Symmetry-Induced Tunnelling in One-Dimensional Disordered Potentials

A new mechanism of tunnelling at macroscopic distances is proposed for a wave packet localized in one-dimensional disordered potential with mirror symmetry, V(-x)=V(x). Unlike quantum tunnelling through a regular potential barrier, which occurs only at the energies lower then the barrier height, the proposed mechanism of tunnelling exists even for weak white-noise-like scattering potentials. It also exists in classical circuits of resonant contours with random resonant frequencies. The latter property may be used as a new method of secure communication, which does not require coding and decoding of the transmitting signal.Comment: 10 pages, 4 figure

Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases

Obesity, the most common nutritional disorder in industrial countries, is associated with increased cardiovascular mortality and morbidity. Nevertheless, the molecular basis linking obesity with cardiovascular disturbances have not yet been fully clarified. Recent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ, but also a secretory organ, producing a variety of bioactive substances, including leptin and adiponectin, that may influence the function as well as the structural integrity of the cardiovascular system. Leptin, besides being a satiety signal for the central nervous system and to be related to insulin and glucose metabolism, may also play an important role in regulating vascular tone because of the widespread distribution of functional receptors in the vascular cells. On the other hand, the more recently discovered protein, adiponectin, seems to play a protective role in experimental models of vascular injury, in probable relation to its ability to suppress the attachment of monocytes to endothelial cells, which is an early event in the atherosclerotic process. There is already considerable evidence linking altered production of some adipocyte hormones with the cardiovascular complications of obesity. Therefore, the knowledge of alterations in the endocrine function of adipose tissue may help to further understand the high cardiovascular risk associated with obesity

Built environment change and change in BMI and waist circumference: Multi‐ethnic S tudy of A therosclerosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109571/1/oby20873.pd

The inhibitory effect of leptin on angiotensin II-induced vasoconstriction in vascular smooth muscle cells is mediated via a nitric oxide-dependent mechanism

Leptin inhibits the contractile response induced by angiotensin (Ang) II in vascular smooth muscle cells (VSMCs) of the aorta. We studied in vitro and ex vivo the role of nitric oxide (NO) in the effect of leptin on the Ang II-induced vasoconstriction of the aorta of 10-wk-old Wistar rats. NO and nitric oxide synthase (NOS) activity were assessed by the Griess and (3)H-arginine/citrulline conversion assays, respectively. Stimulation of inducible NOS (iNOS) as well as Janus kinases/signal transducers and activators of transcription (JAK/STAT) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were determined by Western blot. The contractile responses to Ang II were evaluated in endothelium-denuded aortic rings using the organ bath system. Changes in intracellular Ca(2+) were measured in VSMCs using fura-2 fluorescence. Leptin significantly (P < or = 0.01) stimulated NO release and NOS activity in VSMCs. Leptin's effect on NO was abolished by the NOS inhibitor, N(G)-monomethyl l-arginine, or the iNOS selective inhibitor L-N(6)-(1-iminoethyl)-lysine. Accordingly, leptin increased iNOS protein expression, with a comparable time course with that of NO production and NOS activity. Leptin also significantly increased STAT3 (P < or = 0.01) and Akt (P < or = 0.001) phosphorylation. Moreover, either the JAK2 inhibitor, AG490, or the PI3K inhibitor, wortmannin, significantly (P < or = 0.05) abrogated the leptin-induced increase in iNOS protein. Finally, both N(G)-monomethyl L-arginine and L-N(6)-(1-iminoethyl)-lysine inhibitors completely blunted (P < or = 0.001) the leptin-mediated inhibition of the Ang II-induced VSMC activation and vasoconstriction. These findings suggest that the endothelium-independent depressor action of leptin is mediated by an increase of NO bioavailability in VSMCs. This process requires the up-regulation of iNOS through mechanisms involving JAK2/STAT3 and PI3K/Akt pathways

How much are built environments changing, and where?: Patterns of change by neighborhood sociodemographic characteristics across seven U.S. metropolitan areas

Investments in neighborhood built environments could increase physical activity and overall health. Disproportionate distribution of these changes in advantaged neighborhoods could inflate health disparities. Little information exists on where changes are occurring. This paper aims to 1) identify changes in the built environment in neighborhoods and 2) investigate associations between high levels of change and sociodemographic characteristics. Using Geographic Information Systems, neighborhood land-use, local destinations (for walking, social engagement, and physical activity), and sociodemographics were characterized in 2000 and 2010 for seven U.S. cities. Linear and change on change models estimated associations of built environment changes with baseline (2000) and change (2010–2000) in sociodemographics. Spatial patterns were assessed using Global Moran’s I to measure overall clustering of change and Local Moran’s I to identify statistically significant clusters of high increases surrounded by high increases (HH). Sociodemographic characteristics were compared between HH cluster and other tracts using Analysis of Variance (ANOVA). We observed small land-use changes but increases in the destination types. Greater increases in destinations were associated with higher percentage non-Hispanic whites, percentage households with no vehicle, and median household income. Associations were present for both baseline sociodemographics and changes over time. Greater increases in destinations were associated with lower baseline percentage over 65 but higher increases in percentage over 65 between 2000 and 2010. Global Moran’s indicated changes were spatially clustered. HH cluster tracts started with a higher percentage non-Hispanic whites and higher percentage of households without vehicles. Between 2000 and 2010, HH cluster tracts experienced increases in percent non-Hispanic white, greater increases in median household income, and larger decreases in percent of households without a vehicle. Changes in the built environment are occurring in neighborhoods across a diverse set of U.S. metropolitan areas, but are patterned such that they may lead to increased health disparities over time

Chronic myocardial infarction detection and characterization during coronary artery calcium scoring acquisitions

Background: Hypoenhanced regions on multidetector CT (MDCT) coronary angiography correlate with myocardial hyperperfusion. In addition to a limited capillary density, chronic myocardial infarction (MI) commonly contains a considerable amount of adipose tissue. Objective: We explored whether regional myocardial hypoenhancement on contrast-enhanced MDCT could be identified with standard coronary artery calcium (CAC) scoring acquisitions with noncontrast CT. Methods: Consecutive patients with a history of MI who were referred for contrast-enhanced MDCT from November 2006 until March 2009 were studied. Noncontrast CT for CAC scoring was also performed. The correlation between regional myocardial hypoenhancement on contrast-enhanced CT and regional myocardial hypoattenuated areas on noncontrast CT was defined. Results: Eighty-three patients (mean age, 61.5 ± 12.5 years; n = 67; 81% male) with previous MI were studied. A total of 1411 myocardial segments were evaluated. Two hundred thirty-nine segments (17%) showed myocardial hypoenhancement by MDCT and 140 segments (9.6%) by CAC. On a patient level, noncontrast CT showed a sensitivity, specificity, positive predictive value, (PPV) and negative predictive value (NPV) of 66% (95% CI, 0.53-0.77), 100% (95% CI, 0.76-1.00), 100% (95% CI, 0.90-1.00), and 41% (95% CI, 0.26-0.58), respectively, to detect myocardial hypoenhancement. On a per segment level, noncontrast CT showed a sensitivity, specificity, PPV, and NPV of 58% (95% CI, 0.51-0.64), 100% (95% CI, 0.99-1.00), 99% (95% CI, 0.94-1.00), and 92% (95% CI, 0.90-0.93), respectively, to detect myocardial hypoenhancement. Conclusions: Our findings suggest that chronic MI can be detected with standard CAC scoring acquisitions. © 2010 Society of Cardiovascular Computed Tomography.Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Rosales, Miguel A.. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Renes, Paola. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Diez, Eduardo. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Pereyra, Jorge. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Gomez, Estela. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: De Lillo, Gustavo. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Degrossi, Elina. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Rodriguez, Alfredo E.. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: McFadden, Eugene P.. Cork University Hospital; Irland

Leptin Inhibits Angiotensin II-Induced Intracellular Calcium Increase and Vasoconstriction in the Rat Aorta

Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7) mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to inhibit 65% of the ANG II-induced calcium release from intracellular stores. In endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on basal tension was observed. However, the ANG II-induced isometric contraction was reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also performed in age- and sex-matched Zucker rats, in which no effect of leptin on ANG II-induced calcium increase and vasoconstriction was observed. It is concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These findings provide new insight into the physiological effects of leptin on blood pressure regulation

Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer

PURPOSE: Identification of effective and reliable biomarkers that could be used to predict the efficacy of endocrine therapy is of crucial importance to the management of oestrogen receptor positive (ER+) breast cancer (BC). KIF18A, a key regulator of cell cycle, is overexpressed in many human cancers, including BC. In this study, we investigated the role of KIF18A as a biomarker to predict the benefit from endocrine treatment in early ER + BC patients.METHODS: KIF18A expression was assessed at the genomic level using the METABRIC dataset to explore its prognostic and predictive value in ER + BC patients (n = 1506). Predictive significance of KIF18A mRNA was validated using KM-Plot datasets (n = 2061). KIF18A protein expression was assessed using immunohistochemistry in a large annotated series of early-stage ER + BC (n = 1592) with long-term follow-up.RESULTS: High mRNA and protein expression of KIF18A were associated with short recurrence-free survival (RFS), distant-metastasis free survival (DMFS) and BC specific survival (all P  less than 0.05) in ER + BC in patients who received no adjuvant treatment or adjuvant endocrine therapy. In multivariate analysis, high KIF18A expression was an independent prognostic biomarker for poor RFS (P = 0.027) and DMFS (P = 0.028) in patients treated with adjuvant endocrine therapy.Conclusion: KIF18A appears to be a candidate biomarker of a subgroup of ER + BC characterised by poor clinical outcome. High KIF18A expression has prognostic significance to predict poor benefit from endocrine treatment for patients with ER + BC. Therefore, measurement of KIF18A on ER + BC patients prior to treatment could guide clinician decision on benefit from endocrine therapy