Cross-linguistic study of vocal pathology: perceptual features of spasmodic dysphonia in French-speaking subjects

Clinical characterisation of Spasmodic Dysphonia of the adductor type (SD) in French speakers by Klap and colleagues (1993) appears to differ from that of SD in English. This perceptual analysis aims to describe the phonetic features of French SD. A video of 6 French speakers with SD supplied by Klap and colleagues was analysed for frequency of phonatory breaks, pitch breaks, harshness, creak, breathiness and falsetto voice, rate of production, and quantity of speech output. In contrast to English SD, the French speaking SD patients demonstrated no evidence pitch breaks, but phonatory breaks, harshness and breathiness were prominent features. This verifies the French authors’ (1993) clinical description. These findings suggest that phonetic properties of a specific language may affect the manifestation of pathology in neurogenic voice disorders

Articulatory Tradeoffs Reduce Acoustic Variability During American English /r/ Production

Acoustic and articulatory recordings reveal that speakers utilize systematic articulatory tradeoffs to maintain acoustic stability when producing the phoneme /r/. Distinct articulator configurations used to produce /r/ in various phonetic contexts show systematic tradeoffs between the cross-sectional areas of different vocal tract sections. Analysis of acoustic and articulatory variabilities reveals that these tradeoffs act to reduce acoustic variability, thus allowing large contextual variations in vocal tract shape; these contextual variations in turn apparently reduce the amount of articulatory movement required. These findings contrast with the widely held view that speaking involves a canonical vocal tract shape target for each phoneme.National Institute on Deafness and Other Communication Disorders (1R29-DC02852-02, 5R01-DC01925-04, 1R03-C2576-0l); National Science Foundation (IRI-9310518

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity

Noisy Kondo impurities

The anti-ferromagnetic coupling of a magnetic impurity carrying a spin with the conduction electrons spins of a host metal is the basic mechanism responsible for the increase of the resistance of an alloy such as Cu${}_{0.998}$Fe${}_{0.002}$ at low temperature, as originally suggested by Kondo . This coupling has emerged as a very generic property of localized electronic states coupled to a continuum . The possibility to design artificial controllable magnetic impurities in nanoscopic conductors has opened a path to study this many body phenomenon in unusual situations as compared to the initial one and, in particular, in out of equilibrium situations. So far, measurements have focused on the average current. Here, we report on \textit{current fluctuations} (noise) measurements in artificial Kondo impurities made in carbon nanotube devices. We find a striking enhancement of the current noise within the Kondo resonance, in contradiction with simple non-interacting theories. Our findings provide a test bench for one of the most important many-body theories of condensed matter in out of equilibrium situations and shed light on the noise properties of highly conductive molecular devices.Comment: minor differences with published versio

Landscape effects on the population dynamics of small mammal communities: A preliminary analysis of prey-resource variations

This study aims at estimating the effect of landscape composition on the availability of small mammal preys (in terms of biomass) to predators on a sectorial scale (n x 1 km2). Four study sites, representative of different stages of agriculture intensification, were selected in eastern France according to landscape composition. The population dynarnics of Microtus arvalis, Arvicola terrestris, Clethrionomys glareolus and Apodemus sp. were monitored from 1992 to 1996 by using index methods and trapping. M. arvalis and A. terrestris population biomasses were stable in landscapes with low percentage of permanent grassland. M. arvalis populations displayed greater biomass variations with sharp declines in the sites where the proportion of permanent grassland to farmland was greater than 50 %. A. terrestris populations were very unstable in one study site where the proportion of permanent grassland to farmland was greater than 85 %. Synchronic patterns between M. arvalis populations and the populations of hedgerow rodents were suspected at sites with large fluctuations of M. arvalis: every decline of the populations of hedgerow rodents was concomitant with the M. arvalis decline. These results suggest that two kinds of ecological systems in terms of prey-resource variations for mammalian predators can be distinguished: (i) stable in landscapes with lower proportion of permanent grassland, and (ii) unstable, with grassland species crashes and synchronous declines of the rodent community, in landscapes with higher proportion of permanent grassland. Moreover, the population dynamics of small mammals were asynchronous between the four sites situated at relatively short distance (some tens kilometres)L'objectif de cette étude est d'estimer l'effet de la composition du paysage sur les variations de disponibilité en biomasse de micro-mammifères pour les prédateurs, à l'échelle sectorielle (n × 1 km2), Quatre sites d'étude représentatifs d'un gradient d'intensification agricole ont été choisis dans l'est de la France en fonction de la composition du paysage. Les fluctuations de biomasses de Microtus arvalis et Arvicola terrestris (espèces prairiales), de Clethrionomys glareolus et Apodemus sp. (espèces de milieux fermés) ont été suivies de 1992 à 1996 par méthodes indiciaires et piégeage. Les synchronies entre les populations de M. arvalis et celles de rongeurs de milieux fermés ont été recherchées. Les fluctuations de biomasse de M. arvalis et A. terrestris sont stables dans les sites où la proportion de prairie permanente est la plus faible. Les populations de M. arvalis présentent les plus larges amplitudes de variation de biomasse et les déclins les plus prononcés dans les sites où la proportion de prairie permanente sur la surface agricole est supérieure à 50 %. Les populations d'A. terrestris ne sont instables que dans un site, là où la proportion de prairie permanente sur surface agricole est supérieure à 85 %. Les déclins de populations de rongeurs de milieux fermés (Clethrionomys glareolus et Apodemus sp.) sont concomitants de ceux de M. arvalis dans les sites à fortes variations de biomasse de cette dernière espèce. Ces résultats suggèrent deux types de fonctionnement, en terme de variation de disponibilité en proies pour les prédateurs: (i) stable dans les paysages à faible proportion de prairie permanente, et (ii) instable, avec des déclins prononcés et rapides des populations d'espèces prairiales, entraînant des déclins synchrones du peuplement de micro-mammifères étudié, dans les paysages à forte proportion de prairie permanente. Aucune synchronie dans les dynamiques de population de ces micro-mammifères n'est observée entre les sites d'étude, éloignés de quelques dizaines de kilomètres seulement

Índice de vegetação por diferença normalizada (NDVI) de cultivares de soja sob três níveis de disponibilidade hídirca no solo.

bitstream/item/71971/1/ID-30959.pd

Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma

BACKGROUND: The presence of tumor-specific mutations in the cancer genome represents a potential opportunity for pharmacologic intervention to therapeutic benefit. Unfortunately, many classes of oncoproteins (e.g., transcription factors) are not amenable to conventional small-molecule screening. Despite the identification of tumor-specific somatic mutations, most cancer therapy still utilizes nonspecific, cytotoxic drugs. One illustrative example is the treatment of Ewing sarcoma. Although the EWS/FLI oncoprotein, present in the vast majority of Ewing tumors, was characterized over ten years ago, it has never been exploited as a target of therapy. Previously, this target has been intractable to modulation with traditional small-molecule library screening approaches. Here we describe a gene expression–based approach to identify compounds that induce a signature of EWS/FLI attenuation. We hypothesize that screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application. METHODS AND FINDINGS: A gene expression signature for the EWS/FLI off state was determined with microarray expression profiling of Ewing sarcoma cell lines with EWS/FLI-directed RNA interference. A small-molecule library enriched for FDA-approved drugs was screened with a high-throughput, ligation-mediated amplification assay with a fluorescent, bead-based detection. Screening identified cytosine arabinoside (ARA-C) as a modulator of EWS/FLI. ARA-C reduced EWS/FLI protein abundance and accordingly diminished cell viability and transformation and abrogated tumor growth in a xenograft model. Given the poor outcomes of many patients with Ewing sarcoma and the well-established ARA-C safety profile, clinical trials testing ARA-C are warranted. CONCLUSIONS: We demonstrate that a gene expression–based approach to small-molecule library screening can identify, for rapid clinical testing, candidate drugs that modulate previously intractable targets. Furthermore, this is a generic approach that can, in principle, be applied to the identification of modulators of any tumor-associated oncoprotein in the rare pediatric malignancies, but also in the more common adult cancers

An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma

The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60-80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects. Clinical features aside from stage have proven inadequate to meaningfully classify patients for risk-stratified therapy. Therefore, there is a critical need to develop approaches to risk stratify patients with EwS based on molecular features. Over the past decade, new technology has enabled the study of multiple molecular biomarkers in EwS. Preliminary evidence requiring validation supports copy number changes, and loss of function mutations in tumor suppressor genes as biomarkers of outcome in EwS. Initial studies of circulating tumor DNA demonstrated that diagnostic ctDNA burden and ctDNA clearance during induction are also associated with outcome. In addition, fusion partner should be a pre-requisite for enrollment on EwS clinical trials, and the fusion type and structure require further study to determine prognostic impact. These emerging biomarkers represent a new horizon in our understanding of disease risk and will enable future efforts to develop risk-adapted treatment

First Evidence of Shape Coexistence in the Ni-78 Region : Intruder 0(2)(+) State in Ge-80

The N = 48 Ge-80 nucleus is studied by means of beta-delayed electron-conversion spectroscopy at ALTO. The radioactive Ga-80 beam is produced through the isotope separation on line photofission technique and collected on a movable tape for the measurement of gamma and e(-) emission following beta decay. An electric monopole E0 transition, which points to a 639(1) keV intruder 0(2)(+) state, is observed for the first time. This new state is lower than the 2(1)(+) level in Ge-80, and provides evidence of shape coexistence close to one of the most neutron-rich doubly magic nuclei discovered so far, Ni-78. This result is compared with theoretical estimates, helping to explain the role of monopole and quadrupole forces in the weakening of the N = 50 gap at Z = 32. The evolution of intruder 0(2)(+) states towards Ni-78 is discussed.Peer reviewe

An international parentage and identification panel for the domestic cat (Felis catus)

Seventeen commercial and research laboratories participated in two comparison tests under the auspices of the International Society for Animal Genetics to develop an internationally tested, microsatellite-based parentage and identification panel for the domestic cat (Felis catus). Genetic marker selection was based on the polymorphism information content and allele ranges from seven random-bred populations (n = 261) from the USA, Europe and Brazil and eight breeds (n = 200) from the USA. Nineteen microsatellite markers were included in the comparison test and genotyped across the samples. Based on robustness and efficiency, nine autosomal microsatellite markers were ultimately selected as a single multiplex ‘core’ panel for cat identification and parentage testing. Most markers contained dinucleotide repeats. In addition to the autosomal markers, the panel included two gender-specific markers, amelogenin and zinc-finger XY, which produced genotypes for both the X and Y chromosomes. This international cat parentage and identification panel has a power of exclusion comparable to panels used in other species, ranging from 90.08% to 99.79% across breeds and 99.47% to 99.87% in random-bred cat populations