Synthesis and Recognition Properties of Higher Order Tetrathiafulvalene (Ttf) Calix N Pyrroles (N=4-6)

Two new benzoTTF-annulated calix[n]pyrroles (n = 5 and 6) were synthesized via a one-step acid catalyzed condensation reaction and fully characterized via single crystallographic analyses. As compared to the known tetra-TTF annulated calix[4]pyrrole, which is also produced under the conditions of the condensation reaction, the expanded calix[n]pyrroles (n = 5 and 6) are characterized by a larger cavity size and a higher number of TTF units (albeit the same empirical formula). Analysis of the binding isotherms obtained from UV-Vis spectroscopic titrations carried out in CHCl3 in the presence of both anionic (Cl-, Br-, I-, CH3COO-, H2PO4-, and HSO4-) and neutral (1,3,5-trinitrobenzene (TNB) and 2,4,6-trinitrotoluene (TNT)) substrates revealed that as a general rule the calix[6]pyrrole derivative proved to be the most efficient molecular receptor for anions, while the calix[4]pyrrole congener proves most effective for the recognition of TNB and TNT. These findings are rationalized in terms of the number of electron rich TTF subunits and NH hydrogen bond donor groups within the series, as well as an ability to adopt conformations suitable for substrate recognition, and are supported by solid state structural analyses.National Science Foundation CHE 1057904, 0741973Robert A. Welch Foundation F-1018Danish Natural Science Research Council (FNU) 272-08-0047, 11-106744WCU (World Class University) program of Korea R32-2010-10217-0Villum FoundationChemistr

Genotator: A disease-agnostic tool for genetic annotation of disease

<p>Abstract</p> <p>Background</p> <p>Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone.</p> <p>Methods</p> <p>We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at <url>http://genotator.hms.harvard.edu</url>.</p> <p>Results</p> <p>Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease.</p> <p>Conclusions</p> <p>As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real-time aggregation of ranked data that remains current with the pace of research in the disease fields. Genotator's algorithm appropriately transforms query terms to match the input requirements of each targeted databases and accurately resolves named synonyms to ensure full coverage of the genetic results with official nomenclature. Genotator generates an excel-style output that is consistent across disease queries and readily importable to other applications.</p

Urban Gravity: a Model for Intercity Telecommunication Flows

We analyze the anonymous communication patterns of 2.5 million customers of a Belgian mobile phone operator. Grouping customers by billing address, we build a social network of cities, that consists of communications between 571 cities in Belgium. We show that inter-city communication intensity is characterized by a gravity model: the communication intensity between two cities is proportional to the product of their sizes divided by the square of their distance

Gene expression time delays & Turing pattern formation systems

The incorporation of time delays can greatly affect the behaviour of partial differential equations and dynamical systems. In addition, there is evidence that time delays in gene expression due to transcription and translation play an important role in the dynamics of cellular systems. In this paper, we investigate the effects of incorporating gene expression time delays into a one-dimensional putative reaction diffusion pattern formation mechanism on both stationary domains and domains with spatially uniform exponential growth. While oscillatory behaviour is rare, we find that the time taken to initiate and stabilise patterns increases dramatically as the time delay is increased. In addition, we observe that on rapidly growing domains the time delay can induce a failure of the Turing instability which cannot be predicted by a naive linear analysis of the underlying equations about the homogeneous steady state. The dramatic lag in the induction of patterning, or even its complete absence on occasions, highlights the importance of considering explicit gene expression time delays in models for cellular reaction diffusion patterning

Percent body fat estimations in college women using field and laboratory methods: a three-compartment model approach

This is the publisher's version, also available electronically from http://www.jissn.com/content/4/1/16.Background Methods used to estimate percent body fat can be classified as a laboratory or field technique. However, the validity of these methods compared to multiple-compartment models has not been fully established. This investigation sought to determine the validity of field and laboratory methods for estimating percent fat (%fat) in healthy college-age women compared to the Siri three-compartment model (3C). Methods Thirty Caucasian women (21.1 ± 1.5 yrs; 164.8 ± 4.7 cm; 61.2 ± 6.8 kg) had their %fat estimated by BIA using the BodyGram™ computer program (BIA-AK) and population-specific equation (BIA-Lohman), NIR (Futrex® 6100/XL), a quadratic (SF3JPW) and linear (SF3WB) skinfold equation, air-displacement plethysmography (BP), and hydrostatic weighing (HW). Results All methods produced acceptable total error (TE) values compared to the 3C model. Both laboratory methods produced similar TE values (HW, TE = 2.4%fat; BP, TE = 2.3%fat) when compared to the 3C model, though a significant constant error (CE) was detected for HW (1.5%fat, p ≤ 0.006). The field methods produced acceptable TE values ranging from 1.8 – 3.8 %fat. BIA-AK (TE = 1.8%fat) yielded the lowest TE among the field methods, while BIA-Lohman (TE = 2.1%fat) and NIR (TE = 2.7%fat) produced lower TE values than both skinfold equations (TE > 2.7%fat) compared to the 3C model. Additionally, the SF3JPW %fat estimation equation resulted in a significant CE (2.6%fat, p ≤ 0.007). Conclusion Data suggest that the BP and HW are valid laboratory methods when compared to the 3C model to estimate %fat in college-age Caucasian women. When the use of a laboratory method is not feasible, NIR, BIA-AK, BIA-Lohman, SF3JPW, and SF3WB are acceptable field methods to estimate %fat in this population

Sismicità all’Etna dal 1989 al 2010: evidenze sull’evoluzione spazio-temporale dell’attività sismica

Il Monte Etna, uno dei più attivi vulcani basaltici tra i più monitorati al mondo, è sede di una notevole attività sismica e vulcanica. Esso è ubicato in Sicilia orientale in un complesso quadro geodinamico, dove le principali strutture tettoniche regionali giocano un ruolo chiave nei processi dinamici del vulcano. La sismicità dell’Etna si manifesta con un elevato rate di terremoti di bassa e moderata energia che, a volte, a causa dell’estrema superficialità della sorgente, provocano danni ai centri abitati prossimi all’area epicentrale. Il monitoraggio sistematico dell’attività sismica etnea è effettuato sin dal 1989, mediante una rete sismica locale permanente che nel tempo è stata oggetto di importanti miglioramenti. La prima configurazione di rete era costituita da circa 10 stazioni analogiche con sensori a corto periodo gestita dall’Istituto Internazionale di Vulcanologia (IIV-CNR). Nel 1994, una rete sismica costituita da circa 40 stazioni (analogiche con sensori a corto periodo) fu installata sull’Etna nell’ambito del Progetto Poseidon. Nel 2001, le reti gestite dall’IIV-CNR e dal Progetto Poseidon confluirono nell’Istituto Nazionale di Geofisica e Vulcanologia (INGV); attualmente la rete sismica, costituita da circa 50 stazioni digitali equipaggiate con sismometri broadband a tre componenti, è gestita dalla Sezione di Catania dell’INGV. Nel periodo 1989-1999, il catalogo dei terremoti risulta costituito da circa 2000 eventi con soglia di completezza per magnitudo pari a 2.0; dal 1999 ad oggi contiene circa 6000 terremoti con soglia di completezza per magnitudo 1.5. La capacità di detezione della rete è migliorata nel tempo permettendo di registrare e localizzare anche gli eventi meno energetici (M≥1.0). In questo lavoro, vengono presentati i caratteri predominanti della sismicità etnea negli ultimi 20 anni, con un maggiore dettaglio della distribuzione spazio-temporale della sismicità verificatasi dal 1999. L’analisi della attività sismica rappresenta un utile strumento per l’interpretazione delle dinamiche che hanno contraddistinto numerose ed importanti eruzioni (2001, 2002-03, 2004, 2006, 2008-09). In particolare, la variazione del rilascio energetico della sismicità ha contribuito in maniera significativa ad identificare i probabili processi geodinamici legati alla ricarica del sistema magmatico del vulcano. La distribuzione spaziale della sismicità ha consentito di evidenziare inoltre l’esistenza di diverse aree sismogenetiche caratterizzate da un differente rate sismico, profondità focali e cinematica delle strutture associate. Infine, osservando le caratteristiche della sismicità nel lungo periodo, differenti settori del vulcano sono risultati maggiormente attivi in relazione ai più importanti recenti eventi eruttivi

A role for ΔfosB in calorie restriction-induced metabolic changes

Background: Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism. Methods: After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor ΔFosB. The ΔFosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted. Results: We show that accumulation of ΔFosB in the NAc shell after CR in mice corresponds to a period of increased motivation for high fat reward and reduced energy expenditure. Furthermore, ΔFosB overexpression in this region increases instrumental responding for a high fat reward via an orexin-dependent mechanism while also decreasing energy expenditure and promoting adiposity. Conclusions: These results suggest that ΔFosB signaling in NAc mediates adaptive responses to CR.Instituto Multidisciplinario de Biología Celula

Effects of molecular contamination and sp2^2 carbon on oxidation of (100) single-crystal diamond surfaces

The efficacy of oxygen (O) surface terminations of specific moieties and densities on diamond depends on factors such as crystallinity, roughness, and crystal orientation. Given the wide breadth of diamond-like materials and O-termination techniques, it can be difficult to discern which method would yield the highest and most consistent O coverage on a particular subset of diamond. We first review the relevant physical parameters for O-terminating single-crystalline diamond (SCD) surfaces and summarize prior oxidation work on (100) SCD. We then report on our experimental study on X-ray Photoelectron Spectroscopy (XPS) characterization of (100) diamond surfaces treated with oxidation methods that include wet chemical oxidation, photochemical oxidation with UV illumination, and steam oxidation using atomic layer deposition. We describe a rigorous XPS peak-fitting procedure for measuring the functionalization of O-terminated samples and recommend that the reporting of peak energy positions, line shapes, and full-width-half-maximum values of the individual components, along with the residuals, are important for evaluating the quality of the peak fit. Two chemical parameters on the surface, sp$^2$ C and molecular contaminants, are also crucial towards interpreting the O coverage on the diamond surface and may account for the inconsistency in prior reported values in literature

A role for ΔfosB in calorie restriction-induced metabolic changes

Background: Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism. Methods: After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor ΔFosB. The ΔFosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted. Results: We show that accumulation of ΔFosB in the NAc shell after CR in mice corresponds to a period of increased motivation for high fat reward and reduced energy expenditure. Furthermore, ΔFosB overexpression in this region increases instrumental responding for a high fat reward via an orexin-dependent mechanism while also decreasing energy expenditure and promoting adiposity. Conclusions: These results suggest that ΔFosB signaling in NAc mediates adaptive responses to CR.Instituto Multidisciplinario de Biología Celula

Staphylococcus aureus Resistance to Human Defensins and Evasion of Neutrophil Killing via the Novel Virulence Factor Mprf Is Based on Modification of Membrane Lipids with l-Lysine

Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria