Corneal Viscoelastic Properties from Finite-Element Analysis of In Vivo Air-Puff Deformation

Biomechanical properties are an excellent health marker of biological tissues, however they are challenging to be measured in-vivo. Non-invasive approaches to assess tissue biomechanics have been suggested, but there is a clear need for more accurate techniques for diagnosis, surgical guidance and treatment evaluation. Recently air-puff systems have been developed to study the dynamic tissue response, nevertheless the experimental geometrical observations lack from an analysis that addresses specifically the inherent dynamic properties. In this study a viscoelastic finite element model was built that predicts the experimental corneal deformation response to an air-puff for different conditions. A sensitivity analysis reveals significant contributions to corneal deformation of intraocular pressure and corneal thickness, besides corneal biomechanical properties. The results show the capability of dynamic imaging to reveal inherent biomechanical properties in vivo. Estimates of corneal biomechanical parameters will contribute to the basic understanding of corneal structure, shape and integrity and increase the predictability of corneal surgery.     

LIP index for peptide classification using MS/MS and SEQUEST search via logistic regression

This study addresses the issue of peptide identification resulting from tandem mass spectrometry proteomics analysis followed by database search. This work shows that the Logistic Identification of Peptides (LIP) Index achieves high sensitivity and specificity for peptide classification relative to a manually verified "gold" standard and also accurately estimates the probability of a correct peptide match. The LIP Index is a weighted average of SEQUEST output variables based on logistic regression models and is a transparent, easy to use, inclusive, extendable, and statistically sound approach to classify correct peptide identifications. Modifications, such as normalizing cross-correlations (Xcorr) for peptide length, adjusting for charge state, and the number of tryptic termini, significantly improve the fit the logistic regression models, as well as increase sensitivity and specificity. The LIP Index also incorporates earlier developed statistical models on spectral quality assessment and peptide identification, which further improves sensitivity and specificity.     

Statistical aspects in physical mapping application to the genome of O. oeni strain GM

This work addresses issues around physical maps, in particular, for circular genomes. The overlapping relationship between two fragments obtained by applying two different restriction enzymes, separately, is classified as nonoverlapping, partial overlapping, and total overlapping. A double partial overlapping can also appear in a particular situation. Taking into account DNA fragment lengths and under the assumption that the left-hand endpoints of the two restriction fragments are independent random variables, each of which with a uniform distribution along a circular genome, we present expressions for prior probabilities of those events. This information is combined with hybridization data via Bayes' theorem, in order to evaluate corresponding posterior probabilities. Additionally, we explore a sensitivity analysis to quantify the effect of length variation in the results.     

DivergentSet, a tool for picking non-redundant sequences from large sequence collections

DivergentSet addresses the important but so far neglected bioinformatics task of choosing a representative set of sequences from a larger collection. We found that using a phylogenetic tree to guide the construction of divergent sets of sequences can be up to 2 orders of magnitude faster than the naive method of using a full distance matrix. By providing a user-friendly interface (available online) that integrates the tasks of finding additional sequences, building and refining the divergent set, producing random divergent sets from the same sequences, and exporting identifiers, this software facilitates a wide range of bioinformatics analyses including finding significant motifs and covariations. As an example application of DivergentSet, we demonstrate that the motifs identified by the motif-finding package MEME (Motif Elicitation by Maximum Entropy) are highly unstable with respect to the specific choice of sequences. This instability suggests that the types of sensitivity analysis enabled by DivergentSet may be widely useful for identifying the motifs of biological significance.     

Morningness-eveningness and social anxiety symptoms: the influence of depression symptoms on the indirect effect through punishment sensitivity and experiential avoidance

Social anxiety has recently been linked to morningness-eveningness; however, the psychological mechanisms underlying this relationship are not well known. As such, the purpose of the current study is to propose a model by which morningness-eveningness is related to social anxiety symptoms through punishment sensitivity and experiential avoidance within an adult American, community sample recruited via Amazon’s Mechanical Turk (MTurk). It was hypothesized that experiential avoidance and punishment sensitivity would be associated with increased social anxiety symptoms and that morningness-eveningness would be negatively related to social anxiety symptoms. Furthermore, eveningness was hypothesized to be associated with increased punishment sensitivity and in turn, greater experiential avoidance. Lastly, the relationship between morningness-eveningness and social anxiety was hypothesized to be mediated by punishment sensitivity among the group with high depression levels, but not among the group with lesser depression symptoms. The results indicated that eveningness was related to social anxiety symptoms through experiential avoidance, and that depression symptoms influenced the relationship between morningness-eveningness and punishment sensitivity such that, in those high in depression symptoms, there was a significant association between eveningness and punishment sensitivity, but not among those with lower depression levels. The study findings build upon existing chronobiological research and addresses inconsistencies in previous literature.     

A transformed murine Leydig cell line expresses the ETA receptor subtype

We recently demonstrated that transformed murine Leydig cells (MA-10) responded to endothelin-1 (ET-1) via increased steroidogenesis. This study addresses the endothelin receptor subtype present on this cell line and whether or not the cells produce ET-1. The expression of the preproendothelin-1 (PPET-1) gene was investigated by Northern blot analysis, and PPET-1 mRNA was found to be <0.2% of that present in pulmonary endothelial cells. The medium from MA-10 cells, maintained under serum-free conditions, was analyzed by radio-immunoassay to determine immunoreactive-ET-1 production and ET-1 levels were found to be below the sensitivity of the assay (<10 pg/ml). The data from competitive binding experiments with [¹²⁵I]ET-1 and unlabeled ET-1, ET-3 and receptor subtype selective ligands yielded a single class of high affinity binding sites with ET_A receptor subtype characteristics. The results of this study demonstrate that MA-10 cells possess the ET_A receptor subtype but do not produce significant quantities of ET-1 under basal conditions.     

The Role of ATM in the Deficiency in Nonhomologous End-Joining near Telomeres in a Human Cancer Cell Line

Telomeres distinguish chromosome ends from double-strand breaks (DSBs) and prevent chromosome fusion. However, telomeres can also interfere with DNA repair, as shown by a deficiency in nonhomologous end joining (NHEJ) and an increase in large deletions at telomeric DSBs. The sensitivity of telomeric regions to DSBs is important in the cellular response to ionizing radiation and oncogene-induced replication stress, either by preventing cell division in normal cells, or by promoting chromosome instability in cancer cells. We have previously proposed that the telomeric protein TRF2 causes the sensitivity of telomeric regions to DSBs, either through its inhibition of ATM, or by promoting the processing of DSBs as though they are telomeres, which is independent of ATM. Our current study addresses the mechanism responsible for the deficiency in repair of DSBs near telomeres by combining assays for large deletions, NHEJ, small deletions, and gross chromosome rearrangements (GCRs) to compare the types of events resulting from DSBs at interstitial and telomeric DSBs. Our results confirm the sensitivity of telomeric regions to DSBs by demonstrating that the frequency of GCRs is greatly increased at DSBs near telomeres and that the role of ATM in DSB repair is very different at interstitial and telomeric DSBs. Unlike at interstitial DSBs, a deficiency in ATM decreases NHEJ and small deletions at telomeric DSBs, while it increases large deletions. These results strongly suggest that ATM is functional near telomeres and is involved in end protection at telomeric DSBs, but is not required for the extensive resection at telomeric DSBs. The results support our model in which the deficiency in DSB repair near telomeres is a result of ATM-independent processing of DSBs as though they are telomeres, leading to extensive resection, telomere loss, and GCRs involving alternative NHEJ.     

黄河三角洲国家级自然保护区生态敏感性评价

基于GIS下的网格分析,建立了结合生境适宜性评价和人为干扰特征分析的生态敏感性评价模型.首先建立被列为世界自然保护联盟(IUCN)红色名录濒危等级(截止到2007)的水禽数据库,并结合相关文献及实地调查,识别评价所选物种的生境需求.再基于GIS下的200m×200m网格系统,依据生境适宜性评价模型,从景观水平上进行生境现状评价,提出"综合生境适宜性的概念"并计算综合生境适宜性指数, 再根据综合指数进行生境适宜性评价;然后从已建立的数据库中选取典型物种鹤类作为指示种,同样基于200m×200m的网格,借助GIS技术分析研究区内的人为干扰因子(道路和油井)造成的生境损失;最后在以上的研究基础上,将生境适宜性评价和人为干扰特征分析的结果叠加运算进行生态敏感性分析.结果表明:研究区生态敏感性整体上较高,总的分布规律是靠近沿海的区域敏感性较高,内陆区域的敏感性较低;并按生态敏感度的高低,将研究区划分为极敏感区、敏感区、较敏感区、一般敏感区和不敏感区5个等级,其中极敏感区和敏感区面积共占研究区面积的55.74%,较敏感区约占16.26%,一般敏感区和不敏感区各占22.81%和5.19%.此外,为更有效地保护重要生境,对照保护区现有的功能分区,并结合评价结果,讨论了功能分区调整的相关建议.     

噬菌体抗体库的优化

噬菌体抗体组合文库技术作为噬菌体展示和抗体组合文库两种技术的集成,由于它具有库容量大、特异性高、和敏感性强的优点而被誉为抗体技术的第三次革命。但是由于一些技术上的原因,使得它无法得到广泛的应用,本文就其优化进行综述。     

Increasing Sequence Search Sensitivity with Transitive Alignments

Sequence alignment is an important bioinformatics tool for identifying homology, but searching against the full set of available sequences is likely to result in many hits to poorly annotated sequences providing very little information. Consequently, we often want alignments against a specific subset of sequences: for instance, we are looking for sequences from a particular species, sequences that have known 3d-structures, sequences that have a reliable (curated) function annotation, and so on. Although such subset databases are readily available, they only represent a small fraction of all sequences. Thus, the likelihood of finding close homologs for query sequences is smaller, and the alignments will in general have lower scores. This makes it difficult to distinguish hits to homologous sequences from random hits to unrelated sequences. Here, we propose a method that addresses this problem by first aligning query sequences against a large database representing the corpus of known sequences, and then constructing indirect (or transitive) alignments by combining the results with alignments from the large database against the desired target database. We compare the results to direct pairwise alignments, and show that our method gives us higher sensitivity alignments against the target database.     

Landscape,regional and global estimates of nitrogen flux from land to sea: Errors and uncertainties

Regional to global scale modelling of N fluxfrom land to ocean has progressed to datethrough the development of simple empiricalmodels representing bulk N flux rates fromlarge watersheds, regions, or continents on thebasis of a limited selection of modelparameters. Watershed scale N flux modellinghas developed a range of physically-basedapproaches ranging from models where N fluxrates are predicted through a physicalrepresentation of the processes involved,through to catchment scale models which providea simplified representation of true systemsbehaviour. Generally, these watershed scalemodels describe within their structure thedominant process controls on N flux at thecatchment or watershed scale, and take intoaccount variations in the extent to which theseprocesses control N flux rates as a function oflandscape sensitivity to N cycling and export. This paper addresses the nature of the errorsand uncertainties inherent in existing regionalto global scale models, and the nature of errorpropagation associated with upscaling fromsmall catchment to regional scale through asuite of spatial aggregation and conceptuallumping experiments conducted on a validatedwatershed scale model, the export coefficientmodel. Results from the analysis support thefindings of other researchers developingmacroscale models in allied research fields. Conclusions from the study confirm thatreliable and accurate regional scale N fluxmodelling needs to take account of theheterogeneity of landscapes and the impact thatthis has on N cycling processes withinhomogenous landscape units.     

Frequency responses of age-structured populations: Pacific salmon as an example

Increasing evidence of the effects of changing climate on physical ocean conditions and long-term changes in fish populations adds to the need to understand the effects of stochastic forcing on marine populations. Cohort resonance is of particular interest because it involves selective sensitivity to specific time scales of environmental variability, including that of mean age of reproduction, and, more importantly, very low frequencies (i.e., trends). We present an age-structured model for two Pacific salmon species with environmental variability in survival rate and in individual growth rate, hence spawning age distribution. We use computed frequency response curves and analysis of the linearized dynamics to obtain two main results. First, the frequency response of the population is affected by the life history stage at which variability affects the population; varying growth rate tends to excite periodic resonance in age structure, while varying survival tends to excite low frequency fluctuation with more effect on total population size. Second, decreasing adult survival strengthens the cohort resonance effect at all frequencies, a finding that addresses the question of how fishing and climate change will interact.     

基于空间距离指数的青藏高原生态敏感性综合评价及时空演变分析

生态敏感性是生态系统对外界压力的适应性及遭受破坏的恢复力,开展生态敏感性评价是识别区域生态环境问题的有效手段之一。根据青藏高原的区域特性和主要生态环境问题,在定量构建土地荒漠化敏感性、水土流失敏感性、滑坡灾害敏感性和冻融侵蚀敏感性的基础上,通过空间距离指数法对青藏高原生态敏感性进行综合评价,并采用空间自相关分析和生态敏感性变化模式分析,探讨其时空演变特征和保护管理区划。结果表明：（1）青藏高原综合生态敏感性由西北向东南递减,极度和重度敏感区主要集中在西北部和高大山脉区,不敏感区主要集中在东南部;（2）2000-2018年间青藏高原综合生态敏感性指数值从1.49上升到1.51,表明该区域生态敏感性逐步下降,生态环境改善明显;（3）青藏高原生态敏感性存在显著的空间正相关,低-低聚集网格数量波动上升,从2000年的7277增至2018年7357,表明青藏高原部分地区的生态环境仍存在着一定恶化的风险;（4）根据区域生态敏感性变化模式分析,将青藏高原划分为严格保护区、生态退化区、潜在治理区、生态改善区和综合发展区五个区域,并提出了相应保护与管理对策。研究结果可以为青藏高原生态保护和可持续发展提供参考,从而有效推动保护管理措施的制定。     

Transcutaneous FES of the paralyzed quadriceps: is knee torque affected by unintended activation of the hamstrings?

This study addresses the question whether unintended response of the knee flexors (hamstrings) accompanies transcutaneous functional electrical stimulation (FES) of the quadriceps and whether the knee torque is hereby affected. Transcutaneous FES of the right quadriceps of two paraplegic subjects was applied and measurements were made of the net torque and of the myoelectric activities of the quadriceps and hamstrings muscles of the right leg. A low correlation was obtained between the peak-to-peak amplitudes of the M-waves of the two muscles. This correlation decreased further with the development of fatigue, which indicated that the electromyography (EMG) signals from the hamstrings were not the result of cross-talk between adjacent recording sites. The force profile of each muscle was determined from a developed model incorporating EMG-based activation, muscle anthropometry as obtained from in vivo magnetic resonance imaging of the thigh, and metabolic fatigue function, based on data acquired by 31P nuclear magnetic resonance spectroscopy. A sensitivity analysis revealed that the muscle specific tension and the muscle moment arms have a major influence on the resulting muscle forces and should therefore be accurately provided. The results show that during the unfatigued phase of contraction the estimated maximal force in the hamstrings was lower than 20% of that in the quadriceps and could be considered to be practically negligible. As fatigue progressed the hamstrings-to-quadriceps force ratio increased, reaching up to 45%, and the effect of co-activation on the torque partition between the two muscles was no longer negligible.     

The climate sensitivity of carbon,timber, and species richness covaries with forest age in boreal–temperate North America

Climate change threatens the provisioning of forest ecosystem services and biodiversity (ESB). The climate sensitivity of ESB may vary with forest development from young to old‐growth conditions as structure and composition shift over time and space. This study addresses knowledge gaps hindering implementation of adaptive forest management strategies to sustain ESB. We focused on a number of ESB indicators to (a) analyze associations among carbon storage, timber growth rate, and species richness along a forest development gradient; (b) test the sensitivity of these associations to climatic changes; and (c) identify hotspots of climate sensitivity across the boreal–temperate forests of eastern North America. From pre‐existing databases and literature, we compiled a unique dataset of 18,507 forest plots. We used a full Bayesian framework to quantify responses of nine ESB indicators. The Bayesian models were used to assess the sensitivity of these indicators and their associations to projected increases in temperature and precipitation. We found the strongest association among the investigated ESB indicators in old forests (>170 years). These forests simultaneously support high levels of carbon storage, timber growth, and species richness. Older forests also exhibit low climate sensitivity of associations among ESB indicators as compared to younger forests. While regions with a currently low combined ESB performance benefitted from climate change, regions with a high ESB performance were particularly vulnerable to climate change. In particular, climate sensitivity was highest east and southeast of the Great Lakes, signaling potential priority areas for adaptive management. Our findings suggest that strategies aimed at enhancing the representation of older forest conditions at landscape scales will help sustain ESB in a changing world.     

Importance of Initial Concentration of Factor VIII in a Mechanistic Model of In Vitro Coagulation

This computational study generates a hypothesis for the coagulation protein whose initial concentration greatly influences the course of coagulation. Many clinical malignancies of blood coagulation arise due to abnormal initial concentrations of coagulation factors. Sensitivity analysis of mechanistic models of blood coagulation is a convenient method to assess the effect of such abnormalities. Accordingly, the study presents sensitivity analysis, with respect to initial concentrations, of a recently developed mechanistic model of blood coagulation. Both the model and parameters to which model sensitivity is being analyzed provide newer insights into blood coagulation: the model incorporates distinct equations for plasma-phase and platelet membrane-bound species, and sensitivity to initial concentrations is a new dimension in sensitivity analysis. The results show that model predictions are most uncertain with respect to changes in initial concentration of factor VIII, and this hypothesis is supported by results from other models developed independently.