Intrinsic symmetry groups of links with 8 and fewer crossings

We present an elementary derivation of the "intrinsic" symmetry groups for knots and links of 8 or fewer crossings. The standard symmetry group for a link is the mapping class group \MCG(S^3,L) or \Sym(L) of the pair $(S^3,L)$. Elements in this symmetry group can (and often do) fix the link and act nontrivially only on its complement. We ignore such elements and focus on the "intrinsic" symmetry group of a link, defined to be the image $\Sigma(L)$ of the natural homomorphism \MCG(S^3,L) \rightarrow \MCG(S^3) \cross \MCG(L). This different symmetry group, first defined by Whitten in 1969, records directly whether $L$ is isotopic to a link $L'$ obtained from $L$ by permuting components or reversing orientations. For hyperbolic links both \Sym(L) and $\Sigma(L)$ can be obtained using the output of \texttt{SnapPea}, but this proof does not give any hints about how to actually construct isotopies realizing $\Sigma(L)$. We show that standard invariants are enough to rule out all the isotopies outside $\Sigma(L)$ for all links except $7^2_6$, $8^2_{13}$ and $8^3_5$ where an additional construction is needed to use the Jones polynomial to rule out "component exchange" symmetries. On the other hand, we present explicit isotopies starting with the positions in Cerf's table of oriented links which generate $\Sigma(L)$ for each link in our table. Our approach gives a constructive proof of the $\Sigma(L)$ groups.Comment: 72 pages, 66 figures. This version expands the original introduction into three sections; other minor changes made for improved readabilit

Evaluation of a global blended learning MBA programme

This paper evaluates the design and implementation of a UK university’s global blended learning MBA programme which combines e-learning with face-to-face teaching. The primary aim of the research was to investigate the learning experience and perceptions of the students, and to use the findings to evaluate the effectiveness of the course design and delivery system. Action research was used, with longitudinal data collected over a threeyear period (2008–2010). Three survey rounds were conducted focussing on Oman, one of the UK University’s main overseas learning collaborating centres. The three rounds yielded 116 valid responses in total. The first survey showed a fairly high level of student satisfaction with the programme but also indicated areas that needed further improvement. The impacts of subsequent changes in the programme were investigated in the second and third surveys. Feedback from these helped develop further changes in the learning content and delivery approach of the programme. The study contributes to a better understanding of global blended learning initiatives, and offers insights to managers on improving course management, enriching learning content, enhancing teaching quality, and improving students’ satisfaction levels

MAPping out distribution routes for kinesin couriers

In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long-distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarized, compartmentalized and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio-temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of subdomain-specific microtubule (MT) tracks, sign-posted by different tubulin isoforms, tubulin post-translational modifications (PTMs), tubulin GTPase activity and MT associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that – especially for axonal cargo – alterations to the MT track can influence transport, although in vivo, it is likely that multiple track-based effects act synergistically to ensure accurate cargo distribution

Physiological responses and productivity of the seaweed Ulva ohnoi (Chlorophyta) under changing cultivation conditions in pilot large land-based ponds

Land based intensive cultivation systems have been proposed as an ideal option for the commercial production of high value products from seaweeds. However, many cultures on Ulva and other seaweeds are based on relatively small-scale facilities. The high variability of culture conditions can strongly affect the physiological performance of seaweeds, but few studies examine their phenotypic plasticity by integrating critical biological descriptors, e.g. photobiology, oxidative stress, nutrient acquisition. The purpose of this study was to determine the physiological plasticity and growth of Ulva ohnoi during its cultivation in land-based 40 m3 ponds. Through an entire culti-vation cycle (four-weeks), photosynthesis, respiration, pigments, antioxidant capacity and nutrient content were measured. Light, temperature, pH, and dissolved inorganic nitrogen (DIN) were simultaneously monitored in seawater. Additionally, the N-uptake kinetics of U. ohnoi were examined in the laboratory in order to explain the efficiency of the seaweed biomass for DIN-incorporation in the ponds after fertilization. Generally, the gradual increase in seaweed density throughout the cultivation period was directly associated to a drop in light avail-ability and dissolved inorganic carbon (i.e. higher pH) within the ponds. These changes in cultivation conditions were related to a reduction of photosynthetic capacities, nutrient content and growth of U. ohnoi. N-uptake kinetics of U. ohnoi and the behavior of DIN within the ponds after fertilization, indicated that U. ohnoi was able to incorporate ammonium more efficiently than nitrate, and the presence of the former likely inhibits nitrate acquisition. The understanding of the capacity of U. ohnoi to acclimate to the extreme changing culture condi-tions, could be applied to improve its productivity and chemical composition.En prens

Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

<p>Abstract</p> <p>Background</p> <p>Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells.</p> <p>Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells.</p> <p>Methods</p> <p>We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays.</p> <p>Results</p> <p>The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4⁺, activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed.</p> <p>Conclusion</p> <p>Cellular fusions of MSI⁺carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and this approach should be further analyzed in preclinical as well as clinical trials. Moreover, this is the first report on the induction of frameshift-specific T cell responses without the use of synthetic peptides.</p

Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets

Tumor-infiltrating lymphocytes (TILs) are widely associated with positive outcomes, yet carry key indicators of a systemic failed immune response against unresolved cancer. Cancer immunotherapies can reverse their tolerance phenotypes while preserving tumor reactivity and neoantigen specificity shared with circulating immune cells. We performed comprehensive transcriptomic analyses to identify gene signatures common to circulating and TILs in the context of clear cell renal cell carcinoma. Modulated genes also associated with disease outcome were validated in other cancer types. Through comprehensive bioinformatics analyses, we identified practical diagnostic markers and actionable targets of the failed immune response. On circulating lymphocytes, 3 genes (LEF1, FASLG, and MMP9) could efficiently stratify patients from healthy control donors. From their associations with resistance to cancer immunotherapies and microbial infections, we uncovered not only pan-cancer, but pan-pathology, failed immune response profiles. A prominent lymphocytic matrix metallopeptidase cell migration pathway is central to a panoply of diseases and tumor immunogenicity, correlates with multi-cancer recurrence, and identifies a feasible noninvasive approach to pan-pathology diagnoses. The differentially expressed genes we have identified warrant future investigation into the development of their potential in noninvasive precision diagnostics and precision pan-disease immunotherapeutics. - 2019, American Society for Clinical Investigation.We thank all study participants and patients; The Cancer Genome Atlas; Mathieu Latour and Roula Albadine and supporting staff of the CHUM pathology department; Manon de Ladurantaye and Anne-Marie Mes-Masson from the CRCHUM for RNA quality profiling, Geneviève Cormier and Fred Saad from the CRCHUM for drawing blood from control donors; Gilles Corbeil of the CRCHUM genomics department for RNA quality testing and microarray profiling; Francois Harvey of the CRCHUM bioinformatics department; Peter Graf and Patrick Sabourin from Affymetrix for providing reagents and technical assistance; Zeeshan Farroq and Ofir Goldberger from Fluidigm; Erika Diaz from StemCell; Andrew Mouland from McGill University; Simon Turcotte from University of Montreal; and Sascha Ring from Biostars for their advice. This work was partially performed at the Institut du Cancer de Montréal CRCHUM and University of Montreal, in Montreal, Quebec, Canada. This work was supported by a Canadian Cancer Society Research Institute grant (CCSRI) (702036, to RL and IJ) and a Biomedical Research Grant from the Kidney Foundation of Canada (KFOC130019 to RL). RL is supported by the Quebec Cell, Tissue and Gene Therapy Network—ThéCell (a thematic network supported by the Fonds de recherche du Québec–Santé [FRQS]), the FRQS, and the Immunotherapy Network (iTNT) from the Terry Fox Research Institute (TFRI), A. Monette is supported by Mitacs, Merck, l’Institut du cancer de Montréal (ICM), the Society for Immunotherapy of Cancer, and the Lady Davis Institute for Medical Research. NAB is supported by the FRQS post-doctoral award and Qatar University. JBL is supported by l’Institut du Cancer de Montréal. JPR holds the Louis Lowenstein Chair, McGill University. DEK is supported by an FRQS Research Scholar Award (grant 31035), CIHR 377124, NHLBI RO1-HL-092565, and the Canada Foundation for Innovation (CFI) (grant 31756). IJ and computational analysis were supported by the Canada Research Chair Program (CRC) (grant 225404), Ontario Research Fund (grant 34876), the Natural Sciences Research Council (NSERC) (grant 203475), the CFI (grants 203373 and 30865), the Krembil Foundation, and IBM.Scopu

The Shapes of Tight Composite Knots

We present new computations of tight shapes obtained using the constrained gradient descent code RIDGERUNNER for 544 composite knots with 12 and fewer crossings, expanding our dataset to 943 knots and links. We use the new data set to analyze two outstanding conjectures about tight knots, namely that the ropelengths of composite knots are at least 4\pi-4 less than the sums of the prime factors and that the writhes of composite knots are the sums of the writhes of the prime factors.Comment: Summary text file of tight knot lengths and writhing numbers stored in anc/ropelength_data.txt. All other data freely available at http:://www.jasoncantarella.com/ and through Data Conservanc

Caracterización de la fibrilación auricular y riesgo tromboembólico en pacientes del Hospital León Cuervo Rubio

Introduction: among cardiac pathologies, atrial fibrillation is related to a high incidence of thromboembolic diseases. Objective: to clinically and epidemiologically characterize atrial fibrillation and thromboembolic risk in patients attended at the León Cuervo Rubio Hospital in Pinar del Río between 2017 and 2019. Methods: an observational, descriptive, cross-sectional, descriptive study was conducted on patients with atrial fibrillation attended at the León Cuervo Rubio Hospital in Pinar del Río from 2017 to 2019. The study universe consisted of 198 patients diagnosed with atrial arrhythmias in that hospital, the sample was constituted by 68 patients who met the inclusion and exclusion criteria. Results: female sex predominated (58.8%). The most representative age group was 75 to 85 years old (45.5 %). Some type of heart disease associated with atrial fibrillation was present in 69.1% of patients. Persistent atrial fibrillation predominated (35.2%). Palpitations predominated as symptoms of atrial fibrillation (91.1%). Most patients with atrial fibrillation were in the moderate thromboembolic risk category (66.1%). Conclusions: the predominant sex was female, the most affected age group was over 85 years, ischemic heart disease was the most prevalent history, persistent atrial fibrillation was the most frequent, palpitations were the main symptom, and according to the thromboembolic risk category, most patients were at moderate risk.Introducción: dentro de las patologías cardiacas, la fibrilación auricular se relaciona con una alta incidencia de enfermedades tromboembólicas. Objetivo: caracterizar clínica y epidemiológicamente la fibrilación auricular y el riesgo tromboembólico en pacientes atendidos en el Hospital León Cuervo Rubio de Pinar del Río entre 2017 y 2019. Método: se realizó un estudio observacional, descriptivo, de corte transversal a pacientes con fibrilación auricular atendidos en el Hospital León Cuervo Rubio de Pinar del Río de 2017 a 2019. El universo de estudio estuvo conformado por 198 pacientes con diagnóstico de arritmias auriculares en dicho hospital, la muestra quedó constituida por 68 pacientes que cumplieron con los criterios de inclusión y exclusión. Resultados: predominó el sexo femenino (58,8 %). El grupo etario más representativo fue el de 75 a 85 años (45,5 %). El 69,1 % presentaban algún tipo de cardiopatía asociada a la fibrilación auricular. Predominó la fibrilación auricular de tipo persistente (35,2 %). Predominaron las palpitaciones como síntomas de la fibrilación auricular (91,1 %). La mayoría de los pacientes con fibrilación auricular estaban en la categoría de riesgo tromboembólico moderado (66,1 %). Conclusiones: el sexo que predominó fue el femenino, el grupo etáreo más afectado fue el de más de 85 años, la cardiopatía isquémica fue el antecedente de mayor prevalencia, la fibrilación auricular de tipo persistente fue la más frecuente, las palpitaciones constituyeron el síntoma principal y según la categoría de riesgo tromboembólico la mayoría de los pacientes presentaban riesgo moderado

Water Quality and Herbivory Interactively Drive Coral-Reef Recovery Patterns in American Samoa

BACKGROUND: Compared with a wealth of information regarding coral-reef recovery patterns following major disturbances, less insight exists to explain the cause(s) of spatial variation in the recovery process. METHODOLOGY/PRINCIPAL FINDINGS: This study quantifies the influence of herbivory and water quality upon coral reef assemblages through space and time in Tutuila, American Samoa, a Pacific high island. Widespread declines in dominant corals (Acropora and Montipora) resulted from cyclone Heta at the end of 2003, shortly after the study began. Four sites that initially had similar coral reef assemblages but differential temporal dynamics four years following the disturbance event were classified by standardized measures of 'recovery status', defined by rates of change in ecological measures that are known to be sensitive to localized stressors. Status was best predicted, interactively, by water quality and herbivory. Expanding upon temporal trends, this study examined if similar dependencies existed through space; building multiple regression models to identify linkages between similar status measures and local stressors for 17 localities around Tutuila. The results highlighted consistent, interactive interdependencies for coral reef assemblages residing upon two unique geological reef types. Finally, the predictive regression models produced at the island scale were graphically interpreted with respect to hypothesized site-specific recovery thresholds. CONCLUSIONS/SIGNIFICANCE: Cumulatively, our study purports that moving away from describing relatively well-known patterns behind recovery, and focusing upon understanding causes, improves our foundation to predict future ecological dynamics, and thus improves coral reef management

RNAi-Mediated Knock-Down of Arylamine N-acetyltransferase-1 Expression Induces E-cadherin Up-Regulation and Cell-Cell Contact Growth Inhibition

Arylamine N-acetyltransferase-1 (NAT1) is an enzyme that catalyzes the biotransformation of arylamine and hydrazine substrates. It also has a role in the catabolism of the folate metabolite p-aminobenzoyl glutamate. Recent bioinformatics studies have correlated NAT1 expression with various cancer subtypes. However, a direct role for NAT1 in cell biology has not been established. In this study, we have knocked down NAT1 in the colon adenocarcinoma cell-line HT-29 and found a marked change in cell morphology that was accompanied by an increase in cell-cell contact growth inhibition and a loss of cell viability at confluence. NAT1 knock-down also led to attenuation in anchorage independent growth in soft agar. Loss of NAT1 led to the up-regulation of E-cadherin mRNA and protein levels. This change in E-cadherin was not attributed to RNAi off-target effects and was also observed in the prostate cancer cell-line 22Rv1. In vivo, NAT1 knock-down cells grew with a longer doubling time compared to cells stably transfected with a scrambled RNAi or to parental HT-29 cells. This study has shown that NAT1 affects cell growth and morphology. In addition, it suggests that NAT1 may be a novel drug target for cancer therapeutics