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SummaryEarly during neuromuscular development, acetylcholine receptors (AChRs) accumulate at the center of muscle fibers, precisely where motor growth cones navigate and synapses eventually form. Here, we show that Wnt11r binds to the zebrafish unplugged/MuSK ectodomain to organize this central muscle zone. In the absence of such a zone, prepatterned AChRs fail to aggregate and, as visualized by live-cell imaging, growth cones stray from their central path. Using inducible unplugged/MuSK transgenes, we show that organization of the central muscle zone is dispensable for the formation of neural synapses, but essential for AChR prepattern and motor growth cone guidance. Finally, we show that blocking noncanonical dishevelled signaling in muscle fibers disrupts AChR prepatterning and growth cone guidance. We propose that Wnt ligands activate unplugged/MuSK signaling in muscle fibers to restrict growth cone guidance and AChR prepatterns to the muscle center through a mechanism reminiscent of the planar cell polarity pathway.

Los canceres de la orofaringe se producen en pacientes que suelen tener un mal estado general y, por lo general, se diagnostican de forma tardia. Por consiguiente, los tratamientos que se realizan son complejos, con un papel destacado de la cirugia cuando el paciente es operable y el tumor es resecable. Las bucofaringectomias estan bien sistematizadas y no justifican por si solas un enesimo articulo. En cambio, las tecnicas de reconstruccion han experimentado un desarrollo considerable. El planteamiento quirurgico que precede a la posible tecnica de reconstruccion se basa en un enfoque metodico de la indicacion y de la eleccion del colgajo, lo que se desarrollara en este articulo. Los aspectos que rodean a esta intervencion se han modificado en gran medida. Estas operaciones complejas se enmarcan en un tratamiento cada vez mas especifico del estado general del paciente. Ademas, recurren a un plan terapeutico en el que se suele asociar la radioterapia con la quimioterapia, cuyas modalidades tambien han experimentado una intensa evolucion en la ultima decada. La bucofaringectomia y su reconstruccion son esenciales en el arsenal del cirujano oncologico para ofrecer a los pacientes las mejores posibilidades de curacion en unas condiciones aceptables.

Twenty-two tandemly arranged protocadherin-gamma (Pcdh-gamma) genes encode transmembrane proteins with distinct cadherin-related extracellular domains and a common intracellular domain. Genetic studies have implicated Pcdh-gamma genes in the regulation of neuronal survival and synapse formation. Because mice lacking the Pcdh-gamma cluster die perinatally, we generated conditional mutants to analyze roles of Pcdh-gamma genes in the development and function of neural circuits. Retina-specific deletion of Pcdh-gammas led to accentuation of naturally occurring death of interneurons and retinal ganglion cells (RGCs) during the first two postnatal weeks. Nonetheless, many neuronal subtypes formed lamina-specific arbors. Blocking apoptosis by deletion of the pro-apoptotic gene Bax showed that even neurons destined to die formed qualitatively and quantitatively appropriate connections. Moreover, electrophysiological analysis indicated that processing of visual information was largely normal in the absence of Pcdh-gamma genes. These results suggest that Pcdh-gamma genes are dispensable for elaboration of specific connections in retina, but play a primary role in sculpting neuronal populations to appropriate sizes or proportions during the period of naturally occurring cell death.

Objective—To characterize and evaluate risk factors for suture-associated cystoliths in dogs and cats. Design—Retrospective case-control study. Animals—163 dogs and 13 cats with suture-associated cystoliths and 326 control dogs and 26 control cats with non–suture-associated cystoliths. Procedures—Submissions to the Canadian Veterinary Urolith Centre received from 1999 to 2006 were reviewed. Case dogs and cats had cystoliths associated with visible suture or with hollow, cylindrical channels or suture knot impressions consistent with dissolved suture. Control dogs and cats had at least a single recurrent non–suture-associated cystolith submitted closest in time to the sample case. Associations among cystolith composition, recurrence times, sex, age, and breed were evaluated. Results—Cases consisted of 92 dogs and 7 cats with visible suture and 71 dogs and 6 cats with dissolved suture. Suture-associated cystoliths represented 0.6% of canine cystoliths, 9.4% of recurrent canine cystoliths, 0.17% of feline cystoliths, and 4% of recurrent feline cystoliths. Sexually intact and neutered males were at increased odds of suture-associated cystoliths, relative to spayed female dogs. Shih Tzus, Lhasa Apsos, and Pomeranians were significantly predisposed to form suture-associated cystoliths. In dogs, compound suture-associated cystoliths were significantly more likely than other cystolith types (OR, 8.6). Dogs with suture-associated cystoliths had significantly shorter recurrence times than did control dogs. Conclusions and Clinical Relevance—Suture remnants in the bladder have an important role in recurrent cystolithiasis in dogs. Identification of risk factors is important for avoiding recurrence of iatrogenic cystoliths.

