Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure and Function of the PriC DNA Replication Restart Protein*

Collisions between DNA replication complexes (replisomes) and barriers such as damaged DNA or tightly bound protein complexes can dissociate replisomes from chromosomes prematurely. Replisomes must be reloaded under these circumstances to avoid incomplete replication and cell death. Bacteria have evolved multiple pathways that initiate DNA replication restart by recognizing and remodeling abandoned replication forks and reloading the replicative helicase. In vitro, the simplest of these pathways is mediated by the single-domain PriC protein, which, along with the DnaC helicase loader, can load the DnaB replicative helicase onto DNA bound by the single-stranded DNA (ssDNA)-binding protein (SSB). Previous biochemical studies have identified PriC residues that mediate interactions with ssDNA and SSB. However, the mechanisms by which PriC drives DNA replication restart have remained poorly defined due to the limited structural information available for PriC. Here, we report the NMR structure of full-length PriC from Cronobacter sakazakii. PriC forms a compact bundle of α-helices that brings together residues involved in ssDNA and SSB binding at adjacent sites on the protein surface. Disruption of these interaction sites and of other conserved residues leads to decreased DnaB helicase loading onto SSB-bound DNA. We also demonstrate that PriC can directly interact with DnaB and the DnaB·DnaC complex. These data lead to a model in which PriC acts as a scaffold for recruiting DnaB·DnaC to SSB/ssDNA sites present at stalled replication forks.
Preferential Interactions and the Effect of Protein PEGylation

Background PEGylation is a strategy used by the pharmaceutical industry to prolong systemic circulation of protein drugs, whereas formulation excipients are used for stabilization of proteins during storage. Here we investigate the role of PEGylation in protein stabilization by formulation excipients that preferentially interact with the protein. Methodology/Principal Findings The model protein hen egg white lysozyme was doubly PEGylated on two lysines with 5 kDa linear PEGs (mPEG-succinimidyl valerate, MW 5000) and studied in the absence and presence of preferentially excluded sucrose and preferentially bound guanine hydrochloride. Structural characterization by far- and near-UV circular dichroism spectroscopy was supplemented by investigation of protein thermal stability with the use of differential scanning calorimetry, far and near-UV circular dichroism and fluorescence spectroscopy. It was found that PEGylated lysozyme was stabilized by the preferentially excluded excipient and destabilized by the preferentially bound excipient in a similar manner as lysozyme. However, compared to lysozyme in all cases the melting transition was lower by up to a few degrees and the calorimetric melting enthalpy was decreased to half the value for PEGylated lysozyme. The ratio between calorimetric and van’t Hoff enthalpy suggests that our PEGylated lysozyme is a dimer. Conclusion/Significance The PEGylated model protein displayed similar stability responses to the addition of preferentially active excipients. This suggests that formulation principles using preferentially interacting excipients are similar for PEGylated and non-PEGylated proteins.
Enhanced ${\mu }$ Rhythm Extraction Using Blind Source Separation and Wavelet Transform

The mu rhythm is an electroencephalogram (EEG) signal located at the central region of the brain that is frequently used for studies concerning motor activity. Quite often, the EEG data are contaminated with artifacts and the application of blind source separation (BSS) alone is insufficient to extract the mu rhythm component. We present a new two-stage approach to extract the mu rhythm component. The first stage uses second-order blind identification (SOBI) with stationary wavelet transform (SWT) to automatically remove the artifacts. In the second stage, SOBI is applied again to find the mu rhythm component. Our method is first compared with independent component analysis with discrete wavelet transform (ICA-DWT) as well as SOBI-DWT, ICA-SWT, and regression method for artifact removal using simulated EEG data. The results showed that the regression method is more effective in removing electrooculogram (EOG) artifacts, while SOBI-SWT is more effective in removing electromyogram (EMG) artifacts as compared to the other artifact removal methods. Then, all the methods are compared with the direct application of SOBI in extracting mu rhythm components on simulated and actual EEG data from ten subjects. The results showed that the proposed method of SOBI-SWT artifact removal enhances the extraction of the mu rhythm component.
Les stratégies de portefeuille de produits des entreprises industrielles françaises face à la concurrence des pays à bas coût de production

Les ecarts de couts de production entre pays developpes et pays en developpement incitent les entreprises implantees dans les premiers a elaborer des strategies specifiques pour faire face a la concurrence des seconds. En effet, les strategies d'amelioration de la competitivite-couts, fondees par exemple sur l'amelioration des techniques de production (innovation de procede), sont le plus souvent vouees a l'echec, compte tenu de l'importance des ecarts initiaux de couts de production. La litterature suggere une strategie alternative, l'innovation de produit, davantage susceptible de repondre a la concurrence du Sud. Cette strategie conduit souvent l'entreprise a s'engager dans des activites de Recherche et Developpement et lui permet de tirer parti des avantages comparatifs dont elle dispose: competence technologique, acces a une main-d'œuvre hautement qualifiee, etc. Une analyse empirique des strategies mises en œuvre par les entreprises francaises face a la concurrence du Sud montre que les entreprises soumises a ce type de concurrence sont significativement plus diversifiees ; elles modifient davantage, et plus frequemment, leur profil de production. Seules les entreprises les plus productives associent a ces strategies un veritable effort d'innovation, pour partie susceptible d'expliquer leurs meilleures performances en termes de survie precedemment mises en evidence dans la litterature.
Robust adaptive control of nonlinear systems with asymmetric non-smooth saturation

In this paper, the robust adaptive control is proposed for a class of parametric uncertain nonlinear system with asymmetric non-smooth input saturation. By introducing a well-defined smooth function, a robust adaptive control algorithms are developed to deal with the problem of asymmetric non-smooth saturation. Unlike most of the existing control schemes for the uncertain nonlinear system, which requires an assumption that the control gain is an unknown constant, the developed controller only needs that the control gain is a bounded and unknown time-varying function. In this work, the robust adaptive controller can guarantee global uniform boundedness of the closed-loop system signals as rigorously proved by Lyapunov analysis. A simulation results is presented to illustrate the effectiveness of the proposed adaptive control technique.
Acyclovir susceptibility and genetic characteristics of sequential herpes simplex virus type 1 corneal isolates from patients with recurrent herpetic keratitis.

PURPOSE The incidence and clinical significance of herpes simplex virus type 1 (HSV-1) acyclovir resistance were determined in patients with recurrent herpetic keratitis (RHK). METHODS Sequential corneal isolates (n = 39) from 15 immunocompetent patients with RHK were assayed for acyclovir susceptibility and genotyped by analyzing the hypervariable regions of the HSV-1 genes US1 and US12. The thymidine kinase (TK) gene of each isolate was sequenced, and the proportion of acyclovir-resistant viruses within isolates was determined. RESULTS Uniform acyclovir-resistant or acyclovir-sensitive sequential isolates were identified in 4 and 2 patients, respectively. Notably, the acyclovir susceptibility of sequential isolates changed from acyclovir sensitive to acyclovir resistant (5 patients) or from acyclovir resistant to acyclovir sensitive (3 patients). The acyclovir-resistant phenotype of the isolates correlated with the patient's unresponsiveness to acyclovir therapy. Combined analyses of the TK gene and genotype of sequential isolates showed that acyclovir-sensitive isolates contained multiple acyclovir-resistant variants of the same virus and that an identical acyclovir-resistant HSV-1 strain reappeared in the patient's cornea during RHK episodes. CONCLUSIONS Corneal HSV-1 isolates are mixtures of acyclovir-sensitive and acyclovir-resistant viruses that share the same genotype but have different TK sequences. Recovery of the same acyclovir-resistant virus during consecutive herpetic keratitis episodes suggests that acyclovir-resistant HSV-1 establishes latency and reactivates intermittently to cause acyclovir-refractory RHK.
South African renewable energy investment barriers: An investor perspective

As recently as the year 2010, renewable energy contributed less than 1% of all the energy sources in South Africa. Possible reasons include the lack of private sector investment in Renewable Energy technologies. By way of a structured interview methodology, this paper explores the reasons why private investors are reluctant to invest in renewables. The responses point to political, economic, social and technological barriers limiting private investment in renewable energy. Other barriers that were identified include poverty, low levels of education, limited technological readiness and access to the electricity grid. Some of these barriers are specific to the South African context. The paper concludes that a closer relationship between government and the private sector is required to stimulate innovation in the renewable energy sector.
The unusual inheritance pattern of the courtship songs in closely related grasshopper species of the Chorthippus albomarginatus‐group (Orthoptera: Gomphocerinae)

Sibling species of the Chorthippus albomarginatus‐group are exceptional among all European grasshopper species because they have an extremely elaborate courtship behaviour. Here, we present a genetic analysis of the courtship song differences between two closely related grasshopper species Ch. albomarginatus and Ch. oschei. Measurements of seven courtship song characters and one parameter of courtship visual display were compared among parentals, F1 and F2 hybrids, and backcrosses. Variation in one morphological character, the number of stridulatory pegs, was studied as well. The distributions of song phenotypes were more consistent with a type‐III genetic architecture, which involves complementary or duplicate pairs of loci. We suggest that this type of architecture may provide the novel elements of the hybrid songs, even more complex than the parental ones, which may offer a new starting point for sexual selection. One parameter of the visual display appeared to be controlled by a single locus, but differences in other characters of visual display could be explained by a more complex inheritance pattern. Inheritance of the peg number differences was consistent with a simple polygenic additive model. Sex linkage and/or maternal effects were not detected for any trait. We found a disproportionate influence of the Ch. albomarginatus parent on most hybrid song characteristics and the visual display, and this may support a previously suggested idea that Ch. albomarginatus is an ancestral form and Ch. oschei is a derived species.
Neural losses correlated with visual losses in clinical perimetry.

PURPOSE The validity of clinical perimetry for evaluation of the pathology of glaucoma is based on correlated losses in retinal ganglion cells and visual sensitivity, but procedures to quantify neural losses from visual field defects have not been developed. The purpose of the present study was to investigate the neural and sensitivity losses from experimental glaucoma to establish the framework for a quantitative model for the structure-function relationships of standard clinical perimetry. METHODS Perimetry, by behavioral testing, and retinal histology data were obtained from rhesus monkeys with significant visual field defects caused by experimental glaucoma. Ganglion cell densities were obtained from sections of retina that corresponded to 16 perimetry test locations. Perimetry sensitivity as a function of ganglion cell density at corresponding retina/visual field locations was analyzed. RESULTS The structure-function relationships were linear on log-log coordinates, with parameters that varied systematically with eccentricity. The slope value varied from 1.25 dB/dB at 4.2 degrees from fixation to a value of 2.32 dB/dB at 24 degrees from fixation, whereas the intercept value varied from -25.2 dB to -55.7 dB over the same range of eccentricities. The structure-function relationships produced a model to predict the ganglion cell density underlying a given level of visual sensitivity and location in the visual field. The model, with no free parameters, produced an accurate and relatively precise quantification of retinal ganglion cell losses caused by experimental glaucoma in monkeys. However, because the early detection of glaucoma is limited by intersubject variability, ganglion cell losses of 40% to 50% were necessary before visual sensitivity losses exceeded the normal 95% confidence limits. CONCLUSIONS With retinal eccentricity as a factor, the neural losses from glaucoma are predictable from visual sensitivity measurements by clinical perimetry. The relationships derived from experimental glaucoma in monkeys also accurately predict the rate of age-related losses of retinal ganglion cells in humans, based on the normative perimetry data for age-related reductions in visual sensitivity. The success of the model in this study suggested that it is potentially applicable to the clinical interpretation of the state of glaucomatous optic neuropathy.
Building an infrastructure for everyday lives

Abstract This paper takes as its focus the practical solutions and new ways of thinking being forwarded by women across Europe under the umbrella of EuroFEM. It sets these case studies in the context of the developing importance of the ‘everyday life concept’. This concept has grown from two routes, firstly, feminist concerns for the way in which much of women's time is spent attempting to overcome the separation of home, waged work, the market and public institutions, secondly, arising out of stmcturation theory, the discussion of the opportunity/constraint negotiation through which life is lived and the possibility of public policy enhancing survival and coping strategies. The paper goes on to ask how these ways of thinking about daily life can be mainstreamed. The paper draws upon research currently funded under the fourth action programme of equal opportunities for women and men.
In silico model of an antenna of a phycobilisome and energy transfer rates determination by theoretical Förster approach

Energy transfer (ET) in phycobilisomes, a macrocomplex of phycobiliproteins and linker proteins, is a process that is difficult to understand completely. A model for a rod composed of two hexamers of Phycocyanin and two hexamers of Phycoerythrin was built using an in silico approach and the three‐dimensional structures of both phycobiliproteins from Gracilaria chilensis. The model was characterized and showed 125 Å wide and 230 Å high, which agree with the dimensions of a piling of four hexamers as observed in the images of subcomplexes of phycobilisomes obtained by transmission electron microscopy. ET rates between every pair of chromophores in the model were calculated using the Förster approach, and the fastest rates were selected to draw preferential ET pathways along the rod. Every path indicates that the ET is funneled toward the chromophores located at Cysteines 82 in Phycoerythrin and 84 in Phycocyanin. The chromophores that face the exterior of the rod are phycoerythrobilins, and they also show a preferential ET toward the chromophores located at the center of the rod. The values calculated, in general, agree with the experimental data reported previously, which validates the use of this experimental approach.
Evidence of Nonlinearity in Daily Stock Returns

This article applies a newly developed statistical technique to time series of daily rates of return of 15 common stocks. The technique involves estimating the bispectrum of the observed time series. The bispectrum is defined as the double Fourier transform of the third-order cumulant function. If the process generating rates of return is linear with independent innovations, then the skewness of the bispectrum will be constant. The article describes a test that can detect nonconstant skewness in the bispectrum. Hence if the test rejects constant skewness, a nonlinear process is implied. As a consequence, the test can distinguish between white noise and purely random noise. The results suggest that daily stock returns are generated by a nonlinear process.
Images of Italy, France and Morocco as tourist destinations

For a geographic area to become successful as a tourist destination, it is crucially important to recognise the tourist destination's perceived images since they effect the individual's subjective perception and consequent behaviour and destination choice. This importance has led to a growing body of research on tourism destination image. In this research, image differences of three competing Mediterranean destinations – Italy, France and Morocco – were examined in terms of how they are perceived by university students. Research data were analysed by stepwise discriminant analysis. According to research results it was found that perceived images of the three destinations are significantly different. Also, results showed that, potential customers for Italy, France and Morocco destinations could be predicted by using a discriminant function.
Double dissociation in the anatomy of socioemotional disinhibition and executive functioning in dementia.

OBJECTIVE To determine whether socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobes, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. METHOD Subjects included 157 patients with neurodegenerative disease. A semiautomated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including 3 tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single-factor score to represent EF. RESULTS Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, Mini-Mental State Examination, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition, and MFG significantly predicted EF performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. CONCLUSIONS These results support a specific association between orbitofrontal areas and behavioral management as compared with dorsolateral areas and EF.
Regulation of Cl− secretion by α2‐adrenergic receptors in mouse colonic epithelium

Previous studies have shown that α2 adrenoceptor (α2AR) agonists inhibit electrolyte secretion in colonic epithelia, but little is known about the molecular mechanisms involved in this process. In this study we examined the effect of α2AR activation on transepithelial anion secretion across isolated murine colonic epithelium. We found that α2AR agonists, UK 14,304, clonidine and medetomidine were potent inhibitors of anion secretion, especially in the proximal colon. Short circuit current measurements (Isc) in colonic epithelia from normal and cystic fibrosis (CF) mice showed that α2AR agonists inhibited basal cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated Cl− secretion but had no effect on CFTR activation by cAMP‐dependent phosphorylation. Apical administration of an ionophore, nystatin (90 μg ml−1), was used to investigate the effect of UK 14,304 on basolateral K+ transport. The Na+–K+‐ATPase current, measured as ouabain‐sensitive current in the absence of ion gradients, was unaltered by pretreatment of the tissue with UK 14,304 (1 μm). In the presence of a basolaterally directed K+ gradient, UK 14,304 significantly reduced nystatin‐activated Isc indicating that activation of α2ARs inhibits basolateral K+ channels. Studies with selective K+ channel inhibitors and openers showed that α2AR agonists inhibited KATP channels that were tonically active in mouse colonic epithelia. RT‐PCR and pharmacological studies suggested that these channels could be similar to vascular smooth muscle KATP channels comprising Kir6.1/SUR2B or Kir6.2/SUR2B subunits. Inhibition of anion secretion by α2AR agonists required activation of pertussis toxin‐sensitive Gi/o proteins, but did not involve classical second messengers, such as cAMP or Ca2+. In summary, α2ARs inhibit anion secretion in colonic epithelia by acting on basolateral KATP channels, through a process that does not involve classical second messengers.
CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury

Although the role of CD4 T cells in tissue inflammation and organ injury resulting from ischemia and reperfusion injury (IRI) has been well documented, it remains unclear how CD4 T cells are activated and function in the absence of a specific antigen (Ag). We used a murine liver warm IRI model to determine first whether de novo Ag‐specific CD4 T cell activation was required and then what its functional mechanism was. The critical role of CD4 T cells in liver immune activation against ischemia and reperfusion (IR) was confirmed in CD4 knockout mice and CD4 depleted wild‐type mice. Interestingly, the inhibition of CD4 T cell activation without target cell depletion failed to protect livers against IRI, and this suggested that T cells function in liver IRI without Ag‐specific de novo activation. To dissect the T cell functional mechanism, we found that CD154 blockade, but not interferon γ (IFN‐γ) neutralization, inhibited local immune activation and protected livers from IRI. Furthermore, agonist anti‐CD40 antibodies restored liver IRI in otherwise protected CD4‐deficient hosts. Finally, fluorescence‐activated cell sorting analysis of liver CD4 T cells revealed the selective infiltration of effector cells, which constitutively expressed a higher level of CD154 in comparison with their peripheral counterparts. IR triggered a significant liver increase in CD40 expression but not CD154 expression, and macrophages responded to toll‐like receptor 4 and type I IFN stimulation to up‐regulate CD40 expression. Conclusion: These novel findings provide evidence that CD4 T cells function in liver IRI via CD154 without de novo Ag‐specific activation, and innate immunity–induced CD40 up‐regulation may trigger the engagement of CD154‐CD40 to facilitate tissue inflammation and injury. (HEPATOLOGY 2009.)