Representative structural element approach for assessing the mechanical properties of automated fibre placement-induced defects

In this paper, a 3D finite element modelling approach is presented to assess the effects of manufacturing defects within composite structures. The mesoscale modelling approach derives the stress-strain response of a composite structure from a representative structural element. A set of tensile and bending loads is used to compute its ABD-Matrix. The boundary conditions of the model are described in detail as is the extraction of the strain and curvature response. The derived stiffness from the presented modelling approach is compared to the classical lamination theory and the models' shortcomings are discussed. Finally, the influence of a gap, an overlap and two different-sized fuzzballs on the macroscopic mechanical properties of a composite structure are evaluated using the presented multiscale modelling approach, thereby providing stiffness matrices influenced by the defects for the use in global models of composite parts

The Alternative for Germany’s radicalization in historical-comparative perspective

This article chronicles the AfD’s rightward repositioning and compares it with the programmatic development of three postwar German parties on the ideological wings. By highlighting factors that tilt the balance of power away from moderate reformers towards hardliners, this comparative analysis sheds light on the conditions that lead a relatively successful party on the ideological wings, such as the AfD, to radicalize its programme. Four variables stand out: whether party hardliners take the blame for the recent election loss; whether they offer a convincing programmatic and strategic alternative to the reformers; whether changes in party composition strengthen hardliners; and whether external factors enhance their weight within the party. The essay concludes that the AfD’s radicalization was unusual, but not exceptional. It is however too early to conclude that the Federal Republic’s distinctive institutions and political culture no longer impose significant costs on parties that shift their programmes away from the centre

Individualized Biventricular Epicardial Augmentation Technology in a Drug-Induced Porcine Failing Heart Model

For treatment of advanced heart failure, current strategies include cardiac transplantation or blood-contacting pump technology associated with complications, including stroke and bleeding. This study investigated an individualized biventricular epicardial augmentation technology in a drug-induced porcine failing heart model. A total of 11 pigs were used, for the assessment of hemodynamics and cardiac function under various conditions of support pressures and support durations (n = 4), to assess device positioning and function by in vivo computer tomographic imaging (n = 3) and to investigate a minimally invasive implantation on the beating heart (n = 4). Support pressures of 20-80 mmHg gradually augmented cardiac function parameters in this animal model as indicated by increased left ventricular stroke volume, end-systolic pressures, and decreased end-diastolic pressures. Strong evidence was found regarding the necessity of mechanical synchronization of support end with the isovolumetric relaxation phase of the heart. In addition, the customized, self-expandable implant enabled a marker-guided minimally invasive implantation through a 4cm skin incision using fluoroscopy. Correct positioning was confirmed in computer tomographic images. Continued long-term survival investigations will deliver preclinical evidence for further development of this concept

Spreading depolarization and angiographic spasm are separate mediators of delayed infarcts

In DISCHARGE-1, a recent Phase III diagnostic trial in aneurysmal subarachnoid haemorrhage patients, spreading depolarization variables were found to be an independent real-time biomarker of delayed cerebral ischaemia. We here investigated based on prospectively collected data from DISCHARGE-1 whether delayed infarcts in the anterior, middle, or posterior cerebral artery territories correlate with (i) extravascular blood volumes; (ii) predefined spreading depolarization variables, or proximal vasospasm assessed by either (iii) digital subtraction angiography or (iv) transcranial Doppler-sonography; and whether spreading depolarizations and/or vasospasm are mediators between extravascular blood and delayed infarcts. Relationships between variable groups were analysed using Spearman correlations in 136 patients. Thereafter, principal component analyses were performed for each variable group. Obtained components were included in path models with a priori defined structure. In the first path model, we only included spreading depolarization variables, as our primary interest was to investigate spreading depolarizations. Standardised path coefficients were 0.22 for the path from extravascular bloodcomponent to depolarizationcomponent (P = 0.010); and 0.44 for the path from depolarizationcomponent to the first principal component of delayed infarct volume (P < 0.001); but only 0.07 for the direct path from bloodcomponent to delayed infarctcomponent (P = 0.36). Thus, the role of spreading depolarizations as a mediator between blood and delayed infarcts was confirmed. In the principal component analysis of extravascular blood volume, intraventricular haemorrhage was not represented in the first component. Therefore, based on the correlation analyses, we also constructed another path model with bloodcomponent without intraventricular haemorrhage as first and intraventricular haemorrhage as second extrinsic variable. We found two paths, one from (subarachnoid) bloodcomponent to delayed infarctcomponent with depolarizationcomponent as mediator (path coefficients from bloodcomponent to depolarizationcomponent = 0.23, P = 0.03; path coefficients from depolarizationcomponent to delayed infarctcomponent = 0.29, P = 0.002), and one from intraventricular haemorrhage to delayed infarctcomponent with angiographic vasospasmcomponent as mediator variable (path coefficients from intraventricular haemorrhage to vasospasmcomponent = 0.24, P = 0.03; path coefficients from vasospasmcomponent to delayed infarctcomponent = 0.35, P < 0.001). Human autopsy studies shaped the hypothesis that blood clots on the cortex surface suffice to cause delayed infarcts beneath the clots. Experimentally, clot-released factors induce cortical spreading depolarizations that trigger (i) neuronal cytotoxic oedema and (ii) spreading ischaemia. The statistical mediator role of spreading depolarization variables between subarachnoid blood volume and delayed infarct volume supports this pathogenetic concept. We did not find that angiographic vasospasm triggers spreading depolarizations, but angiographic vasospasm contributed to delayed infarct volume. This could possibly result from enhancement of spreading depolarization-induced spreading ischaemia by reduced upstream blood supply.Peer Reviewe

Building in China - Study trip of the faculty of Civil Engineering of the HTWG Konstanz 2008

Im März 2008 führte die Fakultät Bauingenieurwesen der HTWG Konstanz eine studentische Exkursion nach China durch. Auf dem Programm standen interessante Baustellen Shanghai, Nanjing, Zhenjiang und Beijing sowie der Besuch von Hochschulen. Der Exkursionsbericht beschreibt die besuchten Bauvorhaben und gibt persönliche Eindrücke der Exkursionsteilnehmer wieder.In March 2008 the faculty of civil engineering of the University of Applied Sciences Konstanz, Germany, conducted a study trip for students of civil engineering to China. Construction sites and universities in Shanghai, Nanjing, Zhenjiang and Beijing have been visited. The report describes the places seen and reflects the personal impressions of the participants

XUV Fluorescence Detection of Laser-Cooled Stored Relativistic Ions

An improved moveable in vacuo XUV fluorescence detection system was employed for the laser cooling of bunched relativistic ( β = 0.47) carbon ions at the Experimental Storage Ring (ESR) of GSI Helmholtzzentrum Darmstadt, Germany. Strongly Doppler boosted XUV fluorescence (∼90 nm) was emitted from the ions in a forward light cone after laser excitation of the 2s–2p transition (∼155 nm) by a new tunable pulsed UV laser system (257 nm). It was shown that the detected fluorescence strongly depends on the position of the detector around the bunched ion beam and on the delay (∼ns) between the ion bunches and the laser pulses. In addition, the fluorescence information could be directly combined with the revolution frequencies of the ions (and their longitudinal momentum spread), which were recorded using the Schottky resonator at the ESR. These fluorescence detection features are required for future laser cooling experiments at highly relativistic energies (up to γ ∼ 13) and high intensities (up to 10 11 particles) of ion beams in the new heavy ion synchrotron SIS100 at FAIR

Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

<p>Abstract</p> <p>Background</p> <p>Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.</p> <p>Methods</p> <p>Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.</p> <p>Results</p> <p>1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).</p> <p>Conclusions</p> <p>Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.</p> <p>Trial Registration</p> <p>clinicaltrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00451412">NCT00451412</a></p

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis