Glows Co Automated Chemical Etching Machine for Fiber Optic Cable

This report summarizes the conceptualization and development of an automated machine designed for a fiber optic cable stripping process used by Lumentum LLC. This process is currently manually operated by Lumentum’s technicians and involves unavoidable handling of corrosive chemicals. To increase technician safety, the process will be automated to reduce chemical - operator interactions. Improving safety conditions for technicians is the primary motivation for automating this process. Automation will also decrease process variation and increase product quality. GLOWS CO was tasked with creating this automated solution, leading to the design of the Automatic Chemical Etching Machine (or A-CHEM) for the fiber etching process for Lumentum LLC. At the conclusion of this project, the A-CHEM successfully fulfilled all of the requirements set out by Lumentum, namely improving technician safety and making the process more ergonomic

Elite interviewing in professional organizations

Interviewing elites presents distinctive methodological challenges, which are exacerbated when interviewing elite professionals. These individuals (i.e. senior professionals and professionals in elite professional organizations) are typically relatively powerful, highly educated, and self-assured, and work in organizations which guard their external image very carefully. Over the past 25 years I have interviewed many hundreds of senior professionals in elite professional organizations. For this article, I have reflected on my experiences and have asked senior professionals to reflect on their own experience of research interviews. Bringing together insights of both interviewees and interviewers, this article provides an opportunity for researchers to reflect upon and improve their professional practice when conducting elite interviews

Revisiting the missing protein-coding gene catalog of the domestic dog

<p>Abstract</p> <p>Background</p> <p>Among mammals for which there is a high sequence coverage, the whole genome assembly of the dog is unique in that it predicts a low number of protein-coding genes, ~19,000, compared to the over 20,000 reported for other mammalian species. Of particular interest are the more than 400 of genes annotated in primates and rodent genomes, but missing in dog.</p> <p>Results</p> <p>Using over 14,000 orthologous genes between human, chimpanzee, mouse rat and dog, we built multiple pairwise synteny maps to infer short orthologous intervals that were targeted for characterizing the canine missing genes. Based on gene prediction and a functionality test using the ratio of replacement to silent nucleotide substitution rates (<it>d</it>_N/<it>d</it>_S), we provide compelling structural and functional evidence for the identification of 232 new protein-coding genes in the canine genome and 69 gene losses, characterized as undetected gene or pseudogenes. Gene loss phyletic pattern analysis using ten species from chicken to human allowed us to characterize 28 canine-specific gene losses that have functional orthologs continuously from chicken or marsupials through human, and 10 genes that arose specifically in the evolutionary lineage leading to rodent and primates.</p> <p>Conclusion</p> <p>This study demonstrates the central role of comparative genomics for refining gene catalogs and exploring the evolutionary history of gene repertoires, particularly as applied for the characterization of species-specific gene gains and losses.</p

Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer.

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and A

An integrated 4249 marker FISH/RH map of the canine genome

BACKGROUND: The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. RESULTS: To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH) map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs) localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH). The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS) between the dog and human genomes, dramatically extending the length of most previously described CS. CONCLUSIONS: These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps

Building relationships and facilitating immigrant community integration: An evaluation of a Cultural Navigator Program

Despite the United States’ long history of immigration, large and small communities around the country struggle to integrate newcomers into the social, economic, cultural, and political spheres of society. Utilizing results from the program evaluation of one public library’s Cultural Navigator Program (CNP), the authors illustrate how communities and public institutions can promote integration and relationship building between newly arrived immigrants and long-time residents. Existing social networks, conceptualized in this article as social capital, within receiving communities were leveraged to build capacity among newly arrived immigrants and foster inclusivity and integration at the community level. As a place of intervention, public libraries are suggested as a safe and shared space where community integration can be fostered. The program model is provided as an approach to immigrant community integration. Insights derived from the evaluation inform a discussion on engaging approaches to immigrant integration. The CNP utilized community networks to deliberately and systematically facilitate integration and relationship building between newly arrived immigrants and community members. Lessons learned and recommendations for program evaluators and administrators are provided

Survey sequencing and radiation hybrid mapping to construct comparative maps.

In MURPHY WJ (ed.) Phylogenomics, Humana Press. (Methods in Molecular Biology, 422)International audienceRadiation hybrid (RH) mapping has become one of the most well-established techniques for economically and efficiently navigating genomes of interest. The success of the technique relies on random chromosome breakage of a target genome, which is then captured by recipient cells missing a preselected marker. Selection for hybrid cells that have DNA fragments bearing the marker of choice, plus a random set of DNA fragments from the initial irradiation, generates a set of cell lines that recapitulates the genome of the target organism several-fold. Markers or genes of interest are analyzed by PCR using DNA isolated from each cell line. Statistical tools are applied to determine both the linear order of markers on each chromosome, and the confidence of each placement. The resolution of the resulting map relies on many factors, most notably the degree of breakage from the initial radiation as well as the number of hybrid clones and mean retention value.A high-resolution RH map of a genome derived from low pass or survey sequencing (coverage from 1 to 2 times) can provide essentially the same comparative data on gene order that is derived from high-coverage (greater than x7) genome sequencing. When combined with fluorescence in situ hybridization, RH maps are complete and ordered blueprints for each chromosome. They give information about the relative order and spacing of genes and markers, and allow investigators to move between target and reference genomes, such as those of mouse or human, with ease although the approach is not limited to mammal genomes

Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e−8) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e−11). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer pre-disposition locus

An ADAMTS3 Missense Variant is Associated with Norwich Terrier Upper Airway Syndrome

In flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome (BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers, a mesocephalic breed, are predisposed to Upper Airway Syndrome (UAS), a disease whose pathological features overlap with BOAS. Our health screening clinic examined and scored the airways of 401 Norwich terriers by laryngoscopy. Genome-wide association analyses of UAS-related pathologies revealed a genetic association on canine chromosome 13 (rs9043975, p = 7.79x10-16). Whole genome resequencing was used to identify causal variant(s) within a 414 kb critical interval. This approach highlighted an error in the CanFam3.1 dog assembly, which when resolved, led to the discovery of a c.2786G>A missense variant in exon 20 of the positional candidate gene, ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3). In addition to segregating with UAS amongst Norwich Terriers, the ADAMTS3 c.2786G>A risk allele frequency was enriched among the BOAS-susceptible French and (English) Bulldogs. Previous studies indicate that ADAMTS3 loss of function results in lymphoedema. Our results suggest a new paradigm in the understanding of canine upper airway disease aetiology: airway oedema caused by disruption of ADAMTS3 predisposes dogs to respiratory obstruction. These findings will enhance breeding practices and could refine the prognostics of surgical interventions that are often used to treat airway obstruction