Note of Caution for the Aqueous Behaviour of Metal-Based Drug Candidates

Poor aqueous solubility is one of the recurrent drawbacks of many compounds in medicinal chemistry. To overcome this limitation, the dilution of drug candidates from stock solutions of an organic solvent is common practice. However, the precise characterisation of these compounds in aqueous solutions is often neglected, leading to some uncertainties regarding the nature of the actual active species. In this communication, we demonstrate that two ruthenium complexes previously reported by our group for their chemotherapeutic potential against cancer, namely [Ru(DIP)₂(sq)](PF₆) and [Ru(DIP)₂(3-methoxysq)](PF₆), where DIP is 4,7-diphenyl-1,10-phenanthroline, sq=semiquinonate and 3-methoxysq=3-methoxysemiquinonate, form colloids in water-DMSO (1 % v/v) mixtures that are invisible to the naked eyes. [Ru(DIP)₂(3-methoxysq)](PF₆) was found to form a highly stable and monodispersed colloid with nanoaggregates of ∼25 nm. In contrast, [Ru(DIP)₂(sq)](PF₆) was found to form large reticulates of mostly spherical aggregates which size was found to increase over time. The difference in size and shape distribution of drug candidates is of tremendous significance as the study of their biological activity might be severely affected. Overall, we strongly believe that these observations should be taken into account by the scientific community working on the development of metal-based drugs with poor water solubility.     

Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Similarities and differences between male and female novice designers on color‐concept associations for warnings,action required,and signs and equipment status messages

This research examined the male and female novice designers toward color associations for the concepts used for ‘warnings’, ‘action required’, and ‘signs and equipment status’ through a questionnaire‐based study. A total of 178 Hong Kong Chinese final year undergraduate design students (89 males and 89 females) participated in the study. The test used required the participants to indicate their choice of one of nine colors to associations with each of 38 concepts in a color‐concept table, so that any one color could be associated with any one of the concepts. For both male and female groups of novice designers, chi‐square tests revealed a strong color association for each concept tested in this study (P < .05). The results showed males and females agreed on some color‐concept association stereotypes which were therefore gender neutral. The male and female novice designers had the same color associations and similar levels of stereotype strengths for 21 concepts. The nine strongest and therefore most useful color‐concept association stereotypes for both male and female novice designers were: red‐danger, red‐fire, red‐hot, red‐stop, red‐emergency, red‐error, blue‐cold, blue‐male, and green‐exit. However, the male and female novice designers had different color association stereotypes for the standby (green vs. yellow), emergency exit (green vs. red), and toxic (purple vs. black) concepts, and the strengths of the 14 remaining associations for both groups were not at equivalent levels. Overall, it is anticipated that the findings of this study will act as a useful reference for novice designers and other design practitioners to optimize color coding in the design of ‘warnings’, ‘action required’, and ‘signs and equipment status’ messages.     

Night and Day: Are Siblings as Different in Temperament as Parents Say They Are?

Twin studies suggest that parent ratings of temperament exaggerate differences between twins. The present study examined whether such contrast effects also operate for nontwin siblings. The activity level (AL) and shyness of 95 nontwin sibling pairs (ages 3 to 8 years) were assessed via parent ratings and objective measures (actigraph and observer ratings). Siblings showed no resemblance in either parent-rated AL or shyness; however, sibling resemblance for actigraph AL and observer-rated shyness was substantial. Thus, parents do contrast their nontwin siblings when rating these 2 temperament dimensions. Moreover, the importance of sibling differences in temperament to the sibling relationship and differential maternal treatment varied across the different measures of AL and shyness, suggesting that parent perceptions may play a role in these associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

HIPAA's Effect on Web Site Privacy Policies

Healthcare institutions typically post their privacy practices online as privacy policy documents. We conducted a longitudinal study that examines the effects of HIPAA's enactment on a collection of privacy policy documents for a fixed set of organizations over a four-year period. We present our analysis of 24 healthcare privacy policy documents from nine healthcare Web sites, analyzed using goal mining, a content-analysis method that supports extraction of useful information about institutions' privacy practices from documents. We compare our results to our pre-HIPAA study of these same institutions' online privacy practices and evaluate their evolution in the presence of privacy laws     

Preliminary<Emphasis Type="Italic">in vitro</Emphasis> and<Emphasis Type="Italic">in vivo</Emphasis> characterizations of a sol-gel derived bioactive glass-ceramic system

This study investigates quantitatively and qualitatively the sol-gel derived bioactive glass-ceramic system (BGS)—apatite-wollastonite (AW) type granules in the size range of 0.5–1 mm, as an effective graft material for bone augmentation and restoration. Scanning electron micrographs (SEM) of the sintered granules revealed the rough material surface with micropores in the range 10–30 μm. X-ray diffraction (XRD) pattern of the granules revealed the presence of crystalline phases of the hydroxyapatite and wollastonite, and the functional groups of the silicate and phosphates were identified by Fourier transform infrared spectroscopy (FT-IR). Thein vitro cell culture studies with L929 mouse fibroblast cell line showed very few cells adhered on the BGS disc after 24 h. This could be due to the highly reactive surface of the disc concomitant with the crystallization but not due to the cytotoxicity of the material, since the cellular viability (MTT assay) with the material was 80‰ Cytotoxicity and cytocompatibility studies proved that the material was non-toxic and biocompatible. After 12 weeks of implantation of the BGS granules in the tibia bone of New Zealand white rabbits, the granules were found to be well osteointegrated, as observed in the radiographs. Angiogram with barium sulphate and Indian ink after 12 weeks showed the presence of microcapillaries in the vicinity of the implant site implicating high vascularity. Gross observation of the implant site did not show any inflammation or necrosis. SEM of the implanted site after 24 weeks revealed good osteointegration of the material with the newly formed bone and host bone. New bone was also observed within the material, which was degrading. Histological evaluation of the bone healing with the BGS granules in the tibial defect at all time intervals was without inflammation or fibrous tissue encapsulation. After 2 weeks the new bone was observed as a trabeculae network around the granules, and by 6 weeks the defect was completely closed with immature woven bone. By 12 weeks mature woven bone was observed, and new immature woven bone was seen within the cracks of the granules. After 24 weeks the defect was completely healed with lamellar bone and the size of the granules decreased. Histomorphometrically the area percentage of new bone formed was 67.77% after 12 weeks and 63.37% after 24 weeks. Less bone formation after 24 weeks was due to an increased implant surface area contributed by the material degradation and active bone remodeling. The osteostimulative and osteoconductive potential of the BGS granules was established by tetracycline labelling of the mineralizing areas by 2 and 6 weeks. This sol-gel derived BGS granules proved to be bioactive and resorbable which in turn encouraged active bone formation.     

La capacité d'imitation à la naissance: Elle existe, mais que signifie-t-elle?

Much of the research on early imitations is restricted to the problem of their existence, without trying to describe them. The aim of this research is to analyze the principal characteristics of neonatal imitations in order to differentiate them from the later imitations. The behaviours of 16 neonates were filmed. A facial and a manual model were used. A detailed analysis of newborn behaviour revealed several features of early imitations: They were selective, quite exact, integrated, and occurred with short-time latencies. These results are interpreted within a cognitive framework. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular aspects of the transport and toxicity of ochratoxin a

Ochratoxins are a class of naturally occurring compounds produced by several fungi. The most toxic is ochratoxin A (OTA), and occurrence of some human nephropathies and tumors correlate with enhanced OTA exposure. In this Account, the following areas are examined: molecular details of the binding of OTA to human serum albumin (HSA), the influences of binding to HSA on the trans-port of OTA across epithelial cell membranes by organic anion transport proteins, the oxidative activation of OTA, and the formation of OTA adducts with biological molecules. These studies are beginning to provide a detailed chemical model for the trans-port, accumulation, and genotoxic and carcinogenic effects of OTA.     

Residual encoder-decoder up-sampling for structural preservation in noise removal

Multimedia Tools and Applications - While denoising 3D MRI, structural preservation is a very critical process in the medical region. However, Rician noise in MRI has affected the image quality...     

A new algorithm for sparse interpolation of multivariate polynomials

To reconstruct a black box multivariate sparse polynomial from its floating point evaluations, the existing algorithms need to know upper bounds for both the number of terms in the polynomial and the partial degree in each of the variables. Here we present a new technique, based on Rutishauser’s qd$qd$-algorithm, in which we overcome both drawbacks.