Impact of UV Radiation on the Raman Signal of Cystine: Implications for the Detection of S-rich Organics on Mars.

Traces of life may have been preserved in ancient martian rocks in the form of molecular fossils. Yet the surface of Mars is continuously exposed to intense UV radiation detrimental to the preservation of organics. Because the payload of the next rovers going to Mars to seek traces of life will comprise Raman spectroscopy tools, laboratory simulations that document the effect of UV radiation on the Raman signal of organics appear critically needed. The experiments conducted here evidence that UV radiation is directly responsible for the increase of disorder and for the creation of electronic defects and radicals within the molecular structure of S-rich organics such as cystine, enhancing the contribution of light diffusion processes to the Raman signal. The present results suggest that long exposure to UV radiation would ultimately be responsible for the total degradation of the Raman signal of cystine. Yet because the degradation induced by UV is not instantaneous, it should be possible to detect freshly excavated S-rich organics with the Raman instruments on board the rovers. Alternatively, given the very short lifetime of organic fluorescence (nanoseconds) compared to most mineral luminescence (micro- to milliseconds), exploiting fluorescence signals might allow the detection of S-rich organics on Mars. In any case, as illustrated here, we should not expect to detect pristine S-rich organic compounds on Mars, but rather by-products of their degradation.

The GALAXIES inelastic hard X-ray scattering end-station at Synchrotron SOLEIL.

GALAXIES is an in-vacuum undulator hard X-ray micro-focused beamline dedicated to the study of the electronic structure of materials with high energy resolution using both photoelectron spectroscopy and inelastic X-ray scattering and under both non-resonant (NR-IXS) and resonant (RIXS) conditions. Due to the penetrating power of hard X-rays and the `photon-in/photon-out' technique, the sample environment is not a limitation. Materials under extreme conditions, for example in diamond anvil cells or catalysis chambers, thus constitute a major research direction. Here, the design and performance of the inelastic X-ray scattering end-station that operates in the energy range from ∼4 keV up to 12 keV is reported, and its capabilities are highlighted using a selection of data taken from recently performed experiments. The ability to scan `on the fly' the incident and scattered/emitted X-ray energies, and the sample position enables fast data collection and high experimental throughput. A diamond X-ray transmission phase retarder, which can be used to generate circularly polarized light, will also be discussed in the light of the recent RIXS-MCD approach.

Thermodynamic properties of liquid gallium from picosecond acoustic velocity measurements.

Due to discrepancies in the literature data the thermodynamic properties of liquid gallium are still in debate. Accurate measurements of adiabatic sound velocities as a function of pressure and temperature have been obtained by the combination of laser picosecond acoustics and surface imaging on sample loaded in diamond anvil cell. From these results the thermodynamic parameters of gallium have been extracted by a numerical procedure up to 10 GPa and 570 K. It is demonstrated that a Murnaghan equation of state accounts well for the whole data set since the isothermal bulk modulus BT has been shown to vary linearly with pressure in the whole temperature range. No evidence for a previously reported liquid-liquid transition has been found in the whole pressure and temperature range explored.

Picosecond acoustics method for measuring the thermodynamical properties of solids and liquids at high pressure and high temperature.

Based on the original combination of picosecond acoustics and diamond anvils cell, recent improvements to accurately measure hypersonic sound velocities of liquids and solids under extreme conditions are described. To illustrate the capability of this technique, results are given on the pressure and temperature dependence of acoustic properties for three prototypical cases: polycrystal (iron), single-crystal (silicon) and liquid (mercury) samples. It is shown that such technique also enables the determination of the density as a function of pressure for liquids, of the complete set of elastic constants for single crystals, and of the melting curve for any kind of material. High pressure ultrafast acoustic spectroscopy technique clearly opens opportunities to measure thermodynamical properties under previously unattainable extreme conditions. Beyond physics, this state-of-the-art experiment would thus be useful in many other fields such as nonlinear acoustics, oceanography, petrology, in of view. A brief description of new developments and future directions of works conclude the article.

Equation of state of liquid mercury to 520 K and 7 GPa from acoustic velocity measurements.

Ultrafast acoustics measurements on liquid mercury have been performed at high pressure and temperature in a diamond anvil cell using picosecond acoustic interferometry. We extract the density of mercury from adiabatic sound velocities using a numerical iterative procedure. We also report the pressure and temperature dependence of the thermal expansion, isothermal and adiabatic compressibility, bulk modulus, and pressure derivative of the latter up to 7 GPa and 520 K. We finally show that the sound velocity follows a scaling law as a function of density in the overall measured metallic state.

How surface composition of high milk proteins powders is influenced by spray-drying temperature.

High milk proteins powders are common ingredients in many food products. The surface composition of these powders is expected to play an essential role during their storage, handling and/or final application. Therefore, an eventual control of the surface composition by modifying the spray-drying temperature could be very useful in the improvement of powder quality and the development of new applications. For this purpose, the influence of five spray-drying temperatures upon the surface composition of the powders was investigated by X-ray photoelectron spectroscopy. The major milk proteins were studied: native micellar casein and native whey, both more or less enriched in lactose. The results show a surface enrichment in lipids for all the powders and in proteins for many powders. Whatever the drying temperature, lipids and proteins are preferentially located near the surface whereas lactose is found in the core. This surface enrichment is also highly affected by the spray-drying temperature. More lipids, more proteins and less lactose are systematically observed at the surface of powders spray-dried at lower outlet air temperatures. The nature of proteins is also found essential; surface enrichment in lipids being much stronger for whey proteins containing powders than for casein containing powders. Additionally, we found a direct correlation between the lipids surface concentration and the wetting ability for the 25 powders studied.

All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial.

BACKGROUND: This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC). METHODS: Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m(-2) (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m(-2) (750 if >or=65 years of age) twice daily, on days 1-14. Treatment was continued until progression or unacceptable toxicity. RESULTS: A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36-66), including complete response in 4%. The clinical benefit rate (response or stable disease for >or=6 months) was 63% (95% CI, 48-77). The median duration of response was 7.2 months (95% CI, 6.4-10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8-9.7) and median overall survival was 29.2 months (95% CI, 18.2-40.1). Treatment-related adverse events were manageable, the main grade 3-4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed. CONCLUSION: These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MBC.

Assessing the unmet supportive care needs of newly diagnosed patients with cancer.

Adequate monitoring in cancer control needs to include measures of psychosocial outcomes so as to take account of the totality of the felt cancer experience. There is a need to know whether the experience of cancer is changing, as well as a need for tools to identify where supportive care interventions or services could be targeted to good effect. The aim of this study was to investigate the utility of using a telephone-administered survey to identify the unmet needs of cancer patients. Participants were identified from a statewide population-based cancer registry following an episode of hospitalized care in Victoria (Australia). Of the 506 eligible patients, 236 completed a telephone adaptation of the Supportive Care Needs Survey-Short Form (SCNS-SF31). Sampling from the cancer registry was shown to provide timely contact with patients. Results from the survey indicated that perceived needs for this newly diagnosed group of cancer patients were mostly in the area of information provision. Results also showed that some socio-demographic and disease-specific variables affected the level of perceived unmet needs. Overall, this study indicated that registry-based sampling was practical and the telephone adaptation of the SCNS-SF31 provided a reliable method to explore the unmet needs of newly diagnosed patients with cancer.

Detection of Echinococcus multilocularis in wild boars in France using PCR techniques against larval form.

Recently, new data have been collected on the distribution and ecology of Echinococcus multilocularis in European countries. Different ungulates species such as pig, goat, sheep, cattle and horse are known to host incomplete development of larval E. multilocularis. We report a case of E. multilocularis portage in two wild boars from a high endemic area in France (Department of Jura). Histological examination was performed and the DNA was isolated from hepatic lesions then amplified by using three PCR methods in two distinct institutes. Molecular characterisation of PCR products revealed 99% nucleotide sequence homology with the specific sequence of the U1 sn RNA gene of E. multilocularis, 99 and 99.9% nucleotide sequence homology with the specific sequence of the cytochrome oxydase gene of Echinococcus genus and 99.9% nucleotide sequence homology with a genomic DNA sequence of Echinococcus genus for the first and the second wild boar, respectively.

In vitro immunomodulating influence of methisoprinol on the head kidney phagocyte and lymphocyte activity after suppression induced by VHSV in rainbow trout (Oncorhynchus mykiss).

The aim of this study was to evaluate the in vitro influence of methisoprinol on head kidney phagocyte and lymphocyte activity after suppression induced by VHSV. The VHSV statistically significantly decreased the respiratory burst activity of head kidney phagocytes and the proliferative response of lymphocytes stimulated by ConA. The results of our study showed that methisoprinol at a concentration of 100 microl/ml modulated and restored the phagocyte and lymphocyte activity suppressed by VHSV.

Influence of methisoprinol on the replication of rhabdoviruses isolated from carp (Cyprinus carpio) and catfish (Ictalurus melas): in vitro study.

Rhabdoviruses constitute one of the most pathogenic viruses isolated from rainbow trout and carp culture. Several viruses were also isolated from other species of fish. These viruses are mostly associated with epizootics and heavy losses. Spring viraemia of carp virus (SVCV) and pike fry rhabdovirus (PFRV) have been the most extensively studied, due to their significant economic impact. Significant progress has been made towards controlling the major bacterial fish diseases using vaccines, but this approach has not yet been successful in preventing viral diseases in fish culture. However, for an effective therapeutic approach, specific drugs should be developed to selectively inhibit virus replication and/or stimulate antiviral protection. In this investigation we examined the in vitro influence of methisoprinol on the SVCV and virus isolated from catfish (Ictalurus melas) replication by measuring their RNA synthesis. The viruses were propagated in EPC cells and cell cultures containing methisoprinol were followed by infection with SVCV or catfish rhabdovirus suspension containing 10(7) TCID50/ml. Methisoprinol (Polfa, Poland) at concentrations of 0, 100, 200, 300, 400 and 500 microg/ml of medium (Glasgow MEM) was used in this study. The results of this study show the strong inhibition of incorporation (cpm) of [3H]-uridine into SVCV and catfish rhabdovirus RNA in cell culture exposed to methisoprinol at various concentrations. The highest percent of inhibition of viral RNA at 72 h after infection with two rhabdoviruses were observed in doses of 400 and 500 microg/ml of methisoprinol in medium. The results of this in vitro study showed that methisoprinol inhibits the rhabdoviruses isolated from carp and catfish.

A generalized heterozygote deficiency assessed with microsatellites in French common ash populations.

Common ash is a temperate forest tree with a colonizing behaviour, a discontinuous spatial distribution and a peculiar and poorly known mating system. Microsatellite markers were used to study the genetic structure in natural populations of common ash. Twelve populations located in northeastern France were analysed at five loci. Levels of genetic variability within and among stands were estimated for the seedling and adult stages. As expected for a forest tree, our results reveal high levels of intrapopulation diversity and a low genetic differentiation between stands. However, a general and significant heterozygote deficiency was found, with a mean F(IS) of 0.163 for the seedlings and of 0.292 for the adult trees. The different explanations for such an excess homozygosity are discussed: a nonMendelian inheritance of alleles, the presence of null alleles, a Wahlund effect and assortative mating.

Influence of HMB (beta-hydroxy-beta-methylbutyrate) on antibody secreting cells (ASC) after in vitro and in vivo immunization with the anti-Yersinia ruckeri vaccine of rainbow trout (Oncorhynchus mykiss).

