Evidence-based urology in practice : heterogeneity in a systematic review meta-analysis

The definitive version is available at www3.interscience.wiley.com.Peer reviewedPreprin

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

Del Pezzo surfaces with 1/3(1,1) points

We classify del Pezzo surfaces with 1/3(1,1) points in 29 qG-deformation families grouped into six unprojection cascades (this overlaps with work of Fujita and Yasutake), we tabulate their biregular invariants, we give good model constructions for surfaces in all families as degeneracy loci in rep quotient varieties and we prove that precisely 26 families admit qG-degenerations to toric surfaces. This work is part of a program to study mirror symmetry for orbifold del Pezzo surfaces.Comment: 42 pages. v2: model construction added of last remaining surface, minor corrections, minor changes to presentation, references adde

Recent advances in the structural and molecular biology of type IV secretion systems

Bacteria use type IV secretion (T4S) systems to deliver DNA and protein substrates to a diverse range of prokaryotic and eukaryotic target cells. T4S systems have great impact on human health, as they are a major source of antibiotic resistance spread among bacteria and are central to infection processes of many pathogens. Therefore, deciphering the structure and underlying translocation mechanism of T4S systems is crucial to facilitate development of new drugs. The last five years have witnessed considerable progress in unraveling the structure of T4S system subassemblies, notably that of the T4S system core complex, a large 1 MegaDalton (MDa) structure embedded in the double membrane of Gram-negative bacteria and made of 3 of the 12 T4S system components. However, the recent determination of the structure of ∼3 MDa assembly of 8 of these components has revolutionized our views of T4S system architecture and opened up new avenues of research, which are discussed in this review

Using SRAM Based FPGAs for Power-Aware High Performance Wireless Sensor Networks

While for years traditional wireless sensor nodes have been based on ultra-low power microcontrollers with sufficient but limited computing power, the complexity and number of tasks of today’s applications are constantly increasing. Increasing the node duty cycle is not feasible in all cases, so in many cases more computing power is required. This extra computing power may be achieved by either more powerful microcontrollers, though more power consumption or, in general, any solution capable of accelerating task execution. At this point, the use of hardware based, and in particular FPGA solutions, might appear as a candidate technology, since though power use is higher compared with lower power devices, execution time is reduced, so energy could be reduced overall. In order to demonstrate this, an innovative WSN node architecture is proposed. This architecture is based on a high performance high capacity state-of-the-art FPGA, which combines the advantages of the intrinsic acceleration provided by the parallelism of hardware devices, the use of partial reconfiguration capabilities, as well as a careful power-aware management system, to show that energy savings for certain higher-end applications can be achieved. Finally, comprehensive tests have been done to validate the platform in terms of performance and power consumption, to proof that better energy efficiency compared to processor based solutions can be achieved, for instance, when encryption is imposed by the application requirements

Schistosoma haematobium infection levels determine the effect of praziquantel treatment on anti-schistosome and anti-mite antibodies

Field studies show an association between schistosome infection and atopy, but the effects of anti-helminthic treatment on this association have not yet been investigated in human populations with different schistosome endemicity levels. This study aimed to compare the effects of anti-helminthic treatment on responses directed against the house dust mite Dermatophagoides pteronyssinus (Derp1) and Schistosoma haematobium in Zimbabwean populations living in high and low schistosome infection areas. Derp1- and schistosome-specific IgE and IgG4 antibodies were quantified by ELISA before and 6 weeks after anti-helminthic treatment. Following treatment, there were changes in the immune responses, which varied with place of residence. After allowing for the effects of sex, age and baseline infection intensity, there was no significant treatment effect on the change in anti-schistosome IgE and IgG4 in the high infection area. However, the anti-schistosome IgE/IgG4 ratio increased significantly, while anti-Derp1 IgE responses decreased as a result of treatment. In the low infection area, treatment resulted in a significant increase in anti-worm IgE levels, but there was no significant treatment effect on anti-schistosome or anti-Derp1 IgE/IgG4 ratios. Thus, the study shows that the level of schistosome endemicity affects the host responses to schistosome and mite antigens following anti-helminthic treatment

