Implantation and atomic scale investigation of self-interstitials in graphene

Crystallographic defects play a key role in determining the properties of crystalline materials. The new class of two-dimensional materials, foremost graphene, have enabled atomically resolved studies of defects, such as vacancies, grain boundaries, dislocations, and foreign atom substitutions. However, atomic resolution imaging of implanted self-interstitials has so far not been reported in any three- but also not in any two-dimensional material. Here, we deposit extra carbon into single-layer graphene at soft landing energies of ~1 eV using a standard carbon coater. We identify all the self-interstitial dimer structures theoretically predicted earlier, employing 80 kV aberration-corrected high-resolution transmission electron microscopy. We demonstrate accumulation of the interstitials into larger aggregates and dislocation dipoles, which we predict to have strong local curvature by atomistic modeling, and to be energetically favourable configurations as compared to isolated interstitial dimers. Our results contribute to the basic knowledge on crystallographic defects, and lay out a pathway into engineering the properties of graphene by pushing the crystal into a state of metastable supersaturation

Influence of miR-221/222 on GIRK1/4 channel function and LTCC-dependent calcium handling in cardiomyocytes

Kardiales elektrisches Remodeling kann die Herzfunktion stark beeinträchtigen. Diese Arbeit untersuchte den Einfluss von miR-221/222 auf das elektrische Remodeling in Kardiomyozyten. Es wurde gezeigt, dass die Ionenkanaluntereinheiten Cacna1c und Girk4 direkt von beiden miRs reguliert werden. Der Einstrom von Tl+ über GIRK1/4 war signifikant vermindert in miR-transfizierten HL-1 Zellen. Weiterhin führten beide miRs zu einem langsameren Ca2+ Einstrom nach Depolarisation. Der Effekt von β-adrenerger Stimulation auf Calciumtransienten und spontane Kontraktionsfrequenz in neonatalen Kardiomyozyten war durch miR-222 stark reduziert. Diese Regulation der Ionenkanäle könnte im Herzen zu verminderter Kontraktilität und systolischer Dysfunktion führen. Insgesamt konnte mit dieser Arbeit eine neue Rolle von miR-221/222 im Kontext des elektrischen Remodelings aufgezeigt werden.Cardiac electrical remodeling can have detrimental effects on cardiac function. This study analysed the role of miR-221/222 in electrical remodeling in cardiomyocytes (CM). Ion channel subunits Cacna1c and Girk4 were shown to be direct targets of both miRs. Tl+ flux through GIRK1/4 was significantly reduced in miR-221- or miR-222-transfected cells. Furthermore, in HL-1 cells, miR-221/222 led to slower depolarization-dependent Ca2+ entry. In miR-222-transfected neonatal CMs the isoprenaline-induced effect on intracellular Ca2+ transients was lost and the effect on spontaneous beating frequency was strongly reduced. This could have severe consequences for cardiomyocytes, leading to reduced contractility and systolic dysfunction of the whole heart. Overall, this study adds a new role of miR-221/222 in cardiac electrical remodeling by showing the impact on GIRK1/4-mediated ion flux, β-adrenergic regulation of L-type Ca2+ channel function, cardiomyocyte calcium handling and contractility

Auswirkungen der Korngröße auf das Kontaktermüdungsverhalten von Nickel

Der Einfluss der Korngröße von Nickel auf das Kontaktermüdungsverhalten in zyklischen Eindruckversuchen sowie zyklischen Gleitversuchen wurde untersucht. Für den zyklischen Eindruckversuch wurde ein Versagenskriterium auf Basis der in situ gemessenen Kontaktsteifigkeit definiert. Beim zyklischen Gleitversuch wurde die Änderung der Härte des Materials aufgrund der Gleitversuche gemessen. Zudem wurden mikrostrukturelle Änderungen mittels fokussierter Ionenstrahlmikroskopie untersucht

Influence of miR-221/222 on cardiomyocyte calcium handling and function

Background: Cardiovascular disease is the leading cause of death worldwide. Cardiac electrical remodeling including altered ion channel expression and imbalance of calcium homeostasis can have detrimental effects on cardiac function. While it has been extensively reported that miR-221/222 are involved in structural remodeling, their role in electrical remodeling still has to be evaluated. We previously reported that subunits of the L-type Ca2+ channel (LTCC) are direct targets of miR-221/222. Furthermore, HL-1 cells transfected with miR-221 or -222 mimics showed a reduction in LTCC current density while the voltage-dependence of activation was not altered. The aim of the present study was to determine the influence of miR-221/222 on cardiomyocyte calcium handling and function. Results: Transient transfection of HL-1 cells with miR-221/222 mimics led to slower depolarization-dependent Ca2+ entry and increased proportion of non-responding cells. Angiotensin II-induced Ca2+ release from the SR was not affected by miR-221/222. In miR-222-transfected neonatal cardiomyocytes the isoprenaline-induced positive inotropic effect on the intracellular Ca2+ transient was lost and the positive chronotropic effect on spontaneous beating activity was strongly reduced. This could have severe consequences for cardiomyocytes and could lead to a reduced contractility and systolic dysfunction of the whole heart. Conclusions: This study adds a new role of miR-221/222 in cardiomyocytes by showing the impact on β-adrenergic regulation of LTCC function, calcium handling and beating frequency. Together with the previous report that miR-221/222 reduce GIRK1/4 function and LTCC current density, it expands our knowledge about the role of these miRs on cardiac ion channel regulation.Publikationsfonds ML

Evidence-Based Decompression in Malignant Biliary Obstruction

As recent advances in chemotherapy and surgical treatment have improved outcomes in patients with biliary cancers, the search for an optimal strategy for relief of their obstructive jaundice has become even more important. Without satisfactory relief of biliary obstruction, many patients would be ineligible for treatment. We review all prospective randomized trials and recent retrospective non-randomized studies for evidence that would support such a strategy. For distal malignant biliary obstruction, an optimal strategy would be insertion of metallic stents either endoscopically or percutaneously. Evidence shows that a metallic stent inserted percutaneously has better outcomes than plastic stents inserted endoscopically. For malignant hilar obstruction, percutaneous biliary drainage with or without metallic stents is preferred

Low skeletal muscle mass in stented esophageal cancer predicts poor survival : A retrospective observational study

Background Methods In esophageal cancer, nutritional challenges are extremely common. Malignant obstruction resulting from esophageal cancer (EC) is often treated by the insertion of expandable stents, but little is known as to the role and evolution of sarcopenia in this patient population. The aim of this article was to determine the effects of body mass parameters on survival of advanced EC patients who received a stent for palliation of malignant obstruction. This was a retrospective observational study of 238 EC patients who had a stent inserted for palliation of malignant obstruction between 2005 and 2013. Skeletal muscle mass was calculated from abdominal computed tomography scans, and the patients were divided into sarcopenic and non-sarcopenic groups. A follow-up computed tomography scan was available in 118 patients. The primary outcome was survival, and complication rates and the need for an alternative enteral feeding route were secondary outcomes. Results Conclusions Sarcopenia occurred in 199 (85%) patients. Median survival was 146 (range: 76-226) days in the sarcopenia group and 152 (range: 71-249) days in the non-sarcopenic group (P = 0.61). Complication rates between the groups were not significantly different (P = 0.85). In Cox regression analysis, the skeletal muscle index was inversely correlated with overall survival (hazard ratio 0.98, 95% confidence interval 0.97-0.99; P = 0.033). Sarcopenia, defined by consensus thresholds, at the time of stent insertion cannot effectively predict poor survival in this patient cohort, but a lower skeletal muscle index correlates with poor prognosis as a continuous variable.Peer reviewe

Mid-esophagus unresectable cancer treated with a low cost stent. First experience

<p>Abstract</p> <p>Background</p> <p>In the cancer of the esophagus, with recent technologic advances, self-expanding metal stents (SEMS) are at the forefront of the armamentarium for re-establishing luminal patency. Weighed against the numerous advantages of stents are the import conditions and the cost. In light of this, we tested new low cost prostheses having the basic needs and characteristics to aim a significant benefit to poor people having advanced esophageal cancer, in a Brazilian regional public hospital.</p> <p>Methods</p> <p>This initial experience included fifteen patients (eleven men and four women, 55 ± 6.17 years old), presenting esophageal cancer, located at the medium third of the thoracic esophagus, extending for 5.5-8 cm long, not suitable for surgical procedure because they had been staged on fourth grade of the disease, two of them having fistula communicating esophagus to respiratory tree. The stents were placed under endoscopic and fluoroscopic guidance, after attempting an esophageal dilatation. An appropriate covered stent was then deployed, twelve of 10 cm and three of 13 cm in length. A chest X-ray was done 2 h after the procedure and a barium swallow was performed within 12 hours. Seven days and monthly until complete a six month follow-up after the procedure the patients were questioned about presence of pain, regurgitation, heartburn, cough, and their alimentary behavior.</p> <p>Results</p> <p>There were no severe complications and transient mild chest pain resolved until the seventh day after the stent deployment. Chest X-ray demonstrated expansion of the stent in all patients. In 2 cases of fistula, a barium swallow showed its complete sealing. The completion of the proposed follow-up was not achieved in three cases, limited by the patient's death until the third month, due to cancer progression. Recurrent dysphagia to paste food accounted for by tumor overgrowth proximal or distal to the stent and stent migration were not observed in the series.</p> <p>Conclusions</p> <p>The new low cost endoprostheses is effective and forthcoming increased experience and prospective trials including questionnaires to analyze quality of life will allow for more informed decisions tailoring to a particular patient situation or to unexpected complications.</p

Bi-weekly Chemotherapy of Paclitaxel and Cisplatin in Patients with Metastatic or Recurrent Esophageal Cancer

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m2) followed by cisplatin (50 mg/m2). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer