New Maximum Likelihood Estimators for Eukaryotic Intron Evolution

The evolution of spliceosomal introns remains poorly understood. Although many approaches have been used to infer intron evolution from the patterns of intron position conservation, the results to date have been contradictory. In this paper, we address the problem using a novel maximum likelihood method, which allows estimation of the frequency of intron insertion target sites, together with the rates of intron gain and loss. We analyzed the pattern of 10,044 introns (7,221 intron positions) in the conserved regions of 684 sets of orthologs from seven eukaryotes. We determined that there is an average of one target site per 11.86 base pairs (bp) (95% confidence interval, 9.27 to 14.39 bp). In addition, our results showed that: (i) overall intron gains are ~25% greater than intron losses, although specific patterns vary with time and lineage; (ii) parallel gains account for ~18.5% of shared intron positions; and (iii) reacquisition following loss accounts for ~0.5% of all intron positions. Our results should assist in resolving the long-standing problem of inferring the evolution of spliceosomal introns

SafeWeb: A Middleware for Securing Ruby-Based Web Applications

Web applications in many domains such as healthcare and finance must process sensitive data, while complying with legal policies regarding the release of different classes of data to different parties. Currently, software bugs may lead to irreversible disclosure of confidential data in multi-tier web applications. An open challenge is how developers can guarantee these web applications only ever release sensitive data to authorised users without costly, recurring security audits. Our solution is to provide a trusted middleware that acts as a “safety net” to event-based enterprise web applications by preventing harmful data disclosure before it happens. We describe the design and implementation of SafeWeb, a Ruby-based middleware that associates data with security labels and transparently tracks their propagation at different granularities across a multi-tier web architecture with storage and complex event processing. For efficiency, maintainability and ease-of-use, SafeWeb exploits the dynamic features of the Ruby programming language to achieve label propagation and data flow enforcement. We evaluate SafeWeb by reporting our experience of implementing a web-based cancer treatment application and deploying it as part of the UK National Health Service (NHS)

Can a frustrated spin-cluster model describe the low-temperature physics of NaV_2O_5 ?

Recent experimental evidence suggest the existence of three distinct V-valence states (V^{+4}, V^{+4.5} and V^{+5}) in the low-temperature phase of NaV_2O_5 in apparent discrepancy with the observed spin-gap. We investigate a novel spin cluster model, consisting of weakly coupled, frustrated four-spin clusters aligned along the crystallographic b-axis that was recently proposed to reconcile these experimental observations. We have studied the phase diagram and the magnon dispersion relation of this model using DMRG, exact diagonalization and a novel cluster-operator theory. We find a spin-gap for all parameter values and two distinct phases, a cluster phase and a Haldane phase. We evaluate the size of the gap and the magnon dispersion and find no parameter regime which would reproduce the experimental results. We conclude that this model is inappropriate for the low-temperature regime of NaV_2O_5

High frequency ESR investigation on dynamical charge disproportionation and spin gap excitation in NaV_2O_5

A significant frequency dependence of the ESR line width is found in NaV_2O_5 between 34-100 K and the line width increases as the resonance frequency is increased from 95 GHz to 760 GHz. The observed frequency dependence is qualitatively explained in terms of the dynamical charge disproportionation. The present results show the essential role of the internal charge degree of freedom in a V-O-V bond. We have also proposed the existence of the Dzyaloshinsky-Moriya interaction in the low temperature charge ordered phase considering the breaking of the selection rule of ESR realized as the direct observation of the spin gap excitation.Comment: 9 figures submitted to J. Phys.Soc. Jp

