Intra-Operative Frozen Sections for Ovarian Tumors – A Tertiary Center Experience

PubMed Central

Arshad, Nur Zaiti Md; Ng, Beng Kwang; Paiman, Noor Asmaliza Md; Mahdy, Zaleha Abdullah; Noor, Rushdan Mohd

2018-01-01

Background: Accuracy of diagnosis with intra-operative frozen sections is extremely important in the evaluation of ovarian tumors so that appropriate surgical procedures can be selected. Study design: All patients who with intra-operative frozen sections for ovarian masses in a tertiary center over nine years from June 2008 until April 2017 were reviewed. Frozen section diagnosis and final histopathological reports were compared. Main outcome measures: Sensitivity, specificity, positive and negative predictive values of intra-operative frozen section as compared to final histopathological results for ovarian tumors. Results: A total of 92 cases were recruited for final evaluation. The frozen section diagnoses were comparable with the final histopathological reports in 83.7% of cases. The sensitivity, specificity, positive predictive value and negative predictive value for benign and malignant ovarian tumors were 95.6%, 85.1%, 86.0% and 95.2% and 69.2%, 100%, 100% and 89.2% respectively. For borderline ovarian tumors, the sensitivity and specificity were 76.2% and 88.7%, respectively; the positive predictive value was 66.7% and the negative predictive value was 92.7%. Conclusion: The accuracy of intra-operative frozen section diagnoses for ovarian tumors is high and this approach remains a reliable option in assessing ovarian masses intra-operatively. PMID:29373916

Sucrose metabolism gene families and their biological functions

PubMed Central

Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

2015-01-01

Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

Distribution and predictors of wing shape and size variability in three sister species of solitary bees

PubMed Central

Prunier, Jérôme G.; Dewulf, Alexandre; Kuhlmann, Michael; Michez, Denis

2017-01-01

Morphological traits can be highly variable over time in a particular geographical area. Different selective pressures shape those traits, which is crucial in evolutionary biology. Among these traits, insect wing morphometry has already been widely used to describe phenotypic variability at the inter-specific level. On the contrary, fewer studies have focused on intra-specific wing morphometric variability. Yet, such investigations are relevant to study potential convergences of variation that could highlight micro-evolutionary processes. The recent sampling and sequencing of three solitary bees of the genus Melitta across their entire species range provides an excellent opportunity to jointly analyse genetic and morphometric variability. In the present study, we first aim to analyse the spatial distribution of the wing shape and centroid size (used as a proxy for body size) variability. Secondly, we aim to test different potential predictors of this variability at both the intra- and inter-population levels, which includes genetic variability, but also geographic locations and distances, elevation, annual mean temperature and precipitation. The comparison of spatial distribution of intra-population morphometric diversity does not reveal any convergent pattern between species, thus undermining the assumption of a potential local and selective adaptation at the population level. Regarding intra-specific wing shape differentiation, our results reveal that some tested predictors, such as geographic and genetic distances, are associated with a significant correlation for some species. However, none of these predictors are systematically identified for the three species as an important factor that could explain the intra-specific morphometric variability. As a conclusion, for the three solitary bee species and at the scale of this study, our results clearly tend to discard the assumption of the existence of a common pattern of intra-specific signal/structure within the intra-specific wing shape and body size variability. PMID:28273178

Graph-based network analysis of resting-state functional MRI.

PubMed

Wang, Jinhui; Zuo, Xinian; He, Yong

2010-01-01

In the past decade, resting-state functional MRI (R-fMRI) measures of brain activity have attracted considerable attention. Based on changes in the blood oxygen level-dependent signal, R-fMRI offers a novel way to assess the brain's spontaneous or intrinsic (i.e., task-free) activity with both high spatial and temporal resolutions. The properties of both the intra- and inter-regional connectivity of resting-state brain activity have been well documented, promoting our understanding of the brain as a complex network. Specifically, the topological organization of brain networks has been recently studied with graph theory. In this review, we will summarize the recent advances in graph-based brain network analyses of R-fMRI signals, both in typical and atypical populations. Application of these approaches to R-fMRI data has demonstrated non-trivial topological properties of functional networks in the human brain. Among these is the knowledge that the brain's intrinsic activity is organized as a small-world, highly efficient network, with significant modularity and highly connected hub regions. These network properties have also been found to change throughout normal development, aging, and in various pathological conditions. The literature reviewed here suggests that graph-based network analyses are capable of uncovering system-level changes associated with different processes in the resting brain, which could provide novel insights into the understanding of the underlying physiological mechanisms of brain function. We also highlight several potential research topics in the future.

MRI of the sacroiliac joints in spondyloarthritis: the added value of intra-articular signal changes for a 'positive MRI'.

PubMed

Laloo, Frederiek; Herregods, N; Jaremko, J L; Verstraete, K; Jans, L

2018-05-01

To determine if intra-articular signal changes at the sacroiliac joint space on MRI have added diagnostic value for spondyloarthritis, when compared to bone marrow edema (BME). A retrospective study was performed on the MRIs of sacroiliac joints of 363 patients, aged 16-45 years, clinically suspected of sacroiliitis. BME of the sacroiliac joints was correlated to intra-articular sacroiliac joint MR signal changes: high T1 signal, fluid signal, ankylosis and vacuum phenomenon (VP). These MRI findings were correlated with final clinical diagnosis. Sensitivity (SN), specificity (SP), likelihood ratios (LR), predictive values and post-test probabilities were calculated. BME had SN of 68.9%, SP of 74.0% and LR+ of 2.6 for diagnosis of spondyloarthritis. BME in absence of intra-articular signal changes had a lower SN and LR+ for spondyloarthritis (SN = 20.5%, LR+ 1.4). Concomitant BME and high T1 signal (SP = 97.2%, LR + = 10.5), BME and fluid signal (SP = 98.6%, LR + = 10.3) or BME and ankylosis (SP = 100%) had higher SP and LR+ for spondyloarthritis. Concomitant BME and VP had low LR+ for spondyloarthritis (SP = 91%, LR + =0.9). When BME was absent, intra-articular signal changes were less prevalent, but remained highly specific for spondyloarthritis. Our results suggest that both periarticular and intra-articular MR signal of the sacroiliac joint should be examined to determine whether an MRI is 'positive' or 'not positive' for sacroiliitis associated with spondyloarthritis.

Selection of a DNA barcode for Nectriaceae from fungal whole-genomes.

PubMed

Zeng, Zhaoqing; Zhao, Peng; Luo, Jing; Zhuang, Wenying; Yu, Zhihe

2012-01-01

A DNA barcode is a short segment of sequence that is able to distinguish species. A barcode must ideally contain enough variation to distinguish every individual species and be easily obtained. Fungi of Nectriaceae are economically important and show high species diversity. To establish a standard DNA barcode for this group of fungi, the genomes of Neurospora crassa and 30 other filamentous fungi were compared. The expect value was treated as a criterion to recognize homologous sequences. Four candidate markers, Hsp90, AAC, CDC48, and EF3, were tested for their feasibility as barcodes in the identification of 34 well-established species belonging to 13 genera of Nectriaceae. Two hundred and fifteen sequences were analyzed. Intra- and inter-specific variations and the success rate of PCR amplification and sequencing were considered as important criteria for estimation of the candidate markers. Ultimately, the partial EF3 gene met the requirements for a good DNA barcode: No overlap was found between the intra- and inter-specific pairwise distances. The smallest inter-specific distance of EF3 gene was 3.19%, while the largest intra-specific distance was 1.79%. In addition, there was a high success rate in PCR and sequencing for this gene (96.3%). CDC48 showed sufficiently high sequence variation among species, but the PCR and sequencing success rate was 84% using a single pair of primers. Although the Hsp90 and AAC genes had higher PCR and sequencing success rates (96.3% and 97.5%, respectively), overlapping occurred between the intra- and inter-specific variations, which could lead to misidentification. Therefore, we propose the EF3 gene as a possible DNA barcode for the nectriaceous fungi.

Role of imprint cytology in intra operative diagnosis of thyroid lesions.

PubMed

Anila, K R; Krishna, G

2014-07-01

Intra-operative imprint cytology is an important diagnostic modality in the diagnosis of thyroid lesions. A correct intra-operative diagnosis helps eliminate the need for second surgery. To study diagnostic accuracy of imprint cytology and to compare the imprint cytology results with that of the corresponding paraffin section diagnosis in thyroidectomy cases. This is a prospective study of 84 patients who have undergone thyroidectomies over a period of one year at the Department of Surgery, Thiruvananthapuram, Kerala, India. The intraoperative imprint cytology smears were stained by Papanicolaou method. The imprint cytology interpretation was later compared with the paraffin section diagnosis. Of the 84 patients using haematoxylin and eosin stained histopathology sections as the gold standard, the diagnostic sensitivity of imprint cytology was 75% and specificity was 100%. Positive predictive value was 100%. Negative predictive value was 98.74%. Imprint cytology has high sensitivity and specificity in diagnosing lesions of the thyroid. The problems faced were in diagnosing follicular carcinomas and differentiating low grade lymphoma from lymphocytic thyroiditis. Imprint cytology is a simple, reliable diagnostic technique. It has high sensitivity and specificity in intra-operative diagnosis of lesions of thyroid. In spite of the advent of newer diagnostic modalities like frozen sections, imprint cytology still holds its unique position in the current perspective.

Huperzine alkaloids from Australasian and southeast Asian Huperzia.

PubMed

Lim, Wei-Han; Goodger, Jason Q D; Field, Ashley R; Holtum, Joseph A M; Woodrow, Ian E

2010-09-01

The pharmaceutical alkaloid huperzine A (HupA), currently used in herbal supplements and medicines worldwide, is predominantly sourced from the Chinese lycopod Huperzia serrata (Thunb. ex Murray) Trev. (Lycopodiaceae), which on average contains only 0.08 mg HupA g(-1) dry weight, and is experiencing a rapid decline in China due to over-harvesting. To find a high-yielding, natural source of HupA and/or the related huperzine B (HupB) that could potentially be used as the starting material in a commercial propagation program. We surveyed 17 Huperzia species (15 indigenous to Australia and southeast Asia) for their foliar HupA and HupB concentrations. We also studied intra-specific variation for the huperzines in four species that were available in sufficient numbers, and determined tissue-specific accumulation in larger specimens. HupA was detected in 11 Australasian and southeast Asian species, with eight also containing HupB, albeit at much lower concentrations. A H. elmeri (Herter) Holub plant from the Philippines had one of the highest HupA concentrations recorded (1.01 mg g(-1) dry wt) and it also had the highest HupB content of all plants surveyed (0.34 mg g(-1) dry wt). Intra-specific HupA and HupB concentrations were extremely variable, and at the intra-plant level, reproductive strobili were found to accumulate the highest HupA concentrations. Select Huperzia species from Australia and southeast Asia have potential as the starting material for establishing commercial HupA plantations, but the high intra-specific variability observed suggests that detailed screening is needed to isolate high huperzine-yielding individuals.

A path-based measurement for human miRNA functional similarities using miRNA-disease associations

NASA Astrophysics Data System (ADS)

Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

2016-09-01

Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

Effects of immunization with the rNfa1 protein on experimental Naegleria fowleri-PAM mice.

PubMed

Lee, Y J; Kim, J H; Sohn, H J; Lee, J; Jung, S Y; Chwae, Y J; Kim, K; Park, S; Shin, H J

2011-07-01

Free-living Naegleria fowleri causes primary amoebic meningoencephalitis (PAM) in humans and animals. To examine the effect of immunization with Nfa1 protein on experimental murine PAM because of N. fowleri, BALB/c mice were intra-peritoneally or intra-nasally immunized with a recombinant Nfa1 protein. We analysed Nfa1-specific antibody and cytokine induction, and the mean survival time of infected mice. Mice immunized intra-peritoneally or intra-nasally with rNfa1 protein developed specific IgG, IgA and IgE antibodies; the IgG response was dominated by IgG1, followed by IgG2b, IgG2a and IgG3. High levels of the Th1 cytokine, IFN-γ, and the regulatory cytokine, IL-10, were also induced. The mean survival time of mice immunized intra-peritoneally with rNfa1 protein was prolonged compared with controls, (25.0 and 15.5 days, respectively). Similarly, the mean survival time of mice immunized intra-nasally with rNfa1 protein was 24.7 days, compared with 15.0 days for controls. © 2011 Blackwell Publishing Ltd.

Sex and species specific isotopic niche specialisation increases with trophic complexity: evidence from an ephemeral pond ecosystem

PubMed Central

Dalu, Tatenda; Wasserman, Ryan J.; Vink, Tim J. F.; Weyl, Olaf L. F.

2017-01-01

It is generally accepted that organisms that naturally exploit an ecosystem facilitate coexistence, at least partially, through resource partitioning. Resource availability is, however, highly variable in space and time and as such the extent of resource partitioning must be somewhat dependent on availability. Here we test aspects of resource partitioning at the inter- and intra-specific level, in relation to resource availability in an atypical aquatic environment using an isotope approach. Using closely related key organisms from an ephemeral pond, we test for differences in isotopic signatures between two species of copepod and between sexes within each species, in relation to heterogeneity of basal food resources over the course of the ponds hydroperiod. We show that basal food resource heterogeneity increases over time initially, and then decreases towards the end of the hydroperiod, reflective of the expected evolution of trophic complexity for these systems. Resource partitioning also varied between species and sexes, over the hydroperiod with intra- and inter-specific specialisation relating to resource availability. Intra-specific specialisation was particularly evident in the omnivorous copepod species. Our findings imply that trophic specialisation at both the intra- and inter-specific level is partly driven by basal food resource availability. PMID:28233858

Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells

PubMed Central

Jia, Pingping; Chastain, Megan; Zou, Ying; Her, Chengtao

2017-01-01

Abstract Aberrant formation of interstitial telomeric sequences (ITSs) promotes genome instabilities. However, it is unclear how aberrant ITS formation is suppressed in human cells. Here, we report that MLH1, a key protein involved in mismatch repair (MMR), suppresses telomeric sequence insertion (TSI) at intra-chromosomal regions. The frequency of TSI can be elevated by double-strand break (DSB) inducer and abolished by ATM/ATR inhibition. Suppression of TSI requires MLH1 recruitment to DSBs, indicating that MLH1's role in DSB response/repair is important for suppressing TSI. Moreover, TSI requires telomerase activity but is independent of the functional status of p53 and Rb. Lastly, we show that TSI is associated with chromosome instabilities including chromosome loss, micronuclei formation and chromosome breakage that are further elevated by replication stress. Our studies uncover a novel link between MLH1, telomerase, telomere and genome stability. PMID:28180301

It's time to change perspective! New diagnostic tools for lateral elbow pain.

PubMed

Arrigoni, P; Cucchi, D; Menon, A; Randelli, P

2017-12-01

The presence of intra-articular findings that may complement the extra-articular pathology in lateral epicondilytis has been suggested, and a role for minor instability of the elbow as part of the causative process of this disease has been postulated. This study was designed to describe two new clinical tests, aimed at detecting intra-articular pathology in patients affected by recalcitrant lateral epicondylitis and investigate their diagnostic performance. Ten patients suffering of atraumatic lateral elbow pain unresponsive to conservative treatment were considered in this study. Two clinical tests were developed and administrated prior to arthroscopy: Supination and Antero-Lateral pain Test (SALT); Posterior Elbow Pain by Palpation-Extension of the Radiocapitellar joint (PEPPER). Sensitivity, specificity, predictive values and accuracy of SALT and PEPPER as diagnostic tests for seven intra-articular findings were calculated. In 90% of the patients, at least one test was positive. All patients with signs of lateral ligamentous patholaxity or intra-articular abnormal findings had a positive response to at least one of the two tests. SALT proved to have a high sensitivity but a low specificity and is accurate in detecting the presence of intra-articular abnormal findings, especially synovitis. PEPPER test was sensible, specific and accurate in the detection of radial head chondropathy. Two new diagnostic tests (SALT and PEPPER) were specifically designed to evoke pain from intra-articular structures. These tests could be a valid support in the diagnostic algorithm of recalcitrant lateral elbow pain. Positive findings may be indicative of a minor instability of the lateral elbow condition. Diagnostic study, development of diagnostic criteria on basis of consecutive patients, level II.

Computational Analysis of Intra-Ventricular Flow Pattern Under Partial and Full Support of BJUT-II VAD.

PubMed

Zhang, Qi; Gao, Bin; Chang, Yu

2017-02-27

BACKGROUND Partial support, as a novel support mode, has been widely applied in clinical practice and widely studied. However, the precise mechanism of partial support of LVAD in the intra-ventricular flow pattern is unclear. MATERIAL AND METHODS In this study, a patient-specific left ventricular geometric model was reconstructed based on CT data. The intra-ventricular flow pattern under 3 simulated conditions - "heart failure", "partial support", and "full support" - were simulated by using fluid-structure interaction (FSI). The blood flow pattern, wall shear stress (WSS), time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated to evaluate the hemodynamic effects. RESULTS The results demonstrate that the intra-ventricular flow pattern is significantly changed by the support level of BJUT-II VAD. The intra-ventricular vortex was enhanced under partial support and was eliminated under full support, and the high OSI and RRT regions changed from the septum wall to the cardiac apex. CONCLUSIONS In brief, the support level of the BJUT-II VAD has significant effects on the intra-ventricular flow pattern. The partial support mode of BJUT-II VAD can enhance the intra-ventricular vortex, while the distribution of high OSI and RRT moved from the septum wall to the cardiac apex. Hence, the partial support mode of BJUT-II VAD can provide more benefit for intra-ventricular flow pattern.

Plant Trait Variation along an Altitudinal Gradient in Mediterranean High Mountain Grasslands: Controlling the Species Turnover Effect

PubMed Central

Pescador, David S.; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

2015-01-01

Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m–2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes. PMID:25774532

Plant trait variation along an altitudinal gradient in mediterranean high mountain grasslands: controlling the species turnover effect.

PubMed

Pescador, David S; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

2015-01-01

Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m-2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes.

Solvent screening for a hard-to-dissolve molecular crystal.

PubMed

Maiti, A; Pagoria, P F; Gash, A E; Han, T Y; Orme, C A; Gee, R H; Fried, L E

2008-09-01

Materials with a high-degree of inter- and intra-molecular hydrogen bonding generally have limited solubility in conventional organic solvents. This presents a problem for the dissolution, manipulation and purification of these materials. Using a state-of-the-art density-functional-theory based quantum chemical solvation model we systematically evaluated solvents for a known hydrogen-bonded molecular crystal. This, coupled with direct solubility measurements, uncovered a class of ionic liquids involving fluoride anions that possess more than two orders of magnitude higher solvation power as compared with the best conventional solvents. The crystal structure of one such ionic liquid, determined by X-ray diffraction spectroscopy, indicates that F- ions are stabilized through H-bonded chains with water. The presence of coordinating water in such ionic liquids seems to facilitate the dissolution process by keeping the chemical activity of the F- ions in check.

Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk

PubMed Central

Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

2015-01-01

Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

Nitrogen Level Changes the Interactions between a Native (Scirpus triqueter) and an Exotic Species (Spartina anglica) in Coastal China

PubMed Central

Li, Hong-li; Lei, Guang-chun; Zhi, Ying-biao; An, Shu-qing; Huang, He-ping; Ouyang, Yan; Zhao, Lei; Deng, Zi-fa; Liu, Yu-hong

2011-01-01

The exotic species Spartina anglica, introduced from Europe in 1963, has been experiencing a decline in the past decade in coastal China, but the reasons for the decline are still not clear. It is hypothesized that competition with the native species Scirpus triqueter may have played an important role in the decline due to niche overlap in the field. We measured biomass, leaf number and area, asexual reproduction and relative neighborhood effect (RNE) of the two species in both monoculture and mixture under three nitrogen levels (control, low and high). S. anglica showed significantly lower biomass accumulation, leaf number and asexual reproduction in mixture than in monoculture. The inter- and intra-specific RNE of S. anglica were all positive, and the inter-specific RNE was significantly higher than the intra-specific RNE in the control. For S. triqueter, inter- and intra-specific RNE were negative at the high nitrogen level but positive in the control and at the low nitrogen level. This indicates that S. triqueter exerted an asymmetric competitive advantage over S. anglica in the control and low nitrogen conditions; however, S. anglica facilitated growth of S. triqueter in high nitrogen conditions. Nitrogen level changed the interactions between the two species because S. triqueter better tolerated low nitrogen. Since S. anglica is increasingly confined to upper, more nitrogen-limited marsh areas in coastal China, increased competition from S. triqueter may help explain its decline. PMID:21998676

Food choice effects on herbivory: Intra-specific seagrass palatability and inter-specific macrophyte palatability in seagrass communities

NASA Astrophysics Data System (ADS)

Jiménez-Ramos, Rocío; Brun, Fernando G.; Egea, Luis G.; Vergara, Juan J.

2018-05-01

Interactions between the palatability and abundance of different food sources may influence herbivory patterns in seagrass-dominated communities. In addition, intra-specific differences in nutrient and structural quality of leaves may also alter seagrass palatability and generate different rates of consumption within these communities. We offered two temperate seagrasses species, (Cymodocea nodosa and Zostera noltei) from two different locations to look at intraspecific differences, and two other macrophytes, both of which occur at the same location as seagrasses but represent the extremes of palatability, to a generalist herbivore Paracentrotus lividus (purple sea urchin). Using feeding assays, we compared the consumption rates in individual (single plant species) and combined diets at different food availabilities. Intra-specific differences between seagrass species growing at different locations (inner and outer bay) were indeed found to significantly modify the consumption rate for one species. Structural traits such as carbon content were linked to the low consumption found in Cymodocea nodosa from the inner bay location. In addition, we found that the co-occurrence of different macrophyte species can result in preferential consumption of the more palatable macrophyte with high nutritional content and low structural defence over seagrasses, especially when P. lividus has an abundant food supply. Overall, our findings suggest that intra- and inter-specific differences in seagrass traits and the relative abundance of other macrophytes may explain the variability in patterns of herbivory found within seagrass communities.

Bimanual Capacity of Children With Cerebral Palsy: Intra- and Interrater Reliability of a Revised Edition of the Bimanual Fine Motor Function Classification.

PubMed

Elvrum, Ann-Kristin G; Beckung, Eva; Sæther, Rannei; Lydersen, Stian; Vik, Torstein; Himmelmann, Kate

2017-08-01

To develop a revised edition of the Bimanual Fine Motor Function (BFMF 2), as a classification of fine motor capacity in children with cerebral palsy (CP), and establish intra- and interrater reliability of this edition. The content of the original BFMF was discussed by an expert panel, resulting in a revised edition comprising the original description of the classification levels, but in addition including figures with specific explanatory text. Four professionals classified fine motor function of 79 children (3-17 years; 45 boys) who represented all subtypes of CP and Manual Ability Classification levels (I-V). Intra- and inter-rater reliability was assessed using overall intra-class correlation coefficient (ICC), and Cohen's quadratic weighted kappa. The overall ICC was 0.86. Cohen's weighted kappa indicated high intra-rater (к w : >0.90) and inter-rater (к w : >0.85) reliability. The revised BFMF 2 had high intra- and interrater reliability. The classification levels could be determined from short video recordings (<5 minutes), using the figures and precise descriptions of the fine motor function levels included in the BFMF 2. Thus, the BFMF 2 may be a feasible and useful classification of fine motor capacity both in research and in clinical practice.

O-GlcNAc: a novel regulator of immunometabolism.

PubMed

Machacek, Miranda; Slawson, Chad; Fields, Patrick E

2018-06-01

The rapidly expanding field of immunometabolism focuses on how metabolism controls the function of immune cells. CD4 + T cells are essential for the adaptive immune response leading to the eradication of specific pathogens. However, when T cells are inappropriately over-active, they can drive autoimmunity, allergic disease, and chronic inflammation. The mechanisms by which metabolic changes influence function in CD4 + T cells are not fully understood. The post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine), dynamically cycles on and off of intracellular proteins as cells respond to their environment and flux through metabolic pathways changes. As the rate of O-GlcNAc cycling fluctuates, protein function, stability, and/or localization can be affected. Thus, O-GlcNAc is critically poised at the nexus of cellular metabolism and function. This review highlights the intra- and extracellular metabolic factors that influence CD4 + T cell activation and differentiation and how O-GlcNAc regulates these processes. We also propose areas of future research that may illuminate O-GlcNAc's role in the plasticity and pathogenicity of CD4 + T cells and uncover new potential therapeutic targets.

Intra-sexual competition alters the relationship between testosterone and ornament expression in a wild territorial bird.

PubMed

Martínez-Padilla, J; Pérez-Rodríguez, L; Mougeot, F; Ludwig, S; Redpath, S M

2014-05-01

In a reliable signalling system, individual quality is expected to mediate the costs associated with ornamental displays, with relatively lower costs being paid by individuals of higher quality. These relative costs should depend not only on individual quality, but also on levels of intra-sexual competition. We explored the current and delayed effects that testosterone implants have on bird ornamentation in populations with contrasted population densities, as a proxy for intra-sexual competition. In a replicated experiment, we manipulated testosterone in 196 yearling male red grouse Lagopus lagopus scoticus in autumn in populations of high and low levels of intra-sexual competition. Males were assigned to one of three exogenous testosterone (T) treatments: empty implants (T0), small T implants (T1) or larger T implants (T2). We monitored subsequent changes in testosterone levels, ornament size and carotenoid-based colouration, carotenoid levels and body condition from autumn to spring. Testosterone implants increased testosterone levels, comb redness and comb size, and decreased body condition but these effects depended on levels of intra-sexual competition. Specifically, T2-implanted birds increased testosterone levels and comb size more, and reduced body condition more, in populations where intra-sexual competition was low. In the following spring, testosterone levels of T2-treated birds kept increasing in populations where intra-sexual competition was high but not in populations where intra-sexual competition was low. Our results highlight that levels of intra-sexual competition alter the relationship between testosterone levels and ornament expression, influencing their condition-dependence; they also indicate that the outcome of standard hormone manipulation conducted in free-living animals vary depending on the population context. Copyright © 2014 Elsevier Inc. All rights reserved.

Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

PubMed Central

Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

2015-01-01

Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

Contact Networks in a Wildlife-Livestock Host Community: Identifying High-Risk Individuals in the Transmission of Bovine TB among Badgers and Cattle

PubMed Central

Böhm, Monika; Hutchings, Michael R.; White, Piran C. L.

2009-01-01

Background The management of many pathogens, which are of concern to humans and their livestock, is complicated by the pathogens' ability to cross-infect multiple host species, including wildlife. This has major implications for the management of such diseases, since the dynamics of infection are dependent on the rates of both intra- and inter-specific transmission. However, the difficulty of studying transmission networks in free-living populations means that the relative opportunities for intra- versus inter-specific disease transmission have not previously been demonstrated empirically within any wildlife-livestock disease system. Methodology/Principal Findings Using recently-developed proximity data loggers, we quantify both intra-and inter-specific contacts in a wildlife-livestock disease system, using bovine tuberculosis (bTB) in badgers and cattle in the UK as our example. We assess the connectedness of individuals within the networks in order to identify whether there are certain ‘high-risk’ individuals or groups of individuals for disease transmission within and between species. Our results show that contact patterns in both badger and cattle populations vary widely, both between individuals and over time. We recorded only infrequent interactions between badger social groups, although all badgers fitted with data loggers were involved in these inter-group contacts. Contacts between badgers and cattle occurred more frequently than contacts between different badger groups. Moreover, these inter-specific contacts involved those individual cows, which were highly connected within the cattle herd. Conclusions/Significance This work represents the first continuous time record of wildlife-host contacts for any free-living wildlife-livestock disease system. The results highlight the existence of specific individuals with relatively high contact rates in both livestock and wildlife populations, which have the potential to act as hubs in the spread of disease through complex contact networks. Targeting testing or preventive measures at high-contact groups and individuals within livestock populations would enhance the effectiveness and efficiency of disease management strategies. PMID:19401755

A systematic analysis of a mi-RNA inter-pathway regulatory motif

PubMed Central

2013-01-01

Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and “indirect” paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules. PMID:24152805

Integrated genomic and interfacility patient-transfer data reveal the transmission pathways of multidrug-resistant Klebsiella pneumoniae in a regional outbreak.

PubMed

Snitkin, Evan S; Won, Sarah; Pirani, Ali; Lapp, Zena; Weinstein, Robert A; Lolans, Karen; Hayden, Mary K

2017-11-22

Development of effective strategies to limit the proliferation of multidrug-resistant organisms requires a thorough understanding of how such organisms spread among health care facilities. We sought to uncover the chains of transmission underlying a 2008 U.S. regional outbreak of carbapenem-resistant Klebsiella pneumoniae by performing an integrated analysis of genomic and interfacility patient-transfer data. Genomic analysis yielded a high-resolution transmission network that assigned directionality to regional transmission events and discriminated between intra- and interfacility transmission when epidemiologic data were ambiguous or misleading. Examining the genomic transmission network in the context of interfacility patient transfers (patient-sharing networks) supported the role of patient transfers in driving the outbreak, with genomic analysis revealing that a small subset of patient-transfer events was sufficient to explain regional spread. Further integration of the genomic and patient-sharing networks identified one nursing home as an important bridge facility early in the outbreak-a role that was not apparent from analysis of genomic or patient-transfer data alone. Last, we found that when simulating a real-time regional outbreak, our methodology was able to accurately infer the facility at which patients acquired their infections. This approach has the potential to identify facilities with high rates of intra- or interfacility transmission, data that will be useful for triggering targeted interventions to prevent further spread of multidrug-resistant organisms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Snake venoms from Angola: Intra-specific variations and immunogenicity.

PubMed

Oliveira, Paula Regina Simões de; França, Felipe Silva de; Villas Boas, Isadora Maria; Rocha, Marisa Maria Teixeira da; Sant'Anna, Sávio Stefanini; Bastos, Maria de Lourdes; Tambourgi, Denise V

2018-06-15

Snakebite is a public health problem in many countries of world. These accidents are considered a Neglected Tropical Disease and are responsible for a high morbidity and mortality index in the South and Southeast Asia and Sub-Saharan Africa. Angolan snake venoms are poorly investigated and no specific antivenom against them is available in the country. Thus, the aim of this study was to evaluate biochemical and immunogenic properties of male and female venoms from Naja nigricollis, Bitis arietans and Bitis gabonica snakes. These animals were collected during an expedition covering 1350 km of Angola, including the Provinces of Cuanza Sul, Benguela, Huíla and Malanje. Results showed that Angolan snake venoms present distinctive immunogenic properties and large intra-specific variations, associated to the gender and the geographic origin of the animals. Thus, it is possible to suggest that for the preparation of a therapeutic antivenom, intra-species variability should be taken into account, in order to obtain an efficient serum to neutralize the toxic effects of the Angolan snake venoms. Copyright © 2018 Elsevier Ltd. All rights reserved.

Patient-Specific Biomechanical Modeling for Guidance During Minimally-Invasive Hepatic Surgery.

PubMed

Plantefève, Rosalie; Peterlik, Igor; Haouchine, Nazim; Cotin, Stéphane

2016-01-01

During the minimally-invasive liver surgery, only the partial surface view of the liver is usually provided to the surgeon via the laparoscopic camera. Therefore, it is necessary to estimate the actual position of the internal structures such as tumors and vessels from the pre-operative images. Nevertheless, such task can be highly challenging since during the intervention, the abdominal organs undergo important deformations due to the pneumoperitoneum, respiratory and cardiac motion and the interaction with the surgical tools. Therefore, a reliable automatic system for intra-operative guidance requires fast and reliable registration of the pre- and intra-operative data. In this paper we present a complete pipeline for the registration of pre-operative patient-specific image data to the sparse and incomplete intra-operative data. While the intra-operative data is represented by a point cloud extracted from the stereo-endoscopic images, the pre-operative data is used to reconstruct a biomechanical model which is necessary for accurate estimation of the position of the internal structures, considering the actual deformations. This model takes into account the patient-specific liver anatomy composed of parenchyma, vascularization and capsule, and is enriched with anatomical boundary conditions transferred from an atlas. The registration process employs the iterative closest point technique together with a penalty-based method. We perform a quantitative assessment based on the evaluation of the target registration error on synthetic data as well as a qualitative assessment on real patient data. We demonstrate that the proposed registration method provides good results in terms of both accuracy and robustness w.r.t. the quality of the intra-operative data.

A combinatorial approach of comprehensive QTL-based comparative genome mapping and transcript profiling identified a seed weight-regulating candidate gene in chickpea

PubMed Central

Bajaj, Deepak; Upadhyaya, Hari D.; Khan, Yusuf; Das, Shouvik; Badoni, Saurabh; Shree, Tanima; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Singh, Sube; Sharma, Shivali; Tyagi, Akhilesh K.; Chattopdhyay, Debasis; Parida, Swarup K.

2015-01-01

High experimental validation/genotyping success rate (94–96%) and intra-specific polymorphic potential (82–96%) of 1536 SNP and 472 SSR markers showing in silico polymorphism between desi ICC 4958 and kabuli ICC 12968 chickpea was obtained in a 190 mapping population (ICC 4958 × ICC 12968) and 92 diverse desi and kabuli genotypes. A high-density 2001 marker-based intra-specific genetic linkage map comprising of eight LGs constructed is comparatively much saturated (mean map-density: 0.94 cM) in contrast to existing intra-specific genetic maps in chickpea. Fifteen robust QTLs (PVE: 8.8–25.8% with LOD: 7.0–13.8) associated with pod and seed number/plant (PN and SN) and 100 seed weight (SW) were identified and mapped on 10 major genomic regions of eight LGs. One of 126.8 kb major genomic region harbouring a strong SW-associated robust QTL (Caq'SW1.1: 169.1–171.3 cM) has been delineated by integrating high-resolution QTL mapping with comprehensive marker-based comparative genome mapping and differential expression profiling. This identified one potential regulatory SNP (G/A) in the cis-acting element of candidate ERF (ethylene responsive factor) TF (transcription factor) gene governing seed weight in chickpea. The functionally relevant molecular tags identified have potential to be utilized for marker-assisted genetic improvement of chickpea. PMID:25786576

Three Australian whistleblowing sagas: lessons for internal and external regulation.

PubMed

Faunce, Thomas A; Bolsin, Stephen N C

2004-07-05

The protracted and costly investigations into Camden and Campbelltown hospitals (New South Wales), The Canberra Hospital (Australian Capital Territory), and King Edward Memorial Hospital (Western Australia) recently uncovered significant problems with quality and safety at these institutions. Each investigation arose after whistleblowers alerted politicians directly, having failed to resolve the problems using existing intra-institutional structures. None of the substantiated problems had been uncovered or previously resolved by extensive accreditation or national safety and quality processes; in each instance, the problems were exacerbated by a poor institutional culture of self-regulation, error reporting or investigation. Even after substantiation of their allegations, the whistleblowers, who included staff specialists, administrators and nurses, received little respect and support from their institutions or professions. Increasing legislative protections indicate the role of whistleblowers must now be formally acknowledged and incorporated as a "last resort" component in clinical-governance structures. Portable digital technology, if adequately funded and institutionally supported, may help to transform the conscience-based activity of whistleblowing into a culture of self-reporting, linked to personal and professional development.

Robust model-based 3d/3D fusion using sparse matching for minimally invasive surgery.

PubMed

Neumann, Dominik; Grbic, Sasa; John, Matthias; Navab, Nassir; Hornegger, Joachim; Ionasec, Razvan

2013-01-01

Classical surgery is being disrupted by minimally invasive and transcatheter procedures. As there is no direct view or access to the affected anatomy, advanced imaging techniques such as 3D C-arm CT and C-arm fluoroscopy are routinely used for intra-operative guidance. However, intra-operative modalities have limited image quality of the soft tissue and a reliable assessment of the cardiac anatomy can only be made by injecting contrast agent, which is harmful to the patient and requires complex acquisition protocols. We propose a novel sparse matching approach for fusing high quality pre-operative CT and non-contrasted, non-gated intra-operative C-arm CT by utilizing robust machine learning and numerical optimization techniques. Thus, high-quality patient-specific models can be extracted from the pre-operative CT and mapped to the intra-operative imaging environment to guide minimally invasive procedures. Extensive quantitative experiments demonstrate that our model-based fusion approach has an average execution time of 2.9 s, while the accuracy lies within expert user confidence intervals.

Barcoding and species recognition of opportunistic pathogens in Ochroconis and Verruconis.

PubMed

Samerpitak, Kittipan; Gerrits van den Ende, Bert H G; Stielow, J Benjamin; Menken, Steph B J; de Hoog, G Sybren

2016-02-01

The genera Ochroconis and Verruconis (Sympoventuriaceae, Venturiales) have remarkably high molecular diversity despite relatively high degrees of phenotypic similarity. Tree topologies, inter-specific and intra-specific heterogeneities, barcoding gaps and reciprocal monophyly of all currently known species were analyzed. It was concluded that all currently used genes viz. SSU, ITS, LSU, ACT1, BT2, and TEF1 were unable to reach all 'gold standard' criteria of barcoding markers. They could nevertheless be used for reasonably reliable identification of species, because the markers, although variable, were associated with large inter-specific heterogeneity. Of the coding protein-genes, ACT1 revealed highest potentiality as barcoding marker in mostly all parts of the investigated sequence. SSU, LSU, ITS, and ACT1 yielded consistent monophyly in all investigated species, but only SSU and LSU generated clear barcoding gaps. For phylogeny, LSU was an informative marker, suitable to reconstruct gene-trees showing correct phylogenetic relationships. Cryptic species were revealed especially in complexes with very high intra-specific variability. When all these complexes will be taxonomically resolved, ACT1 will probably appear to be the most reliable barcoding gene for Ochroconis and Verruconis. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials.

PubMed

Shear, Neil H; Paul, Carle; Blauvelt, Andrew; Gooderham, Melinda; Leonardi, Craig; Reich, Kristian; Ohtsuki, Mamitaro; Pangallo, Beth; Xu, Wen; Ball, Susan; Ridenour, Terri; Torisu-Itakura, Hitoe; Agada, Noah; Mallbris, Lotus

2018-02-01

BACKGROUND: Injection-site reactions (ISRs) are reported with biologic therapies. The objective of this study was to comprehensively characterize ISRs among moderate-to-severe psoriasis patients treated with ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A.

METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12 weeks) and all ixekizumab-exposed patients in 11 controlled and uncontrolled trials (156 weeks).

RESULTS: At week 12, reported ISR frequency with 80 mg ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W, ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in the first 2 weeks (median onset, 6.6 days), and most commonly characterized as nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas pain occurred around drug administration. Discontinuation from ixekizumab due to ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency decreased and remained stable (≤4.2%) through week 156. No ISR-related serious adverse events were reported in ixekizumab-treated patients. ISR data were solicited if patients reported injection-associated events. Since nonspecified ISR was the most commonly reported term, specific types might be underreported.

CONCLUSIONS: ISRs have been reported with ixekizumab during clinical trials. These reactions are typically tolerable, manageable, and decrease over time.

Clinicaltrials.gov: NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS); NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW-RHBZ)

J Drugs Dermatol. 2018;17(2):200-206.

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Intra- and intergroup vocal behavior in resident killer whales, Orcinus orca.

PubMed

Weiss, Brigitte M; Symonds, Helena; Spong, Paul; Ladich, Friedrich

2007-12-01

Vocal communication within and between groups of individuals has been described extensively in birds and terrestrial mammals, however, little is known about how cetaceans utilize their sounds in their natural environment. Resident killer whales, Orcinus orca, live in highly stable matrilines and exhibit group-specific vocal dialects. Single call types cannot exclusively be associated with particular behaviors and calls are thought to function in group identification and intragroup communication. In the present study call usage of three closely related matrilines of the Northern resident community was compared in various intra- and intergroup contexts. In two out of the three matrilines significant changes in vocal behavior depending both on the presence and identity of accompanying whales were found. Most evidently, family-specific call subtypes, as well as aberrant and variable calls, were emitted at higher rates, whereas "low arousal" call types were used less in the presence of matrilines from different pods, subclans, or clans. Ways in which the observed changes may function both in intra- and intergroup communication.

A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells

PubMed Central

Lane, Darius J. R.; Lawen, Alfons

2014-01-01

Vitamin C (ascorbate) plays numerous important roles in cellular metabolism, many of which have only come to light in recent years. For instance, within the brain, ascorbate acts in a neuroprotective and neuromodulatory manner that involves ascorbate cycling between neurons and vicinal astrocytes - a relationship that appears to be crucial for brain ascorbate homeostasis. Additionally, emerging evidence strongly suggests that ascorbate has a greatly expanded role in regulating cellular and systemic iron metabolism than is classically recognized. The increasing recognition of the integral role of ascorbate in normal and deregulated cellular and organismal physiology demands a range of medium-throughput and high-sensitivity analytic techniques that can be executed without the need for highly expensive specialist equipment. Here we provide explicit instructions for a medium-throughput, specific and relatively inexpensive microplate assay for the determination of both intra- and extracellular ascorbate in cell culture. PMID:24747535

Mass-transport limitations in spot-based microarrays.

PubMed

Zhao, Ming; Wang, Xuefeng; Nolte, David

2010-09-20

Mass transport of analyte to surface-immobilized affinity reagents is the fundamental bottleneck for sensitive detection in solid-support microarrays and biosensors. Analyte depletion in the volume adjacent to the sensor causes deviation from ideal association, significantly slows down reaction kinetics, and causes inhomogeneous binding across the sensor surface. In this paper we use high-resolution molecular interferometric imaging (MI2), a label-free optical interferometry technique for direct detection of molecular films, to study the inhomogeneous distribution of intra-spot binding across 100 micron-diameter protein spots. By measuring intra-spot binding inhomogeneity, reaction kinetics can be determined accurately when combined with a numerical three-dimensional finite element model. To ensure homogeneous binding across a spot, a critical flow rate is identified in terms of the association rate k(a) and the spot diameter. The binding inhomogeneity across a spot can be used to distinguish high-affinity low-concentration specific reactions from low-affinity high-concentration non-specific binding of background proteins.

Development of a 63K SNP array for Gossypium and high-density mapping of intra- and inter-specific populations of cotton (G. hirsutum L.)

USDA-ARS?s Scientific Manuscript database

High-throughput genotyping arrays provide a standardized resource for crop research communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), candidate marker and quantitative trait loci (QTL) ide...

Measurement of elasticity and transepidermal water loss rate of burn scars with the Dermalab(®).

PubMed

Anthonissen, Mieke; Daly, Daniel; Fieuws, Steffen; Massagé, Patrick; Van Brussel, Michel; Vranckx, Jan; Van den Kerckhove, Eric

2013-05-01

This cross-sectional study investigated the reproducibility of repeated elasticity and transepidermal water loss (TEWL) measurements with the DermaLab(®) on 32 active burn scars and healthy skin. Intra- and inter-observer reproducibility was examined by means of intra-class correlation coefficients (ICC) and standard error of measurements (SEM). Results showed good ICC values and rather high SEM values for inter- and intra-observer reproducibility of elasticity measurements. For TEWL measurements, ICC values were good and SEM values were high for inter- and intra-observer reproducibility. There was a significant difference between the estimated mean elasticity values of normal skin and grafted scars and between normal skin and spontaneously healed scars (p≤0.003). For the estimated mean TEWL values, there was a significant difference between normal skin and spontaneously healed scars (p=0.036). A significant negative relation was reported between mean TEWL and time after burn (p=0.008). In clinical trials it is necessary to interpret patient-specific changes in elasticity and TEWL with caution, since the SEMs of both modes are rather high. We therefore recommend the use of a mean of repeated measurements of elasticity and TEWL to decrease the SEM. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

The Evolution of Vp1 Gene in Enterovirus C Species Sub-Group That Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

PubMed Central

Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

2014-01-01

Genus Enterovirus (Family Picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21), CVA-24, Enterovirus C95 (EV-C95), EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific ‘signature’ amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific ‘signature’ amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent) positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared. PMID:24695547

The evolution of Vp1 gene in enterovirus C species sub-group that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.

PubMed

Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

2014-01-01

Genus Enterovirus (Family Picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21), CVA-24, Enterovirus C95 (EV-C95), EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific 'signature' amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific 'signature' amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent) positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared.

Accuracy assessment of high frequency 3D ultrasound for digital impression-taking of prepared teeth

NASA Astrophysics Data System (ADS)

Heger, Stefan; Vollborn, Thorsten; Tinschert, Joachim; Wolfart, Stefan; Radermacher, Klaus

2013-03-01

Silicone based impression-taking of prepared teeth followed by plaster casting is well-established but potentially less reliable, error-prone and inefficient, particularly in combination with emerging techniques like computer aided design and manufacturing (CAD/CAM) of dental prosthesis. Intra-oral optical scanners for digital impression-taking have been introduced but until now some drawbacks still exist. Because optical waves can hardly penetrate liquids or soft-tissues, sub-gingival preparations still need to be uncovered invasively prior to scanning. High frequency ultrasound (HFUS) based micro-scanning has been recently investigated as an alternative to optical intra-oral scanning. Ultrasound is less sensitive against oral fluids and in principal able to penetrate gingiva without invasively exposing of sub-gingival preparations. Nevertheless, spatial resolution as well as digitization accuracy of an ultrasound based micro-scanning system remains a critical parameter because the ultrasound wavelength in water-like media such as gingiva is typically smaller than that of optical waves. In this contribution, the in-vitro accuracy of ultrasound based micro-scanning for tooth geometry reconstruction is being investigated and compared to its extra-oral optical counterpart. In order to increase the spatial resolution of the system, 2nd harmonic frequencies from a mechanically driven focused single element transducer were separated and corresponding 3D surface models were calculated for both fundamentals and 2nd harmonics. Measurements on phantoms, model teeth and human teeth were carried out for evaluation of spatial resolution and surface detection accuracy. Comparison of optical and ultrasound digital impression taking indicate that, in terms of accuracy, ultrasound based tooth digitization can be an alternative for optical impression-taking.

Two distinct, geographically overlapping lineages of the corallimorpharian Ricordea florida (Cnidaria: Hexacorallia: Ricordeidae)

NASA Astrophysics Data System (ADS)

Torres-Pratts, H.; Lado-Insua, T.; Rhyne, A. L.; Rodríguez-Matos, L.; Schizas, N. V.

2011-06-01

We examined the genetic variation of the corallimorpharian Ricordea florida; it is distributed throughout the Caribbean region and is heavily harvested for the marine aquarium trade. Eighty-four distinct individuals of R. florida were sequenced from four geographically distant Caribbean locations (Curaçao, Florida, Guadeloupe, and Puerto Rico). Analysis of the ribosomal nuclear region (ITS1, 5.8S, ITS2) uncovered two geographically partially overlapping genetic lineages in R. florida, probably representing two cryptic species. Lineage 1 was found in Florida and Puerto Rico, and Lineage 2 was found in Florida, Puerto Rico, Guadeloupe, and Curaçao. Because of the multi-allelic nature of the ITS region, four individuals from Lineage 1 and six from Lineage 2 were cloned to evaluate the levels of hidden intra-individual variability. Pairwise genetic comparisons indicated that the levels of intra-individual and intra-lineage variability (<1%) were approximately an order of magnitude lower than the divergence (~9%) observed between the two lineages. The fishery regulations of the aquarium trade regard R. florida as one species. More refined regulations should take into account the presence of two genetic lineages, and they should be managed separately in order to preserve the long-term evolutionary potential of this corallimorpharian. The discovery of two distinct lineages in R. florida illustrates the importance of evaluating genetic variability in harvested species prior to the implementation of management policies.

Self-focusing therapeutic gene delivery with intelligent gene vector swarms: intra-swarm signalling through receptor transgene expression in targeted cells.

PubMed

Tolmachov, Oleg E

2015-01-01

Gene delivery in vivo that is tightly focused on the intended target cells is essential to maximize the benefits of gene therapy and to reduce unwanted side-effects. Cell surface markers are immediately available for probing by therapeutic gene vectors and are often used to direct gene transfer with these vectors to specific target cell populations. However, it is not unusual for the choice of available extra-cellular markers to be too scarce to provide a reliable definition of the desired therapeutically relevant set of target cells. Therefore, interrogation of intra-cellular determinants of cell-specificity, such as tissue-specific transcription factors, can be vital in order to provide detailed cell-guiding information to gene vector particles. An important improvement in cell-specific gene delivery can be achieved through auto-buildup in vector homing efficiency using intelligent 'self-focusing' of swarms of vector particles on target cells. Vector self-focusing was previously suggested to rely on the release of diffusible chemo-attractants after a successful target-specific hit by 'scout' vector particles. I hypothesize that intelligent self-focusing behaviour of swarms of cell-targeted therapeutic gene vectors can be accomplished without the employment of difficult-to-use diffusible chemo-attractants, instead relying on the intra-swarm signalling through cells expressing a non-diffusible extra-cellular receptor for the gene vectors. In the proposed model, cell-guiding information is gathered by the 'scout' gene vector particles, which: (1) attach to a variety of cells via a weakly binding (low affinity) receptor; (2) successfully facilitate gene transfer into these cells; (3) query intra-cellular determinants of cell-specificity with their transgene expression control elements and (4) direct the cell-specific biosynthesis of a vector-encoded strongly binding (high affinity) cell-surface receptor. Free members of the vector swarm loaded with therapeutic cargo are then attracted to and internalized into the intended target cells via the expressed cognate strongly binding extra-cellular receptor, causing escalation of gene transfer into these cells and increasing the copy number of the therapeutic gene expression modules. Such self-focusing swarms of gene vectors can be either homogeneous, with 'scout' and 'therapeutic' members of the swarm being structurally identical, or, alternatively, heterogeneous (split), with 'scout' and 'therapeutic' members of the swarm being structurally specialized. It is hoped that the proposed self-focusing cell-targeted gene vector swarms with receptor-mediated intra-swarm signalling could be particularly effective in 'top-up' gene delivery scenarios, achieving high-level and sustained expression of therapeutic transgenes that are prone to shut-down through degradation and silencing. Crucially, in contrast to low-precision 'general location' vector guidance by diffusible chemo-attractants, ear-marking non-diffusible receptors can provide high-accuracy targeting of therapeutic vector particles to the specific cell, which has undergone a 'successful cell-specific hit' by a 'scout' vector particle. Opportunities for cell targeting could be expanded, since in the proposed model of self-focusing it could be possible to probe a broad selection of intra-cellular determinants of cell-specificity and not just to rely exclusively on extra-cellular markers of cell-specificity. By employing such self-focusing gene vectors for the improvement of cell-targeted delivery of therapeutic genes, e.g., in cancer therapy or gene addition therapy of recessive genetic diseases, it could be possible to broaden a leeway for the reduction of the vector load and, consequently, to minimize undesired vector cytotoxicity, immune reactions, and the risk of inadvertent genetic modification of germline cells in genetic treatment in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

High-resolution definition of the Vibrio cholerae essential gene set with hidden Markov model–based analyses of transposon-insertion sequencing data

PubMed Central

Chao, Michael C.; Pritchard, Justin R.; Zhang, Yanjia J.; Rubin, Eric J.; Livny, Jonathan; Davis, Brigid M.; Waldor, Matthew K.

2013-01-01

The coupling of high-density transposon mutagenesis to high-throughput DNA sequencing (transposon-insertion sequencing) enables simultaneous and genome-wide assessment of the contributions of individual loci to bacterial growth and survival. We have refined analysis of transposon-insertion sequencing data by normalizing for the effect of DNA replication on sequencing output and using a hidden Markov model (HMM)-based filter to exploit heretofore unappreciated information inherent in all transposon-insertion sequencing data sets. The HMM can smooth variations in read abundance and thereby reduce the effects of read noise, as well as permit fine scale mapping that is independent of genomic annotation and enable classification of loci into several functional categories (e.g. essential, domain essential or ‘sick’). We generated a high-resolution map of genomic loci (encompassing both intra- and intergenic sequences) that are required or beneficial for in vitro growth of the cholera pathogen, Vibrio cholerae. This work uncovered new metabolic and physiologic requirements for V. cholerae survival, and by combining transposon-insertion sequencing and transcriptomic data sets, we also identified several novel noncoding RNA species that contribute to V. cholerae growth. Our findings suggest that HMM-based approaches will enhance extraction of biological meaning from transposon-insertion sequencing genomic data. PMID:23901011

High fear of intra-oral injections: prevalence and relationship to dental fear and dental avoidance among 10- to 16-yr-old children.

PubMed

Berge, Karin G; Agdal, Maren L; Vika, Margrethe; Skeie, Marit S

2016-12-01

The present study aimed to: (i) estimate the prevalence of self-reported high fear of intra-oral injections, high blood-injury fear, and injection fear; (ii) explore the overlap between high fear of intra-oral injections and high fear of dental treatment; and (iii) evaluate the possible consequence of high fear of intra-oral injections in terms of avoidance of dental care. The sample included 1,441 subjects, 10- to 16-yr of age, attending elementary schools in a county of Norway. Data were collected using questionnaires that were completed in classrooms. The survey instruments used were the Intra-Oral Injection Fear-scale, the Children's Fear Survey Schedule-Dental Subscale, the Injection Phobia scale for children, and the Mutilation Questionnaire for children. In total, 13.9% of the children reported high intra-oral injection fear. A strong association was found between fear of intra-oral injections and dental fear. When an intra-oral injection was needed, 10.6% would avoid dental treatment. In multiple regression analysis, high intra-oral injection fear was found to be associated with avoidance of dental treatment (OR = 6.52; 95% CI: 3.99-10.67). It was concluded that high fear of intra-oral injections was prevalent and might lead to avoidance of necessary dental treatment. Hence, intra-oral injection fear should be addressed before treatment of dental fear. © 2016 Eur J Oral Sci.

Electrostatic forces govern the binding mechanism of intrinsically disordered histone chaperones

PubMed Central

Liu, Chuanbo; Wang, Tianshu; Bai, Yawen; Wang, Jin

2017-01-01

A unified picture to understand the protein recognition and function must include the native binding complex structure ensembles and the underlying binding mechanisms involved in specific biological processes. However, quantifications of both binding complex structures and dynamical mechanisms are still challenging for IDP. In this study, we have investigated the underlying molecular mechanism of the chaperone Chz1 and histone H2A.Z-H2B association by equilibrium and kinetic stopped-flow fluorescence spectroscopy. The dependence of free energy and kinetic rate constant on electrolyte mean activity coefficient and urea concentration are uncovered. Our results indicate a previous unseen binding kinetic intermediate. An initial conformation selection step of Chz1 is also revealed before the formation of this intermediate state. Based on these observations, a mixed mechanism of three steps including both conformation selection and induced fit is proposed. By combination of the ion- and denaturant-induced experiments, we demonstrate that electrostatic forces play a dominant role in the recognition of bipolar charged intrinsically disordered protein Chz1 to its preferred partner H2A.Z-H2B. Both the intra-chain and inter-chain electrostatic interactions have direct impacts on the native collapsed structure and binding mechanism. PMID:28552960

PATIENT-SPECIFIC FINITE ELEMENT ANALYSIS OF CHRONIC CONTACT STRESS EXPOSURE AFTER INTRA-ARTICULAR FRACTURE OF THE TIBIAL PLAFOND

PubMed Central

Li, Wendy; Anderson, Donald D.; Goldsworthy, Jane K.; Marsh, J. Lawrence; Brown, Thomas D.

2008-01-01

SUMMARY The role of altered contact mechanics in the pathogenesis of post-traumatic osteoarthritis (PTOA) following intra-articular fracture remains poorly understood. One proposed etiology is that residual incongruities lead to altered joint contact stresses that, over time, predispose to PTOA. Prevailing joint contact stresses following surgical fracture reduction were quantified in this study using patient-specific contact finite element (FE) analysis. FE models were created for 11 ankle pairs from tibial plafond fracture patients. Both (reduced) fractured ankles and their intact contralaterals were modeled. A sequence of 13 loading instances was used to simulate the stance phase of gait. Contact stresses were summed across loadings in the simulation, weighted by resident time in the gait cycle. This chronic exposure measure, a metric of degeneration propensity, was then compared between intact and fractured ankle pairs. Intact ankles had lower peak contact stress exposures that were more uniform, and centrally located. The series-average peak contact stress elevation for fractured ankles was 38% (p=0.0015; peak elevation was 82%). Fractured ankles had less area with low contact stress exposure than intacts, and a greater area with high exposure. Chronic contact stress overexposures (stresses exceeding a damage threshold) ranged from near zero to a high of 18 times the matched intact value. The patient-specific FE models utilized in this study represent substantial progress towards elucidating the relationship between altered contact stresses and the outcome of patients treated for intra-articular fractures. PMID:18404662

Inter-rater and intra-rater reliability of the Bahasa Melayu version of Rose Angina Questionnaire.

PubMed

Hassan, N B; Choudhury, S R; Naing, L; Conroy, R M; Rahman, A R A

2007-01-01

The objective of the study is to translate the Rose Questionnaire (RQ) into a Bahasa Melayu version and adapt it cross-culturally, and to measure its inter-rater and intrarater reliability. This cross sectional study was conducted in the respondents' homes or workplaces in Kelantan, Malaysia. One hundred respondents aged 30 and above with different socio-demographic status were interviewed for face validity. For each inter-rater and intra-rater reliability, a sample of 150 respondents was interviewed. Inter-rater and intra-rater reliabilities were assessed by Cohen's kappa. The overall inter-rater agreements by the five pair of interviewers at point one and two were 0.86, and intrarater reliability by the five interviewers on the seven-item questionnaire at poinone and two was 0.88, as measured by kappa coefficient. The translated Malay version of RQ demonstrated an almost perfect inter-rater and intra-rater reliability and further validation such as sensitivity and specificity analysis of this translated questionnaire is highly recommended.

Tailoring the Ag + Content within the Tunnels and on the Exposed Surfaces of α-MnO 2 Nanowires: Impact on Impedance and Electrochemistry

DOE PAGES

Zhang, Bingjie; Smith, Paul F.; Lee, Seung-Yong; ...

2016-12-01

Efficient conduction of both electrons and cations (e.g., Li +) has a profound effect on the current and capacity of lithium-based batteries. With this study, we focus on cathode effects, with the preparation of pure silver hollandite materials with variable silver ion content within (intra-tunnel) and on the surface of α-MnO 2 tunneled materials, followed by the measurement and analysis of impedance and electrochemistry data. Specifically, pure Ag xMn 8O 16-y materials with low (x = 1.13) and high (x = 1.54) intra-tunnel silver content are compared with Ag xMn 8O 16-y·aAg 2O (a = 0.25, 0.63, 1.43) composites preparedmore » via a new Ag 2O coating strategy. When the Ag 2O (a = 0, 0.25) content is low, the material with higher intra-tunnel silver (x = 1.53) content delivers up to ~5-fold higher capacity accounted for by a ~10-fold lower impedance than its lower intra-tunnel silver (x = 1.13) counterpart. In the presence of high Ag 2O content (a = 0.63, 1.43), both composites exhibit comparable impedance but the lower intra-tunnel silver (x = 1.13) composite delivers up to ~1.5-fold higher capacity than higher intra-tunnel silver composite, highlighting the key role of Li + transport under those conditions. Our results demonstrate material design strategies which can significantly increase electronic and ionic conductivities.« less

Tailoring the Ag + Content within the Tunnels and on the Exposed Surfaces of α-MnO 2 Nanowires: Impact on Impedance and Electrochemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bingjie; Smith, Paul F.; Lee, Seung-Yong

Efficient conduction of both electrons and cations (e.g., Li +) has a profound effect on the current and capacity of lithium-based batteries. With this study, we focus on cathode effects, with the preparation of pure silver hollandite materials with variable silver ion content within (intra-tunnel) and on the surface of α-MnO 2 tunneled materials, followed by the measurement and analysis of impedance and electrochemistry data. Specifically, pure Ag xMn 8O 16-y materials with low (x = 1.13) and high (x = 1.54) intra-tunnel silver content are compared with Ag xMn 8O 16-y·aAg 2O (a = 0.25, 0.63, 1.43) composites preparedmore » via a new Ag 2O coating strategy. When the Ag 2O (a = 0, 0.25) content is low, the material with higher intra-tunnel silver (x = 1.53) content delivers up to ~5-fold higher capacity accounted for by a ~10-fold lower impedance than its lower intra-tunnel silver (x = 1.13) counterpart. In the presence of high Ag 2O content (a = 0.63, 1.43), both composites exhibit comparable impedance but the lower intra-tunnel silver (x = 1.13) composite delivers up to ~1.5-fold higher capacity than higher intra-tunnel silver composite, highlighting the key role of Li + transport under those conditions. Our results demonstrate material design strategies which can significantly increase electronic and ionic conductivities.« less

Uncovering the inertia of dislocation motion and negative mechanical response in crystals.

PubMed

Tang, Yizhe

2018-01-09

Dislocations are linear defects in crystals and their motion controls crystals' mechanical behavior. The dissipative nature of dislocation propagation is generally accepted although the specific mechanisms are still not fully understood. The inertia, which is undoubtedly the nature of motion for particles with mass, seems much less convincing for configuration propagation. We utilize atomistic simulations in conditions that minimize dissipative effects to enable uncovering of the hidden nature of dislocation motion, in three typical model metals Mg, Cu and Ta. We find that, with less/no dissipation, dislocation motion is under-damped and explicitly inertial at both low and high velocities. The inertia of dislocation motion is intrinsic, and more fundamental than the dissipative nature. The inertia originates from the kinetic energy imparted from strain energy and stored in the moving core. Peculiar negative mechanical response associated with the inertia is also discovered. These findings shed light on the fundamental nature of dislocation motion, reveal the underlying physics, and provide a new physical explanation for phenomena relevant to high-velocity dislocations.

Spectrally Encoded Confocal Microscopy (SECM) for Diagnosing of Breast Cancer in Excision and Margin Specimens

PubMed Central

Brachtel, Elena F.; Johnson, Nicole B.; Huck, Amelia E.; Rice-Stitt, Travis L.; Vangel, Mark G.; Smith, Barbara L.; Tearney, Guillermo J.; Kang, Dongkyun

2016-01-01

A large percentage of breast cancer patients treated with breast conserving surgery need to undergo multiple surgeries due to positive margins found during post-operative margin assessment. Carcinomas could be removed completely during the initial surgery and additional surgery avoided if positive margins can be determined intra-operatively. Spectrally-encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has a potential to rapidly image the entire surgical margin at sub-cellular resolution and accurately determine margin status intra-operatively. In this paper, in order to test feasibility of using SECM for intra-operative margin assessment, we have evaluated the diagnostic accuracy of SECM for detecting various types of breast cancers. Forty-six surgically-removed breast specimens were imaged with a SECM system. Side-by-side comparison between SECM and histologic images showed that SECM images can visualize key histomorphologic patterns of normal/benign and malignant breast tissues. Small (500 µm × 500 µm) spatially-registered SECM and histologic images (n=124 for each) were diagnosed independently by three pathologists with expertise in breast pathology. Diagnostic accuracy of SECM for determining malignant tissues was high, average sensitivity of 0.91, specificity of 0.93, positive predictive value of 0.95, and negative predictive value of 0.87. Intra-observer agreement and inter-observer agreement for SECM were also high, 0.87 and 0.84, respectively. Results from this study suggest that SECM may be developed into an intra-operative margin assessment tool for guiding breast cancer excisions. PMID:26779830

Ultra-high density intra-specific genetic linkage maps accelerate identification of functionally relevant molecular tags governing important agronomic traits in chickpea

PubMed Central

Kujur, Alice; Upadhyaya, Hari D.; Shree, Tanima; Bajaj, Deepak; Das, Shouvik; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

2015-01-01

We discovered 26785 and 16573 high-quality SNPs differentiating two parental genotypes of a RIL mapping population using reference desi and kabuli genome-based GBS assay. Of these, 3625 and 2177 SNPs have been integrated into eight desi and kabuli chromosomes, respectively in order to construct ultra-high density (0.20–0.37 cM) intra-specific chickpea genetic linkage maps. One of these constructed high-resolution genetic map has potential to identify 33 major genomic regions harbouring 35 robust QTLs (PVE: 17.9–39.7%) associated with three agronomic traits, which were mapped within <1 cM mean marker intervals on desi chromosomes. The extended LD (linkage disequilibrium) decay (~15 cM) in chromosomes of genetic maps have encouraged us to use a rapid integrated approach (comparative QTL mapping, QTL-region specific haplotype/LD-based trait association analysis, expression profiling and gene haplotype-based association mapping) rather than a traditional QTL map-based cloning method to narrow-down one major seed weight (SW) robust QTL region. It delineated favourable natural allelic variants and superior haplotype-containing one seed-specific candidate embryo defective gene regulating SW in chickpea. The ultra-high-resolution genetic maps, QTLs/genes and alleles/haplotypes-related genomic information generated and integrated strategy for rapid QTL/gene identification developed have potential to expedite genomics-assisted breeding applications in crop plants, including chickpea for their genetic enhancement. PMID:25942004

Genetics of Sleep and Sleep disorders

PubMed Central

Sehgal, Amita; Mignot, Emmanuel

2011-01-01

Sleep remains one of the least understood phenomena in biology – even its role in synaptic plasticity remains debatable. Since sleep was recognized to be regulated genetically, intense research has launched on two fronts: the development of model organisms for deciphering the molecular mechanisms of sleep and attempts to identify genetic underpinnings of human sleep disorders. In this Review, we describe how unbiased, high-throughput screens in model organisms are uncovering sleep regulatory mechanisms and how pathways, such as the circadian clock network and specific neurotransmitter signals, have conserved effects on sleep from Drosophila to humans. At the same time, genome-wide association (GWA) studies have uncovered ~14 loci increasing susceptibility to sleep disorders, such as narcolepsy and restless leg syndrome. To conclude, we discuss how these different strategies will be critical to unambiguously defining the function of sleep. PMID:21784243

Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease.

PubMed

Winfree, Seth; Dagher, Pierre C; Dunn, Kenneth W; Eadon, Michael T; Ferkowicz, Michael; Barwinska, Daria; Kelly, Katherine J; Sutton, Timothy A; El-Achkar, Tarek M

2018-06-05

Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease. © 2018 S. Karger AG, Basel.

Pan-cancer analysis of somatic copy number alterations implicates IRS4 and IGF2 in enhancer hijacking

PubMed Central

Weischenfeldt, Joachim; Dubash, Taronish; Drainas, Alexandros P.; Mardin, Balca R.; Chen, Yuanyuan; Stütz, Adrian M.; Waszak, Sebastian M.; Bosco, Graziella; Halvorsen, Ann Rita; Raeder, Benjamin; Efthymiopoulos, Theocharis; Erkek, Serap; Siegl, Christine; Brenner, Hermann; Brustugun, Odd Terje; Dieter, Sebastian M.; Northcott, Paul A.; Petersen, Iver; Pfister, Stefan M.; Schneider, Martin; Solberg, Steinar K.; Thunissen, Erik; Weichert, Wilko; Zichner, Thomas; Thomas, Roman; Peifer, Martin; Helland, Aslaug; Ball, Claudia R.; Jechlinger, Martin; Sotillo, Rocio; Glimm, Hanno; Korbel, Jan O.

2018-01-01

Extensive prior research has focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearranging cis-regulatory elements remains unclear. Here, we present a framework for inferring cancer-related gene overexpression resulting from cis-regulatory element reorganization (e.g., enhancer hijacking), by integrating SCNAs, gene expression data, and information on chromatin interaction domains. Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer associates with recurrent deletions in cis, and present evidence supporting a tumor-promoting role. We additionally pursued cancer type-specific analyses, uncovering IGF2 as a target for enhancer hijacking in colorectal cancer. IGF2-containing tandem duplications result in the de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, which mediates high-level gene activation. Our framework enables systematic inference of cis-regulatory element rearrangements mediating dysregulation in cancer. PMID:27869826

Intra-specific competition (crowding) of giant sequoias (Sequoiadendron giganteum)

USGS Publications Warehouse

Stohlgren, Thomas J.

1993-01-01

Information on the size and location of 1916 giant sequoias (Sequoiadendron giganteum (Lindl.) Buchholz) in Muir Grove, Sequoia National Park, in the southern Sierra Nevada of California was used to assess intra-specific crowding. Study objectives were to: (1) determine which parameters associated with intra-specific competition (i.e. size and distance to nearest neighbor, crowding/root system area overlap, or number of neighbors) might be important in spatial pattern development, growth, and survivorship of established giant sequoias; (2) quantify the level of intra-specific crowding of different sized live sequoias based on a model of estimated overlapping root system areas (i.e. an index of relative crowding); (3) compare the level of intra-specific crowding of similarly sized live and dead giant sequoias (less than 30 cm diameter at breast height (dbh) at the time of inventory (1969). Mean distances to the nearest live giant sequoia neighbor were not significantly different (at α = 0.05) for live and dead sequoias in similar size classes. A zone of influence competition model (i.e. index of crowding) based on horizontal overlap of estimated root system areas was developed for 1753 live sequoias. The model, based only on the spatial arrangement of live sequoias, was then tested on dead sequoias of less than 30 cm dbh (n = 163 trees; also recorded in 1969). The dead sequoias had a significantly higher crowding index than 561 live trees of similar diameter. Results showed that dead sequoias of less than 16.6 cm dbh had a significantly greater mean number of live neighbors and mean crowding index than live sequoias of similar size. Intra-specific crowding may be an important mechanism in determining the spatial distribution of sequoias in old-growth forests.

High occurrence of mitochondrial heteroplasmy in nepalese indigenous sheep (Ovis aries) compared to chinese sheep.

PubMed

Gorkhali, Neena Amatya; Jiang, Lin; Shrestha, Bhola Shankar; He, Xiao-Hong; Junzhao, Qian; Han, Jian-Lin; Ma, Yue-Hui

2016-07-01

Heteroplasmy due to length polymorphism with tandem repeats in mtDNAs within individual was hardly studied in domestic animals. In the present study, we identified intra-individual length variation in the control region of mtDNAs in Nepalese sheep by molecular cloning and sequencing techniques. We observed one to four tandem repeats of a 75-bp nucleotide sequences in the mtDNA control region in 45% of the total Nepalese sheep sampled in contrast to the Chinese sheep, indicating that the heteroplasmy is specific to Nepalese sheep. The high rate of heteroplasmy in Nepalese sheep could be a resultant of the mtDNA mutation and independent segregation at intra-individual level or a strand slippage and mispairing during the replication.

Adaptation of the Estuarine Fish, Fundulus heterclitus (Atlantic Killifish) to Polychlorinated Biphenyls (PCBs)

EPA Science Inventory

To characterize intra-specific variation in sensitivity to highly toxic pollutants in the non-migratory estuarine Atlantic killifish (Fundulus heteroclitus), we compared early life stage responses to the prototypical dioxin-like compound, 3,3’4,4’,5 hexachlorobiphenyl (PCB126). ...

Comparative hi-density intraspecific linkage mapping using three elite populations from common parents

USDA-ARS?s Scientific Manuscript database

High-density linkage maps are fundamental to contemporary organismal research and scientific approaches to genetic improvement, especially in paleopolyploids with exceptionally complex genomes, e.g., Upland cotton (Gossypium hirsutum L., 2n=52). Using 3 full-sib intra-specific mapping populations fr...

Proteogenemic Approaches for the Molecular Characterization of Natural Microbial Communities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banfield, Jillian F.

2014-04-25

Microbial biofilms involved in acid mine drainage formation have served as a model systems for the study of microbial communities. Over the grant period we developed community metagenomic methods for recovery of genomes of uncultivated bacteria, archaea, viruses/phage, and plasmids from natural systems. We leveraged highly curated metagenomic datasets to develop methods to monitor microbial function in situ. Beyond new insight into extremophilic microbial ecosystems, we have shown that our strain-resolved proteogenomic methods can be applied to other systems. Our studies have uncovered new patters of inter-species recombination that likely lead to fine-scale environmental adaptation, defined the importance of inter-speciesmore » vs. intra-species recombination in archaea, and evaluated the processes shaping fine-scale sequence variation. The project was the subject of study for six Ph.D. students, two of whom are now Associate Professors, the others are post docs; for M.S. or undergraduate researchers, and thirteen post docs, ten of which are now Assistant or Associate professors. The research generated 53 publications, five of which appeard in Science or Nature.« less

The role of high-risk HPV-DNA testing in the male sexual partners of women with HPV-induced lesions.

PubMed

Giraldo, Paulo C; Eleutério, Jose; Cavalcante, Diane Isabelle M; Gonçalves, Ana Katherine S; Romão, Juliana A A; Eleutério, Renata M N

2008-03-01

The objectives were to assess the prevalence of high-risk HPV in the male sexual partners of women with HPV-induced lesions, and correlate it with biopsies guided by peniscopy. Fifty-four asymptomatic male sexual partners of women with low-grade squamous intra-epithelial lesions (LSIL) associated with high-risk HPV were examined between April 2003 and June 2005. The DNA-HPV was tested using a second-generation hybrid capture technique in scraped penile samples. Peniscopy identified acetowhite lesions leading to biopsy. High-risk HPV was present in 25.9% (14 out of 54) of the cases. Peniscopy led to 13 biopsies (24.07%), which resulted in two cases of condyloma, two cases of intra-epithelial neoplasia (PIN) I, one case of PIN II, and eight cases of normal tissue. The high-risk HPV test demonstrated 80% sensitivity, 100% specificity, 100% positive predictive value, and 88.9% negative predictive value for the identification of penile lesions. There was a greater chance of finding HPV lesions in the biopsy in the positive cases of high-risk HPV with abnormal peniscopy (p=0.007); OR=51 (CI 1.7-1527.1). Among asymptomatic male sexual partners of women with low-grade intra-epithelial squamous lesions, those infected by high-risk HPV have a higher chance of having abnormal penile tissue compared with male partners without that infection.

Spatial and temporal variation in plant hydraulic traits and their relevance for climate change impacts on vegetation.

PubMed

Anderegg, William R L

2015-02-01

Plant hydraulics mediate terrestrial woody plant productivity, influencing global water, carbon, and biogeochemical cycles, as well as ecosystem vulnerability to drought and climate change. While inter-specific differences in hydraulic traits are widely documented, intra-specific hydraulic variability is less well known and is important for predicting climate change impacts. Here, I present a conceptual framework for this intra-specific hydraulic trait variability, reviewing the mechanisms that drive variability and the consequences for vegetation response to climate change. I performed a meta-analysis on published studies (n = 33) of intra-specific variation in a prominent hydraulic trait - water potential at which 50% stem conductivity is lost (P50) - and compared this variation to inter-specific variability within genera and plant functional types used by a dynamic global vegetation model. I found that intra-specific variability is of ecologically relevant magnitudes, equivalent to c. 33% of the inter-specific variability within a genus, and is larger in angiosperms than gymnosperms, although the limited number of studies highlights that more research is greatly needed. Furthermore, plant functional types were poorly situated to capture key differences in hydraulic traits across species, indicating a need to approach prediction of drought impacts from a trait-based, rather than functional type-based perspective.

What works: a realist evaluation case study of intermediaries in infection control practice.

PubMed

Williams, Lynne; Burton, Christopher; Rycroft-Malone, Jo

2013-04-01

To report a study of an intermediary programme in infection control practice in one hospital in the UK. Promoting best evidence in everyday practice is a constant problem in infection control. Intermediaries can influence the transfer and use of evidence in health care, but there remains a lack of evidence and theory about the specific actions and change processes, which can be successful in improving infection control practices. An in-depth mixed methods case study. The study was undertaken in 2011. Participants were recruited through purposive sampling and included frontline staff, managers and nurses in intermediary roles in infection control. For frontline staff, intermediary presence triggered a modification in behaviour. Different reactions were noted from the intermediaries' high level of physical presence in clinical areas, the facilitative approaches they used to give feedback and the specific teaching strategies they employed to meet frontline staff needs. The specific intermediary actions uncovered in this study were contingent on the prevailing systems for performance management, organisational commitment and efforts in clinical areas to foster a collegiate environment. The study provides theoretical threads of how intermediaries can be successful in promoting evidence use under certain contextual conditions. Further testing of the specific intermediary mechanisms uncovered in this study will contribute to understanding different approaches that work in infection control in embedding evidence in practice. © 2012 Blackwell Publishing Ltd.

Student-generated reading questions: diagnosing student thinking with diverse formative assessments.

PubMed

Offerdahl, Erika G; Montplaisir, Lisa

2014-01-01

Formative assessment has long been identified as a critical element to teaching for conceptual development in science. It is therefore important for university instructors to have an arsenal of formative assessment tools at their disposal which enable them to effectively uncover and diagnose all students' thinking, not just the most vocal or assertive. We illustrate the utility of one type of formative assessment prompt (reading question assignment) in producing high-quality evidence of student thinking (student-generated reading questions). Specifically, we characterized student assessment data using three distinct analytic frames to exemplify their effectiveness in diagnosing student learning in relationship to three sample learning outcomes. Our data will be useful for university faculty, particularly those engaged in teaching upper-level biochemistry courses and their prerequisites, as they provide an alternative mechanism for uncovering and diagnosing student understanding. © 2013 by The International Union of Biochemistry and Molecular Biology.

Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data

PubMed Central

Liu, Hui; Zhang, Fan; Mishra, Shital Kumar; Zhou, Shuigeng; Zheng, Jie

2016-01-01

Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine. PMID:27774993

Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone.

PubMed

Trajkovski, Branko; Petersen, Ansgar; Strube, Patrick; Mehta, Manav; Duda, Georg N

2012-09-01

Bone is one of the few tissues in the human body with high endogenous healing capacity. However, failure of the healing process presents a significant clinical challenge; it is a tremendous burden for the individual and has related health and economic consequences. To overcome such healing deficits, various concepts for a local drug delivery to bone have been developed during the last decades. However, in many cases these concepts do not meet the specific requirements of either surgeons who must use these strategies or individual patients who might benefit from them. We describe currently available methods for local drug delivery and their limitations in therapy. Various solutions for drug delivery to bone focusing on clinical applications and intra-operative constraints are discussed and drug delivery by implant coating is highlighted. Finally, a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed. In the future, these requirements may improve approaches for local and intra-operative treatment of patients. Copyright © 2012 Elsevier B.V. All rights reserved.

The effect of Malaysia general election on stock market returns.

PubMed

Liew, Venus Khim-Sen; Rowland, Racquel

2016-01-01

During the latest episode of general election held in Malaysia, it is observed that the FBMKLCI index was lifted 62.52 points in a day soon after the announcement of election outcome. Moreover, the index registered a highest gain of 96.29 points in the middle of the intra-day trade. This suggests that investors who had got the right direction could make profitable intra-day trading the next trading day of the general election date. Results from statistical analysis uncover significant before-election-effect and after-election-effect from the most recent general elections held in Malaysia. Different subsets of macroeconomic variables are found to have significant role on stock market return depending on the market situation. Remarkably, when there was close fight between the two major political parties during the 2008 and 2013 election years, political uncertainty showed up its negative and significant role in influencing the stock market return. The major implication of these findings is that while investors may seek abnormal returns before and after the next general election, which is around the corner, they will have to pay attention on the influence of macroeconomic variables and political uncertainty on stock market return during the election year.

When violence pays: a cost-benefit analysis of aggressive behavior in animals and humans.

PubMed

Georgiev, Alexander V; Klimczuk, Amanda C E; Traficonte, Daniel M; Maestripieri, Dario

2013-07-18

An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability) while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships). Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females.

Mutational analysis of the extracellular disulphide bridges of the atypical chemokine receptor ACKR3/CXCR7 uncovers multiple binding and activation modes for its chemokine and endogenous non-chemokine agonists.

PubMed

Szpakowska, Martyna; Meyrath, Max; Reynders, Nathan; Counson, Manuel; Hanson, Julien; Steyaert, Jan; Chevigné, Andy

2018-07-01

The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor. So far, the molecular basis accounting for these atypical binding and signalling properties remains elusive. Noteworthy, ACKR3 extracellular domains bear three disulphide bridges. Two of them lie on top of the two main binding subpockets and are conserved among chemokine receptors, and one, specific to ACKR3, forms an intra-N terminus four-residue-loop of so far unknown function. Here, by mutational and functional studies, we examined the impact of the different disulphide bridges for ACKR3 folding, ligand binding and activation. We showed that, in contrast to most classical chemokine receptors, none of the extracellular disulphide bridges was essential for ACKR3 function. However, the disruption of the unique ACKR3 N-terminal loop drastically reduced the binding of CC chemokines whereas it only had a mild impact on CXC chemokine binding. Mutagenesis also uncovered that chemokine and endogenous non-chemokine ligands interact and activate ACKR3 according to distinct binding modes characterized by different transmembrane domain subpocket occupancy and N-terminal loop contribution, with BAM22 mimicking the binding mode of CC chemokine N terminus. Copyright © 2018 Elsevier Inc. All rights reserved.

Professional relations in sport healthcare: workplace responses to organisational change.

PubMed

Malcolm, Dominic; Scott, Andrea

2011-02-01

This article examines the impact of organisational changes in UK elite sport on the professional relations among and between different healthcare providers. The article describes the processes by which demand for elite sport healthcare has increased in the UK. It further charts the subsequent response within medicine and physiotherapy and, in particular, the institutionalisation of sport-specific sub-disciplines through the introduction of specialist qualifications. Drawing on semi-structured interviews with 14 doctors and 14 physiotherapists, the article argues that organisational changes have led to intra-professional tensions within both professional groups but in qualitatively different forms reflecting the organisational traditions and professional identities of the respective disciplines. Organisational changes promoting multi-disciplinary healthcare teams have also fostered an environment conducive to high levels of inter-professional cooperation though significant elements of inter-professional conflict remain. This study illustrates how intra-professional relations are affected by specialisation, how legitimation discourses are used by different professions, and how intra- and inter-professional conflict and cooperation should be seen as highly interdependent processes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Africa's middle class women bring entrepreneurial opportunities in breast care medical tourism to South Africa.

PubMed

Ahwireng-Obeng, Frederick; van Loggerenberg, Charl

2011-01-01

Africa's distribution of specialized private health services is severely disproportionate. Mismatch between South Africa's excess supply and a huge demand potential in an under-serviced continent represents an entrepreneurial opportunity to attract patients to South Africa for treatment and recuperative holidays. However, effective demand for intra-African medical tourism could be constrained by sub-Saharan poverty. Results from interviewing 320 patients and five staff at the Johannesburg Breast care Centre of Excellence, however, reject this proposition, Africa's middle class women being the target market estimated to grow annually by one million while breast cancer incidence increases with middle-class lifestyles. Uncovering this potential involves an extensive marketing strategy. Copyright © 2010 John Wiley & Sons, Ltd.

The value of arthrography in the decision-making process regarding surgery for internal derangement of the temporomandibular joint.

PubMed

Nitzan, D W; Dolwick, F M; Marmary, Y

1991-04-01

In this study, the clinical and arthrographic findings from 43 internally deranged temporomandibular joints (TMJs) were compared with the intra-surgical observations. In 40 of 43 joints, arthrography did not provide any additional information useful for diagnosis or treatment. In six joints, the problem was misdiagnosed. Only in three joints did arthrography demonstrate the existence of perforation in the posterior attachment that had not been suspected during the clinical examination. Because of the doubtful importance of arthrographic information for the decision-making process, it is suggested that the method be applied only in cases in which clinical examination and plain radiographs have failed to uncover the signs and symptoms indicative of a TMJ disorder.

Inter-Observer, Intra-Observer and Intra-Individual Reliability of Uroflowmetry Tests in Aged Men: A Generalizability Theory Approach.

PubMed

Liu, Ying-Buh; Yang, Stephen S; Hsieh, Cheng-Hsing; Lin, Chia-Da; Chang, Shang-Jen

2014-05-01

To evaluate the inter-observer, intra-observer and intra-individual reliability of uroflowmetry and post-void residual urine (PVR) tests in adult men. Healthy volunteers aged over 40 years were enrolled. Every participant underwent two sets of uroflowmetry and PVR tests with a 2-week interval between the tests. The uroflowmetry tests were interpreted by four urologists independently. Uroflowmetry curves were classified as bell-shaped, bell-shaped with tail, obstructive, restrictive, staccato, interrupted and tower-shaped and scored from 1 (highly abnormal) to 5 (absolutely normal). The agreements between the observers, interpretations and tests within individuals were analyzed using kappa statistics and intraclass correlation coefficients. Generalizability theory with decision analysis was used to determine how many observers, tests, and interpretations were needed to obtain an acceptable reliability (> 0.80). Of 108 volunteers, we randomly selected the uroflowmetry results from 25 participants for the evaluation of reliability. The mean age of the studied adults was 55.3 years. The intra-individual and intra-observer reliability on uroflowmetry tests ranged from good to very good. However, the inter-observer reliability on normalcy and specific type of flow pattern were relatively lower. In generalizability theory, three observers were needed to obtain an acceptable reliability on normalcy of uroflow pattern if the patient underwent uroflowmetry tests twice with one observation. The intra-individual and intra-observer reliability on uroflowmetry tests were good while the inter-observer reliability was relatively lower. To improve inter-observer reliability, the definition of uroflowmetry should be clarified by the International Continence Society. © 2013 Wiley Publishing Asia Pty Ltd.

Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments

PubMed Central

Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N.

2015-01-01

The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions. PMID:26712748

Intra-population variation in activity ranges, diel patterns, movement rates, and habitat use of American alligators in a subtropical estuary

NASA Astrophysics Data System (ADS)

Rosenblatt, Adam E.; Heithaus, Michael R.; Mazzotti, Frank J.; Cherkiss, Michael; Jeffery, Brian M.

2013-12-01

Movement and habitat use patterns are fundamental components of the behaviors of mobile animals and help determine the scale and types of interactions they have with their environments. These behaviors are especially important to quantify for top predators because they can have strong effects on lower trophic levels as well as the wider ecosystem. Many studies of top predator movement and habitat use focus on general population level trends, which may overlook important intra-population variation in behaviors that now appear to be common. In an effort to better understand the prevalence of intra-population variation in top predator movement behaviors and the potential effects of such variation on ecosystem dynamics, we examined the movement and habitat use patterns of a population of adult American alligators (Alligator mississippiensis) in a subtropical estuary for nearly four years. We found that alligators exhibited divergent behaviors with respect to activity ranges, movement rates, and habitat use, and that individualized behaviors were stable over multiple years. We also found that the variations across the three behavioral metrics were correlated such that consistent behavioral types emerged, specifically more exploratory individuals and more sedentary individuals. Our study demonstrates that top predator populations can be characterized by high degrees of intra-population variation in terms of movement and habitat use behaviors that could lead to individuals filling different ecological roles in the same ecosystem. By extension, one-size-fits-all ecosystem and species-specific conservation and management strategies that do not account for potential intra-population variation in top predator behaviors may not produce the desired outcomes in all cases.

Interactions of nitric oxide with α2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine.

PubMed

Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M; Ugale, Rajesh R

2016-09-01

Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra-LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S-nitrosoglutathione, non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), the α2 -adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra-LC before agmatine. Intra-hippocampal injections of the NMDA antagonist, MK-801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Agmatine (intra-LC or i.p.) facilitated memory retrieval in the IA test. S-nitrosoglutathione potentiated, while L-NAME and L-NIO decreased, these effects of agmatine. L-NIL and 7-NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S-nitrosoglutathione and yohimbine were blocked by intra-hippocampal MK-801. Agmatine increased the population of TH- and eNOS-immunoreactive elements in the LC. The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. © 2016 The British Pharmacological Society.

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

PubMed

Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

CircularLogo: A lightweight web application to visualize intra-motif dependencies.

PubMed

Ye, Zhenqing; Ma, Tao; Kalmbach, Michael T; Dasari, Surendra; Kocher, Jean-Pierre A; Wang, Liguo

2017-05-22

The sequence logo has been widely used to represent DNA or RNA motifs for more than three decades. Despite its intelligibility and intuitiveness, the traditional sequence logo is unable to display the intra-motif dependencies and therefore is insufficient to fully characterize nucleotide motifs. Many methods have been developed to quantify the intra-motif dependencies, but fewer tools are available for visualization. We developed CircularLogo, a web-based interactive application, which is able to not only visualize the position-specific nucleotide consensus and diversity but also display the intra-motif dependencies. Applying CircularLogo to HNF6 binding sites and tRNA sequences demonstrated its ability to show intra-motif dependencies and intuitively reveal biomolecular structure. CircularLogo is implemented in JavaScript and Python based on the Django web framework. The program's source code and user's manual are freely available at http://circularlogo.sourceforge.net . CircularLogo web server can be accessed from http://bioinformaticstools.mayo.edu/circularlogo/index.html . CircularLogo is an innovative web application that is specifically designed to visualize and interactively explore intra-motif dependencies.

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study).

PubMed

Sartelli, Massimo; Abu-Zidan, Fikri M; Catena, Fausto; Griffiths, Ewen A; Di Saverio, Salomone; Coimbra, Raul; Ordoñez, Carlos A; Leppaniemi, Ari; Fraga, Gustavo P; Coccolini, Federico; Agresta, Ferdinando; Abbas, Asrhaf; Abdel Kader, Saleh; Agboola, John; Amhed, Adamu; Ajibade, Adesina; Akkucuk, Seckin; Alharthi, Bandar; Anyfantakis, Dimitrios; Augustin, Goran; Baiocchi, Gianluca; Bala, Miklosh; Baraket, Oussama; Bayrak, Savas; Bellanova, Giovanni; Beltràn, Marcelo A; Bini, Roberto; Boal, Matthew; Borodach, Andrey V; Bouliaris, Konstantinos; Branger, Frederic; Brunelli, Daniele; Catani, Marco; Che Jusoh, Asri; Chichom-Mefire, Alain; Cocorullo, Gianfranco; Colak, Elif; Costa, David; Costa, Silvia; Cui, Yunfeng; Curca, Geanina Loredana; Curry, Terry; Das, Koray; Delibegovic, Samir; Demetrashvili, Zaza; Di Carlo, Isidoro; Drozdova, Nadezda; El Zalabany, Tamer; Enani, Mushira Abdulaziz; Faro, Mario; Gachabayov, Mahir; Giménez Maurel, Teresa; Gkiokas, Georgios; Gomes, Carlos Augusto; Gonsaga, Ricardo Alessandro Teixeira; Guercioni, Gianluca; Guner, Ali; Gupta, Sanjay; Gutierrez, Sandra; Hutan, Martin; Ioannidis, Orestis; Isik, Arda; Izawa, Yoshimitsu; Jain, Sumita A; Jokubauskas, Mantas; Karamarkovic, Aleksandar; Kauhanen, Saila; Kaushik, Robin; Kenig, Jakub; Khokha, Vladimir; Kim, Jae Il; Kong, Victor; Koshy, Renol; Krasniqi, Avidyl; Kshirsagar, Ashok; Kuliesius, Zygimantas; Lasithiotakis, Konstantinos; Leão, Pedro; Lee, Jae Gil; Leon, Miguel; Lizarazu Pérez, Aintzane; Lohsiriwat, Varut; López-Tomassetti Fernandez, Eudaldo; Lostoridis, Eftychios; Mn, Raghuveer; Major, Piotr; Marinis, Athanasios; Marrelli, Daniele; Martinez-Perez, Aleix; Marwah, Sanjay; McFarlane, Michael; Melo, Renato Bessa; Mesina, Cristian; Michalopoulos, Nick; Moldovanu, Radu; Mouaqit, Ouadii; Munyika, Akutu; Negoi, Ionut; Nikolopoulos, Ioannis; Nita, Gabriela Elisa; Olaoye, Iyiade; Omari, Abdelkarim; Ossa, Paola Rodríguez; Ozkan, Zeynep; Padmakumar, Ramakrishnapillai; Pata, Francesco; Pereira Junior, Gerson Alves; Pereira, Jorge; Pintar, Tadeja; Pouggouras, Konstantinos; Prabhu, Vinod; Rausei, Stefano; Rems, Miran; Rios-Cruz, Daniel; Sakakushev, Boris; Sánchez de Molina, Maria Luisa; Seretis, Charampolos; Shelat, Vishal; Simões, Romeo Lages; Sinibaldi, Giovanni; Skrovina, Matej; Smirnov, Dmitry; Spyropoulos, Charalampos; Tepp, Jaan; Tezcaner, Tugan; Tolonen, Matti; Torba, Myftar; Ulrych, Jan; Uzunoglu, Mustafa Yener; van Dellen, David; van Ramshorst, Gabrielle H; Vasquez, Giorgio; Venara, Aurélien; Vereczkei, Andras; Vettoretto, Nereo; Vlad, Nutu; Yadav, Sanjay Kumar; Yilmaz, Tonguç Utku; Yuan, Kuo-Ching; Zachariah, Sanoop Koshy; Zida, Maurice; Zilinskas, Justas; Ansaloni, Luca

2015-01-01

To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Microstructure effects on the recrystallization of low-symmetry alpha-uranium

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCabe, Rodney James; Richards, Andrew Walter; Coughlin, Daniel Robert

2015-10-01

We employ electron backscatter diffraction (EBSD) to investigate microstructural evolution of uranium during recrystallization. To understand the relationship between microstructure and recrystallization, we use measures of intra-granular misorientation within grains and near grain boundaries in both deformed (non-recrystallized) uranium and recrystallizing uranium. The data show that the level of intra-granular misorientation depends on crystallographic orientation. However, contrary to expectation, this relationship does not significantly affect the recrystallization texture. Rather, the analysis suggests that recrystallization nucleation occurs along high angle grain boundaries in the deformed microstructure. Specifically, we show that the nucleation of recrystallized grains correlates well with the spatially heterogeneousmore » distribution of high angle boundaries. Due to the inhomogeneous distribution of high angle boundaries, the recrystallized microstructure after long times exhibits clustered distributions of small and large grains. Twin boundaries do not appear to act as recrystallization nucleation sites.« less

Local immunological mechanisms of sublingual immunotherapy.

PubMed

Allam, Jean-Pierre; Novak, Natalija

2011-12-01

To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective. To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response. Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.

SWIM: a computational tool to unveiling crucial nodes in complex biological networks

PubMed Central

Paci, Paola; Colombo, Teresa; Fiscon, Giulia; Gurtner, Aymone; Pavesi, Giulio; Farina, Lorenzo

2017-01-01

SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called “fight-club hubs”, characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called “switch genes”, appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer. PMID:28317894

SWIM: a computational tool to unveiling crucial nodes in complex biological networks.

PubMed

Paci, Paola; Colombo, Teresa; Fiscon, Giulia; Gurtner, Aymone; Pavesi, Giulio; Farina, Lorenzo

2017-03-20

SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer.

Contemporary trends in cardiogenic shock: Incidence, intra-aortic balloon pump utilisation and outcomes from the London Heart Attack Group.

PubMed

Rathod, Krishnaraj S; Koganti, Sudheer; Iqbal, M Bilal; Jain, Ajay K; Kalra, Sundeep S; Astroulakis, Zoe; Lim, Pitt; Rakhit, Roby; Dalby, Miles C; Lockie, Tim; Malik, Iqbal S; Knight, Charles J; Whitbread, Mark; Mathur, Anthony; Redwood, Simon; MacCarthy, Philip A; Sirker, Alexander; O'Mahony, Constantinos; Wragg, Andrew; Jones, Daniel A

2018-02-01

Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment elevation myocardial infarction. We aimed to assess the current trends in cardiogenic shock management, looking specifically at the incidence, use of intra-aortic balloon pump therapy and outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. We undertook an observational cohort study of 21,210 ST-segment elevation myocardial infarction patients treated between 2005-2015 at the eight Heart Attack Centres in London, UK. Patients' details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society percutaneous coronary intervention dataset. There were 1890 patients who presented with cardiogenic shock. The primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2-5.8 years). Increasing rates of cardiogenic shock were seen over the course of the study with consistently high mortality rates of 45-70%. A total of 685 patients underwent intra-aortic balloon pump insertion during primary percutaneous coronary intervention for cardiogenic shock with decreasing rates over time. Those patients undergoing intra-aortic balloon pump therapy were younger, more likely to have poor left ventricular function and less likely to have had previous percutaneous coronary intervention compared to the control group. Procedural success rates were similar (86.0% vs 87.1%, p=0.292) although crude, in-hospital major adverse cardiac event rates were higher (43.8% vs 33.7%, p<0.0001) in patients undergoing intra-aortic balloon pump therapy. Kaplan-Meier analysis demonstrated significantly higher mortality rates in patients receiving intra-aortic balloon pump therapy (50.9% intra-aortic balloon pump vs 39.9% control, p<0.0001) during the follow-up period. After multivariate Cox analysis (hazard ratio 1.04, 95% confidence interval 0.62-1.89) and the use of propensity matching (hazard ratio: 1.29, 95% confidence interval: 0.68-1.45) intra-aortic balloon pump therapy was not associated with mortality. Cardiogenic shock treated by percutaneous coronary intervention is increasing in incidence and remains a condition associated with high mortality and limited treatment options. Intra-aortic balloon pump therapy was not associated with a long-term survival benefit in this cohort and may be associated with increased early morbidity.

Development of a high-density intra-specific linkage map of lettuce using genotyping by sequencing (GBS)

USDA-ARS?s Scientific Manuscript database

Genotyping by sequencing (GBS) has been developed as an affordable application of next-generation sequencing for the purposes of discovering and genotyping SNPs in a variety of crop species and populations. In this study we employed a double restriction enzyme digestion protocol (HindIII and NlaIII)...

Comparison of the 9-month intra-stent conditions and 2-year clinical outcomes after Resolute zotarolimus-eluting stent implantation between 3-month and standard dual antiplatelet therapy.

PubMed

Fujimoto, Wataru; Sawada, Takahiro; Toba, Takayoshi; Takahashi, Yu; Miyata, Taishi; Oishi, Shogo; Osue, Tsuyoshi; Onishi, Tetsuari; Takaya, Tomofumi; Shimane, Akira; Taniguchi, Yasuyo; Kawai, Hiroya; Yasaka, Yoshinori

2018-07-01

The use of short-duration dual antiplatelet therapy (DAPT) remains controversial. To investigate efficacy and safety of short-duration DAPT, we performed a detailed comparison of intra-stent conditions by optical coherence tomography (OCT) after second-generation drug-eluting stent implantation with short-term and standard DAPT. Eighty-two consecutive patients with stable angina pectoris who received Resolute zotarolimus-eluting stents (R-ZESs; Medtronic Cardiovascular, Santa Rosa, CA, USA) were enrolled. Patients were assigned to 3-month (3M group: 41 patients) and standard (standard group: 41 patients) DAPT. In the 3M group, clopidogrel was discontinued 3 months after stent implantation. In the standard group, DAPT was maintained until follow-up OCT. At 9 months, neointimal proliferation was significantly larger in the 3M group, but there were no significant between-group differences in the proportion of uncovered and malapposed strut. The prevalence of abnormal intra-stent tissue (AIT) at 9 months was equivalent between groups. A multiple regression analysis revealed malapposition at 9 months as the strongest independent predictor of AIT at 9 months, and the prevalence of AIT was not associated with DAPT duration. Over 2 years, cardiac events were equal between groups; however, major bleeding was higher tendency in the standard group than in the 3M group. This OCT study indicated that reducing DAPT's duration may provide acceptable arterial healing in patients with implanted R-ZESs. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Comparing intra- and inter-specific effects on litter decomposition in an old-field ecosystem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crutsinger, Greg; Sanders, Dr. Nathan James; Classen, Aimee T

2009-09-01

Plant species can differ in the quantity and quality of leaf litter they produce, and many studies have examined whether plant species diversity affects leaf-litter decomposition and nutrient release. A growing number of studies have indicated that intra-specific variation within plant species can also affect key ecosystem processes. However, the relative importance of intra- versus inter-specific variation for the functioning of ecosystems remains poorly known. Here, we investigate the effects of intra-specific variation in a dominant old-field plant species, tall goldenrod (Solidago altissima), and inter-specific variation among goldenrod species on litter quality, decomposition, and nitrogen (N) release. We found thatmore » the nutrient concentration of leaf litter varied among genotypes, which translated into 50% difference in decomposition rates. Variation among other goldenrod species in decomposition rate was more than twice that of genetic variation within S. altissima. Furthermore, by manipulating litterbags to contain 1, 3, 6, or 9 genotypes, we found that S. altissima genotype identity had much stronger effects than did genotypic diversity on leaf-litter quality, decomposition, and N release. Taken together, these results suggest that the order of ecological importance for controlling leaf-litter decomposition and N release dynamics is plant species identitygenotype identity>genotypic diversity.« less

Differing foraging strategies influence mercury (Hg) exposure in an Antarctic penguin community.

PubMed

Polito, Michael J; Brasso, Rebecka L; Trivelpiece, Wayne Z; Karnovsky, Nina; Patterson, William P; Emslie, Steven D

2016-11-01

Seabirds are ideal model organisms to track mercury (Hg) through marine food webs as they are long-lived, broadly distributed, and are susceptible to biomagnification due to foraging at relatively high trophic levels. However, using these species as biomonitors requires a solid understanding of the degree of species, sexual and age-specific variation in foraging behaviors which act to mediate their dietary exposure to Hg. We combined stomach content analysis along with Hg and stable isotope analyses of blood, feathers and common prey items to help explain inter and intra-specific patterns of dietary Hg exposure across three sympatric Pygoscelis penguin species commonly used as biomonitors of Hg availability in the Antarctic marine ecosystem. We found that penguin tissue Hg concentrations differed across species, between adults and juveniles, but not between sexes. While all three penguins species diets were dominated by Antarctic krill (Euphausia superba) and to a lesser extent fish, stable isotope based proxies of relative trophic level and krill consumption could not by itself sufficiently explain the observed patterns of inter and intra-specific variation in Hg. However, integrating isotopic approaches with stomach content analysis allowed us to identify the relatively higher risk of Hg exposure for penguins foraging on mesopelagic prey relative to congeners targeting epipelagic or benthic prey species. When possible, future seabird biomonitoring studies should seek to combine isotopic approaches with other, independent measures of foraging behavior to better account for the confounding effects of inter and intra-specific variation on dietary Hg exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Effects of water level fluctuation on the inter- and intra-specific relationships between Wedelia trilobata and W. chinensis].

PubMed

Bu, Xiang Qi; Liu, Lin; Mu, Ya Nan; Guan, Yu Ting; Li, Hong Li; Yu, Fei Hai

2017-03-18

A controlled greenhouse experiment was designed with the invasive Wedelia trilobata and native W. chinensis. Three water level fluctuation treatments (no fluctuation, change pattern by 15 cm-0 cm-15 cm, change pattern by 0 cm-15 cm-0 cm) were crossed with five plant arrangement treatments (an individual invasive plant per pot, an individual native plant per pot, 6 invasive plants per pot, 6 native plants per pot, six plants per pot with three invasive and three native plants) to explore the effects of water level fluctuation on inter- and intra-specific relationships between W. trilobata and W. chinensis. The results showed that water level fluctuation decreased signifi-cantly the total biomass, stem biomass, leaf biomass, root biomass, stem length, number of nodes, number of leaves and leaf area of W. trilobata and W. chinensis. Meantime it had significant effects on the inter- and intra-specific competition between W. trilobata and W. chinensis. Water level fluctuation changed the inter- and intra-specific competition of W. trilobata. It indicated that W. trilobata was more sensitive to water level fluctuation with stronger adaptability.

Teacher Attitudes toward Subject-Specific Acceleration: Instrument Development and Validation

ERIC Educational Resources Information Center

Rambo, Karen E.; McCoach, D. Betsy

2012-01-01

Despite the research supporting acceleration, some teachers are still hesitant to recommend acceleration for advanced students. The Teacher Attitudes Toward Subject-Specific Acceleration (TATSSA) instrument was designed to uncover the factors that influence teacher decisions to recommend students for subject-specific acceleration. First, we…

Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion.

PubMed

Bibo-Verdugo, Betsaida; O'Donoghue, Anthony J; Rojo-Arreola, Liliana; Craik, Charles S; García-Carreño, Fernando

2016-04-01

Crustaceans are a diverse group, distributed in widely variable environmental conditions for which they show an equally extensive range of biochemical adaptations. Some digestive enzymes have been studied by purification/characterization approaches. However, global analysis is crucial to understand how digestive enzymes interplay. Here, we present the first proteomic analysis of the digestive fluid from a crustacean (Homarus americanus) and identify glycosidases and peptidases as the most abundant classes of hydrolytic enzymes. The digestion pathway of complex carbohydrates was predicted by comparing the lobster enzymes to similar enzymes from other crustaceans. A novel and unbiased substrate profiling approach was used to uncover the global proteolytic specificity of gastric juice and determine the contribution of cysteine and aspartic acid peptidases. These enzymes were separated by gel electrophoresis and their individual substrate specificities uncovered from the resulting gel bands. This new technique is called zymoMSP. Each cysteine peptidase cleaves a set of unique peptide bonds and the S2 pocket determines their substrate specificity. Finally, affinity chromatography was used to enrich for a digestive cathepsin D1 to compare its substrate specificity and cold-adapted enzymatic properties to mammalian enzymes. We conclude that the H. americanus digestive peptidases may have useful therapeutic applications, due to their cold-adaptation properties and ability to hydrolyze collagen.

Body Fat Patterning, Hepatic Fat and Pancreatic Volume of Non-Obese Asian Indians with Type 2 Diabetes in North India: A Case-Control Study

PubMed Central

Misra, Anoop; Anoop, Shajith; Gulati, Seema; Mani, Kalaivani; Bhatt, Surya Prakash; Pandey, Ravindra Mohan

2015-01-01

Objective To evaluate body fat patterning and phenotype including hepatic fat and pancreatic volume of non-obese (BMI: < 25 kg/m2) Asian Indians with type 2 diabetes residing in North India. Methods Non-obese patients with type 2 diabetes (n = 93) and non-obese, normo-glycemic subjects (n = 40) were recruited. BMI, waist & hip circumferences, skinfold thickness at 8 sites, body fat, lean mass and detailed abdominal fat evaluation [total abdominal fat, total subcutaneous fat (superficial, deep, anterior, and posterior), total intra-abdominal fat (intra-peritoneal, retroperitoneal)], liver span, grades of fatty liver and pancreatic volume were compared. Results Waist circumference, subscapular skinfolds and total truncal fat (on DEXA) were higher whereas calf, total peripheral skinfolds and total leg fat (on DEXA) lower in patients. Specifically, the following volumes were higher in cases as compared to controls; total abdominal fat (19.4%), total intra-abdominal fat (49.7%), intra-peritoneal fat (47.7%), retroperitoneal fat (70.7%), pancreatic volume (26.6%), pancreatic volume index (21.3%) and liver span (10.8%). In cases, significant positive correlations were observed for pancreatic volume with BMI, waist and hip circumferences, W-HR, subscapular, abdominal and total truncal skinfolds, truncal, total subcutaneous, total intra-abdominal, intra-peritoneal, retroperitoneal fat depots, liver span and fatty liver. Conclusions In non-obese Asian Indians with type 2 diabetes, subcutaneous and intra-abdominal obesity, including fatty liver, and pancreatic volume were higher and peripheral subcutaneous adiposity was lower than BMI matched non-diabetic subjects. Importantly, increased pancreatic volume in patients was highly correlated with multiple measures of abdominal obesity and liver fat. PMID:26474415

Inter-view prediction of intra mode decision for high-efficiency video coding-based multiview video coding

NASA Astrophysics Data System (ADS)

da Silva, Thaísa Leal; Agostini, Luciano Volcan; da Silva Cruz, Luis A.

2014-05-01

Intra prediction is a very important tool in current video coding standards. High-efficiency video coding (HEVC) intra prediction presents relevant gains in encoding efficiency when compared to previous standards, but with a very important increase in the computational complexity since 33 directional angular modes must be evaluated. Motivated by this high complexity, this article presents a complexity reduction algorithm developed to reduce the HEVC intra mode decision complexity targeting multiview videos. The proposed algorithm presents an efficient fast intra prediction compliant with singleview and multiview video encoding. This fast solution defines a reduced subset of intra directions according to the video texture and it exploits the relationship between prediction units (PUs) of neighbor depth levels of the coding tree. This fast intra coding procedure is used to develop an inter-view prediction method, which exploits the relationship between the intra mode directions of adjacent views to further accelerate the intra prediction process in multiview video encoding applications. When compared to HEVC simulcast, our method achieves a complexity reduction of up to 47.77%, at the cost of an average BD-PSNR loss of 0.08 dB.

When Violence Pays: A Cost-Benefit Analysis of Aggressive Behavior in Animals and Humans

PubMed Central

Georgiev, Alexander V.; Klimczuk, Amanda C. E.; Traficonte, Daniel M.

2013-01-01

An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability) while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships). Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females. PMID:23864299

Fluoroscopically Guided Diagnostic and Therapeutic Intra-Articular Sacroiliac Joint Injections: A Systematic Review.

PubMed

Kennedy, David J; Engel, Andrew; Kreiner, D Scott; Nampiaparampil, Devi; Duszynski, Belinda; MacVicar, John

2015-08-01

To assess the validity of fluoroscopically guided diagnostic intra-articular injections of local anesthetic and effectiveness of intra-articular steroid injections in treating sacroiliac joint (SIJ) pain. Systematic review. Ten reviewers independently assessed 45 publications on diagnostic validity or effectiveness of fluoroscopically guided intra-articular SIJ injections. For diagnostic injections, the primary outcome was validity; for therapeutic injections, analgesia. Secondary outcomes were also described. Of 45 articles reviewed, 39 yielded diagnostic data on physical exam findings, provocation tests, and SIJ injections for diagnosing SIJ pain, and 15 addressed therapeutic effectiveness. When confirmed by comparative local anesthetic blocks with a high degree of pain relief, no single physical exam maneuver predicts response to diagnostic injections. When at least three physical exam findings are present, sensitivity, and specificity increases significantly. The prevalence of SIJ pain is likely 20-30% among patients that have suspected SIJ pain based on history and physical examination. This estimate may be higher in certain subgroups such as the elderly and fusion patients. Two randomized controlled trials and multiple observational studies supported the effectiveness of therapeutic sacroiliac joint injections. Based on this literature, it is unclear whether image-guided intra-articular diagnostic injections of local anesthetic predict positive responses to therapeutic agents. The overall quality of evidence is moderate for the effectiveness of therapeutic SIJ injections. Wiley Periodicals, Inc.

Viscosupplementation with high molecular weight native hyaluronan. Focus on a 1500-2000 KDa fraction (Hyalubrix®).

PubMed

Guidolin, D; Franceschi, F

2014-01-01

Joint disease reduces the rheological properties of synovial fluid, increasing the susceptibility of the articular cartilage to damage. Thus, a therapeutic strategy, called viscosupplementation, was proposed in which intra-articular injections of a suitable material are used to restore the viscoelastic properties of the synovial fluid. Solutions of high-MW native HA, which is the main component of the synovial fluid, were a natural choice to reach this goal, but HA-derived materials, engineered to achieve greater elastoviscosity and intra-articular residence time, were also developed. In the last twenty years the clinical experience showed that viscosupplementation is effective in joint diseases such as osteoarthritis, with beneficial effects on pain, function and patient global assessment. However, a marked variability between different preparations on different outcome parameters was reported to exist. In the present paper the available data on Hyalubrix®, a specific 1.5% formulation of natural HA with MW in the range 1500-2000 kDa, were reviewed, trying to outline, in the framework of the available intra-articular therapies, the role it can play for the symptomatic management of patients with degenerative joint arthropathy.

Comparison of classification methods for voxel-based prediction of acute ischemic stroke outcome following intra-arterial intervention

NASA Astrophysics Data System (ADS)

Winder, Anthony J.; Siemonsen, Susanne; Flottmann, Fabian; Fiehler, Jens; Forkert, Nils D.

2017-03-01

Voxel-based tissue outcome prediction in acute ischemic stroke patients is highly relevant for both clinical routine and research. Previous research has shown that features extracted from baseline multi-parametric MRI datasets have a high predictive value and can be used for the training of classifiers, which can generate tissue outcome predictions for both intravenous and conservative treatments. However, with the recent advent and popularization of intra-arterial thrombectomy treatment, novel research specifically addressing the utility of predictive classi- fiers for thrombectomy intervention is necessary for a holistic understanding of current stroke treatment options. The aim of this work was to develop three clinically viable tissue outcome prediction models using approximate nearest-neighbor, generalized linear model, and random decision forest approaches and to evaluate the accuracy of predicting tissue outcome after intra-arterial treatment. Therefore, the three machine learning models were trained, evaluated, and compared using datasets of 42 acute ischemic stroke patients treated with intra-arterial thrombectomy. Classifier training utilized eight voxel-based features extracted from baseline MRI datasets and five global features. Evaluation of classifier-based predictions was performed via comparison to the known tissue outcome, which was determined in follow-up imaging, using the Dice coefficient and leave-on-patient-out cross validation. The random decision forest prediction model led to the best tissue outcome predictions with a mean Dice coefficient of 0.37. The approximate nearest-neighbor and generalized linear model performed equally suboptimally with average Dice coefficients of 0.28 and 0.27 respectively, suggesting that both non-linearity and machine learning are desirable properties of a classifier well-suited to the intra-arterial tissue outcome prediction problem.

Reliability of sagittal plane hip, knee, and ankle joint angles from a single frame of video data using the GAITRite camera system.

PubMed

Ross, Sandy A; Rice, Clinton; Von Behren, Kristyn; Meyer, April; Alexander, Rachel; Murfin, Scott

2015-01-01

The purpose of this study was to establish intra-rater, intra-session, and inter-rater, reliability of sagittal plane hip, knee, and ankle angles with and without reflective markers using the GAITRite walkway and single video camera between student physical therapists and an experienced physical therapist. This study included thirty-two healthy participants age 20-59, stratified by age and gender. Participants performed three successful walks with and without markers applied to anatomical landmarks. GAITRite software was used to digitize sagittal hip, knee, and ankle angles at two phases of gait: (1) initial contact; and (2) mid-stance. Intra-rater reliability was more consistent for the experienced physical therapist, regardless of joint or phase of gait. Intra-session reliability was variable, the experienced physical therapist showed moderate to high reliability (intra-class correlation coefficient (ICC) = 0.50-0.89) and the student physical therapist showed very poor to high reliability (ICC = 0.07-0.85). Inter-rater reliability was highest during mid-stance at the knee with markers (ICC = 0.86) and lowest during mid-stance at the hip without markers (ICC = 0.25). Reliability of a single camera system, especially at the knee joint shows promise. Depending on the specific type of reliability, error can be attributed to the testers (e.g. lack of digitization practice and marker placement), participants (e.g. loose fitting clothing) and camera systems (e.g. frame rate and resolution). However, until the camera technology can be upgraded to a higher frame rate and resolution, and the software can be linked to the GAITRite walkway, the clinical utility for pre/post measures is limited.

Intra-and inter-observer reliability of nailfold videocapillaroscopy - A possible outcome measure for systemic sclerosis-related microangiopathy.

PubMed

Dinsdale, Graham; Moore, Tonia; O'Leary, Neil; Tresadern, Philip; Berks, Michael; Roberts, Christopher; Manning, Joanne; Allen, John; Anderson, Marina; Cutolo, Maurizio; Hesselstrand, Roger; Howell, Kevin; Pizzorni, Carmen; Smith, Vanessa; Sulli, Alberto; Wildt, Marie; Taylor, Christopher; Murray, Andrea; Herrick, Ariane L

2017-07-01

Our aim was to assess the reliability of nailfold capillary assessment in terms of image evaluability, image severity grade ('normal', 'early', 'active', 'late'), capillary density, capillary (apex) width, and presence of giant capillaries, and also to gain further insight into differences in these parameters between patients with systemic sclerosis (SSc), patients with primary Raynaud's phenomenon (PRP) and healthy control subjects. Videocapillaroscopy images (magnification 300×) were acquired from all 10 digits from 173 participants: 101 patients with SSc, 22 with PRP and 50 healthy controls. Ten capillaroscopy experts from 7 European centres evaluated the images. Custom image mark-up software allowed extraction of the following outcome measures: overall grade ('normal', 'early', 'active', 'late', 'non-specific', or 'ungradeable'), capillary density (vessels/mm), mean vessel apical width, and presence of giant capillaries. Observers analysed a median of 129 images each. Evaluability (i.e. the availability of measures) varied across outcome measures (e.g. 73.0% for density and 46.2% for overall grade in patients with SSc). Intra-observer reliability for evaluability was consistently higher than inter- (e.g. for density, intra-class correlation coefficient [ICC] was 0.71 within and 0.14 between observers). Conditional on evaluability, both intra- and inter-observer reliability were high for grade (ICC 0.93 and 0.78 respectively), density (0.91 and 0.64) and width (0.91 and 0.85). Evaluability is one of the major challenges in assessing nailfold capillaries. However, when images are evaluable, the high intra- and inter-reliabilities suggest that overall image grade, capillary density and apex width have potential as outcome measures in longitudinal studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Separating the effects of intra- and interspecific age-structured interactions in an experimental fish assemblage

USGS Publications Warehouse

Taylor, R.C.; Trexler, J.C.; Loftus, W.F.

2001-01-01

We documented patterns of age-structured biotic interactions in four mesocosm experiments with an assemblage of three species of co-occurring fishes from the Florida Everglades, the eastern mosquitofish (Gambusia holbrooki), sailfin molly (Poecilia latipinna), and bluefin killifish (Lucania goodei). These species were chosen based on their high abundance and overlapping diets. Juvenile mosquitofish and sailfin mollies, at a range of densities matching field estimates, were maintained in the presence of adult mosquitofish, sailfin mollies, and bluefin killifish to test for effects of competition and predation on juvenile survival and growth. The mesocosms held 1,200 1 of water and all conditions were set to simulate those in Shark River Slough, Everglades National Park (ENP), USA. We placed floating mats of periphyton and bladderwort in each tank in standard volumes that matched field values to provide cover and to introduce invertebrate prey. Of 15 possible intra- and interspecific age-structured interactions, we found 7 to be present at the densities of these fish found in Shark River Slough marshes. Predation by adult mosquitofish on juvenile fish, including conspecifics, was the strongest effect observed. We also observed growth limitation in mosquitofish and sailfin molly juveniles from intra- and interspecific competition. When maintained at high densities, juvenile mosquitofish changed their diets to include more cladocerans and fewer chironomid larvae relative to low densities. We estimated size-specific gape limitation by adult mosquitofish when consuming juvenile mosquitofish and sailfin mollies. At high field densities, intraspecific competition might prolong the time period when juveniles are vulnerable to predation by adult mosquitofish. These results suggest that path analysis, or other techniques used to document food-web interactions, must include age-specific roles of these fishes.

Increased overall cortical connectivity with syndrome specific local decreases suggested by atypical sleep-EEG synchronization in Williams syndrome.

PubMed

Gombos, Ferenc; Bódizs, Róbert; Kovács, Ilona

2017-07-21

Williams syndrome (7q11.23 microdeletion) is characterized by specific alterations in neurocognitive architecture and functioning, as well as disordered sleep. Here we analyze the region, sleep state and frequency-specific EEG synchronization of whole night sleep recordings of 21 Williams syndrome and 21 typically developing age- and gender-matched subjects by calculating weighted phase lag indexes. We found broadband increases in inter- and intrahemispheric neural connectivity for both NREM and REM sleep EEG of Williams syndrome subjects. These effects consisted of increased theta, high sigma, and beta/low gamma synchronization, whereas alpha synchronization was characterized by a peculiar Williams syndrome-specific decrease during NREM states (intra- and interhemispheric centro-temporal) and REM phases of sleep (occipital intra-area synchronization). We also found a decrease in short range, occipital connectivity of NREM sleep EEG theta activity. The striking increased overall synchronization of sleep EEG in Williams syndrome subjects is consistent with the recently reported increase in synaptic and dendritic density in stem-cell based Williams syndrome models, whereas decreased alpha and occipital connectivity might reflect and underpin the altered microarchitecture of primary visual cortex and disordered visuospatial functioning of Williams syndrome subjects.

The zinc dyshomeostasis hypothesis of Alzheimer's disease.

PubMed

Craddock, Travis J A; Tuszynski, Jack A; Chopra, Deepak; Casey, Noel; Goldstein, Lee E; Hameroff, Stuart R; Tanzi, Rudolph E

2012-01-01

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline.

Comparative mRNA analysis of behavioral and genetic mouse models of aggression.

PubMed

Malki, Karim; Tosto, Maria G; Pain, Oliver; Sluyter, Frans; Mineur, Yann S; Crusio, Wim E; de Boer, Sietse; Sandnabba, Kenneth N; Kesserwani, Jad; Robinson, Edward; Schalkwyk, Leonard C; Asherson, Philip

2016-04-01

Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and C57BL/6J) × stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBC gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors. © 2016 Wiley Periodicals, Inc.

Intra-vaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes

PubMed Central

Antoine, Thessicar E.; Hadigal, Satvik R.; Yakoub, Abraam; Mishra, Yogendra K.; Bhattacharya, Palash; Haddad, Christine; Valyi-Nagy, Tibor; Adelung, Rainer; Prabhakar, Bellur S.; Shukla, Deepak

2016-01-01

Virtually all efforts to generate an effective protection against the life-long, recurrent genital infections caused by Herpes simplex virus-2 (HSV-2) have failed. Apart from sexual transmission, the virus can also be transmitted from mothers to neonates, and is a key facilitator of HIV co-acquisition. Here, we uncover a nanoimmunotherapy using specially designed Zinc Oxide Tetrapod Nanoparticles (ZOTEN) with engineered oxygen vacancies. We demonstrate that ZOTEN, when used intravaginally as a microbicide, is an effective suppressor of HSV-2 genital infection in female BALB/c mice. The strong HSV-2 trapping ability of ZOTEN significantly reduced the clinical signs of vaginal infection and effectively decreased animal mortality. In parallel, ZOTEN promoted the presentation of bound HSV-2 virions to mucosal antigen presenting cells, enhancing T cell- mediated and antibody-mediated responses to the infection, and thereby, suppressing a re-infection. We also found that ZOTEN exhibits strong adjuvant-like properties, which is highly comparable to alum, a commonly used adjuvant. Overall, our study provides very first evidence for the protective efficacy of an intravaginal microbicide/vaccine or microbivac platform against primary and secondary female genital herpes infections. PMID:27183601

High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner*

PubMed Central

Kugler, Jamie E.; Horsch, Marion; Huang, Di; Furusawa, Takashi; Rochman, Mark; Garrett, Lillian; Becker, Lore; Bohla, Alexander; Hölter, Sabine M.; Prehn, Cornelia; Rathkolb, Birgit; Racz, Ildikó; Aguilar-Pimentel, Juan Antonio; Adler, Thure; Adamski, Jerzy; Beckers, Johannes; Busch, Dirk H.; Eickelberg, Oliver; Klopstock, Thomas; Ollert, Markus; Stöger, Tobias; Wolf, Eckhard; Wurst, Wolfgang; Yildirim, Ali Önder; Zimmer, Andreas; Gailus-Durner, Valérie; Fuchs, Helmut; Hrabě de Angelis, Martin; Garfinkel, Benny; Orly, Joseph; Ovcharenko, Ivan; Bustin, Michael

2013-01-01

The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1tm1/tm1, Hmgn3tm1/tm1, and Hmgn5tm1/tm1 mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgntm1/tm1 lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes. We conclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner. PMID:23620591

Intra- and interspecific trait variations reveal functional relationships between specific leaf area and soil niche within a subtropical forest.

PubMed

He, Dong; Chen, Yongfa; Zhao, Kangning; Cornelissen, J H C; Chu, Chengjin

2018-02-03

How functional traits vary with environmental conditions is of fundamental importance in trait-based community ecology. However, how intraspecific variability in functional traits is connected to species distribution is not well understood. This study investigated inter- and intraspecific variation of a key functional trait, i.e. specific leaf area (leaf area per unit dry mass; SLA), in relation to soil factors and tested if trait variation is more closely associated with specific environmental regimes for low-variability species than for high-variability species. In a subtropical evergreen forest plot (50 ha, southern China), 106 700 leaves from 5335 individuals of 207 woody species were intensively collected, with 30 individuals sampled for most species to ensure a sufficient sample size representative of intraspecific variability. Soil conditions for each plant were estimated by kriging from more than 1700 observational soil locations across the plot. Intra- and interspecific variation in SLA were separately related to environmental factors. Based on the species-specific variation of SLA, species were categorized into three groups: low-, intermediate- and high-intraspecific variability. Intraspecific habitat ranges and the strength of SLA-habitat relationships were compared among these three groups. Interspecific variation in SLA overrides the intraspecific variation (77 % vs. 8 %). Total soil nitrogen (TN, positively) and total organic carbon (TOC, negatively) are the most important explanatory factors for SLA variation at both intra- and interspecific levels. SLA, both within and between species, decreases with decreasing soil nitrogen availability. As predicted, species with low intraspecific variability in SLA have narrower habitat ranges with respect to soil TOC and TN and show a stronger SLA-habitat association than high-variability species. For woody plants low SLA is a phenotypic and probably adaptive response to nitrogen stress, which drives the predominance of species with ever-decreasing SLA towards less fertile habitats. Intraspecific variability in SLA is positively connected to species' niche breadth, suggesting that low-variability species may play a more deterministic role in structuring plant assemblages than high-variability species. This study highlights the importance of quantifying intraspecific trait variation to improve our understanding of species distributions across a vegetated landscape. © The Author(s) 2018. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Consistency and similarity of MEG- and fMRI-signal time courses during movie viewing.

PubMed

Lankinen, Kaisu; Saari, Jukka; Hlushchuk, Yevhen; Tikka, Pia; Parkkonen, Lauri; Hari, Riitta; Koskinen, Miika

2018-06-01

Movie viewing allows human perception and cognition to be studied in complex, real-life-like situations in a brain-imaging laboratory. Previous studies with functional magnetic resonance imaging (fMRI) and with magneto- and electroencephalography (MEG and EEG) have demonstrated consistent temporal dynamics of brain activity across movie viewers. However, little is known about the similarities and differences of fMRI and MEG or EEG dynamics during such naturalistic situations. We thus compared MEG and fMRI responses to the same 15-min black-and-white movie in the same eight subjects who watched the movie twice during both MEG and fMRI recordings. We analyzed intra- and intersubject voxel-wise correlations within each imaging modality as well as the correlation of the MEG envelopes and fMRI signals. The fMRI signals showed voxel-wise within- and between-subjects correlations up to r = 0.66 and r = 0.37, respectively, whereas these correlations were clearly weaker for the envelopes of band-pass filtered (7 frequency bands below 100 Hz) MEG signals (within-subjects correlation r < 0.14 and between-subjects r < 0.05). Direct MEG-fMRI voxel-wise correlations were unreliable. Notably, applying a spatial-filtering approach to the MEG data uncovered consistent canonical variates that showed considerably stronger (up to r = 0.25) between-subjects correlations than the univariate voxel-wise analysis. Furthermore, the envelopes of the time courses of these variates up to about 10 Hz showed association with fMRI signals in a general linear model. Similarities between envelopes of MEG canonical variates and fMRI voxel time-courses were seen mostly in occipital, but also in temporal and frontal brain regions, whereas intra- and intersubject correlations for MEG and fMRI separately were strongest only in the occipital areas. In contrast to the conventional univariate analysis, the spatial-filtering approach was able to uncover associations between the MEG envelopes and fMRI time courses, shedding light on the similarities of hemodynamic and electromagnetic brain activities during movie viewing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population.

PubMed

Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N

2017-03-30

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ 2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

PubMed Central

Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J.; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N.

2017-01-01

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype. PMID:28358038

New insights into the biogenesis of nuclear RNA polymerases?

PubMed

Cloutier, Philippe; Coulombe, Benoit

2010-04-01

More than 30 years of research on nuclear RNA polymerases (RNAP I, II, and III) has uncovered numerous factors that regulate the activity of these enzymes during the transcription reaction. However, very little is known about the machinery that regulates the fate of RNAPs before or after transcription. In particular, the mechanisms of biogenesis of the 3 nuclear RNAPs, which comprise both common and specific subunits, remains mostly uncharacterized and the proteins involved are yet to be discovered. Using protein affinity purification coupled to mass spectrometry (AP-MS), we recently unraveled a high-density interaction network formed by nuclear RNAP subunits from the soluble fraction of human cell extracts. Validation of the dataset using a machine learning approach trained to minimize the rate of false positives and false negatives yielded a high-confidence dataset and uncovered novel interactors that regulate the RNAP II transcription machinery, including a set of proteins we named the RNAP II-associated proteins (RPAPs). One of the RPAPs, RPAP3, is part of an 11-subunit complex we termed the RPAP3/R2TP/prefoldin-like complex. Here, we review the literature on the subunits of this complex, which points to a role in nuclear RNAP biogenesis.

Whole field tendencies in transcranial magnetic stimulation: A systematic review with data and text mining.

PubMed

Dias, Alvaro Machado; Mansur, Carlos Gustavo; Myczkowski, Martin; Marcolin, Marco

2011-06-01

Transcranial magnetic stimulation (TMS) has played an important role in the fields of psychiatry, neurology and neuroscience, since its emergence in the mid-1980s; and several high quality reviews have been produced since then. Most high quality reviews serve as powerful tools in the evaluation of predefined tendencies, but they cannot actually uncover new trends within the literature. However, special statistical procedures to 'mine' the literature have been developed which aid in achieving such a goal. This paper aims to uncover patterns within the literature on TMS as a whole, as well as specific trends in the recent literature on TMS for the treatment of depression. Data mining and text mining. Currently there are 7299 publications, which can be clustered in four essential themes. Considering the frequency of the core psychiatric concepts within the indexed literature, the main results are: depression is present in 13.5% of the publications; Parkinson's disease in 2.94%; schizophrenia in 2.76%; bipolar disorder in 0.158%; and anxiety disorder in 0.142% of all the publications indexed in PubMed. Several other perspectives are discussed in the article. Copyright © 2011 Elsevier B.V. All rights reserved.

New insights into the biogenesis of nuclear RNA polymerases?1

PubMed Central

Cloutier, Philippe; Coulombe, Benoit

2015-01-01

More than 30 years of research on nuclear RNA polymerases (RNAP I, II, and III) has uncovered numerous factors that regulate the activity of these enzymes during the transcription reaction. However, very little is known about the machinery that regulates the fate of RNAPs before or after transcription. In particular, the mechanisms of biogenesis of the 3 nuclear RNAPs, which comprise both common and specific subunits, remains mostly uncharacterized and the proteins involved are yet to be discovered. Using protein affinity purification coupled to mass spectrometry (AP–MS), we recently unraveled a high-density interaction network formed by nuclear RNAP subunits from the soluble fraction of human cell extracts. Validation of the dataset using a machine learning approach trained to minimize the rate of false positives and false negatives yielded a high-confidence dataset and uncovered novel interactors that regulate the RNAP II transcription machinery, including a set of proteins we named the RNAP II-associated proteins (RPAPs). One of the RPAPs, RPAP3, is part of an 11-subunit complex we termed the RPAP3/R2TP/prefoldin-like complex. Here, we review the literature on the subunits of this complex, which points to a role in nuclear RNAP biogenesis. PMID:20453924

DNA barcodes for two scale insect families, mealybugs (Hemiptera: Pseudococcidae) and armored scales (Hemiptera: Diaspididae).

PubMed

Park, D-S; Suh, S-J; Hebert, P D N; Oh, H-W; Hong, K-J

2011-08-01

Although DNA barcode coverage has grown rapidly for many insect orders, there are some groups, such as scale insects, where sequence recovery has been difficult. However, using a recently developed primer set, we recovered barcode records from 373 specimens, providing coverage for 75 species from 31 genera in two families. Overall success was >90% for mealybugs and >80% for armored scale species. The G·C content was very low in most species, averaging just 16.3%. Sequence divergences (K2P) between congeneric species averaged 10.7%, while intra-specific divergences averaged 0.97%. However, the latter value was inflated by high intra-specific divergence in nine taxa, cases that may indicate species overlooked by current taxonomic treatments. Our study establishes the feasibility of developing a comprehensive barcode library for scale insects and indicates that its construction will both create an effective system for identifying scale insects and reveal taxonomic situations worthy of deeper analysis.

Rational steering of insulin binding specificity by intra-chain chemical crosslinking

NASA Astrophysics Data System (ADS)

Viková, Jitka; Collinsová, Michaela; Kletvíková, Emília; Buděšínský, Miloš; Kaplan, Vojtěch; Žáková, Lenka; Veverka, Václav; Hexnerová, Rozálie; Aviñó, Roberto J. Tarazona; Straková, Jana; Selicharová, Irena; Vaněk, Václav; Wright, Daniel W.; Watson, Christopher J.; Turkenburg, Johan P.; Brzozowski, Andrzej M.; Jiráček, Jiří

2016-01-01

Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22-B30 segment, using the CuI-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26-B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormone’s B-chain C-terminus for its IR-B specificity.

Detection of Inter- and Intra-Specific Competition in the Insect Communities of British Trees: A Practical Exercise in Community Ecology.

ERIC Educational Resources Information Center

Putman, R. J.