Summary Dogs that participate in animal-assisted interventions (AAIs), often called ‘therapy dogs’, commonly interact with humans whose immune systems are not functioning optimally. The advisability of feeding raw meat (including poultry) to these animals remains a highly contentious issue, in spite of increasing evidence that raw meat is frequently contaminated with Salmonella. We set out to determine if consuming raw meat influences the risk of therapy dogs shedding Salmonella and other pathogens. Two hundred healthy therapy dogs from Ontario and Alberta were enrolled. Between May 2005 and November 2006, fecal specimens were collected from each dog every 2 months for 1 year, along with a log of places visited, antimicrobial use within the home, dog health status and diet. Specimens were cultured for Salmonella, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum cephalosporinase (ESC) Escherichia coli and Clostridium difficile. Forty (20%) of the dogs were reported to have been fed raw meat at some point during the year. The incidence rate of Salmonella shedding in the raw meat-fed dogs was 0.61 cases/dog-year, compared with 0.08 cases/dog-year in dogs that were not fed raw meat (P < 0.001). Controlling for therapy dog group, the repeated measures, and pig ear consumption and diarrhoea in the 2 months prior to specimen submission, dogs that consumed raw meat were significantly more likely to test positive for Salmonella at least once during the year than dogs that did not eat raw meat [odds ratio (OR) 22.7; 95% confidence interval (CI) 3.1–58.8; P < 0.001]. Specific Salmonella serovars were more common among dogs that consumed raw meat versus those that did not include S. Typhimurium, S. Heidelberg and S. Kentucky. Raw meat consumption was also significantly associated with shedding ESC E. coli (OR 17.2; 95% CI 9.4–32.3). No associations between C. difficile, MRSA or VRE and consumption of raw meat were detected. We recommend that dogs fed raw meat should be excluded from AAI programmes, particularly when the programmes involve interaction with humans at high risk of infection or adverse sequelae attributable to infection. Furthermore, although AAI dogs may not be representative

26Al was the first cosmic radioactivity ever detected in the galaxy as well as one of the first extinct radioactivity observed in refractory phases of meteorites. Its nucleosynthesis in massive stars is still uncertain mainly due to the lack of nuclear information concerning the 26Al(n,p)26Mg and 26Al(n,α)23Na reactions. We report on a single and coincidence measurement of the 27Al(p,p’)27Al(p)26Mg and 27Al(p,p’)27Al(α)23Na reactions performed at the Orsay TANDEM facility aiming at the spectroscopy study of 27Al above the neutron threshold. Fourteen states are observed for the first time within 350 keV above the 26Al+n threshold.

Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.

Background: Previously our group associated early life gut microbial alterations in one-year-old children with risk of active asthma at school age. These early life alterations were characterized by significant reductions in four bacterial genera and a decreased production of microbial derived metabolites. We hypothesize that this early life gut microbial dysbiotic state is also associated with asthma diagnosed in children by three years of age and aim to identify additional bacterial populations that might be contributing to this asthmatic phenotype. Methods: 286 children enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified according to the diagnosis of asthma by three years of age. Bacterial 16S rDNA from 3-month and 1-year stool samples from these children was extracted, amplified, and subjected to high throughput Illumina sequencing. Bacterial genera were quantified by quantitative PCR in 16S rDNA samples from all asthmatic children and a subset of controls. An exact logistic regression model was used to assess the effects of potentially confounding variables (i.e. antibiotic exposure, mode of birth). Results: 16S sequence analysis of our sample cohort (286 subjects) identified differentially abundant bacterial populations between asthmatics and controls at 3-months of age. Additionally, qPCR identified significant shifts in the abundance of specific bacterial genera at 3-months and 1-year of age in the asthmatic group when compared to controls. Conclusions: Shifts in the relative abundance of certain gut bacterial populations in early life are associated with asthma diagnosed in children by three years of age.

International audience; Pairing and quartetting are competing phenomena in nuclei. In the selfconjugate nuclei from the fp-shell, the competition between T=0 pairing (deuteron-like) and alpha clusterisation is predicted to be a_ected by the spin-orbit interaction. In order to probe the alpha structure of fp-shell nuclei, the nuclear break-up of ^40Ca and ^40Ar has been measured at GANIL. The alpha spectroscopic factors obtained for the N=Z nucleus and the N!=Z nuclei do not reflect any difference. This might be an indication that the tail of the wave function in not sensitive to nuclear asymmetry. Perspectives for probing the deuteron-like pairing (T=0) are given.

The cosmological 7Li problem arises from the signi cant discrepancy of about a factor 3 between the predicted primordial 7Li abundance and the observed one. The main process for the production of 7Li during Big-Bang nucleosynthesis is the decay of 7Be. Many key nuclear reactions involved in the production and destruction of 7Be were investigated in attempt to explain the 7Li de cit but none of them led to successful conclusions. However, some authors suggested recently the possibility that the destruction of 7Be by 3He and 4He may reconcile the predictions and observations if missing resonant states in the compound nuclei 10C and 11C exist. Hence, a search of these missing resonant states in 10C and 11C was investigated at the Orsay Tandem-Alto facility through 10B(3He,t)10C and 11B(3He,t)11C charge-exchange reactions respectively. After a short overview of the cosmological 7Li problem from a nuclear physics point of view, a description of the Orsay experiment will be given as well as the obtained results and their impact on the 7Li problem.

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.

Induction and patterning of the mesodermal germ layer is a key early step of vertebrate embryogenesis. We report that FoxD3 function in the Xenopus gastrula is essential for dorsal mesodermal development and for Nodal expression in the Spemann organizer. In embryos and explants, FoxD3 induced mesodermal genes, convergent extension movements, and differentiation of axial tissues. Engrailed-FoxD3, but not VP16-FoxD3, was identical to native FoxD3 in mesoderm-inducing activity, indicating that FoxD3 functions as a transcriptional repressor to induce mesoderm. Antagonism of FoxD3 with VP16-FoxD3 or morpholino-knockdown of FoxD3 protein resulted in a complete block to axis formation, a loss of mesodermal gene expression, and an absence of axial mesoderm, indicating that transcriptional repression by FoxD3 is required for mesodermal development. FoxD3 induced mesoderm in a non-cell-autonomous manner, indicating a role for secreted inducing factors in the response to FoxD3. Consistent with this mechanism, FoxD3 was necessary and sufficient for the expression of multiple Nodal-related genes, and inhibitors of Nodal signaling blocked mesoderm induction by FoxD3. Therefore, FoxD3 is required for Nodal expression in the Spemann organizer and this function is essential for dorsal mesoderm formation.

Objective.To determine the distribution of canine-visitation programs in Ontario and to characterize the nature of the programs the dogs are affiliated with.Design.A cross-sectional survey of hospitals in Ontario was used to determine whether they permitted dogs to visit patients and, if so, where the dogs originated. On the basis of this information, dog owners were then contacted through their respective associations and interviewed using a standardized questionnaire.Setting.A cross-section of hospitals in Ontario.Participants.A total of 223 (97%) of the 231 hospitals surveyed responded. Ninety owners of 102 visitation dogs were interviewed.Results.A total of 201 (90%) of the 223 hospitals indicated that dogs were permitted in their facilities. Origins ranged from national therapy-dog agencies to the patients' families. Acute care wards were 5.1 times as likely than other wards to disallow animals (95% confidence interval, 2.2-12.2; PConclusions.Although canine-visitation programs have become standard practice in nonacute human healthcare facilities, infection control and dog-screening practices are highly variable and potentially deficient. Hospital staff, visitation groups, pet owners, and veterinarians need to work together to protect both people and pets.

Los canceres de la hipofaringe suelen aparecer en pacientes que presentan mal estado general y de forma habitual su diagnostico es tardio. Cuando son operables, requieren a menudo una intervencion radical. Los progresos de la quimioterapia han permitido iniciar investigaciones clinicas para evitar esta cirugia tan mutilante, lo que se ha conseguido en algunos casos. Sin embargo, la cirugia conserva numerosas indicaciones. La cirugia endoscopica con laser de CO2 permite, en casos muy seleccionados, la reseccion de pequenos tumores de localizacion alta. La faringectomia parcial lateral permite la reseccion de tumores relativamente limitados de la pared externa de la hipofaringe, mientras que las hemilaringofaringectomias supragloticas o supracricoideas permiten la extirpacion de los tumores limitados de la parte superior del muro faringolaringeo. La faringolaringectomia total sigue siendo, aunque es muy mutilante, un tratamiento excelente para los tumores mas avanzados que no son susceptibles de la conservacion laringea. Las faringolaringectomias circulares pueden permitir la exeresis de tumores mas evolucionados cuando la extension locorregional y el estado del paciente lo permiten. Por ultimo, la cirugia reconstructiva ha permitido efectuar mejores exeresis y ha mejorado de forma considerable los resultados de la cirugia en el paciente irradiado.

El cancer de laringe es frecuente en Europa mediterranea, donde representa el 3% de los canceres en el varon. El factor esencial de la oncogenesis laringea es el tabaco, a menudo asociado a un consumo excesivo de bebidas alcoholicas. Ciertas exposiciones profesionales tambien parecen responsables de la aparicion de este tipo de cancer. A pesar de los signos de aparicion precoz, un gran numero de tumores laringeos, sobre todo supragloticos, se diagnostica en un estado relativamente avanzado. El estudio de extension se basa en una endoscopia minuciosa y en las pruebas de imagenes con cortes de calidad. Existen multiples tecnicas quirurgicas parciales y radicales que permiten adaptar la exeresis a cada tipo de extension local. La cirugia endoscopica con laser ha adquirido un lugar indiscutible en el tratamiento de este tipo de cancer. La radioterapia transcutanea es una alternativa para los tumores muy localizados y exofiticos, y su lugar en el tratamiento de las formas mas avanzadas esta en evolucion gracias a la aparicion de nuevas modalidades tecnicas y a la asociacion a la quimioterapia, sobre todo en las estrategias de conservacion laringea. El pronostico global es el mejor dentro del grupo de los distintos tumores de las vias aerodigestivas superiores. En conjunto, mas del 50% de los pacientes sobrevive a los 5 anos.

Longtemps la chirurgie radicale et la radiotherapie ont ete les deux seules options du traitement des tumeurs avancees du pharyngo-larynx. Les progres de la chirurgie partielle, endoscopique ou non, et ceux de la radiotherapie exclusive ont permis d’eviter dans un certain nombre de cas la mutilation laryngee. La chimiotherapie a acquis une place de choix dans ces strategies de preservation de la fonction laryngee. Plusieurs sequences sont realisables: chimiotherapie et radiotherapie sequentielles, chimiotherapie et radiotherapie concomitantes ou, plus recemment, radio-chimiotherapie sequentielle. L’apparition de nouveaux agents cyto-toxiques et des therapeutiques ciblees doit egalement etre prise en compte. Plus que jamais une approche pluridisciplinaire s’impose pour adapter le traitement le plus approprie et pour determiner les futures etudes cliniques.

