Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX)

<p>Abstract</p> <p>Background</p> <p>The human X chromosome has a biased gene content. One group of genes that is over-represented on the human X are those expressed in the brain, explaining the large number of sex-linked mental retardation (MRX) syndromes.</p> <p>Results</p> <p>To determine if MRX genes were recruited to the X, or whether their brain-specific functions were acquired after relocation to the mammalian X chromosome, we examined the location and expression of their orthologues in marsupials, which diverged from human approximately 180 million years ago. We isolated and mapped nine tammar wallaby MRX homologues, finding that six were located on the tammar wallaby X (which represents the ancient conserved mammal X) and three on chromosome 5, representing the recently added region of the human X chromosome. The location of MRX genes within the same synteny groups in human and wallaby does not support the hypothesis that genes with an important function in the brain were recruited in multiple independent events from autosomes to the mammalian X chromosome. Most of the tammar wallaby MRX homologues were more widely expressed in tammar wallaby than in human. Only one, the tammar wallaby <it>ARX </it>homologue (located on tammar chromosome 5p), has a restricted expression pattern comparable to its pattern in human. The retention of the brain-specific expression of <it>ARX </it>over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function.</p> <p>Conclusion</p> <p>Our results suggest all the genes in this study may have originally had more general functions that became more specialised and important in brain function during evolution of humans and other placental mammals.</p

Predicting risk of dementia with machine learning and survival models using routine primary care records

Worldwide, it is forecasted that 131.5 million people will suffer from dementia by 2050, and the annual cost of care will increase from 818 billion USD in 2016 to 2 trillion USD by 2030, with burgeoning social consequences. Given a timely prediction of a dementia outcome in patients, appropriate mitigating interventions can be applied to reduce risk. However such prediction facilities need to be made available to wider populations, and these facilities cannot rely on specialised, costly and invasive testing (such as neuroimaging, cerebrospinal fluid collection, etc which constitute important instruments used in diagnosis), for interventions to have a meaningful quantitative impact. Hence an emerging need exists for the wider application of prognostic measures which can be deployed using lower cost data sources such as longitudinal records routinely collected by general practices. This paper proposes an efficient prediction modelling approach to the risk of dementia, using CPRD data collected from GP practices in UK, and based on machine learning in particular the Gradient Boosting Machines model combined with a survival model such as the Cox Proportional Hazard, encapsulated in a semi-supervised learning and model calibration methodology

Absolute spin-valve effect with superconducting proximity structures

We investigate spin dependent transport in hybrid superconductor(S)--normal-metal(N)--ferromagnet(F) structures under conditions of proximity effect. We demonstrate the feasibility of the absolute spin-valve effect for a certain interval of voltages in a system consisting of two coupled tri-layer structures. Our results are also valid for non-collinear magnetic configurations of the ferromagnets.Comment: 1 TEX file, 2 Postscript files. Accepted for publication in Physical Review Letter

Inflammation and performance status:the cornerstones of prognosis in advanced cancer

Context: In advanced cancer, although performance status (PS), systemic inflammatory response and nutritional status are known to have prognostic value, geographical variations and sociodemographic indexes may also impact survival. Objectives: This study compares validated prognostic factors in two international cohorts and establishes a prognostic framework for treatment. Methods: Two international biobanks of patients (n=1.518) with advanced cancer were analyzed. Prognostic factors (Eastern Cooperative Oncology Group Performance Status [ECOG-PS], body mass index [BMI] and modified Glasgow Prognostic Score [mGPS]) were assessed. The relationship between these and survival was examined using Kaplan–Meier and Cox regression methods. Results: According to multivariate analysis, in the European cohort the most highly predictive factors were BMI &lt;20 kg/m2 (hazard ratio [HR] 1.644), BMI 20-21.9 kg/m2 (HR 1.347), ECOG-PS (HR 1.597–11.992) and mGPS (HR 1.843–2.365). In the Brazilian cohort, the most highly predictive factors were ECOG-PS (HR 1.678–8.938) and mGPS (HR 2.103–2.837). Considering gastrointestinal cancers in particular (n=551), the survival rate at 3 months in both cohorts together ranged from 93% (mGPS 0, PS 0–1) to 0% (mGPS 2, PS 4), and from 81% (mGPS 0, BMI &gt;28 kg/m2) to 44% (mGPS 2, BMI &lt;20 kg/m2). Conclusion: The established prognostic factors that were compared had similar prognostic capacity in both cohorts. A high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer survival of patients with advanced cancer in the prospective European and Brazilian cohorts

Quantum Collective Creep: a Quasiclassical Langevin Equation Approach

The dynamics of an elastic medium driven through a random medium by a small applied force is investigated in the low-temperature limit where quantum fluctuations dominate. The motion proceeds via tunneling of segments of the manifold through barriers whose size grows with decreasing driving force $f$. In the limit of small drive, at zero-temperature the average velocity has the form $v\propto\exp[-{\rm const.}/\hbar^{\alpha} f^{\mu}]$. For strongly dissipative dynamics, there is a wide range of forces where the dissipation dominates and the velocity--force characteristics takes the form $v\propto\exp[-S(f)/\hbar]$, with $S(f)\propto 1/ f^{(d+2\zeta)/(2-\zeta)}$ the action for a typical tunneling event, the force dependence being determined by the roughness exponent $\zeta$ of the $d$-dimensional manifold. This result agrees with the one obtained via simple scaling considerations. Surprisingly, for asymptotically low forces or for the case when the massive dynamics is dominant, the resulting quantum creep law is {\it not} of the usual form with a rate proportional to $\exp[-S(f)/\hbar]$; rather we find $v\propto \exp\{-[S(f)/\hbar]^2\}$ corresponding to $\alpha=2$ and $\mu= 2(d+2\zeta-1)/(2-\zeta)$, with $\mu/2$ the naive scaling exponent for massive dynamics. Our analysis is based on the quasi-classical Langevin approximation with a noise obeying the quantum fluctuation--dissipation theorem. The many space and time scales involved in the dynamics are treated via a functional renormalization group analysis related to that used previously to treat the classical dynamics of such systems. Various potential difficulties with these approaches to the multi-scale dynamics -- both classical and quantum -- are raised and questions about the validity of the results are discussed.Comment: RevTeX, 30 pages, 8 figures inserte

Geriatric assessment in surgical oncology: A systematic review

The comprehensive geriatric assessment (CGA) has developed as an important prognostic tool to risk stratify older adults and has recently been applied to the surgical field. In this systematic review, we examined the utility of CGA components as predictors of adverse outcomes among geriatric patients undergoing major oncologic surgery

Energy gap in superconducting fullerides: optical and tunneling studies

Tunneling and optical transmission studies have been performed on superconducting samples of Rb3C60. At temperatures much below the superconducting transition temperature Tc the energy gap is 2 Delta=5.2 +- 0.2meV, corresponding to 2 Delta/kB Tc = 4.2. The low temperature density of states, and the temperature dependence of the optical conductivity resembles the BCS behavior, although there is an enhanced ``normal state" contribution. The results indicate that this fulleride material is an s-wave superconductor, but the superconductivity cannot be described in the weak coupling limit.Comment: RevTex file with four .EPS figures. Prints to four pages. Also available at http://buckminster.physics.sunysb.edu/papers/pubrece.htm

The three-dimensional random field Ising magnet: interfaces, scaling, and the nature of states

The nature of the zero temperature ordering transition in the 3D Gaussian random field Ising magnet is studied numerically, aided by scaling analyses. In the ferromagnetic phase the scaling of the roughness of the domain walls, $w\sim L^\zeta$, is consistent with the theoretical prediction $\zeta = 2/3$. As the randomness is increased through the transition, the probability distribution of the interfacial tension of domain walls scales as for a single second order transition. At the critical point, the fractal dimensions of domain walls and the fractal dimension of the outer surface of spin clusters are investigated: there are at least two distinct physically important fractal dimensions. These dimensions are argued to be related to combinations of the energy scaling exponent, $\theta$, which determines the violation of hyperscaling, the correlation length exponent $\nu$, and the magnetization exponent $\beta$. The value $\beta = 0.017\pm 0.005$ is derived from the magnetization: this estimate is supported by the study of the spin cluster size distribution at criticality. The variation of configurations in the interior of a sample with boundary conditions is consistent with the hypothesis that there is a single transition separating the disordered phase with one ground state from the ordered phase with two ground states. The array of results are shown to be consistent with a scaling picture and a geometric description of the influence of boundary conditions on the spins. The details of the algorithm used and its implementation are also described.Comment: 32 pp., 2 columns, 32 figure

Global Estimates of CO Sources with High Resolution by Adjoint Inversion of Multiple Satellite Datasets (MOPITT, AIRS, SCIAMACHY, TES)

We combine CO column measurements from the MOPITT, AIRS, SCIAMACHY, and TES satellite instruments in a full-year (May 2004–April 2005) global inversion of CO sources at 4°×5° spatial resolution and monthly temporal resolution. The inversion uses the GEOS-Chem chemical transport model (CTM) and its adjoint applied to MOPITT, AIRS, and SCIAMACHY. Observations from TES, surface sites (NOAA/GMD), and aircraft (MOZAIC) are used for evaluation of the a posteriori solution. Using GEOS-Chem as a common intercomparison platform shows global consistency between the different satellite datasets and with the in situ data. Differences can be largely explained by different averaging kernels and a priori information. The global CO emission from combustion as constrained in the inversion is $1350 Tg a^{−1}$. This is much higher than current bottom-up emission inventories. A large fraction of the correction results from a seasonal underestimate of CO sources at northern mid-latitudes in winter and suggests a larger-than-expected CO source from vehicle cold starts and residential heating. Implementing this seasonal variation of emissions solves the long-standing problem of models underestimating CO in the northern extratropics in winter-spring. A posteriori emissions also indicate a general underestimation of biomass burning in the GFED2 inventory. However, the tropical biomass burning constraints are not quantitatively consistent across the different datasets.Engineering and Applied Science