Miracle-dz/UniFAR-FTUs huggingface dataset:
Three Distinct Modes of Mec1/ATR and Tel1/ATM Activation Illustrate Differential Checkpoint Targeting during Budding Yeast Early Meiosis

ABSTRACT Recombination and synapsis of homologous chromosomes are hallmarks of meiosis in many organisms. Meiotic recombination is initiated by Spo11-induced DNA double-strand breaks (DSBs), whereas chromosome synapsis is mediated by a tripartite structure named the synaptonemal complex (SC). Previously, we proposed that budding yeast SC is assembled via noncovalent interactions between the axial SC protein Red1, SUMO chains or conjugates, and the central SC protein Zip1. Incomplete synapsis and unrepaired DNA are monitored by Mec1/Tel1-dependent checkpoint responses that prevent exit from the pachytene stage. Here, our results distinguished three distinct modes of Mec1/Tec1 activation during early meiosis that led to phosphorylation of three targets, histone H2A at S129 (γH2A), Hop1, and Zip1, which are involved, respectively, in DNA replication, the interhomolog recombination and chromosome synapsis checkpoint, and destabilization of homology-independent centromere pairing. γH2A phosphorylation is Red1 independent and occurs prior to Spo11-induced DSBs. DSB- and Red1-dependent Hop1 phosphorylation is activated via interaction of the Red1-SUMO chain/conjugate ensemble with the Ddc1-Rad17-Mec3 (9-1-1) checkpoint complex and the Mre11-Rad50-Xrs2 complex. During SC assembly, Zip1 outcompetes 9-1-1 from the Red1-SUMO chain ensemble to attenuate Hop1 phosphorylation. In contrast, chromosome synapsis cannot attenuate DSB-dependent and Red1-independent Zip1 phosphorylation. These results reveal how DNA replication, DSB repair, and chromosome synapsis are differentially monitored by the meiotic checkpoint network.
Detection of Oropouche virus segment S in patients and inCulex quinquefasciatus in the state of Mato Grosso, Brazil

This study aimed to investigate the circulation of Orthobunyavirus species in the state of Mato Grosso (MT) Brazil. During a dengue outbreak in 2011/2012, 529 serum samples were collected from patients with acute febrile illness with symptoms for up to five days and 387 pools of female Culex quinquefasciatus captured in 2013 were subjected to nested-reverse transcription-polymerase chain reaction for segment S of the Simbu serogroup followed by nucleotide sequencing and virus isolation in Vero cells. Patients (5/529; 0.9%) from Cuiabá (n = 3), Várzea Grande (n = 1) and Nova Mutum (n = 1) municipalities were positive for the S segment of Oropouche virus (OROV). Additionally, eight/387 Cx. quinquefasciatus pools were positive for the segment, with a minimum infection rate of 2.3. Phylogenetic analysis indicated that all the samples belong to the subgenotype Ia, presenting high homology with OROV strains obtained from humans and animals in the Brazilian Amazon. The present paper reports the first detection of an Orthobunyavirus, possibly OROV, in patients and in Cx. quinquefasciatus mosquitoes in MT. This finding reinforces the notion that arboviruses frequently reported in the Amazon Region circulate sporadically in MT during dengue outbreaks.
The levelling off of the obesity epidemic since the year 1999 – a review of evidence and perspectives

The purpose was to investigate a possible levelling off in the obesity epidemic, by systematically reviewing literature and web‐based sources. Eligible studies and data sources were required to have at least two measures of obesity prevalence since 1999. A literature and Internet search resulted in 52 studies from 25 different countries. The findings supported an overall levelling off of the epidemic in children and adolescents from Australia, Europe, Japan and the USA. In adults, stability was found in the USA, while increases were still observed in some European and Asian countries. Some evidence for heterogeneity in the obesity trends across socioeconomic status (SES) groups was found. The levelling off was less evident in the lower‐SES groups. No obvious differences between genders were identified. We discussed potential explanations for a levelling off and the utility of investigating obesity trends to identify the driving forces behind the epidemic. It is important to emphasize that the levelling off is not tantamount to calling off the epidemic. Additionally, it is worthwhile to keep in mind that previous stable phases have been followed by further increases in the prevalence of obesity. Therefore, research into the causes, prevention and treatment of obesity should remain a priority.
Use of an In Vivo FTA Assay to Assess the Magnitude, Functional Avidity and Epitope Variant Cross-Reactivity of T Cell Responses Following HIV-1 Recombinant Poxvirus Vaccination

Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.
Combined Handwriting and Speech Modalities for User Authentication

In this paper, we report on the development of an efficient user authentication system based on a combined acquisition of online pen and speech signals. The novelty of our approach is in the simultaneous recording of these two modalities, simply asking the user to utter what she/he is writing. The main benefit of this multimodal approach is a better accuracy at no extra costs in terms of access time or inconvenience. Another benefit comes from an increased difficulty for forgers willing to perform imitation attacks as two signals need to be reproduced. We are comparing here two potential scenarios of use. The first one is called spoken signatures where the user signs and says the content of the signature. The second scenario is based on spoken handwriting where the user is prompted to write and read the content of sentences randomly extracted from a text. Data according to these two scenarios have been recorded from a set of 70 users. In the first part of this paper, we describe the acquisition procedure, and we comment on the viability and usability of such simultaneous recordings. Our conclusions are supported by a short survey performed with the users. In the second part, we present the authentication systems that we have developed for both scenarios. More specifically, our strategy was to model independently both streams of data and to perform a fusion at the score level. Starting from a state-of-the-art-modeling algorithm based on Gaussian Mixture Models trained with an Expectation-Maximization procedure, we report on several significant improvements that are brought. As a general observation, the use of both modalities outperforms significantly the modalities used alone.
The Photon-Assisted Cascaded Electron Multiplier: a concept for potential avalanche-ion blocking

We present a Photon-Assisted Cascaded Electron Multipliers (PACEM) which has a potential for ion back-flow blocking in gaseous radiation detectors: the avalanche from a first multiplication stage propagates to the successive one via its photons, which in turn induce photoelectron emission from a photocathode deposited on the second multiplier stage; the multiplication process may further continue via electron-avalanche propagation. The photonmediated stage allows, by a proper choice of geometry and fields, complete blocking of the ion back-flow into the first element; thus, only ions from the latter will flow back to the drift region. The PACEM concept was validated in a double-MHSP (Micro-Hole & Strip Plate) cascaded multiplier operated in xenon, where the intermediate scintillation stage provided optical gain of ∼60. The double-MHSP detector had a total gain above 104 and energy resolution of 18% FWHM for 5.9 keV x-rays.
Should one use electrocardiographic or Finapres-derived pulse intervals for calculation of cardiac baroreceptor sensitivity?

BACKGROUND: Cardiac baroreceptor sensitivity (BRS) can now be calculated non-invasively with the advent of new beat-to-beat blood pressure monitors and simulatneous surface electrocardiographic recording. However, it is not known whether BRS values calculated using a pulse interval obtained from the pulse wave are different from those using the electrocardiographic trace. This is important with the advent of new portable monitors (e.g. Portapres), which do not record a simultaneous electrocardiographic trace. OBJECTIVE: To determine whether pulse interval derivations from pulse wave data and electrocardiographic data are comparable.METHODS: Twenty healthy volunteers (10 men) aged 48 +/- 17 years with mean blood pressure 134 +/- 13/77 +/- 7 mmHg were examined. Supine beat-to-beat arterial blood pressure (measured using a Finapres 2300 device from Ohmeda) and surface electrocardiographic readings were recorded and spectral analysis, using fast Fourier transformation (FFT), and sequence analysis used to calculate BRS. Pulse interval was marked using both electrocardiographic and blood pressure traces and we compared the resulting variability of pulse interval and BRS values obtained using the two methodologies. RESULTS: There was good agreement between the two methods for pulse interval power in the low-frequency bandwidth and for BRS sequence analysis, especially for 'down' sequences, (limits of agreement -26.3 to 77.1 ms2 and -1.6 to 2.7 ms/mmHg, respectively). However, in the high frequency bandwidth (0.15-0.35 Hz) and for the combined BRS, the agreement was less good (-69 to 153.8 ms2 and -0.3 to 1.5 ms/mmHg). Overall differences between methods were smaller for BRS calculated in the low frequency rather than high-frequency band, but only in the low-frequency band was the difference positively correlated to mean BRS values. CONCLUSION: Cardiac BRS values calculated using pulse intervals derived from the pulse wave are different from those on the surface electrocardiographic trace, the greatest differences occurring in BRS derived from the high-frequency bandwidth. However, these differences are small, especially in the low-frequency band at lower mean BRS values, and should not discourage use of these newer methods of BRS measurement that do not involve an electrocardiographic recording.
Gratitude that changes attitude: Positive organisational behaviour as responses to servant leadership

Servant leadership (SL) is an emerging model of leadership that goes beyond the popular construct of transformational leadership. Building on Fredrickson’s (2001) broaden and-build theory of emotion, we propose a cyclical model of positive affect where followers’ gratitude in response to SL will not only result in followers’ adaptive behaviors but will perpetuate SL behaviors. Followers’ experiences and reactions will in turn mediate the relationship between SL and organizational citizenship behaviors. In addition, we argue that followers’ reactions in the context of SL will be partly dependent on followers’ self-esteem and self-concept. In this manner, followers’ self-concept will moderate their affective experiences and reactions to SL.
To Be or Not To Be a Poly(3-Hydroxybutyrate) (PHB) Depolymerase: PhaZd1 (PhaZ6) and PhaZd2 (PhaZ7) of Ralstonia eutropha, Highly Active PHB Depolymerases with No Detectable Role in Mobilization of Accumulated PHB

ABSTRACT The putative physiological functions of two related intracellular poly(3-hydroxybutyrate) (PHB) depolymerases, PhaZd1 and PhaZd2, of Ralstonia eutropha H16 were investigated. Purified PhaZd1 and PhaZd2 were active with native PHB granules in vitro. Partial removal of the proteinaceous surface layer of native PHB granules by trypsin treatment or the use of PHB granules isolated from ΔphaP1 or ΔphaP1-phaP5 mutant strains resulted in increased specific PHB depolymerase activity, especially for PhaZd2. Constitutive expression of PhaZd1 or PhaZd2 reduced or even prevented the accumulation of PHB under PHB-permissive conditions in vivo. Expression of translational fusions of enhanced yellow fluorescent protein (EYFP) with PhaZd1 and PhaZd2 in which the active-site serines (S190 and Ser193) were replaced with alanine resulted in the colocalization of only PhaZd1 fusions with PHB granules. C-terminal fusions of inactive PhaZd2(S193A) with EYFP revealed the presence of spindle-like structures, and no colocalization with PHB granules was observed. Chromosomal deletion of phaZd1, phaZd2, or both depolymerase genes had no significant effect on PHB accumulation and mobilization during growth in nutrient broth (NB) or NB-gluconate medium. Moreover, neither proteome analysis of purified native PHB granules nor lacZ fusion studies gave any indication that PhaZd1 or PhaZd2 was detectably present in the PHB granule fraction or expressed at all during growth on NB-gluconate medium. In conclusion, PhaZd1 and PhaZd2 are two PHB depolymerases with a high capacity to degrade PHB when artificially expressed but are apparently not involved in PHB mobilization in the wild type. The true in vivo functions of PhaZd1 and PhaZd2 remain obscure.
Evaluating Characteristics of De Novo Assembly Software on 454 Transcriptome Data: A Simulation Approach

Background The quantity of transcriptome data is rapidly increasing for non-model organisms. As sequencing technology advances, focus shifts towards solving bioinformatic challenges, of which sequence read assembly is the first task. Recent studies have compared the performance of different software to establish a best practice for transcriptome assembly. Here, we adapted a simulation approach to evaluate specific features of assembly programs on 454 data. The novelty of our study is that the simulation allows us to calculate a model assembly as reference point for comparison. Findings The simulation approach allows us to compare basic metrics of assemblies computed by different software applications (CAP3, MIRA, Newbler, and Oases) to a known optimal solution. We found MIRA and CAP3 are conservative in merging reads. This resulted in comparably high number of short contigs. In contrast, Newbler more readily merged reads into longer contigs, while Oases produced the overall shortest assembly. Due to the simulation approach, reads could be traced back to their correct placement within the transcriptome. Together with mapping reads onto the assembled contigs, we were able to evaluate ambiguity in the assemblies. This analysis further supported the conservative nature of MIRA and CAP3, which resulted in low proportions of chimeric contigs, but high redundancy. Newbler produced less redundancy, but the proportion of chimeric contigs was higher. Conclusion Our evaluation of four assemblers suggested that MIRA and Newbler slightly outperformed the other programs, while showing contrasting characteristics. Oases did not perform very well on the 454 reads. Our evaluation indicated that the software was either conservative (MIRA) or liberal (Newbler) about merging reads into contigs. This suggested that in choosing an assembly program researchers should carefully consider their follow up analysis and consequences of the chosen approach to gain an assembly.
Semidefinite Relaxation-Based Optimization of Multiple-Input Wireless Power Transfer Systems

An optimization procedure for multitransmitter multiple-input single-output (MISO) wireless power transfer (WPT) systems based on tight semidefinite relaxation (SDR) is presented. This method ensures physical realizability of MISO WPT systems designed via convex optimization—a robust, semianalytical, and intuitive route to optimizing such systems. To that end, the nonconvex constraints requiring that power is fed into rather than drawn from the system via all transmitter ports are incorporated in a convex SDR, which is efficiently and reliably solvable by dedicated algorithms. A test of the solution then confirms that this modified problem is equivalent (tight relaxation) to the original (nonconvex) one and that the true global optimum has been found. This is a clear advantage over global optimization methods (e.g., genetic algorithms), where convergence to the true global optimum cannot be ensured or tested. Discussions of numerical results yielded by both the closed-form expressions and the refined technique illustrate the importance and practicability of the new method. It is shown that this technique offers a rigorous optimization framework for a broad range of current and emerging WPT applications.
The Circadian System Is a Target and Modulator of Prenatal Cocaine Effects

Background Prenatal exposure to cocaine can be deleterious to embryonic brain development, but the results in humans remain controversial, the mechanisms involved are not well understood and effective therapies are yet to be designed. We hypothesize that some of the prenatal effects of cocaine might be related to dysregulation of physiological rhythms due to alterations in the integrating circadian clock function. Methodology and Principle Findings Here we introduce a new high-throughput genetically well-characterized diurnal vertebrate model for studying the mechanisms of prenatal cocaine effects by demonstrating reduced viability and alterations in the pattern of neuronal development following repeated cocaine exposure in zebrafish embryos. This effect is associated with acute cocaine-induced changes in the expression of genes affecting growth (growth hormone, zGH) and neurotransmission (dopamine transporter, zDAT). Analysis of circadian gene expression, using quantitative real-time RT-PCR (QPCR), demonstrates that cocaine acutely and dose-dependently changes the expression of the circadian genes (zPer-3, zBmal-1) and genes encoding melatonin receptors (zMelR) that mediate the circadian message to the entire organism. Moreover, the effects of prenatal cocaine depend on the time of treatment, being more robust during the day, independent of whether the embryos are raised under the light-dark cycle or in constant light. The latter suggests involvement of the inherited circadian factors. The principal circadian hormone, melatonin, counteracts the effects of cocaine on neuronal development and gene expression, acting via specific melatonin receptors. Conclusions/Significance These findings demonstrate that, in a diurnal vertebrate, prenatal cocaine can acutely dysregulate the expression of circadian genes and those affecting melatonin signaling, growth and neurotransmission, while repeated cocaine exposure can alter neuronal development. Daily variation in these effects of cocaine and their attenuation by melatonin suggest a potential prophylactic or therapeutic role for circadian factors in prenatal cocaine exposure.
Compressible turbulence in galaxy clusters: physics and stochastic particle re-acceleration

We attempt to explain the non-thermal emission arising from galaxy clusters as a result of the re-acceleration of electrons by compressible turbulence induced by cluster mergers. On the basis of the available observational facts we put forward a simplified model of turbulence in clusters of galaxies focusing our attention on the compressible motions. In our model intracluster medium (ICM) is represented by a high-beta plasma in which turbulent motions are driven at large scales. The corresponding injection velocities are higher than the Alfven velocity. As a result, the turbulence is approximately isotropic up to the scale at which the turbulent velocity gets comparable with the Alfven velocity. These motions are most important for the energetic particle acceleration, but at the same time they are subjected to most of the plasma damping. Under the hypothesis that turbulence in the ICM is highly super-Alfvenic the magnetic field is passively advected and the field lines are bended on scales smaller than that of the classical, unmagnetized, ion-ion mean free path. This affects ion diffusion and the strength of the effective viscosity. Under these conditions the bulk of turbulence in hot (5-10 keV temperature) galaxy clusters is likely to be dissipated at collisionless scales via resonant coupling with thermal and fast particles. We use collisionless physics to derive the amplitude of the different components of the energy of the compressible modes, and review and extend the treatment of plasma damping in the ICM. We calculate the acceleration of both protons and electrons taking into account both transit time damping acceleration and non-resonant acceleration by large-scale compressions. We find that relativistic electrons can be re-accelerated in the ICM up to energies of several GeV provided that the rms velocity of the compressible turbulent-eddies is (V L /c s ) 2 ≈ 0.15-0.3; c s is the sound speed in the ICM. We find that under typical conditions ≈2-5 per cent of the energy flux of the cascading of compressible motions injected at large scales goes into the acceleration of fast particles and that this may explain the observed non-thermal emission from merging galaxy clusters.
Negative U traps in HfO/sub 2/ gate dielectrics and frequency dependence of dynamic BTI in MOSFETs

We report for the first time the following new findings in charge trapping in HfO/sub 2/ gate dielectrics: 1) Using an ultra-fast electronic method to measure the MOSFET V/sub th/, two different traps (fast and slow) are identified, each leading to charge trapping characteristics with different dependence on the frequency of dynamic stress; 2) First-principle calculation of oxygen vacancy related traps in HfO/sub 2/ reveals the negative U (-U) property of traps in the strongly ionized HfO/sub 2/ dielectric. Each trap can trap two electrons and lower the trap energy due to a large lattice relaxation; 3) A physic-based model for the frequency dependence of dynamic BTI is established. The BTI frequency dependence of the slow traps is explained by the -U property of these traps. Excellent agreement between the simulation and experimental data was achieved.