Crossover from time-correlated single-electron tunneling to that of Cooper pairs

We have studied charge transport in a one-dimensional chain of small Josephson junctions using a single-electron transistor. We observe a crossover from time-correlated tunneling of single electrons to that of Cooper pairs as a function of both magnetic field and current. At relatively high magnetic field, single-electron transport dominates and the tunneling frequency is given by f=I/e, where I is the current through the chain and e is the electron's charge. As the magnetic field is lowered, the frequency gradually shifts to f=I/2e for I>200 fA, indicating Cooper-pair transport. For the parameters of the measured sample, we expect the Cooper-pair transport to be incoherent.Comment: 5 pages, 4 figures; v2: minor changes, clarifications, addition

Principles for dialogue design in man-machine systems

This paper emphasises the cognitive engineering of complex systems. It is clear that a unifying approach is required to bring together the otherwise complementary but disparate display based and task based methodologies. What is missing is an interaction or dialogue centred aspect to the design (Hollnagel and Weir, 1988), which can accommodate the exigencies of both display design and task design

Impairment of the Postural Venoarteriolar Response in Young Type 1 Diabetic Patients A Study by Laser Doppler Flowmetry

The skin blood flow and venoarteriolar response (VAR) in the feet of young type 1 diabetic patients were studied with laser Doppler flowmetry. The findings were correlated with diabetic microangiopathy in 24 young patients without neuropathy—14 with diabetic microangiopathy, 10 without—and 10 healthy controls. In type 1 diabetic patients the skin blood flow, after lowering of the leg, was significantly higher in the microangiopathic patients than in the healthy controls, 5.3 ± 1.4 vs 3 ± 1.5, (P < 0.01). The VAR index was significantly lower in both groups of diabetics as compared with controls. In conclusion laser Doppler flowmetry is an easy and reliable noninvasive technique to evaluate skin blood flow abnormalities in the feet of young type 1 diabetic patients, including those without neuropathy. The VAR has been found abnormal in the feet of young diabetic patients with and without microangiopathy, regardless of the presence of peripheral neuropathy

Cardiac leptin overexpression in the context of acute MI and reperfusion potentiates myocardial remodeling and left ventricular dysfunction.

BACKGROUND:Acute MI induces leptin expression in the heart, however the role of myocardial leptin in cardiac ischemia and reperfusion (IR) remains unknown. To shed light on the effects of elevated levels of leptin in the myocardium, we overexpressed cardiac leptin and assessed local remodeling and myocardial function in this context. METHODS AND RESULTS:Cardiac leptin overexpression was stimulated in mice undergoing IR by a single intraperitoneal injection of leptin antagonist (LepA). All mice exhibited a normal pattern of body weight gain. A rapid, long-term upregulation of leptin mRNA was demonstrated in the heart, adipose, and liver tissues in IR/LepA-treated mice. Overexpressed cardiac leptin mRNA extended beyond postoperative day (POD) 30. Plasma leptin peaked 7.5 hours postoperatively, especially in IR/LepA-treated mice, subsiding to normal levels by 24 hours. On POD-30 IR/LepA-treated mice demonstrated cardiomyocyte hypertrophy and perivascular fibrosis compared to IR/saline controls. Echocardiography on POD-30 demonstrated eccentric hypertrophy and systolic dysfunction in IR/LepA. We recorded reductions in Ejection Fraction (p<0.001), Fraction Shortening (p<0.01), and Endocardial Fraction Area Change (p<0.01), and an increase in Endocardial Area Change (p<0.01). Myocardial remodeling in the context of IR and cardiac leptin overexpression was associated with increased cardiac TGFβ ligand expression, activated Smad2, and downregulation of STAT3 activity. CONCLUSIONS:Cardiac IR coinciding with increased myocardial leptin synthesis promotes cardiomyocyte hypertrophy and fibrosis and potentiates myocardial dysfunction. Plasma leptin levels do not reflect cardiac leptin synthesis, and may not predict leptin-related cardiovascular morbidity. Targeting cardiac leptin is a potential treatment for cardiac IR damage