Optimum drilled flange moment resisting connections for seismic regions

Extensive damage in welded unreinforced flange (WUF) connections in previous earthquakes has led to the idea of using reduced beam section (RBS) connections to prevent brittle failure modes in welded joints. Using a similar concept, drilled flange (DF) moment resisting connections are established by a series of holes drilling on the top and the bottom flanges of the beam to create an intentional weak area to shift nonlinear deformations. DF connections are very easy-to-construct and they can also prevent the premature local buckling modes in the reduced section of RBS connections. This study aims to improve the performance of DF connections to make them viable alternatives to RBS connections for ductile steel frames in seismic regions. A wide range of experimentally validated non-linear FE models are used to investigate the effects of different design parameters such as drilled flange hole locations, hole configurations, panel zone shear strength ratio and doubler plate thickness. The results indicate that there is an optimum location and configuration for the drilled flange holes, which can reduce by up to 40% the maximum Equivalent Plastic Strain and Rupture Index of DF connections. It is shown that using strong panel zones can also improve the seismic performance of DF connections by reducing stress concentrations at the CJP groove weld lines. The results of this study are used to develop optimum design solutions for DF connections, which should prove useful in practical applications

Speaker- versus listener-oriented disfluency: A re-examination of arguments and assumptions from autism spectrum disorder

We re-evaluate conclusions about disfluency production in high-functioning forms of autism spectrum disorder (HFA). Previous studies examined individuals with HFA to address a theoretical question regarding speaker- and listener-oriented disfluencies. Individuals with HFA tend to be self-centric and have poor pragmatic language skills, and should be less likely to produce listener-oriented disfluency. However, previous studies did not account for individual differences variables that affect disfluency. We show that both matched and unmatched controls produce fewer repairs than individuals with HFA. For silent pauses, there was no difference between matched controls and HFA, but both groups produced more than unmatched controls. These results identify limitations in prior research and shed light on the relationship between autism spectrum disorders and disfluent speech

Direct measurements of the nucleosome-forming preferences of periodic DNA motifs challenge established models

Several periodic motifs have been implicated in facilitating the bending of DNA around the histone core of the nucleosome. For example, di-nucleotides AA/TT/TA and GC at ∼10-bp periods, but offset by 5 bp, are found with higher-than-expected occurrences in aligned nucleosomal DNAs in vitro and in vivo. Additionally, regularly oscillating period-10 trinucleotide motifs non-T, A/T, G and their complements have been implicated in the formation of regular nucleosome arrays. The effects of these periodic motifs on nucleosome formation have not been systematically tested directly by competitive reconstitution assays. We show that, in general, none of these period-10 motifs, except TA, in certain sequence contexts, facilitates nucleosome formation. The influence of periodic TAs on nucleosome formation is appreciable; with some of the 200-bp DNAs out-competing bulk nucleosomal DNA by more than 400-fold. Only the nucleotides immediately flanking TA influence its nucleosome-forming ability. Period-10 TA, when flanked by a pair of permissive nucleotides, facilitates DNA bending through compression of the minor groove. The free energy change for nucleosome formation decreases linearly with the number of consecutive TAs, up to eight. We suggest how these data can be reconciled with previous findings

Polycomb repressor complex 1 member, BMI1 contributes to urothelial tumorigenesis through p16-independent mechanisms

Urothelial carcinoma (UC) causes significant morbidity and remains the most expensive cancer to treat due to the need for repeated resections and life-long monitoring for patients with non-muscle-invasive bladder cancer (NMIBC). Novel therapeutics and stratification approaches are needed to improve the outlook for both NMIBC and muscle-invasive bladder cancer (MIBC). We investigated the expression and effects of B Lymphoma Mo-MLV Insertion Region 1 (BMI1) in UC. BMI1 was found to be over-expressed in most UC cell lines and primary tumors by quantitative-real-time-PCR and immunohistochemistry. In contrast to some previous reports, no association with tumor stage or grade was observed in 2 independent tumor panels. Furthermore, up-regulation of BMI1 was detected in premalignant bladder lesions, suggesting a role early in tumorigenesis. BMI1 is not located within a common region of genomic amplification in UC. The CDKN2A locus (which encodes the p16 tumor suppressor gene) is a transcriptional target of BMI1 in some cellular contexts. In UC cell lines and primary tissues, no correlation between BMI1 and p16 expression was observed. Retroviral-mediated over-expression of BMI1 immortalized normal human urothelial cells (NHUC) in vitro and was associated with induction of telomerase activity, bypass of senescence and repression of differentiation. The effects of BMI1 on gene expression were identified by expression microarray analysis of NHUC-BMI1. MetacoreTM analysis of the gene expression profile implicated downstream effects of BMI1 on α4/β1 integrin-mediated adhesion, cytoskeleton remodelling and CREB1-mediated transcription

Magnified image spatial spectrum (MISS) microscopy for nanometer and millisecond scale label-free imaging

Label-free imaging of rapidly moving, sub-diffraction sized structures has important applications in both biology and material science, as it removes the limitations associated with fluorescence tagging. However, unlabeled nanoscale particles in suspension are difficult to image due to their transparency and fast Brownian motion. Here we describe a novel interferometric imaging technique referred to as Magnified Image Spatial Spectrum (MISS) microscopy, which overcomes these challenges. The MISS microscope provides quantitative phase information and enables dynamic light scattering investigations with an overall optical path length sensitivity of 0.95 nm at 833 frames per second acquisition rate. Using spatiotemporal filtering, we find that the sensitivity can be further pushed down to 10−3-10−2 nm. We demonstrate the instrument???s capability through colloidal nanoparticle sizing down to 20 nm diameter and measurements of live neuron membrane dynamics. MISS microscopy is implemented as an upgrade module to an existing microscope, which converts it into a powerful light scattering instrument. Thus, we anticipate that MISS will be adopted broadly for both material and life sciences applications

Radiation Induces Acute Alterations in Neuronal Function

Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABAARs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study

Simple robust parameter estimation for the Birnbaum-Saunders distribution

© 2015, Wang et al. We study the problem of robust estimation for the two-parameter Birnbaum-Saunders distribution. It is well known that the maximum likelihood estimator (MLE) is efficient when the underlying model is true but at the same time it is quite sensitive to data contamination that is often encountered in practice. In this paper, we propose several estimators which have simple closed forms and are also robust to data contamination. We study the breakdown points and asymptotic properties of the proposed estimators. These estimators are then applied to both simulated and real datasets. Numerical results show that the proposed estimators are attractive alternative to the MLE in that they are quite robust to data contamination and also highly efficient when the underlying model is true

Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation

Amongst all the internal gene segments (PB2. PB1, PA, NP, M and NS), the avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis, we tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature. These viruses were potent inducers of proinflammatory cytokines and chemokines in primary human macrophages and pneumocytes. Viruses with this specific PB2-PB1 combination were also found to be more capable to generate adaptive mutations under a new selection pressure. These results suggested that the viral polymerase activity might be relevant for the genesis of influenza viruses of human health concern

Identification and functional annotation of genes differentially expressed in the reproductive tissues of the olive tree (Olea europaea L.) through the generation of subtractive libraries

© 2017 Zafra, Carmona, Traverso, Hancock, Goldman, Claros, Hiscock and Alche. The olive tree is a crop of high socio-economical importance in the Mediterranean area. Sexual reproduction in this plant is an essential process, which determines the yield. Successful fertilization is mainly favored and sometimes needed of the presence of pollen grains from a different cultivar as the olive seizes a self-incompatibility system allegedly determined of the sporophytic type. The purpose of the present study was to identify key gene products involved in the function of olive pollen and pistil, in order to help elucidate the events and signaling processes, which happen during the courtship, pollen grain germination, and fertilization in olive. The use of subtractive SSH libraries constructed using, on the one hand one specific stage of the pistil development with germinating pollen grains, and on the other hand mature pollen grains may help to reveal the specific transcripts involved in the cited events. Such libraries have also been created by subtracting vegetative mRNAs (from leaves), in order to identify reproductive sequences only. A variety of transcripts have been identified in the mature pollen grains and in the pistil at the receptive stage. Among them, those related to defense, transport and oxidative metabolism are highlighted mainly in the pistil libraries where transcripts related to stress, and response to biotic and abiotic stimulus have a prominent position. Extensive lists containing information as regard to the specific transcripts determined for each stage and tissue are provided, as well as functional classifications of these gene products. Such lists were faced up to two recent datasets obtained in olive after transcriptomic and genomic approaches. The sequences and the differential expression level of the SSH-transcripts identified here, highly matched the transcriptomic information. Moreover, the unique presence of a representative number of these transcripts has been validated by means of qPCR approaches. The construction of SSH libraries using pistil and pollen, considering the high interaction between male-female counterparts, allowed the identification of transcripts with important roles in stigma physiology. The functions of many of the transcripts obtained are intimately related, and most of them are of pivotal importance in defense, pollen-stigma interaction and signaling