The gravitational path integral and trace of the diffeomorphisms

I give a resolution of the conformal mode divergence in the Euclidean gravitational path-integral by isolating the trace of the diffeomorphisms and its contribution to the Faddeev-Popov measure.Comment: 20 pgs

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties

Patterns and consequences of invasion of tropical montane forests by Cestrum aurantiacum Lindl. in the Western Ghats

In the montane forest-grassland mosaics of the Western Ghats, land cover conversion to silviculture and agriculture over the last five decades has resulted in both loss of natural habitats and widespread invasion of remnant habitat patches. While invasion of the grassland habitats of the mosaic has been relatively well studied, there have been few attempts to understand the extent to which forest habitats (locally known as sholas) have been affected by the spread of exotic species. Here we examine the patterns and impacts of invasion of shola forest understoreys by Cestrum aurantiacum Lindl., an exotic shrub species. At the landscape scale, we demonstrate that the presence and abundance of this invasive in shola understories is negatively related to distance from tea plantations. Further, the intensity of invasion is higher in areas with greater seasonality of temperature and lower mean annual precipitation. At the patch scale, invasion is greatest at shola edges and away from stream courses. We find that C. aurantiacum abundance has negatively affected the regeneration of native shola tree species as well as the abundance of native shola understorey shrubs. Fifty three percent of invaded plots had no native shrubs present. In plots where both C. aurantiacum and native shrubs were present in large enough numbers, we found evidence of negative spatial dependence between stem locations of C. aurantiacum and native shrubs. Our findings have important implications for the management and conservation of these mosaics

Semiclassical quantisation of space-times with apparent horizons

Coherent or semiclassical states in canonical quantum gravity describe the classical Schwarzschild space-time. By tracing over the coherent state wavefunction inside the horizon, a density matrix is derived. Bekenstein-Hawking entropy is obtained from the density matrix, modulo the Immirzi parameter. The expectation value of the area and curvature operator is evaluated in these states. The behaviour near the singularity of the curvature operator shows that the singularity is resolved. We then generalise the results to space-times with spherically symmetric apparent horizons.Comment: 52 pages, 4 figure

Analogues of Disulfides from Allium stipitatum demonstrate potent anti-tubercular activities through drug efflux pump and Biofilm inhibition

Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB)

Quantum Minimal Length and Transplanckian Photons

In this paper we first give arguments supporting the idea that a B.T.Z black hole can face a transplankian problem even when its mass is small. K.M.M quantum theory is applied to the Hawking evaporation of the Schwarzchild and B.T.Z black holes. Working in the physically safe quasi position representation, we argue that the oscillating term present in a previous analysis is removed so that actually one doesn't need an average procedure. We expand the s wave function as the exponential of a series in the minimal length of the new quantum theory. This reduces an infinite order differential equation to a numerable set of finite order ones. We obtain the striking result that the infinity of arbitrary constants induced by the order of the wave equation has no physical meaning due to normalization. We finally construct gaussian wave pacqets and study their trajectories. We suggest a quantitative description of the non locality zone and its dependance on the K.M.M energy scale. Potential incidences on unitarity are briefly evoqued.Comment: 25 pages, 7 figure

Coherent States for Black Holes

We determine coherent states peaked at classical space-time of the Schwarzschild black hole in the frame-work of canonical quantisation of general relativity. The information about the horizon is naturally encoded in the phase space variables, and the perturbative quantum fluctuations around the classical geometry depend on the distance from the horizon. For small black holes, space near the vicinity of the singularity appears discrete with the singular point excluded from the spectrum.Comment: 48 pages, 18+1 figures, some modifications, references adde

RDH12 retinopathy: novel mutations and phenotypic description

PurposeTo identify patients with autosomal recessive retinal dystrophy caused by mutations in the gene, retinal dehydrogenase 12 (RDH12), and to report the associated phenotype.MethodsAfter giving informed consent, all patients underwent full clinical evaluation. Patients were selected for mutation analysis based upon positive results from the Asper Ophthalmics Leber congenital amaurosis arrayed primer extansion (APEX) microarray screening, linkage analysis, or their clinical phenotype. All coding exons of RDH12 were screened by direct Sanger sequencing. Potential variants were checked for segregation in the respective families and screened in controls, and their pathogenicity analyzed using in silico prediction programs.ResultsScreening of 389 probands by the APEX microarray and/or direct sequencing identified bi-allelic mutations in 29 families. Seventeen novel mutations were identified. The phenotype in these patients presented with a severe early-onset rod-cone dystrophy. Funduscopy showed severe generalized retinal pigment epithelial and retinal atrophy, which progressed to dense, widespread intraretinal pigment migration by adulthood. The macula showed severe atrophy, with pigmentation and yellowing, and corresponding loss of fundus autofluorescence. Optical coherence tomography revealed marked retinal thinning and excavation at the macula.ConclusionsRDH12 mutations account for approximately 7% of disease in our cohort of patients diagnosed with Leber congenital amaurosis and early-onset retinal dystrophy. The clinical features of this disorder are highly characteristic and facilitate candidate gene screening. The term RDH12 retinopathy is proposed as a more accurate description

Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens