1-(10,11-Di­hydro­dibenz­[b,f]­azepin-5-yl)­ethano­ne

The asymmetric unit of the title compound, Csb 16Hsb 15NO, comprises two independent mol-ecules (it A and it B), both adopting a half-boat conformation, or butterfly shape. The intramolecular dihedral angles between the benzene rings in it A and it B are 64.40(4) and 65.24(5)circ, respectively

Förbättring av den Mekatroniska Utvecklingsprocessen med Software in the loop Simulering : En fallstudie för ett reglertekniskt system

This master thesis is performed at the mechatronic department at the company Mycronic, which are responsible for the embedded software in their pick and place machines. Today the embedded code can be executed and tested on a PIL simulation, where the control code runs on the actual target processor and the dynamic of the system (plant model) is modeled by a mathematical equation implemented as a C-function on the target board. The task is to find away to run the simulation with the real embedded code on a desktop computer. The aim is to investigate and examine how this simulation can be achieved and the advantages and opportunities it brings to the development process of the embedded system. For embedded system, Model-based Development usually refers to control and plant modelsand simulations and in the loop simulations. In a model-based workflow it starts with Model in the loop (MIL), then Software in the loop (SIL), Processor in the loop (PIL) and finally Hardware in the loop (HIL). Software in the loop simulation means that the plant is modeled but the control is executed in a low level language such as C and the simulation runs on a desktop computer. The investigation on how to implement a simulation resulted in a prototype SIL simulator, representing one of the axes. The simulation executes the control C-code together with a z-axis plant model on a Linux desktop computer. It is realized in two ways, where both are based on compiling the control code for a Linux computer and the difference is the implementation of the plant model. For the first simulation method, the plant models is represented in the same way as the PIL simulation and for the second simulation method the plant model is represented in Simulink. The result from this master thesis is that the SIL simulation has shown to be very useful andhave a lot of advantages. The SIL simulation gives an opportunity to execute and test the code and the control before it is integrated with the target processor. Problems and errors can thus be detected early. One of the big advantages is that it is not dependent of any hardware and any other software/tool. With the SIL simulation the code gets easier to debug, longer logscan be achieved and the simulation gets closer to reality than when modeling the control. A very important part of the SIL simulation is that it includes the interaction between the mechanical design, the control design and the software design which is very important in mechatronics system. The SIL simulation contributes to be able to run the main software together with the simulation, which helps in the integration tests.Detta examensarbete är utfört på företaget Mycronic på deras mekatronikavdelning, vilka är ansvarig för utvecklingen av den inbyggda mjukvaran i deras ytmonteringsmaskiner. I dagsläget kan den inbyggda koden köras och testas i en PIL simulering, där kontrollkoden körs på det inbyggda systemet medan dynamiken av systemet är modellerad och uttryckt med matematiska ekvationer implementerat i en C-funktion. Uppgiften är att hitta ett sätt att köra en simulering med den riktiga inbyggda koden på en dator. Syftet med examensarbetet är att utreda och undersöka hur denna simulering kan förbättra utvecklingsprocessen för den inbyggda koden hos Mycronic. För inbyggda system och reglerteknik syftar Model-based Development (modellbaserad utveckling) oftast på att modeller och simulering av styrsystemet och det dynamiska systemet. Ett modellbaserat arbetsflöde startar med Model in the loop (MIL), sedan Software in the loop (SIL), Processor in the loop (PIL) och sist Hardware in the loop (HIL). Software in the loop simulering betyder att det dynamiska systemet är modellerat men styrsystemet är implementerat i en lågnivå programmeringsspråk så som C. Resultatet från undersökning som innefattade att hitta ett sätta att implementera en simulering var en SIL simulering som representerar en av axlarna och körs på två olika sätt. Simuleringen kör styrsystemets kod tillsammans med en modellering av det dynamiska systemet där skillnaden är implementeringen av denna modell. För den första metoden implementeras dynamiken på samma sätta som PIL simuleringen och för den andra metoden implementeras dynamiken i en modell i Simulink. Resultatet från detta examensarbete är att SIL simuleringen har visat sig vara väldigt användbar och har många fördelar. SIL simuleringen ger en möjlighet att köra och testa koden och regleringen innan den köra på det inbyggda systemets processor. Problem och fel kan på sätt upptäckas tidigt. En stor fördel är att SIL simuleringen inte är beroende av någon hårdvara eller annan mjukvara. Det blir enklare att felsöka koden med SIL simuleringen och längre loggningar kan göras då minnet inte är så begränsat som på det inbyggda systemet. En väldigt viktig fördel med SIL simuleringen är att den inkluderar interaktionen mellan den mekaniska, regler och mjukvaru designen. Den bidrar även till att kunna köra huvudmjukvaran ihop med det inbyggda systemets simulering, vilket hjälper till i integrationsprocessen

p53-mediated control of gene expression via mRNA translation during Endoplasmic Reticulum stress

p53 is activated by different stress and damage pathways and regulates cell biological responses including cell cycle arrest, repair pathways, apoptosis and senescence. Following DNA damage, the levels of p53 increase and via binding to target gene promoters, p53 induces expression of multiple genes including p21(CDKN1A) and mdm2. The effects of p53 on gene expression during the DNA damage response are well mimicked by overexpressing p53 under normal conditions. However, stress to the Endoplasmic Reticulum (ER) and the consequent Unfolded Protein Response (UPR) leads to the induction of the p53/47 isoform that lacks the first 40 aa of p53 and to an active suppression of p21(CDKN1A) transcription and mRNA translation. We now show that during ER stress p53 also suppresses MDM2 protein levels via a similar mechanism. These observations not only raise questions about the physiological role of MDM2 during ER stress but it also reveals a new facet of p53 as a repressor toward 2 of its major target genes during the UPR. As suppression of p21(CDKN1A) and MDM2 protein synthesis is mediated via their coding sequences, it raises the possibility that p53 controls mRNA translation via a common mechanism that might play an important role in how p53 regulates gene expression during the UPR, as compared to the transcription-dependent gene regulation taking place during the DNA damage response

Robynrobot – design and development of a mechatronic media robot with a touchfree user interface

Denna rapport beskriver, från idé till färdig prototyp, arbetsgången för att tillverka en robot i kommersiellt syfte. Tanken med roboten är att den ska stå på scen med den svenska artisten Robyn och interagera med henne, musiken och publiken. Interaktionen mellan robot och omgivning sker på två sätt; framsidan är uppbyggd av LED-remsor som känner av närhet och byter färg, baksidan reagerar till musik och blinkar i takt. Dessutom går det att styra roboten med en handske genom att vinkla den åt fyra olika håll.This report describes the workflow for building a robot for commercial purposes. The idea for this robot is that it will stand on stage with the Swedish artist Robyn and interact with her, with the music and with the audience. The interaction between the robot and its environment happens in two ways; the front side of the robot is made up of LED-strips which act as proximity sensors and change colors according to closeness, the backside reacts to music by flashing to the beats. Moreover, it is possible to navigate the robot with a glove by angling it in four different directions

Low potential of circulating interleukin 1 receptor antagonist as a prediction marker for squamous cell carcinoma of the head and neck

Background: Circulating markers are attractive molecules for prognosis and management of cancer that allow sequential monitoring of patients during and after treatment. Based on previous protein profiling data, circulating interleukin 1 receptor antagonist (IL-1Ra) was evaluated as a potential diagnostic and prognostic marker for squamous cell carcinomas of the head and neck (SCCHN). In this study, we aimed at confirming the clinical relevance of plasma IL-1Ra in SCCHN and exploring its potential as a prediction marker for SCCHN. Methods: Plasma from 87 patients with SCCHN, control plasma from 28 healthy individuals and pre-diagnostic plasma from 44 patients with squamous cell carcinoma of the oral tongue (SCCOT) and 88 matched controls were analysed with IL-1Ra electrochemiluminescence immunoassays from mesoscale diagnostics. Results: Plasma IL-1Ra was found to be up-regulated in patients with oral tongue, gingiva and base of tongue tumours compared to healthy individuals (p < 0.01). IL-1Ra levels positively correlated with tumour size (p < 0.01) and body mass index (p = 0.013). Comparing pre-diagnostic plasma to the matched controls, similar IL1-Ra levels were seen (p = 0.05). Conclusion: The anti-inflammatory cytokine IL-1Ra could be a diagnostic marker for SCCHN, whereas its potential as a cancer prediction marker was not supported by our data

PI3Kδ delta activates E2F1 synthesis in response to mRNA translation stress

The c-myc oncogene stimulates ribosomal biogenesis and protein synthesis to promote cellular growth. However, the pathway by which cells sense and restore dysfunctional mRNA translation and how this is linked to cell proliferation and growth is not known. We here show that mRNA translation stress in cis triggered by the gly-ala repeat sequence of Epstein–Barr virus (EBV)-encoded EBNA1, results in PI3Kδ-dependent induction of E2F1 mRNA translation with the consequent activation of c-Myc and cell proliferation. Treatment with a specific PI3Kδ inhibitor Idelalisib (CAL-101) suppresses E2F1 and c-Myc levels and causes cell death in EBNA1-induced B cell lymphomas. Suppression of PI3Kδ prevents E2F1 activation also in non-EBV-infected cells. These data illustrate an mRNA translation stress–response pathway for E2F1 activation that is exploited by EBV to promote cell growth and proliferation, offering new strategies to treat EBV-carrying cancers

Transfer-RNA-Derived Fragments Are Potential Prognostic Factors in Patients with Squamous Cell Carcinoma of the Head and Neck

Transfer-RNA-derived fragments (tRFs) are a class of small non-coding RNAs that are functionally different from their parental transfer RNAs (tRNAs). tRFs can regulate gene expression by several mechanisms, and are involved in a variety of pathological processes. Here, we aimed at understanding the composition and abundance of tRFs in squamous cell carcinoma of the head and neck (SCCHN), and evaluated the potential of tRFs as prognostic markers in this cancer type. We obtained tRF expression data from The Cancer Genome Atlas (TCGA) HNSC cohort (523 patients) using MINTbase v2.0, and correlated to available TCGA clinical data. RNA-binding proteins were predicted according to the calculated Position Weight Matrix (PWM) score from the RNA-Binding Protein DataBase (RBPDB). A total of 10,158 tRFs were retrieved and a high diversity in expression levels was seen. Fifteen tRFs were found to be significantly associated with overall survival (Kaplan-Meier survival analysis, log rank test p-value < 0.01). The top prognostic marker, tRF-20-S998LO9D (p < 0.001), was further measured in tumor and tumor-free samples from 16 patients with squamous cell carcinoma of the oral tongue and 12 healthy controls, and was significantly upregulated in tumor compared to matched tumor-free tongue (p < 0.001). Results suggest that tRFs are useful prognostic markers in SCCH

AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck

A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan-Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor