Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1

We report several receptor tyrosine kinase (RTK) ligands increase RhoA-guanosine triphosphate (GTP) in untransformed and transformed cell lines and determine this phenomenon depends on the RTKs activating the AKT serine/threonine kinase. The increased RhoA-GTP results from AKT phosphorylating three serines (S298, S329, and S567) in the DLC1 tumor suppressor, a Rho GTPase-activating protein (RhoGAP) associated with focal adhesions. Phosphorylation of the serines, located N-terminal to the DLC1 RhoGAP domain, induces strong binding of that N-terminal region to the RhoGAP domain, converting DLC1 from an open, active dimer to a closed, inactive monomer. That binding, which interferes with the interaction of RhoA-GTP with the RhoGAP domain, reduces the hydrolysis of RhoA-GTP, the binding of other DLC1 ligands, and the colocalization of DLC1 with focal adhesions and attenuates tumor suppressor activity. DLC1 is a critical AKT target in DLC1-positive cancer because AKT inhibition has potent antitumor activity in the DLC1-positive transgenic cancer model and in a DLC1-positive cancer cell line but not in an isogenic DLC1-negative cell line

Astrophysical constraints on primordial black holes in Brans-Dicke theory

We consider cosmological evolution in Brans-Dicke theory with a population of primordial black holes. Hawking radiation from the primordial black holes impacts various astrophysical processes during the evolution of the Universe. The accretion of radiation by the black holes in the radiation dominated era may be effective in imparting them a longer lifetime. We present a detailed study of how this affects various standard astrophysical constraints coming from the evaporation of primordial black holes. We analyze constraints from the present density of the Universe, the present photon spectrum, the distortion of the cosmic microwave background spectrum and also from processes affecting light element abundances after nucleosynthesis. We find that the constraints on the initial primordial black hole mass fractions are tightened with increased accretion efficiency.Comment: 15 page

Why do naked singularities form in gravitational collapse?

We investigate what are the key physical features that cause the development of a naked singularity, rather than a black hole, as the end-state of spherical gravitational collapse. We show that sufficiently strong shearing effects near the singularity delay the formation of the apparent horizon. This exposes the singularity to an external observer, in contrast to a black hole, which is hidden behind an event horizon due to the early formation of an apparent horizon.Comment: revised for clarity, new figure included; version accepted by Phys. Rev. D (RC

Running Spectral Index and Formation of Primordial Black Hole in Single Field Inflation Models

A broad range of single field models of inflation are analyzed in light of all relevant recent cosmological data, checking whether they can lead to the formation of long-lived Primordial Black Holes (PBHs). To that end we calculate the spectral index of the power spectrum of primordial perturbations as well as its first and second derivatives. PBH formation is possible only if the spectral index increases significantly at small scales, i.e. large wave number $k$. Since current data indicate that the first derivative $\alpha_S$ of the spectral index $n_S(k_0)$ is negative at the pivot scale $k_0$, PBH formation is only possible in the presence of a sizable and positive second derivative ("running of the running") $\beta_S$. Among the three small-field and five large-field models we analyze, only one small-field model, the "running mass" model, allows PBH formation, for a narrow range of parameters. We also note that none of the models we analyze can accord for a large and negative value of $\alpha_S$, which is weakly preferred by current data.Comment: 26 pages, 5 figures, Refs. added, Minor textual change; version to appear in JCA

Brans-Dicke Theory and primordial black holes in Early Matter-Dominated Era

We show that primordial black holes can be formed in the matter-dominated era with gravity described by the Brans-Dicke theory. Considering an early matter-dominated era between inflation and reheating, we found that the primordial black holes formed during that era evaporate at a quicker than those of early radiation-dominated era. Thus, in comparison with latter case, less number of primordial black holes could exist today. Again the constraints on primordial black hole formation tend towards the larger value than their radiation-dominated era counterparts indicating a significant enhancement in the formation of primordial black holes during the matter-dominaed era.Comment: 9 page

