Additional file 8: of Harmful somatic amino acid substitutions affect key pathways in cancers

This file contains supplementary Figure S9. Numbers of genes containing SNVs leading to AASs in cancers. Numbers of genes corresponding to selected proteins, genes with at least one SNV leading to harmful AASs and genes with SNVs leading to AASs are shown, respectively, from left to right for each cancer type. The grey bar represents genes catalogued in CGC (genes in which SNVs leading to AASs have been implicated in cancer) and the white bar represents all other genes. (PDF 17 kb

Organizational change and change readiness : employees’ attitudes during times of proposed merger

The objective in this thesis is to investigate the effects of organizational change. This is done through the review of literature and empirical analysis. An important part of this process involves developing measurements of the main constructs of interest; job satisfaction, uncertainty, commitment and change readiness. The relationship between the main constructs and change readiness is then investigated with special emphasis on testing hypotheses introduced under the first of three propositions. Further analysis then investigates two more propositions, one testing the assimilation of attitudes of Executive Managers and employees’ to organizational change, and one testing the relationship between the rate of change and change readiness. The study is based on two types of primary data. One is a questionnaire survey administered among employees of three Icelandic governmental organizations, all considered applicable for a merger. Another type of data was gathered by conducting interviews with Executive Managers of all three organizations. Findings suggest that change readiness increases as measured levels of job satisfaction increases. Findings also suggest that change readiness increases as uncertainty decreases, but the relationship between change readiness and commitment is not determined by the findings. Two of the three organizations surveyed had significantly different levels of change readiness. Findings suggest that employees’ change readiness is reflected in the attitudes of Executive Managers. Findings also suggest that employees and Executive Managers in organizations facing discontinuous or radical change do not report lower levels of change readiness, than those facing incremental organizational change

Får hjerneinfarktspasienter i Tromsø adekvat utredning for å avdekke karotisstenose og hvordan påvirkes utredningen av alder, kjønn og slagets alvorlighetsgrad?

Bakgrunn: Vi vet i dag lite om hva slags utredning som blir gjort blant hjerneslagspasienter i Tromsø. I henhold til nasjonale faglige retningslinjer bør man som hovedregel gjøre utredning med tanke på karotisstenose hos alle pasienter med hjerneinfarkt. I denne studien kartlegges utredningsfrekvensen for karotisstenose blant hjerneinfarktpasienter som deltok i den 5. tromsøundersøkelsen i 2001-02 (Tromsø 5) og hvorvidt alder, kjønn og slagets alvorlighetsgrad påvirker denne. Materiale og metode: I alt 7852 deltakere i Tromsø 5 uten tidligere hjerneinfarkt ble fulgt opp med registrering av førstegangs hjerneinfarkt t.o.m. 2007. Av disse fikk 268 personer førstegangs hjerneinfarkt i oppfølgingsperioden og ble inkludert i studien. Adekvat stenoseutredning ble definert som ultralydsundersøkelse og/eller angiografisk (CT, MR eller konvensjonell angiografi) framstilling av det precerebrale forløp av karotisarteriene. Resultater: Totalt var det 62 % som gjennomgikk adekvat stenoseutredning. Færre ble utredet i de eldste aldersgruppene (p<0,0001), blant dem med registrert demensdiagnose (p=0,06) og de som hadde svekket bevissthet ved innkomst (p=0,01). Det var ingen forskjell i utredning mellom kjønnene. Med 10 års økning i alder ble sjansen for stenoseutredning redusert med 76 % (OR 0,24, KI 0,14 – 0,39). Svekket bevissthet reduserte sjansen for utredning med 72 % (OR 0,27, KI 0,11 – 0,53). Diskusjon: En høy andel av hjerneinfarktpasientene ble ikke utredet for å avdekke eventuell karotisstenose. Selv når man tar hensyn til forhold som bevissthetssvekkelse som uttrykk for slagets alvorlighetsgrad og komorbiditiet i form av demens, synes utredningsfrekvensen å være lavere enn det som er anbefalt i gjeldende nasjonale anbefalinger

Table_2_Simulation of the Dynamics of Primary Immunodeficiencies in B Cells.docx

<p>Primary immunodeficiencies (PIDs) are a group of over 300 hereditary, heterogeneous, and mainly rare disorders that affect the immune system. Various aspects of immune system and PID proteins and genes have been investigated and facilitate systems biological studies of effects of PIDs on B cell physiology and response. We reconstructed a B cell network model based on data for the core B cell receptor activation and response processes and performed semi-quantitative dynamic simulations for normal and B cell PID failure modes. The results for several knockout simulations correspond to previously reported molecular studies and reveal novel mechanisms for PIDs. The simulations for CD21, CD40, LYN, MS4A1, ORAI1, PLCG2, PTPRC, and STIM1 indicated profound changes to major transcription factor signaling and to the network. Significant effects were observed also in the BCL10, BLNK, BTK, loss-of-function CARD11, IKKB, MALT1, and NEMO, simulations whereas only minor effects were detected for PIDs that are caused by constitutively active proteins (PI3K, gain-of-function CARD11, KRAS, and NFKBIA). This study revealed the underlying dynamics of PID diseases, confirms previous observations, and identifies novel candidates for PID diagnostics and therapy.</p

Tuned parameters of nodes in the Odefy-simulated T cell network model.

<p>Tuned parameters of nodes in the Odefy-simulated T cell network model.</p

The strongly connected components of the interaction graph.

<p>The strongly connected component of the interaction graph consists of 25 nodes and 48 links. This subnet shows the interconnectedness and cross-talk of the early signals after the antigen-TCR ligation.</p

Attractor basin of the CD4+ T-cell network model normalized HillCube simulation.

<p>The basin of attractors of the CD4+ T-cell network model simulated using the normalized HillCube algorithm. The horizontal axis denotes time in arbitrary units.</p

Boolean model transformed into its underlying interaction graph.

<p>The network consists of nodes and links derived from the Boolean network model without the AND operator. The interaction graph consists of 85 nodes and 146 links, and represents the underlying interaction network of the model. The nodes are as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176500#pone.0176500.g001" target="_blank">Fig 1</a>. The network shows the paths through which signals from the receptors are channeled through the network to the TFs, which turn on the response genes.</p

Table_1_Simulation of the Dynamics of Primary Immunodeficiencies in B Cells.docx

<p>Primary immunodeficiencies (PIDs) are a group of over 300 hereditary, heterogeneous, and mainly rare disorders that affect the immune system. Various aspects of immune system and PID proteins and genes have been investigated and facilitate systems biological studies of effects of PIDs on B cell physiology and response. We reconstructed a B cell network model based on data for the core B cell receptor activation and response processes and performed semi-quantitative dynamic simulations for normal and B cell PID failure modes. The results for several knockout simulations correspond to previously reported molecular studies and reveal novel mechanisms for PIDs. The simulations for CD21, CD40, LYN, MS4A1, ORAI1, PLCG2, PTPRC, and STIM1 indicated profound changes to major transcription factor signaling and to the network. Significant effects were observed also in the BCL10, BLNK, BTK, loss-of-function CARD11, IKKB, MALT1, and NEMO, simulations whereas only minor effects were detected for PIDs that are caused by constitutively active proteins (PI3K, gain-of-function CARD11, KRAS, and NFKBIA). This study revealed the underlying dynamics of PID diseases, confirms previous observations, and identifies novel candidates for PID diagnostics and therapy.</p

Naïve CD4+ T-cell activation Boolean network model.

<p>The network consists of 182 links and 118 nodes (including Boolean operators), 19 of which are input nodes, i.e., no link points to them (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176500#pone.0176500.s001" target="_blank">S1 Table</a>). The Boolean network represents the naïve CD4+ T-cell activation events. The boxes represent non-PID (white) and PID proteins (gray). Spheres denote the AND gate. Activating links have a pointed head and solid line while inhibiting links have a blunt head and dashed line. Signal 1 represents peptide-MHC/TCR complex while Signal 2 represents co-receptor-ligand association, e.g. CD80-B7. Since the network focuses on TCR/CD28 signaling events, some events, e.g. for survival signaling that occur after antigen mediated T-cell activation and response through interleukin 2 (IL2), have not been fully considered.</p