Possible Hypoxia Signaling Induced Alteration of Glucose Homeostasis in Rats Exposed to Chronic Intermittent Hypoxia - Role of Antioxidant (Vitamin C) and Ca2+ Channel Blocker (Cilnidipine)

Background: Hyperglycemia is found to be a regulator of HIF-1α gene expression but the regulation of HIF-1α on glucose homeostasis is unclear. Objective: To determine whether chronic intermittent hypoxia (CIH) alters glucose regulation and such alterations can revert through treatments with either antioxidant (vitamin c) or calcium channel blocker (cilnidipine) in male albino rats. Methods: The rats were divided into six groups i.e. normoxia (21% oxygen), CIH (10% oxygen with cycle time 3:1.5; 8h/day), normoxia with vitamin c (50 mg /100g. b.wt, orally), CIH with vitamin c, normoxia with cilnidipine (1 mg/kg/day; ip) and CIH with cilnidipine. Serum MDA, HIF-1α, fasting plasma glucose, insulin, GTT, HOMA-IR and insulinogenic index were evaluated. Results: Serum HIF-1α and MDA concentration in rats exposed to CIH increased significantly whereas simultaneous CIH with vitamin c and CIH with cilnidipine treatment show reversion of both serum HIF- 1α and MDA concentrations towards normoxic status. CIH rats showed increased fasting glucose level with unchanged plasma insulin level but both vitamin c and cilnidipine treatment improved the status. Elevated HOMA-IR and insulinogenic index along with impaired GTT were found in CIH groups although vitamin c and cilnidipine improved the glucose homeostasis in CIH exposed rats. Conclusion: CIH induces over production of reactive oxygen species as well as hyper activities of sympathetic N-type Ca2+ channels possibly through HIF 1-α expression and influence on insulin signaling by causing hyperglycemia, glucose intolerance and insulin resistance in rats. Simultaneous treatment with vitamin c or cilnidipine improves glucose homeostasis in CIH exposed rats

Intertwining Relations for the Deformed D1D5 CFT

The Higgs branch of the D1D5 system flows in the infrared to a two-dimensional N=(4,4) SCFT. This system is believed to have an "orbifold point" in its moduli space where the SCFT is a free sigma model with target space the symmetric product of copies of four-tori; however, at the orbifold point gravity is strongly coupled and to reach the supergravity point one needs to turn on the four exactly marginal deformations corresponding to the blow-up modes of the orbifold SCFT. Recently, technology has been developed for studying these deformations and perturbing the D1D5 CFT off its orbifold point. We present a new method for computing the general effect of a single application of the deformation operators. The method takes the form of intertwining relations that map operators in the untwisted sector before application of the deformation operator to operators in the 2-twisted sector after the application of the deformation operator. This method is computationally more direct, and may be of theoretical interest. This line of inquiry should ultimately have relevance for black hole physics.Comment: latex, 23 pages, 3 figure

Drug resistance in non-B subtype HIV-1: Impact of HIV-1 reverse transcriptase inhibitors

Human immunodeficiency virus (HIV) causes approximately 2.5 million new infections every year, and nearly 1.6 million patients succumb to HIV each year. Several factors, including cross-species transmission and error-prone replication have resulted in extraordinary genetic diversity of HIV groups. One of these groups, known as group M (main) contains nine subtypes (A-D, F-H and J-K) and causes ∼95% of all HIV infections. Most reported data on susceptibility and resistance to anti-HIV therapies are from subtype B HIV infections, which are prevalent in developed countries but account for only ∼12% of all global HIV infections, whereas non-B subtype HIV infections that account for ∼88% of all HIV infections are prevalent primarily in low and middle-income countries. Although the treatments for subtype B infections are generally effective against non-B subtype infections, there are differences in response to therapies. Here, we review how polymorphisms, transmission efficiency of drug-resistant strains, and differences in genetic barrier for drug resistance can differentially alter the response to reverse transcriptase-targeting therapies in various subtypes

Splice Site Mutations in the ATP7A Gene

Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12 mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to in vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations identified in 12 patients with milder phenotypes were predicted to have no significant effect on splicing, which concurs with the presence of wild-type transcript in 7 out of 9 patients investigated in vivo. Both the in silico predictions and the in vivo results support the hypothesis previously suggested by us and others, that the presence of some wild-type transcript is correlated to a milder phenotype

Towards highly homogeneous self-regulating heating of smart nanocomposites

Smart self-regulating heating devices utilising the positive temperature coefficient (PTC) effect have shown great potential in advancing applications across healthcare, soft robotics, and energy-efficient manufacturing. However, achieving homogeneous resistive heating within such temperature self-controllable nanocomposites remains a significant challenge, falling short of meeting the requirements of advanced heating systems. This study explores and evaluates multiple innovative strategies aimed at enhancing the temperature uniformity of PTC nanocomposites. By identifying and analysing the primary physical mechanisms behind the inhomogeneous heating observed in conductive polymer composites, we propose a series of targeted strategies, ranging from customised material formulations to novel electrode configurations. Recycled carbon fibres have also been explored and upcycled as an effective solution for homogenous self-regulating heating. Through a comprehensive analysis of experimental results, the effectiveness of each strategy has been evaluated with a significantly improved temperature uniformity (from 32.6 to 2.7 % variation at 125 °C), providing valuable insights for the design and development of advanced self-regulating heating devices based on conductive polymer nanocomposites, while offering promising prospects for achieving more energy-efficient and uniform heating in various industrial applications

Comments on black holes I: The possibility of complementarity

We comment on a recent paper of Almheiri, Marolf, Polchinski and Sully who argue against black hole complementarity based on the claim that an infalling observer 'burns' as he approaches the horizon. We show that in fact measurements made by an infalling observer outside the horizon are statistically identical for the cases of vacuum at the horizon and radiation emerging from a stretched horizon. This forces us to follow the dynamics all the way to the horizon, where we need to know the details of Planck scale physics. We note that in string theory the fuzzball structure of microstates does not give any place to 'continue through' this Planck regime. AMPS argue that interactions near the horizon preclude traditional complementarity. But the conjecture of 'fuzzball complementarity' works in the opposite way: the infalling quantum is absorbed by the fuzzball surface, and it is the resulting dynamics that is conjectured to admit a complementary description.Comment: 34 pages, 6 figures, v3: clarifications & references adde

New instability of non-extremal black holes: spitting out supertubes

We search for stable bound states of non-extremal rotating three-charge black holes in five dimensions (Cvetic-Youm black holes) and supertubes. We do this by studying the potential of supertube probes in the non-extremal black hole background and find that generically the marginally bound state of the supersymmetric limit becomes metastable and disappears with non-extremality (higher temperature). However near extremality there is a range of parameters allowing for stable bound states, which have lower energy than the supertube-black hole merger. Angular momentum is crucial for this effect. We use this setup in the D1-D5 decoupling limit to map a thermodynamic instability of the CFT (a new phase which is entropically dominant over the black hole phase) to a tunneling instability of the black hole towards the supertube-black hole bound state. This generalizes the results of ArXiv:1108.0411 [hep-th], which mapped an entropy enigma in the bulk to the dual CFT in a supersymmetric setup.Comment: 28 pages + appendix, 15 figures, v2: References added, typos corrected. Version published in JHE

Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2

OBJECTIVE: Subfield-specific measurements provide superior information in the early stages of neurodegenerative diseases compared to global hippocampal measurements. The overall goal was to systematically compare the performance of five representative manual and automated T1 and T2 based subfield labeling techniques in a sub-set of the ADNI2 population. METHODS: The high resolution T2 weighted hippocampal images (T2-HighRes) and the corresponding T1 images from 106 ADNI2 subjects (41 controls, 57 MCI, 8 AD) were processed as follows. A. T1-based: 1. Freesurfer + Large-Diffeomorphic-Metric-Mapping in combination with shape analysis. 2. FreeSurfer 5.1 subfields using in-vivo atlas. B. T2-HighRes: 1. Model-based subfield segmentation using ex-vivo atlas (FreeSurfer 6.0). 2. T2-based automated multi-atlas segmentation combined with similarity-weighted voting (ASHS). 3. Manual subfield parcellation. Multiple regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. RESULTS: Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between controls and MCI (ES: 0.27 vs 0.11). T2-HighRes approaches outperformed T1 approaches for the detection of early stage atrophy (ES: 0.27 vs.0.10), amyloid positivity (ES: 0.11 vs 0.04), and cognitive associations (ES: 0.22 vs 0.19). CONCLUSIONS: T2-HighRes subfield approaches outperformed whole hippocampus and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry

Stringy effects in black hole decay

We compute the low energy decay rates of near-extremal three(four) charge black holes in five(four) dimensional N=4 string theory to sub-leading order in the large charge approximation. This involves studying stringy corrections to scattering amplitudes of a scalar field off a black hole. We adapt and use recently developed techniques to compute such amplitudes as near-horizon quantities. We then compare this with the corresponding calculation in the microscopic configuration carrying the same charges as the black hole. We find perfect agreement between the microscopic and macroscopic calculations; in the cases we study, the zero energy limit of the scattering cross section is equal to four times the Wald entropy of the black hole.Comment: 32 page

Detecting a conditional extrme value model

In classical extreme value theory probabilities of extreme events are estimated assuming all the components of a random vector to be in a domain of attraction of an extreme value distribution. In contrast, the conditional extreme value model assumes a domain of attraction condition on a sub-collection of the components of a multivariate random vector. This model has been studied in \cite{heffernan:tawn:2004,heffernan:resnick:2007,das:resnick:2008a}. In this paper we propose three statistics which act as tools to detect this model in a bivariate set-up. In addition, the proposed statistics also help to distinguish between two forms of the limit measure that is obtained in the model.Comment: 21 pages, 4 figure