Construction safety and digital design: a review

As digital technologies become widely used in designing buildings and infrastructure, questions arise about their impacts on construction safety. This review explores relationships between construction safety and digital design practices with the aim of fostering and directing further research. It surveys state-of-the-art research on databases, virtual reality, geographic information systems, 4D CAD, building information modeling and sensing technologies, finding various digital tools for addressing safety issues in the construction phase, but few tools to support design for construction safety. It also considers a literature on safety critical, digital and design practices that raises a general concern about ‘mindlessness’ in the use of technologies, and has implications for the emerging research agenda around construction safety and digital design. Bringing these strands of literature together suggests new kinds of interventions, such as the development of tools and processes for using digital models to promote mindfulness through multi-party collaboration on safet

Hepatitis C virus 3'UTR regulates viral translation through direct interactions with the host translation machinery.

The 3' untranslated region (3'UTR) of hepatitis C virus (HCV) messenger RNA stimulates viral translation by an undetermined mechanism. We identified a high affinity interaction, conserved among different HCV genotypes, between the HCV 3'UTR and the host ribosome. The 3'UTR interacts with 40S ribosomal subunit proteins residing primarily in a localized region on the 40S solvent-accessible surface near the messenger RNA entry and exit sites. This region partially overlaps with the site where the HCV internal ribosome entry site was found to bind, with the internal ribosome entry site-40S subunit interaction being dominant. Despite its ability to bind to 40S subunits independently, the HCV 3'UTR only stimulates translation in cis, without affecting the first round translation rate. These observations support a model in which the HCV 3'UTR retains ribosome complexes during translation termination to facilitate efficient initiation of subsequent rounds of translation

Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease

The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DDB1–CUL4 associated factors substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. Aberrant expression of the cullin 4A (CUL4A) gene is found in many tumor types, while mutations of the cullin 4B (CUL4B) gene are causally associated with human X-linked mental retardation. This focused review will summarize our current knowledge of the two CUL4 family members in the pathogenesis of human malignancy and neuronal disease, and discuss their potential as new targets for cancer prevention and therapeutic intervention

CRISPR/Cas9-mediated gene manipulation to create single-amino-acid-substituted and floxed mice with a cloning-free method.

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology is a powerful tool to manipulate the genome with extraordinary simplicity and speed. To generate genetically modified animals, CRISPR/Cas9-mediated genome editing is typically accomplished by microinjection of a mixture of Cas9 DNA/mRNA and single-guide RNA (sgRNA) into zygotes. However, sgRNAs used for this approach require manipulation via molecular cloning as well as in vitro transcription. Beyond these complexities, most mutants obtained with this traditional approach are genetically mosaic, yielding several types of cells with different genetic mutations. Recently, a growing body of studies has utilized commercially available Cas9 protein together with sgRNA and a targeting construct to introduce desired mutations. Here, we report a cloning-free method to target the mouse genome by pronuclear injection of a commercial Cas9 protein:crRNA:tracrRNA:single-strand oligodeoxynucleotide (ssODN) complex into mouse zygotes. As illustration of this method, we report the successful generation of global gene-knockout, single-amino-acid-substituted, as well as floxed mice that can be used for conditional gene-targeting. These models were produced with high efficiency to generate non-mosaic mutant mice with a high germline transmission rate

The Sapheos Project: Transparency in Multi-image Collation, Analysis, and Representation

Our proposal for a Level II Start-Up grant for the Sapheos project seeks to develop innovative software to analyze, represent, and collate images in the humanities. While there are an array of text based digital projects underway that offer increasingly powerful tools for marking up, analyzing, and visualizing textual data in the humanities, image-based analysis has not received similar attention. From the project's inception, our aim has been to develop extensible open-source software that researchers across the humanities can use to link image to text in a discrete, granular fashion. Working with the NEH-funded Spenser Project, a multi-institutional Scholarly Editions project, we're developing two significant image-based software tools: (a) digital collation software that builds on and extends the work of optical methods, using transparency to "stack" and collate multiple copies, and (b) software for automatically sectioning and identifying (x,y) coordinate pairs for images

Cryo-EM structure of the mature dengue virus at 3.5-Å resolution.

Regulated by pH, membrane-anchored proteins E and M function during dengue virus maturation and membrane fusion. Our atomic model of the whole virion from cryo-electron microscopy at 3.5-Å resolution reveals that in the mature virus at neutral extracellular pH, the N-terminal 20-amino-acid segment of M (involving three pH-sensing histidines) latches and thereby prevents spring-loaded E fusion protein from prematurely exposing its fusion peptide. This M latch is fastened at an earlier stage, during maturation at acidic pH in the trans-Golgi network. At a later stage, to initiate infection in response to acidic pH in the late endosome, M releases the latch and exposes the fusion peptide. Thus, M serves as a multistep chaperone of E to control the conformational changes accompanying maturation and infection. These pH-sensitive interactions could serve as targets for drug discovery

The Validity of Online Patient Ratings of Physicians

Background: Information from ratings sites are increasingly informing patient decisions related to health care and the selection of physicians. Objective: The current study sought to determine the validity of online patient ratings of physicians through comparison with physician peer review. Methods: We extracted 223,715 reviews of 41,104 physicians from 10 of the largest cities in the United States, including 1142 physicians listed as “America’s Top Doctors” through physician peer review. Differences in mean online patient ratings were tested for physicians who were listed and those who were not. Results: Overall, no differences were found between the online patient ratings based upon physician peer review status. However, statistical differences were found for four specialties (family medicine, allergists, internal medicine, and pediatrics), with online patient ratings significantly higher for those physicians listed as a peer-reviewed “Top Doctor” versus those who were not. Conclusions: The results of this large-scale study indicate that while online patient ratings are consistent with physician peer review for four nonsurgical, primarily in-office specializations, patient ratings were not consistent with physician peer review for specializations like anesthesiology. This result indicates that the validity of patient ratings varies by medical specialization