Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear.</p> <p>Methods</p> <p>Diabetic Akita (Ins2+/-) and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/-) were used for M-mode echocardiography at the age of four and twenty four weeks. The cardiac rings from WT, Akita and hybrid (Ins2+/-/CBS+/-) of Akita and CBS+/- were treated with different doses of acetylcholine (an endothelial dependent vasodilator). High performance liquid chromatography (HPLC) was performed for determining plasma homocysteine (Hcy) level in the above groups. Akita was treated with ciglitazone (CZ) - a PPAR gamma agonist and tempol-an anti-oxidant, separately and their effects on cardiac remodeling were assessed.</p> <p>Results</p> <p>At twenty four week, Akita mice were hyperglycemic and HHcy. They have increased end diastolic diameter (EDD). In their heart PPAR gamma, tissue inhibitor of metalloproteinase-4 (TIMP-4) and anti-oxidant thioredoxin were attenuated whereas matrix metalloproteinase (MMP)-9, TIMP-3 and NADPH oxidase 4 (NOX4) were induced. Interestingly, they showed synergism between HHcy and hyperglycemia for endothelial-myocyte (E-M) uncoupling. Additionally, treatment with CZ alleviated MMP-9 activity and fibrosis, and improved EDD. On the other hand, treatment with tempol reversed cardiac remodeling in part by restoring the expressions of TIMP-3,-4, thioredoxin and MMP-9.</p> <p>Conclusions</p> <p>Endogenous homocysteine exacerbates diabetic cardiomyopathy by attenuating PPAR gamma and inducing E-M uncoupling leading to diastolic dysfunction. PPAR gamma agonist and tempol mitigates oxidative stress and ameliorates diastolic dysfunction in diabetes.</p

Fluctuation Induced Non-Fermi Liquid Behavior near a Quantum Phase Transition in Itinerant Electron Systems

The signature for a non-Fermi liquid behavior near a quantum phase transition has been observed in thermal and transport properties of many metallic systems at low temperatures. In the present work we consider specific examples of itinerant ferromagnet as well as antiferromagnet in the limit of vanishing transition temperature. The temperature variation of spin susceptibility, electrical resistivity, specific heat, and NMR relaxation rates at low temperatures is calculated in the limit of infinite exchange enhancement within the frame work of a self consistent spin fluctuation theory. The resulting non-Fermi liquid behavior is due to the presence of the low lying critically damped spin fluctuations in these systems. The theory presented here gives the leading low temperature behavior, as it turns out that the fluctuation correlation term is always smaller than the mean fluctuation field term in three as well as in two space dimensions. A comparison with illustrative experimental results of these properties in some typical systems has been done. Finally we make some remarks on the effect of disorder in these systems.Comment: File RevTex, 7 Figures available on request, Abstract and text modified, To appear in Phys. Rev.

Characterization of PARIS LaBr3_3(Ce)-NaI(Tl) phoswich detectors upto EγE_\gamma ∼\sim 22 MeV

In order to understand the performance of the PARIS (Photon Array for the studies with Radioactive Ion and Stable beams) detector, detailed characterization of two individual phoswich (LaBr$_3$(Ce)-NaI(Tl)) elements has been carried out. The detector response is investigated over a wide range of $E_{\gamma}$ = 0.6 to 22.6 MeV using radioactive sources and employing $^{11}B(p,\gamma)$ reaction at $E_p$ = 163 keV and $E_p$ = 7.2 MeV. The linearity of energy response of the LaBr$_3$(Ce) detector is tested upto 22.6 MeV using three different voltage dividers. The data acquisition system using CAEN digitizers is set up and optimized to get the best energy and time resolution. The energy resolution of $\sim$ 2.1% at $E_\gamma$ = 22.6~MeV is measured for the configuration giving best linearity upto high energy. Time resolution of the phoswich detector is measured with a $^{60}$Co source after implementing CFD algorithm for the digitized pulses and is found to be excellent (FWHM $\sim$ 315~ps). In order to study the effect of count rate on detectors, the centroid position and width of the $E_{\gamma}$ = 835~keV peak were measured upto 220 kHz count rate. The measured efficiency data with radioactive sources are in good agreement with GEANT4 based simulations. The total energy spectrum after the add-back of energy signals in phoswich components is also presented.Comment: Accepted in JINS

Data Analytics for Dynamic Urban Operations: A Test-Based Study on Data Analytics Efficiency

This paper explores the field of data analytics for dynamic urban operations and provides a systematic analysis of the importance and possible implications of this field. Our investigation indicates significant data volumes in an urban setting that is data-rich: 500 GB are generated by traffic sensors, 300 GB by environmental monitors, 150 GB by mobile apps, and 75 GB by emergency calls. A variety of analytics techniques, each with a different processing time, are built upon these data sources. These techniques include descriptive, predictive, prescriptive, and diagnostic analytics. The outcomes, which include 90% accuracy, an average processing time of 40 minutes, 80% resource utilization, and 4.2 user satisfaction ratings, highlight the benefits of data analytics. According to the comparison study, diagnostic analytics has a score of 7.8, indicating room for development, while prescriptive analytics leads with an efficiency score of 8.4. As urban stakeholders and academics work to improve urban systems and solve urban issues, the results give a thorough understanding of the effectiveness and application of data analytics in the context of dynamic urban operations

Quantum Griffiths phase in disordered Mn1-xFexSi

We show the presence of magnetic rare regions consistent with the quantum Griffiths phase in Fe-doped MnSi using detailed heat capacity, magnetization, and muon spin relaxation (μSR) measurements down to millikelvin temperatures. The slow dynamics of these rare regions at low temperatures leads to the non-Fermi-liquid behavior in heat capacity and magnetization. The μSR and magnetization results further indicate that the dynamics freezes into a cluster-glass state below Tf ∼ 1.25 K. The results are in agreement with theoretical models proposed in the literature for metallic systems with Heisenberg symmetry that exhibit the quantum Griffiths phase in the presence of strong disorder

Human protein reference database—2006 update

Human Protein Reference Database (HPRD) () was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein–protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein–protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far