Well-posedness and numerical solution of these boundary integral equations are presented, and a proof of convergence of the procedure for the inverse problem to the original solution is given. Numerical investigations are presented both for the direct and inverse problems, and these results show in particular that the displacement vector on the boundary of the inclusion can be found in an accurate and stable way with small computational cost.

Laser-induced breakdown spectroscopy quantitative analysis method via adaptive analytical line selection and relevance vector machine regression model

Abstract A new LIBS quantitative analysis method based on analytical line adaptive selection and Relevance Vector Machine (RVM) regression model is proposed. First, a scheme of adaptively selecting analytical line is put forward in order to overcome the drawback of high dependency on a priori knowledge. The candidate analytical lines are automatically selected based on the built-in characteristics of spectral lines, such as spectral intensity, wavelength and width at half height. The analytical lines which will be used as input variables of regression model are determined adaptively according to the samples for both training and testing. Second, an LIBS quantitative analysis method based on RVM is presented. The intensities of analytical lines and the elemental concentrations of certified standard samples are used to train the RVM regression model. The predicted elemental concentration analysis results will be given with a form of confidence interval of probabilistic distribution, which is helpful for evaluating the uncertainness contained in the measured spectra. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples have been carried out. The multiple correlation coefficient of the prediction was up to 98.85%, and the average relative error of the prediction was 4.01%. The experiment results showed that the proposed LIBS quantitative analysis method achieved better prediction accuracy and better modeling robustness compared with the methods based on partial least squares regression, artificial neural network and standard support vector machine.

Map of 1st. distrt. Campbell Co. Georgia : south of the Cherokee boundy. line /

Shows local topography, roads, and names of some residents.

Design, synthesis and antiproliferative activity of hydroxyacetamide derivatives against HeLa cervical carcinoma cell and breast cancer cell line

Purpose: To design and develop a new series of histone deacetylase inhibitors (FP1 - FP12) and evaluate their inhibitory activity against hydroxyacetamide (HDAC) enzyme mixture-derived HeLa cervical carcinoma cell and MCF-7. Methods: The designed molecules (FP1 - FP12) were docked using AUTODOCK 1.4.6. FP3 and FP8 showed higher interaction comparable to the prototypical HDACI. The designed series of 2-[[(3- Phenyl/substituted Phenyl-[4-{(4-(substituted phenyl)ethylidine-2-Phenyl-1,3-Imidazol-5-One}](-4H- 1,2,4-triazol-5-yl)sulfanyl]-N-hydroxyacetamide derivatives (FP1-FP12) was synthesized by merging 2- [(4-amino-3-phenyl-4H- 1, 2, 4-triazol-5-yl) sulfanyl]-N-hydroxyacetamide and 2-{[4-amino-3-(2- hydroxyphenyl)-4H-1,2, 4-triazol-5-yl]sulfanyl}-N hydroxyacetamide derivatives with aromatic substituted oxazolone. The biological activity of the synthesized molecule (FP1-FP12) was evaluated against HDAC enzyme mixture-derived HeLa cervical carcinoma cell and breast cancer cell line (MCF-7). Results: HDAC inhibitory activity of FP10 showed higher IC50 (half-maximal concentration inhibitory activity) of 0.09 μM, whereas standard SAHA molecule showed IC50 of 0.057 μM. On the other hand, FP9 exhibited higher GI50 (50 % of maximal concentration that inhibited cell proliferation) of 22.8 μM against MCF-7 cell line, compared with the standard, adriamycin, with GI50 of (-) 50.2 μM. Conclusion: Synthesis, spectral characterization, and evaluation of HDAC inhibition activity and in vitro anticancer evaluation of novel hydroxyacetamide derivatives against MCF-7 cell line have been achieved. The findings indicate the emergence of potentialanticancer compounds.

Inhibition of proliferation, migration and invasion of human non-small cell lung cancer cell line A549 by phlomisoside F from Phlomis younghusbandii Mukerjee

Purpose: To determine the effect of phlomisoside F (PMF) on the proliferation, migration and invasion of human non-small cell lung cancer cell line A549 and explore the possible mechanisms. Methods: The anti-proliferative effect of PMF on A549 cells was determined by CCK-8. Subsequently, migration and invasion were evaluated by Transwell and Transwell with matrigel assays, respectively. Furthermore, cell cycle and apoptosis were assessed by flow cytometry, while the mechanisms of action were determined by Western blotting. Results: PMF exhibited significant anti-proliferative effect on A549 cells in concentration-dependent and time-dependent manners, with half maximal inhibitory concentration (IC50) of 54.51 μM. Treatment with PMF (10, 20 and 40 μM) for 48 h resulted in significantly decreased migration and invasion in A549 cells. In addition, PMF at concentrations of 25, 50 and 75 μM induced cell cycle arrest in G0/G1phase and enhanced cell apoptosis in A549 cells. Furthermore, caspase-3, caspase-9 and Bax protein expressions were up-regulated while Bacl-2 and COX-2 protein expressions were significantly downregulated at 10, 20 and 40 μM concentrations of PMF. Conclusion: PMF suppresses A549 cell growth, migration and invasion. The mechanism may be related to the induction of mitochondria-mediated apoptosis pathway via regulation of caspase-3, caspase-9, Bcl-2 and Bax expressions, and inhibition of PGE2 synthesis by reducing COX-2 expression.