Current-induced highly dissipative domains in high Tc thin films

We have investigated the resistive response of high Tc thin films submitted to a high density of current. For this purpose, current pulses were applied into bridges made of Nd(1.15)Ba(1.85)Cu3O7 and Bi2Sr2CaCu2O8. By recording the time dependent voltage, we observe that at a certain critical current j*, a highly dissipative domain develops somewhere along the bridge. The successive formation of these domains produces stepped I-V characteristics. We present evidences that these domains are not regions with a temperature above Tc, as for hot spots. In fact this phenomenon appears to be analog to the nucleation of phase-slip centers observed in conventional superconductors near Tc, but here in contrast they appear in a wide temperature range. Under some conditions, these domains will propagate and destroy the superconductivity within the whole sample. We have measured the temperature dependence of j* and found a similar behavior in the two investigated compounds. This temperature dependence is just the one expected for the depairing current, but the amplitude is about 100 times smaller.Comment: 9 pages, 9 figures, Revtex, to appear in Phys. Rev.

Characterization of the GlnK protein of Escherichia coli

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75120/1/j.1365-2958.1999.01349.x.pd

Generalized pricing formulas for stochastic volatility jump diffusion models applied to the exponential Vasicek model

Path integral techniques for the pricing of financial options are mostly based on models that can be recast in terms of a Fokker-Planck differential equation and that, consequently, neglect jumps and only describe drift and diffusion. We present a method to adapt formulas for both the path-integral propagators and the option prices themselves, so that jump processes are taken into account in conjunction with the usual drift and diffusion terms. In particular, we focus on stochastic volatility models, such as the exponential Vasicek model, and extend the pricing formulas and propagator of this model to incorporate jump diffusion with a given jump size distribution. This model is of importance to include non-Gaussian fluctuations beyond the Black-Scholes model, and moreover yields a lognormal distribution of the volatilities, in agreement with results from superstatistical analysis. The results obtained in the present formalism are checked with Monte Carlo simulations.Comment: 9 pages, 2 figures, 1 tabl

A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data

Background: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people. Methods: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014. Participants were followed up with annual face-to-face visits, biennial assessments of cognitive function, and biannual visits for physical function until death or June 12, 2017, whichever occurred first. We used multistate models to examine transitions from a healthy state to first intermediate disease events (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and, ultimately, to death. We also examined the effects of age and sex on transition rates using Cox proportional hazards regression models. Findings: 19 114 participants with a median age of 74·0 years (IQR 71·6–77·7) were included in our analyses. During a median follow-up of 4·7 years (IQR 3·6–5·7), 1933 (10·1%) of 19 114 participants had an incident cancer event, 487 (2·5%) had an incident cardiac event, 398 (2·1%) had an incident stroke event, 924 (4·8%) developed persistent physical disability or dementia, and 1052 (5·5%) died. 15 398 (80·6%) individuals did not have any of these events during follow-up. The highest proportion of deaths followed incident cancer (501 [47·6%] of 1052) and 129 (12·3%) participants transitioned from disability or dementia to death. Among 12 postulated transitions, transitions from the intermediate states to death had much higher rates than transitions from a healthy state to death. The progression rates to death were 158 events per 1000 person-years (95% CI 144–172) from cancer, 112 events per 1000 person-years (86–145) from stroke, 88 events per 1000 person-years (68–111) from cardiac disease, 69 events per 1000 person-years (58–82) from disability or dementia, and four events per 1000 person-years (4–5) from a healthy state. Age was significantly associated with an accelerated rate for most transitions. Male sex (vs female sex) was significantly associated with an accelerate rate for five of 12 transitions. Interpretation: We describe a multistate model in a healthy older population in whom the most common transition was from a healthy state to cancer. Our findings provide unique insights into the frequency of events, their transition rates, and the impact of age and sex. These results have implications for preventive health interventions and planning for appropriate levels of residential care in healthy ageing populations. Funding: The National Institutes of Health

Primary accumulation in the Soviet transition

The Soviet background to the idea of primary socialist accumulation is presented. The mobilisation of labour power and of products into public sector investment from outside are shown to have been the two original forms of the concept. In Soviet primary accumulation the mobilisation of labour power was apparently more decisive than the mobilisation of products. The primary accumulation process had both intended and unintended results. Intended results included bringing most of the economy into the public sector, and industrialisation of the economy as a whole. Unintended results included substantial economic losses, and the proliferation of coercive institutions damaging to attainment of the ultimate goal - the building of a communist society