Comprehensive Modeling of Multimode Fiber Sensors for Refractive Index Measurement and Experimental Validation

We propose and develop a comprehensive model for estimating the refractive index (RI) response over three potential sensing zones in a multimode fiber. The model has been developed based on a combined ray optics, Gaussian beam, and wave optics analysis coupled to the consideration of the injected interrogating lightwave characteristics and validated experimentally through the realization of three sensors with different lengths of stripped cladding sections as the sensing region. The experimental results highly corroborate and validate the simulation output from the model for the three RI sensing zones. The sensors can be employed over a very wide dynamic RI range from 1.316 to over 1.608 at a wavelength of 1550 nm, with the best resolution of 2.2447 × 10−5 RI unit (RIU) obtained in Zone II for a 1-cm sensor length

Loss of Function of the Cik1/Kar3 Motor Complex Results in Chromosomes with Syntelic Attachment That Are Sensed by the Tension Checkpoint

The attachment of sister kinetochores by microtubules emanating from opposite spindle poles establishes chromosome bipolar attachment, which generates tension on chromosomes and is essential for sister-chromatid segregation. Syntelic attachment occurs when both sister kinetochores are attached by microtubules from the same spindle pole and this attachment is unable to generate tension on chromosomes, but a reliable method to induce syntelic attachments is not available in budding yeast. The spindle checkpoint can sense the lack of tension on chromosomes as well as detached kinetochores to prevent anaphase onset. In budding yeast Saccharomyces cerevisiae, tension checkpoint proteins Aurora/Ipl1 kinase and centromere-localized Sgo1 are required to sense the absence of tension but are dispensable for the checkpoint response to detached kinetochores. We have found that the loss of function of a motor protein complex Cik1/Kar3 in budding yeast leads to syntelic attachments. Inactivation of either the spindle or tension checkpoint enables premature anaphase entry in cells with dysfunctional Cik1/Kar3, resulting in co-segregation of sister chromatids. Moreover, the abolished Kar3-kinetochore interaction in cik1 mutants suggests that the Cik1/Kar3 complex mediates chromosome movement along microtubules, which could facilitate bipolar attachment. Therefore, we can induce syntelic attachments in budding yeast by inactivating the Cik1/Kar3 complex, and this approach will be very useful to study the checkpoint response to syntelic attachments

Overexpression of cathepsin K during silica-induced lung fibrosis and control by TGF-β

BACKGROUND: Lung fibrosis is characterized by tissue remodeling resulting from an imbalance between synthesis and degradation of extracellular organic matrices. To examine whether cathepsin(s) (Cat) are important in the development of pulmonary fibrosis, we assessed the expression of four Cat known for their collagenolytic activity in a model of silica-induced lung fibrosis. METHODS: Different strains of mice were transorally instilled with 2.5 mg crystalline silica or other particles. Cat expression (Cat K, S, L and B) was quantified in lung tissue and isolated pulmonary cells by quantitative RT-PCR. In vitro, we assessed the effect of different cytokines, involved in lung inflammatory and fibrotic responses, on the expression of Cat K by alveolar macrophages and fibroblasts. RESULTS: In lung tissue, Cat K transcript was the most strongly upregulated in response to silica, and this upregulation was intimately related to the fibrotic process. In mouse strains known for their differential response to silica, we showed that the level of Cat K expression following silica treatment was inversely related to the level of TGF-β expression and the susceptibility of these strains to develop fibrosis. Pulmonary macrophages and fibroblasts were identified as Cat K overproducing cells in the lung of silicotic mice. In vitro, Cat K was downregulated in mouse and human lung fibroblasts by the profibrotic growth factor TGF-β1. CONCLUSION: Altogether, these data suggest that while Cat K may contribute to control lung fibrosis, TGF-β appears to limit its overexpression in response to silica particles

Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis

BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis

Sleep disturbances in an arctic population: The Tromsø Study

<p>Abstract</p> <p>Background</p> <p>Prevalence estimates for insomnia range from 10 to 50% in the adult general population. Sleep disturbances cause great impairment in quality of life, which might even rival or exceed the impairment in other chronic medical disorders. The economic implications and use of health-care services related to chronic insomnia represent a clinical concern as well as a pronounced public health problem. Hypnotics are frequently prescribed for insomnia, but alcohol and over-the-counter sleep aids seem to be more widely used by insomniacs than prescription medications. Despite the complex relationship between insomnia and physical and mental health factors, the condition appears to be underrecognized and undertreated by health care providers, probably due to the generally limited knowledge of the causes and natural development of insomnia.</p> <p>Methods/Design</p> <p>The Tromsø Study is an ongoing population-based cohort study with five previous health studies undertaken between 1974 and 2001. This protocol outlines a planned study within the sixth Tromsø Study (Tromsø VI), aiming at; 1) describing sleep patterns in a community-based sample representative of the general population of northern Norway, and 2) examining outcome variables of sleep disturbances against possible explanatory and confounding variables, both within a cross-sectional approach, as well as retrospectively in a longitudinal study – exploring sleep patterns in subjects who have attended two or more of the previous Tromsø studies between 1974 and 2009. First, we plan to perform a simple screening in order to identify those participants with probable sleep disturbances, and secondly to investigate these sleep disturbances further, using an extensive sleep-questionnaire. We will also collect biological explanatory variables, i.e. blood samples, weight, height and blood pressure. We plan to merge data on an individual level from the Tromsø VI Study with data from the Norwegian Prescription Database (NorPD), which is a national registry including data for all prescription drugs issued at Norwegian pharmacies. Participants with sleep disturbances will be compared with pair-matched controls without sleep disturbances.</p> <p>Discussion</p> <p>Despite ongoing research, many challenges remain in the characterization of sleep disturbances and its correlates. Future mapping of the biological dimensions, natural history, as well as the behavioral and drug-related aspects of sleep disturbances in a representative population samples is clearly needed.</p

Mutability and mutational spectrum of chromosome transmission fidelity genes

It has been more than two decades since the original chromosome transmission fidelity (Ctf) screen of Saccharomyces cerevisiae was published. Since that time the spectrum of mutations known to cause Ctf and, more generally, chromosome instability (CIN) has expanded dramatically as a result of systematic screens across yeast mutant arrays. Here we describe a comprehensive summary of the original Ctf genetic screen and the cloning of the remaining complementation groups as efforts to expand our knowledge of the CIN gene repertoire and its mutability in a model eukaryote. At the time of the original screen, it was impossible to predict either the genes and processes that would be overrepresented in a pool of random mutants displaying a Ctf phenotype or what the entire set of genes potentially mutable to Ctf would be. We show that in a collection of 136 randomly selected Ctf mutants, >65% of mutants map to 13 genes, 12 of which are involved in sister chromatid cohesion and/or kinetochore function. Extensive screening of systematic mutant collections has shown that ~350 genes with functions as diverse as RNA processing and proteasomal activity mutate to cause a Ctf phenotype and at least 692 genes are required for faithful chromosome segregation. The enrichment of random Ctf alleles in only 13 of ~350 possible Ctf genes suggests that these genes are more easily mutable to cause genome instability than the others. These observations inform our understanding of recurring CIN mutations in human cancers where presumably random mutations are responsible for initiating the frequently observed CIN phenotype of tumors

Climate simulations for 1880-2003 with GISS modelE

We carry out climate simulations for 1880-2003 with GISS modelE driven by ten measured or estimated climate forcings. An ensemble of climate model runs is carried out for each forcing acting individually and for all forcing mechanisms acting together. We compare side-by-side simulated climate change for each forcing, all forcings, observations, unforced variability among model ensemble members, and, if available, observed variability. Discrepancies between observations and simulations with all forcings are due to model deficiencies, inaccurate or incomplete forcings, and imperfect observations. Although there are notable discrepancies between model and observations, the fidelity is sufficient to encourage use of the model for simulations of future climate change. By using a fixed well-documented model and accurately defining the 1880-2003 forcings, we aim to provide a benchmark against which the effect of improvements in the model, climate forcings, and observations can be tested. Principal model deficiencies include unrealistically weak tropical El Nino-like variability and a poor distribution of sea ice, with too much sea ice in the Northern Hemisphere and too little in the Southern Hemisphere. The greatest uncertainties in the forcings are the temporal and spatial variations of anthropogenic aerosols and their indirect effects on clouds.Comment: 44 pages; 19 figures; Final text accepted by Climate Dynamic

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

Viability selection creates negative heterozygosity–fitness correlations in female Black Grouse Lyrurus tetrix

There is widespread interest in the relationship between individual genetic diversity and fitness–related traits (heterozygosity–fitness correlations, HFC). Most studies found weak continuous increases of fitness with increasing heterozygosity while negative HFC have rarely been reported. Negative HFC are expected in cases of outbreeding depression and outbreeding is rare in natural populations; but negative HFC may also arise through viability selection acting on low heterozygosity individuals at an early stage producing a skew in the heterozygosity distribution leading to negative HFCs. We tested this idea using survival and clutch parameters (egg mass, egg volume, chick mass, clutch size) collected in female black grouse Lyrurus tetrix and carried out simulations to determine how survival selection may impact the HFCs measured using clutch parameters. We show that survival is positively related to both individual heterozygosity and female body mass. There is a positive effect of body mass on all clutch parameters, but the selective mortality of females with both low heterozygosity and low body mass led to over representation of high heterozygosity-low body mass females and hence a negative relationship between egg volume and heterozygosity. Using simulated data, we show that survival selection acting on both low body mass and low heterozygosity leads to a skew in the quality of females breeding, resulting in negative HFCs with egg volume. Our results indicate that survival selection can strongly influence the strength and direction of any HFC that occur later in life and that only an integration of all aspects of individuals’ reproductive investment and reproductive success can enable us to fully understand how heterozygosity can shape individual’s fitness

Viability selection creates negative heterozygosity–fitness correlations in female Black Grouse Lyrurus tetrix

There is widespread interest in the relationship between individual genetic diversity and fitness–related traits (heterozygosity–fitness correlations, HFC). Most studies found weak continuous increases of fitness with increasing heterozygosity while negative HFC have rarely been reported. Negative HFC are expected in cases of outbreeding depression and outbreeding is rare in natural populations; but negative HFC may also arise through viability selection acting on low heterozygosity individuals at an early stage producing a skew in the heterozygosity distribution leading to negative HFCs. We tested this idea using survival and clutch parameters (egg mass, egg volume, chick mass, clutch size) collected in female black grouse Lyrurus tetrix and carried out simulations to determine how survival selection may impact the HFCs measured using clutch parameters. We show that survival is positively related to both individual heterozygosity and female body mass. There is a positive effect of body mass on all clutch parameters, but the selective mortality of females with both low heterozygosity and low body mass led to over representation of high heterozygosity-low body mass females and hence a negative relationship between egg volume and heterozygosity. Using simulated data, we show that survival selection acting on both low body mass and low heterozygosity leads to a skew in the quality of females breeding, resulting in negative HFCs with egg volume. Our results indicate that survival selection can strongly influence the strength and direction of any HFC that occur later in life and that only an integration of all aspects of individuals’ reproductive investment and reproductive success can enable us to fully understand how heterozygosity can shape individual’s fitness