Communicating Uncertainty and Risk in Air Quality Maps

Environmental sensors provide crucial data for understanding our surroundings. For example, air quality maps based on sensor readings help users make decisions to mitigate the effects of pollution on their health. Standard maps show readings from individual sensors or colored contours indicating estimated pollution levels. However, showing a single estimate may conceal uncertainty and lead to underestimation of risk, while showing sensor data yields varied interpretations. We present several visualizations of uncertainty in air quality maps, including a frequency-framing "dotmap" and small multiples, and we compare them with standard contour and sensor-based maps. In a user study, we find that including uncertainty in maps has a significant effect on how much users would choose to reduce physical activity, and that people make more cautious decisions when using uncertainty-aware maps. Additionally, we analyze think-aloud transcriptions from the experiment to understand more about how the representation of uncertainty influences people's decision-making. Our results suggest ways to design maps of sensor data that can encourage certain types of reasoning, yield more consistent responses, and convey risk better than standard maps

Crystal structure of the signaling helix coiled-coil domain of the β1 subunit of the soluble guanylyl cyclase

<p>Abstract</p> <p>Background</p> <p>The soluble guanylyl cyclase (sGC) is a heterodimeric enzyme that, upon activation by nitric oxide, stimulates the production of the second messenger cGMP. Each sGC subunit harbor four domains three of which are used for heterodimerization: H-NOXA/H-NOBA domain, coiled-coil domain (CC), and catalytic guanylyl cyclase domain. The CC domain has previously been postulated to be part of a larger CC family termed the signaling helix (S-helix) family. Homodimers of sGC have also been observed but are not functionally active yet are likely transient awaiting their intended heterodimeric partner.</p> <p>Results</p> <p>To investigate the structure of the CC S-helix region, we crystallized and determined the structure of the CC domain of the sGCβ1 subunit comprising residues 348-409. The crystal structure was refined to 2.15 Å resolution.</p> <p>Conclusions</p> <p>The CC structure of sGCβ1 revealed a tetrameric arrangement comprised of a dimer of CC dimers. Each monomer is comprised of a long a-helix, a turn near residue P399, and a short second a-helix. The CC structure also offers insights as to how sGC homodimers are not as stable as (functionally) active heterodimers via a possible role for inter-helix salt-bridge formation. The structure also yielded insights into the residues involved in dimerization. In addition, the CC region is also known to harbor a number of congenital and man-made mutations in both membrane and soluble guanylyl cyclases and those function-affecting mutations have been mapped onto the CC structure. This mutant analysis indicated an importance for not only certain dimerization residue positions, but also an important role for other faces of the CC dimer which might perhaps interact with adjacent domains. Our results also extend beyond guanylyl cyclases as the CC structure is, to our knowledge, the first S-helix structure and serves as a model for all S-helix containing family members.</p

Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.

BackgroundHomozygous Familial Hypercholesterolemia (HoFH) is an inherited recessive condition associated with extremely high levels of low-density lipoprotein (LDL) cholesterol in affected individuals. It is usually caused by homozygous or compound heterozygous functional mutations in the LDL receptor (LDLR). A number of mutations causing FH have been reported in literature and such genetic heterogeneity presents great challenges for disease diagnosis.ObjectiveWe aim to determine the likely genetic defects responsible for three cases of pediatric HoFH in two kindreds.MethodsWe applied whole exome sequencing (WES) on the two probands to determine the likely functional variants among candidate FH genes. We additionally applied 10x Genomics (10xG) Linked-Reads whole genome sequencing (WGS) on one of the kindreds to identify potentially deleterious structural variants (SVs) underlying HoFH. A PCR-based screening assay was also established to detect the LDLR structural variant in a cohort of 641 patients with elevated LDL.ResultsIn the Caucasian kindred, the FH homozygosity can be attributed to two compound heterozygous&nbsp;LDLR damaging variants, an exon 12 p.G592E missense mutation and a novel 3kb exon 1 deletion. By analyzing the 10xG phased data, we ascertained that this deletion allele was most likely to have originated from a Russian ancestor. In the Mexican kindred, the strikingly elevated LDL cholesterol level can be attributed to a homozygous frameshift LDLR variant p.E113fs.ConclusionsWhile the application of WES can provide a cost-effective way of identifying the genetic causes of FH, it often lacks sensitivity for detecting structural variants. Our finding of the LDLR exon 1 deletion highlights the broader utility of Linked-Read WGS in detecting SVs in the clinical setting, especially when HoFH patients remain undiagnosed after WES

Embedding Chinese Atypical Workers in the Indigenous ‘Unequal Pay for Equal Work’: Introduction and Implications

The employment relationships in the Chinese context have attracted increasing scholarly attention, especially after the last amendment of its labour law in 2008. Despite the growing scholarship studying various aspects of Chinese employment and practices, many indigenous employment phenomena remain veiled in the English literature. In this paper, we aim to make a preliminary attempt to bring to the fore an indigenous feature of the atypical workers in China, i.e., embedding these workers in the ‘unequal pay for equal work' phenomenon. The opportunities and challenges brought on to management scholars interested in doing future research in the Chinese context are discussed

Zac1 functions through TGFβII to negatively regulate cell number in the developing retina

<p>Abstract</p> <p>Background</p> <p>Organs are programmed to acquire a particular size during development, but the regulatory mechanisms that dictate when dividing progenitor cells should permanently exit the cell cycle and stop producing additional daughter cells are poorly understood. In differentiated tissues, tumor suppressor genes maintain a constant cell number and intact tissue architecture by controlling proliferation, apoptosis and cell dispersal. Here we report a similar role for two tumor suppressor genes, the <it>Zac1 </it>zinc finger transcription factor and that encoding the cytokine TGFβII, in the developing retina.</p> <p>Results</p> <p>Using loss and gain-of-function approaches, we show that <it>Zac1 </it>is an essential negative regulator of retinal size. <it>Zac1 </it>mutants develop hypercellular retinae due to increased progenitor cell proliferation and reduced apoptosis at late developmental stages. Consequently, supernumerary rod photoreceptors and amacrine cells are generated, the latter of which form an ectopic cellular layer, while other retinal cells are present in their normal number and location. Strikingly, <it>Zac1 </it>functions as a direct negative regulator of a rod fate, while acting cell non-autonomously to modulate amacrine cell number. We implicate TGFβII, another tumor suppressor and cytokine, as a <it>Zac1</it>-dependent amacrine cell negative feedback signal. TGFβII and phospho-Smad2/3, its downstream effector, are expressed at reduced levels in <it>Zac1 </it>mutant retinae, and exogenous TGFβII relieves the mutant amacrine cell phenotype. Moreover, treatment of wild-type retinae with a soluble TGFβ inhibitor and TGFβ receptor II (TGFβRII) conditional mutants generate excess amacrine cells, phenocopying the <it>Zac1 </it>mutant phenotype.</p> <p>Conclusion</p> <p>We show here that <it>Zac1 </it>has an essential role in cell number control during retinal development, akin to its role in tumor surveillance in mature tissues. Furthermore, we demonstrate that <it>Zac1 </it>employs a novel cell non-autonomous strategy to regulate amacrine cell number, acting in cooperation with a second tumor suppressor gene, <it>TGFβII</it>, through a negative feedback pathway. This raises the intriguing possibility that tumorigenicity may also be associated with the loss of feedback inhibition in mature tissues.</p

Simple messages to improve dietary quality: A pilot investigation

Public health recommendations for a healthy diet often involve complex messages, requiring in-depth knowledge for understanding and compliance. The present study compared the feasibility and initial efficacy of two simple messages (a high fiber diet or a low saturated fat diet) to a combination message (high fiber and low saturated fat) on the potential to impact dietary quality and metabolic health. Conclusions: A simple dietary message appears to improve overall dietary quality and aid in weight management. Simple messages are a novel approach which could make a significant impact on the prevention and treatment of chronic disease as well as weight management. Results support the need for a larger randomized controlled trial that is powered to examine the efficacy of a simplified dietary recommendation for dietary quality and metabolic health. It would be worth exploring the impact of simple messages in a larger trial to determine their usefulness as simple public health messages as an alternative the current complex recommendations

Prosodic distances between different survey sites in Romance-speaking Europe

[eng] The aim of this paper is to classify Romanian dialects from a prosodic point of view within the European Romance-speaking area. The data is part of the Multimedia Atlas of Romance Prosody - AMPER (Contini, 1992) and is analysed dialectometrically by means of ProDis (Elvira-García et al., 2015; Fernández Planas, 2016). The database includes more than 17,000 utterances produced by 48 speakers from 26 survey sites of 15 varieties of 6 Romance languages (Catalan, Spanish, Italian, Sardinian, Friulian and Romanian). The results show that the two main prosodic areas of Romanian (see Roseano, 2016b) remain separate when they are dialectometrized with data from other Romance languages. In addition, if one analyses questions and statements separately, it can be seen that questions allow us to distinguish geoprosodic areas more effectively than statements do (as suggested by previous studies such as Fernández Planas et al., 2015)

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (&gt;2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome