Squeezed-light generation in a nonlinear planar waveguide with a periodic corrugation

Two-mode nonlinear interaction (second-harmonic and second-subharmonic generation) in a planar waveguide with a small periodic corrugation at the surface is studied. Scattering of the interacting fields on the corrugation leads to constructive interference that enhances the nonlinear process provided that all the interactions are phase matched. Conditions for the overall phase matching are found. Compared with a perfectly quasi-phase-matched waveguide, better values of squeezing as well as higher intensities are reached under these conditions. Procedure for finding optimum values of parameters for squeezed-light generation is described.Comment: 14 pages, 14 figure

Prediction of rehabilitation induced motor recovery after stroke using a multi-dimensional and multi-modal approach

Background: Stroke is a debilitating disease affecting millions of people worldwide. Despite the survival rate has significantly increased over the years, many stroke survivors are left with severe impairments impacting their quality of life. Rehabilitation programs have proved to be successful in improving the recovery process. However, a reliable model of sensorimotor recovery and a clear identification of predictive markers of rehabilitation-induced recovery are still needed. This article introduces the cross-modality protocols designed to investigate the rehabilitation treatment’s effect in a group of stroke survivors. Methods/design: A total of 75 stroke patients, admitted at the IRCCS San Camillo rehabilitation Hospital in Venice (Italy), will be included in this study. Here, we describe the rehabilitation programs, clinical, neuropsychological, and physiological/imaging [including electroencephalography (EEG), transcranial magnetic stimulation (TMS), and magnetic resonance imaging (MRI) techniques] protocols set up for this study. Blood collection for the characterization of predictive biological biomarkers will also be taken. Measures derived from data acquired will be used as candidate predictors of motor recovery. Discussion/summary: The integration of cutting-edge physiological and imaging techniques, with clinical and cognitive assessment, dose of rehabilitation and biological variables will provide a unique opportunity to define a predictive model of recovery in stroke patients. Taken together, the data acquired in this project will help to define a model of rehabilitation induced sensorimotor recovery, with the final aim of developing personalized treatments promoting the greatest chance of recovery of the compromised functions

NUCLEAR FACTOR Y, Subunit C (NF-YC) Transcription Factors Are Positive Regulators of Photomorphogenesis in Arabidopsis thaliana

We thank Dr. Ben Smith (University of Oklahoma) for assistance with FLIM-FRET measurements and Dr. Min Ni (University of Minnesota) for critical reading of the manuscript. The cop1-4 mutant allele and cop1-4 co-9 cross were kindly provided by George Coupland (Max Planck Institute).Author Summary Light perception is critically important for the fitness of plants in both natural and agricultural settings. Plants not only use light for photosynthesis, but also as a cue for proper development. As a seedling emerges from soil it must determine the light environment and adopt an appropriate growth habit. When blue and red wavelengths are the dominant sources of light, plants will undergo photomorphogenesis. Photomorphogenesis describes a number of developmental responses initiated by light in a seedling, and includes shortened stems and establishing the ability to photosynthesize. The genes regulating photomorphogenesis have been studied extensively, but a complete picture remains elusive. Here we describe the finding that NUCLEAR FACTOR-Y (NF-Y) genes are positive regulators of photomorphogenesis—i.e., in plants where NF-Y genes are mutated, they display some characteristics of dark grown plants, even though they are in the light. Our data suggests that the roles of NF-Y genes in light perception do not fit in easily with those of other described pathways. Thus, studying these genes promises to help develop a more complete picture of how light drives plant development.Yeshttp://www.plosgenetics.org/static/editorial#pee

Predicting the fate of basketball throws: a psychophysics and EEG study in healthy and paraplegics athletes

Elite athletes can predict successful free shots more rapidly and accurately, with cues of body kinematics, also reflected in their motor activation for successful and unsuccessful shots (Aglioti et al., 2008). Psychophysics studies indicate that paraplegic athletes may fine tune their ability to process pictures of body parts involved in the practiced sport (Pernigo et al, 2012). Here we explored the behavioral and electrocortical underpinnings of wheelchair athletes who predict the fate of throws to basket performed by paraplegic athletes. Using EEG, we searched for the possible electrocortical correlates of observing domain specific actions and predicting their outcome. Expert wheelchair basketball (WCB) players with two levels of physical movement capability were chosen (Points 1 and 4; former with most severe disability, least trunk movement and latter with least severe disability, most trunk movement). Thus far no study has focused on the AON modulation contingent upon expertise and severity injury in people with body-brain somatosensory and motor disconnection. 10 athletes and 19 healthy participants observed free throw videos (“IN” – correct movement execution; "OUT" – incorrect movement execution). They were asked to predict the outcome of the shot which was occluded by a black screen. Preliminary behavioral results highlight a significantly higher performance for the expert players to detect the error in OUT shots, while the healthy subjects only were able to predict shot outcomes at chance level. Furthermore, the players had significantly stronger P300 response compared to naïve healthy subjects over parietal electrodes, both for IN and for OUT videos. Moreover, the P300 response was greater for Point 4 players, which are not only experts, but also have a wider range of motor representations due to less injury, compared to Point 1 players. This suggests that the P300 modulation might be a correlate of motor expertise during action observation

A NEW IN-VITRO MODEL TO PREDICT THE IN VIVO BEHAVIOR OF DRUGS BASED ON PARALLEL ARTIFICIAL MEMBRANE AND PLASMA PROTEIN BINDING

Biopharmaceutical properties of drug candidates are commonly taken into account at early stage in the drug discovery process to lower the attrition rate in later clinical development stages and reduce the overall time and cost of the development of new drugs [1]. Lipophilicity and Plasma Protein Binding of a candidate drug molecule are important parameters influencing pharmacokinetic and metabolic properties [2,3]. At present, several assays exist to determine these two fundamental parameters individually [4,5], but there is no approach to assess simultaneously the two parameters and their reciprocal influence. So the main objective of this work is to develop an in vitro model to investigate the influence of a lipidic membrane on the protein binding of drugs, and to obtain a rank ordering of them. Compatibly with the needs of the modern drug discovery process, a highly automated process has been developed, allowing the rapid turnaround of in vitro data using LC-MS/MS methods to assess widely diverse compounds. The assay runs in a 96-well format using commercially available parts [6]. The protein used in this assay is Human Serum Albumin; it is not immobilized on any surface. The lipophilic distribution of drugs is guaranteed by use of an artificial lipidic membrane coated on a porous filter plate. A series of highly protein-bound compounds (PPB> 95%) having high membrane retention in PAMPA assay (>90%) were selected and tested. Distribution kinetics between lipidic membrane and HSA were measured. A different behavior of these compounds has allowed their rank ordering. Compounds with these features are not ranked by current assays, so this new approach would help early discovery process predicting better the in vivo behavior of candidate drugs from in vitro data. The impact of nonspecific binding was also investigated. REFERENCES [1] Kerns EH. J. Pharm. Sci. 2001, 90, 1838-1858 [2] Caron G, Ermondi G, Lorenti M.. J. Med. Chem. 2004, 47, 3949-3961. [3] Testa B, Crivori P, Reinst M, Carrupt PA. Kluvert Academic Publisher: Norwell, MA, 2000, pp 179-211. [4] Schuhmecher J, Buhner K, Witt-laido A. J Pharm Sci, 2000, 89, 1008-1021. [5] Loidl-Stahlhofen A, Hartmann T, Schottner M, Rohring C, Brodowsky H, Schmitt J, Keldenich J. Pharmaceutical Research, 2001, 18, 12, 1782-1788. [6] Elisabet Lazaro, Philip J. Lowe, Xavier Briand, Bernard Faller. J. Med. Chem. 2008, 51, 2009-2017

EVALUATION OF COMPOUND RE-PRECIPITATION FROM SALT SOLUTION FORMULATIONS : A NOVEL SCREENING TOOL FOR DISCOVERY SUPPORT

A novel tool was developed to optimize the selection of drug development candidates and identify, in an early discovery phase, potential issues for the development of formulations suitable for the preclinical and clinical trials. In the preclinical laboratories, the intravenous (IV) formulation intended for the preliminary \u201cin vivo\u201d assessment of the animal pharmacokinetics is always a challenge. In this early stage, the restricted timelines, the limited compound availability, the incomplete physico-chemical characterization and, quite often, the low water solubility of discovery compounds are important limits and impediments to develop an IV formulation screening. To overcome these limitations and to be able to formulate the discovery compounds the pharmaceutical scientists have to be aware of and understand some common solubilization strategies. pH adjustment and soluble salt formation, cosolvents, complexation, surfactants, emulsion, micelles and nano-microparticulate suspensions are the most frequently used formulation approaches. Among these methods, the pH adjustment and the soluble salt formation of an ionisable compound is the most biologically and clinically acceptable. An \u201cin situ salt formation technique\u201d is in house available for compounds with weak basic properties: this technique consists in a direct salification of a weak base powder with an equimolar quantity of strong acid. A potential drawback of this formulation approach is the occurrence of re-precipitation of the weak base upon dilution in the bloodstream at pH 7.4. The work described in this poster was aimed at setting-up and optimizing a fast automated screen for the \u201cin vitro\u201d evaluation of the potential \u201cin vivo\u201d re-precipitation. The results of this re-precipitation test were correlated with the solubility of the compounds in aqueous buffer at pH 7 and outcomes were obtained allowing to predict the potential \u201cin vivo\u201d re-precipitatio