Molecular mechanisms of action of herbal antifungal alkaloid berberine, in Candida albicans.

Candida albicans causes superficial to systemic infections in immuno-compromised individuals. The concomitant use of fungistatic drugs and the lack of cidal drugs frequently result in strains that could withstand commonly used antifungals, and display multidrug resistance (MDR). In search of novel fungicidals, in this study, we have explored a plant alkaloid berberine (BER) for its antifungal potential. For this, we screened an in-house transcription factor (TF) mutant library of C. albicans strains towards their susceptibility to BER. Our screen of TF mutant strains identified a heat shock factor (HSF1), which has a central role in thermal adaptation, to be most responsive to BER treatment. Interestingly, HSF1 mutant was not only highly susceptible to BER but also displayed collateral susceptibility towards drugs targeting cell wall (CW) and ergosterol biosynthesis. Notably, BER treatment alone could affect the CW integrity as was evident from the growth retardation of MAP kinase and calcineurin pathway null mutant strains and transmission electron microscopy. However, unlike BER, HSF1 effect on CW appeared to be independent of MAP kinase and Calcineurin pathway genes. Additionally, unlike hsf1 null strain, BER treatment of Candida cells resulted in dysfunctional mitochondria, which was evident from its slow growth in non-fermentative carbon source and poor labeling with mitochondrial membrane potential sensitive probe. This phenotype was reinforced with an enhanced ROS levels coinciding with the up-regulated oxidative stress genes in BER-treated cells. Together, our study not only describes the molecular mechanism of BER fungicidal activity but also unravels a new role of evolutionary conserved HSF1, in MDR of Candida.

Développement durable et urbanisme de projet : une nouvelle configuration de l'action publique

La notion de développement durable structure le débat contemporain sur les finalités et les instruments des politiques publiques. La montée en puissance des préoccupations environnementales et de qualité des cadres de vie déplace les enjeux traditionnels de l'aménagement. Cette refonte s'inscrit dans une prise de conscience de la transversalité des problèmes de développement territorial. Une attention accrue est aussi portée aux acteurs et à leur participation invitant à repenser les articulations entre les élus, l'administration et la société civile. L'aménagement du territoire est à un tournant. La complexité accrue du champ décisionnel liée à la multiplicité des objectifs à prendre en compte, à la diversification des acteurs concernés, mais aussi à l'interférence des échelles de gouvernance bouscule les pratiques professionnelles. Cette note vise à montrer les principaux changements observés au cours des dernières années. Elle met l'accent sur la redéfinition des objectifs et des instruments d'aménagement et l'émergence des nouvelles pratiques de conduite de projets.

Action publique concertée et gestion des sports de nature : une ethnographie participative au Conseil général du Bas-Rhin

En France, la décentralisation et la territorialisation de l'action publique ont fait des sports de nature un objet d'action publique légitime en donnant naissance à de nouveaux outils de management public dédiés à la concertation et à la planification des usages de la nature. Nés de l'article 52 de la Loi sur le sport modifiée en 2000, la Commission Départementale des Espaces, Sites et Itinéraires relatifs aux sports de nature (CDESI) et le Plan Départemental des Espaces Sites et Itinéraires relatifs aux sports de nature (PDESI) sont des outils de concertation territoriale dédiés à la gestion publique des sports de nature au niveau départemental. Un enjeu de ce travail tient à l'appréhension des transformations de l'action publique en s'attachant à l'étude des dispositifs de concertation sur les sports de nature. Un deuxième enjeu de ce travail s'attache à mettre en évidence les effets de la concertation en analysant les interactions et les différents modes d'engagements des acteurs au cours de la « chose publique en train de se faire » (Cefaï, 2002). Les acteurs s'engagent non seulement dans la concertation comprise comme une activité sociale faite d'interactions, mais ils s'engagent également dans la concertation en tant que processus d'action publique. Aussi, un autre enjeu de ce travail est d'appréhender les effets de la concertation par une analyse processuelle des engagements (Fillieule, 2004) des acteurs et des organisations. En mobilisant les outils conceptuels de la sociologie interactionniste, de la sociologie pragmatique, ainsi que de la sociologie structuraliste, l'analyse des situations interactionnelles a notamment permis d'identifier les procédures de cadrage et les techniques dramaturgiques mises en oeuvre par les interactants, ainsi que les répertoires argumentatifs mobilisés par ces acteurs pendant l « 'épreuve » de la concertation. Les confrontations des points de vue et les justifications des prises de positions des acteurs peuvent faire évoluer la configuration initiale des jeux d'acteurs même si, pour certains, ces changements ne restent parfois qu'éphémères. Les organisations s'engagent dans la concertation en fonction de la revendication d'une légitimité qui est à comprendre comme une forme militantisme institutionnel s'articulant autour de la valorisation d'une expertise militante, environnementale, institutionnelle, ou encore de leur statut de partenaire institutionnel. In France, decentralization and territorialization of public action have made outdoor sports become an object of public policies justifiable by giving birth to new tools of public management dedicated to the public consultation, the dialogue, and the planning of the uses of the landscapes. Indeed, born of article 52 of the Law on sport modified in 2000, the Departmental committee for Spaces, Sites and Routes relative to natural sports ( CDESI) and the Departmental Plan of Spaces Sites and Routes relative to natural sports ( PDESI) are governance tools dedicated to the public management of outdoor sports for counties. A challenge of this work is to understand the changes of public policy by focusing on the study of mechanisms for consultation on outdoor sports. A second item of this work is to highlight the effects of cooperation by focusing on the analysis of interactions and actor's commitments during the "public thing in the making" (Cefaï, 2002). Actors commit themselves not only in the dialogue included as a social activity made by interactions, but they also take part to the dialogue included as a process of public action. Also, another issue of this work is to understand the effects of consultation by a processual approach of individual commitments (Fillieule, 2004) of actors and organizations. Using the conceptual tools of symbolic interactionism, pragmatic sociology, and structuralist sociology, the analysis of interactional situations has highlighted the framing work and procedures implemented by the interactants, as well as the dramaturgical techniques and argumentative directories which, they mobilize during the "test" of the consultation. Confrontation of viewpoints and justifications of interactants' positions can evolve from their initial configuration sets, even if for some of them these changes are sometimes ephemeral. Organizations involve themselves according to demands of legitimacy which, are to understand as a shape institutional militancy articulating around the valuation of a militant, environmental, institutional expertise, or still around their status of institutional partner.

Thermal and back-action noises in dual-sphere gravitational-wave detectors

We study the sensitivity limits of a broadband gravitational-wave detector based on dual resonators such as nested spheres. We determine both the thermal and back-action noises when the resonators displacements are read out with an optomechanical sensor. We analyze the contributions of all mechanical modes, using a new method to deal with the force-displacement transfer functions in the intermediate frequency domain between the two gravitational-wave sensitive modes associated with each resonator. This method gives an accurate estimate of the mechanical response, together with an evaluation of the estimate error. We show that very high sensitivities can be reached on a wide frequency band for realistic parameters in the case of a dual-sphere detector.

Iowa Disaster Recovery Tabletop Exercise After Action Report/Improvement Plan, August 2010

On June 24, 2010, the Rebuild Iowa Office (RIO) held a discussion-based tabletop exercise for the purpose of creating a framework to support disaster recovery coordination within the State of Iowa. The exercise design team was composed of RIO and Iowa Homeland Security and Emergency Management Division (HSEMD) staff. Initial planning for the Iowa Disaster Recovery Tabletop Exercise began in February 2010, in response to recommendations by the Rebuild Iowa Advisory Commission and the Rebuild Iowa Coordinating Council. Both of these groups were organized in direct response to the 2008 Iowa disasters to help establish a path for Iowa’s recovery and monitor progress toward meeting established goals. Recommendations included formalizing the responsibilities of the RIO as they relate to 2008 disasters, capturing lessons learned, and determining what a recovery model should look like for Iowa’s future disasters.

State of Iowa Affirmative Action/Diversity Plan and Report, FY2008

Each department will submit by July 31st an Affirmative Action/Diversity Plan to DAS, who will receive it on behalf of the Diversity Council. This document is to report on your activities and accomplishments for FY 2008, and report on your intended activities for FY 2009. For the purposes of this document, the term protected classes refers specifically to females, minorities, and persons with disabilities. Protected classes may be subject to numerical goal setting in employment. The term diversity includes the protected classes, but also includes broader differences, such as age, sexual orientation, and religion. These differences are not subject to numerical goal setting in employment, but may be protected by non-discrimination statutes and policies. Please refer to Executive Order Four and the State’s EEO/AA Policy for more details.

State of Iowa Diversity/Affirmative Action FY 2009 Progress Report, July 31, 2009

In July 2008, you submitted an FY 2009 State of Iowa Diversity Plan and Report to DAS. In this report, your agency outlined your goals in the areas of hiring practices, recruitment, retention, training, and general programs to promote diversity. In the following pages, please summarize your stated goals for FY 2009 and the progress you made in achieving those goals in FY 2009. You may attach supplemental information as needed. Please note that the State of Iowa Diversity Plan and Report is being replaced by the FY 2010 Workforce Plan, which is due to DAS by July 31, 2009.

State of Iowa Diversity Plan and Report Affirmative Action/Equal Employment FY 2010 Progress, 2010

The State prohibits discrimination on the basis of race, creed, color, religion, national origin, sex and sexual orientation, age, or mental and physical disability in its employment policies and practices and is an equal employment opportunity and affirmative action employer. Please insert any additional statements of policy or commitment to achieving and maintaining a diverse workforce in your agency.

A CT-based study investigating the relationship between pedicle screw placement and stimulation threshold of compound muscle action potentials measured by intraoperative neurophysiological monitoring.

PURPOSE: Neurophysiological monitoring aims to improve the safety of pedicle screw placement, but few quantitative studies assess specificity and sensitivity. In this study, screw placement within the pedicle is measured (post-op CT scan, horizontal and vertical distance from the screw edge to the surface of the pedicle) and correlated with intraoperative neurophysiological stimulation thresholds. METHODS: A single surgeon placed 68 thoracic and 136 lumbar screws in 30 consecutive patients during instrumented fusion under EMG control. The female to male ratio was 1.6 and the average age was 61.3 years (SD 17.7). Radiological measurements, blinded to stimulation threshold, were done on reformatted CT reconstructions using OsiriX software. A standard deviation of the screw position of 2.8 mm was determined from pilot measurements, and a 1 mm of screw-pedicle edge distance was considered as a difference of interest (standardised difference of 0.35) leading to a power of the study of 75 % (significance level 0.05). RESULTS: Correct placement and stimulation thresholds above 10 mA were found in 71 % of screws. Twenty-two percent of screws caused cortical breach, 80 % of these had stimulation thresholds above 10 mA (sensitivity 20 %, specificity 90 %). True prediction of correct position of the screw was more frequent for lumbar than for thoracic screws. CONCLUSION: A screw stimulation threshold of >10 mA does not indicate correct pedicle screw placement. A hypothesised gradual decrease of screw stimulation thresholds was not observed as screw placement approaches the nerve root. Aside from a robust threshold of 2 mA indicating direct contact with nervous tissue, a secondary threshold appears to depend on patients' pathology and surgical conditions.

General Interaction Picture from Action Principle for Mechanics

In this paper we consider a general action principle for mechanics written by means of the elements of a Lie algebra. We study the physical reasons why we have to choose precisely a Lie algebra to write the action principle. By means of such an action principle we work out the equations of motion and a technique to evaluate perturbations in a general mechanics that is equivalent to a general interaction picture. Classical or quantum mechanics come out as particular cases when we make realizations of the Lie algebra by derivations into the algebra of products of functions or operators, respectively. Later on we develop in particular the applications of the action principle to classical and quantum mechanics, seeing that in this last case it agrees with Schwinger's action principle. The main contribution of this paper is to introduce a perturbation theory and an interaction picture of classical mechanics on the same footing as in quantum mechanics.