Raman Scattering in the Inorganic Spin-Peierls System alpha'-Na_{1-delta}V_2O_5

We have studied the spin-Peierls (SP) transition in alpha'-Na_{1-delta}V_2O_5 (delta = 0, 0.01 and 0.1) by means of Raman scattering. At room temperature, we observe six A_1 and three A_2 phonon modes and a broad Raman band. Below T_{SP}several new peaks and a new broad band appear. The new peak at 62 cm^{-1} originates from the SP-gap excitation. The new peak at 128 cm^{-1} and the new broad band between 130 and 400 cm^{-1} come from two magnetic excitations. The new peaks at 102, 646 and 944 cm^{-1} are assigned to the folded phonon modes and their Na^+-ion deficiency dependence shows that the defect of Na^+ ion suppresses the SPtransition. The polarized Raman spectra below T_{SP} suggest that the possible crystal symmetry is C_s^2(Pn) or C_1^1(P1). The asymmetric lineshape of the 531-cm^{-1} peak superimposed on the electronic Raman band from the d-d transition around 600 cm^{-1} is interpreted in terms of the Fano resonance between the electronic continuous band and the phonon with a finite lifetime. The defects of the Na^+ ions reduce the Fano effect because the life time of the phonon and the phonon-continuum interaction are decreased.Comment: 24 pages, 10 Postscript figures,uses jpsj.sty and epsf.sty. in press in J. Phys. Soc. Jp

Spin gap behavior and charge ordering in \alpha^{\prime}-NaV_2O_5 probed by light scattering

We present a detailed analysis of light scattering experiments performed on the quarter-filled spin ladder compound $\alpha^\prime$-NaV$_{2}$O$_{5}$ for the temperature range 5 K$\le$T$\le$300 K. This system undergoes a phase transition into a singlet ground state at T=34 K accompanied by the formation of a super structure. For T$\leq$34 K several new modes were detected. Three of these modes are identified as magnetic bound states. Experimental evidence for charge ordering on the V sites is detected as an anomalous shift and splitting of a V-O vibration at 422 cm$^{-1}$ for temperatures above 34 K. The smooth and crossover-like onset of this ordering at T$_{\rm CO}$= 80 K is accompanied by pretransitional fluctuations both in magnetic and phononic Raman scattering. It resembles the effect of stripe order on the super structure intensities in La$_2$NiO$_{4+\delta}$.Comment: 36 pages, 11 figures, accepted for publication in PRB (sept.99

X-ray Investigation of the Magneto-elastic Instability of alpha'-NaV2O5

We present an X-ray diffuse scattering study of the pretransitional structural fluctuations of the magneto-elastic transition in alpha'-NaV2O5. This transition is characterized by the appearance below Tsp~35K of satellite reflections at the reduced wave vector (1/2,1/2,1/4). A large regime of structural fluctuations is measured up to 90 K. These fluctuations are three dimensional between Tsp and ~50K and quasi-one dimensional above ~60K. At 40 K the anisotropy ratio is found to be (xib :xia :xic)= (3.8 : 1.8 : 1), which reveals the importance of transverse interactions in the stabilization of the low temperature phase. We discuss our results within the framework of recent theories dealing with the simultaneous occurrence of a charge ordering, a spin gap and a lattice distortion in this intriguing compound.Comment: Accepted in PRB Rapid.comm. Corrected typos, references added, figures improve

Mapping targets for small nucleolar RNAs in yeast

Background: Recent analyses implicate changes in the expression of the box C/D class of small nucleolar RNAs (snoRNAs) in several human diseases. Methods: Here we report the identification of potential novel RNA targets for box C/D snoRNAs in budding yeast, using the approach of UV crosslinking and sequencing of hybrids (CLASH) with the snoRNP proteins Nop1, Nop56 and Nop58. We also developed a bioinformatics approach to filter snoRNA-target interactions for bona fide methylation guide interactions. Results: We recovered 241,420 hybrids, out of which 190,597 were classed as reproducible, high energy hybrids. As expected, the majority of snoRNA interactions were with the ribosomal RNAs (rRNAs). Following filtering, 117,047 reproducible hybrids included 51 of the 55 reported rRNA methylation sites. The majority of interactions at methylation sites were predicted to guide methylation. However, competing, potentially regulatory, binding was also identified. In marked contrast, following CLASH performed with the RNA helicase Mtr4 only 7% of snoRNA-rRNA interactions recovered were predicted to guide methylation. We propose that Mtr4 functions in dissociating inappropriate snoRNA-target interactions. Numerous snoRNA-snoRNA interactions were recovered, indicating potential cross regulation. The snoRNAs snR4 and snR45 were recently implicated in site-directed rRNA acetylation, and hybrids were identified adjacent to the acetylation sites. We also identified 1,368 reproducible snoRNA-mRNA interactions, representing 448 sites of interaction involving 39 snoRNAs and 382 mRNAs. Depletion of the snoRNAs U3, U14 or snR4 each altered the levels of numerous mRNAs. Targets identified by CLASH were over-represented among these species, but causality has yet to be established. Conclusions: Systematic mapping of snoRNA-target binding provides a catalogue of high-confidence binding sites and indicates numerous potential regulatory interactions

The prevalence of exposure to domestic violence and the factors associated with co-occurrence of psychological and physical violence exposure: a sample from primary care patients

<p>Abstract</p> <p>Background</p> <p>Since many health problems are associated with abuse and neglect at all ages, domestic violence victims may be considered as a group of primary care patients in need of special attention.</p> <p>Methods</p> <p>The aim of this multi-centre study was to assess the prevalence of domestic violence in primary care patients, and to identify those factors which influence the co-occurrence of psychological and physical violence exposure and their consequences (physical, sexual and reproductive and psychological) as obtained from medical records.</p> <p>A study was carried out in 28 family practices in Slovenia in 2009. Twenty-eight family physicians approached every fifth family practice attendee, regardless of gender, to be interviewed about their exposure to domestic violence and asked to specify the perpetrator and the frequency. Out of 840 patients asked, 829 individuals, 61.0% women (n = 506) and 39.0% men (n = 323) were assessed (98.7% response rate). They represented a randomised sample of general practice attendees, aged 18 years and above, who had visited their physician for health problems and who were given a physical examination. Visits for administrative purposes were excluded.</p> <p>Multivariate binary logistic regression analysis was used to determine the factors associated with exposure to both psychological and physical violence.</p> <p>Results</p> <p>Of 829 patients, 15.3% reported some type of domestic violence experienced during the previous five years; 5.9% reported physical and 9.4% psychological violence; of these 19.2% of men and 80.8% of women had been exposed to psychological violence, while 22.4% of men and 77.6% of women had been exposed to physical violence. The domestic violence victims were mostly women (p < 0.001) aged up to 35 years (p = 0.001). Exposure to psychological violence was more prevalent than exposure to physical violence. Of the women, 20.0% were exposed to either type of violence, compared to 8.0% of male participants, who reported they were rarely exposed to physical violence, while women reported often or constant exposure to physical violence. Their partners were mostly the perpetrators of domestic violence towards women, while amongst men the perpetrators were mostly other family members.</p> <p>In univariate analysis female gender was shown to be a risk factor for domestic violence exposure. Regression modelling, explaining 40% of the variance, extracted two factors associated with psychological and physical violence exposure: the abuse of alcohol in the patient (OR 4.7; 95% CI 1.54-14.45) and their unemployment (OR 13.3; 95% CI 1.53-116.45).</p> <p>Conclusions</p> <p>As far as the study design permits, the identified factors associated with both psychological and physical violence exposure could serve as determinants to raise family physicians' awareness when exploring the prevalence of domestic violence. The results of previous research, showing at least 15% prevalence of exposure to domestic violence among primary care patients in Slovenia, and the female gender as a risk factor, were confirmed.</p

Lattice vibrations of alpha'-NaV2O5

We have measured far infrared reflectance and transmittance spectra as well as Raman scattering spectra of \alpha'-NaV2O5 single crystals for all the principal polarizations. The temperature range above the phase transition temperature T_c=35 K was investigated, mainly. On the basis of this experimental study and of the lattice dynamics calculations we conclude that the symmetry of NaV2O5 in the high temperature phase is described by the centrosymmetric D_{2h}^{13} space group. The assignment of the observed phonons is given. Values of dielectric constants are obtained from the infrared data. Asymmetric shapes of several infrared lines as well as higher order infrared vibrational spectra are discussed. The crystal field energy levels of the 3d electron localized at the V^{4+} site have been calculated in the framework of the exchange charge model using the values of effective charges obtained from the lattice dynamics calculations. According to the results of these calculations, the earlier observed broad optical bands in the region of 1 eV can be interpreted as phonon assisted d-d transitions.Comment: 12 pages, 8 figures, 5 tables; submitted to PR