Transformation properties and microstructure of sputter-deposited Ni-Ti shape memory alloy thin films

The influence of annealing parameters on the martensitic phase transformation in sputter-deposited Ti rich Ni-Ti films is systematically studied by differential scanning calorimetry and by transmission electron microscopy. The annealing temperature range extends from the crystallization temperature of the films up to 900°C. For increasing temperature, multiple phase transformations, transformations via an R-phase or direct martensite/austenite transformations are observed. A similar behavior is found for increasing annealing time. Related changes of the film microstructure, such as the strongly varying distribution of round Ti2Ni precipitates in the grains, are analyzed. Transformation temperatures could be shifted over a wide range by adjusting the film composition from 48 to 54 at.% Ti. The corresponding transformation curves, grain structure as well as nature and amount of precipitates were investigated. No subsequent annealing process is required for films deposited on substrates heated above about 500°C. In this case, the as-deposited films have a very fine-grained and homogeneous microstructur

Neurophysiologische Studien zu raumzeitlichen Mustern induzierter und evozierter Oszillationen

Für ein besseres Verständnis der kortikalen Informationsverarbeitung ist es wichtig, die funktionelle Konnektivität der an der Lösung einer Aufgabe beteiligten Areale zu kennen. Eine Möglichkeit funktionelle Konnektivität zu untersuchen, besteht in der Analyse raumzeitlicher Aktivierungsmuster. Aus der Aktivierungsabfolge der beteiligten Areale kann unter bestimmten Annahmen, die Richtung des Informationsflusses zwischen diesen Arealen hergeleitet werden. Es ist bekannt, dass die Dynamik kortikaler Gammaoszillationen eng mit den neuronalen Prozessen der Reizverarbeitung, Aufmerksamkeit und des Gedächtnisses verknüpft sind. Da Gammaoszillationen in den meisten kortikalen Arealen auftreten, eignen sie sich besonders gut, um die raum-zeitliche Koordination multipler Verarbeitungsstufen höherer kognitiver Leistungen zu untersuchen

Synthesis and post-synthetic modification of amine-, alkyne-, azide- and nitro-functionalized metal-organic frameworks based on DUT-5

Functionalized 4,4′-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal-organic frameworks and mixed-linker metal-organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials. © The Royal Society of Chemistry 2015

Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor

Non-physiological activation of the mineralocorticoid receptor (MR), e.g. by aldosterone under conditions of high salt intake, contributes to the pathogenesis of cardiovascular diseases, although beneficial effects of aldosterone also have been described. The epidermal growth factor receptor (EGFR) contributes to cardiovascular alterations and mediates part of the MR effects. Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals. We hypothesize that moderate high aldosterone/NaCl, at normal blood pressure, affects the cardiovascular system depending on cardiovascular EGFR. Therefore we performed an experimental series in male and female animals each, using a recently established mouse model with EGFR knockout in vascular smooth muscle cells and cardiomyocytes and determined the effects of a mild-high aldosterone-to-NaCl constellation on a.o. marker gene expression, heart size, systolic blood pressure, impulse conduction and heart rate. Our data show that (i) cardiac tissue of male but not of female mice is sensitive to mild aldosterone/NaCl treatment, (ii) EGFR knockout induces stronger cardiac disturbances in male as compared to female animals and (iii) mild aldosterone/NaCl treatment requires the EGFR in order to disturb cardiac tissue homeostasis whereas beneficial effects of aldosterone seem to be independent of EGFR

In Pursuit of Prehistoric Caribou on Thandlät, Southern Yukon

In 1997, the first author noted a large concentration of caribou (Rangifer sp.) fecal pellets and a caribou antler on a permanent snow patch in the Kusawa Lake area of southern Yukon. Caribou are completely absent from this area today. Coring of the snow patch revealed continuous deposits of fecal pellets to depths of at least 160 cm. The proximal portion of a wooden dart or arrow shaft fragment recovered on the edge of the snow patch represents one of the few organic examples of mid-Holocene hunting technology ever found in Canada. An age of 2450 BP ± 50 years was obtained for the fecal material from approximately 1.6 m below the surface of the snow patch, and the dart was dated at 4360 BP ± 50 years. These dates indicate that aboriginal Yukon hunters have been harvesting caribou at this location for at least 4000 years. The Thandlät site offers a rare opportunity to explore a number of questions regarding the prehistoric ecology of large caribou populations, the implications of climate change for caribou populations, and human use of high-elevation hunting sites.En 1997, le premier auteur a découvert une concentration élevée de boulettes fécales (Rangifer sp.) et des bois de caribou sur une congère dans la région du lac Kusawa, dans le sud du Yukon. Il n'y a plus de caribous dans cette région. Le carottage de la congère a révélé des dépôts de boulettes jusqu'à une profondeur de 160 cm. Un fragment de dard ou de la flèche en bois trouvé sur le bord de la congère représente une des rares découvertes au Canada relatives à ce type d'arme. Il a été déterminé que les matières fécales prélevées dans la congère, à environ 1,6 m de profondeur, sont âgées de 2450 BP ± 50 ans, et que le dard aurait 4360 BP ± 50 ans. Ces dates montrent que les Autochtones du Yukon chassaient déjà le caribou à cet endroit il y a 4000 ans. Le site Thandlät est un des rares endroits où l'on peut observer divers aspects préhistoriques des grandes populations de caribou, des effets des changements climatiques sur les populations de caribous et des activités de chasse à grande altitude

Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma

Purpose: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in a high percentage of medullary thyroid carcinomas (MTC). Analogous to somatostatin receptors, CCK-2 receptors might be viable targets for radionuclide scintigraphy and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed, and some have been carried through into clinical studies. However, these studies are mostly limited and difficult to compare. The aim of this study was to evaluate the diagnostic and therapeutic potential of three promising CCK-2 receptor-binding radiopeptides in patients with MTC. Methods: 111In-DOTA-(D)Asp-Tyr-Nle-Gly-Trp-Nle- Asp-Phe-NH2 (111In-DOTA-CCK), a CCK analogue, and the gastrin-based ligands 99mTc-N4-Gly-(D)Glu-(Glu) 5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (99mTc- demogastrin 2) and 111In-DOTA-(D)Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe- NH2 (111In-DOTA-MG11) were each administered to the same group of six patients. Planar images made at 3-5, 7 and 24 h p.i. were used for comparison of tumour visualisation and renal uptake. Results: 99mTc-demogastrin 2 scintigraphy visualised all known lesions and new lesions in four of six patients. 111In-DOTA-CCK and 111In-DOTA-MG11 on the other hand missed several lesions; tumour uptake of these two radiopharmaceuticals was quite low. Comparison of retention of renal activity showed no major differences between the three radiopeptides. Conclusion: 99mTc-demogastrin 2 scintigraphy appeared most promising as a diagnostic tool in patients with MTC. Further studies are required to evaluate its value in patient management. Direct comparisons of the compounds studied strongly suggests that 111In-DOTA-CCK and 111In-DOTA-MG11 have less potential as imaging agents than 99mTc-demogastrin 2. These DOTA-linked compounds are considered unlikely to be useful for radionuclide therapy because of low tumour uptake

Phrenologyand the Insanity Defence: Medical Jurisprudence in the McNaughtan Trial

This thesis argues that phrenology shaped the defence argument in the McNaughtan trial. The role of this now-discredited science exemplifies the negotiation of scientific, legal and lay knowledge in the early nineteenth century, at a time when science was challenging the primacy of lay understandings of insanity. Phrenological ideas allowed the defence to privilege medical opinion over lay opinion, and propose a model of the mind that could account for McNaughtan’s insanity. This was possible because the medical and professional communities accepted some elements of the science. They applied these principles when explaining and verifying insanity in a courtroom setting

Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic

Indexación: Web of ScienceTwo ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile. We reconstituted IPA-activation of PERK-mediated eIF2α phosphorylation from purified components. We estimate that under conditions of maximal activation less than 15% of PERK molecules in the reaction are occupied by IPA. We propose that IPA binding biases the PERK kinase towards its active conformation, which trans-activates apo-PERK molecules. The mechanism by which partial occupancy with an inhibitor can activate kinases may be wide-spread and carries major implications for design and therapeutic application of kinase inhibitors.https://elifesciences.org/content/4/e0543

The Src Homology and Collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development

ShcA (Src Homology and Collagen A) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca2+/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere