Generalized Skein Modules of Surfaces

Frobenius extensions play a central role in the link homology theories based upon the sl(n) link variants, and each of these Frobenius extensions may be recast geometrically via a category of marked cobordisms in the manner of Bar-Natan. Here we explore a large family of such marked cobordism categories that are relevant to generalized sl(n) link homology theories. We also investigate the skein modules that result from embedding these marked cobordisms within 3-manifolds, and arrive at an explicit presentation for several of these generalized skein modules.Comment: 23 pages, multiple figure

A systematic review of loneliness in bereavement:Current research and future directions

Bereaved people suffer from loneliness and loneliness is associated with poor mental health. In this study, this topic is reviewed. An agenda is suggested for future research. Research that is theory-driven, addresses measurement consistency, correlates of loneliness in bereaved and non-bereaved, and treatment is necessary for prevention and intervention

SH2- and SH3-mediated Interactions between Focal Adhesion Kinase and Src

Intramolecular SH2 and SH3 interactions mediate enzymatic repression of the Src kinases. One mechanism of activation is disruption of these interactions by the formation of higher affinity SH2 and SH3 interactions with specific ligands. We show that a consensus Src SH3-binding site residing upstream of the Src SH2-binding site in FAK can function as a ligand for the Src SH3 domain. Surface plasmon resonance experiments indicate that a FAK peptide containing both the Src SH2- and SH3-binding sites exhibits increased affinity for Src. Furthermore, the presence of both sites in vitro more potently activates c-Src. A FAK mutant (FAKPro-2) with substitutions destroying the SH3-binding site shows reduced binding to Src in vivo. This mutation also reduces Src-dependent tyrosine phosphorylation on the mutant itself and downstream substrates, such as paxillin. These observations suggest that an SH3-mediated interaction between Src-like kinases and FAK may be important for complex formation and downstream signaling in vivo

Recurrence After Liver Resection of Colorectal Liver Metastases: Repeat Resection or Ablation Followed by Hepatic Arterial Infusion Pump Chemotherapy

Background: The aim of this study was to investigate the effectiveness of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after complete resection or ablation of recurrent colorectal liver metastases (CRLM). Methods: A retrospective cohort study was conducted of patients from two centers who were treated with resection and/or ablation of recurrent CRLM only between 1992 and 2018. Overall survival (OS) and hepatic disease-free survival (hDFS) were estimated using the Kaplan–Meier method. The Cox regression method was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Results: Of 374 eligible patients, 81 (22%) were treated with adjuvant HAIP chemotherapy. The median follow-up for survivors was 65 months (IQR 32–118 months). Patients receiving adjuvant HAIP were more likely to have multifocal disease and receive perioperative systemic chemotherapy at time of resection for recurrence. A median hDFS of 46 months (95% CI 29–81 months) was found in patients treated with adjuvant HAIP compared with 18 months (95% CI 15–26 months) in patients treated with resection and/or ablation alone (p = 0.001). The median OS and 5-year OS were 89 months (95% CI 52–126 months) and 66%, respectively, in patients treated with adjuvant HAIP compared with 57 months (95% CI 47–67 months) and 47%, respectively, in patients treated with resection and/or ablation only (p = 0.002). Adjuvant HAIP was associated with superior hDFS (adjusted HR 0.599, 95% CI 0.38–0.93, p = 0.02) and OS (adjusted HR 0.59, 95% CI 0.38–0.92, p = 0.02) in multivariable analysis. Conclusion: Adjuvant HAIP chemotherapy after resection and/or ablation of recurrent CRLM is associated with superior hDFS and OS

Correlation between infectivity and disease associated prion protein in the nervous system and selected edible tissues of naturally affected scrapie sheep

<div><p>The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow the use of high-throughput laboratory based tests, avoiding the limitations of bioassays. We used scrapie, a prototype TSE, to examine the relationship between infectivity and laboratory based diagnostic tools. The data may help to optimise strategies to prevent exposure of humans to small ruminant TSE material via the food chain. Abnormal PrP distribution/accumulation was assessed by immunohistochemistry (IHC), Western blot (WB) and ELISA in samples from four animals. In addition, infectivity was detected using a sensitive bank vole bioassay with selected samples from two of the four sheep and protein misfolding cyclic amplification using bank vole brain as substrate (vPMCA) was also carried out in selected samples from one animal. Lymph nodes, oculomotor muscles, sciatic nerve and kidney were positive by IHC, WB and ELISA, although at levels 100–1000 fold lower than the brain, and contained detectable infectivity by bioassay. Tissues not infectious by bioassay were also negative by all laboratory tests including PMCA. Although discrepancies were observed in tissues with very low levels of abnormal PrP, there was an overall good correlation between IHC, WB, ELISA and bioassay results. Most importantly, there was a good correlation between the detection of abnormal PrP in tissues using laboratory tests and the levels of infectivity even when the titre was low. These findings provide useful information for risk modellers and represent a first step toward the validation of laboratory tests used to quantify prion infectivity, which would greatly aid TSE risk assessment policies.</p></div

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements