Alterations in Colorectal Cancer Cell-extracellular Matrix Interactions Upon Acquisition of Chemotherapy Resistance.

Adjuvant chemotherapy is an essential component in the treatment of advanced colorectal cancer (CRC). Unfortunately, many patients experience recurrence with aggressive, chemotherapy-resistant disease for which the prognosis is poor and treatment options are limited. Understanding the changes that cancer cells undergo during the acquisition of a drug-resistant phenotype is therefore of critical importance in improving CRC patient outcomes. We chose to study resistance to the CRC chemotherapy agent, irinotecan, by first creating a CRC cell line that is highly resistant to its active metabolite (SN-38). In particular, we were interested in how SN-38 resistant CRC cells (HT-29S) were altered from parental, drug-sensitive CRC cells (HT-29) in their relationship with a feature of their microenvironment, the extracellular matrix (ECM). We found that HT-29S cells form a matrix composed of the ECM glycoprotein fibronectin when cultured as 3-dimensional spheroids, whereas HT-29 cells do not. The increase in fibronectin matrix deposition coincided with an increased fibronectin adhesive capacity of the SN-38-resistant cells, likely due to an increased expression of the integrin α5 subunit, which together with integrin β1 forms the primary fibronectin receptor. Furthermore, we demonstrated an activation of a phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pro-survival signalling pathway downstream of integrin α5β1 ligation to fibronectin. Inhibition of this signalling pathway with the PI3K inhibitor LY294002 sensitized HT-29S cells to SN-38, but did not alter the response of the parental cell line to the chemotherapy agent. Finally, we have determined that HT-29S cells appear to undergo an epithelial to mesenchymal transition during the acquisition of chemotherapy resistance, and that this transition may be responsible for the upregulation of integrin α5 in the resistant population

Risks to job quality from digital technologies: Are industrial relations in Europe ready for the challenge?

We examine job quality effects of new digital technologies, using the European frame of seven job quality domains: Pay, Working Time Quality, Prospects, Skills and Discretion, Work Intensity, Social Environment, and Physical Environment. Theoretical effects are ambivalent across all domains. The analysis of these effects confirms that digital technologies can both improve and harm job quality depending on how they are used. In light of this analysis and to think through the challenge of regulating digital technologies, we review emerging regulations across several European countries. Drawing on the principles of human-centred design, we argue that worker participation is important for securing good job quality outcomes, at both the innovation and adoption stages. We also consider the application of data protection legislation to the regulation of job quality. Overall, the paper extends debate about the future of work beyond employment and pay, on to a consideration of job quality more broadly

Instanton size distribution in O(3)

We present calculations of the size distribution of instantons in the 2d O(3) non-linear sigma-model, and briefly discuss the effects cooling has upon the configurations and the topological objects. (This preprint is also available via anonymous ftp to suna.amtp.liv.ac.uk in /pub/pss/ as instdist.uue.)Comment: 17 pages, LaTeX, needs cite.sty (appended), with appended uuencoded compressed tarfile of PostScript figures, Liverpool preprint LTH-33

Graphics for relatedness research

Studies of relatedness have been crucial in molecular ecology over the last decades. Good evidence of this is the fact that studies of population structure, evolution of social behaviours, genetic diversity and quantitative genetics all involve relatedness research. The main aim of this article is to review the most common graphical methods used in allele sharing studies for detecting and identifying family relationships. Both IBS and IBD based allele sharing studies are considered. Furthermore, we propose two additional graphical methods from the field of compositional data analysis: the ternary diagram and scatterplots of isometric log-ratios of IBS and IBD probabilities. We illustrate all graphical tools with genetic data from the HGDP-CEPH diversity panel, using mainly 377 microsatellites genotyped for 25 individuals from the Maya population of this panel. We enhance all graphics with convex hulls obtained by simulation and use these to confirm the documented relationships. The proposed compositional graphics are shown to be useful in relatedness research, as they also single out the most prominent related pairs. The ternary diagram is advocated for its ability to display all three allele sharing probabilities simultaneously. The log-ratio plots are advocated as an attempt to overcome the problems with the Euclidean distance interpretation in the classical graphics.Peer ReviewedPostprint (published version

The association between prenatal atrioventricular septal defects and chromosomal abnormalities

Objective Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21. Methods Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250. Results A total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95%CI: 36-56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95%CI: 27-57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly higher than in the low risk group (p = 0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p = 0.055). Conclusions The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process

Segment Anything

We introduce the Segment Anything (SA) project: a new task, model, and dataset for image segmentation. Using our efficient model in a data collection loop, we built the largest segmentation dataset to date (by far), with over 1 billion masks on 11M licensed and privacy respecting images. The model is designed and trained to be promptable, so it can transfer zero-shot to new image distributions and tasks. We evaluate its capabilities on numerous tasks and find that its zero-shot performance is impressive -- often competitive with or even superior to prior fully supervised results. We are releasing the Segment Anything Model (SAM) and corresponding dataset (SA-1B) of 1B masks and 11M images at https://segment-anything.com to foster research into foundation models for computer vision.Comment: Project web-page: https://segment-anything.co

LMDA Review, volume 9, issue 1

Contents include: Mid-Year Meetings, Words of Thanks from Jayme Koszyn Outgoing President of LMDA, Anne Cattaneo of Lincoln Center Theater Receives Dramaturgy Award, May I have the Envelope, Please?, Rent Settlement, On Advocacy, A VP is a VIP is a VP, LMDA Canada, Next Annual LMDA Conference, Early Career Dramaturg Program, Script Exchange, ATHE \u2799 Toronto Border to Board, ATHE \u2799 Toronto Debut Panel, ATHE \u27 99 Toronto Call for Directors, Actors, Dramaturgs for the New Play Development Workshop, Report on Last June\u27s Conference, Report on Last June\u27s Conference LMDA University Caucus Pre-Conference and Source Books, Minutes June 1998, LMDA Job Line, Job Listings, and the Membership Directory, LMDA Online, Supplement to the LMDA Bibliography, and Call for Papers Theatre Topics: Dramaturgy, Pedagogy, Performance.https://soundideas.pugetsound.edu/lmdareview/1018/thumbnail.jp

Snow petrel stomach-oil deposits as a new biological archive of Antarctic sea ice

Where snow petrels forage is predominantly a function of sea ice. They spit stomach oil in defence, and accumulated deposits at nesting sites are providing new opportunities to reconstruct their diet, and, in turn, the sea-ice environment over past millennia

Radar absorption, basal reflection, thickness and polarization measurements from the Ross Ice Shelf, Antarctica

Radio-glaciological parameters from the Moore’s Bay region of the Ross Ice Shelf, Antarctica, have been measured. The thickness of the ice shelf in Moore’s Bay was measured from reflection times of radio-frequency pulses propagating vertically through the shelf and reflecting from the ocean, and is found to be 576 ± 8 m. Introducing a baseline of 543 ± 7m between radio transmitter and receiver allowed the computation of the basal reflection coefficient, R, separately from englacial loss. The depth-averaged attenuation length of the ice column, 〈L〉 is shown to depend linearly on frequency. The best fit (95% confidence level) is 〈L(ν)〉= (460±20) − (180±40)ν m (20 dB km−1), for the frequencies ν = [0.100–0.850] GHz, assuming no reflection loss. The mean electric-field reflection coefficient is (1.7 dB reflection loss) across [0.100–0.850] GHz, and is used to correct the attenuation length. Finally, the reflected power rotated into the orthogonal antenna polarization i