Hexagonal silicon-germanium nanowire branches with tunable composition.

Hexagonal SiGe-2H has been recently shown to have a direct bandgap, and holds the promise to be compatible with silicon technology. Hexagonal Si and Ge have been grown on an epitaxial lattice matched template consisting of wurtzite GaP and GaAs, respectively. Here, we present the growth of hexagonal Si and SiGe nanowire branches grown from a wurtzite stem by the vapor-liquid-solid growth mode, which is substantiated byin situtransmission electron microscopy. We show that the composition can be tuned through the whole range of stoichiometry from Si to Ge, and the possibility to realize Si and SiGe heterostructures in these branches.

Shear-driven phase transformation in silicon nanowires.

We report on an unprecedented formation of allotrope heterostructured Si nanowires by plastic deformation based on applied radial compressive stresses inside a surrounding matrix. Si nanowires with a standard diamond structure (3C) undergo a phase transformation toward the hexagonal 2H-allotrope. The transformation is thermally activated above 500 °C and is clearly driven by a shear-stress relief occurring in parallel shear bands lying on {115} planes. We have studied the influence of temperature and axial orientation of nanowires. The observations are consistent with a martensitic phase transformation, but the finding leads to clear evidence of a different mechanism of deformation-induced phase transformation in Si nanowires with respect to their bulk counterpart. Our process provides a route to study shear-driven phase transformation at the nanoscale in Si.

An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease.

Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis.

Biochemical analysis of cerebrospinal fluid in the laboratories of deployed medical treatment facilities: are Multistix 10 SG strip and iSTAT useful?

INTRODUCTION: During military deployment, the diagnosis and the management of acute bacterial meningitis can be problematic, as deployed Medical Treatment Facilities (MTFs) often have a limited laboratory diagnostic capability. However, French Role 2 and 3 MTFs have point-of-care (POC) testing to perform urinary (Multistix 10 SG strip) and blood (iSTAT handheld analyser) biochemical testing mentioned in AMedP8.5. The purpose of this study was to compare the accuracy of this urine test strip and of the iSTAT CHEM8 and CG4 cartridges with a standard hospital bench top analyser in order to determine if these POC devices have a potential role in the biochemical analysis of cerebrospinal fluid (CSF protein, CSF glucose and CSF lactate, respectively). METHODS: Agreement between the index methods and the reference methods (suitable kits on the Cobas 6 000 System) was evaluated by parallel testing of 30 CSF samples by both techniques. For CSF protein, agreement between the strip and the reference method was evaluated determining the κ coefficient. For CSF glucose and CSF lactate subgroups, least squares linear regressions were calculated and Bland-Altman analyses were performed. RESULTS: The Multistix 10 SG strip can be used to make a semiquantitative determination of CSF protein. A good agreement between the strip and the reference method was observed (κ coefficient: 0.93 (IC95 0.82 to 1)). This strip is thus well adapted to demonstrate an elevation of CSF protein level as observed in acute bacterial meningitis. The iSTAT CHEM8 and CG4+ cartridges correlated well with the reference methods for the determination of CSF glucose and CSF lactate, respectively (r2>0.98) but exhibited a negative bias (∼ -7% and ∼ -15%, respectively). CONCLUSIONS: The combined use of the Multistix 10 SG strip and of the iSTAT system appears to be an attractive solution for the biochemical investigation of CSF in medical treatment facilities with limited laboratory diagnostic capability.

Allelic variation and differential expression of the mSIN3A histone deacetylase complex gene Arid4b promote mammary tumor growth and metastasis.

Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT-rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA-mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer.

Cadm1 is a metastasis susceptibility gene that suppresses metastasis by modifying tumor interaction with the cell-mediated immunity.

Metastasis is a complex process utilizing both tumor-cell-autonomous properties and host-derived factors, including cellular immunity. We have previously shown that germline polymorphisms can modify tumor cell metastatic capabilities through cell-autonomous mechanisms. However, how metastasis susceptibility genes interact with the tumor stroma is incompletely understood. Here, we employ a complex genetic screen to identify Cadm1 as a novel modifier of metastasis. We demonstrate that Cadm1 can specifically suppress metastasis without affecting primary tumor growth. Unexpectedly, Cadm1 did not alter tumor-cell-autonomous properties such as proliferation or invasion, but required the host's adaptive immune system to affect metastasis. The metastasis-suppressing effect of Cadm1 was lost in mice lacking T cell-mediated immunity, which was partially phenocopied by depleting CD8(+) T cells in immune-competent mice. Our data show a novel function for Cadm1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms, and this is the first report of a heritable metastasis susceptibility gene engaging tumor non-autonomous factors.

[The VR, the Russian version of the nerve agent VX]. / Le VR, version russe du neurotoxique organophosphoré VX.

A product of the arms race during the Cold War, the Russian VX, or VR, is an organophosphorus compound that is a structural isomer of the western VX compound (or A4), with which it shares a very high toxicity. It is much less studied and known than VX because the knowledge of its existence is relatively recent. A very low volatility and high resistance in the environment make it a persistent agent. Poisoning occurs mainly following penetration through skin and mucosa but vapour inhalation is a credible risk in some circumstances. The clinical presentation may be differed by several hours and despite the absence of signs and symptoms, the casualty should not be considered as contamination or intoxication-free. This agent has a long residence time in blood, a characteristics that clearly differentiates it from other compounds such as sarin. The protocols for antidote administration may thus have to be changed accordingly. The fact that VR poisoned individuals will less respond to the current oxime therapy used in France, the 2-PAM and that VR represents a higher threat than VX, being probably possessed by some proliferating states, justify the interest for this toxic product.

FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages.

SUMMARY: The hormone fibroblast growth factor 23 (FGF23) is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. In a cohort of 142 patients with CKD stages 2-5D, plasma FGF23 was independently associated with aortic calcification but not with pulse wave velocity or bone mineral density. INTRODUCTION: FGF23 is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. Previous studies related to FGF23 and vascular and bone outcomes have been restricted to dialysis patients. The aim of the present study was to establish whether or not plasma FGF23 is associated with aortic and coronary calcification, arterial stiffness, and bone mineral density in patients with early as well as late stages of CKD. METHODS: In a cohort of 142 patients with CKD stages 2-5D, we made routine biochemistry and intact FGF23 determinations, and assessed aortic and coronary calcification, bone mineral density (BMD), and arterial stiffness by multislice spiral computed tomography and automated pulse wave velocity (PWV). RESULTS: Plasma intact FGF23 levels were elevated in CKD patients; the elevation preceded that of serum phosphate in early-stage CKD. Patients with elevated FGF23 levels had higher aortic and coronary calcification scores than patients with lower FGF23 levels. Multivariate linear regression analysis indicated that only age (p < 0.001) and FGF23 (p = 0.008) were independently associated with aortic calcification score. Plasma FGF23 was neither associated with PWV nor with BMD. CONCLUSION: Our data suggest that plasma FGF23 is an independent biomarker of vascular calcification in patients with various CKD stages including early stages. The association between vascular calcification and FGF23 levels appears to be independent of BMD. It remains to be seen whether this association is independent of bone turnover and bone mass.

Interactions between polyphenols and macromolecules: quantification methods and mechanisms.

Non-covalent and covalent associations of polyphenols with food macromolecules are two of the most fundamental factors affecting the quality of polyphenol-rich food products. This review therefore describes the biochemical bases of associations between polyphenols and macromolecules, that is, proteins and polysaccharides. Our intent is to provide a level of understanding that can be used to underpin future research directions. This will help to resolve existing issues that limit organoleptic and nutritional qualities of polyphenol-rich foods and drinks. It will also allow a better understanding of the functional consequences of these interactions on food/biological systems. The methods used to study non-covalent and covalent interactions are described, and the limiting factors of each method are emphasized. The biochemical mechanisms of interaction between polyphenols and macromolecules are also described. In processed food, non-covalent polyphenol/macromolecule interactions are largely due to weak associations, and result from a combination of hydrogen bonds and hydrophobic interactions. The biochemical mechanisms for covalent interactions involve oxidation of phenolic compounds, whether enzymatically mediated or not, with the formation of o-quinones or o-semi-quinones, or the cleavage of procyanidin interflavanic bonds in acid medium with the formation of carbocations. The effects of factors such as polyphenol structure, macromolecule structure, relative concentrations of both polyphenol and macromolecule, solvent composition, ionic strength, temperature, and pH are discussed.

Composition and local strain mapping in Au-catalyzed axial Si/Ge nanowires.

For most applications, heterostructures in nanowires (NWs) with lattice mismatched materials are required and promise certain advantages thanks to lateral strain relaxation. The formation of Si/Ge axial heterojunctions is a challenging task to obtain straight, defect free and extended NWs. And the control of the interface will determine the future device properties. This paper reports the growth and analysis of NWs consisting of an axial Si/Ge heterostructure grown by a vapor-liquid-solid process. The composition gradient and the strain distribution at the heterointerface were measured by advanced quantitative electron microscopy methods with a resolution at the nanometer scale. The transition from pure Ge to pure Si shows an exponential slope with a transition width of 21 nm for a NW diameter of 31 nm. Although diffuse, the heterointerface makes possible strain engineering along the axis of the NW. The interface is dislocation-free and a tensile out-of-plane strain is noticeable in the Ge section of the NW, indicating a lattice accommodation. Experimental results were compared to finite element calculations.

Speech audiometry in noise: SNR Loss per age-group in normal hearing subjects.

OBJECTIVES: The present study aimed to determine normal SNR values per age group for the 50% speech reception threshold in noise (SNR Loss) on the VRB (Vocale Rapide dans le Bruit: rapid speech in noise) test. MATERIAL AND METHODS: Two hundred patients underwent pure-tone threshold and VRB speech-in-noise audiometry. Six ages groups were distinguished: 20-30, 30-40, 40-50, 50-60, 60-70 and>70 years. All subjects had normal hearing for age according to ISO 7029. SNR Loss was measured according to age group. RESULTS: Mean SNR Loss ranged from -0.37dB in the youngest age group (20-30 years) to +6.84dB in the oldest (>70 years). Range and interquartile range increased with age: 3.66 and 1.49dB respectively for 20-30 year-olds; 6 and 3.5dB for>70 year-olds. Linear regression between SNR Loss and age showed a coefficient R2 of 0.83. CONCLUSION: The present study reports SNR Loss values per age group in normal-hearing subjects (ISO 7029), confirming that SNR Loss increases with age. Scatter also increased with age, suggesting that other age-related factors combine with inner-ear aging to impair hearing in noise.

Guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL) and the French Society of Audiology (SFA) for Speech-in-Noise Testing in Adults.

OBJECTIVES: This document presents the fundamentals of speech audiometry in noise, general requirements for implementation and criteria for choice among the tests available in French according to the health-professional's needs. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors, audiologists and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: Eight tests of speech audiometry in noise can be used in France. CONCLUSION: To be complete, evaluation of hearing status requires testing understanding of speech in noise. The examination must begin with a minimum of two measurements familiarizing the subject with the test procedure. For initial diagnosis, adaptive procedures establishing the 50% speech reception threshold (SRT50) in noise are to be preferred in order to obtain a rapid and standardized measurement of perception of speech in noise. When the aim is to measure real-life speech comprehension, tests based on sentences, cocktail-party noise and free-field stimulation are to be preferred. Prosthetic gain is evaluated exclusively in free field. This is the only way to evaluate the contribution of binaurality and to measure perception in noise in an environment as close as possible to real life. In order to avoid acoustic interference in free field, at least five loudspeakers should be used, in particular for evaluating the effectiveness of directional microphones, CROS devices enabling sounds picked up in the damaged ear to be rerouted to the functional ear, or bimodal fitting (i.e., when hearing is enabled by two modalities: for example, hearing aid for one ear, cochlear implant for the other).

Effect of polyethylene glycol-based preservation solutions on graft injury in experimental kidney transplantation.

BACKGROUND: New preservation solutions are emerging, of various ionic compositions and with hydroxyethyl starch replaced by polymers such as polyethylene glycols (PEGs), offering the potential for 'immunocamouflage'. This experimental study investigated which of three clinically available preservation protocols offered the best graft protection, based on epithelial-to-mesenchymal transition (EMT) and fibrosis. METHODS: Kidneys were preserved for 24 h at 4° C with University of Wisconsin solution (UW)as standard, compared with solutions containing either 1 g/l PEG 35 kDa (Institute Georges Lopez solution, IGL) or 30 g/l PEG 20 kDa (solution de conservation des organes et des tissus, SCOT). Animals were followed for up to 3 months and development of EMT, tubular atrophy and fibrosis was evaluated in comparison with sham-operated animals. RESULTS: Functional recovery was better in the SCOT group compared with the other groups. Chronic fibrosis, EMT and inflammation were observed in the UW and IGL groups, but limited in the SCOT group. Levels of profibrosis markers such as transforming growth factor ß1, plasminogen activator inhibitor 1 and connective tissue growth factor were increased in IGL and UW groups compared with the SCOT group. Hypoxia-inducible factor (HIF) 1α and 2α expression was increased at 3 months in grafts preserved in UW and IGL, but detected transiently on day 14 when SCOT was used. Expression of HIF-regulated genes vascular endothelial growth factor and erythropoietin was increased in UW and IGL groups. CONCLUSION: The choice of colloid and ionic content is paramount in providing long-term protection against chronic graft injury after renal transplantation. Preservation solutions based on PEGs may optimize graft quality.

Bromodomain 4 activation predicts breast cancer survival.

Previous work identified the Rap1 GTPase-activating protein Sipa1 as a germ-line-encoded metastasis modifier. The bromodomain protein Brd4 physically interacts with and modulates the enzymatic activity of Sipa1. In vitro analysis of a highly metastatic mouse mammary tumor cell line ectopically expressing Brd4 demonstrates significant reduction of invasiveness without altering intrinsic growth rate. However, a dramatic reduction of tumor growth and pulmonary metastasis was observed after s.c. implantation into mice, implying that activation of Brd4 may somehow be manipulating response to tumor microenvironment in the in vivo setting. Further in vitro analysis shows that Brd4 modulates extracellular matrix gene expression, a class of genes frequently present in metastasis-predictive gene signatures. Microarray analysis of the mammary tumor cell lines identified a Brd4 activation signature that robustly predicted progression and/or survival in multiple human breast cancer datasets analyzed on different microarray platforms. Intriguingly, the Brd4 signature also almost perfectly matches a molecular classifier of low-grade tumors. Taken together, these data suggest that dysregulation of Brd4-associated pathways may play an important role in breast cancer progression and underlies multiple common prognostic signatures.

[Arsine: an unknown industrial chemical toxic]. / L'arsine : un toxique chimique industriel peu connu.

Arsines family includes many compounds with various toxicities. Arsenic trihydride or arsine is the most toxic form of arsenic. Powerful haemolytic gas, it has never been used as a chemical weapon because its toxicity is not immediate and it is non persistent. However, cases of industrial poisoning with arsine are still identified in spite of a strict regulation at work. It is also identified as a potential toxic of chemical terrorism. This agent, of which the mechanism of action is still not well defined, is badly recognized because of intoxications rarity. However, fast detection means are available. Health professionals and especially those who are involved in piratox plan need to learn to recognize arsine intoxication (hematuria, oliguria, haemolytic anemia) in order to provide early, specific treatment and avoid damages.

Protective proteins are differentially expressed in tomato genotypes differing for their tolerance to low-temperature storage.

When stored at low temperature, tomato fruits exhibit chilling injury symptoms, such as rubbery texture and irregular ripening. To identify proteins related to chilling tolerance, we compared two tomato near isogenic lines differing for their texture phenotype at harvest in a fruit-storage trial including two temperatures (4 and 20 degrees C) along several days of conservation. Fruit evolution was followed by assessing fruit color, ethylene emission and texture parameters. The most contrasted samples were submitted to proteomic analysis including two-dimensional electrophoresis and mass spectrometry of protein spots to identify the proteins, whose expression varied according to the genotype or the storage conditions. Unexpectedly, the most firm genotype at harvest was the most sensitive to cold storage. The other genotype exhibited a delay in fruit firmness loss leading to the texture differences observed after 20 days of 4 degrees C storage. The proteome analysis of these contrasted fruits identified 85 proteins whose quantities varied with temperature or genotype. As expected, cold storage decreased the expression of proteins related to maturation process, such as acidic invertase, possibly controlled post-translational regulation of polygalacturonase and up-regulated proteins related to freezing tolerance. However, the study point out proteins involved in the differential resistance to chilling conditions of the two lines. This includes specific isoforms among the large family of small heat shocked proteins, and a set of proteins involved in the defense against of the reticulum endoplasmic stress.

Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM) genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

Azimuthal sound source localization of various sound stimuli under different conditions.

AIM: To evaluate azimuthal sound-source localization performance under different conditions, with a view to optimizing a routine sound localization protocol. MATERIAL AND METHOD: Two groups of healthy, normal-hearing subjects were tested identically, except that one had to keep their head still while the other was allowed to turn it. Sound localization was tested without and then with a right ear plug (acute auditory asymmetry) for each of the following sound stimuli: pulsed narrow-band centered on 250Hz, continuous narrowband centered on 2000Hz, 4000Hz and 8000Hz, continuous 4000Hz warble, pulsed white noise, and word ("lac" (lake)). Root mean square error was used to calculate sound-source localization accuracy. RESULTS: With fixed head, localization was significantly disturbed by the earplug for all stimuli (P<0.05). The most discriminating stimulus was continuous 4000Hz narrow-band: area under the ROC curve (AUC), 0.99 [95% CI, 0.95-1.01] for screening and 0.85 [0.82-0.89] for diagnosis. With mobile head, localization was significantly better than with fixed head for 4000 and 8000Hz stimuli (P<0.05). The most discriminating stimulus was continuous 2000Hz narrow-band: AUC, 0.90 [0.83-0.97] for screening and 0.75 [0.71-0.79] for diagnosis. In both conditions, pulsed noise (250Hz narrow-band, white noise or word) was less difficult to localize than continuous noise. CONCLUSION: The test was more sensitive with the head immobile. Continuous narrow-band stimulation centered on 4000Hz most effectively explored interaural level difference. Pulsed narrow-band stimulation centered on 250Hz most effectively explored interaural time difference. Testing with mobile head, closer to real-life conditions, was most effective with continuous narrow-band stimulation centered on 2000Hz.

Interactions between globular proteins and procyanidins of different degrees of polymerization.

Interactions of proteins with phenolic compounds occur in food products containing vegetable sources, such as cocoa, cereals, or yogurts containing fruit. Such interactions can modify protein digestion and protein industrial properties. Noncovalent interactions between globular proteins (proteins important in industry) and procyanidins (phenolic compounds present in large quantity in fruits) were studied. The affinity constants between procyanidins of various average degrees of polymerization (DP) and lysozyme or alpha-lactalbumin were measured by isothermal titration calorimetry. The effects of these interactions on protein solubility and foam properties were examined using alpha-lactalbumin and BSA. Weak interactions were found with epicatechin and procyanidin dimers. Procyanidins of n = 5.5 and n = 7.4 showed medium (1.5 x 10(5) M(-1)) and high (8.69 x 10(9) M(-1)) affinities, respectively, for alpha-lactalbumin at pH 5.5, with n the average number of subunits per oligomer. A positive cooperativity of binding at low procyanidin:protein molar ratios was observed. The affinities of alpha-lactalbumin and lysozyme for procyanidins increased when the pH was close to the isoelectric pH. Solubility of lysozyme was strongly decreased by procyanidins of n = 5.5, whereas alpha-lactalbumin and BSA were less affected. Protein solubility in the presence of procyanidins was not affected by increased ionic strength but increased slightly with temperature. Procyanidins of n = 5.5 and n = 7.4 stabilized the average bubble diameter of foam formed with alpha-lactalbumin but had no effect on foam made from BSA. These results indicate that procyanidins of medium can lead to an undesirable decrease of protein solubility, but may play a positive role in foam stability.