Blue Obelisk - Interoperability in chemical informatics

The Blue Obelisk Movement (http://www.blueobelisk.org/) is the name used by a diverse Internet group promoting reusable chemistry via open source software development, consistent and complimentary chemoinformatics research, open data, and open standards. We outline recent examples of cooperation in the Blue Obelisk group:  a shared dictionary of algorithms and implementations in chemoinformatics algorithms drawing from our various software projects; a shared repository of chemoinformatics data including elemental properties, atomic radii, isotopes, atom typing rules, and so forth; and Web services for the platform-independent use of chemoinformatics programs

Heat shock protein 10 inhibits lipopolysaccharide-induced inflammatory mediator production

Heat shock protein 10 (Hsp10) and heat shock protein 160 (Hsp60) were originally described as essential mitochondrial proteins involved in protein folding. How,ever, both proteins have also been shown to have a number of extracellular immunomodulatory activities. Here we show that purified recombinant human Hsp10 incubated with cells in vitro reduced lipopolysaccharide (LPS)-induced nuclear factor-kappaB activation and secretion of several inflammatory mediators from RAW264.7 cells, murine macrophages, and human peripheral blood mononuclear cells. Induction of tolerance by contaminating LPS was formally excluded as being responsible for Hsp10 activity. Treatment of mice with Hsp10 before,endotoxin challenge resulted in the reduction of serum tumor necrosis factor-a and RANTES (regulated upon activation, normal T cell expressed and secreted) levels and an elevation of serum interleukin-10 levels. Hsp10 treatment also delayed mortality in a murine graft-ver-sus-host disease model, where gut-derived LPS contributes to pathology. We were unable to confirm previous reports that Hsp10 has tumor growth factor properties and suggest that Hsp10 exerts anti-inflammatory activity by inhibiting Toll-like receptor signaling possibly by interacting with extracellular Hsp60

Turbulent ‘stopping plumes’ and plume pinch-off in uniform surroundings

Observations of turbulent convection in the environment are of variously sus- tained plume-like flows or intermittent thermal-like flows. At different times of the day the prevailing conditions may change and consequently the observed flow regimes may change. Understanding the link between these flows is of practical importance meteorologically, and here we focus our interest upon plume-like regimes that break up to form thermal-like regimes. It has been shown that when a plume rises from a boundary with low conductivity, such as arable land, the inability to maintain a rapid enough supply of buoyancy to the plume source can result in the turbulent base of the plume separating and rising away from the source. This plume ‘pinch-off’ marks the onset of the intermittent thermal-like behavior. The dynamics of turbulent plumes in a uniform environment are explored in order to investigate the phenomenon of plume pinch-off. The special case of a turbulent plume having its source completely removed, a ‘stopping plume’, is considered in particular. The effects of forcing a plume to pinch-off, by rapidly reducing the source buoyancy flux to zero, are shown experi- mentally. We release saline solution into a tank filled with fresh water generating downward propagating steady turbulent plumes. By rapidly closing the plume nozzle, the plumes are forced to pinch-off. The plumes are then observed to detach from the source and descend into the ambient. The unsteady buoyant region produced after pinch-off, cannot be described by the power-law behavior of either classical plumes or thermals, and so the terminology ‘stopping plume’ (analogous to a ‘starting plume’) is adopted for this type of flow. The propagation of the stopping plume is shown to be approximately linearly dependent on time, and we speculate therefore that the closure of the nozzle introduces some vorticity into the ambient, that may roll up to form a vortex ring dominating the dynamics of the base of a stopping plume

Solid-phase molecular recognition of cytosine based on proton-transfer reaction. Part II. supramolecular architecture in the cocrystals of cytosine and its 5-Fluoroderivative with 5-Nitrouracil

<p>Abstract</p> <p>Background</p> <p>Cytosine is a biologically important compound owing to its natural occurrence as a component of nucleic acids. Cytosine plays a crucial role in DNA/RNA base pairing, through several hydrogen-bonding patterns, and controls the essential features of life as it is involved in genetic codon of 17 amino acids. The molecular recognition among cytosines, and the molecular heterosynthons of molecular salts fabricated through proton-transfer reactions, might be used to investigate the theoretical sites of cytosine-specific DNA-binding proteins and the design for molecular imprint.</p> <p>Results</p> <p>Reaction of cytosine (Cyt) and 5-fluorocytosine (5Fcyt) with 5-nitrouracil (Nit) in aqueous solution yielded two new products, which have been characterized by single-crystal X-ray diffraction. The products include a dihydrated molecular salt (CytNit) having both ionic and neutral hydrogen-bonded species, and a dihydrated cocrystal of neutral species (5FcytNit). In CytNit a protonated and an unprotonated cytosine form a triply hydrogen-bonded aggregate in a self-recognition ion-pair complex, and this dimer is then hydrogen bonded to one neutral and one anionic 5-nitrouracil molecule. In 5FcytNit the two neutral nucleobase derivatives are hydrogen bonded in pairs. In both structures conventional N-H^...O, O-H^...O, N-H^+...N and N-H^...N^-intermolecular interactions are most significant in the structural assembly.</p> <p>Conclusion</p> <p>The supramolecular structure of the molecular adducts formed by cytosine and 5-fluorocytosine with 5-nitrouracil, CytNit and 5FcytNit, respectively, have been investigated in detail. CytNit and 5FcytNit exhibit widely differing hydrogen-bonding patterns, though both possess layered structures. The crystal structures of CytNit (D<it>p</it>k_a= -0.7, molecular salt) and 5FcytNit (D<it>p</it>k_a= -2.0, cocrystal) confirm that, at the present level of knowledge about the nature of proton-transfer process, there is not a strict correlation between the D<it>p</it>k_avalues and the proton transfer, in that the acid/base <it>p</it>k_astrength is not a definite guide to predict the location of H atoms in the solid state. Eventually, the absence in 5FcytNit of hydrogen bonds involving fluorine is in agreement with findings that covalently bound fluorine hardly ever acts as acceptor for available Brønsted acidic sites in the presence of competing heteroatom acceptors.</p

Designer nanocarriers for navigating the systemic delivery of oncolytic viruses

Nanotechnology is paving the way for new carrier systems designed to overcome the greatest challenges of oncolytic virotherapy; systemic administration and subsequent implications of immune responses and specific cell binding and entry. Systemic administration of oncolytic agents is vital for disseminated neoplasms, however transition of nanoparticles (NP) to virotherapy has yielded modest results. Their success relies on how they navigate the merry-go-round of often-contradictory phases of NP delivery: circulatory longevity, tissue permeation and cellular interaction, with many studies postulating design features optimal for each phase. This review discusses the optimal design of NPs for the transport of oncolytic viruses within these phases, to determine whether improved virotherapeutic efficacy lies in the pharmacokinetic/pharmacodynamics characteristics of the NP–oncolytic viruses complexes rather than manipulation of the virus and targeting ligands

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

Problem formulation by medical students: an observation study

<p>Abstract</p> <p>Background</p> <p>Medical problems are often complex and ill-structured. In formulating the problem, one has to discriminate pertinent elements from irrelevant information in order to effectively find a solution. In this observation study, we describe how medical students formulate the problem of a complex case.</p> <p>Methods</p> <p>32 third year medical students were presented with a complex case of endocarditis. They were asked to synthesize the case and give the best formulation of the problem. They were then asked to provide a diagnosis. A subsequent group of 25 students were presented with the problem already formulated and were also asked for the diagnosis. We analyzed the student's problem formulations using the presence or absence of essential elements of the case, the use of higher-order concepts and the use of relations between concepts.</p> <p>Results</p> <p>12/32 students presented with the case made the correct diagnosis. Diagnostic accuracy was significantly associated with the use of higher-order concepts and relations between concepts. Establishing explicit relations was particularly important. Almost all students who missed the diagnosis could not elicit any relations between concepts but only reported factual observations. When presented with an already formulated problem, 19/25 students made the correct diagnosis. (p < 0.05)</p> <p>Conclusion</p> <p>When faced with a complex new case, students may not have the structured knowledge to recognize the nature of the problem. They have to build new schema or problem representation. Our observations suggest that this process involves using higher-order concepts and establishing new relations between concepts. The fact that students could recognize the disease when presented with a formulated problem but had more difficulty when presented with the original complex case indicates that knowledge of the clinical features may be necessary but not sufficient for problem formulation. Our hypothesis is that problem formulation represents a distinct ability.</p

Explosive Nucleosynthesis: What we learned and what we still do not understand

This review touches on historical aspects, going back to the early days of nuclear astrophysics, initiated by B$^2$FH and Cameron, discusses (i) the required nuclear input from reaction rates and decay properties up to the nuclear equation of state, continues (ii) with the tools to perform nucleosynthesis calculations and (iii) early parametrized nucleosynthesis studies, before (iv) reliable stellar models became available for the late stages of stellar evolution. It passes then through (v) explosive environments from core-collapse supernovae to explosive events in binary systems (including type Ia supernovae and compact binary mergers), and finally (vi) discusses the role of all these nucleosynthesis production sites in the evolution of galaxies. The focus is put on the comparison of early ideas and present, very recent, understanding.Comment: 11 pages, to appear in Springer Proceedings in Physics (Proc. of Intl. Conf. "Nuclei in the Cosmos XV", LNGS Assergi, Italy, June 2018

An estimate of carbon emissions from 2004 wildfires across Alaskan Yukon River Basin

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