In practice, protection of fish against disease by immunization is of limited effectiveness. Therefore, research is concentrated on how to improve the potency and efficacy of vaccines and how to optimally activate the cell-mediated immunity and the specific antibody response. In the present study, the influence of HMB (beta-Hydroxy-beta-methylbutyrate) on the antibody secreting cells (ASC) after both in vitro and in vivo immunization of rainbow trout (Oncorhynchus mykiss) with the anti-yersiniosis vaccine was studied. For in vitro immunization, the spleens from 160 fish were sampled and placed each in 35 mm sterile wells with medium containing HMB at concentrations of 0, 0.1, 1, 5, 10, 25, 50 or 100 microg/mL of medium. The spleens from 80 fish were injected with the vaccine and incubated at 14 degrees C for 10 days. For the in vivo study, fish were fed pellets containing HMB at doses of 0, 10, 25 and 50 mg/kg bw per day. After 2 weeks of HMB supplementation, the fish were immunized by intraperitoneal injection of the vaccine. At 7, 14, 18, 21, 28 and 35 days after immunization, pronephros were taken from 10 fish in each group for testing. When analyzed by the ELISPOT assay, HMB increased the number of splenic ASC after in vitro immunization at concentrations between 10 and 100 microg/mL (P < 0.05). Dietary HMB also increased the number of total and specific ASC when the fish were vaccinated in vivo. In conclusion, the results of the present study showed that HMB increases the levels of specific ASC after both in vitro and in vivo immunization of rainbow trout with the anti-Yersinia ruckeri vaccine.

Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11.

Congenital hyperinsulinism (CHI), previously named persistent hyperinsulinemic hypoglycemia of infancy, is characterized by profound hypoglycemia because of excessive insulin secretion. CHI presents as two different morphological forms: a diffuse form with functional abnormality of islets throughout the pancreas and a focal form with focal islet cell adenomatous hyperplasia, which can be cured by partial pancreatectomy. Recently, we have shown that focal adenomatous hyperplasia involves the specific loss of the maternal 11p15 region and a constitutional mutation of a paternally inherited allele of the gene encoding the regulating subunit of the K(+)(ATP) channel, the sulfonylurea receptor (ABCC8 or SUR1). In the present study on a large series of 31 patients, describing both morphological features and molecular data, we report that 61% of cases (19 out of 31) carried a paternally inherited mutation not only in the ABCC8 gene as previously described but also in the second gene encoding the K(+)(ATP) channel, the inward rectifying potassium channel (KCNJ11 or KIR6.2), in 15 cases and 4 cases, respectively. Moreover our results are consistent with the presence of a duplicated paternal 11p15 allele probably because of mitotic recombination or reduplication of the paternal chromosome after somatic loss of the maternal chromosome. In agreement with the loss of the maternal chromosome, the level of expression of a maternally expressed tumor suppressor gene, H19, was greatly reduced compared to the level of expression of the paternally expressed growth promoter gene, IGF2. The expression of IGF2 was on average only moderately increased. Thus, focal forms of CHI can be considered to be a recessive somatic disease, associating an imbalance in the expression of imprinted genes in the 11p15.5 region to a somatic reduction to homozygosity of an ABCC8- or KCNJ11-recessive mutation. The former is responsible for the abnormal growth rate, as in embryonic tumors, whereas the latter leads to unregulated secretion of insulin.

[Guided tissue regeneration in endodontics (2)]. / La régénération tissulaire guidée en endodontie (2e partie).

Part I of this article (J Can Dent Assoc 65:394-8) looked at the application of guided tissue regeneration (GTR) in endodontics, the mechanisms of action of GTR and its various presentations. Part II examines the technique for surgically inserting a membrane for GTR, based on a review of the current literature.

Effects of iridovirus-like agent on the cell-mediated immunity in sheatfish (Silurus glanis)--an in vitro study.

An iridovirus-like agent was tested for the first time in vitro on cell-mediated immunity in sheatfish (Silurus glanis). The influence of the iridovirus-like agent on pronephric macrophage metabolism was examined at two temperatures, 20 and 30 degrees C, by studying the respiratory burst activity stimulated by phorbol myristate acetate as well as the proliferative ability of lymphocytes stimulated by concanavalin A (ConA) and lipopolysaccharide (LPS) measured by MTT assay. The results showed that the iridovirus-like agent decreased the macrophage activity at incubation temperatures of 20 and 30 degrees C. The highest inhibitory effect was observed at 30 degrees C. The proliferative ability of pronephric lymphocytes had a similar pattern. The results showed that applying a virus at the same time or after the mitogen at 20 and 30 degrees C decreased the lymphocyte proliferation that was stimulated by either ConA or LPS. The highest suppressive effect was observed when virus was applied 14 h after the mitogen. This preliminary in vitro study demonstrated a strong suppressive influence of the iridovirus-like agent on pronephric macrophage and lymphocyte activity in sheatfish.

Effects of dimerized lysozyme (KLP-602) on the cellular and humoral defence mechanisms in sheatfish (Silurus glanis): in vitro and in vivo study.

This study examined the effects of the dimerized lysozyme (KLP-602) on the immunocompetence cell activity in sheatfish (Silurus glanis) and its influence in vivo on the non-specific defence mechanisms and protection against motile aeromonad septicaemia (MAS). The in vitro study showed that the lysozyme dimer (KLP-602), at concentrations between 5 and 50 micrograms/mL of medium significantly (P < 0.05) increased the respiratory burst activity and potential killing activity of pronephric macrophages, as well as the proliferative ability of pronephric lymphocytes stimulated by ConA and LPS. The in vivo study showed that injecting lysozyme dimer (Lydium-KLP) intraperitoneally at doses of 50 micrograms/kg bw stimulated cell-mediated and humoral-mediated imunity. On day 5, after application of Lydium-KLP in vivo, a statistically higher (P < 0.05) respiratory burst activity and potential killing activity of blood and pronephros phagocytes were observed. A higher proliferative ability of blood and pronephros lymphocytes stimulated by Concanavaline A (ConA) or lipopolysaccharide (LPS) was also observed. At the same time, the myeloperoxidase activity in the PMN cells and the lysozyme activity and total Ig levels in serum were significantly higher (P < 0.05), compared to the control group. A challenge test with Aeromonas hydrophila showed that dimerized lysozyme increased the protection against MAS. Dimerized lysozyme stimulates non-specific cellular and humoral mechanisms and protection against MAS in sheatfish.

[Guided tissue regeneration in endodontics. Part 1]. / La régénération tissulaire guidée en endodontie. (1re partie).

Over the past twenty years, Guided Tissue Regeneration (GTR) has become an accepted technique for the treatment of tissue loss consequent to periodontal disease. The principles of GTR have recently begun to be employed in endodontics since pulpal necrosis often leads to periodontal tissue loss as a result of the leakage of noxious irritants through apical foramina and accessory canals. This treatment modality is still in its early days for the management of endo-perio lesions and is most appropriately used in specific types of cases. This article, the first of a two-part series, presents a review of the literature about the mechanisms of action of GTR and discusses some of the products used to bring about GTR.

Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.

Congenital hyperinsulinism, or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is a glucose metabolism disorder characterized by unregulated secretion of insulin and profound hypoglycemia. From a morphological standpoint, there are two types of histopathological lesions, a focal adenomatous hyperplasia of islet cells of the pancreas in approximately 30% of operated sporadic cases, and a diffuse form. In sporadic focal forms, specific losses of maternal alleles (LOH) of the imprinted chromosomal region 11p15, restricted to the hyperplastic area of the pancreas, were observed. Similar mechanisms are observed in embryonal tumors and in the Beckwith-Wiedemann syndrome (BWS), also associated with neonatal but transient hyperinsulinism. However, this region also contains the sulfonylurea receptor (SUR1) gene and the inward rectifying potassium channel subunit (KIR6.2) gene, involved in recessive familial forms of PHHI, but not known to be imprinted. Although the parental bias in loss of maternal alleles did not argue in favor of their direct involvement, the LOH may also unmask a recessive mutation leading to persistent hyperinsulinism. We now report somatic reduction to hemizygosity or homozygosity of a paternal SUR1 constitutional heterozygous mutation in four patients with a focal form of PHHI. Thus, this somatic event which leads both to beta cell proliferation and to hyperinsulinism can be considered as the somatic equivalent, restricted to a microscopic focal lesion, of constitutional uniparental disomy associated with unmasking of a heterozygous parental mutation leading to a somatic recessive disorder.