Designing Primary Prevention for People Living with HIV

Today, there are new reasons for a sharper focus on prevention for people living with HIV. Growing numbers of people with the disease are living more healthy, sexual lives. Recent evidence suggests that risk taking among both HIV-positive and negative people is increasing. After nearly two decades of life in the shadow of AIDS, communities are growing weary of traditional prevention messages and many people are openly grappling with difficult questions of intimacy and sex. Increasingly, people living with HIV also face multiple complex economic and substance abuse challenges that complicate prevention efforts.There is an urgent need -- and sufficient expertise -- to move forward with prevention campaigns focused on helping people living with HIV and AIDS avoid passing their infection along to others. Numerous innovative interventions for people with HIV show promise, including:a social marketing campaign for gay men and a five-session group intervention for women living with HIV in Massachusetts,a chat line for positives and a group session program for Latinas/Latinos in Los Angeles,Internet chat room interventions in Atlanta,a group session for gay Asian American-Pacific Islander Americans living with HIV in San Francisco, andPrevention Case Management programs newly funded by the Centers for Disease Control

Special Issue “BIM Implementation to Meet the Changing Demands of the Construction Industry”

Effective Building Information Modelling implementation continues to evolve, aligning itself to the changing needs of the construction industry. These activities can be considered from a range of perspectives. We can adopt a people-centric, process centric, product-centric approach or a combination of these approaches.A total of 10 papers were received covering these different aspects and the different stages of project delivery. Collectively, they add to the body of knowledge in the BIM implementation domain and align to the changes happening within the construction industries. Semaan et al. [1] investigated work-based education and training needs as part of effective BIM adoption. Dermirdogen et al. [2] considered the business intelligence and analytics aspects of the subject area. Two of the papers submitted took a tool-based approach. Hagedorn et al. [3] looked at toolchains for interoperable BIM workflows in Web-based integration platforms. In comparison, Keibach et al. [4] undertook an evaluation of software tools based on ISO 25010 for landscape design and improving climate adaptation planning. Focusing on BIM applied to specific tasks, several papers were received. Bazan et al. [5] focused on a BIM—Based methodology for the Management of Public Heritage. In comparison, Mayer et al. [6] focused on Hazard Detection processes in BIM. Specific project types were addressed in two papers. BIM and GIS applications in Bridge Projects were addressed by Wei et al. [7]. In comparison, BIM in High Rise buildings towards sustainability was addressed by Manzoor et al. [8]. Considering a specific stage for addressing in one paper, Pinti et al. [9] undertook a review of Building Information Modelling for facilities management. Focusing on improvement, Zheng et al. [10] undertook an analysis of the improvement of BIM Based Digitalization in Engineering, Procurement, and Construction (EPC) on projects in China.Although submissions for this Special Issue have been closed, more in-depth research in the field of BIM implementation continues to address the challenges the construction industry faces today, such as climate change, changes in technology, and drive for faster, cheaper, and higher quality building and infrastructure development

Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks.

Repair of single-ended DNA double-strand breaks (seDSBs) by homologous recombination (HR) requires the generation of a 3' single-strand DNA overhang by exonuclease activities in a process called DNA resection. However, it is anticipated that the highly abundant DNA end-binding protein Ku sequesters seDSBs and shields them from exonuclease activities. Despite pioneering works in yeast, it is unclear how mammalian cells counteract Ku at seDSBs to allow HR to proceed. Here we show that in human cells, ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on seDSBs. We also provide evidence for a hitherto unsuspected additional mechanism that contributes to prevent Ku accumulation at seDSBs, acting downstream of MRE11 endonuclease activity and in parallel with MRE11 exonuclease activity. Finally, we show that Ku persistence at seDSBs compromises Rad51 focus assembly but not DNA resection.EMBO (long-term fellowship (ALTF 93-2010)), Cancer Research UK (Grant IDs: C6/A11224, C6/A18796, C6946/A14492), La Ligue Nationale Contre le Cancer (senior post-doctoral fellowship, Equipe Labellisée 2013), Wellcome Trust (WT092096), University of Cambridge, INSERMThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1288

Unexpectedly uneven distribution of functional trade-offs explains cranial morphological diversity in carnivores

Functional trade-offs can affect patterns of morphological and ecological evolution as well as the magnitude of morphological changes through evolutionary time. Using morpho-functional landscape modelling on the cranium of 132 carnivore species, we focused on the macroevolutionary effects of the trade-off between bite force and bite velocity. Here, we show that rates of evolution in form (morphology) are decoupled from rates of evolution in function. Further, we found theoretical morphologies optimising for velocity to be more diverse, while a much smaller phenotypic space was occupied by shapes optimising force. This pattern of differential representation of different functions in theoretical morphological space was highly correlated with patterns of actual morphological disparity. We hypothesise that many-to-one mapping of cranium shape on function may prevent the detection of direct relationships between form and function. As comparatively only few morphologies optimise bite force, species optimising this function may be less abundant because they are less likely to evolve. This, in turn, may explain why certain clades are less variable than others. Given the ubiquity of functional trade-offs in biological systems, these patterns may be general and may help to explain the unevenness of morphological and functional diversity across the tree of life

The proposed Caroline ESA M3 mission to a Main Belt Comet

We describe Caroline, a mission proposal submitted to the European Space Agency in 2010 in response to the Cosmic Visions M3 call for medium-sized missions. Caroline would have travelled to a Main Belt Comet (MBC), characterizing the object during a flyby, and capturing dust from its tenuous coma for return to Earth. MBCs are suspected to be transition objects straddling the traditional boundary between volatile–poor rocky asteroids and volatile–rich comets. The weak cometary activity exhibited by these objects indicates the presence of water ice, and may represent the primary type of object that delivered water to the early Earth. The Caroline mission would have employed aerogel as a medium for the capture of dust grains, as successfully used by the NASA Stardust mission to Comet 81P/Wild 2. We describe the proposed mission design, primary elements of the spacecraft, and provide an overview of the science instruments and their measurement goals. Caroline was ultimately not selected by the European Space Agency during the M3 call; we briefly reflect on the pros and cons of the mission as proposed, and how current and future mission MBC mission proposals such as Castalia could best be approached

Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice.

Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 micro m aerodynamic diameter; PM(2.5)) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM(2.5) from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM(2.5) from Hettstedt, but not PM(2.5) from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM(2.5) whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM(2.5) before challenge. Both Hettstedt and Zerbst PM(2.5) significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM(2.5) influences the severity of allergic respiratory disease

A convenient and efficient synthesis of (S)-lysine and (S)-arginine homologues via olefin cross-metathesis

A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine