Radiation-induced transient cisplatin resistance in murine fibrosarcoma cells associated with elevated metallothionein content.

Cisplatin resistant mouse fibrosarcoma cells were isolated after fractionated irradiation in the absence of any drug treatment. Several sublines have been established; clone SSK-rad1 was used for further studies. These cells exhibit unchanged radiosensitivity and are compared to cisplatin resistant sublines, SSK-cis2, previously induced by low dose cisplatin exposure. Both resistant sublines are characterised by reduced CdCl2 sensitivity, indicating enhanced metallothionein content; loss of cisplatin resistance occurs after 10 to 25 generations and correlates with rising CdCl2 toxicity. Increase of MT is demonstrated directly by 109Cd binding to the MT containing region after FPLC. Both sublines differ in GSH level, which is increased only in SSK-rad1 cells, and in cellular platinum content, which is reduced in SSK-cis2 cells compared to the parental SSK cell line. These factors may contribute to cisplatin resistance but are not the main cause responsible for the transient nature of the drug resistance observed. Our results indicate that transient cisplatin resistance in SSK cells can be induced not only by the drug itself but also by gamma-irradiation and is based on the same mechanism of increased cellular MT content

Valuing end-of-life care:translation and content validation of the ICECAP-SCM measure

Background: The evaluation of care strategies at the end of life is particularly important due to the globally increasing proportion of very old people in need of care. The ICECAP-Supportive Care Measure is a self-complete questionnaire developed in the UK to evaluate palliative and supportive care by measuring patient’s wellbeing in terms of ‘capability’. It is a new measure with high potential for broad and international use. The aims of this study were the translation of the ICECAP-Supportive Care Measure from English into German and the content validation of this version. Methods: A multi-step and team-based translation process based on the TRAPD model was performed. An expert survey was carried out to assess content validity. The expert panel (n = 20) consisted of four expert groups: representative seniors aged 65+, patients aged 65+ living in residential care, patients aged 65+ receiving end-of-life care, and professionals in end-of-life care. Results: The German version of the ICECAP-Supportive Care Measure showed an excellent content validity on both item- and scale-level. In addition, a high agreement regarding the length of the single items and the total length of the questionnaire as well as the number of answer categories was reached. Conclusions: The German ICECAP-SCM is a valid tool to assess the quality of life at the end of life that is suitable for use in different settings. The questionnaire may be utilized in multinational clinical and economic evaluations of end-of-life care

Avaliação de rendimento e características morfométricas do curimbatá Prochilodus Lineatus (valenciennes, 1836), e do piavuçu leporinus macrocephalus (garavello & britski, 1988) machos e fêmeas

Foram avaliados machos e fêmeas, sendo analisados os parâmetros como o rendimento corporal, composição e características morfométricas entre as duas espécies de peixes, o curimbatá (Prochilodus lineatus) e o piavuçu (Leporinus macrocephalus). Foram analisados os seguintes parâmetros: comprimento total, peso total, rendimentos de carcaça, tronco limpo e filé e as relações apresentadas entre comprimento da cabeça/comprimento padrão, comprimento da cabeça/altura da cabeça, comprimento padrão/comprimento total e altura total/comprimento do tronco. Avaliações sobre a quantidade de extrato etéreo e umidade no filé dos animais também foram consideradas como base nos resultados obtidos. Pode-se observar que os curimbatás machos são menores que as fêmeas (P<0,05) e apresentaram rendimento de filé menor. A fração do comprimento da cabeça em relação ao comprimento padrão foi maior para os curimbatás machos do que para as fêmeas, indicando que eles possuem cabeça relativamente maior. Quanto aos piavuçus, os machos são menores que as fêmeas e apresentaram rendimento de filé significantemente (P<0,01) maior

E-cigarette use causes a unique innate immune response in the lung, involving increased neutrophilic activation and altered mucin secretion

Rationale: E-cigarettes have become increasingly popular and little is known about their potential adverse health effects. Objectives: To determine the effects of e-cigarette use on the airways. Methods: Induced sputum samples from cigarette smokers, e-cigarette users, and nonsmokers were analyzed by quantitative proteomics, and the total and individual concentrations of mucins MUC5AC and MUC5B were determined by light scattering/refractometry and labeled mass spectrometry, respectively. Neutrophil extracellular trap (NET) formation rates were also determined for the same groups. Measurements and Main Results: E-cigarette users exhibited significant increases in aldehyde-detoxification and oxidative stress-related proteins associated with cigarette smoke compared with nonsmokers. The levels of innate defense proteins associated with chronic obstructive pulmonary disease, such as elastase and matrix metalloproteinase-9, were significantly elevated in e-cigarette users as well. E-cigarette users' sputum also uniquely exhibited significant increases in neutrophil granulocyte-related and NET-related proteins, such as myeloperoxidase, azurocidin, and protein-arginine deiminase 4, despite no significant elevation in neutrophil cell counts. Peripheral neutrophils from e-cigarette users showed increased susceptibility to phorbol 12-myristate 13-acetate-induced NETosis. Finally, a compositional change in the gel-forming building blocks of airway mucus (i.e., an elevated concentration of mucin MUC5AC) was observed in both cigarette smokers and e-cigarette users. Conclusions: Together, our results indicate that e-cigarette use alters the profile of innate defense proteins in airway secretions, inducing similar and unique changes relative to cigarette smoking. These data challenge the concept that e-cigarettes are a healthier alternative to cigarettes

On Distant Speech Recognition for Home Automation

The official version of this draft is available at Springer via http://dx.doi.org/10.1007/978-3-319-16226-3_7International audienceIn the framework of Ambient Assisted Living, home automation may be a solution for helping elderly people living alone at home. This study is part of the Sweet-Home project which aims at developing a new home automation system based on voice command to improve support and well-being of people in loss of autonomy. The goal of the study is vocal order recognition with a focus on two aspects: distance speech recognition and sentence spotting. Several ASR techniques were evaluated on a realistic corpus acquired in a 4-room flat equipped with microphones set in the ceiling. This distant speech French corpus was recorded with 21 speakers who acted scenarios of activities of daily living. Techniques acting at the decoding stage, such as our novel approach called Driven Decoding Algorithm (DDA), gave better speech recognition results than the baseline and other approaches. This solution which uses the two best SNR channels and a priori knowledge (voice commands and distress sentences) has demonstrated an increase in recognition rate without introducing false alarms

Affective processes as network hubs

The practical problems of designing and coding a web-based flight simulator for teachers has led to a ‘three-tier plus environment’ model (COVE model) for a software agent’s cognition (C), psychologicsal (O), physical (V) processes and responses to tasks and interpersonal relationships within a learning environment (E). The purpose of this article is to introduce how some of the COVE model layers represent preconscious processing hubs in an AI human-agent’s representation of learning in a serious game, and how an application of the Five Factor Model of psychology in the O layer determines the scope of dimensions for a practical computational model of affective processes. The article illustrates the model with the classroom-learning context of the simSchool application (www.simschool.org); presents details of the COVE model of an agent’s reactions to academic tasks; discusses the theoretical foundations; and outlines the research-based real world impacts from external validation studies as well as new testable hypotheses of simSchool

Elemental fragmentation cross sections for a O-16 beam of 400 MeV/u kinetic energy interacting with a graphite target using the FOOT Delta E-TOF detectors

The study of nuclear fragmentation plays a central role in many important applications: from the study of Particle Therapy (PT) up to radiation protection for space (RPS) missions and the design of shielding for nuclear reactors. The FragmentatiOn Of Target (FOOT) collaboration aims to study the nuclear reactions that describe the interactions with matter of different light ions (like H-1, He-4, C-12, O-16) of interest for such applications, performing double differential fragmentation cross section measurements in the energy range of interest for PT and RPS. In this manuscript, we present the analysis of the data collected in the interactions of an oxygen ion beam of 400 MeV/u with a graphite target using a partial FOOT setup, at the GSI Helmholtz Center for Heavy Ion Research facility in Darmstadt. During the data taking the magnets, the silicon trackers and the calorimeter foreseen in the final FOOT setup were not yet available, and hence precise measurements of the fragments kinetic energy, momentum and mass were not possible. However, using the FOOT scintillator detectors for the time of flight (TOF) and energy loss (Delta E) measurements together with a drift chamber, used as beam monitor, it was possible to measure the elemental fragmentation cross sections. The reduced detector set-up and the limited available statistics allowed anyway to obtain relevant results, providing statistically significant measurements of cross sections eagerly needed for PT and RPS applications. Whenever possible the obtained results have been compared with existing measurements helping in discriminating between conflicting results in the literature and demonstrating at the same time the proper functioning of the FOOT Delta E-TOF system. Finally, the obtained fragmentation cross sections are compared to the Monte Carlo predictions obtained with the FLUKA software

Organotypic Culture of Physiologically Functional Adult Mammalian Retinas

BACKGROUND: The adult mammalian retina is an important model in research on the central nervous system. Many experiments require the combined use of genetic manipulation, imaging, and electrophysiological recording, which make it desirable to use an in vitro preparation. Unfortunately, the tissue culture of the adult mammalian retina is difficult, mainly because of the high energy consumption of photoreceptors. METHODS AND FINDINGS: We describe an interphase culture system for adult mammalian retina that allows for the expression of genes delivered to retinal neurons by particle-mediated transfer. The retinas retain their morphology and function for up to six days— long enough for the expression of many genes of interest—so that effects upon responses to light and receptive fields could be measured by patch recording or multielectrode array recording. We show that a variety of genes encoding pre- and post-synaptic marker proteins are localized correctly in ganglion and amacrine cells. CONCLUSIONS: In this system the effects on neuronal function of one or several introduced exogenous genes can be studied within intact neural circuitry of adult mammalian retina. This system is flexible enough to be compatible with genetic manipulation, imaging, cell transfection, pharmacological assay, and electrophysiological recordings

A Component of Retinal Light Adaptation Mediated by the Thyroid Hormone Cascade

Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2–3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4–8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation

Seroprevalence of 34 Human Papillomavirus Types in the German General Population

The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life