Statistical properties of eigenstate amplitudes in complex quantum systems

We study the eigenstates of quantum systems with large Hilbert spaces, via their distribution of wavefunction amplitudes in a real-space basis. For single-particle 'quantum billiards', these real-space amplitudes are known to have Gaussian distribution for chaotic systems. In this work, we formulate and address the corresponding question for many-body lattice quantum systems. For integrable many-body systems, we examine the deviation from Gaussianity and provide evidence that the distribution generically tends toward power-law behavior in the limit of large sizes. We relate the deviation from Gaussianity to the entanglement content of many-body eigenstates. For integrable billiards, we find several cases where the distribution has power-law tails.Comment: revised version, with appendices; 15 pages, 10 figure

Experimental evidence on promotion of electric and improved biomass cookstoves.

Improved cookstoves (ICS) can deliver "triple wins" by improving household health, local environments, and global climate. Yet their potential is in doubt because of low and slow diffusion, likely because of constraints imposed by differences in culture, geography, institutions, and missing markets. We offer insights about this challenge based on a multiyear, multiphase study with nearly 1,000 households in the Indian Himalayas. In phase I, we combined desk reviews, simulations, and focus groups to diagnose barriers to ICS adoption. In phase II, we implemented a set of pilots to simulate a mature market and designed an intervention that upgraded the supply chain (combining marketing and home delivery), provided rebates and financing to lower income and liquidity constraints, and allowed households a choice among ICS. In phase III, we used findings from these pilots to implement a field experiment to rigorously test whether this combination of upgraded supply and demand promotion stimulates adoption. The experiment showed that, compared with zero purchase in control villages, over half of intervention households bought an ICS, although demand was highly price-sensitive. Demand was at least twice as high for electric stoves relative to biomass ICS. Even among households that received a negligible price discount, the upgraded supply chain alone induced a 28 percentage-point increase in ICS ownership. Although the bundled intervention is resource-intensive, the full costs are lower than the social benefits of ICS promotion. Our findings suggest that market analysis, robust supply chains, and price discounts are critical for ICS diffusion

Phenotypic Screens, Chemical Genomics, and Antimalarial Lead Discovery

No grant i

Establishment and characterization of immortalized Gli-null mouse embryonic fibroblast cell lines

<p>Abstract</p> <p>Background</p> <p>Hedgehog (Hh) signaling is a conserved morphogenetic pathway which plays critical roles in embryonic development, with emerging evidence also supporting a role in healing and repair processes and tumorigenesis. The Gli family of transcription factors (Gli1, 2 and 3) mediate the Hedgehog morphogenetic signal by regulating the expression of downstream target genes. We previously characterized the individual and cooperative roles of the Gli proteins in Hh target gene regulation using a battery of primary embryonic fibroblasts from Gli null mice.</p> <p>Results</p> <p>Here, we describe the establishment of spontaneously immortalized mouse embryonic fibroblast (iMEF) cell lines lacking single and multiple Gli genes. These non-clonal cell lines recapitulate the unique ligand mediated transcriptional response of primary MEFs. While loss of Gli1 had no effect on target gene induction, Gli2 null cells demonstrated reduced target gene induction while Gli3 null cells exhibited elevated basal and ligand-induced expression. Target gene response in <it>Gli1</it>^-/-<it>2</it>^-/-iMEFs was severely reduced while <it>Gli2</it>^-/-<it>3</it>^-/-iMEFs were incapable of ligand-induced transcriptional response. However, we found that both <it>Gli1</it>^-/-<it>2</it>^-/-and <it>Gli2</it>^-/-<it>3</it>^-/-iMEFs exhibited robust leukotriene synthesis-dependent migration responses to Hh ligand, demonstrating that this response is not transcriptionally-dependent.</p> <p>Conclusion</p> <p>This study provides fundamental characterizations of the transcriptional and non-transcriptional Hh responsiveness of a battery of Gli-null iMEFs. Moving forward, these cell lines should prove a valuable tool set to study the unique functional regulation of the Gli proteins in a Hh-responsive cell-type.</p

Requirements for a lead compound to become a clinical candidate

A drug candidate suitable for clinical testing is expected to bind selectively to the receptor site on the target, to elicit the desired functional response of the target molecule, and to have adequate bioavailability and biodistribution to elicit the desired responses in animals and humans; it must also pass formal toxicity evaluation in animals. The path from lead to clinical drug candidate represents the most idiosyncratic segment of drug discovery and development. Each program is unique and setbacks are common, making it difficult to predict accurately the duration or costs of this segment. Because of incidents of unpredicted human toxicity seen in recent years, the regulatory agencies and public demands for safety of new drug candidates have become very strict, and safety issues are dominant when identifying a clinical drug candidate

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity

Semantic Web integration of Cheminformatics resources with the SADI framework

<p>Abstract</p> <p>Background</p> <p>The diversity and the largely independent nature of chemical research efforts over the past half century are, most likely, the major contributors to the current poor state of chemical computational resource and database interoperability. While open software for chemical format interconversion and database entry cross-linking have partially addressed database interoperability, computational resource integration is hindered by the great diversity of software interfaces, languages, access methods, and platforms, among others. This has, in turn, translated into limited reproducibility of computational experiments and the need for application-specific computational workflow construction and semi-automated enactment by human experts, especially where emerging interdisciplinary fields, such as systems chemistry, are pursued. Fortunately, the advent of the Semantic Web, and the very recent introduction of RESTful Semantic Web Services (SWS) may present an opportunity to integrate all of the existing computational and database resources in chemistry into a machine-understandable, unified system that draws on the entirety of the Semantic Web.</p> <p>Results</p> <p>We have created a prototype framework of Semantic Automated Discovery and Integration (SADI) framework SWS that exposes the QSAR descriptor functionality of the Chemistry Development Kit. Since each of these services has formal ontology-defined input and output classes, and each service consumes and produces RDF graphs, clients can automatically reason about the services and available reference information necessary to complete a given overall computational task specified through a simple SPARQL query. We demonstrate this capability by carrying out QSAR analysis backed by a simple formal ontology to determine whether a given molecule is drug-like. Further, we discuss parameter-based control over the execution of SADI SWS. Finally, we demonstrate the value of computational resource envelopment as SADI services through service reuse and ease of integration of computational functionality into formal ontologies.</p> <p>Conclusions</p> <p>The work we present here may trigger a major paradigm shift in the distribution of computational resources in chemistry. We conclude that envelopment of chemical computational resources as SADI SWS facilitates interdisciplinary research by enabling the definition of computational problems in terms of ontologies and formal logical statements instead of cumbersome and application-specific tasks and workflows.</p

Molecular dynamics and physical stability of amorphous nimesulide drug and its binary drug-polymer systems

yesIn this paper we study the effectiveness of three well known polymers: inulin, Soluplus and PVP in stabilizing amorphous form of nimesulide (NMS) drug. The re-crystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by using broadband dielectric spectroscopy (BDS), and at non-isothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 minutes. We found that this time can be prolonged to 40 years after adding to NMS 20% of PVP polymer. This polymer proved to be the best NMS’s stabilizer, while the worst stabilization effect was found after adding the inulin to NMS. Additionally, our DSC, BDS and FTIR studies indicate that for suppression of NMS’s re-crystallization in NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances as well as the antiplastization effect excerted by the excipient.The authors J.K., Z.W., K.G. and M.P., are grateful for the financial support received within the Project No. 2015/16/W/NZ7/00404 (SYMFONIA 3) from the National Science Centre, Poland. H.M. and L.T. are supported by Science Foundation Ireland under grant No. 12/RC/2275 (Synthesis and Solid State Pharmaceuticals Centre)

Endothelial C-type natriuretic peptide maintains vascular homeostasis

PMCID: PMC4151218Wellcome Trust (084449/Z/07/Z and 078496/Z/05/Z

Manejo de suelos en cultivos intensivos

En el manejo del suelo en cultivos intensivos se aplican diversas técnicas en función de variados factores, las cuales pueden afectar la calidad física, química y biológica del mismo. Por un lado esto depende de la intensidad del sistema productivo, que puede ir desde rotaciones más cortas que las habituales en cultivos extensivos, a los monocultivos (e.g. cultivo de tomate bajo cubierta). Por otro lado, es difícil hacer generalizaciones debido al amplio rango de especies cultivadas, desde plantas herbáceas hortícolas con ciclos de algunas semanas de duración (e.g. espinaca), hasta frutícolas leñosas con varios años de permanencia en los lotes cultivados. A todo esto se le deben sumar otras variables como el tipo de suelo, el clima y la calidad del agua disponible en el caso de cultivos bajo riego. En general la situación más extrema de degradación se encuentra en los suelos que se cultivan bajo cobertura plástica que, en escasas temporadas, ven deteriorada su estructura a causa del intenso laboreo; se salinizan y alcalinizan como consecuencia de la sobrefertilización y el riego con aguas salinas y/o bicarbonatadas sódicas. El proceso se agrava debido a que no contemplan los requerimientos de lixiviación o por velocidades de infiltración muy bajas que anulan la percolación profunda natural. La disminución de los niveles de materia orgánica como consecuencia del incremento de la velocidad de su mineralización por el laboreo frecuente, y por último, el vacío biológico producido por el uso de agroquímicos fumigantes de amplio espectro que alteran el equilibrio ecológico, son las principales consecuencias sobre el suelo en este tipo de producción. En estos ambientes, la degradación se intenta morigerar a través de técnicas de laboreo como el subsolado, que incrementa la lixiviación y el alomado, que junto al aporte de materia orgánica con alto contenido de lignina, permiten mejorar la infiltración, el agua útil y la concentración de oxígeno en el suelo. Para contrarrestar la sodificación se aplican enmiendas cálcicas que, al mantener el estado de floculación del complejo arcillo-húmico, favorecen la estructura, confiriendo friabilidad a los suelos arcillosos y agregación a los arenosos. Por otro lado, el empleo de este tipo de enmiendas estimula la actividad biológica debido a que el calcio también es un elemento esencial para los microorganismos benéficos. En casos extremos de alcalinización y sodificación se instalan drenajes artificiales y se realiza un lavado de los suelos mediante la aplicación de abundantes láminas de riego. En el caso del cultivo de papa en el SE bonaerense, como ejemplo de otra situación de cultivo intensivo, el tipo y frecuencia de las labranzas empleadas, las numerosas fumigaciones, la intensa aplicación de fertilizantes y pesticidas, el laboreo a favor de la pendiente que favorece el proceso de erosión hídrica, sumado a la baja calidad del agua de riego, describen una situación que deriva en un impacto ambiental sumamente desfavorable. En estas situaciones, con el fin de evitar la erosión hídrica se aconseja escoger lotes sin pendiente o con pendientes menores al 1% orientando los surcos en sentido contrario a la pendiente (máximo 4-5%). Se deben disminuir las labranzas, aplicar agroquímicos de acuerdo al resultado de monitoreos, así como fertilizantes, previo diagnóstico edáfico y/o foliar. En los cultivos intensivos cuyanos las prácticas habituales son la rotación con abonos verdes compuestos por leguminosas y gramíneas que se incorporan cuando estas últimas emiten la espiga floral, la realización de verdeos invernales y la incorporación de guanos en dosis de 5 a 20 t ha-1 que mejoran las condiciones físicas del suelo como la aireación y la retención de agua, además de aportar nutrientes.Facultad de Ciencias Agrarias y Forestale