Planar and van der Waals heterostructures for vertical tunnelling single electron transistors

Despite a rich choice of two-dimensional materials, which exists these days, heterostructures, both vertical (van der Waals) and in-plane, offer an unprecedented control over the properties and functionalities of the resulted structures. Thus, planar heterostructures allow p-n junctions between different two-dimensional semiconductors and graphene nanoribbons with well-defined edges; and vertical heterostructures resulted in the observation of superconductivity in purely carbon-based systems and realisation of vertical tunnelling transistors. Here we demonstrate simultaneous use of in-plane and van der Waals heterostructures to build vertical single electron tunnelling transistors. We grow graphene quantum dots inside the matrix of hexagonal boron nitride, which allows a dramatic reduction of the number of localised states along the perimeter of the quantum dots. The use of hexagonal boron nitride tunnel barriers as contacts to the graphene quantum dots make our transistors reproducible and not dependent on the localised states, opening even larger flexibility when designing future devices

Impact of comorbid psychiatric disorders on the outcome of substance abusers: a six year prospective follow-up in two Norwegian counties

BACKGROUND: Most help-seeking substance abusers have comorbid psychiatric disorders. The importance of such disorders for the long-term course of substance abuse is, however, still unclear. The aim of this paper is to describe six-year outcomes regarding death and relapse among alcoholics and poly-substance abusers and to analyse the predictive value of lifetime psychiatric disorders on relapse. METHODS: A consecutive sample of substance-dependent patients who received treatment in two counties in Norway (n = 287) was followed up after approximately six years. Information on socio-demographics, Axis I (CIDI) and II disorders (MCMI-II) and mental distress (HSCL-25) was gathered at baseline. At follow-up, detailed information regarding socio-demographics, use of substances (AUDIT and DUDIT) and mental distress (HSCL-25) was recorded (response rate: 63%). RESULTS: At six-year follow-up, 11% had died, most often male alcoholics (18%). Among the surviving patients, 70% had drug or alcohol related problems the year prior to follow-up. These patients were, classified as "relapsers". There were no significant differences in the relapse rate between women and men and among poly-substance abusers and alcoholics. The relapsers had an earlier onset of a substance use disorder, and more frequently major depression and agoraphobia. Multivariate analysis indicated that both psychiatric disorders (major depression) and substance use factors (early onset of a substance use disorder) were independent predictors of relapse. CONCLUSION: For reducing the risk of long-term relapse, assessment and treatment of major depression (and agoraphobia) are important. In addition, we are in need of a comprehensive treatment and rehabilitation program that also focuses on the addictive behaviour

Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders

Mesoangioblasts at 20: from the embryonic aorta to the patient bed

In 2002 we published an article describing a population of vessel-associated progenitors that we termed mesoangioblasts (MABs). During the past decade evidence had accumulated that during muscle development and regeneration things may be more complex than a simple sequence of binary choices (e.g., dorsal vs. ventral somite). LacZ expressing fibroblasts could fuse with unlabelled myoblasts but not among themselves or with other cell types. Bone marrow derived, circulating progenitors were able to participate in muscle regeneration, though in very small percentage. Searching for the embryonic origin of these progenitors, we identified them as originating at least in part from the embryonic aorta and, at later stages, from the microvasculature of skeletal muscle. While continuing to investigate origin and fate of MABs, the fact that they could be expanded in vitro (also from human muscle) and cross the vessel wall, suggested a protocol for the cell therapy of muscular dystrophies. We tested this protocol in mice and dogs before proceeding to the first clinical trial on Duchenne Muscular Dystrophy patients that showed safety but minimal efficacy. In the last years, we have worked to overcome the problem of low engraftment and tried to understand their role as auxiliary myogenic progenitors during development and regeneration

Inner/Outer Nuclear Membrane Fusion in Nuclear Pore Assembly: Biochemical Demonstration and Molecular Analysis

The nuclear pore complex (NPC) is characterized by a long-lived membrane-lined channel connecting the inner and outer nuclear membranes. This stabilized membrane channel, within which the nuclear pore is built, has little evolutionary precedent. In this report we demonstrate and map the inner/outer nuclear membrane fusion in NPC assembly

Expression pattern of the epithelial V\u2010like antigen (Eva) transcript suggests a possible role in placental morphogenesis

Adhesive mechanisms are considered to be of crucial importance for blastocyst adherence to the uterine wall, as well as for the interactions between embryonal and decidual tissues during hemochorial placenta formation. Epithelial V-like Antigen (Eva) is a novel homophilic adhesion molecule of the immunoglobulin superfamily, which during mouse embryonic development is expressed by various differentiating epithelia. In the present paper we describe Eva expression during mouse trophoblast invasion and placental morphogenesis, analysing day 5.5 to 18.5 postcoitum (p.c.) placentas and deciduomas by in situ hybridization. Eva transcripts were detected in spongiotrophoblast cells from 7.5 to 18.5 days p.c. Expression was uniform at early stages, but after day 11.5, p.c. became limited to the invasive subpopulation of spongiotrophoblasts (known as glycogen cells). Trophoblast giant cells did not express Eva in any of the stages analysed. Besides trophoblasts, also early postimplantation decidua was positive for Eva transcripts. In decidual tissue, Eva expression was present at day 5.5 p.c., peaked at day 7.5 p.c., and declined on successive days. The expression pattern of Eva transcripts suggests that during mouse placenta formation, its protein product may play a role in the processes of trophoblast invasion, decidual response, and trophoblast-decidual interaction

Lohnt sich betriebliche Suchtprävention? Zu Effektivität und Effizienz betrieblicher Alkoholprävention

Zielsetzung: Mitarbeitende mit Suchtproblemen können den betroffenen Betrieben erhebliche Kosten verursachen. Um erfolgreich zu sein, müssen sich präventive Maßnahmen jedoch für Betriebe in betriebswirtschaftlicher Hinsicht „lohnen”. Methode: Mittels einer umfassenden Literaturrecherche wurden Arbeiten aus dem angelsächsischen und hauptsächlich dem deutschen Sprachraum zu Effektivität und Effizienz von betrieblichen Maßnahmen im Alkoholbereich begutachtet. Ergebnisse: Es zeigte sich, dass nur wenige Arbeiten aus dem deutschsprachigen Raum vorliegen. Durch alkoholbedingte Fehlzeiten verursachte Kosten stehen im Mittelpunkt der meisten Studien. Auch wenn die Studien untereinander schlecht vergleichbar sind, wird aufgezeigt, dass durch präventive Maßnahmen ein wirtschaftlicher Nutzen entsteht, der die Kosten solcher Maßnahmen übersteigt. Schlussfolgerungen: Im Sinne eines eher primärpräventiven Ansatzes, der die Betriebe relativ wenig kostet und sich als effektiv erwiesen hat, wird für die Schweiz die Einführung von Kurzinterventionen bei Personen mit risikoreichem Alkoholkonsum auch auf betrieblicher Ebene vorgeschlagen

Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect.

Physiological concentrations of urokinase plasminogen activator (uPA) stimulated a chemotactic response in human monocytic THP-1 through binding to the urokinase receptor (uPAR). The effect did not require the protease moiety of uPA, as stimulation was achieved also with the N-terminal fragment (ATF), while the 33 kDa low molecular weight uPA was ineffective. Co-immunoprecipitation experiments showed association of uPAR with intracellular kinase(s), as demonstrated by in vitro kinase assays. Use of specific antibodies identified p56/p59hck as a kinase associated with uPAR in THP-1 cell extracts. Upon addition of ATF, p56/p59hck activity was stimulated within 2 min and returned to normal after 30 min. Since uPAR lacks an intracellular domain capable of interacting with intracellular kinase, activation of p56/p59hck must require a transmembrane adaptor. Evidence for this was strongly supported by the finding that a soluble form of uPAR (suPAR) was capable of inducing chemotaxis not only in THP-1 cells but also in cells lacking endogenous uPAR (IC50, 5 pM). However, activity of suPAR require chymotrypsin cleavage between the N-terminal domain D1 and D2 + D3. Chymotrypsin-cleaved suPAR also induced activation of p56/p59hck in THP-1 cells, with a time course comparable with ATF. Our data show that uPA-induced signal transduction takes place via uPAR, involves activation of intracellular tyrosine kinase(s) and requires an as yet undefined adaptor capable of connecting the extracellular ligand binding uPAR to intracellular transducer(s)