Structure and Function of a Mycobacterial NHEJ DNA Repair Polymerase

Non homologous end-joining (NHEJ)-mediated repair of DNA double-strand breaks in prokaryotes requires Ku and a specific multidomain DNA ligase (LigD). We present crystal structures of the primase/polymerisation domain (PolDom) of Mycobacterium tuberculosis LigD, alone and complexed with nucleotides. The PolDom structure combines the general fold of the archaeo-eukaryotic primase (AEP) superfamily with additional loops and domains that together form a deep cleft on the surface, likely used for DNA binding. Enzymatic analysis indicates that the PolDom of LigD, even in the absence of accessory domains and Ku proteins, has the potential to recognise DNA end-joining intermediates. Strikingly, one of the main signals for the specific and efficient binding of PolDom to DNA is the presence of a 5'-phosphate group, located at the single/double-stranded junction at both gapped and 3'-protruding DNA molecules. Although structurally unrelated, Pol lambda and Pol mu, the two eukaryotic DNA polymerases involved in NHEJ, are endowed with a similar capacity to bind a 5'-phosphate group. Other properties that are beneficial for NHEJ, such as the ability to generate template distortions and realignments of the primer, displayed by Pol lambda and Pol mu, are shared by the PolDom of bacterial LigD. In addition, PolDom can perform non-mutagenic translesion synthesis on termini containing modified bases. Significantly, ribonucleotide insertion appears to be a recurrent theme associated with NHEJ, maximised in this case by the deployment of a dedicated primase, although its in vivo relevance is unknown

Nativity Differences in Stress among Asian and Pacific Islander American Women

According to the Stress Process Theory, people who are marginalized in society encounter more stress than those in more advantaged positions. Immigrants are one such marginalized group in the United States (US) who may experience greater psychological stress than their US-born counterparts due to (1) severing of social ties; (2) social disadvantage and marginalization; and (3) adaptation to a new environment. This study examines the disparity in stress by nativity, and how social factors contribute to this disparity for Asian and Pacific Islander (API) women. Data come from the Asian Community Health Initiative, which included a sample of 291 foreign-born and 155 US-born API women in the San Francisco Bay Area. Multivariable linear regression was used to estimate associations between nativity status and stress, measured using the Cohen Perceived Stress Scale, accounting for various social stressors. Foreign-born women had higher levels of stress compared to US-born. Stress was greater among women experiencing fewer socioeconomic resources, more discrimination, more acculturative stress, and low English proficiency. English proficiency accounted for much of the disparity in stress between foreign-born and US-born API women. This study contributes to our understanding of how stress among APIs is influenced by social disadvantage and marginalization in US society. Future research should further study how aspects of the immigrant experience are associated with stress among APIs over time

Sensor fusion of camera, GPS and IMU using fuzzy adaptive multiple motion models

A tracking system that will be used for augmented reality applications has two main requirements: accuracy and frame rate. The first requirement is related to the performance of the pose estimation algorithm and how accurately the tracking system can find the position and orientation of the user in the environment. Accuracy problems of current tracking devices, considering that they are low-cost devices, cause static errors during this motion estimation process. The second requirement is related to dynamic errors (the end-to-end system delay, occurring because of the delay in estimating the motion of the user and displaying images based on this estimate). This paper investigates combining the vision-based estimates with measurements from other sensors, GPS and IMU, in order to improve the tracking accuracy in outdoor environments. The idea of using Fuzzy Adaptive Multiple Models was investigated using a novel fuzzy rule-based approach to decide on the model that results in improved accuracy and faster convergence for the fusion filter. Results show that the developed tracking system is more accurate than a conventional GPS–IMU fusion approach due to additional estimates from a camera and fuzzy motion models. The paper also presents an application in cultural heritage context running at modest frame rates due to the design of the fusion algorithm

Do breast implants after a mastectomy affect subsequent prognosis and survival?

In a large study, published in this issue of Breast Cancer Research, Le and colleagues report that women receiving implants after mastectomies for early-stage breast cancer experience lower breast cancer mortality than women not receiving implants. Assessment of survival patterns among women receiving reconstructive implants is complex given unique patient characteristics, disease attributes, and treatment patterns. The interpretation of reduced mortality from breast cancer must be assessed in light of significantly reduced risks of death from most other causes. In contrast, patients receiving post-mastectomy implants had elevated rates of suicide, consistent with findings among women with cosmetic implants. Additional well-designed investigations are needed to clarify survival patterns among women receiving reconstructive implants