Through process control, from BOF down to finishing lines, has been developed and implemented. It features real time on line control of defects, risk assessment and the prediction of the mechanical properties. This innovative process control makes it possible to reduce drastically the standard work load of the Metallurgy and Quality Department. The experienced staff can then be appointed new ambitious objectives towards the industrial excellence: “The right product at the right time for the right cost”, “Meeting customer needs” and “Respect the firm's economic objectives”. To achieve this, business organization must be adapted. Key factors are intelligent listening to the final customer needs and process route optimization from the BOF to our customer facilities, paying particular attention to synergies between the hot and the cold mills.

SNARK is a member of the AMPK subfamily of serine/threonine protein kinases. In this study, we examined the regulation of SNARK activity in kidney (BHK, HEK293), pancreatic beta-cell insulinoma (INS-1), hepatocarcinoma (H4IIE) and keratinocyte (NRKC)-derived cell lines in response to diverse cellular stresses. We show that SNARK activity is regulated by glucose- or glutamine-deprivation, induction of endoplasmic reticulum stress by homocysteine or DTT, elevation of cellular AMP and/or depletion of ATP, hyperosmotic stress, salt stress, ultraviolet B radiation and oxidative stress caused by hydrogen peroxide. Moreover, the regulation of SNARK activity in response to cellular stresses depends greatly upon cell type. Furthermore, SNARK activity is downregulated by metformin in a dose- and time-dependent manner in H4IIE cells. These observations support a role for SNARK as a molecular component of the cellular stress response.

Lymph node metastases of squamous cell carcinomas in the neck can appear cystic. Without a clinically apparent primary tumour they can classically be considered to originate in a branchial cleft. We report two cases of cystic squamous cell carcinoma with histopathologic criteria of branchial cleft carcinoma. After a review of the literature, diagnostic strategies, histopathologic features, and therapeutic options for this very controversial clinical situation are discussed. We conclude by suggesting that Martin's criteria, largely used to differentiate between a cystic metastasis of a squamous cell carcinoma and a very theoretical branchial cleft carcinoma should be abandoned for lack of applicability.

Head and neck cancer can be a devastating disease. The mainstays of treatment for early stage disease are either radiotherapy or surgery. However, although disease responds well at this stage, the risk of a second primary cancer is high, with a development rate of about 4% per year. Advanced diseases are treated either by surgery with postoperative radiotherapy or by definitive radiotherapy, with surgery in reserve for salvage if necessary. Over the past two decades major advances have been made in surgery (reconstructive surgery, non-mutilating surgery). Either definitive or postoperative, radiotherapy is an integral part of the treatment for the majority of non-metastatic stages of disease and ways of improving the effects of radiotherapy are constantly being explored. Good activity has been reported for the use of altered radiation fractionation regimens, which allow the delivery of intensified radiation doses. In addition, in recent years randomized trials and meta-analyses have confirmed the survival benefit of adding chemotherapy to radiotherapy in a number of different settings. Cisplatin-based regimens have been identified as the most active and are now standard treatment choices. The survival benefits of chemotherapy appear to be limited to concomitant administration and do not extend to neoadjuvant administration, although this has demonstrated clinical utility in preserving organ function. Platinum-based combination chemotherapy is by many clinicians considered the standard approach to the treatment of recurrent/metastatic disease for patients who are able to tolerate such regimens, but the prognosis for these patients remains poor; this is particularly true for those whose disease progresses on such therapy. This paper discusses current approaches and recent advances in the treatment of head and neck cancer, specifically squamous cell carcinoma, and suggests future management aims for the different disease stages.

Resumen El pronostico de los canceres de la hipofaringe sigue siendo muy desfavorable, a pesar de los progresos que han experimentado las tecnicas de diagnostico por imagen, la cirugia y la radioterapia, asi como el desarrollo de tratamientos quimioterapicos cada vez mas eficaces. Estos canceres suelen aparecer en pacientes con antecedentes importantes de consumo de alcohol y tabaco, haciendo que en la mitad de los casos la comorbilidad dificulte la aplicacion de tratamientos agresivos. En mas de las tres cuartas partes de los casos, estos canceres se diagnostican en estadios avanzados. Mientras que en los pocos casos que se diagnostican en fase incipiente puede plantearse la radioterapia o la cirugia parcial, los tumores avanzados casi siempre se tratan mediante cirugia radical y radioterapia postoperatoria. La supervivencia a los 5 anos no supera el 50% en el primer caso y el 35% en el segundo. La supervivencia de los pacientes que reciben tratamiento paliativo es muy baja (inferior al 10% a los 2 anos). El unico avance real que se ha producido en los ultimos 20 anos es la aparicion de estrategias de preservacion de la laringe, que se indican unicamente en casos seleccionados, permitiendo asi evitar la laringectomia total en la mitad de ellos, aunque sin conseguir mejorar la supervivencia. Las principales vias de investigacion se centran actualmente en las modernas modalidades de irradiacion, los protocolos de radioquimioterapia concomitante y los tratamientos biorreductores.

Previously we have identified a cis-acting regulatory domain in the human type X collagen gene upstream of the transcription start site which acts as a strong enhancer in hypertrophic, but not in resting chondrocytes. Here we show that this enhancer is highly conserved also in the murine and bovine Col10a1 genes, but not found in the known promoter sequences of chicken Col10a1. It contains a functionally active AP-1 site (TPA Responsive Element, TRE) which is essential for the high transcriptional activity of the COL10A1 enhancer in transiently transfected hypertrophic chondrocytes. Gel-shift experiments with nuclear extracts of hypertrophic chondrocytes revealed FosB and Fra-1 as candidates regulating AP-1 factors binding to the TRE site. In fact, coexpression of FosB and Fra-1 in reporter gene assays greatly stimulated transcriptional activity of enhancer bearing reporter genes. Quantitative analysis of AP-1 factor mRNA levels in distinct fractions of fetal bovine epiphyseal chondrocytes by real-time PCR confirmed significant levels of FosB and Fra-1 mRNA besides other AP-1 factors in hypertrophic chondrocytes. A key role of the enhancer element in regulating tissue-specific expression of the Col10a1 gene was shown by establishing transgenic mouse lines with a reporter gene containing a 4.6 kb murine Col10a1 promoter fragment which included the enhancer, exon 1, part of exon 2 and the first intron. Reporter gene expression was seen exclusively in hypertrophic cartilages in the growth plates of long bones, ribs, vertebrae, sternum and mandibles of 17.5-18.5 dpc embryos, confirming that the 4.6 kb promoter is able to drive specific expression of Col10a1 in hypertrophic cartilage. These established transgenic lines should facilitate the genetic analysis of regulatory pathways of chondrocyte maturation and Col10a1 gene expression in the future.

Rearrangement of the FLI-1 locus and ensuing overexpression of FLI-1 protein is an early event in Friend murine leukemia virus (F-MuLV)-induced erythroleukemia. When overexpressed in primary erythroblasts, FLI-1 converts erythropoietin (Epo)-induced terminal differentiation into a proliferative response. We found that SLAP, a gene encoding a recently described negative regulator of T-cell antigen receptor function during thymocyte development, is up-regulated both at the RNA and protein levels in FLI-1-transformed erythroblasts. Src-like adaptor protein (SLAP) was found in a specific complex with erythropoietin receptor (EpoR), a cytokine receptor essential to erythroid differentiation. Constitutive expression of SLAP severely impairs hemoglobinization and late survival during Epo-induced terminal differentiation of erythroblasts. This impairment is associated with the specific inhibition of several critical Epo-dependent signaling events, including signal transducer and activator of transcription 5 (STAT5) activation and up-regulation of the expression of the antiapoptotic BCL-X gene. Our data support a model by which FLI-1 inhibits normal erythroid differentiation through the deregulation of genes encoding adaptors/effectors that modify the signaling output of cytokine receptors normally required for terminal differentiation. (Blood. 2003; 102:4555-4562)

An experimental and numerical study was performed about the influence of incoming wakes and the calming effect on a very high lift low pressure turbine rotor blade. The first part of the paper describes the experimental determination of the pressure loss coefficient and the heat transfer around the blade mounted in a high speed linear cascade. The cascade is exposed to incoming wakes generated by high speed rotating bars. Their aim is to act upon the transition/separation phenomena. The measurements were conducted at a constant exit Mach number equal to 0.8 and at three Reynolds number values, namely 190000, 350000 and 650000. The inlet turbulence level was fixed at 0.8%. An additional feature of this work is to identify the boundary layer status through heat transfer measurements. Compared to the traditionally used hot films, thin film heat flux gages provide fully quantitative data required for code validation. Numerical computations are presented in the second part of the paper.Copyright © 2002 by ASME

The strength functions of the πf5/2πf5/2, πp3/2πp3/2 and πf7/2πf7/2 orbitals in neutron-rich 71Cu were obtained in a 72Zn(d,3He)71Cu proton pick-up reaction in inverse kinematics using a radioactive beam of 72Zn at 38 MeV/u. A dedicated set-up was developed to overcome the experimental challenges posed by the low cross section of the reaction and the low energy of the outgoing 3He particles. The excitation-energy spectrum was reconstructed and spectroscopic factors were obtained after analysis of the angular distributions with the finite-range Distorted-Wave Born Approximation (DWBA). The results show that unlike for the πf5/2πf5/2 orbital and contrary to earlier interpretation, the πf7/2πf7/2 single-particle strength distribution is not appreciably affected by the addition of neutrons beyond N=40N=40., The authors are thankful to the Ganil accelerator staff, informatics service and to the IPN design office. We are grateful for the grant of the Romanian National Authority for Scientific Research, CNCS - UEFISCDI, project number PN-II-ID-PCE-2011-3-048, to the grant FPA2010-22131-C02-01 from the Spanish government and to the OTKA contract No. K100835.

The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3–4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set.

Discontinuous isoperibolic thermal analysis (ΔITA) is a phase diagram investigation technique applicable to organic components systems (with at least one liquid phase). The elementary signal is composed by the evolution of the temperature of the system vs. time after a composition shift. A theoretical analysis and a mathematical modeling of this signal show that the overall enthalpy exchanged multiplied by a proportional factor can be obtained. From different experiments, evidence is given that this semi-quantitative calorimetric measurement is reliable. Thus, ΔITA allows consistent and accurate descriptions of phase diagrams and is a real relative calorimetric measurement technique.

Objectif de l’etude Notre equipe a demontre l’impact de la sarcopenie sur la survie chez des patients atteints de cancers de l’œsophage pris en charge par chimioradiotherapie. L’objectif de cette etude est de d’analyser l’impact de la sarcopenie comme facteur predictif de realisation d’une radiotherapie ou d’une chimioradiotherapie complete, de la survenue de toxicite ainsi que sur la survie globale chez des patients traites pour un cancer des voies aerodigestives superieures. Materiel et methode Dans le cadre d’une etude unicentrique prospective sur les parametres nutritionnels des patients en cours de radiotherapie pour un cancers des voies aerodigestives superieures, l’ensemble des patients a beneficie d’une scanographie avec des coupes en L3 pour le calcul de la surface musculaire en centimetres carre rapportee a la taille au carre pour etablir l’indice de masse musculaire (en centimetres carre par metre carre). Resultats Un total de 180 patients a ete inclus entre avril 2014 et aout 2016 et les dossiers de 169 patients etaient analysables. La duree moyenne de suivi etait de 21 mois. Quarante et un cancers ont recidive, dont 37 locoregionalement et quatre sous forme de metastases. Soixante-quinze pour cent des patients ont recu un traitement complet. Trente-cinq pour cent des patients etaient sarcopeniques au moment de la scanographie de planification avec un indice de masse musculaire moyen de 155,2 cm2 contre 61 % des patients a 3 mois avec un indice de masse musculaire moyen de 135,7 cm2 (p = 0,001). La sarcopenie n’etait pas associee a la non realisation du traitement complet (p = 0,93) ou a la survenue d’une toxicite aigue de grade 3 ou plus (p = 0,92), que le traitement soit associe ou pas a une chimiotherapie. Quatre-vingt-neuf pour cent des patients non sarcopeniques et 81 % des sarcopeniques etaient vivants a 18 mois (p = 0,72). Conclusion La presence d’une sarcopenie avant la radiotherapie pour un cancer des voies aerodigestives superieures n’est pas associee a une toxicite aigue plus importante, a une diminution des doses de traitement ou a une diminution de la probabilite de survie a 18 mois.

It is hypothesised that complex interactions between genetic and environmental factors give rise to allergy and asthma in childhood. The Canadian Healthy Infant Longitudinal Development (CHILD) study was designed to explore these factors.CHILD is a longitudinal, general population birth cohort study following infants from mid-pregnancy to age 5 years. Over this time period, biological samples, questionnaires, clinical measures and environmental data are collected.A total of 3624 families have been recruited, and many thousands of samples and questionnaires have been collected, annotated, and archived. This report outlines the rationale and methodology for collecting and storing diverse biological samples from parents and children in this study, and the mechanisms for their release for analyses.The CHILD sample and data repository is a tremendous current and future resource and will provide a wealth of information not only informing studies of asthma and allergy, but also potentially in many other aspects of health relevant for Canadian infants and children.

Limatulichthys nasarcus n. sp. is described as a new species based on 15 specimens from the Ventuari and Caura Rivers in Southern Venezuela. The new species can be distinguished from its only congener, L. griseus, by the presence of anterior abdominal plates half the size of those at center of abdomen (vs. plates similar in size); distinct spots less than half of diameter of naris across entire dorsum, including snout and head (vs. indistinct dorsal spots larger or equal than diameter of naris); lateral portions of head and opercle with dark well-defined spots larger than those on dorsum (vs. spots on lateral portions of head and opercle equal in size to those on remainder of body); snout profile in dorsal view broadly rounded (vs. acutely triangular); head longer (21.4-24.2 SL vs. 17.7-21.0%); and anal fin longer (15.7-18.0 SL vs. 13.7-15.6%). Distinctiveness of the two species is further supported by their non-overlapping distribution in multivariate morphospace. The disjunct distribution of L. nasarcus across both the Caura and Ventuari rivers exclusive of the main Orinoco River channel contributes to a growing body of evidence supporting the historical connection between headwaters of these drainages. The hypothesized existence of a 'proto-Berbice' paleodrainage provides one explanation for such a connection.

Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts.

The ${}^{26}\mathrm{Al}$ radioisotope is of great importance for understanding the chemical and dynamical evolution of our galaxy. Among the possible stellar sources, massive stars are believed to be the main producer of this radioisotope. Understanding ${}^{26}\mathrm{Al}$ nucleosynthesis in massive stars requires estimates of the thermonuclear reaction rates of the $^{26}\mathrm{Al}$${(n,p)}^{26}$Mg, $^{26}\mathrm{Al}$${(n,\ensuremath{\alpha})}^{23}$Na, and $^{23}\mathrm{Na}$${(\ensuremath{\alpha},p)}^{26}$Mg reactions. These reaction rates depend on the spectroscopic properties of ${}^{27}\mathrm{Al}$ states above the neutron and alpha thresholds. In this context, the $^{27}\mathrm{Al}$${(p,{p}^{\ensuremath{'}})}^{27}$Al* reaction was studied at 18 MeV using a high-resolution Enge Split-Pole spectrometer. States from the ground state up to excitation energies of $\ensuremath{\approx}$14 MeV were populated. While up to the ${}^{23}\mathrm{Na}$ + $\ensuremath{\alpha}$ threshold no additional states are observed, we report for the first time 30 new levels above the ${}^{23}\mathrm{Na}$ + $\ensuremath{\alpha}$ threshold and more than 30 new states above the ${}^{26}\mathrm{Al}$ + n threshold for which excitation energies are determined with an uncertainty of 4--5 keV.

Radiotherapy is used for inoperable lung cancers, sometimes in association with chemotherapy. Outcomes of conventional radiotherapy are disappointing. New techniques improve adaptation to tumour volume, decrease normal tissue irradiation and lead to increasing tumour dose with the opportunity for improved survival. With intensity-modulated radiation therapy, isodoses can conform to complex volumes. It is widely used and seems to be indicated in locally advanced stages. Its dosimetric improvements have been demonstrated but outcomes are still heterogeneous. Stereotactic radiotherapy allows treatment of small volumes with many narrow beams. Dedicated devices or appropriate equipment on classical devices are needed. In early stages, its efficacy is comparable to surgery with an acceptable toxicity. Endobronchial brachytherapy could be used for early stages with specific criteria. Hadrontherapy is still experimental regarding lung cancer. Hadrons have physical properties leading to very accurate dose distribution. In the rare published studies, toxicities are roughly lower than others techniques but for early stages its effectiveness is not better than stereotactic radiotherapy. These techniques are optimized by metabolic imaging which precisely defines the target volume and assesses the therapeutic response; image-guided radiation therapy which allows a more accurate patient set up and by respiratory tracking or gating which takes account of tumour respiratory motions.

Expérience GANIL/MUST2; International audience; We have measured the 72Zn(d, 3He) 71Cu proton pickup reaction in inverse kinematics at 38 MeV/u. A dedicated setup was developed to overcome the experimental challenges posed by the low cross section of the reaction and the low energy of the outgoing 3He particles. The excitation-energy spectrum was reconstructed and spectroscopic factors were obtained after analysis of the angular distributions in the finite-range Distorted-Wave Born Approximation (DWBA). The results show that unlike for the πf5/2 orbital, the πf7/2 single-particle strength is not appreciably affected by the addition of neutrons beyond N = 40.

The purpose was to assess three treatments planning techniques including one in intensity-modulated radiation therapy (IMRT) for cerebral irradiation of pregnant woman, in order to limit the dose delivered to the foetus. The treatment provided was 60 Gy to the planning target volume. Estimated foetal dose was measured using an anthropomorphic phantom, on the upper and middle part of the uterus. The first plan consisted in four beams in conformational technique delivered from a Varian accelerator with a 120 leaves collimator, the second one used non-coplanar fields and the third one assessed IMRT. With the conformational technique, the dose at the upper part of the uterus was 8.3 mGy and 6.3 mGy at the middle part. The dose delivered to the foetus was higher with the non-coplanar fields. In IMRT, the dose at the upper part of the uterus was 23.8 mGy and 14.3 mGy at the middle part. The three plans used 6 MV X-rays. Because of the use of leaves and non-coplanar fields, IMRT does not seem to be the optimal technique for the treatment of pregnant woman. However, the dose delivered to the foetus remains low and below the dose of 100 mGy recommended by the International Commission of Radiological Protection. It seems possible to consider the use of this technique for a better sparing of organs at risk for the mother.

Subtraction hybridization after the exposure of keratinocytes to ultraviolet radiation identified a differentially expressed cDNA that encodes a protein of 630 amino acid residues possessing significant similarity to the catalytic domain of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. Northern blotting and reverse-transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK-related kinase (SNARK) were widely expressed in rodent tissues. The SNARK gene was localized to human chromosome 1q32 by fluorescent in situ hybridization. SNARK was translated in vitro to yield a single protein band of approx. 76kDa; Western analysis of transfected baby hamster kidney (BHK) cells detected two SNARK-immunoreactive bands of approx. 76-80kDa. SNARK was capable of autophosphorylation in vitro; immunoprecipitated SNARK exhibited phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR (SAMS) as a kinase substrate. SNARK activity was significantly increased by AMP and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte cells, implying that SNARK might be activated by an AMPK kinase-dependent pathway. Furthermore, glucose deprivation increased SNARK activity 3-fold in BHK fibroblasts. These findings identify SNARK as a glucose- and AICAriboside-regulated member of the AMPK-related gene family that represents a new candidate mediator of the cellular response to metabolic stress.

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.com

The susceptibility of adult male and female dampwood termites (Zootermopsis angusticollis) to an infection carried by a mate was studied by exposing dealates to a 4 × 107 or a 6 × 104 spores/ml solution of the fungus Metarhizium anisopliae. Following exposure to spores, male and female dealates were paired randomly in four treatments: (1) male and female exposed to spores; (2) male exposed to spores/female exposed to a control solution lacking fungal spores; (3) male exposed to a control solution/female exposed to spores and (4) male and female exposed to a control solution. Males and females exposed to 4 × 107 spores/ml acquired and transmitted the infection to their unexposed mate, and had significantly lower survival relative to controls. When males and females were exposed to 6 × 104 spores/ml, however, there were no significant differences in survivorship among the four treatments. Therefore, at the lower pathogen load, dealates were able to control infection. To compare the susceptibility of exposed...

The antifungal property of two of the principal components of the terpenoid frontal gland secretions of nasute termite soldiers was studied by incubating spore suspensions of the fungus Metarhizium anisopliae with α-pinene and limonene singly or in combination at different concentrations. In vitro assays showed that these substances reduced spore germination through direct and indirect (vapor) contact. To determine if the frontal gland secretions protected termites from fungal infection in vivo, the effect of M. anisopliae on the time course of survival of Nasutitermes costalis and N. nigriceps was studied by exposing termites to either a 4.3 × 107 spores/ml or a control sporeless suspension. The caste composition of experimental groups was manipulated to create mixed-caste subcolonies and monocaste groups. Relative to Coptotermes formosanus, a species that relies on the mechanical defenses of soldiers, N. costalis and N. nigriceps were less susceptible to fungal infection. Spore-exposed N. costalis and N. nigriceps termites had 1.2 times the hazard ratio of death of controls, while the hazard ratio of death of spore-exposed C. formosanus was 11.4 times that of controls. Although the lower susceptibility to infection in Nasutitermes may be explained in part by the antifungal properties of α-pinene and limonene, group composition also played a major role in the survival of spore-exposed termites. Mixed-caste and soldier monocaste groups had 3.4 and 4.7 times the hazard ratio of death, respectively, relative to the worker monocaste treatment. These results suggest that although Nasutitermes terpenoid secretions may have antifungal properties, the caste composition of groups and the social interactions of termites also play a role in determining susceptibility to fungal infection.

The myelin basic protein (MBP)-phosphorylating enzymes present during maturation and early embryogenesis of the sea star (Pisaster ochraceus) were investigated. The major maturation-activated MBP kinase (p45 Mapk) was molecularly cloned based on tryptic sequence information obtained with the purified enzyme and shown to be highly related to human Erk1 with 76% amino acid identity. Kinase assays and immunoblotting studies revealed that Mapk remained highly active until 12 h post-fertilization (PF), after which it declined. By 4 days PF, Mapk protein was no longer detectable. At 3 h PF, about half of the detectable MBP phosphotransferase activity could be attributed to a 75 kDa protein kinase that was distinct from Mapk. Like Mapk, this protein phosphorylated MBP mostly on threonine residues, but it failed to phosphorylate a peptide (APRTPGGRR) based upon the Thr-97 MAP kinase phosphorylation site in MBP. Rather, it phosphorylated a peptide (AAQKRPSQRTKYLA) patterned after the N-terminus of MBP. Our studies also showed a dramatic increase in MBP phosphotransferase activity occurred by 4 days PF that arose from a third kinase that phosphorylated MBP solely on serine residues. This kinase exhibited the following substrate substrate preference: AAQKRPSQRTKYLA, peptide substrate for S6 kinases (AKRRRLSSLRASTSKSESSQK) > MBP > histone H1 > prota-mine > casein > APRTPGGRR. This kinase was not appreciably affected by addition of phosphatidylserine/diacylglycerol, or the staurosporine analogue Roche Compound 3, but it was partly inhibited by a protein kinase C pseudosubstrate peptide. Gel filtration analysis revealed an apparent molecular mass of 41 kDa for the enzyme. Therefore, at least two novel MBP-phosphorylating enzymes distinct from Mapk are preferentially activated following fertilization and early embryogenesis of the sea star.

Ultraviolet B radiation produces an array of cellular perturbations in the skin. We isolated a keratinocyte cDNA encoding the rat 60S ribosomal subunit protein L13a following differential cDNA library screening with UVB-enriched probes. In contrast to the reported structure of liver L13a, the keratinocyte L13a cDNA contains a longer 3'-untranslated region. Northern blot analysis detected two L13a mRNA transcripts, approximately 800 bp and approximately 1.2 kb, in keratinocytes and a variety of rat tissues. Both L13a mRNA transcripts were induced by UVB irradiation, forskolin and gamma-irradiation. In contrast, no induction of L13a mRNA transcript levels was observed following exposure of keratinocytes to 12-O-tetradecanoylphorbol-13-acetate, serum and the DNA damage-inducing agents methyl methanesulfonate or 4-nitroquinoline-N-oxide. These observations suggest that increased expression of ribosomal subunit genes may be a molecular component of the keratinocyte response to UVB in particular and not part of a nonspecific response to DNA damage.

Body dissatisfaction among pregnant women can provoke behaviors to control weight gain and make them more vulnerable to eating disorders. Body dissatisfaction and strategies to control weight during pregnancy can have many consequences for both the mother and baby. Excessive weight gain may cause complications during childbirth and, reciprocally, a too weak weight gain could be associated with the risk of having a baby with a very low birth weight. Thus, it appears important to have a tool to detect these body image disorders in this population. As far as we know, no French-speaking tool exists, and the objective of this study was to investigate the psychometric properties of the French translation of the Pregnancy and Weight Gain Attitude Scale (PWGAS), which assesses the attitudes about weight gain during pregnancy.The sample consisted of 553 women (29.32±4.82 years) in their third trimester of pregnancy. Participants were volunteer women recruited in hospitals during obstetric consultation. All participants completed an anamnestic questionnaire, the PWGAS and a questionnaire assessing body dissatisfaction (Body Shape Questionnaire [BSQ]). The PWGAS, in its original version, includes 18 items and consists of four subscales: Positive Pregnancy Body Image; Negative Pregnancy Body Image; Indifference toward Weight Gain and Weight Gain Restrictive Behaviors. The instrument was translated and verified by expert translators.Confirmatory factor analysis of the original version showed fit indices below recommended limits. An exploratory factor analysis on the PWGAS revealed the existence of five factors: "Fear about weight gain" (4 items); "Absence of weight gain preoccupation" (2 items); "Positive attitudes about weight gain" (4 items); "Feeling overwhelmed by weight gain" (3 items); and "Control over weight gain" (3 items). The goodness-of-fit of the five-factor model was satisfactory. The PWGAS (total and factors) is negatively correlated with the BSQ demonstrating its concurrent validity.The PWGAS has satisfactory psychometric properties. This questionnaire could certainly be integrated in the monitoring of pregnant women in order to detect and guide those who show negative attitudes about the weight gain so that they can benefit from adequate care and prevent the development of eating disorders.