Copy Number Variation Analysis in Single-Suture Craniosynostosis: Multiple Rare Variants Including RUNX2 Duplication in Two Cousins With Metopic Craniosynostosis

Little is known about genes that underlie isolated single-suture craniosynostosis. In this study, we hypothesize that rare copy number variants (CNV) in patients with isolated single-suture craniosynostosis contain genes important for cranial development. Using whole genome array comparative genomic hybridization (CGH), we evaluated DNA from 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications. We identified a 1.1 Mb duplication encompassing RUNX2 in two affected cousins with metopic synostosis and hypodontia. Given that RUNX2 is required as a master switch for osteoblast differentiation and interacts with TWIST I, mutations in which also cause craniosynostosis, we conclude that the duplication in this family is pathogenic, albeit with reduced penetrance. In addition, we find that a total of 7.5% of individuals with single-suture synostosis in our series have at least one rare deletion or duplication that contains genes and that has not been previously reported in unaffected individuals. The genes within and disrupted by CNVs in this cohort are potential novel candidate genes for craniosynostosis. (C) 2010 Wiley-Liss, Inc

The lower mass function of the young open cluster Blanco 1: from 30 Mjup to 3 Mo

We performed a deep wide field optical survey of the young (~100-150 Myr) open cluster Blanco1 to study its low mass population well down into the brown dwarf regime and estimate its mass function over the whole cluster mass range.The survey covers 2.3 square degrees in the I and z-bands down to I ~ z ~ 24 with the CFH12K camera. Considering two different cluster ages (100 and 150 Myr), we selected cluster member candidates on the basis of their location in the (I,I-z) CMD relative to the isochrones, and estimated the contamination by foreground late-type field dwarfs using statistical arguments, infrared photometry and low-resolution optical spectroscopy. We find that our survey should contain about 57% of the cluster members in the 0.03-0.6 Mo mass range, including 30-40 brown dwarfs. The candidate's radial distribution presents evidence that mass segregation has already occured in the cluster. We took it into account to estimate the cluster mass function across the stellar/substellar boundary. We find that, between 0.03Mo and 0.6Mo, the cluster mass distribution does not depend much on its exact age, and is well represented by a single power-law, with an index alpha=0.69 +/- 0.15. Over the whole mass domain, from 0.03Mo to 3Mo, the mass function is better fitted by a log-normal function with m0=0.36 +/- 0.07Mo and sigma=0.58 +/- 0.06. Comparison between the Blanco1 mass function, other young open clusters' MF, and the galactic disc MF suggests that the IMF, from the substellar domain to the higher mass part, does not depend much on initial conditions. We discuss the implications of this result on theories developed to date to explain the origin of the mass distribution.Comment: 18 pages, 15 figures and 5 tables accepted in A&

A graphical vector autoregressive modelling approach to the analysis of electronic diary data

<p>Abstract</p> <p>Background</p> <p>In recent years, electronic diaries are increasingly used in medical research and practice to investigate patients' processes and fluctuations in symptoms over time. To model dynamic dependence structures and feedback mechanisms between symptom-relevant variables, a multivariate time series method has to be applied.</p> <p>Methods</p> <p>We propose to analyse the temporal interrelationships among the variables by a structural modelling approach based on graphical vector autoregressive (VAR) models. We give a comprehensive description of the underlying concepts and explain how the dependence structure can be recovered from electronic diary data by a search over suitable constrained (graphical) VAR models.</p> <p>Results</p> <p>The graphical VAR approach is applied to the electronic diary data of 35 obese patients with and without binge eating disorder (BED). The dynamic relationships for the two subgroups between eating behaviour, depression, anxiety and eating control are visualized in two path diagrams. Results show that the two subgroups of obese patients with and without BED are distinguishable by the temporal patterns which influence their respective eating behaviours.</p> <p>Conclusion</p> <p>The use of the graphical VAR approach for the analysis of electronic diary data leads to a deeper insight into patient's dynamics and dependence structures. An increasing use of this modelling approach could lead to a better understanding of complex psychological and physiological mechanisms in different areas of medical care and research.</p

Entangled-State Cycles of Atomic Collective-Spin States

We study quantum trajectories of collective atomic spin states of $N$ effective two-level atoms driven with laser and cavity fields. We show that interesting ``entangled-state cycles'' arise probabilistically when the (Raman) transition rates between the two atomic levels are set equal. For odd (even) $N$, there are $(N+1)/2$ ($N/2$) possible cycles. During each cycle the $N$-qubit state switches, with each cavity photon emission, between the states $(|N/2,m>\pm |N/2,-m>)/\sqrt{2}$, where $|N/2,m>$ is a Dicke state in a rotated collective basis. The quantum number $m$ ($>0$), which distinguishes the particular cycle, is determined by the photon counting record and varies randomly from one trajectory to the next. For even $N$ it is also possible, under the same conditions, to prepare probabilistically (but in steady state) the Dicke state $|N/2,0>$, i.e., an $N$-qubit state with $N/2$ excitations, which is of particular interest in the context of multipartite entanglement.Comment: 10 pages, 9 figure

High Energy Neutrinos from Quasars

We review and clarify the assumptions of our basic model for neutrino production in the cores of quasars, as well as those modifications to the model subsequently made by other workers. We also present a revised estimate of the neutrino background flux and spectrum obtained using more recent empirical studies of quasars and their evolution. We compare our results with other thoeretical calculations and experimental upper limits on the AGN neutrino background flux. We also estimate possible neutrino fluxes from the jets of blazars detected recently by the EGRET experiment on the Compton Gamma Ray Observatory. We discuss the theoretical implications of these estimates.Comment: 14 pg., ps file (includes figures), To be published in Space Science Review

Decaying into the Hidden Sector

The existence of light hidden sectors is an exciting possibility that may be tested in the near future. If DM is allowed to decay into such a hidden sector through GUT suppressed operators, it can accommodate the recent cosmic ray observations without over-producing antiprotons or interfering with the attractive features of the thermal WIMP. Models of this kind are simple to construct, generic and evade all astrophysical bounds. We provide tools for constructing such models and present several distinct examples. The light hidden spectrum and DM couplings can be probed in the near future, by measuring astrophysical photon and neutrino fluxes. These indirect signatures are complimentary to the direct production signals, such as lepton jets, predicted by these models.Comment: 40 pages, 5 figure

Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry

Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124

Electrical tuning of elastic wave propagation in nanomechanical lattices at MHz frequencies

Nanoelectromechanical systems (NEMS) that operate in the megahertz (MHz) regime allow energy transducibility between different physical domains. For example, they convert optical or electrical signals into mechanical motions and vice versa. This coupling of different physical quantities leads to frequency-tunable NEMS resonators via electromechanical non-linearities. NEMS platforms with single- or low-degrees of freedom have been employed to demonstrate quantum-like effects, such as mode cooling, mechanically induced transparency, Rabi oscillation, two-mode squeezing and phonon lasing. Periodic arrays of NEMS resonators with architected unit cells enable fundamental studies of lattice-based solid-state phenomena, such as bandgaps, energy transport, non-linear dynamics and localization, and topological properties, directly transferrable to on-chip devices. Here we describe one-dimensional, non-linear, nanoelectromechanical lattices (NEML) with active control of the frequency band dispersion in the radio-frequency domain (10–30 MHz). The design of our systems is inspired by NEMS-based phonon waveguides and includes the voltage-induced frequency tuning of the individual resonators. Our NEMLs consist of a periodic arrangement of mechanically coupled, free-standing nanomembranes with circular clamped boundaries. This design forms a flexural phononic crystal with a well-defined bandgap, 1.8 MHz wide. The application of a d.c. gate voltage creates voltage-dependent on-site potentials, which can significantly shift the frequency bands of the device. Additionally, a dynamic modulation of the voltage triggers non-linear effects, which induce the formation of a phononic bandgap in the acoustic branch, analogous to Peierls transition in condensed matter. The gating approach employed here makes the devices more compact than recently proposed systems, whose tunability mostly relies on materials’ compliance and mechanical non-linearities

Selection upon Genome Architecture: Conservation of Functional Neighborhoods with Changing Genes

An increasing number of evidences show that genes are not distributed randomly across eukaryotic chromosomes, but rather in functional neighborhoods. Nevertheless, the driving force that originated and maintains such neighborhoods is still a matter of controversy. We present the first detailed multispecies cartography of genome regions enriched in genes with related functions and study the evolutionary implications of such clustering. Our results indicate that the chromosomes of higher eukaryotic genomes contain up to 12% of genes arranged in functional neighborhoods, with a high level of gene co-expression, which are consistently distributed in phylogenies. Unexpectedly, neighborhoods with homologous functions are formed by different (non-orthologous) genes in different species. Actually, instead of being conserved, functional neighborhoods present a higher degree of synteny breaks than the genome average. This scenario is compatible with the existence of selective pressures optimizing the coordinated transcription of blocks of functionally related genes. If these neighborhoods were broken by chromosomal rearrangements, selection would favor further rearrangements reconstructing other neighborhoods of similar function. The picture arising from this study is a dynamic genomic landscape with a high level of functional organization