Conductance fluctuations in mesoscopic normal-metal/superconductor samples

We study the magnetoconductance fluctuations of mesoscopic normal-metal/superconductor (NS) samples consisting of a gold-wire in contact with a niobium film. The magnetic field strength is varied over a wide range, including values that are larger than the upper critical field B_c2 of niobium. In agreement with recent theoretical predictions we find that in the NS sample the rms of the conductance fluctuations (CF) is by a factor of 2.8 +/- 0.4 larger than in the high field regime where the entire system is driven normal conducting. Further characteristics of the CF are discussed.Comment: 4 pages, REVTEX, 3 eps-figures included. To be published in Phys. Rev. Lett.. Changes: one misplaced figure correcte

Superconducting Proximity Effect and Universal Conductance Fluctuations

We examine universal conductance fluctuations (UCFs) in mesoscopic normal-superconducting-normal (N-S-N) structures using a numerical solution of the Bogoliubov - de Gennes equation. We discuss two cases depending on the presence (``open'' structure) or absence (``closed'' structure) of quasiparticle transmission. In contrast to N-S structures, where the onset of superconductivity increases fluctuations, we find that UCFs are suppressed by superconductivity for N-S-N structures. We demonstrate that the fluctuations in ``open'' and ``closed'' structures exhibit distinct responses to an applied magnetic field and to an imposed phase variation of the superconducting order parameter.Comment: (4 pages, 5 figures). Corrected typos in equations, added references, changed Fig. 5 and its discussions. Phys. Rev. B, accepted for publicatio

The C-Terminal Domain of the Novel Essential Protein Gcp Is Critical for Interaction with Another Essential Protein YeaZ of Staphylococcus aureus

Previous studies have demonstrated that the novel protein Gcp is essential for the viability of various bacterial species including Staphylococcus aureus; however, the reason why it is required for bacterial growth remains unclear. In order to explore the potential mechanisms of this essentiality, we performed RT-PCR analysis and revealed that the gcp gene (sa1854) was co-transcribed with sa1855, yeaZ (sa1856) and sa1857 genes, indicating these genes are located in the same operon. Furthermore, we demonstrated that Gcp interacts with YeaZ using a yeast two-hybrid (Y2H) system and in vitro pull down assays. To characterize the Gcp-YeaZ interaction, we performed alanine scanning mutagenesis on the residues of C-terminal segment of Gcp. We found that the mutations of the C-terminal Y317-F322 region abolished the interaction of Gcp and YeaZ, and the mutations of the D324-N329 and S332-Y336 regions alleviated Gcp binding to YeaZ. More importantly, we demonstrated that these key regions of Gcp are also necessary for the bacterial survival since these mutated Gcp could not complement the depletion of endogenous Gcp. Taken together, our data suggest that the interaction of Gcp and YeaZ may contribute to the essentiality of Gcp for S. aureus survival. Our findings provide new insights into the potential mechanisms and biological functions of this novel essential protein

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Analysis and Practical Guideline of Constraint-Based Boolean Method in Genetic Network Inference

Boolean-based method, despite of its simplicity, would be a more attractive approach for inferring a network from high-throughput expression data if its effectiveness has not been limited by high false positive prediction. In this study, we explored factors that could simply be adjusted to improve the accuracy of inferring networks. Our work focused on the analysis of the effects of discretisation methods, biological constraints, and stringency of Boolean function assignment on the performance of Boolean network, including accuracy, precision, specificity and sensitivity, using three sets of microarray time-series data. The study showed that biological constraints have pivotal influence on the network performance over the other factors. It can reduce the variation in network performance resulting from the arbitrary selection of discretisation methods and stringency settings. We also presented the master Boolean network as an approach to establish the unique solution for Boolean analysis. The information acquired from the analysis was summarised and deployed as a general guideline for an efficient use of Boolean-based method in the network inference. In the end, we provided an example of the use of such a guideline in the study of Arabidopsis circadian clock genetic network from which much interesting biological information can be inferred

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Response of Methicillin-Resistant Staphylococcus aureus to Amicoumacin A

Amicoumacin A exhibits strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), hence we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in transcription of genes specifying several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which is induced in cells undergoing a collapse of Δψ. Consistent with the notion that LrgA modulates murein hydrolase activity, COL grown in the presence of amicoumacin A showed reduced autolysis, which was primarily caused by lower hydrolase activity. To gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by a serial passage method was carried out. Single point mutations generating codon substitutions were uncovered in ksgA (encoding RNA dimethyltransferase), fusA (elongation factor G), dnaG (primase), lacD (tagatose 1,6-bisphosphate aldolase), and SACOL0611 (a putative glycosyl transferase). The codon substitutions in EF-G that cause amicoumacin A resistance and fusidic acid resistance reside in separate domains and do not bring about cross resistance. Taken together, these results suggest that amicoumacin A might cause perturbation of the cell membrane and lead to energy dissipation. Decreased rates of cellular metabolism including protein synthesis and DNA replication in resistant strains might allow cells to compensate for membrane dysfunction and thus increase cell survivability

Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at √s=7 TeV

Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the form of an enhancement of pairs of like-sign charged pions with small four-momentum difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source is investigated, determining both the correlation radius and the chaoticity parameter. The measured correlation radius is found to increase as a function of increasing charged-particle multiplicity, while the chaoticity parameter is seen to decreas