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Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

Purpose - The aim of this paper is to present a sampling method using virtual networks to study \"hard-to-reach\" populations. In the ambit of social research, the use of new technologies is still questioned because the selection bias is an obstacle to carry on scientific research on the Internet. In this regard, the authors' hypothesis is that the use of social networking sites (Web 2.0) can be effective for the study of \"hard-to-reach\" populations. The main advantages of this technique are that it can expand the geographical scope and facilitates the identification of individuals with barriers to access. Therefore, the use of virtual networks in non-probabilistic samples can increase the sample size and its representativeness.Design methodology approach - To test this hypothesis, a virtual method was designed using Facebook to identify Argentinean immigrant entrepreneurs in Spain (214 cases). A characteristic of this population is that some individuals are administratively invisible in national statistics because they have double nationality (non-EU and EU). The use of virtual sampling was combined with an online questionnaire as a complementary tool for Web 2.0 research in behavioural sciences.Findings - The number of cases detected by Facebook and the virtual response rate is higher than traditional snowball technique. The explanation is that people increase their level of confidence because the researcher shows his personal information (Facebook's profile) and also participates in their groups of interest (Facebook's groups). Moreover, the online questionnaires administration allows the quality of the information to be controlled and avoids duplication of cases.Originality value - The present article is the first that uses Facebook as an instrument to study immigrants. Therefore its adoption represents a great challenge in the social research field because there are many barriers of access and search. It also proposes a novel mix of traditional methodologies updated with the use of new virtual possibilities of studying hard to reach populations, especially in areas of social research where the contributions of these methods are less developed.

Certain social groups are often difficult for researchers to access because of their social or physical location, vulnerability, or otherwise hidden nature. This unique review article based on both the small body of relevant literature and our own experiences as researchers is meant as a guide for those seeking to include hard-to-reach, hidden, and vulnerable populations in research. We make recommendations for research process starting from early stages of study design to dissemination of study results. Topics covered include participant mistrust of the research process; social, psychological, and physical risks to participation; participant resource constraints; and challenges inherent in nonprobability sampling, snowball sampling, and derived rapport. This article offers broadly accessible solutions for qualitative researchers across social science disciplines attempting to research a variety of different populations.

A Digraph D consists of two finite sets ), where denotes the vertex set and denotes the arc set. For vertices if there exists a directed path from to then is said to be reachable from and vice versa. The Reachability matrix of D is the matrix , where if is reachable from and otherwise. The eigen values corresponding to the reachability matrix are called reach eigen values. The reach energy of a digraph is defined by where is the eigen value of the reachability matrix. In this paper we introduce the reach spectrum of a digraph and study its properties and bounds. Moreover, we compute reachspectrum for some digraphs.

Deep-water navigation channels in the tidal reaches of the lower Yangtze River are affected by water and sediment fluxes that produce complex shoals and unstable channel conditions. The Fujiangsha reach is particularly difficult to manage, as it has many braided channels within the tidal fluctuation zone. In this study, hydrologic and topographic data from the Fujiangsha reach from 2012 to 2017 were used to examine the variations in deposition and erosion, flow diversion, shoals, and channel conditions. Since the Three Gorges Dam became operational and water storage was initiated, the Fujiangsha reach has shown an overall tendency toward erosion. Channels deeper than 10 m accounted for 83.7% of the total erosion of the Fujiangsha reach during 2012–2017. Moreover, the dominant channel-forming sediments have gradually changed from suspended sediments to a mixed load of suspended and bed-load sediments. Deposition volumes of these sediments has varied significantly among different channels, but has mainly occurred in the Fubei channel. Furthermore, periodic variations in the Jingjiang point bar have followed a deposition-erosion-deposition pattern, and the downstream Shuangjian shoal mid-channel bar has been scoured and shortened. Approximately 44.0% of the bed load from the upstream Fujiangsha reach is deposited within the 12.5-m deep Fubei channel. The increased erosion and river flow from the Jingjiang point bar and the Shuangjian shoal during the flood season constituted 59.3% and 40.7%, respectively, of the total amount of siltation in the Fubei channel.

•Premotor frontoparietal cortex encodes the spatial goals for movement plans.•Activity patterns appear interchangeable when planning eye and arm movements.•Implicates an efficient and effector-general mechanism for movement planning. In the nonhuman primate, discrete parts of premotor frontal and parietal cortex appear to code for movements of different effectors. However, the evidence regarding homologous effector selectivity within the human brain remains inconclusive. Here, we measured neural activity in the human brain using functional magnetic resonance imaging while participants remembered a target location and planned either saccades or reaches that matched the rich kinematics used in seminal monkey studies. We compared activity patterns during the planning period and used assumption-free multivariate searchlight analysis to identify brain regions that could decode the spatial goals of planned movements. Critically, we performed two types of decoding analyses to determine if the spatial information embedded in activation patterns was effector-specific or effector-general. For effector-specific spatial coding, we compared brain regions that could decode target locations within each effector. However, we did not identify areas that coded spatial information in one effector but not the other. For effector-general spatial coding, we performed spatial decoding using trials across effectors and conducted cross-effector decoding. Both analyses identified several areas in the frontal and parietal regions that encoded spatial information for both effectors, including precentral sulcus, superior parietal lobe, and intraparietal sulcus. Our results indicate that premotor frontal and parietal cortex encode the spatial metrics of movement goals that can be read out and converted into effector-specific motor metrics for saccades and reaches.

Respondent-driven sampling (RDS) is a widely used method for sampling from hard-to-reach human populations, especially populations at higher risk for human immunodeficiency virus or acquired immune deficiency syndrome. Data are collected through a peer referral process over social networks. RDS has proven practical for data collection in many difficult settings and has been adopted by leading public health organizations around the world. Unfortunately, inference from RDS data requires many strong assumptions because the sampling design is partially beyond the control of the researcher and not fully observable. We introduce diagnostic tools for most of these assumptions and apply them in 12 high risk populations. These diagnostics empower researchers to understand their RDS data better and encourage future statistical research on RDS sampling and inference.

Social media is a popular online tool that allows users to communicate and exchange information. It allows digital content such as pictures, videos and websites to be shared, discussed, republished and endorsed by its users, their friends and businesses. Adverts can be posted and promoted to specific target audiences by demographics such as region, age or gender. Recruiting for health research is complex with strict requirement criteria imposed on the participants. Traditional research recruitment relies on flyers, newspaper adverts, radio and television broadcasts, letters, emails, website listings, and word of mouth. These methods are potentially poor at recruiting hard to reach demographics, can be slow and expensive. Recruitment via social media, in particular Facebook, may be faster and cheaper. The aim of this study was to systematically review the literature regarding the current use and success of Facebook to recruit participants for health research purposes. A literature review was completed in March 2017 in the English language using MEDLINE, EMBASE, Web of Science, PubMed, PsycInfo, Google Scholar, and a hand search of article references. Papers from the past 12 years were included and number of participants, recruitment period, number of impressions, cost per click or participant, and conversion rate extracted. A total of 35 studies were identified from the United States (n=22), Australia (n=9), Canada (n=2), Japan (n=1), and Germany (n=1) and appraised using the Critical Appraisal Skills Programme (CASP) checklist. All focused on the feasibility of recruitment via Facebook, with some (n=10) also testing interventions, such as smoking cessation and depression reduction. Most recruited young age groups (16-24 years), with the remaining targeting specific demographics, for example, military veterans. Information from the 35 studies was analyzed with median values being 264 recruited participants, a 3-month recruitment period, 3.3 million impressions, cost per click of US $0.51, conversion rate of 4% (range 0.06-29.50), eligibility of 61% (range 17-100), and cost per participant of US $14.41. The studies showed success in penetrating hard to reach populations, finding the results representative of their control or comparison demographic, except for an over representation of young white women. There is growing evidence to suggest that Facebook is a useful recruitment tool and its use, therefore, should be considered when implementing future health research. When compared with traditional recruitment methods (print, radio, television, and email), benefits include reduced costs, shorter recruitment periods, better representation, and improved participant selection in young and hard to reach demographics. It however, remains limited by Internet access and the over representation of young white women. Future studies should recruit across all ages and explore recruitment via other forms of social media.

Model tools for estimating hazardous substance exposure are an accepted part of regulatory risk assessments in Europe, and models underpin control banding tools used to help manage chemicals in workplaces. Of necessity the models are simplified abstractions of real-life working situations that aim to capture the essence of the scenario to give estimates of actual exposures with an appropriate margin of safety. The basis for existing inhalation exposure assessment tools has recently been discussed by some scientists who have argued for the use of more complex models. In our opinion, the currently accepted tools are documented to be the most robust way for workplace health and safety practitioners and others to estimate inhalation exposure. However, we recognise that it is important to continue the scientific development of exposure modelling to further elaborate and improve the existing methodologies.

Nanoparticles (NPs) of copper oxide (CuO), zinc oxide (ZnO) and especially nanosilver are intentionally used to fight the undesirable growth of bacteria, fungi and algae. Release of these NPs from consumer and household products into waste streams and further into the environment may, however, pose threat to the ‘non-target’ organisms, such as natural microbes and aquatic organisms. This review summarizes the recent research on (eco)toxicity of silver (Ag), CuO and ZnO NPs. Organism-wise it focuses on key test species used for the analysis of ecotoxicological hazard. For comparison, the toxic effects of studied NPs toward mammalian cells in vitro were addressed. Altogether 317 L(E)C50 or minimal inhibitory concentrations (MIC) values were obtained for algae, crustaceans, fish, bacteria, yeast, nematodes, protozoa and mammalian cell lines. As a rule, crustaceans, algae and fish proved most sensitive to the studied NPs. The median L(E)C50 values of Ag NPs, CuO NPs and ZnO NPs (mg/L) were 0.01, 2.1 and 2.3 for crustaceans; 0.36, 2.8 and 0.08 for algae; and 1.36, 100 and 3.0 for fish, respectively. Surprisingly, the NPs were less toxic to bacteria than to aquatic organisms: the median MIC values for bacteria were 7.1, 200 and 500 mg/L for Ag, CuO and ZnO NPs, respectively. In comparison, the respective median L(E)C50 values for mammalian cells were 11.3, 25 and 43 mg/L. Thus, the toxic range of all the three metal-containing NPs to target- and non-target organisms overlaps, indicating that the leaching of biocidal NPs from consumer products should be addressed.