Moduli Stabilization and Inflationary Cosmology with Poly-Instantons in Type IIB Orientifolds

Equipped with concrete examples of Type IIB orientifolds featuring poly-instanton corrections to the superpotential, the effects on moduli stabilization and inflationary cosmology are analyzed. Working in the framework of the LARGE volume scenario, the Kaehler modulus related to the size of the four-cycle supporting the poly-instanton contributes sub-dominantly to the scalar potential. It is shown that this Kaehler modulus gets stabilized and, by displacing it from its minimum, can play the role of an inflaton. Subsequent cosmological implications are discussed and compared to experimental data.Comment: 38 pages, 7 figures, Reference added, Typo fixed, Published versio

Odontoid metastasis: a potential lethal complication

Nearly one third of cervical spine metastasis has a primary breast malignancy. Patients with cervical metastasis have higher mortality due to advanced stage of the malignancy. Treatment is palliative to relieve pain, prevent pathological fracture, improve mobility and function, and prolong survival. We describe a 40-year-old woman with a history of breast cancer who presented with neck and shoulder pain of 1 week duration with no neurological deficit. Following clinical examination, radiographs taken of the cervical spine was normal. Radiographs repeated 3 weeks later revealed a large lytic lesion of the odontoid occupying 70–80% of the peg. Further investigation including magnetic resonance imaging and bone scan showed no further spinal lesions. She underwent cyclical radiotherapy with complete resolution of the odontoid peg lesion and clinically was asymptomatic at 2 years. Metastatic lesions of the odontoid are atypical, and this case reinforces the necessity of early detection to evade disastrous consequences

Diagnostic and prognostic utility of an inexpensive rapid on site malaria diagnostic test (ParaHIT f) among ethnic tribal population in areas of high, low and no transmission in central India

BACKGROUND: Malaria presents a diagnostic challenge in most tropical countries. Rapid detection of the malaria parasite and early treatment of infection still remain the most important goals of disease management. Therefore, performance characteristics of the new indigenous ParaHIT f test (Span diagnostic Ltd, Surat, India) was determined among ethnic tribal population in four districts of different transmission potential in central India to assess whether this rapid diagnostic test (RDT) could be widely applied as a diagnostic tool to control malaria. Beyond diagnosis, the logical utilization of RDTs is to monitor treatment outcome. METHODS: A finger prick blood sample was collected from each clinically suspected case of malaria to prepare blood smear and for testing with the RDT after taking informed consent. The blood smears were read by an experienced technician blinded to the RDT results and clinical status of the subjects. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. RESULTS: The prevalence of malaria infection estimated by RDT in parallel with microscopy provide evidence of the type of high, low or no transmission in the study area. Analysis revealed (pooled data of all four epidemiological settings) that overall sensitivity, specificity and accuracy of the RDT were >90% in areas of different endemicity. While, RDT is useful to confirm the diagnosis of new symptomatic cases of suspected P. falciparum infection, the persistence of parasite antigen leading to false positives even after clearance of asexual parasitaemia has limited its utility as a prognostic tool. CONCLUSION: The study showed that the ParaHIT f test was easy to use, reliable and cheap. Thus this RDT is an appropriate test for the use in the field by paramedical staff when laboratory facilities are not available and thus likely to contribute greatly to an effective control of malaria in resource poor countries

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Managing patients with ICD shocks and programming tachycardia therapies during acute heart failure syndromes

We review the pharmacologic, interventional and device programming treatment options for patients with implantable cardioverter-defibrillators who present with acute heart failure and implantable cardioverter-defibrillator shocks

Genetic dissection of heterosis using epistatic association mapping in a partial NCII mating design

Heterosis refers to the phenomenon in which an F1 hybrid exhibits enhanced growth or agronomic performance. However, previous theoretical studies on heterosis have been based on bi-parental segregating populations instead of F1 hybrids. To understand the genetic basis of heterosis, here we used a subset of F1 hybrids, named a partial North Carolina II design, to perform association mapping for dependent variables: original trait value, general combining ability (GCA), specific combining ability (SCA) and mid-parental heterosis (MPH). Our models jointly fitted all the additive, dominance and epistatic effects. The analyses resulted in several important findings: 1) Main components are additive and additive-by-additive effects for GCA and dominance-related effects for SCA and MPH, and additive-by-dominant effect for MPH was partly identified as additive effect; 2) the ranking of factors affecting heterosis was dominance > dominance-by-dominance > over-dominance > complete dominance; and 3) increasing the proportion of F1 hybrids in the population could significantly increase the power to detect dominance-related effects, and slightly reduce the power to detect additive and additive-by-additive effects. Analyses of cotton and rapeseed datasets showed that more additive-by-additive QTL were detected from GCA than from trait phenotype, and fewer QTL were from MPH than from other dependent variables

A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions

Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes

<p>Abstract</p> <p>Background</p> <p>Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the <it>Uncaria </it>tomentosa, <it>Boswellia spp</it>., <it>Lepidium meyenii and L-Leucine </it>on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants.</p> <p>Methods</p> <p>Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-<it>Leucine </it>mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits.</p> <p>Results</p> <p>HLM tested in these <it>in vitro </it>studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-<it>Leucine </it>mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β.</p> <p>Conclusion</p> <p>Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery.</p