Bis[5-oxo-4,5-dihydro-8H-2-azonia-4,8,9-trizabicyclo[4.3.0]nona-2,6,9(1)-triene] sulfate

In the crystal structure of the title compound, 2C5H5N4O+·SO4 2−, N—H⋯O hydrogen bonds assemble the mol­ecules into a two-dimensional network structure parallel to the cb plane. The S atom of the sulfate ion lies on a special position on a twofold axis

Interference effects in isolated Josephson junction arrays with geometric symmetries

As the size of a Josephson junction is reduced, charging effects become important and the superconducting phase across the link turns into a periodic quantum variable. Isolated Josephson junction arrays are described in terms of such periodic quantum variables and thus exhibit pronounced quantum interference effects arising from paths with different winding numbers (Aharonov-Casher effects). These interference effects have strong implications for the excitation spectrum of the array which are relevant in applications of superconducting junction arrays for quantum computing. The interference effects are most pronounced in arrays composed of identical junctions and possessing geometric symmetries; they may be controlled by either external gate potentials or by adding/removing charge to/from the array. Here we consider a loop of N identical junctions encircling one half superconducting quantum of magnetic flux. In this system, the ground state is found to be non-degenerate if the total number of Cooper pairs on the array is divisible by N, and doubly degenerate otherwise (after the stray charges are compensated by the gate voltages).Comment: 9 pages, 6 figure

nu=1/2 quantum Hall effect in the Aharonov-Casher geometry in a mesoscopic ring

We study the effect of an electric charge in the middle of a ring of electrons in a magnetic field such as $\nu = 1/2$. In the absence of the central charge, a residual current should appear due to an Aharanov-Bohm effect. As the charge varies, periodic currents should appear in the ring. We evaluate the amplitude of these currents, as well as their period as the central charge varies. The presence of these currents should be a direct signature of the existence of a statistical gauge field in the $\nu=1/2$ quantum Hall effect. Numerical diagonalizations for a small number of electrons on the sphere are also carried out. The numerical results up to 9 electrons are qualitatively consistent with the mean field picture.Comment: 23 pages,14 included postscript figures, submitted to Phys. Rev.

Possible realization of Josephson charge qubits in two coupled Bose-Einstein condensates

We demonstrate that two coupled Bose-Einstein condensates (BEC) at zero temperature can be used to realize a qubit which is the counterpart of Josephson charge qubits. The two BEC are weakly coupled and confined in an asymmetric double-well trap. When the "charging energy" of the system is much larger than the Josephson energy and the system is biased near a degeneracy point, the two BEC represent a qubit with two states differing only by one atom. The realization of the BEC qubits in realistic BEC experiments is briefly discussed.Comment: 4 pages; comments are welcome / Corrected typos in Eq. (16); a note adde

Antimalarial Iron Chelator, FBS0701, Shows Asexual and Gametocyte Plasmodium falciparum Activity and Single Oral Dose Cure in a Murine Malaria Model

Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S)3”-(HO)-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC50) of 6 µM for Plasmodium falciparum in contrast to the IC50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials

Recruitment of rare 3-grams at functional sites: Is this a mechanism for increasing enzyme specificity?

<p>Abstract</p> <p>Background</p> <p>A wealth of unannotated and functionally unknown protein sequences has accumulated in recent years with rapid progresses in sequence genomics, giving rise to ever increasing demands for developing methods to efficiently assess functional sites. Sequence and structure conservations have traditionally been the major criteria adopted in various algorithms to identify functional sites. Here, we focus on the distributions of the 20³different types of <it>3</it>-grams (or triplets of sequentially contiguous amino acid) in the entire space of sequences accumulated to date in the UniProt database, and focus in particular on the rare <it>3</it>-grams distinguished by their high entropy-based information content.</p> <p>Results</p> <p>Comparison of the UniProt distributions with those observed near/at the active sites on a non-redundant dataset of 59 enzyme/ligand complexes shows that the active sites preferentially recruit <it>3</it>-grams distinguished by their low frequency in the UniProt. Three cases, Src kinase, hemoglobin, and tyrosyl-tRNA synthetase, are discussed in details to illustrate the biological significance of the results.</p> <p>Conclusion</p> <p>The results suggest that recruitment of rare <it>3</it>-grams may be an efficient mechanism for increasing specificity at functional sites. Rareness/scarcity emerges as a feature that may assist in identifying key sites for proteins function, providing information complementary to that derived from sequence alignments. In addition it provides us (for the first time) with a means of identifying potentially functional sites from sequence information alone, when sequence conservation properties are not available.</p

The European Hematology Association Roadmap for European Hematology Research: a consensus document

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients

The European Hematology Association Roadmap for European Hematology Research. A Consensus Document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundatio

Multiple Signals Converge on a Differentiation MAPK Pathway

An important emerging question in the area of signal transduction is how information from different pathways becomes integrated into a highly coordinated response. In budding yeast, multiple pathways regulate filamentous growth, a complex differentiation response that occurs under specific environmental conditions. To identify new aspects of filamentous growth regulation, we used a novel screening approach (called secretion profiling) that measures release of the extracellular domain of Msb2p, the signaling mucin which functions at the head of the filamentous growth (FG) MAPK pathway. Secretion profiling of complementary genomic collections showed that many of the pathways that regulate filamentous growth (RAS, RIM101, OPI1, and RTG) were also required for FG pathway activation. This regulation sensitized the FG pathway to multiple stimuli and synchronized it to the global signaling network. Several of the regulators were required for MSB2 expression, which identifies the MSB2 promoter as a target “hub” where multiple signals converge. Accessibility to the MSB2 promoter was further regulated by the histone deacetylase (HDAC) Rpd3p(L), which positively regulated FG pathway activity and filamentous growth. Our findings provide the first glimpse of a global regulatory hierarchy among the pathways that control filamentous growth. Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors