Shot Noise and Full Counting Statistics from Non-equilibrium Plasmons in Luttinger-Liquid Junctions

We consider a quantum wire double junction system with each wire segment described by a spinless Luttinger model, and study theoretically shot noise in this system in the sequential tunneling regime. We find that the non-equilibrium plasmonic excitations in the central wire segment give rise to qualitatively different behavior compared to the case with equilibrium plasmons. In particular, shot noise is greatly enhanced by them, and exceeds the Poisson limit. We show that the enhancement can be explained by the emergence of several current-carrying processes, and that the effect disappears if the channels effectively collapse to one due to, {\em e.g.}, fast plasmon relaxation processes.Comment: 9 pages; IOP Journal style; several changes in the tex

Small substrate, big surprise: fold, function and phylogeny of dihydroxyacetone kinases

Abstract.: Dihydroxyacetone (Dha) kinases are a family of sequence-conserved enzymes which utilize either ATP (in animals, plants and eubacteria) or phosphoenolpyruvate (PEP, in eubacteria) as their source of high-energy phosphate. The kinases consist of two domains/subunits: DhaK, which binds Dha covalently in hemiaminal linkage to the Nε2 of a histidine, and DhaL, an eight-helix barrel that contains the nucleotide-binding site. The PEP-dependent kinases comprise a third subunit, DhaM, which rephosphorylates in situ the firmly bound ADP cofactor. DhaM serves as the shuttle for the transfer of phosphate from the bacterial PEP: carbohydrate phosphotransferase system (PTS) to the Dha kinase. The DhaL and DhaK subunits of the PEP-dependent Escherichia coli kinase act as coactivator and corepressor of DhaR, a transcription factor from the AAA+ family of enhancerbinding proteins. In Gram-positive bacteria genes for homologs of DhaK and DhaL occur in operons for putative transcription factors of the TetR and DeoR families. Proteins with the Dha kinase fold can be classified into three families according to phylogeny and function: Dha kinases, DhaK and DhaL homologs (paralogs) associated with putative transcription regulators of the TetR and DeoR families, and proteins with a circularly permuted domain order that belong to the DegV famil

Atypisches Erythema induratum Bazin bei tuberkulöser Osteomyelitis

Zusammenfassung: Hauttuberkulosen können sich mit sehr unterschiedlichen klinischen Bildern manifestieren und damit die Diagnosestellung erschweren. Wir stellen den Fall einer 79-jährigen Patientin vor, mit einer atypischen Präsentation eines Erythema induratum Bazin (EIB) am Oberkörper und einer tuberkulösen Osteomyelitis des Olekranon links. Aus den Biopsien der EIB-Knoten konnte M.tuberculosis kulturell nachgewiesen werden. Das widerspricht der klassischen Vorstellung, dass das EIB als Folge einer Hypersensitivitätsreaktion auf Mykobakterien entsteht, und unterstützt die Hypothese, dass das EIB auch durch eine hämatogene oder lymphogene Streuung von lebenden M.tuberculosis entstehen kan

Arsenic trioxide down-regulates antiapoptotic genes and induces cell death in mycosis fungoides tumors in a mouse model

Background: Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma (CTCL). Arsenic trioxide (As2O3) has recently been shown to be effective against leukemias, so we studied whether As2O3 induces apoptosis of CTCL cells in vitro. We further investigated if As2O3 is effective in a MF mouse model. Material and methods: Annexin V/7-amino-actinomycin-D stainings were carried out to investigate if As2O3 induced apoptosis of CTCL cell lines. To study the underlying mechanisms, the effects of As2O3 on various transcription factors and apoptosis regulating proteins were analyzed by western blots, electrophoretic mobility shift assays and transcription factor enzyme-linked immunosorbent assays. The ability of As2O3 to induce tumor regression was investigated in a MF mouse model. Results: As2O3-induced apoptosis was paralleled by a reduction of the DNA-binding activities of transcription factors of the NFkB and signal transducer and activator of transcription gene families and reduced expression of the antiapoptotic proteins bcl-1, bcl-xL and mcl-1. Local injections of 200 μM As2O3 into tumors caused complete remissions in five of six mice and one partial remission. Conclusions: As2O3 induced apoptosis of CTCL cells by the down-regulation of transcription factors that stimulate the expression of antiapoptotic genes. Local injection of As2O3 into MF tumor-bearing mice resulted in tumor regressio

Ehrenfest time dependent suppression of weak localization

The Ehrenfest time dependence of the suppression of the weak localization correction to the conductance of a {\em clean} chaotic cavity is calculated. Unlike in earlier work, no impurity scattering is invoked to imitate diffraction effects. The calculation extends the semiclassical theory of K. Richter and M. Sieber [Phys. Rev. Lett. {\bf 89}, 206801 (2002)] to include the effect of a finite Ehrenfest time.Comment: 3 Pages, 1 Figure, RevTe

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

The Antimicrobial Peptide Histatin-5 Causes a Spatially Restricted Disruption on the Candida albicans Surface, Allowing Rapid Entry of the Peptide into the Cytoplasm

Antimicrobial peptides play an important role in host defense against microbial pathogens. Their high cationic charge and strong amphipathic structure allow them to bind to the anionic microbial cell membrane and disrupt the membrane bilayer by forming pores or channels. In contrast to the classical pore-forming peptides, studies on histatin-5 (Hst-5) have suggested that the peptide is transported into the cytoplasm of Candida albicans in a non-lytic manner, and cytoplasmic Hst-5 exerts its candicidal activities on various intracellular targets, consistent with its weak amphipathic structure. To understand how Hst-5 is internalized, we investigated the localization of FITC-conjugated Hst-5. We find that Hst-5 is internalized into the vacuole through receptor-mediated endocytosis at low extracellular Hst-5 concentrations, whereas under higher physiological concentrations, Hst-5 is translocated into the cytoplasm through a mechanism that requires a high cationic charge on Hst-5. At intermediate concentrations, two cell populations with distinct Hst-5 localizations were observed. By cell sorting, we show that cells with vacuolar localization of Hst-5 survived, while none of the cells with cytoplasmic Hst-5 formed colonies. Surprisingly, extracellular Hst-5, upon cell surface binding, induces a perturbation on the cell surface, as visualized by an immediate and rapid internalization of Hst-5 and propidium iodide or rhodamine B into the cytoplasm from the site using time-lapse microscopy, and a concurrent rapid expansion of the vacuole. Thus, the formation of a spatially restricted site in the plasma membrane causes the initial injury to C. albicans and offers a mechanism for its internalization into the cytoplasm. Our study suggests that, unlike classical channel-forming antimicrobial peptides, action of Hst-5 requires an energized membrane and causes localized disruptions on the plasma membrane of the yeast. This mechanism of cell membrane disruption may provide species-specific killing with minimal damage to microflora and the host and may be used by many other antimicrobial peptides

Diagnostic accuracy of contrast-enhanced MR angiography in severe carotid stenosis: meta-analysis with metaregression of different techniques

Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a well-established noninvasive imaging method for the assessment of severe carotid stenosis (70–99% by NASCET criteria). However, CE-MRA is not a standardised technique, but encompasses different concurrent techniques. This review analyses possible differences. A bivariate random effects meta-analysis of 17 primary diagnostic accuracy studies confirmed a high pooled sensitivity of 94.3% and specificity of 93.0% for carotid CE-MRA in severe carotid stenosis. Sensitivity was fairly uniform among the studies, while specificity showed significant variation (I2 = 73%). Metaregressions found significant differences for specificity with two covariates: specificity was higher when using not only maximum intensity projection (MIP) images, but also three-dimensional (3D) images (P = 0.01). Specificity was also higher with electronic images than with hardcopies (P = 0.02). The timing technique (bolus-timed, fluoroscopically triggered or time-resolved) did not result in any significant differences in diagnostic accuracy. Some nonsignificant trends were found for the percentages of severe carotid disease, acquisition time and voxel size. In conclusion, in CE-MRA of severe carotid stenosis the three major timing techniques yield comparably high diagnostic accuracy, electronic images are more specific than hardcopies, and 3D images should be used in addition to MIP images to increase the specificity

Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle

<p>Abstract</p> <p>Background</p> <p>Mutations in methylmalonyl-CoA mutase cause methylmalonic acidemia, a common organic aciduria. Current treatment regimens rely on dietary management and, in severely affected patients, liver or combined liver-kidney transplantation. For undetermined reasons, transplantation does not correct the biochemical phenotype.</p> <p>Methods</p> <p>To study the metabolic disturbances seen in this disorder, we have created a murine model with a null allele at the methylmalonyl-CoA mutase locus and correlated the results observed in the knock-out mice to patient data. To gain insight into the origin and magnitude of methylmalonic acid (MMA) production in humans with methylmalonyl-CoA mutase deficiency, we evaluated two methylmalonic acidemia patients who had received different variants of combined liver-kidney transplants, one with a complete liver replacement-kidney transplant and the other with an auxiliary liver graft-kidney transplant, and compared their metabolite production to four untransplanted patients with intact renal function.</p> <p>Results</p> <p>Enzymatic, Western and Northern analyses demonstrated that the targeted allele was null and correctable by lentiviral complementation. Metabolite studies defined the magnitude and tempo of plasma MMA concentrations in the mice. Before a fatal metabolic crisis developed in the first 24–48 hours, the methylmalonic acid content per gram wet-weight was massively elevated in the skeletal muscle as well as the kidneys, liver and brain. Near the end of life, extreme elevations in tissue MMA were present primarily in the liver. The transplant patients studied when well and on dietary therapy, displayed massive elevations of MMA in the plasma and urine, comparable to the levels seen in the untransplanted patients with similar enzymatic phenotypes and dietary regimens.</p> <p>Conclusion</p> <p>The combined observations from the murine metabolite studies and patient investigations indicate that during homeostasis, a large portion of circulating MMA has an extra-heptorenal origin and likely derives from the skeletal muscle. Our studies suggest that modulating skeletal muscle metabolism may represent a strategy to increase metabolic capacity in methylmalonic acidemia as well as other organic acidurias. This mouse model will be useful for further investigations exploring disease mechanisms and therapeutic interventions in methylmalonic acidemia, a devastating disorder of intermediary metabolism.</p