CDIO Projects in DTU’s B.Eng. in IT Study Program

Since the fall 2008 all B.Eng. study programs at the Technical University of Denmark have been based on the CDIO concept. The adoption of the CDIO standards and principles resulted in new or significantly revised study programs. As part of this effort design-build projects have been introduced on each of the first 4 semesters, and each semester-project spans several courses. The aim of this paper is to describe the four CDIO semester projects in the B.Eng. in IT study, and – along with similar papers describing the other six B.Eng. programs – to provide documentation to accompany an exposition with stands providing additional information and with students demonstrating their projects. The paper is narrowly focused on the IT-study program. At the time of writing this paper the students enrolled in 2008 have completed all four semesters in the new CDIO-based study plan, and the students enrolled in 2009 are currently in the process of finishing the 4 th semester. Consequently, the paper is reporting on curriculum development which has been implemented, and for which experiences have gained

The nuclear radio structure of X-ray bright AGN

The physical nature of the X-ray/radio correlation of AGN is still an unsolved question. High angular resolution observations are necessary to disentangle the associated energy dynamics into nuclear and stellar components. We present MERLIN/EVN 18cm observations of 13 X-raying AGN. The sample consists of Seyfert 1, Narrow Line Seyfert 1, and LINER-like galaxies. We find that for all objects the radio emission is unresolved and that the radio luminosities and brightness temperatures are too high for star formation to play an important role. This indicates that the radio emission in these sources is closely connected to processes that occur in the vicinity of the central massive black hole, also where the X-ray emission is believed to originate in.Comment: 5 pages, 3 figures, submitted to "The Universe under the Microscope - Astrophysics at High Angular Resolution", Bad Honnef, German

The nuclear radio structure of X-ray bright AGN

The physical nature of the X-ray/radio correlation of AGN is still an unsolved question. High angular resolution observations are necessary to disentangle the associated energy dynamics into nuclear and stellar components. We present MERLIN/EVN 18cm observations of 13 X-raying AGN. The sample consists of Seyfert 1, Narrow Line Seyfert 1, and LINER-like galaxies. We find that for all objects the radio emission is unresolved and that the radio luminosities and brightness temperatures are too high for star formation to play an important role. This indicates that the radio emission in these sources is closely connected to processes that occur in the vicinity of the central massive black hole, also where the X-ray emission is believed to originate in.Comment: 5 pages, 3 figures, submitted to "The Universe under the Microscope - Astrophysics at High Angular Resolution", Bad Honnef, German

The nuclear radio structure of X-ray bright AGN

The physical nature of the X-ray/radio correlation of AGN is still an unsolved question. High angular resolution observations are necessary to disentangle the associated energy dynamics into nuclear and stellar components. We present MERLIN/EVN 18cm observations of 13 X-raying AGN. The sample consists of Seyfert 1, Narrow Line Seyfert 1, and LINER-like galaxies. We find that for all objects the radio emission is unresolved and that the radio luminosities and brightness temperatures are too high for star formation to play an important role. This indicates that the radio emission in these sources is closely connected to processes that occur in the vicinity of the central massive black hole, also where the X-ray emission is believed to originate in.Comment: 5 pages, 3 figures, submitted to "The Universe under the Microscope - Astrophysics at High Angular Resolution", Bad Honnef, German

Chiral and deconfinement transition from correlation functions: SU(2) vs. SU(3)

We study a gauge invariant order parameter for deconfinement and the chiral condensate in SU(2) and SU(3) Yang-Mills theory in the vicinity of the deconfinement phase transition using the Landau gauge quark and gluon propagators. We determine the gluon propagator from lattice calculations and the quark propagator from its Dyson-Schwinger equation, using the gluon propagator as input. The critical temperature and a deconfinement order parameter are extracted from the gluon propagator and from the dependency of the quark propagator on the temporal boundary conditions. The chiral transition is determined using the quark condensate as order parameter. We investigate whether and how a difference in the chiral and deconfinement transition between SU(2) and SU(3) is manifest.Comment: 15 pages, 9 figures. For clarification one paragraph and two references added in the introduction and two sentences at the end of the first and last paragraph of the summary. Appeared in EPJ

Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis

<p>Abstract</p> <p>Background</p> <p>Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA) is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC). Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1) to study HA-synthase (HAS) expression and regulation in human ESCC, and (2) to translate the <it>in vitro </it>results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan.</p> <p>Methods</p> <p>mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU), an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3), the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT). HA content, cellular composition and proliferation (Ki67) were determined histologically.</p> <p>Results</p> <p>mRNA of HAS isoform 3 (HAS3) was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF) receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression <it>in vitro</it>. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by ESCC is accountable for major changes in tumour environment <it>in vivo</it>.</p> <p>Conclusions</p> <p>Systemic inhibition of HA-synthesis and knockdown of tumour cell HAS3 cause decreased ESCC progression accompanied by tumour stroma remodelling and may therefore be used in novel approaches to ESCC therapy.</p

Enzymatic Activity Is Not Required for Phospholipase D Mediated TNF-α Regulation and Myocardial Healing

Phospholipase D1 is a regulator of tumor necrosis factor-α expression and release upon LPS-induced sepsis and following myocardial infarction (MI). Lack of PLD1 leads to a reduced TNF-α mediated inflammatory response and to enhanced infarct size with declined cardiac function 21 days after ischemia reperfusion (I/R) injury. Deficiency of both PLD isoforms PLD1 and PLD2 as well as pharmacological inhibition of the enzymatic activity of PLD with the PLD inhibitor FIPI protected mice from arterial thrombosis and ischemic brain infarction. Here we treated mice with the PLD inhibitor FIPI to analyze if pharmacological inhibition of PLD after myocardial ischemia protects mice from cardiac damage. Inhibition of PLD with FIPI leads to reduced migration of inflammatory cells into the infarct border zone 24 h after experimental MI in mice, providing first evidence for immune cell migration to be dependent on the enzymatic activity of PLD. In contrast to PLD1 deficient mice, TNF-α plasma level was not altered after FIPI treatment of mice. Consequently, infarct size and left ventricular (LV) function were comparable between FIPI-treated and control mice 21 days post MI. Moreover, cell survival 24 h post I/R was not altered upon FIPI treatment. Our results indicate that the enzymatic activity of PLD is not responsible for PLD mediated TNF-α signaling and myocardial healing after I/R injury in mice. Furthermore, reduced TNF-α plasma levels in PLD1 deficient mice might be responsible for increased infarct size and impaired cardiac function 21 days post MI

Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption.

Regulation of body temperature critically depends on thyroid hormone (TH). Recent studies revealed that TH induces browning of white adipose tissue, possibly contributing to the observed hyperthermia in hyperthyroid patients and potentially providing metabolic benefits. Here, we show that browning by TH requires TH-receptor β and occurs independently of the sympathetic nervous system. The beige fat, however, lacks sufficient adrenergic stimulation and is not metabolically activated despite high levels of uncoupling protein 1 (UCP1). Studies at different environmental temperatures reveal that TH instead causes hyperthermia by actions in skeletal muscle combined with a central body temperature set-point elevation. Consequently, the metabolic and thermogenic effects of systemic hyperthyroidism were maintained in UCP1 knockout mice, demonstrating that neither beige nor brown fat contributes to the TH-induced hyperthermia and elevated glucose consumption, and underlining that the mere presence of UCP1 is insufficient to draw conclusions on the therapeutic potential of browning agents

Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion.

IMPORTANCE Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce. OBJECTIVE To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching. INTERVENTIONS Mechanical thrombectomy with or without IVT. MAIN OUTCOMES AND MEASURES Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death. RESULTS After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01). CONCLUSIONS AND RELEVANCE These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment