Effects of alpha-Calcitonin Gene-related Peptide on Osteoprotegerin and Receptor Activator of Nuclear Factor-kappaB Ligand Expression in MG-63 Osteoblast-like Cells exposed to Polyethylene Particles

BACKGROUND: Recent studies demonstrated an impact of the nervous system on particle-induced osteolysis, the major cause of aseptic loosening of joint replacements. METHODS: In this study of MG-63 osteoblast-like cells we analyzed the influence of ultra-high molecular weight polyethylene (UHMWPE) particles and the neurotransmitter alpha-calcitonin gene-related peptide (CGRP) on the osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factorκB (OPG/RANKL/RANK) system. MG-63 cells were stimulated by different UHMWPE particle concentrations (1:100, 1:500) and different doses of alpha-CGRP (10(-7 )M, 10(-9 )M, 10(-11 )M). RANKL and OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. RESULTS: Increasing particle concentrations caused an up-regulation of RANKL after 72 hours. Alpha-CGRP showed a dose-independent depressive effect on particle-induced expression of RANKL mRNA in both cell-particle ratios. RANKL gene transcripts were significantly (P < 0.05) decreased by alpha-CGRP treatment after 48 and 72 hours. OPG mRNA was significantly down-regulated in a cell-particle ratio of 1:500 after 72 hours. Alpha-CGRP concentrations of 10(-7 )M lead to an up-regulation of OPG protein. CONCLUSION: In conclusion, a possible osteoprotective influence of the neurotransmitter alpha-CGRP on particle stimulated osteoblast-like cells could be shown. Alpha-CGRP might be important for bone metabolism under conditions of particle-induced osteolysis

Activated partial thromboplastin time waveform analysis as specific sepsis marker in cardiopulmonary bypass surgery

Throughout the last years, several new diagnostic biomarkers have been introduced into clinical routine to identify a systemic inflammatory response syndrome (SIRS) or a septic state and to discriminate between these two entities. According to studies in selected patients, measurement of these biomarkers may be advantageous under certain clinical conditions. On an individual basis, however, these sepsis markers usually lack an adequate negative or positive predictive power. Therefore, physicians in charge still have to rely on a combination of personal experience and results from clinical or laboratory tests when deciding on a patient's therapy. For surgical patients, a key problem consists of the time delay which is associated with the diagnosis of serious postoperative infections and which may negatively affect outcome. It is in this context where the activated partial thromboplastin time waveform analysis may represent a promising new method to discriminate between SIRS and sepsis, thereby shortening the time to therapy. Nevertheless, studies involving large patient populations will be necessary to prove the efficacy of this new diagnostic concept either as a single tool or in combination with the measurement of other biomarkers

The Hypocrea jecorina (Trichoderma reesei) hypercellulolytic mutant RUT C30 lacks a 85 kb (29 gene-encoding) region of the wild-type genome

<p>Abstract</p> <p>Background</p> <p>The hypercellulolytic mutant <it>Hypocrea jecorina </it>(anamorph <it>Trichoderma reesei</it>) RUT C30 is the <it>H. jecorina </it>strain most frequently used for cellulase fermentations and has also often been employed for basic research on cellulase regulation. This strain has been reported to contain a truncated carbon catabolite repressor gene <it>cre1 </it>and is consequently carbon catabolite derepressed. To date this and an additional frame-shift mutation in the glycoprotein-processing β-glucosidase II encoding gene are the only known genetic differences in strain RUT C30.</p> <p>Results</p> <p>In the present paper we show that <it>H. jecorina </it>RUT C30 lacks an 85 kb genomic fragment, and consequently misses additional 29 genes comprising transcription factors, enzymes of the primary metabolism and transport proteins. This loss is already present in the ancestor of RUT C30 – NG 14 – and seems to have occurred in a palindromic AT-rich repeat (PATRR) typically inducing chromosomal translocations, and is not linked to the <it>cre1 </it>locus. The mutation of the <it>cre1 </it>locus has specifically occurred in RUT C30. Some of the genes that are lacking in RUT C30 could be correlated with pronounced alterations in its phenotype, such as poor growth on α-linked oligo- and polyglucosides (loss of maltose permease), or disturbance of osmotic homeostasis.</p> <p>Conclusion</p> <p>Our data place a general caveat on the use of <it>H. jecorina </it>RUT C30 for further basic research.</p

Sampling-Based Trajectory (re)planning for Differentially Flat Systems: Application to a 3D Gantry Crane

In this paper, a sampling-based trajectory planning algorithm for a laboratory-scale 3D gantry crane in an environment with static obstacles and subject to bounds on the velocity and acceleration of the gantry crane system is presented. The focus is on developing a fast motion planning algorithm for differentially flat systems, where intermediate results can be stored and reused for further tasks, such as replanning. The proposed approach is based on the informed optimal rapidly exploring random tree algorithm (informed RRT*), which is utilized to build trajectory trees that are reused for replanning when the start and/or target states change. In contrast to state-of-the-art approaches, the proposed motion planning algorithm incorporates a linear quadratic minimum time (LQTM) local planner. Thus, dynamic properties such as time optimality and the smoothness of the trajectory are directly considered in the proposed algorithm. Moreover, by integrating the branch-and-bound method to perform the pruning process on the trajectory tree, the proposed algorithm can eliminate points in the tree that do not contribute to finding better solutions. This helps to curb memory consumption and reduce the computational complexity during motion (re)planning. Simulation results for a validated mathematical model of a 3D gantry crane show the feasibility of the proposed approach.Comment: Published at IFAC-PapersOnLine (13th IFAC Symposium on Robot Control

Model Predictive Trajectory Optimization With Dynamically Changing Waypoints for Serial Manipulators

Systematically including dynamically changing waypoints as desired discrete actions, for instance, resulting from superordinate task planning, has been challenging for online model predictive trajectory optimization with short planning horizons. This paper presents a novel waypoint model predictive control (wMPC) concept for online replanning tasks. The main idea is to split the planning horizon at the waypoint when it becomes reachable within the current planning horizon and reduce the horizon length towards the waypoints and goal points. This approach keeps the computational load low and provides flexibility in adapting to changing conditions in real time. The presented approach achieves competitive path lengths and trajectory durations compared to (global) offline RRT-type planners in a multi-waypoint scenario. Moreover, the ability of wMPC to dynamically replan tasks online is experimentally demonstrated on a KUKA LBR iiwa 14 R820 robot in a dynamic pick-and-place scenario.Comment: 8 pages, 6 figure

Singularity Avoidance with Application to Online Trajectory Optimization for Serial Manipulators

This work proposes a novel singularity avoidance approach for real-time trajectory optimization based on known singular configurations. The focus of this work lies on analyzing kinematically singular configurations for three robots with different kinematic structures, i.e., the Comau Racer 7-1.4, the KUKA LBR iiwa R820, and the Franka Emika Panda, and exploiting these configurations in form of tailored potential functions for singularity avoidance. Monte Carlo simulations of the proposed method and the commonly used manipulability maximization approach are performed for comparison. The numerical results show that the average computing time can be reduced and shorter trajectories in both time and path length are obtained with the proposed approachComment: 8 pages, 2 figures, Accepted for publication at IFAC World Congress 202

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer

BACKGROUND: Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a “high-risk situation” (such as T4). METHODS: We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12 %); 77 of all T4 patients received postoperative chemotherapy (33 %). Kaplan-Meier analysis and Cox regression models were used for survival analyses. RESULTS: Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (p < 0.001) and recurrence-free survival (p = 0.008). However, no difference was observed between oxaliplatin-containing and non-oxaliplatin-containing treatment regimens. G2 and G3 tumors were found to particularly benefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. CONCLUSION: Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1404-9) contains supplementary material, which is available to authorized users

Princes Town & Akwidaa, Ghana. Early ›Shared Heritage‹ of German-African Interactions: The Brandenburg-Prussian Forts on the West Coast of Ghana and their Local Communities. Research in 2023 and 2024

While the German colonial period in parts of Africa has increasingly become a subject of archaeological investigations, less attention has been paid to the earlier ›shared heritage‹ of German involvement in the transatlantic slave trade. Brandenburg-Prussia entered the race for trading posts on the West African coast in the late 17th century, establishing strongholds in what is today the Western Region of Ghana. Among the most prominent material manifestations of this endeavour are the two forts Gross Friedrichsburg and Dorothea. The German trading venture was short-lived, however. It ended after roughly 30 years when the forts were sold to the Dutch. Nevertheless, during the colonial period in the late 19th/early 20th century, the Brandenburg-Prussian attempt at profiting from the transatlantic slave trade was celebrated by some as the nucleus of German colonial rule in Africa. The Brandenburg-Prussian forts are today part of the serial UNESCO World Heritage site ›Forts and Castles, Volta, Greater Accra, Central and Western Regions‹, which recognises the difficult heritage of the transatlantic slave trade. However, the fortified trading posts also play an important role in local heritage landscapes. At the invitation of the local communities of Princes Town and Akwidaa, a new Ghanaian-German archaeological research and heritage preservation project is focusing on the Brandenburg-Prussian forts in their local contexts, highlighting the agency of local actors in the Early Modern period.Während die deutsche Kolonialzeit in Teilen Afrikas zunehmend zum Gegenstand archäologischer Untersuchungen geworden ist, wurde dem früheren ›gemeinsamen Erbe‹ der deutschen Beteiligung am transatlantischen Versklavungshandel weniger Aufmerksamkeit geschenkt. Brandenburg-Preußen stieg im späten 17. Jahrhundert in den Wettlauf um Handelsposten an der westafrikanischen Küste ein und errichtete Stützpunkte in der heutigen Western Region von Ghana. Zu den bedeutendsten materiellen Zeugnissen dieser Bestrebungen gehören die Befestigungen Gross Friedrichsburg und Dorothea. Die deutsche Handelsunternehmung endete bereits nach etwas mehr als 30 Jahren, als die Festungen an die Niederländer verkauft wurden. Dennoch wurde der brandenburgisch-preußische Versuch, vom transatlantischen Versklavungshandel zu profitieren, in der Kolonialzeit des späten 19. und frühen 20. Jahrhunderts von manchen als Keimzelle der deutschen Kolonialherrschaft in Afrika angesehen. Die brandenburgisch-preußischen Festungsanlagen sind heute Teil der seriellen UNESCO-Welterbestätte »Forts and Castles, Volta, Greater Accra, Central and Western Regions«, die dem schwierigen Erbe des transatlantischen Versklavungshandels gewidmet ist. Aber die befestigten Handelsstützpunkte spielen auch eine wichtige Rolle in der lokalen Kulturlandschaft. Auf Einladung der lokalen Gemeinschaften von Princes Town und Akwidaa konzentriert sich ein neues ghana-isch-deutsches archäologisches Forschungs- und Denkmalschutzprojekt daher auf die brandenburgisch-preußischen Festungen in ihrem lokalen Kontext und beleuchtet die Rolle(n) der lokalen Akteure in der Frühen Neuzeit

Saccades are phase-locked to alpha oscillations in the occipital and medial temporal lobe during successful memory encoding

Efficient sampling of visual information requires a coordination of eye movements and ongoing brain oscillations. Using intracranial and magnetoencephalography (MEG) recordings, we show that saccades are locked to the phase of visual alpha oscillations and that this coordination is related to successful mnemonic encoding of visual scenes. Furthermore, parahippocampal and retrosplenial cortex involvement in this coordination reflects effective vision-to-memory mapping, highlighting the importance of neural oscillations for the interaction between visual and memory domains.publishedVersion© 2017 Staudigl et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Acute and long-term survival in chronically critically ill surgical patients: a retrospective observational study

Introduction Various cohort studies have shown that acute ( short-term) mortality rates in unselected critically ill patients may have improved during the past 15 years. Whether these benefits also affect acute and long-term prognosis in chronically critically ill patients is unclear, as are determinants relevant to prognosis. Methods We conducted a retrospective analysis of data collected from March 1993 to February 2005. A cohort of 390 consecutive surgical patients requiring intensive care therapy for more than 28 days was analyzed. Results The intensive care unit ( ICU) survival rate was 53.6%. Survival rates at one, three and five years were 61.8%, 44.7% and 37.0% among ICU survivors. After adjustment for relevant covariates, acute and long-term survival rates did not differ significantly between 1993 to 1999 and 1999 to 2005 intervals. Acute prognosis was determined by disease severity during ICU stay and by primary diagnosis. However, only the latter was independently associated with long-term prognosis. Advanced age was an independent prognostic determinant of poor short-term and long-term survival. Conclusion Acute and long-term prognosis in chronically critically ill surgical patients has remained unchanged throughout the past 12 years. After successful surgical intervention and intensive care, long-term outcome is reasonably good and is mainly determined by age and underlying disease