1984-01-01

Describes an activity (suitable for high school or college) in which the effects of competition in the structuring of ecological communities are examined. The exercise also offers an introduction into species diversity; more advanced classes may be encouraged to seek reasons for differences in insect diversity on different trees. (Author/JN)

Informatic search strategies to discover analogues and variants of natural product archetypes.

PubMed

Johnston, Chad W; Connaty, Alex D; Skinnider, Michael A; Li, Yong; Grunwald, Alyssa; Wyatt, Morgan A; Kerr, Russell G; Magarvey, Nathan A

2016-03-01

Natural products are a crucial source of antimicrobial agents, but reliance on low-resolution bioactivity-guided approaches has led to diminishing interest in discovery programmes. Here, we demonstrate that two in-house automated informatic platforms can be used to target classes of biologically active natural products, specifically, peptaibols. We demonstrate that mass spectrometry-based informatic approaches can be used to detect natural products with high sensitivity, identifying desired agents present in complex microbial extracts. Using our specialised software packages, we could elaborate specific branches of chemical space, uncovering new variants of trichopolyn and demonstrating a way forward in mining natural products as a valuable source of potential pharmaceutical agents.

Intra- and inter-observer agreement in histological assessment of canine soft tissue sarcoma.

PubMed

Yap, F W; Rasotto, R; Priestnall, S L; Parsons, K J; Stewart, J

2017-12-01

The diagnosis of canine soft tissue sarcoma (STS) is based on histological assessment. Assessment of criteria such as, degree of differentiation, necrosis score and mitotic score, gives rise to a final tumour grade, which is important in the recommendation of treatment and prognosis of patients. Previously diagnosed cases of STS were independently assessed by three board-certified veterinary pathologists. Participating pathologists were blinded to the original results. For the intra-observer study, the cases were assessed by a single pathologist six months apart and slides were randomized between readings. For the inter-observer study, the whole case series was assessed by a single pathologist before being passed onto the next pathologist. Intraclass correlation coefficient (ICC) and Fleiss's Kappa (ƙ) for the intra- (single observer) and inter-observer agreement. Strong agreement was observed for the intra-observer assessment in necrosis score, mitotic score, total score and tumour grading (ICC between 0.78 to 0.91). The intra-observer agreement for differentiation score was rated perfect (ICC 1.00). The agreement between pathologists for the diagnosis and grading of canine STS was moderate (ƙ = 0.60 and 0.43 respectively). Histological assessment of canine STS had high reproducibility by an individual pathologist. The agreement of diagnosis and grading of canine STS was moderate between pathologists. Future studies are required to investigate further assessment criteria to improve the specificity of STS diagnosis and the accuracy of the STS grading in dogs. © 2017 John Wiley & Sons Ltd.

Magnetic resonance imaging of the long head of the biceps tendon: benefit of coplanar image.

PubMed

Lin, Anderson; Ting, Julius; Lee, Kwo-Whei

2007-01-01

To evaluate coplanar imaging of the long head of the biceps tendon. We retrospectively compared coronal oblique magnetic resonance images aligned with the principal supraspinatus tendon and with the intra-articular biceps tendon in 21 patients. Magnetic resonance images were analyzed for lesions depicted, including superior labral anteroposterior (SLAP) tears. Arthroscopic findings were reviewed. Coronal oblique images aligned with intra-articular biceps tendon depicted 18 (86%) of 21 coplanar intra-articular biceps tendons. Coplanar images identified 6 cases of tendinosis, 1 tear, 3 intra-articular ruptures, and 20 (95.2%) of 21 exact origins of the tendon. Arthroscopy revealed 18 SLAP tears. The detection of SLAP lesions between both coronal oblique magnetic resonance images was significantly different (P = 0.007). Advantages included imaging of the intra-articular biceps tendon with least partial-volume effects, definition of SLAP lesions and the tendinous origin at the supraglenoid tubercle, depiction of intra-articular bicipital ruptures, and increased sensitivity and specificity for intra-articular lesions.

How well can step-off and gap distances be reduced when treating intra-articular distal radius fractures with fragment specific fixation when using fluoroscopy.

PubMed

Thiart, M; Ikram, A; Lamberts, R P

2016-12-01

Although fragment specific fixation has proved to be an effective treatment regime, it has not been established how successfully this treatment could be performed using fluoroscopy and what the added value of arthroscopy could be. Establish gap and step-off distances after in intra-articular distal radius fractures that have been treated with fragment specific fixation while using fluoroscopy. Forty-four patients with an intra-articular distal radius fracture were treated with fragment specific fixation while using fluoroscopy. After the treatment of the intra-articular distal radius fracture with fragment specific fixation and the use of fluoroscopy, but before the completion of the surgical intervention, all gap, and step-off distances were determined by using arthroscopy. In addition, the joint was checked for any other wrist pathologies. Arthroscopy after the surgical intervention showed that in 37 patients no gap distances could be detected, while in six patients a gap distance of≤2mm was found and in one patient, a gap distance of 3mm. Similarly, arthroscopy revealed no step-off distances in 33 patients, while in 11 patients a step-off distance of≤2mm was found. Although additional wrist pathologies were found in 48% of our population, only one patient needed surgical intervention. Three months after the surgical intervention wrist flexion was 41±10°, wrist extension 51±17°, ulnar deviation 19±10°, radial deviation 32±12° while patients could pronate and supinate their wrist to 85±5° and 74±20°, respectively. Intra-articular distal radius fractures can be treated successfully with fragment specific fixation and the use of fluoroscopy. As almost all gap and step-off distances could be reduced to an acceptable level, the scope for arthroscopy to further improve this treatment regime is limited. The functional outcome scores that were found 3 months after the surgical intervention were similar to what has been reported in other studies using different treatment option. These findings suggest that fragment specific fixation is a good alternative for treating intra-articular distal radius fractures. As in most cases, only fluoroscopy is needed for fragment specific fixation, this treatment technique is a good treatment option for resource-limited hospitals, setting who do not have access to arthroscopy. III, case-control study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Intra-population variation in activity ranges, diel patterns, movement rates, and habitat use of American alligators in a subtropical estuary

USGS Publications Warehouse

Rosenblatt, Adam E.; Heithaus, Michael R.; Mazzotti, Frank M; Cherkiss, Michael S.; Jeffery, Brian M.

2013-01-01

Movement and habitat use patterns are fundamental components of the behaviors of mobile animals and help determine the scale and types of interactions they have with their environments. These behaviors are especially important to quantify for top predators because they can have strong effects on lower trophic levels as well as the wider ecosystem. Many studies of top predator movement and habitat use focus on general population level trends, which may overlook important intra-population variation in behaviors that now appear to be common. In an effort to better understand the prevalence of intrapopulation variation in top predator movement behaviors and the potential effects of such variation on ecosystem dynamics, we examined the movement and habitat use patterns of a population of adult American alligators (Alligator mississippiensis) in a subtropical estuary for nearly four years. We found that alligators exhibited divergent behaviors with respect to activity ranges, movement rates, and habitat use, and that individualized behaviors were stable over multiple years. We also found that the variations across the three behavioral metrics were correlated such that consistent behavioral types emerged, specifically more exploratory individuals and more sedentary individuals. Our study demonstrates that top predator populations can be characterized by high degrees of intra-population variation in terms of movement and habitat use behaviors that could lead to individuals filling different ecological roles in the same ecosystem. By extension, one-size-fits-all ecosystem and species-specific conservation and management strategies that do not account for potential intra-population variation in top predator behaviors may not produce the desired outcomes in all cases.

Changes in children's sleep domains between 2 and 3 years of age: the Ulm SPATZ Health Study.

PubMed

Braig, Stefanie; Urschitz, Michael S; Rothenbacher, Dietrich; Genuneit, Jon

2017-08-01

There is growing interest in the link between sleep habits and child health but reference values specific to toddlers as well as longitudinal data on sleep are scarce. We aimed to describe parent-reported child sleep habits and their intra-individual changes in two- to three-year-olds using data from a regional birth cohort study. In the Ulm SPATZ Health Study, a birth cohort study conducted at Ulm, Southern Germany, with baseline examination from April 2012 to May 2013, the German version of the Children's Sleep Habits Questionnaire (CSHQ-DE) was used longitudinally at follow-ups at two and three years (N = 615 children). Descriptive statistics including intra-individual differences between three- and two-year scores were reported, the latter using the sign test. The sample-averaged total and subscale CSHQ scores differed only slightly between two and three years (max. Cohen's d = 0.39). Intra-individual comparisons of the CSHQ subscales or single items revealed congruent but also opposing changes in items belonging to the same subscale. Whereas items on bedtime resistance generally improved, sleep duration shortened with older age. With regard to sleep anxiety, we found worsening in the item 'Afraid of sleeping in the dark' in about one-fifth of our children whereas other items on this CSHQ subscale showed an opposing trend with age. A similar opposing trend was detected within the subscale on night wakings. Our data provide initial descriptive information on sleep habits in toddlers. The high intra-individual changes, partly in opposing directions which may be masked by aggregation, indicate a need for age- and item-specific analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

Results of a Formal Methods Demonstration Project

NASA Technical Reports Server (NTRS)

Kelly, J.; Covington, R.; Hamilton, D.

1994-01-01

This paper describes the results of a cooperative study conducted by a team of researchers in formal methods at three NASA Centers to demonstrate FM techniques and to tailor them to critical NASA software systems. This pilot project applied FM to an existing critical software subsystem, the Shuttle's Jet Select subsystem (Phase I of an ongoing study). The present study shows that FM can be used successfully to uncover hidden issues in a highly critical and mature Functional Subsystem Software Requirements (FSSR) specification which are very difficult to discover by traditional means.

A novel standardized algorithm using SPECT/CT evaluating unhappy patients after unicondylar knee arthroplasty--a combined analysis of tracer uptake distribution and component position.

PubMed

Suter, Basil; Testa, Enrique; Stämpfli, Patrick; Konala, Praveen; Rasch, Helmut; Friederich, Niklaus F; Hirschmann, Michael T

2015-03-20

The introduction of a standardized SPECT/CT algorithm including a localization scheme, which allows accurate identification of specific patterns and thresholds of SPECT/CT tracer uptake, could lead to a better understanding of the bone remodeling and specific failure modes of unicondylar knee arthroplasty (UKA). The purpose of the present study was to introduce a novel standardized SPECT/CT algorithm for patients after UKA and evaluate its clinical applicability, usefulness and inter- and intra-observer reliability. Tc-HDP-SPECT/CT images of consecutive patients (median age 65, range 48-84 years) with 21 knees after UKA were prospectively evaluated. The tracer activity on SPECT/CT was localized using a specific standardized UKA localization scheme. For tracer uptake analysis (intensity and anatomical distribution pattern) a 3D volumetric quantification method was used. The maximum intensity values were recorded for each anatomical area. In addition, ratios between the respective value in the measured area and the background tracer activity were calculated. The femoral and tibial component position (varus-valgus, flexion-extension, internal and external rotation) was determined in 3D-CT. The inter- and intraobserver reliability of the localization scheme, grading of the tracer activity and component measurements were determined by calculating the intraclass correlation coefficients (ICC). The localization scheme, grading of the tracer activity and component measurements showed high inter- and intra-observer reliabilities for all regions (tibia, femur and patella). For measurement of component position there was strong agreement between the readings of the two observers; the ICC for the orientation of the femoral component was 0.73-1.00 (intra-observer reliability) and 0.91-1.00 (inter-observer reliability). The ICC for the orientation of the tibial component was 0.75-1.00 (intra-observer reliability) and 0.77-1.00 (inter-observer reliability). The SPECT/CT algorithm presented combining the mechanical information on UKA component position, alignment and metabolic data is highly reliable and proved to be a valuable, consistent and useful tool for analysing postoperative knees after UKA. Using this standardized approach in clinical studies might be helpful in establishing the diagnosis in patients with pain after UKA.

Intra-prosthetic breast MR virtual navigation: a preliminary study for a new evaluation of silicone breast implants.

PubMed

Moschetta, Marco; Telegrafo, Michele; Capuano, Giulia; Rella, Leonarda; Scardapane, Arnaldo; Angelelli, Giuseppe; Stabile Ianora, Amato Antonio

2013-10-01

To assess the contribute of intra-prosthetic MRI virtual navigation for evaluating breast implants and detecting implant ruptures. Forty-five breast implants were evaluated by MR examination. Only patients with a clinical indication were assessed. A 1.5-T device equipped with a 4-channel breast coil was used by performing axial TSE-T2, axial silicone-only, axial silicone suppression and sagittal STIR images. The obtained dicom files were also analyzed by using virtual navigation software. Two blinded radiologists evaluated all MR and virtual images. Eight patients for a total of 13 implants underwent surgical replacement. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both imaging strategies. Intra-capsular rupture was diagnosed in 13 out of 45 (29%) implants by using MRI. Basing on virtual navigation, 9 (20%) cases of intra-capsular rupture were diagnosed. Sensitivity, specificity, accuracy, PPV and NPV values of 100%, 86%, 89%, 62% and 100%, respectively, were found for MRI. Virtual navigation increased the previous values up to 100%, 97%, 98%, 89% and 100%. Intra-prosthetic breast MR virtual navigation can represent an additional promising tool for the evaluation of breast implants being able to reduce false positives and to provide a more accurate detection of intra-capsular implant rupture signs. Copyright © 2013 Elsevier Inc. All rights reserved.

Are both sympatric species Ilex perado and Ilex canariensis secretly hybridizing? Indication from nuclear markers collected in Tenerife

PubMed Central

Manen, Jean-François

2004-01-01

Background Intra-specific and intra-individual polymorphism is frequently observed in nuclear markers of Ilex (Aquifoliaceae) and discrepancy between plastid and nuclear phylogenies is the rule in this genus. These observations suggest that inter-specific plastid or/and nuclear introgression played an important role in the process of evolution of Ilex. With the aim of a precise understanding of the evolution of this genus, two distantly related sympatric species collected in Tenerife (Canary Islands), I. perado and I. canariensis, were studied in detail. Introgression between these two species was previously never reported. One plastid marker (the atpB-rbcL spacer) and two nuclear markers, the ribosomal internal transcribed spacer (ITS) and the nuclear encoded plastid glutamine synthetase (nepGS) were analyzed for 13 and 27 individuals of I. perado and I. canariensis, respectively. Results The plastid marker is intra-specifically constant and correlated with species identity. On the other hand, whereas the nuclear markers are conserved in I. perado, they are highly polymorphic in I. canariensis. The presence of pseudogenes and recombination in ITS sequences of I. canariensis explain this polymorphism. Ancestral sequence polymorphism with incomplete lineage sorting, or past or recent hybridization with an unknown species could explain this polymorphism, not resolved by concerted evolution. However, as already reported for many other plants, past or recent introgression of an alien genotype seem the most probable explanation for such a tremendous polymorphism. Conclusions Data do not allow the determination with certitude of the putative species introgressing I. canariensis, but I. perado is suspected. The introgression would be unilateral, with I. perado as the male donor, and the paternal sequences would be rapidly converted in highly divergent and consequently unidentifiable pseudogenes. At least, this study allows the establishment of precautionary measures when nuclear markers are used in phylogenetic studies of genera having experienced introgression such as the genus Ilex. PMID:15550175

Fitness costs of intrinsic competition in two egg parasitoids of a true bug.

PubMed

Cusumano, Antonino; Peri, Ezio; Boivin, Guy; Colazza, Stefano

2015-10-01

Intrinsic competition in insect parasitoids occurs when supernumerary larvae develop in the same host as consequence of multiple ovipositions by females of the same species (intra-specific competition) or by females of different species (inter-specific competition). Studies on intrinsic competition have mainly focused on understanding the factors that play a role in the outcome of competition, while fitness-related effects for the parasitoid surviving the competition have been poorly investigated, especially in egg parasitoids. Interestingly, even the winning parasitoid can experience fitness costs due to larval development in a host in which multiple factors have been injected by the ovipositing females or released by their larvae. In this paper we studied fitness-related traits associated with intra- and inter-specific competition between Trissolcus basalis (Wollaston) and Ooencyrtus telenomicida (Vassiliev), the main egg parasitoids associated with the southern green stink bug Nezara viridula (L.) in Italy. We investigated the impact of intrinsic competition for the surviving parasitoid in terms of body size, developmental time, number and size of oocytes. Our results indicated that T. basalis adults did not experience fitness-related costs when surviving intra-specific competition; however, adults were smaller, took longer to develop and females produced fewer oocytes after surviving inter-specific competition. A different outcome was found for O. telenomicida where the emerging females were smaller, produced fewer and smaller oocytes when suffering intra-specific competition whereas no fitness costs were found when adults survived inter-specific competition. These results support the hypothesis that the impact of intrinsic competition in egg parasitoids depends on the severity of the competitive interaction, as fitness costs were more pronounced when the surviving parasitoid interacted with the most detrimental competitor. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antibody to the gp120 V1/V2 loops and CD4+and CD8+ T-cell responses in protection from SIVmac251 vaginal acquisition and persistent viremia

PubMed Central

Gordon, Shari N.; Doster, Melvin N; Kines, Rhonda C.; Keele, Brandon F; Cofano, Egidio Brocca; Guan, Yongjun; Pegu, Poonam; Liyanage, Namal P.M.; Vaccari, Monica; Cuburu, Nicolas; Buck, Christopher B.; Ferrari, Guido; Montefiori, David; Piatak, Mike; Lifson, Jeffrey D; Xenophontos, Anastasia M.; Venzon, David; Robert-Guroff, Marjorie; Graham, Barney S.; Lowy, Douglas R.; Schiller, John T.; Franchini, Genoveffa

2015-01-01

The human papilloma virus pseudovirions (HPV-PsVs) approach is an effective gene-delivery system that can prime or boost an immune response in the vaginal tract of non human primates and mice. Intra-vaginal vaccination with HPV-PsVs expressing SIV genes, combined with an intra-muscular gp120 protein injection, induced humoral and cellular SIV-specific responses in macaques. Priming systemic immune responses with intramuscular immunization with ALVAC-SIV vaccines, followed by intra-vaginal HPV-PsV-SIV/gp120 boosting, expanded and/or recruited T-cells in the female genital tract. Using a stringent repeated low dose intra-vaginal challenge with the highly pathogenic SIVmac251, we show that while these regimens did not demonstrate significant protection from virus acquisition, they provided control of viremia in a number of animals. High avidity antibody responses to the envelope gp120 V1/V2 region correlated with delayed SIVmac251 acquisition, while virus levels in mucosal tissues were inversely correlated with anti-envelope CD4+T-cell responses. CD8+T-cell depletion in animals with controlled viremia caused an increase in tissue virus load in some animals, suggesting a role for CD8+T-cells in virus control. This study highlights the importance of CD8+ cells and anti-envelope CD4+ T-cell in curtailing virus replication and anti-envelope V1/V2 antibodies in preventing SIVmac251 acquisition. PMID:25398324

Immunological tools for the assessment of both humoral and cellular immune responses in Foxes (Vulpes vulpes) using ovalbumin and cholera toxin B as an antigenic model.

PubMed

Rolland-Turner, Magali; Farre, Guillaume; Muller, Delphine; Rouet, Nelly; Boue, Franck

2004-10-22

The immune response in the fox (Vulpes vulpes), despite the success of the oral rabies vaccine is not well characterized, and specific immunological tools are needed. To investigate both the humoral and cellular immune response, we used ovalbumin (OVA) and cholera toxin B (CTB) as an antigenic model to set-up ELISA and ELISPOT antibodies secreting cells (ASC) assays in the fox model. Identification of antibodies that cross-react with fox immunoglobulin was performed by Western blot, and their use was adapted for both the ELISA and ELISPOT ASC assay. The humoral and cellular specific immune responses were assessed after intra-muscular or intra-nasal immunization. Intra-muscular immunization resulted in the development of both cellular and humoral anti-OVA and anti-CTB responses in peripheral blood mononuclear cells (PBMCs). Immunization via the intra-nasal route resulted in the development of a cellular and humoral response against CTB in PBMCs. This immune response was confirmed using splenocytes from immunized animals by ELISPOT assay at euthanasia. Females immunized via the intra-nasal route developed specific anti-CTB IgM, IgA and IgG in vaginal fluids after the initial boost (day 26) showing that mucosal immunization produces a vaginal immune response in foxes. These immunological tools developed here are now available to be adapted to other antigenic models to facilitate further immune studies in foxes.

Comparison of the levels of intra-specific genetic variation within Giardia muris and Giardia intestinalis.

PubMed

Andrews, R H; Monis, P T; Ey, P L; Mayrhofer, G

1998-08-01

The extent of intra-specific genetic variation between isolates of Giardia muris was assessed by allozyme electrophoresis. Additionally, the levels of allozymic variation detected within G. muris were compared with those observed between members of the two major assemblages of the morphologically distinct species Giardia intestinalis. Four isolates of G. muris were analysed. Three (Ad-120, -150, -151) were isolated from mice in Australia, while the fourth (R-T) was isolated from a golden hamster in North America. The 11 isolates of G. intestinalis (Ad-1, -12, -2, -62, representing genetic Groups I and II of Assemblage A and BAH-12, BRIS/87/HEPU/694, Ad-19, -22, -28, -45, -52, representing genetic Groups III and IV of Assemblage B) were from humans in Australia. Intra-specific genetic variation was detected between G. muris isolates at four of the 23 enzyme loci examined. Similar levels of variation were found within the genetic groups that comprise Assemblages A and B of G. intestinalis. These levels of intra-specific variation are similar to those observed within other morphologically-distinct species of protozoan parasites. We suggest that the magnitude of the genetic differences detected within G. muris provides an indication of the range of genetic variation within other species of Giardia and that this can be used as a model to delineate morphologically similar but genetically distinct (cryptic) species within this genus.

Individual diet variation in a marine fish assemblage: Optimal Foraging Theory, Niche Variation Hypothesis and functional identity

NASA Astrophysics Data System (ADS)

Cachera, M.; Ernande, B.; Villanueva, M. C.; Lefebvre, S.

2017-02-01

Individual diet variation (i.e. diet variation among individuals) impacts intra- and inter-specific interactions. Investigating its sources and relationship with species trophic niche organization is important for understanding community structure and dynamics. Individual diet variation may increase with intra-specific phenotypic (or "individual state") variation and habitat variability, according to Optimal Foraging Theory (OFT), and with species trophic niche width, according to the Niche Variation Hypothesis (NVH). OFT proposes "proximate sources" of individual diet variation such as variations in habitat or size whereas NVH relies on "ultimate sources" related to the competitive balance between intra- and inter-specific competitions. The latter implies as a corollary that species trophic niche overlap, taken as inter-specific competition measure, decreases as species niche width and individual niche variation increase. We tested the complementary predictions of OFT and NVH in a marine fish assemblage using stomach content data and associated trophic niche metrics. The NVH predictions were tested between species of the assemblage and decomposed into a between- and a within-functional group component to assess the potential influence of species' ecological function. For most species, individual diet variation and niche overlap were consistently larger than expected. Individual diet variation increased with intra-specific variability in individual state and habitat, as expected from OFT. It also increased with species niche width but in compliance with the null expectation, thus not supporting the NVH. In contrast, species niche overlap increased significantly less than null expectation with both species niche width and individual diet variation, supporting NVH corollary. The between- and within-functional group components of the NVH relationships were consistent with those between species at the assemblage level. Changing the number of prey categories used to describe diet (from 16 to 41) did not change the results qualitatively. These results suggest that, besides proximate sources, intra-specific competition favors higher individual diet variation than expected while inter-specific competition limits the increase of individual diet variation and of species niche overlap with species niche expansion. This reveals partial trophic resource partitioning between species. Various niche metrics used in combination allow inferring competition effects on trophic niches' organization within communities.

Research of Face Recognition with Fisher Linear Discriminant

NASA Astrophysics Data System (ADS)

Rahim, R.; Afriliansyah, T.; Winata, H.; Nofriansyah, D.; Ratnadewi; Aryza, S.

2018-01-01

Face identification systems are developing rapidly, and these developments drive the advancement of biometric-based identification systems that have high accuracy. However, to develop a good face recognition system and to have high accuracy is something that’s hard to find. Human faces have diverse expressions and attribute changes such as eyeglasses, mustache, beard and others. Fisher Linear Discriminant (FLD) is a class-specific method that distinguishes facial image images into classes and also creates distance between classes and intra classes so as to produce better classification.

Evidence-based practice: extending the search to find material for the systematic review

PubMed Central

Helmer, Diane; Savoie, Isabelle; Green, Carolyn; Kazanjian, Arminée

2001-01-01

Background: Cochrane-style systematic reviews increasingly require the participation of librarians. Guidelines on the appropriate search strategy to use for systematic reviews have been proposed. However, research evidence supporting these recommendations is limited. Objective: This study investigates the effectiveness of various systematic search methods used to uncover randomized controlled trials (RCTs) for systematic reviews. Effectiveness is defined as the proportion of relevant material uncovered for the systematic review using extended systematic review search methods. The following extended systematic search methods are evaluated: searching subject-specific or specialized databases (including trial registries), hand searching, scanning reference lists, and communicating personally. Methods: Two systematic review projects were prospectively monitored regarding the method used to identify items as well as the type of items retrieved. The proportion of RCTs identified by each systematic search method was calculated. Results: The extended systematic search methods uncovered 29.2% of all items retrieved for the systematic reviews. The search of specialized databases was the most effective method, followed by scanning of reference lists, communicating personally, and hand searching. Although the number of items identified through hand searching was small, these unique items would otherwise have been missed. Conclusions: Extended systematic search methods are effective tools for uncovering material for the systematic review. The quality of the items uncovered has yet to be assessed and will be key in evaluating the value of the systematic search methods. PMID:11837256

Prevalence and Clinical Significance of Sterile Intra-amniotic Inflammation in Patients with Preterm Labor and Intact Membranes

PubMed Central

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Yoon, Bo Hyun; Hassan, Sonia S.; Kim, Chong J.; Yeo, Lami

2014-01-01

Problem Inflammation and infection play a major role in preterm birth. The purpose of this study was to: 1) determine the prevalence and clinical significance of sterile intra-amniotic inflammation; and 2) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis-to-delivery in patients with sterile intra-amniotic inflammation. Method of Study AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). Results 1) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) vs. 11% (15/135); (p=0.005)]; 2) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages, had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation; and 3) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥ 8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (p=0.02). Conclusions 1) sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation; and 2) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor. PMID:25078709

Intraspecific Variation in Wood Anatomical, Hydraulic, and Foliar Traits in Ten European Beech Provenances Differing in Growth Yield

PubMed Central

Hajek, Peter; Kurjak, Daniel; von Wühlisch, Georg; Delzon, Sylvain; Schuldt, Bernhard

2016-01-01

In angiosperms, many studies have described the inter-specific variability of hydraulic-related traits and little is known at the intra-specific level. This information is however mandatory to assess the adaptive capacities of tree populations in the context of increasing drought frequency and severity. Ten 20-year old European beech (Fagus sylvatica L.) provenances representing the entire distribution range throughout Europe and differing significantly in aboveground biomass increment (ABI) by a factor of up to four were investigated for branch wood anatomical, hydraulic, and foliar traits in a provenance trial located in Northern Europe. We quantified to which extend xylem hydraulic and leaf traits are under genetic control and tested whether the xylem hydraulic properties (hydraulic efficiency and safety) trades off with yield and wood anatomical and leaf traits. Our results showed that only three out of 22 investigated ecophysiological traits showed significant genetic differentiations between provenances, namely vessel density (VD), the xylem pressure causing 88% loss of hydraulic conductance and mean leaf size. Depending of the ecophysiological traits measured, genetic differentiation between populations explained 0–14% of total phenotypic variation, while intra-population variability was higher than inter-population variability. Most wood anatomical traits and some foliar traits were additionally related to the climate of provenance origin. The lumen to sapwood area ratio, vessel diameter, theoretical specific conductivity and theoretical leaf-specific conductivity as well as the C:N-ratio increased with climatic aridity at the place of origin while the carbon isotope signature (δ13C) decreased. Contrary to our assumption, none of the wood anatomical traits were related to embolism resistance but were strong determinants of hydraulic efficiency. Although ABI was associated with both VD and δ13C, both hydraulic efficiency and embolism resistance were unrelated, disproving the assumed trade-off between hydraulic efficiency and safety. European beech seems to compensate increasing water stress with growing size mainly by adjusting vessel number and not vessel diameter. In conclusion, European beech has a high potential capacity to cope with climate change due to the high degree of intra-population genetic variability. PMID:27379112

Intraspecific Variation in Wood Anatomical, Hydraulic, and Foliar Traits in Ten European Beech Provenances Differing in Growth Yield.

PubMed

Hajek, Peter; Kurjak, Daniel; von Wühlisch, Georg; Delzon, Sylvain; Schuldt, Bernhard

2016-01-01

In angiosperms, many studies have described the inter-specific variability of hydraulic-related traits and little is known at the intra-specific level. This information is however mandatory to assess the adaptive capacities of tree populations in the context of increasing drought frequency and severity. Ten 20-year old European beech (Fagus sylvatica L.) provenances representing the entire distribution range throughout Europe and differing significantly in aboveground biomass increment (ABI) by a factor of up to four were investigated for branch wood anatomical, hydraulic, and foliar traits in a provenance trial located in Northern Europe. We quantified to which extend xylem hydraulic and leaf traits are under genetic control and tested whether the xylem hydraulic properties (hydraulic efficiency and safety) trades off with yield and wood anatomical and leaf traits. Our results showed that only three out of 22 investigated ecophysiological traits showed significant genetic differentiations between provenances, namely vessel density (VD), the xylem pressure causing 88% loss of hydraulic conductance and mean leaf size. Depending of the ecophysiological traits measured, genetic differentiation between populations explained 0-14% of total phenotypic variation, while intra-population variability was higher than inter-population variability. Most wood anatomical traits and some foliar traits were additionally related to the climate of provenance origin. The lumen to sapwood area ratio, vessel diameter, theoretical specific conductivity and theoretical leaf-specific conductivity as well as the C:N-ratio increased with climatic aridity at the place of origin while the carbon isotope signature (δ(13)C) decreased. Contrary to our assumption, none of the wood anatomical traits were related to embolism resistance but were strong determinants of hydraulic efficiency. Although ABI was associated with both VD and δ(13)C, both hydraulic efficiency and embolism resistance were unrelated, disproving the assumed trade-off between hydraulic efficiency and safety. European beech seems to compensate increasing water stress with growing size mainly by adjusting vessel number and not vessel diameter. In conclusion, European beech has a high potential capacity to cope with climate change due to the high degree of intra-population genetic variability.

Molecular mapping of QTLs for plant type and earliness traits in pigeonpea (Cajanus cajan L. Millsp.).

PubMed

Kumawat, Giriraj; Raje, Ranjeet S; Bhutani, Shefali; Pal, Jitendra K; Mithra, Amitha S V C R; Gaikwad, Kishor; Sharma, Tilak R; Singh, Nagendra K

2012-10-08

Pigeonpea is an important grain legume of the semi-arid tropics and sub-tropical regions where it plays a crucial role in the food and nutritional security of the people. The average productivity of pigeonpea has remained very low and stagnant for over five decades due to lack of genomic information and intensive breeding efforts. Previous SSR-based linkage maps of pigeonpea used inter-specific crosses due to low inter-varietal polymorphism. Here our aim was to construct a high density intra-specific linkage map using genic-SNP markers for mapping of major quantitative trait loci (QTLs) for key agronomic traits, including plant height, number of primary and secondary branches, number of pods, days to flowering and days to maturity in pigeonpea. A population of 186 F2:3 lines derived from an intra-specific cross between inbred lines 'Pusa Dwarf' and 'HDM04-1' was used to construct a dense molecular linkage map of 296 genic SNP and SSR markers covering a total adjusted map length of 1520.22 cM for the 11 chromosomes of the pigeonpea genome. This is the first dense intra-specific linkage map of pigeonpea with the highest genome length coverage. Phenotypic data from the F2:3 families were used to identify thirteen QTLs for the six agronomic traits. The proportion of phenotypic variance explained by the individual QTLs ranged from 3.18% to 51.4%. Ten of these QTLs were clustered in just two genomic regions, indicating pleiotropic effects or close genetic linkage. In addition to the main effects, significant epistatic interaction effects were detected between the QTLs for number of pods per plant. A large amount of information on transcript sequences, SSR markers and draft genome sequence is now available for pigeonpea. However, there is need to develop high density linkage maps and identify genes/QTLs for important agronomic traits for practical breeding applications. This is the first report on identification of QTLs for plant type and maturity traits in pigeonpea. The QTLs identified in this study provide a strong foundation for further validation and fine mapping for utilization in the pigeonpea improvement.

Effect of a Perioperative Intra-Aortic Balloon Pump in High-Risk Cardiac Surgery Patients: A Randomized Clinical Trial.

PubMed

Rocha Ferreira, Graziela Santos; de Almeida, Juliano Pinheiro; Landoni, Giovanni; Vincent, Jean Louis; Fominskiy, Evgeny; Gomes Galas, Filomena Regina Barbosa; Gaiotto, Fabio A; Dallan, Luís Oliveira; Franco, Rafael Alves; Lisboa, Luiz Augusto; Palma Dallan, Luis Roberto; Fukushima, Julia Tizue; Rizk, Stephanie Itala; Park, Clarice Lee; Strabelli, Tânia Mara; Gelas Lage, Silvia Helena; Camara, Ligia; Zeferino, Suely; Jardim, Jaquelline; Calvo Arita, Elisandra Cristina Trevisan; Caldas Ribeiro, Juliana; Ayub-Ferreira, Silvia Moreira; Costa Auler, Jose Otavio; Filho, Roberto Kalil; Jatene, Fabio Biscegli; Hajjar, Ludhmila Abrahao

2018-04-30

The aim of this study was to evaluate the efficacy of perioperative intra-aortic balloon pump use in high-risk cardiac surgery patients. A single-center randomized controlled trial and a meta-analysis of randomized controlled trials. Heart Institute of São Paulo University. High-risk patients undergoing elective coronary artery bypass surgery. Patients were randomized to receive preskin incision intra-aortic balloon pump insertion after anesthesia induction versus no intra-aortic balloon pump use. The primary outcome was a composite endpoint of 30-day mortality and major morbidity (cardiogenic shock, stroke, acute renal failure, mediastinitis, prolonged mechanical ventilation, and a need for reoperation). A total of 181 patients (mean [SD] age 65.4 [9.4] yr; 32% female) were randomized. The primary outcome was observed in 43 patients (47.8%) in the intra-aortic balloon pump group and 42 patients (46.2%) in the control group (p = 0.46). The median duration of inotrope use (51 hr [interquartile range, 32-94 hr] vs 39 hr [interquartile range, 25-66 hr]; p = 0.007) and the ICU length of stay (5 d [interquartile range, 3-8 d] vs 4 d [interquartile range, 3-6 d]; p = 0.035) were longer in the intra-aortic balloon pump group than in the control group. A meta-analysis of 11 randomized controlled trials confirmed a lack of survival improvement in high-risk cardiac surgery patients with perioperative intra-aortic balloon pump use. In high-risk patients undergoing cardiac surgery, the perioperative use of an intra-aortic balloon pump did not reduce the occurrence of a composite outcome of 30-day mortality and major complications compared with usual care alone.

Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions.

PubMed

Wang, Yue; Shang, Yuan; Li, Jianchao; Chen, Weidi; Li, Gang; Wan, Jun; Liu, Wei; Zhang, Mingjie

2018-05-11

The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases. © 2018, Wang et al.

A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

PubMed

Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

2016-08-16

Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body. Copyright © 2016 Elsevier Inc. All rights reserved.

Intra-Family Gamete Donation: A Solution to Concerns Regarding Gamete Donation in China?

PubMed

Liao, Juhong; Devolder, Katrien

2016-09-01

Gamete donation from third parties is controversial in China as it severs blood ties, which are considered of utmost importance in Confucian tradition. In recent years, infertile couples are increasingly demonstrating a preference for the use of gametes donated by family members to conceive children-known as "intra-family gamete donation." The main advantage of intra-family gamete donation is that it maintains blood ties between children and both parents. To date there is no practice of intra-family gamete donation in China. In this paper, we investigate intra-family adoption in China in order to illustrate that intra-family gamete donation is consistent with Confucian tradition regarding the importance of maintaining blood ties within the family. There are several specific ethical issues raised by intra-family gamete donation. It may, for example, result in consanguinity and the semblance of incest, lead to confused family relationships, and raise concerns about possible coercion of familial donors. Confucian tradition provides a new approach to understand and deal with these ethical issues in a way that Western tradition does not. As a result, we suggest intra-family gamete donation could be an acceptable solution to the problem of infertility in China. However, further discussion and open debates on the ethical issues raised by intra-family gamete donation are needed in China.

Resolution of inter and intra-species relationships of the West Indian fruit fly Anastrepha obliqua

USDA-ARS?s Scientific Manuscript database

The West Indian fruit fly, Anastrepha obliqua (Macquart) (Diptera: Tephritidae), is an economically important pest that inhabits areas of South and Central America, Mexico and the Caribbean with occasional infestations in the southern United States. We examine intra-specific variation within Anastre...

Characterizing Microstructural Tissue Properties in Multiple Sclerosis with Diffusion MRI at 7 T and 3 T: The Impact of the Experimental Design.

PubMed

De Santis, Silvia; Bastiani, Matteo; Droby, Amgad; Kolber, Pierre; Zipp, Frauke; Pracht, Eberhard; Stoecker, Tony; Groppa, Sergiu; Roebroeck, Alard

2018-04-07

The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations. While previous studies uncovered global and focal axonal degeneration in MS patients compared to healthy controls, here our aim is to investigate and compare different diffusion MRI acquisition protocols in their ability to highlight microstructural differences between MS and control tissue over several much used models. For comparison, we contrasted the ability of fractional anisotropy measurements to uncover differences between lesion, normal-appearing white matter (WM), gray matter and healthy tissue under the same imaging protocols. We show that: (1) focal and diffuse differences in several microstructural parameters are observed under clinical settings; (2) advanced models (CHARMED, DKI and NODDI) have increased specificity and sensitivity to neurodegeneration when compared to fractional anisotropy measurements; and (3) both high (3 T) and ultra-high fields (7 T) are viable options for imaging tissue change in MS lesions and normal appearing WM, while higher b-values are less beneficial under the tested short-time (10 min acquisition) conditions. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Intra-Theater Air Mobility and Theater Distribution for the Joint Force Commander: Is the United States Central Command Model the Best (Revised)

DTIC Science & Technology

2011-06-01

to ASOCs, each Army Corps possesses Air Mobility Liaison Officers ( AMLO ) at the corps, division, regiment, and brigade levels. These AMLOs may... AMLOs In PACOM, the DIRMOBFOR is expected to be an advisor to the COMAFFOR, JFACC and the JFACC’s AMD Chief, primarily with respect to integration...the AOR, PACAF will provide intra-theater AMLOs in accordance with AMLO -specific directives and theater MOAs. Specifically, PACAF will provide

Function of membranous lysyl-tRNA synthetase and its implication for tumorigenesis.

PubMed

Young, Ho Jeon; Lee, Jung Weon; Kim, Sunghoon

2016-12-01

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes that conjugate specific amino acids to their cognate tRNAs for protein synthesis. Besides their catalytic activity, recent studies have uncovered many additional functions of these enzymes through their interactions with diverse cellular factors. Among human ARSs, cytosolic lysyl-tRNA synthetase (KRS) is often highly expressed in cancer cells and tissues, and facilitates cancer cell migration and invasion through the interaction with the 67kDa laminin receptor on the plasma membrane. Specific modulation of this interaction by small molecule inhibitors has revealed a new way to control metastasis. Here, we summarize the pro-metastatic functions of KRS and their patho-physiological implications. Copyright © 2016 Elsevier B.V. All rights reserved.

MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer.

PubMed

Theodorou, Vassiliki; Kimm, Melanie A; Boer, Mandy; Wessels, Lodewyk; Theelen, Wendy; Jonkers, Jos; Hilkens, John

2007-06-01

We performed a high-throughput retroviral insertional mutagenesis screen in mouse mammary tumor virus (MMTV)-induced mammary tumors and identified 33 common insertion sites, of which 17 genes were previously not known to be associated with mammary cancer and 13 had not previously been linked to cancer in general. Although members of the Wnt and fibroblast growth factors (Fgf) families were frequently tagged, our exhaustive screening for MMTV insertion sites uncovered a new repertoire of candidate breast cancer oncogenes. We validated one of these genes, Rspo3, as an oncogene by overexpression in a p53-deficient mammary epithelial cell line. The human orthologs of the candidate oncogenes were frequently deregulated in human breast cancers and associated with several tumor parameters. Computational analysis of all MMTV-tagged genes uncovered specific gene families not previously associated with cancer and showed a significant overrepresentation of protein domains and signaling pathways mainly associated with development and growth factor signaling. Comparison of all tagged genes in MMTV and Moloney murine leukemia virus-induced malignancies showed that both viruses target mostly different genes that act predominantly in distinct pathways.

Knockdown of HMGB1 in tumor cells attenuates their ability to induce regulatory T cells and uncovers naturally acquired CD8 T cell-dependent antitumor immunity.

PubMed

Liu, Zuqiang; Falo, Louis D; You, Zhaoyang

2011-07-01

Although high mobility group box 1 (HMGB1) in tumor cells is involved in many aspects of tumor progression, its role in tumor immune suppression remains elusive. Host cell-derived IL-10 suppressed a naturally acquired CD8 T cell-dependent antitumor response. The suppressive activity of tumor-associated Foxp3(+)CD4(+)CD25(+) regulatory T cells (Treg) was IL-10 dependent. Neutralizing HMGB1 impaired tumor cell-promoted IL-10 production by Treg. Short hairpin RNA-mediated knockdown of HMGB1 (HMGB1 KD) in tumor cells did not affect tumor cell growth but uncovered naturally acquired long-lasting tumor-specific IFN-γ- or TNF-α-producing CD8 T cell responses and attenuated their ability to induce Treg, leading to naturally acquired CD8 T cell- or IFN-γ-dependent tumor rejection. The data suggest that tumor cell-derived HMGB1 may suppress naturally acquired CD8 T cell-dependent antitumor immunity via enhancing Treg to produce IL-10, which is necessary for Treg-mediated immune suppression.

Uncovering the mechanism(s) of deep brain stimulation

NASA Astrophysics Data System (ADS)

Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

2005-01-01

Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

Evaluation of microvascular anastomosis using real-time ultrahigh resolution Fourier domain Doppler optical coherence tomography

PubMed Central

Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Mao, Qi; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

2014-01-01

Background Evolution and improvements in microsurgical techniques and tools have paved the way for super-microsurgical anastomoses with vessel diameters often approaching below 0.8 mm in the clinical realm and even smaller (0.2–0.3 mm) in murine models. Several imaging and monitoring devices have been introduced for post-operative monitoring but intra-operative guidance, assessment and predictability have remained limited to binocular optical microscope and surgeon’s experience. We present a high-resolution real time 3D imaging modality for intra-operative evaluation of luminal narrowing, thrombus formation and flow alterations. Methods An imaging modality that provides immediate, in-depth high resolution 3D structure view and flow information of the anastomosed site called phase resolved Doppler optical coherence tomography (PRDOCT) was developed. 22 mouse femoral artery anastomoses and 17 mouse venous anastomoses were performed and evaluated with PRDOCT. Flow status, vessel inner lumen 3D structure, and early thrombus detection were analyzed based on PRDOCT imaging results. Initial PRDOCT based predictions were correlated with actual long term surgical outcomes. Eventually four cases of mouse orthotopic limb transplantation were carried out and PRDOCT predicted long term patency were confirmed by actual results. Results PRDOCT was able to provide high-resolution 3D visualization of the vessel flow status and vessel inner lumen. The assessments based on PRDOCT visualization shows a 92% sensitivity and 90% specificity for arterial anastomoses and 90% sensitivity and 86% specificity for venous anastomoses. Conclusions PRDOCT is an effective evaluation tool for microvascular anastomosis. It can predict the long term vessel patency with high sensitivity and specificity. PMID:25811583

Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Trial.

PubMed

Vila-Castelar, Clara; Ly, Jenny J; Kaplan, Lillian; Van Dyk, Kathleen; Berger, Jeffrey T; Macina, Lucy O; Stewart, Jennifer L; Foldi, Nancy S

2018-04-09

Donepezil is widely used to treat Alzheimer's disease (AD), but detecting early response remains challenging for clinicians. Acetylcholine is known to directly modulate attention, particularly under high cognitive conditions, but no studies to date test whether measures of attention under high load can detect early effects of donepezil. We hypothesized that load-dependent attention tasks are sensitive to short-term treatment effects of donepezil, while global and other domain-specific cognitive measures are not. This longitudinal, randomized, double-blind, placebo-controlled pilot trial (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11) groups, and retested after approximately 6 weeks. Cognitive assessment included: (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting tasks) measuring processing speed, top-down accuracy, orienting, intra-individual variability, and fatigue; (b) global measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale); and (c) domain-specific measures (memory, language, visuospatial, and executive function). The Drug but not the Placebo group showed benefits of treatment at high-load measures by preserving top-down accuracy, improving intra-individual variability, and averting fatigue. In contrast, other global or cognitive domain-specific measures could not detect treatment effects over the same treatment interval. The pilot-study suggests that attention measures targeting accuracy, variability, and fatigue under high-load conditions could be sensitive to short-term cholinergic treatment. Given the central role of acetylcholine in attentional function, load-dependent attentional measures may be valuable cognitive markers of early treatment response.

Sensitivity of a juvenile subject-specific musculoskeletal model of the ankle joint to the variability of operator-dependent input

PubMed Central

Hannah, Iain; Montefiori, Erica; Modenese, Luca; Prinold, Joe; Viceconti, Marco; Mazzà, Claudia

2017-01-01

Subject-specific musculoskeletal modelling is especially useful in the study of juvenile and pathological subjects. However, such methodologies typically require a human operator to identify key landmarks from medical imaging data and are thus affected by unavoidable variability in the parameters defined and subsequent model predictions. The aim of this study was to thus quantify the inter- and intra-operator repeatability of a subject-specific modelling methodology developed for the analysis of subjects with juvenile idiopathic arthritis. Three operators each created subject-specific musculoskeletal foot and ankle models via palpation of bony landmarks, adjustment of geometrical muscle points and definition of joint coordinate systems. These models were then fused to a generic Arnold lower limb model for each of three modelled patients. The repeatability of each modelling operation was found to be comparable to those previously reported for the modelling of healthy, adult subjects. However, the inter-operator repeatability of muscle point definition was significantly greater than intra-operator repeatability (p < 0.05) and predicted ankle joint contact forces ranged by up to 24% and 10% of the peak force for the inter- and intra-operator analyses, respectively. Similarly, the maximum inter- and intra-operator variations in muscle force output were 64% and 23% of peak force, respectively. Our results suggest that subject-specific modelling is operator dependent at the foot and ankle, with the definition of muscle geometry the most significant source of output uncertainty. The development of automated procedures to prevent the misplacement of crucial muscle points should therefore be considered a particular priority for those developing subject-specific models. PMID:28427313

Sensitivity of a juvenile subject-specific musculoskeletal model of the ankle joint to the variability of operator-dependent input.

PubMed

Hannah, Iain; Montefiori, Erica; Modenese, Luca; Prinold, Joe; Viceconti, Marco; Mazzà, Claudia

2017-05-01

Subject-specific musculoskeletal modelling is especially useful in the study of juvenile and pathological subjects. However, such methodologies typically require a human operator to identify key landmarks from medical imaging data and are thus affected by unavoidable variability in the parameters defined and subsequent model predictions. The aim of this study was to thus quantify the inter- and intra-operator repeatability of a subject-specific modelling methodology developed for the analysis of subjects with juvenile idiopathic arthritis. Three operators each created subject-specific musculoskeletal foot and ankle models via palpation of bony landmarks, adjustment of geometrical muscle points and definition of joint coordinate systems. These models were then fused to a generic Arnold lower limb model for each of three modelled patients. The repeatability of each modelling operation was found to be comparable to those previously reported for the modelling of healthy, adult subjects. However, the inter-operator repeatability of muscle point definition was significantly greater than intra-operator repeatability ( p < 0.05) and predicted ankle joint contact forces ranged by up to 24% and 10% of the peak force for the inter- and intra-operator analyses, respectively. Similarly, the maximum inter- and intra-operator variations in muscle force output were 64% and 23% of peak force, respectively. Our results suggest that subject-specific modelling is operator dependent at the foot and ankle, with the definition of muscle geometry the most significant source of output uncertainty. The development of automated procedures to prevent the misplacement of crucial muscle points should therefore be considered a particular priority for those developing subject-specific models.

Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes.

PubMed

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I; Yoon, Bo Hyun; Hassan, Sonia S; Kim, Chong Jai; Yeo, Lami

2014-11-01

Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation. AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). (i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02). (i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions.

PubMed Central

Keskin, O.; Bahar, I.; Badretdinov, A. Y.; Ptitsyn, O. B.; Jernigan, R. L.

1998-01-01

Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly more residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99. PMID:9865952

Spatial Topography of Individual-Specific Cortical Networks Predicts Human Cognition, Personality, and Emotion.

PubMed

Kong, Ru; Li, Jingwei; Orban, Csaba; Sabuncu, Mert R; Liu, Hesheng; Schaefer, Alexander; Sun, Nanbo; Zuo, Xi-Nian; Holmes, Avram J; Eickhoff, Simon B; Yeo, B T Thomas

2018-06-06

Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to delineate individual-specific brain networks. A major question is whether individual-specific network topography (i.e., location and spatial arrangement) is behaviorally relevant. Here, we propose a multi-session hierarchical Bayesian model (MS-HBM) for estimating individual-specific cortical networks and investigate whether individual-specific network topography can predict human behavior. The multiple layers of the MS-HBM explicitly differentiate intra-subject (within-subject) from inter-subject (between-subject) network variability. By ignoring intra-subject variability, previous network mappings might confuse intra-subject variability for inter-subject differences. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and task-fMRI data from the same subjects. More specifically, MS-HBM parcellations estimated from a single rs-fMRI session (10 min) showed comparable generalizability as parcellations estimated by 2 state-of-the-art methods using 5 sessions (50 min). We also showed that behavioral phenotypes across cognition, personality, and emotion could be predicted by individual-specific network topography with modest accuracy, comparable to previous reports predicting phenotypes based on connectivity strength. Network topography estimated by MS-HBM was more effective for behavioral prediction than network size, as well as network topography estimated by other parcellation approaches. Thus, similar to connectivity strength, individual-specific network topography might also serve as a fingerprint of human behavior.

GiniClust: detecting rare cell types from single-cell gene expression data with Gini index.

PubMed

Jiang, Lan; Chen, Huidong; Pinello, Luca; Yuan, Guo-Cheng

2016-07-01

High-throughput single-cell technologies have great potential to discover new cell types; however, it remains challenging to detect rare cell types that are distinct from a large population. We present a novel computational method, called GiniClust, to overcome this challenge. Validation against a benchmark dataset indicates that GiniClust achieves high sensitivity and specificity. Application of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and hippocampus. GiniClust also correctly detects a small number of normal cells that are mixed in a cancer cell population.

Genome Reduction Uncovers a Large Dispensable Genome and Adaptive Role for Copy Number Variation in Asexually Propagated Solanum tuberosum[OPEN

PubMed Central

Hardigan, Michael A.; Crisovan, Emily; Hamilton, John P.; Laimbeer, Parker; Leisner, Courtney P.; Manrique-Carpintero, Norma C.; Newton, Linsey; Pham, Gina M.; Vaillancourt, Brieanne; Zeng, Zixian; Jiang, Jiming

2016-01-01

Clonally reproducing plants have the potential to bear a significantly greater mutational load than sexually reproducing species. To investigate this possibility, we examined the breadth of genome-wide structural variation in a panel of monoploid/doubled monoploid clones generated from native populations of diploid potato (Solanum tuberosum), a highly heterozygous asexually propagated plant. As rare instances of purely homozygous clones, they provided an ideal set for determining the degree of structural variation tolerated by this species and deriving its minimal gene complement. Extensive copy number variation (CNV) was uncovered, impacting 219.8 Mb (30.2%) of the potato genome with nearly 30% of genes subject to at least partial duplication or deletion, revealing the highly heterogeneous nature of the potato genome. Dispensable genes (>7000) were associated with limited transcription and/or a recent evolutionary history, with lower deletion frequency observed in genes conserved across angiosperms. Association of CNV with plant adaptation was highlighted by enrichment in gene clusters encoding functions for environmental stress response, with gene duplication playing a part in species-specific expansions of stress-related gene families. This study revealed unique impacts of CNV in a species with asexual reproductive habits and how CNV may drive adaption through evolution of key stress pathways. PMID:26772996

An exploratory comparison of name generator content: Data from rural India.

PubMed

Shakya, Holly B; Christakis, Nicholas A; Fowler, James H

2017-01-01

Since the 1970s sociologists have explored the best means for measuring social networks, although few name generator analyses have used sociocentric data or data from developing countries, partly because sociocentric studies in developing countries have been scant. Here, we analyze 12 different name generators used in a sociocentric network study conducted in 75 villages in rural Karnataka, India. Having unusual sociocentric data from a non-Western context allowed us to extend previous name generator research through the unique analyses of network structural measures, an extensive consideration of homophily, and investigation of status difference between egos and alters. We found that domestic interaction questions generated networks that were highly clustered and highly centralized. Similarity between respondents and their nominated contacts was strongest for gender, caste, and religion. We also found that domestic interaction name generators yielded the most homogeneous ties, while advice questions yielded the most heterogeneous. Participants were generally more likely to nominate those of higher social status, although certain questions, such as who participants talk to uncovered more egalitarian relationships, while other name generators elicited the names of social contacts distinctly higher or lower in status than the respondent. Some questions also seemed to uncover networks that were specific to the cultural context, suggesting that network researchers should balance local relevance with global generalizability when choosing name generators.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bramante, Joseph; Linden, Tim

Recent observations of Reticulum II have uncovered an overabundance of r -process elements compared to similar ultra-faint dwarf spheroidal galaxies (UFDs). Because the metallicity and star formation history of Reticulum II appear consistent with all known UFDs, the high r -process abundance of Reticulum II suggests enrichment through a single, rare event, such as a double neutron star (NS) merger. However, we note that this scenario is extremely unlikely, as binary stellar evolution models require significant supernova natal kicks to produce NS–NS or NS–black hole (BH) mergers, and these kicks would efficiently remove compact binary systems from the weak gravitationalmore » potentials of UFDs. We examine alternative mechanisms for the production of r -process elements in UFDs, including a novel mechanism wherein NSs in regions of high dark matter (DM) density implode after accumulating a BH-forming mass of DM. We find that r -process proto-material ejection by tidal forces, when a single NS implodes into a BH, can occur at a rate matching the r -process abundance of both Reticulum II and the Milky Way. Remarkably, DM models which collapse a single NS in observed UFDs also solve the missing pulsar problem in the Milky Way Galactic Center. We propose tests specific to DM r -process production which may uncover or rule out this model.« less

Impact of normalization methods on high-throughput screening data with high hit rates and drug testing with dose-response data.

PubMed

Mpindi, John-Patrick; Swapnil, Potdar; Dmitrii, Bychkov; Jani, Saarela; Saeed, Khalid; Wennerberg, Krister; Aittokallio, Tero; Östling, Päivi; Kallioniemi, Olli

2015-12-01

Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-response experiments, which pose a more stringent requirement for data quality and for intra- and inter-plate variation. Here, we compared common plate normalization and noise-reduction methods, including the B-score and the Loess a local polynomial fit method under high hit-rate scenarios of drug sensitivity testing. We generated simulated 384-well plate HTS datasets, each with 71 plates having a range of 20 (5%) to 160 (42%) hits per plate, with controls placed either at the edge of the plates or in a scattered configuration. We identified 20% (77/384) as the critical hit-rate after which the normalizations started to perform poorly. Results from real drug testing experiments supported this estimation. In particular, the B-score resulted in incorrect normalization of high hit-rate plates, leading to poor data quality, which could be attributed to its dependency on the median polish algorithm. We conclude that a combination of a scattered layout of controls per plate and normalization using a polynomial least squares fit method, such as Loess helps to reduce column, row and edge effects in HTS experiments with high hit-rates and is optimal for generating accurate dose-response curves. john.mpindi@helsinki.fi. Supplementary information: R code and Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Poplar breeding and testing strategies in the north-central U.S.: Demonstration of potential yield and consideration of future research needs1

Treesearch

Don E. Riemenschneider; William E. Berguson; Donald I. Dickmann; Richard B. Hall; J. G. Isebrands; Carl A. Mohn; Glen R. Stanosz; Gerald A. Tuskan

2001-01-01

We present results from a Populus Regional Testing Program that has been conducted in Minnesota, Iowa, Wisconsin, and Michigan over the past six years. Our objectives have been to: 1) identify highly productive, disease resistant intra- and inter-specific clonal selections and 2) understand patterns of genotype x environment interactions within the region that would,...

Multi-scale modeling of Arabidopsis thaliana response to different CO2 conditions: From gene expression to metabolic flux.

PubMed

Liu, Lin; Shen, Fangzhou; Xin, Changpeng; Wang, Zhuo

2016-01-01

Multi-scale investigation from gene transcript level to metabolic activity is important to uncover plant response to environment perturbation. Here we integrated a genome-scale constraint-based metabolic model with transcriptome data to explore Arabidopsis thaliana response to both elevated and low CO2 conditions. The four condition-specific models from low to high CO2 concentrations show differences in active reaction sets, enriched pathways for increased/decreased fluxes, and putative post-transcriptional regulation, which indicates that condition-specific models are necessary to reflect physiological metabolic states. The simulated CO2 fixation flux at different CO2 concentrations is consistent with the measured Assimilation-CO2intercellular curve. Interestingly, we found that reactions in primary metabolism are affected most significantly by CO2 perturbation, whereas secondary metabolic reactions are not influenced a lot. The changes predicted in key pathways are consistent with existing knowledge. Another interesting point is that Arabidopsis is required to make stronger adjustment on metabolism to adapt to the more severe low CO2 stress than elevated CO2 . The challenges of identifying post-transcriptional regulation could also be addressed by the integrative model. In conclusion, this innovative application of multi-scale modeling in plants demonstrates potential to uncover the mechanisms of metabolic response to different conditions. © 2015 Institute of Botany, Chinese Academy of Sciences.

Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army.

PubMed

Patino, Luz H; Mendez, Claudia; Rodriguez, Omaira; Romero, Yanira; Velandia, Daniel; Alvarado, Maria; Pérez, Julie; Duque, Maria Clara; Ramírez, Juan David

2017-08-01

In Colombia, the cutaneous leishmaniasis (CL) is the most common manifestation across the army personnel. Hence, it is mandatory to determine the species associated with the disease as well as the association with the clinical traits. A total of 273 samples of male patients with CL were included in the study and clinical data of the patients was studied. PCR and sequencing analyses (Cytb and HSP70 genes) were performed to identify the species and the intra-specific genetic variability. A georeferenced database was constructed to identify the spatial distribution of Leishmania species isolated. The identification of five species of Leishmania that circulate in the areas where army personnel are deployed is described. Predominant infecting Leishmania species corresponds to L. braziliensis (61.1%), followed by Leishmania panamensis (33.5%), with a high distribution of both species at geographical and municipal level. The species L. guyanensis, L. mexicana and L. lainsoni were also detected at lower frequency. We also showed the identification of different genotypes within L. braziliensis and L. panamensis. In conclusion, we identified the Leishmania species circulating in the areas where Colombian army personnel are deployed, as well as the high intra-specific genetic variability of L. braziliensis and L. panamensis and how these genotypes are distributed at the geographic level.

Correlation between Preoperative High Resolution Computed Tomography (CT) Findings with Surgical Findings in Chronic Otitis Media (COM) Squamosal Type.

PubMed

Karki, S; Pokharel, M; Suwal, S; Poudel, R

Background The exact role of High resolution computed tomography (HRCT) temporal bone in preoperative assessment of Chronic suppurative otitis media atticoantral disease still remains controversial. Objective To evaluate the role of high resolution computed tomography temporal bone in Chronic suppurative otitis media atticoantral disease and to compare preoperative computed tomographic findings with intra-operative findings. Method Prospective, analytical study conducted among 65 patients with chronic suppurative otitis media atticoantral disease in Department of Radiodiagnosis, Kathmandu University Dhulikhel Hospital between January 2015 to July 2016. The operative findings were compared with results of imaging. The parameters of comparison were erosion of ossicles, scutum, facial canal, lateral semicircular canal, sigmoid and tegmen plate along with extension of disease to sinus tympani and facial recess. Sensitivity, specificity, negative predictive value, positive predictive values were calculated. Result High resolution computed tomography temporal bone offered sensitivity (Se) and specificity (Sp) of 100% for visualization of sigmoid and tegmen plate erosion. The performance of HRCT in detecting malleus (Se=100%, Sp=95.23%), incus (Se=100%,Sp=80.48%) and stapes (Se=96.55%, Sp=71.42%) erosion was excellent. It offered precise information about facial canal erosion (Se=100%, Sp=75%), scutum erosion (Se=100%, Sp=96.87%) and extension of disease to facial recess and sinus tympani (Se=83.33%,Sp=100%). high resolution computed tomography showed specificity of 100% for lateral semicircular canal erosion (Sp=100%) but with low sensitivity (Se=53.84%). Conclusion The findings of high resolution computed tomography and intra-operative findings were well comparable except for lateral semicircular canal erosion. high resolution computed tomography temporal bone acts as a road map for surgeon to identify the extent of disease, plan for appropriate procedure that is required and prepare for potential complications that can be encountered during surgery.

Cre/lox-recombinase-mediated cassette exchange for reversible site-specific genomic targeting of the disease vector, Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Site-specific genome modification is an important tool for mosquito functional genomics studies that help to uncover gene functions, identify gene regulatory elements, and perform comparative gene expression studies, all of which contribute to a better understanding of mosquito biology and are thus ...

Ammonia volatilization from farm tanks containing anaerobically digested animal slurry

NASA Astrophysics Data System (ADS)

Sommer, S. G.

Ammonia (NH 3) volatilization from three full-scale tanks containing anaerobically digested animal slurry from one biogas plant was determined with a meteorological mass balance technique. No surface crust developed on the slurry. This provided an ideal system for analysing loss patterns from slurries without cover and to study the effect of a cover of straw and air-filled clay granules. Ammonia volatilization from uncovered slurry ranged from zero at subzero temperatures to 30 g N m -2 d -1 during summer. The high volatilization rate was attributed to a lack of surface cover, high slurry pH and high TAN (NH 3 + NH 4+) concentration. Ammonia volatilization from the covered slurry was insignificant. From the uncovered slurry the annual loss of NH3 was 3.3 kg N m -2 There was a significant effect of incident global radiation (ICR), air temperature at 20 cm (T_20) and rain on NH3 volatilization from the uncovered slurry. The straw covered slurry was significantly affected by T_20.

The Class I-Specific HDAC Inhibitor MS-275 Decreases Motivation to Consume Alcohol and Relapse in Heavy Drinking Rats

PubMed Central

Lemoine, Sandrine; Jeanblanc, Virginie; Alaux-Cantin, Stéphanie; Naassila, Mickaël

2015-01-01

Background: New strategies for the treatment of alcohol dependence are a pressing need, and recent evidence suggests that targeting enzymes involved in epigenetic mechanisms seems to have great potential. Among these mechanisms, alteration of histone acetylation by histone deacetylases is of great importance for gene expression and has also been implicated in addiction. Here, we examined whether intra-cerebroventricular administration of MS-275, a class I-specific histone deacetylase inhibitor, could alter ethanol self-administration, motivation to consume ethanol, and relapse in heavy drinking rats. Methods: Male Long Evans rats trained to self-administer high levels of ethanol received intra-cerebroventricular micro-infusions of MS-275 (250 µM, 500 µM, and 1000 µM) 3 hours prior to the self-administration sessions. Results: First, we demonstrated that intra-cerebroventricular infusion of MS-275 increases acetylation of Histone 4 within the nucleus accumbens nucleus accumbens and the dorsolateral striatum. Second, we observed that MS-275 decreases ethanol self-administration by about 75%. We found that 2 consecutive daily injections are necessary to decrease ethanol self-administration. Additionally, the dose-response curve test indicated that MS-275 has a U-shape effect on ethanol self-administration with the dose of 500 µM as the most efficient dose. Furthermore, we showed that MS-275 also diminished the motivation to consume ethanol (25% decrease), and finally, we demonstrated that MS-275 reduced relapse (by about 50%) and postponed reacquisition even when the treatment was stopped. Conclusions: Our study confirms the potential therapeutic interest of targeting epigenetic mechanisms in excessive alcohol drinking and strengthens the interest of focusing on specific isoforms of histone deacetylases. PMID:25762717

Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT.

PubMed

Ciet, Pierluigi; Serra, Goffredo; Bertolo, Silvia; Spronk, Sandra; Ros, Mirco; Fraioli, Francesco; Quattrucci, Serena; Assael, M Baroukh; Catalano, Carlo; Pomerri, Fabio; Tiddens, Harm A W M; Morana, Giovanni

2016-03-01

To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100% (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lung disease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lung disease (i.e. pulmonary exacerbations). PROPELLER MRI does not match CT sensitivity to assess CF lung disease. PROPELLER MRI has lower sensitivity than CT to detect severe bronchiectasis. PROPELLER MRI has good to very good intra- and inter-observer variability. PROPELLER MRI can be used for short-term follow-up studies in CF.

Beyond Biodiversity: Fish Metagenomes

PubMed Central

Ardura, Alba; Planes, Serge; Garcia-Vazquez, Eva

2011-01-01

Biodiversity and intra-specific genetic diversity are interrelated and determine the potential of a community to survive and evolve. Both are considered together in Prokaryote communities treated as metagenomes or ensembles of functional variants beyond species limits. Many factors alter biodiversity in higher Eukaryote communities, and human exploitation can be one of the most important for some groups of plants and animals. For example, fisheries can modify both biodiversity and genetic diversity (intra specific). Intra-specific diversity can be drastically altered by overfishing. Intense fishing pressure on one stock may imply extinction of some genetic variants and subsequent loss of intra-specific diversity. The objective of this study was to apply a metagenome approach to fish communities and explore its value for rapid evaluation of biodiversity and genetic diversity at community level. Here we have applied the metagenome approach employing the Barcoding target gene COI as a model sequence in catch from four very different fish assemblages exploited by fisheries: freshwater communities from the Amazon River and northern Spanish rivers, and marine communities from the Cantabric and Mediterranean seas. Treating all sequences obtained from each regional catch as a biological unit (exploited community) we found that metagenomic diversity indices of the Amazonian catch sample here examined were lower than expected. Reduced diversity could be explained, at least partially, by overexploitation of the fish community that had been independently estimated by other methods. We propose using a metagenome approach for estimating diversity in Eukaryote communities and early evaluating genetic variation losses at multi-species level. PMID:21829636

Beyond biodiversity: fish metagenomes.

PubMed

Ardura, Alba; Planes, Serge; Garcia-Vazquez, Eva

2011-01-01

Biodiversity and intra-specific genetic diversity are interrelated and determine the potential of a community to survive and evolve. Both are considered together in Prokaryote communities treated as metagenomes or ensembles of functional variants beyond species limits.Many factors alter biodiversity in higher Eukaryote communities, and human exploitation can be one of the most important for some groups of plants and animals. For example, fisheries can modify both biodiversity and genetic diversity (intra specific). Intra-specific diversity can be drastically altered by overfishing. Intense fishing pressure on one stock may imply extinction of some genetic variants and subsequent loss of intra-specific diversity. The objective of this study was to apply a metagenome approach to fish communities and explore its value for rapid evaluation of biodiversity and genetic diversity at community level. Here we have applied the metagenome approach employing the barcoding target gene coi as a model sequence in catch from four very different fish assemblages exploited by fisheries: freshwater communities from the Amazon River and northern Spanish rivers, and marine communities from the Cantabric and Mediterranean seas.Treating all sequences obtained from each regional catch as a biological unit (exploited community) we found that metagenomic diversity indices of the Amazonian catch sample here examined were lower than expected. Reduced diversity could be explained, at least partially, by overexploitation of the fish community that had been independently estimated by other methods.We propose using a metagenome approach for estimating diversity in Eukaryote communities and early evaluating genetic variation losses at multi-species level.

TH-E-BRF-10: Interim Esophageal Cancer Response Assessment Via 18FDG-PET Scanning During Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, K; Wu, Q; Perez, B

2014-06-15

Purpose: Local failure occurs in a large proportion of esophageal cancer patients treated with chemoradiation. The treatment strategy for non-responders could potentially be modified if they are identified during therapy. This work investigates the utility of an interim 18FDG-PET scan acquired during the course of therapy as a predictor of pathological response post-therapy. Methods: Fifteen patients underwent 18FDG-PET scanning prior to radiation therapy (RT) and once during RT, after delivery of ∼32 Gy. The physician-contoured GTV on the planning CT scan was used to automatically segment a PET-based GTV on the pre-RT PET (GTV-pre-PET) as the volume with >40% ofmore » the maximum GTV PET SUV value. The pre- and intra-RT CTs were deformably registered to each other to transfer the GTV-pre-PET to the intra-RT PET (GTV-intra-PET). The fractional decrease in the maximum SUV, mean SUV and the SUV to the highest intensity 10% – 90% volumes from GTV-pre-PET to GTV-intra-PET were compared to pathological response assessed at the time of post-RT surgery. Results: Based on post-treatment pathology of 15 patients, 7 were classified as achieving favorable response (treatment effect grade ≤ 1) and 8 as unfavorable response (treatment effect grade > 1). Neither fractional decrease in maximum SUV nor mean SUV were significant between the favorable and unfavorable groups. However, the fractional decrease in SUV20% (SUV to the highest 20% volume) was significant (p = 0.02), with an area under the Receiver Operating Characteristics (ROC) curve of 0.84. An optimal cutoff value of 0.46 for this metric was able to distinguish between the two groups with 71% sensitivity (favorable) and 88% specificity (unfavorable). Conclusion: The fractional decrease in SUV to the volume with highest 20% intensity from pre- to intra-RT 18FDG-PET imaging may be used to distinguish between favorable and unfavorable responders with high sensitivity and specificity.« less

Certain Less Invasive Infertility Treatments Associated with Different Levels of Pregnancy-Related Anxiety in Pregnancies Conceived via In Vitro Fertilization.

PubMed

Stevenson, Eleanor Lowndes; Sloane, Richard

2017-01-01

Research supports that in vitro fertilization causes anxiety and that anxiety can continue into the resulting pregnancy. Most women who have IVF will have a less invasive treatment for infertility prior to IVF; however, it is unclear if specific less invasive treatment cycles impact anxiety that is experienced in the pregnancy resulting from IVF. A prospective study was conducted for women who became pregnant via IVF, and data was collected about reported previous non-IVF treatment cycles as well as Pregnancy Related Anxiety Measure. Latent Class Analysis was conducted A p-value of ≤0.05 was considered significant. 144 subjects participated and were highly educated, affluent, married, and primarily white. The LCA process yielded two groups that on average had similar levels on most items except for use of intra uterine insemination and/or ovarian stimulation. This information was used to generate four exhaustive and mutually exclusive groups: Stimulation Only (stim-only), Stimulation and Intra uterine Insemination (stim-IUI), Intra uterine Insemination only (IUI only), or No Treatment (No Tx). ANOVA found that those in the Stim Only group had statistically significantly higher PRAM scores than the Stim IUI (p=0.0036), the IUI only group (p=0.05), and the No Tx group (p=0.0013). Women who become pregnant via IVF and had a history of non- in vitro fertilization cycles that only involved ovarian stimulation experienced more pregnancy-specific anxiety in the pregnancy that results from in vitro fertilization.

Cognitive inconsistency in bipolar patients is determined by increased intra-individual variability in initial phase of task performance.

PubMed

Krukow, Paweł; Szaniawska, Ola; Harciarek, Michał; Plechawska-Wójcik, Małgorzata; Jonak, Kamil

2017-03-01

Bipolar patients show high intra-individual variability during cognitive processing. However, it is not known whether there are a specific fluctuations of variability contributing to the overall high cognitive inconsistency. The objective was to compare dynamic profiles of patients and healthy controls to identify hypothetical differences and their associations with overall variability and processing speed. Changes of reaction times iSD during processing speed test performance over time was measured by dividing the iSD for whole task into four consecutive parts. Motor speed and cognitive effort were controlled. Patients with BD exhibited significantly lower results regarding processing speed and higher intra-individual variability comparing with HC. The profile of intra-individual variability changes over time of performance was significantly different in BD versus HC groups: F(3, 207)=8.60, p<0.0001, η p 2 =0.11. iSD of BD patients in the initial phase of performance was three times higher than in the last. There was no significant differences between four intervals in HC group. Inter-group difference in the initial part of the profiles was significant also after controlling for several cognitive and clinical variables. Applied computer version of Cognitive Speed Test was relatively new and, thus, replication studies are needed. Effect seen in the present study is driven mainly by the BD type I. Patients with BD exhibits problems with setting a stimulus-response association in starting phase of cognitive processing. This deficit may negatively interfere with the other cognitive functions, decreasing level of psychosocial functioning, therefore should be explored in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy and safety of point-of-care ultrasound-guided intra-articular corticosteroid joint injections in patients with haemophilic arthropathy.

PubMed

Martin, E J; Cooke, E J; Ceponis, A; Barnes, R F W; Moran, C M; Holle, S; Hughes, T H; Moore, R E; von Drygalski, A

2017-01-01

Intra-articular corticosteroid injections are standard of care for managing joint pain secondary to osteoarthritis or rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have introduced and evaluated the efficacy and safety of ultrasound-guided corticosteroid injections for pain relief in patients with haemophilic arthropathy. Ultrasound-guided intra-articular injections performed on haemophilia patients at UCSD between March 2012 and January 2016 were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL lidocaine) were performed with musculoskeletal ultrasound and Power Doppler. Analysis included patient demographics, joint-specific parameters such as tissue hypervascularity and effusions, pain relief, and procedure-associated complications. Forty-five injections (14 ankles, 13 elbows, 18 knees) were administered in 25 patients. Advanced arthropathy with hypervascularity and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one per cent of injections resulted in pain relief which was significant in 84% (>30% reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001), usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16 weeks). Haemophilia B patients experienced longer periods of relief, and high Pettersson scores were associated with shorter duration of relief. There were no procedure-associated complications. Repeat ultrasound of eight joints within 4 weeks of injection demonstrated nearly complete resolution of hypervascularity. Point-of-care ultrasound enabled intra-articular corticosteroid injections that provided highly effective, safe, and relatively long-lasting pain relief in haemophilic arthropathy. This approach should be used to improve pain management in haemophilic arthropathy. © 2016 John Wiley & Sons Ltd.

GIANT API: an application programming interface for functional genomics

PubMed Central

Roberts, Andrew M.; Wong, Aaron K.; Fisk, Ian; Troyanskaya, Olga G.

2016-01-01

GIANT API provides biomedical researchers programmatic access to tissue-specific and global networks in humans and model organisms, and associated tools, which includes functional re-prioritization of existing genome-wide association study (GWAS) data. Using tissue-specific interaction networks, researchers are able to predict relationships between genes specific to a tissue or cell lineage, identify the changing roles of genes across tissues and uncover disease-gene associations. Additionally, GIANT API enables computational tools like NetWAS, which leverages tissue-specific networks for re-prioritization of GWAS results. The web services covered by the API include 144 tissue-specific functional gene networks in human, global functional networks for human and six common model organisms and the NetWAS method. GIANT API conforms to the REST architecture, which makes it stateless, cacheable and highly scalable. It can be used by a diverse range of clients including web browsers, command terminals, programming languages and standalone apps for data analysis and visualization. The API is freely available for use at http://giant-api.princeton.edu. PMID:27098035

A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock.

PubMed

Boyd, Joseph S; Cheng, Ryan R; Paddock, Mark L; Sancar, Cigdem; Morcos, Faruck; Golden, Susan S

2016-09-15

Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium Synechococcus elongatus PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct-coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (cikB) in a sasA cikA null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems. Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently confirmed known interactions and revealed a core set of subnetworks within the larger HK-RR set. We validated high-scoring candidate proteins via combinatorial genetics, demonstrating that DCA can be utilized to reduce the search space of complex protein networks and to infer undiscovered specific interactions for signaling proteins in vivo Significantly, new interactions that link circadian response to cell division and fitness in a light/dark cycle were uncovered. The combined analysis also uncovered a more basic core clock, illustrating the synergy and applicability of a combined computational and genetic approach for investigating prokaryotic signaling networks. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Integrated analysis of RNA-binding protein complexes using in vitro selection and high-throughput sequencing and sequence specificity landscapes (SEQRS).

PubMed

Lou, Tzu-Fang; Weidmann, Chase A; Killingsworth, Jordan; Tanaka Hall, Traci M; Goldstrohm, Aaron C; Campbell, Zachary T

2017-04-15

RNA-binding proteins (RBPs) collaborate to control virtually every aspect of RNA function. Tremendous progress has been made in the area of global assessment of RBP specificity using next-generation sequencing approaches both in vivo and in vitro. Understanding how protein-protein interactions enable precise combinatorial regulation of RNA remains a significant problem. Addressing this challenge requires tools that can quantitatively determine the specificities of both individual proteins and multimeric complexes in an unbiased and comprehensive way. One approach utilizes in vitro selection, high-throughput sequencing, and sequence-specificity landscapes (SEQRS). We outline a SEQRS experiment focused on obtaining the specificity of a multi-protein complex between Drosophila RBPs Pumilio (Pum) and Nanos (Nos). We discuss the necessary controls in this type of experiment and examine how the resulting data can be complemented with structural and cell-based reporter assays. Additionally, SEQRS data can be integrated with functional genomics data to uncover biological function. Finally, we propose extensions of the technique that will enhance our understanding of multi-protein regulatory complexes assembled onto RNA. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical meningitis related to intra-CSF liposomal cytarabine.

PubMed

Durand, Bénédicte; Zairi, Fahed; Boulanger, Thomas; Bonneterre, Jacques; Mortier, Laurent; Le Rhun, Emilie

2017-10-01

Therapeutic options of leptomeningeal metastases include intra-cerebrospinal fluid (CSF) chemotherapy. Among intra-CSF agents, liposomal cytarabine has advantages but can induce specific toxicities. A BRAF-V600E-mutated melanoma leptomeningeal metastases patient, treated by dabrafenib and liposomal cytarabine, presented after the first injection of liposomal cytarabine with hyperthermia and headaches. Despite sterile CSF/blood analyses, extended intravenous antibiotics were given and the second injection was delayed. The diagnosis of chemical meningitis was finally made. Dose reduction and appropriate symptomatic treatment permitted the administration of 15 injections of liposomal cytarabine combined with dabrafenib. A confirmation of the diagnosis of chemical meningitis is essential in order (1) not to delay intra-CSF or systemic chemotherapy or (2) to limit the administration of unnecessary but potentially toxic antibiotics.

Computed tomography arthrography using a radial plane view for the detection of triangular fibrocartilage complex foveal tears.

PubMed

Moritomo, Hisao; Arimitsu, Sayuri; Kubo, Nobuyuki; Masatomi, Takashi; Yukioka, Masao

2015-02-01

To classify triangular fibrocartilage complex (TFCC) foveal lesions on the basis of computed tomography (CT) arthrography using a radial plane view and to correlate the CT arthrography results with surgical findings. We also tested the interobserver and intra-observer reliability of the radial plane view. A total of 33 patients with a suspected TFCC foveal tear who had undergone wrist CT arthrography and subsequent surgical exploration were enrolled. We classified the configurations of TFCC foveal lesions into 5 types on the basis of CT arthrography with the radial plane view in which the image slices rotate clockwise centered on the ulnar styloid process. Sensitivity, specificity, and positive predictive values were calculated for each type of foveal lesion in CT arthrography to detect foveal tears. We determined interobserver and intra-observer agreements using kappa statistics. We also compared accuracies with the radial plane views with those with the coronal plane views. Among the tear types on CT arthrography, type 3, a roundish defect at the fovea, and type 4, a large defect at the overall ulnar insertion, had high specificity and positive predictive value for the detection of foveal tears. Specificity and positive predictive values were 90% and 89% for type 3 and 100% and 100% for type 4, respectively, whereas sensitivity was 35% for type 3 and 22% for type 4. Interobserver and intra-observer agreement was substantial and almost perfect, respectively. The radial plane view identified foveal lesion of each palmar and dorsal radioulnar ligament separately, but accuracy results with the radial plane views were not statistically different from those with the coronal plane views. Computed tomography arthrography with a radial plane view exhibited enhanced specificity and positive predictive value when a type 3 or 4 lesion was identified in the detection of a TFCC foveal tear compared with historical controls. Diagnostic II. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment

PubMed Central

Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

2015-01-01

Digital PCR has developed rapidly since it was first reported in the 1990s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products. PMID:26239916

A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

PubMed

Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

2015-08-04

Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

FAST for blunt abdominal trauma: Correlation between positive findings and admission acid-base measurement.

PubMed

Heidari, Kamran; Taghizadeh, Mehrdad; Mahmoudi, Sadrollah; Panahi, Hamidreza; Ghaffari Shad, Ensieh; Asadollahi, Shadi

2017-06-01

This study aimed to determine any association between positive findings in ultrasonography examination and initial BD value with regard to diagnosis of intra-abdominal bleeding following blunt abdominal trauma. A prospective, multi-center study of consecutive adult patients was performed from April to September 2015. Demographics, initial vital signs and arterial BD were evaluated with respect to presence of any association with intra-abdominal bleeding and in-hospital mortality. FAST study was performed to find intra-abdominal bleeding. Receiver operating characteristic (ROC) curves tested the ability of BD to identify patients with intra-abdominal hemorrhage and probable mortality. A total of 879 patients were included in final analysis. The mean (SD) age was 36.68 (15.7) years and 714 patients (81.2%) were male. According to multivariable analysis, statistically significant association was observed between negative admission BD and both intra-abdominal bleeding (OR 3.48, 95% CI 2.06-5.88, p<0.001) and in-hospital mortality (OR 1.55, 95% CI 1.49-1.63, p<0.001). ROC curve analysis demonstrated sensitivity of 92.7% and specificity of 22.1% for the best cut-off value of BD (-8mEq/L) to diagnose internal hemorrhage. Further, a cut-off value of -7mEq/L demonstrated significant predictive performance, 94.8% sensitivity and 53.6% specificity for in-hospital mortality. This study revealed that arterial BD is an early accessible important marker to identify intra-abdominal bleeding, as well as to predict overall in-hospital mortality in patients with blunt abdominal trauma. Copyright © 2017. Published by Elsevier Inc.

Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells

PubMed Central

Chang, Chawnshang; Yeh, Shuyuan; Lee, Soo Ok; Chang, Ta-min

2013-01-01

The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgen/AR-related diseases. PMID:24653668

Energy transport pathway in proteins: Insights from non-equilibrium molecular dynamics with elastic network model.

PubMed

Wang, Wei Bu; Liang, Yu; Zhang, Jing; Wu, Yi Dong; Du, Jian Jun; Li, Qi Ming; Zhu, Jian Zhuo; Su, Ji Guo

2018-06-22

Intra-molecular energy transport between distant functional sites plays important roles in allosterically regulating the biochemical activity of proteins. How to identify the specific intra-molecular signaling pathway from protein tertiary structure remains a challenging problem. In the present work, a non-equilibrium dynamics method based on the elastic network model (ENM) was proposed to simulate the energy propagation process and identify the specific signaling pathways within proteins. In this method, a given residue was perturbed and the propagation of energy was simulated by non-equilibrium dynamics in the normal modes space of ENM. After that, the simulation results were transformed from the normal modes space to the Cartesian coordinate space to identify the intra-protein energy transduction pathways. The proposed method was applied to myosin and the third PDZ domain (PDZ3) of PSD-95 as case studies. For myosin, two signaling pathways were identified, which mediate the energy transductions form the nucleotide binding site to the 50 kDa cleft and the converter subdomain, respectively. For PDZ3, one specific signaling pathway was identified, through which the intra-protein energy was transduced from ligand binding site to the distant opposite side of the protein. It is also found that comparing with the commonly used cross-correlation analysis method, the proposed method can identify the anisotropic energy transduction pathways more effectively.

Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas.

PubMed

Mroz, Edmund A; Tward, Aaron D; Tward, Aaron M; Hammon, Rebecca J; Ren, Yin; Rocco, James W

2015-02-01

Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity's associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having oral-cavity or laryngeal cancers even when standard disease staging was taken into account. Prospective studies, however, will be required before MATH can be used prognostically in clinical trials or practice. Such studies will need to examine homogeneously treated HNSCC at specific head and neck subsites, and determine the influence of cancer therapy on MATH values. Analysis of MATH and outcome in human-papillomavirus-positive oropharyngeal squamous cell carcinoma is particularly needed. To our knowledge this study is the first to combine data from hundreds of patients, treated at multiple institutions, to document a relation between intra-tumor heterogeneity and overall survival in any type of cancer. We suggest applying the simply calculated MATH metric of heterogeneity to prospective studies of HNSCC and other tumor types.

Transposable Elements versus the Fungal Genome: Impact on Whole-Genome Architecture and Transcriptional Profiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castanera, Raul; Lopez-Varas, Leticia; Borgognone, Alessandra

Transposable elements (TEs) are exceptional contributors to eukaryotic genome diversity. Their ubiquitous presence impacts the genomes of nearly all species and mediates genome evolution by causing mutations and chromosomal rearrangements and by modulating gene expression. We performed an exhaustive analysis of the TE content in 18 fungal genomes, including strains of the same species and species of the same genera. Our results depicted a scenario of exceptional variability, with species having 0.02 to 29.8% of their genome consisting of transposable elements. A detailed analysis performed on two strains of Pleurotus ostreatus uncovered a genome that is populated mainly by Classmore » I elements, especially LTR-retrotransposons amplified in recent bursts from 0 to 2 million years (My) ago. The preferential accumulation of TEs in clusters led to the presence of genomic regions that lacked intra- and inter-specific conservation. In addition, we investigated the effect of TE insertions on the expression of their nearby upstream and downstream genes. Our results showed that an important number of genes under TE influence are significantly repressed, with stronger repression when genes are localized within transposon clusters. Our transcriptional analysis performed in four additional fungal models revealed that this TE-mediated silencing was present only in species with active cytosine methylation machinery. We hypothesize that this phenomenon is related to epigenetic defense mechanisms that are aimed to suppress TE expression and control their proliferation.« less

Single nucleotide resolution RNA-seq uncovers new regulatory mechanisms in the opportunistic pathogen Streptococcus agalactiae.

PubMed

Rosinski-Chupin, Isabelle; Sauvage, Elisabeth; Sismeiro, Odile; Villain, Adrien; Da Cunha, Violette; Caliot, Marie-Elise; Dillies, Marie-Agnès; Trieu-Cuot, Patrick; Bouloc, Philippe; Lartigue, Marie-Frédérique; Glaser, Philippe

2015-05-30

Streptococcus agalactiae, or Group B Streptococcus, is a leading cause of neonatal infections and an increasing cause of infections in adults with underlying diseases. In an effort to reconstruct the transcriptional networks involved in S. agalactiae physiology and pathogenesis, we performed an extensive and robust characterization of its transcriptome through a combination of differential RNA-sequencing in eight different growth conditions or genetic backgrounds and strand-specific RNA-sequencing. Our study identified 1,210 transcription start sites (TSSs) and 655 transcript ends as well as 39 riboswitches and cis-regulatory regions, 39 cis-antisense non-coding RNAs and 47 small RNAs potentially acting in trans. Among these putative regulatory RNAs, ten were differentially expressed in response to an acid stress and two riboswitches sensed directly or indirectly the pH modification. Strikingly, 15% of the TSSs identified were associated with the incorporation of pseudo-templated nucleotides, showing that reiterative transcription is a pervasive process in S. agalactiae. In particular, 40% of the TSSs upstream genes involved in nucleotide metabolism show reiterative transcription potentially regulating gene expression, as exemplified for pyrG and thyA encoding the CTP synthase and the thymidylate synthase respectively. This comprehensive map of the transcriptome at the single nucleotide resolution led to the discovery of new regulatory mechanisms in S. agalactiae. It also provides the basis for in depth analyses of transcriptional networks in S. agalactiae and of the regulatory role of reiterative transcription following variations of intra-cellular nucleotide pools.

Mitogen-Activated Protein Kinase Signaling in the Heart: Angels Versus Demons in a Heart-Breaking Tale

PubMed Central

ROSE, BETH A.; FORCE, THOMAS; WANG, YIBIN

2013-01-01

Among the myriad of intra-cellular signaling networks that govern the cardiac development and pathogenesis, mitogen-activated protein kinases (MAPKs) are prominent players that have been the focus of extensive investigations in the past decades. The four best characterized MAPK subfamilies, ERK1/2, JNK, p38, and ERK5, are the targets of pharmacological and genetic manipulations to uncover their roles in cardiac development, function, and diseases. However, information reported in the literature from these efforts has not yet resulted in a clear view about the roles of specific MAPK pathways in heart. Rather, controversies from contradictive results have led to a perception that MAPKs are ambiguous characters in heart with both protective and detrimental effects. The primary object of this review is to provide a comprehensive overview of the current progress, in an effort to highlight the areas where consensus is established verses the ones where controversy remains. MAPKs in cardiac development, cardiac hypertrophy, ischemia/reperfusion injury, and pathological remodeling are the main focuses of this review as these represent the most critical issues for evaluating MAPKs as viable targets of therapeutic development. The studies presented in this review will help to reveal the major challenges in the field and the limitations of current approaches and point to a critical need in future studies to gain better understanding of the fundamental mechanisms of MAPK function and regulation in the heart. PMID:20959622

Transposable Elements versus the Fungal Genome: Impact on Whole-Genome Architecture and Transcriptional Profiles

DOE PAGES

Castanera, Raul; Lopez-Varas, Leticia; Borgognone, Alessandra; ...

2016-06-13

Transposable elements (TEs) are exceptional contributors to eukaryotic genome diversity. Their ubiquitous presence impacts the genomes of nearly all species and mediates genome evolution by causing mutations and chromosomal rearrangements and by modulating gene expression. We performed an exhaustive analysis of the TE content in 18 fungal genomes, including strains of the same species and species of the same genera. Our results depicted a scenario of exceptional variability, with species having 0.02 to 29.8% of their genome consisting of transposable elements. A detailed analysis performed on two strains of Pleurotus ostreatus uncovered a genome that is populated mainly by Classmore » I elements, especially LTR-retrotransposons amplified in recent bursts from 0 to 2 million years (My) ago. The preferential accumulation of TEs in clusters led to the presence of genomic regions that lacked intra- and inter-specific conservation. In addition, we investigated the effect of TE insertions on the expression of their nearby upstream and downstream genes. Our results showed that an important number of genes under TE influence are significantly repressed, with stronger repression when genes are localized within transposon clusters. Our transcriptional analysis performed in four additional fungal models revealed that this TE-mediated silencing was present only in species with active cytosine methylation machinery. We hypothesize that this phenomenon is related to epigenetic defense mechanisms that are aimed to suppress TE expression and control their proliferation.« less

Recurrent Innovation at Genes Required for Telomere Integrity in Drosophila.

PubMed

Lee, Yuh Chwen G; Leek, Courtney; Levine, Mia T

2017-02-01

Telomeres are nucleoprotein complexes at the ends of linear chromosomes. These specialized structures ensure genome integrity and faithful chromosome inheritance. Recurrent addition of repetitive, telomere-specific DNA elements to chromosome ends combats end-attrition, while specialized telomere-associated proteins protect naked, double-stranded chromosome ends from promiscuous repair into end-to-end fusions. Although telomere length homeostasis and end-protection are ubiquitous across eukaryotes, there is sporadic but building evidence that the molecular machinery supporting these essential processes evolves rapidly. Nevertheless, no global analysis of the evolutionary forces that shape these fast-evolving proteins has been performed on any eukaryote. The abundant population and comparative genomic resources of Drosophila melanogaster and its close relatives offer us a unique opportunity to fill this gap. Here we leverage population genetics, molecular evolution, and phylogenomics to define the scope and evolutionary mechanisms driving fast evolution of genes required for telomere integrity. We uncover evidence of pervasive positive selection across multiple evolutionary timescales. We also document prolific expansion, turnover, and expression evolution in gene families founded by telomeric proteins. Motivated by the mutant phenotypes and molecular roles of these fast-evolving genes, we put forward four alternative, but not mutually exclusive, models of intra-genomic conflict that may play out at very termini of eukaryotic chromosomes. Our findings set the stage for investigating both the genetic causes and functional consequences of telomere protein evolution in Drosophila and beyond. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Components of Effective Diversity Training Programmes.

ERIC Educational Resources Information Center

Wentling, Rose Mary; Palma-Rivas, Nilda

1999-01-01

Interviews with 12 diversity experts uncovered components of effective diversity training programs: management commitment and support, inclusion in strategic planning, attention to specific organizational needs, qualified trainers, mandatory attendance, inclusiveness, trust and confidentiality, accountability, and clearly focused evaluation. (SK)

Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

NASA Astrophysics Data System (ADS)

Stemkens, Bjorn; Glitzner, Markus; Kontaxis, Charis; de Senneville, Baudouin Denis; Prins, Fieke M.; Crijns, Sjoerd P. M.; Kerkmeijer, Linda G. W.; Lagendijk, Jan J. W.; van den Berg, Cornelis A. T.; Tijssen, Rob H. N.

2017-09-01

Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to 40% of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

Intra-aneurysmal flow disruption after implantation of the Medina® Embolization Device depends on aneurysm neck coverage.

PubMed

Frölich, Andreas Maximilian; Nawka, Marie Teresa; Ernst, Marielle; Frischmuth, Isabell; Fiehler, Jens; Buhk, Jan-Hendrik

2018-01-01

Flow disruption achieved by braided intrasaccular implants is a novel treatment strategy for cerebrovascular aneurysms. We hypothesized that the degree of intra-aneurysmal flow disruption can be quantified in vitro and is influenced by device position across the aneurysm neck. We tested this hypothesis using the Medina® Embolization Device (MED). Ten different patient-specific elastic vascular models were manufactured. Models were connected to a pulsatile flow circuit, filled with a blood-mimicking fluid and treated by two operators using a single MED. Intra-aneurysmal flow velocity was measured using conventional and high-frequency digital subtraction angiography (HF-DSA) before and after each deployment. Aneurysm neck coverage by the implanted devices was assessed with flat detector computed tomography on a three-point Likert scale. A total of 80 individual MED deployments were performed by the two operators. The mean intra-aneurysmal flow velocity reduction after MED implantation was 33.6% (27.5-39.7%). No significant differences in neck coverage (p = 0.99) or flow disruption (p = 0.84) were observed between operators. The degree of flow disruption significantly correlated with neck coverage (ρ = 0.42, 95% CI: 0.21-0.59, p = 0.002) as well as with neck area (ρ = -0,35, 95% CI: -0.54 --0.13, p = 0.024). On multiple regression analysis, both neck coverage and total neck area were independent predictors of flow disruption. The degree of intra-aneurysmal flow disruption after MED implantation can be quantified in vitro and varies considerably between different aneurysms and different device configurations. Optimal device coverage across the aneurysm neck improves flow disruption and may thus contribute to aneurysm occlusion.

Intra-abdominal fat accumulation is a hypertension risk factor in young adulthood

PubMed Central

Takeoka, Atsushi; Tayama, Jun; Yamasaki, Hironori; Kobayashi, Masakazu; Ogawa, Sayaka; Saigo, Tatsuo; Kawano, Hiroaki; Abiru, Norio; Hayashida, Masaki; Maeda, Takahiro; Shirabe, Susumu

2016-01-01

Abstract Accumulation of intra-abdominal fat is related to hypertension. Despite this, a relationship between hypertension and intra-abdominal fat in young adulthood is not clear. In this study, we verify whether intra-abdominal fat accumulation increases a hypertension risk in young adult subjects. In a cross-sectional study, intra-abdominal fat area was measured using a dual bioelectrical impedance analysis instrument in 697 university students (20.3 ± 0.7 years, 425 men). Blood pressure and anthropometric factors were measured. Lifestyle variables including smoking, drinking, physical activity, and eating behavior were assessed with questionnaire. High blood pressure risk (systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg) with increasing intra-abdominal fat area was evaluated. Participants were divided into 5 groups according to their intra-abdominal fat area (≤24.9, 25–49.9, 50–74.9, 75–99.9, and ≥100 cm2). As compared with the values of the smallest intra-abdominal fat area group, the crude and lifestyle-adjusted odds ratios (ORs) were elevated in larger intra-abdominal fat area groups [OR 1.31, 95% confidence interval (CI) 0.66–2.80; OR 3.38, 95% CI 1.60–7.57; OR 7.71, 95% CI 2.75–22.22; OR 18.74, 95% CI 3.93–105.64, respectively). The risk increase was observed only in men. Intra-abdominal fat accumulation is related to high blood pressure in men around 20 years of age. These results indicate the importance of evaluation and reduction of intra-abdominal fat to prevent hypertension. PMID:27828861

Intra-abdominal fat accumulation is a hypertension risk factor in young adulthood: A cross-sectional study.

PubMed

Takeoka, Atsushi; Tayama, Jun; Yamasaki, Hironori; Kobayashi, Masakazu; Ogawa, Sayaka; Saigo, Tatsuo; Kawano, Hiroaki; Abiru, Norio; Hayashida, Masaki; Maeda, Takahiro; Shirabe, Susumu

2016-11-01

Accumulation of intra-abdominal fat is related to hypertension. Despite this, a relationship between hypertension and intra-abdominal fat in young adulthood is not clear. In this study, we verify whether intra-abdominal fat accumulation increases a hypertension risk in young adult subjects.In a cross-sectional study, intra-abdominal fat area was measured using a dual bioelectrical impedance analysis instrument in 697 university students (20.3 ± 0.7 years, 425 men). Blood pressure and anthropometric factors were measured. Lifestyle variables including smoking, drinking, physical activity, and eating behavior were assessed with questionnaire. High blood pressure risk (systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg) with increasing intra-abdominal fat area was evaluated.Participants were divided into 5 groups according to their intra-abdominal fat area (≤24.9, 25-49.9, 50-74.9, 75-99.9, and ≥100 cm). As compared with the values of the smallest intra-abdominal fat area group, the crude and lifestyle-adjusted odds ratios (ORs) were elevated in larger intra-abdominal fat area groups [OR 1.31, 95% confidence interval (CI) 0.66-2.80; OR 3.38, 95% CI 1.60-7.57; OR 7.71, 95% CI 2.75-22.22; OR 18.74, 95% CI 3.93-105.64, respectively). The risk increase was observed only in men.Intra-abdominal fat accumulation is related to high blood pressure in men around 20 years of age. These results indicate the importance of evaluation and reduction of intra-abdominal fat to prevent hypertension.

The genome of the vervet (Chlorocebus aethiops sabaeus)

PubMed Central

Warren, Wesley C.; Jasinska, Anna J.; García-Pérez, Raquel; Svardal, Hannes; Tomlinson, Chad; Rocchi, Mariano; Archidiacono, Nicoletta; Capozzi, Oronzo; Minx, Patrick; Montague, Michael J.; Kyung, Kim; Hillier, LaDeana W.; Kremitzki, Milinn; Graves, Tina; Chiang, Colby; Hughes, Jennifer; Tran, Nam; Huang, Yu; Ramensky, Vasily; Choi, Oi-wa; Jung, Yoon J.; Schmitt, Christopher A.; Juretic, Nikoleta; Wasserscheid, Jessica; Turner, Trudy R.; Wiseman, Roger W.; Tuscher, Jennifer J.; Karl, Julie A.; Schmitz, Jörn E.; Zahn, Roland; O'Connor, David H.; Redmond, Eugene; Nisbett, Alex; Jacquelin, Béatrice; Müller-Trutwin, Michaela C.; Brenchley, Jason M.; Dione, Michel; Antonio, Martin; Schroth, Gary P.; Kaplan, Jay R.; Jorgensen, Matthew J.; Thomas, Gregg W.C.; Hahn, Matthew W.; Raney, Brian J.; Aken, Bronwen; Nag, Rishi; Schmitz, Juergen; Churakov, Gennady; Noll, Angela; Stanyon, Roscoe; Webb, David; Thibaud-Nissen, Francoise; Nordborg, Magnus; Marques-Bonet, Tomas; Dewar, Ken; Weinstock, George M.; Wilson, Richard K.; Freimer, Nelson B.

2015-01-01

We describe a genome reference of the African green monkey or vervet (Chlorocebus aethiops). This member of the Old World monkey (OWM) superfamily is uniquely valuable for genetic investigations of simian immunodeficiency virus (SIV), for which it is the most abundant natural host species, and of a wide range of health-related phenotypes assessed in Caribbean vervets (C. a. sabaeus), whose numbers have expanded dramatically since Europeans introduced small numbers of their ancestors from West Africa during the colonial era. We use the reference to characterize the genomic relationship between vervets and other primates, the intra-generic phylogeny of vervet subspecies, and genome-wide structural variations of a pedigreed C. a. sabaeus population. Through comparative analyses with human and rhesus macaque, we characterize at high resolution the unique chromosomal fission events that differentiate the vervets and their close relatives from most other catarrhine primates, in whom karyotype is highly conserved. We also provide a summary of transposable elements and contrast these with the rhesus macaque and human. Analysis of sequenced genomes representing each of the main vervet subspecies supports previously hypothesized relationships between these populations, which range across most of sub-Saharan Africa, while uncovering high levels of genetic diversity within each. Sequence-based analyses of major histocompatibility complex (MHC) polymorphisms reveal extremely low diversity in Caribbean C. a. sabaeus vervets, compared to vervets from putatively ancestral West African regions. In the C. a. sabaeus research population, we discover the first structural variations that are, in some cases, predicted to have a deleterious effect; future studies will determine the phenotypic impact of these variations. PMID:26377836

Adaptation to climate change: Using nighttime lights satellite data to explore human response to flood events

NASA Astrophysics Data System (ADS)

Mård, Johanna; Di Baldassarre, Giuliano

2017-04-01

To better understand the impact of climate change, we need to uncover how (and to what extent) societies respond and adapt to it. Yet the dynamics resulting from two-way feedbacks between nature and society remain largely unknown. Here we present an interdisciplinary study aiming to uncover one of the least quantified aspects of human-nature interactions, the spatial-temporal distribution of demographic changes following the occurrence of extreme events. To this end, we use nighttime light satellite data in four contrasting case studies in both low- and high-income countries (Lower Limpopo River in Mozambique, Mekong River in Vietnam and Cambodia, Brisbane River in Australia and Mississippi River at St. Louis in USA), and explore the interplay between flooding events and changes in population distribution in the period 1992-2013. Our study shows the challenges and opportunities of nighttime lights in unraveling the way humans adapt to climate change. Specific results show that population distribution of societies that strongly rely on structural measures ("fighting floods" policies) is not significantly affected by the occurrence of flood events. Conversely, learning dynamics emerge in societies that mainly rely on non-structural measures ("living with floods" policies) in terms of relative population in floodplain areas, i.e. reduced human proximity to rivers. Lastly, we propose the development of a novel approach to exploit the growing availability of worldwide information, such as nighttime lights satellite data, to uncover human adaptation to climate change across scales and along gradients of social and natural conditions.

Functional abilities and cognitive decline in adult and aging intellectual disabilities. Psychometric validation of an Italian version of the Alzheimer's Functional Assessment Tool (AFAST): analysis of its clinical significance with linear statistics and artificial neural networks.

PubMed

De Vreese, L P; Gomiero, T; Uberti, M; De Bastiani, E; Weger, E; Mantesso, U; Marangoni, A

2015-04-01

(a) A psychometric validation of an Italian version of the Alzheimer's Functional Assessment Tool scale (AFAST-I), designed for informant-based assessment of the degree of impairment and of assistance required in seven basic daily activities in adult/elderly people with intellectual disabilities (ID) and (suspected) dementia; (b) a pilot analysis of its clinical significance with traditional statistical procedures and with an artificial neural network. AFAST-I was administered to the professional caregivers of 61 adults/seniors with ID with a mean age (± SD) of 53.4 (± 7.7) years (36% with Down syndrome). Internal consistency (Cronbach's α coefficient), inter/intra-rater reliabilities (intra-class coefficients, ICC) and concurrent, convergent and discriminant validity (Pearson's r coefficients) were computed. Clinical significance was probed by analysing the relationships among AFAST-I scores and the Sum of Cognitive Scores (SCS) and the Sum of Social Scores (SOS) of the Dementia Questionnaire for Persons with Intellectual Disabilities (DMR-I) after standardisation of their raw scores in equivalent scores (ES). An adaptive artificial system (AutoContractive Maps, AutoCM) was applied to all the variables recorded in the study sample, aimed at uncovering which variable occupies a central position and supports the entire network made up of the remaining variables interconnected among themselves with different weights. AFAST-I shows a high level of internal homogeneity with a Cronbach's α coefficient of 0.92. Inter-rater and intra-rater reliabilities were also excellent with ICC correlations of 0.96 and 0.93, respectively. The results of the analyses of the different AFAST-I validities all go in the expected direction: concurrent validity (r=-0.87 with ADL); convergent validity (r=0.63 with SCS; r=0.61 with SOS); discriminant validity (r=0.21 with the frequency of occurrence of dementia-related Behavioral Excesses of the Assessment for Adults with Developmental Disabilities, AADS-I). In our sample age and gender do not correlate with the scale and comparing the distribution of the AFAST-I and DMR-SCS and DMR-SOS expressed as ES, it appears that memory disorders and temporal and spatial disorientation (SCS) precede the loss of functional abilities, whereas changes in social behaviour (SOS) are less specific in detecting cognitive deterioration sufficient to provoke functional disability and vice versa. The results of AutoCM analysis reveal that the hub (core) of the entire network is represented by the functional domain 'personal/oral hygiene' in the entire study sample and 'use of toilet' in a subgroup of subjects who obtained an ES equal to 0 at DMR-SCS. These results confirm the reliability and validity of AFAST-I and emphasise the complexity of the relationship among functional status, cognitive functioning and behaviour also in adults/seniors with ID. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Point-of-care test for cervical cancer in LMICs.

PubMed

Mohammed, Sulma I; Ren, Wen; Flowers, Lisa; Rajwa, Bartek; Chibwesha, Carla J; Parham, Groesbeck P; Irudayaraj, Joseph M K

2016-04-05

Cervical cancer screening using Papanicolaou's smear test has been highly effective in reducing death from this disease. However, this test is unaffordable in low- and middle-income countries, and its complexity has limited wide-scale uptake. Alternative tests, such as visual inspection with acetic acid or Lugol's iodine and human papillomavirus DNA, are sub-optimal in terms of specificity and sensitivity, thus sensitive and affordable tests with high specificity for on-site reporting are needed. Using proteomics and bioinformatics, we have identified valosin-containing protein (VCP) as differentially expressed between normal specimens and those with cervical intra-epithelial neoplasia grade 2/3 (CIN2/CIN3+) or worse. VCP-specific immunohistochemical staining (validated by a point-of-care technology) provided sensitive (93%) and specific (88%) identification of CIN2/CIN3+ and may serve as a critical biomarker for cervical-cancer screening. Future efforts will focus on further refinements to enhance analytic sensitivity and specificity of our proposed test, as well as on prototype development.

Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers

PubMed Central

Steenkeste, Nicolas; Incardona, Sandra; Chy, Sophy; Duval, Linda; Ekala, Marie-Thérèse; Lim, Pharath; Hewitt, Sean; Sochantha, Tho; Socheat, Doung; Rogier, Christophe; Mercereau-Puijalon, Odile; Fandeur, Thierry; Ariey, Frédéric

2009-01-01

Background Several strategies are currently deployed in many countries in the tropics to strengthen malaria control toward malaria elimination. To measure the impact of any intervention, there is a need to detect malaria properly. Mostly, decisions still rely on microscopy diagnosis. But sensitive diagnosis tools enabling to deal with a large number of samples are needed. The molecular detection approach offers a much higher sensitivity, and the flexibility to be automated and upgraded. Methods Two new molecular methods were developed: dot18S, a Plasmodium-specific nested PCR based on the 18S rRNA gene followed by dot-blot detection of species by using species-specific probes and CYTB, a Plasmodium-specific nested PCR based on cytochrome b gene followed by species detection using SNP analysis. The results were compared to those obtained with microscopic examination and the "standard" 18S rRNA gene based nested PCR using species specific primers. 337 samples were diagnosed. Results Compared to the microscopy the three molecular methods were more sensitive, greatly increasing the estimated prevalence of Plasmodium infection, including P. malariae and P. ovale. A high rate of mixed infections was uncovered with about one third of the villagers infected with more than one malaria parasite species. Dot18S and CYTB sensitivity outranged the "standard" nested PCR method, CYTB being the most sensitive. As a consequence, compared to the "standard" nested PCR method for the detection of Plasmodium spp., the sensitivity of dot18S and CYTB was respectively 95.3% and 97.3%. Consistent detection of Plasmodium spp. by the three molecular methods was obtained for 83% of tested isolates. Contradictory results were mostly related to detection of Plasmodium malariae and Plasmodium ovale in mixed infections, due to an "all-or-none" detection effect at low-level parasitaemia. Conclusion A large reservoir of asymptomatic infections was uncovered using the molecular methods. Dot18S and CYTB, the new methods reported herein are highly sensitive, allow parasite DNA extraction as well as genus- and species-specific diagnosis of several hundreds of samples, and are amenable to high-throughput scaling up for larger sample sizes. Such methods provide novel information on malaria prevalence and epidemiology and are suited for active malaria detection. The usefulness of such sensitive malaria diagnosis tools, especially in low endemic areas where eradication plans are now on-going, is discussed in this paper. PMID:19402894

Genetic differentiation of the mitochondrial cytochrome oxidase C subunit I gene in genus Paramecium (Protista, Ciliophora).

PubMed

Zhao, Yan; Gentekaki, Eleni; Yi, Zhenzhen; Lin, Xiaofeng

2013-01-01

The mitochondrial cytochrome c oxidase subunit I (COI) gene is being used increasingly for evaluating inter- and intra-specific genetic diversity of ciliated protists. However, very few studies focus on assessing genetic divergence of the COI gene within individuals and how its presence might affect species identification and population structure analyses. We evaluated the genetic variation of the COI gene in five Paramecium species for a total of 147 clones derived from 21 individuals and 7 populations. We identified a total of 90 haplotypes with several individuals carrying more than one haplotype. Parsimony network and phylogenetic tree analyses revealed that intra-individual diversity had no effect in species identification and only a minor effect on population structure. Our results suggest that the COI gene is a suitable marker for resolving inter- and intra-specific relationships of Paramecium spp.

Genetic Differentiation of the Mitochondrial Cytochrome Oxidase c Subunit I Gene in Genus Paramecium (Protista, Ciliophora)

PubMed Central

Zhao, Yan; Gentekaki, Eleni; Yi, Zhenzhen; Lin, Xiaofeng

2013-01-01

Background The mitochondrial cytochrome c oxidase subunit I (COI) gene is being used increasingly for evaluating inter- and intra-specific genetic diversity of ciliated protists. However, very few studies focus on assessing genetic divergence of the COI gene within individuals and how its presence might affect species identification and population structure analyses. Methodology/Principal findings We evaluated the genetic variation of the COI gene in five Paramecium species for a total of 147 clones derived from 21 individuals and 7 populations. We identified a total of 90 haplotypes with several individuals carrying more than one haplotype. Parsimony network and phylogenetic tree analyses revealed that intra-individual diversity had no effect in species identification and only a minor effect on population structure. Conclusions Our results suggest that the COI gene is a suitable marker for resolving inter- and intra-specific relationships of Paramecium spp. PMID:24204730

TGFβ1-induced leucine limitation uncovered by differential ribosome codon reading.

PubMed

Loayza-Puch, Fabricio; Rooijers, Koos; Zijlstra, Jelle; Moumbeini, Behzad; Zaal, Esther A; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro P; Berkers, Celia R; Agami, Reuven

2017-04-01

Cancer cells modulate their metabolic networks to support cell proliferation and a higher demand of building blocks. These changes may restrict the availability of certain amino acids for protein synthesis, which can be utilized for cancer therapy. However, little is known about the amino acid demand changes occurring during aggressive and invasive stages of cancer. Recently, we developed diricore, an approach based on ribosome profiling that can uncover amino acid limitations. Here, we applied diricore to a cellular model in which epithelial breast cells respond rapidly to TGFβ1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine. Further analyses indicated that TGFβ1 treatment of human breast epithelial cells reduces the expression of SLC3A2, a subunit of the leucine transporter, which diminishes leucine uptake and inhibits cell proliferation. Thus, we identified a specific amino acid limitation associated with the TGFβ1 response, a vulnerability that might be associated with aggressiveness in cancer. © 2017 The Authors.

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome after Abdominal Wall Reconstruction: Quaternary Syndromes?

PubMed

Kirkpatrick, A W; Nickerson, D; Roberts, D J; Rosen, M J; McBeth, P B; Petro, C C; Berrevoet, Frederik; Sugrue, M; Xiao, Jimmy; Ball, C G

2017-06-01

Reconstruction with reconstitution of the container function of the abdominal compartment is increasingly being performed in patients with massive ventral hernia previously deemed inoperable. This situation places patients at great risk of severe intra-abdominal hypertension and abdominal compartment syndrome if organ failure ensues. Intra-abdominal hypertension and especially abdominal compartment syndrome may be devastating systemic complications with systematic and progressive organ failure and death. We thus reviewed the pathophysiology and reported clinical experiences with abnormalities of intra-abdominal pressure in the context of abdominal wall reconstruction. Bibliographic databases (1950-2015), websites, textbooks, and the bibliographies of previously recovered articles for reports or data relating to intra-abdominal pressure, intra-abdominal hypertension, and the abdominal compartment syndrome in relation to ventral, incisional, or abdominal hernia repair or abdominal wall reconstruction. Surgeons should thus consider and carefully measure intra-abdominal pressure and its resultant effects on respiratory parameters and function during abdominal wall reconstruction. The intra-abdominal pressure post-operatively will be a result of the new intra-peritoneal volume and the abdominal wall compliance. Strategies surgeons may utilize to ameliorate intra-abdominal pressure rise after abdominal wall reconstruction including temporizing paralysis of the musculature either temporarily or semi-permanently, pre-operative progressive pneumoperitoneum, permanently removing visceral contents, or surgically releasing the musculature to increase the abdominal container volume. In patients without complicating shock and inflammation, and in whom the abdominal wall anatomy has been so functionally adapted to maximize compliance, intra-abdominal hypertension may be transient and tolerable. Intra-abdominal hypertension/abdominal compartment syndrome in the specific setting of abdominal wall reconstruction without other complication may be considered as a quaternary situation considering the classification nomenclature of the Abdominal Compartment Society. Greater awareness of intra-abdominal pressure in abdominal wall reconstruction is required and ongoing study of these concerns is required.

The Queensland high risk foot form (QHRFF) – is it a reliable and valid clinical research tool for foot disease?

PubMed Central

2014-01-01

Background Foot disease complications, such as foot ulcers and infection, contribute to considerable morbidity and mortality. These complications are typically precipitated by “high-risk factors”, such as peripheral neuropathy and peripheral arterial disease. High-risk factors are more prevalent in specific “at risk” populations such as diabetes, kidney disease and cardiovascular disease. To the best of the authors’ knowledge a tool capturing multiple high-risk factors and foot disease complications in multiple at risk populations has yet to be tested. This study aimed to develop and test the validity and reliability of a Queensland High Risk Foot Form (QHRFF) tool. Methods The study was conducted in two phases. Phase one developed a QHRFF using an existing diabetes foot disease tool, literature searches, stakeholder groups and expert panel. Phase two tested the QHRFF for validity and reliability. Four clinicians, representing different levels of expertise, were recruited to test validity and reliability. Three cohorts of patients were recruited; one tested criterion measure reliability (n = 32), another tested criterion validity and inter-rater reliability (n = 43), and another tested intra-rater reliability (n = 19). Validity was determined using sensitivity, specificity and positive predictive values (PPV). Reliability was determined using Kappa, weighted Kappa and intra-class correlation (ICC) statistics. Results A QHRFF tool containing 46 items across seven domains was developed. Criterion measure reliability of at least moderate categories of agreement (Kappa > 0.4; ICC > 0.75) was seen in 91% (29 of 32) tested items. Criterion validity of at least moderate categories (PPV > 0.7) was seen in 83% (60 of 72) tested items. Inter- and intra-rater reliability of at least moderate categories (Kappa > 0.4; ICC > 0.75) was seen in 88% (84 of 96) and 87% (20 of 23) tested items respectively. Conclusions The QHRFF had acceptable validity and reliability across the majority of items; particularly items identifying relevant co-morbidities, high-risk factors and foot disease complications. Recommendations have been made to improve or remove identified weaker items for future QHRFF versions. Overall, the QHRFF possesses suitable practicality, validity and reliability to assess and capture relevant foot disease items across multiple at risk populations. PMID:24468080

NI-16INTRA-OPERATIVE USE OF FLUORESCEIN FOR MALIGNANT GLIOMA RESECTION DIFFERENTIATES TUMOR FROM NORMAL BRAIN TISSUE BASED ON HISTOPATHOLOGIC ANALYSIS

PubMed Central

Decker, Matthew; Kresak, Jesse; Yachnis, Anthony; Bova, Frank; Rahman, Maryam

2014-01-01

OBJECTIVES: To determine whether the use of IV fluorescein during surgery for malignant glioma can reliably be used to differentiate between infiltrative tumor and normal brain tissue. BACKGROUND: Fluorescein sodium is a molecular compound with fluorescent capabilities between light wavelengths of 520-530nm, appearing yellow-green (1). Neurosurgical application of fluorescein has been studied primarily for increasing intra-operative visibility of malignant gliomas (1). The mechanism of action has been hypothesized to involve disruption of the blood brain barrier (BBB) (2). Cells in areas with disrupted BBB take up fluorescein with a sensitivity of 94% and specificity of 89% for high-grade gliomas (2). We performed histopathologic analysis on tissue obtained during fluorescein-guided tumor resections to evaluate the differences between fluorescent and non-fluorescent tissue. METHODS: Two adult patients with suspected high-grade gliomas underwent surgical resection. Prior to opening of the dura 3mg/kg of IV fluorescein was given. A Zeiss OPMI Pentero microscope (Carl Zeiss Meditech Inc.) with a yellow 560nm filter was used to visualize the tumor. At the tumor margins, tissue was identified as "bright" and "dark" and sent as separate specimens for histopathological analysis. RESULTS: Histological sections of specimens labeled "bright" contained infiltrating glioma with focal microvascular proliferation. Histological sections of specimens labeled "dark" contained gray matter and focal subcortical white matter with no high-grade glioma identified. Final grading for both patients was WHO Grade IV, glioblastoma. CONCLUSION: Intra-operative use of fluorescein in surgical resection of malignant gliomas can help to distinguish between infiltrating tumor and normal brain tissue based on histopathological analysis. Further evaluation of the utility of flurorescein during high and low-grade glioma surgery is necessary.

A sensitive one-step TaqMan amplification approach for detection of rubella virus clade I and II genotypes in clinical samples.

PubMed

Claus, C; Bergs, S; Emmrich, N C; Hübschen, J M; Mankertz, A; Liebert, U G

2017-02-01

Although teratogenic rubella virus (RV) causes a vaccine-preventable disease, it is still endemic in several countries worldwide. Thus, there is a constant risk of RV importation into non-endemic areas. RV monitoring, especially during measles and Zika virus outbreaks, requires reliable diagnostic tools. For this study, a TaqMan-based one-step reverse transcription-quantitative PCR (RT-qPCR) assay, with the p90 gene as a novel and so far unexplored target for detection of clade I and II genotypes, was developed and evaluated. Automated nucleic acid extraction was carried out. Performance characteristics of the TaqMan RT-qPCR assay were determined for a RV plasmid standard and RNA extracted from virus-infected cell culture supernatants representing clade I and II genotypes. Diagnostic specificity and sensitivity were validated against other RNA and DNA viruses, relevant for RV diagnostic approaches and for RV-positive clinical samples, respectively. The assay is specific and highly sensitive with a limit of detection as low as five to one copies per reaction or 200 infectious virus particles per ml. The coefficients of variation (CV) were specified as intra- (within one run) and inter- (between different runs) assay variation, and calculated based on the standard deviations for the obtained Ct values of the respective samples. Intra- and inter-assay CV values were low, with a maximum of 3.4% and 2.4%, respectively. The assay was shown to be suitable and specific for the analysis of clinical samples. With p90 as a novel target, the highly sensitive and specific TaqMan assay outlined in this study is suitable for RV diagnosis worldwide.

Intra-band gap in Lamb modes propagating in a periodic solid structure

NASA Astrophysics Data System (ADS)

Pierre, J.; Rénier, M.; Bonello, B.; Hladky-Hennion, A.-C.

2012-05-01

A laser ultrasonic technique is used to measure the dispersion of Lamb waves at a few MHz, propagating in phononic crystals made of dissymmetric air inclusions drilled throughout silicon plates. It is shown that the specific shape of the inclusions is at the origin of the intra-band gap that opens within the second Brillouin zone, at the crossing of both flexural and dilatational zero-order modes. The magnitude of the intra-band gap is measured as a function of the dissymmetry rate of the inclusions. Experimental data and the computed dispersion curves are in very good agreement.

Point-of-care urine tests for smoking status and isoniazid treatment monitoring in adult patients.

PubMed

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference.

Point-of-Care Urine Tests for Smoking Status and Isoniazid Treatment Monitoring in Adult Patients

PubMed Central

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Background Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. Methodology/Principal Findings 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. Conclusions IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference. PMID:23029310

A new iPhone application for measuring active craniocervical range of motion in patients with non-specific neck pain: a reliability and validity study.

PubMed

Pourahmadi, Mohammad Reza; Bagheri, Rasool; Taghipour, Morteza; Takamjani, Ismail Ebrahimi; Sarrafzadeh, Javad; Mohseni-Bandpei, Mohammad Ali

2018-03-01

Measurement of cervical spine range of motion (ROM) is often considered to be an essential component of cervical spine physiotherapy assessment. This study aimed to investigate the reliability and validity of an iPhone application (app) (Goniometer Pro) for measuring active craniocervical ROM (ACCROM) in patients with non-specific neck pain. A cross-sectional study was conducted at the musculoskeletal biomechanics laboratory located at Iran University of Medical Sciences. Forty non-specific neck pain patients participated in this study. The outcome measure was the ACCROM, including flexion, extension, lateral flexion, and rotation. Following the recruitment process, ACCROM was measured using a universal goniometer (UG) and iPhone 7 app. Two blinded examiners each used the UG and iPhone to measure ACCROM in the following sequences: flexion, extension, lateral flexion, and rotation. The second (2 hours later) and third (48 hours later) sessions were carried out in the same manner as the first session. Intraclass correlation coefficient (ICC) models were used to determine the intra-rater and inter-rater reliability. The Pearson correlation coefficients were used to establish concurrent validity of the iPhone app. Minimum detectable change at the 95% confidence level (MDC 95 ) was also computed. Good intra-rater and inter-rater reliability was demonstrated for the goniometer with ICC values of ≥0.66 and ≥0.70 and the iPhone app with ICC values of ≥0.62 and ≥0.65, respectively. The MDC 95 ranged from 2.21° to 12.50° for the intra-rater analysis and from 3.40° to 12.61° for the inter-rater analysis. The concurrent validity between the two instruments was high, with r valuesof ≥0.63. The magnitude of the differences between the UG and iPhone app values (effect sizes) was small, with Cohen d values of ≤0.17. The iPhone app possesses good reliability and high validity. It seems that this app can be used for measuring ACCROM. Copyright © 2017 Elsevier Inc. All rights reserved.

Shaping highly regular glass architectures: A lesson from nature

PubMed Central

Schoeppler, Vanessa; Reich, Elke; Vacelet, Jean; Rosenthal, Martin; Pacureanu, Alexandra; Rack, Alexander; Zaslansky, Paul; Zolotoyabko, Emil; Zlotnikov, Igor

2017-01-01

Demospongiae is a class of marine sponges that mineralize skeletal elements, the glass spicules, made of amorphous silica. The spicules exhibit a diversity of highly regular three-dimensional branched morphologies that are a paradigm example of symmetry in biological systems. Current glass shaping technology requires treatment at high temperatures. In this context, the mechanism by which glass architectures are formed by living organisms remains a mystery. We uncover the principles of spicule morphogenesis. During spicule formation, the process of silica deposition is templated by an organic filament. It is composed of enzymatically active proteins arranged in a mesoscopic hexagonal crystal-like structure. In analogy to synthetic inorganic nanocrystals that show high spatial regularity, we demonstrate that the branching of the filament follows specific crystallographic directions of the protein lattice. In correlation with the symmetry of the lattice, filament branching determines the highly regular morphology of the spicules on the macroscale. PMID:29057327

Maximum surgical blood order schedule for pancreatoduodenectomy: a long way from uniform applicability!

PubMed

Barreto, Savio G; Singh, Amanjeet; Perwaiz, Azhar; Singh, Tanveer; Singh, Manish Kumar; Chaudhary, Adarsh

2017-04-01

Unnecessary preoperative ordering of blood and blood products results in wastage of a valuable life-saving resource and poses a significant financial burden on healthcare systems. To determine patient-specific factors associated with intra-operative transfusions, and if intra-operative blood transfusions impact postoperative morbidity. Analysis of consecutive patients undergoing pancreatoduodenectomy (PD) for pancreatic tumors. A total of 384 patients underwent a classical PD with an estimated median blood loss of 200 cc and percentage transfused being 9.6%. Pre-existing hypertension, synchronous vascular resection, end-to-side pancreaticojejunostomy and nodal disease burden significantly associated with the need for intra-operative transfusions. Intra-operative blood transfusion not associated with postoperative morbidity. Optimization of MSBOS protocols for PD is required for more judicious use of blood products.

Predicting Where a Radiation Will Occur: Acoustic and Molecular Surveys Reveal Overlooked Diversity in Indian Ocean Island Crickets (Mogoplistinae: Ornebius).

PubMed

Warren, Ben H; Baudin, Rémy; Franck, Antoine; Hugel, Sylvain; Strasberg, Dominique

2016-01-01

Recent theory suggests that the geographic location of island radiations (local accumulation of species diversity due to cladogenesis) can be predicted based on island area and isolation. Crickets are a suitable group for testing these predictions, as they show both the ability to reach some of the most isolated islands in the world, and to speciate at small spatial scales. Despite substantial song variation between closely related species in many island cricket lineages worldwide, to date this characteristic has not received attention in the western Indian Ocean islands; existing species descriptions are based on morphology alone. Here we use a combination of acoustics and DNA sequencing to survey these islands for Ornebius crickets. We uncover a small but previously unknown radiation in the Mascarenes, constituting a three-fold increase in the Ornebius species diversity of this archipelago (from two to six species). A further new species is detected in the Comoros. Although double archipelago colonisation is the best explanation for species diversity in the Seychelles, in situ cladogenesis is the best explanation for the six species in the Mascarenes and two species of the Comoros. Whether the radiation of Mascarene Ornebius results from intra- or purely inter- island speciation cannot be determined on the basis of the phylogenetic data alone. However, the existence of genetic, song and ecological divergence at the intra-island scale is suggestive of an intra-island speciation scenario in which ecological and mating traits diverge hand-in-hand. Our results suggest that the geographic location of Ornebius radiations is partially but not fully explained by island area and isolation. A notable anomaly is Madagascar, where our surveys are consistent with existing accounts in finding no Ornebius species present. Possible explanations are discussed, invoking ecological differences between species and differences in environmental history between islands.

Predicting Where a Radiation Will Occur: Acoustic and Molecular Surveys Reveal Overlooked Diversity in Indian Ocean Island Crickets (Mogoplistinae: Ornebius)

PubMed Central

Warren, Ben H.; Baudin, Rémy; Franck, Antoine; Hugel, Sylvain; Strasberg, Dominique

2016-01-01

Recent theory suggests that the geographic location of island radiations (local accumulation of species diversity due to cladogenesis) can be predicted based on island area and isolation. Crickets are a suitable group for testing these predictions, as they show both the ability to reach some of the most isolated islands in the world, and to speciate at small spatial scales. Despite substantial song variation between closely related species in many island cricket lineages worldwide, to date this characteristic has not received attention in the western Indian Ocean islands; existing species descriptions are based on morphology alone. Here we use a combination of acoustics and DNA sequencing to survey these islands for Ornebius crickets. We uncover a small but previously unknown radiation in the Mascarenes, constituting a three-fold increase in the Ornebius species diversity of this archipelago (from two to six species). A further new species is detected in the Comoros. Although double archipelago colonisation is the best explanation for species diversity in the Seychelles, in situ cladogenesis is the best explanation for the six species in the Mascarenes and two species of the Comoros. Whether the radiation of Mascarene Ornebius results from intra- or purely inter- island speciation cannot be determined on the basis of the phylogenetic data alone. However, the existence of genetic, song and ecological divergence at the intra-island scale is suggestive of an intra-island speciation scenario in which ecological and mating traits diverge hand-in-hand. Our results suggest that the geographic location of Ornebius radiations is partially but not fully explained by island area and isolation. A notable anomaly is Madagascar, where our surveys are consistent with existing accounts in finding no Ornebius species present. Possible explanations are discussed, invoking ecological differences between species and differences in environmental history between islands. PMID:26871932

High resolution ion microprobe investigation of the δ18O of carbonate cements (Jurassic, Paris Basin, France): New insights and pending questions

NASA Astrophysics Data System (ADS)

Vincent, Benoit; Brigaud, Benjamin; Emmanuel, Laurent; Loreau, Jean-Paul

2017-04-01

The scope of this work is to investigate, at a high resolution, the oxygen isotope composition (δ18Ocarb) of diagenetic products (synsedimentary and burial calcite cements) in shallow-marine carbonates. SIMS (Secondary Ion Mass Spectrometry) microprobe analyses were performed on thin sections from Oxfordian and Kimmeridgian Formations of the eastern Paris Basin and compared to data obtained on the same diagenetic products by conventional mass spectrometry (acid digestion). Hereby obtained, δ18O are similar, but the SIMS dataset displays a larger range of values. The isotopic zonation obtained by SIMS transects through sequences of cements filling pores, reveals an (expected) isotopic depletion from older stage synsedimentary calcites to younger stage blocky calcites and that follows the CL (cathodoluminescence) zonation. SIMS analyses however show that synsedimentary cements precipitated in intra-skeletal pores, have heavier δ18O than their inter-particle counterparts, with an offset of + 4‰V-PDB, despite similar petrographical characteristics. This difference is maintained in the δ18O of the first stages of blocky calcite cements, intra-skeletal blocky calcites showing heavier δ18O than the time equivalent and petrographically identical inter-particle calcites, with an offset of + 5‰V-PDB. These offsets are tentatively explained by the precipitation of cements under non-equilibrium conditions in intra-skeletal pores, where organic matter decay may have played a key role, acting notably on the pH. The occurrence of isolated micro-diagenetic environments, co-existing at the thin section scale, is tentatively proposed as an explanation to these small scale and high amplitude δ18O heterogeneities. These results may question the sampling strategy for future works. Microdrilling may miss the observed range of variation, but averaging the values may not necessarily lead to real misinterpretations if a critical selection of samples is performed, targeting potentially similar micro-diagenetic environments and avoiding potentially specific ones, i.e. closed intra-skeletal pores. These results also definitely underscore the need for additional experiments to improve the reliability of SIMS, in order to develop the use of this very high resolution technique for carbonate diagenesis studies.

[Pylephlebitis: a rare but possible complication of intra-abdominal infections].

PubMed

Pérez-Bru, Susana; Nofuentes-Riera, Carmen; García-Marín, Andrés; Luri-Prieto, Paloma; Morales-Calderón, Miguel; García-García, Salvador

2015-01-01

Pylephlebitis or septic thrombophlebitis of the portal venous system is a rare but serious complication of intra-abdominal infections which drain into the portal venous system. Its diagnosis is based on clinical suspicion and imaging tests, mainly a computed tomography scan, given the lack of specificity of the signs and symptoms. Spread of septic emboli is the major cause of morbidity and mortality. The aim of the study was to analyse patients diagnosed in our hospital. Retrospective descriptive study of patients diagnosed with pylephlebitis in our hospital. Four patients were included, 3 men and one woman. In 3 cases it was acute cholecystitis that led to the diagnosis of pylephlebitis at the same time as the intra-abdominal infection. Emergency surgery was performed in one case, whilst the other 2 were treated conservatively. Blood cultures were performed in all cases, and empirical antibiotic treatment was used. In the only case of acute appendicitis, diagnosis of pylephlebitis was achieved during the study of postoperative fever, with empirical antibiotic treatment also being started. The haematologist was requested to start the required anticoagulation therapy in all cases. Pylephlebitis is a rare complication of intra-abdominal infections that may make lead to a worse outcome. A high level of suspicion is required as well as imaging tests to make an early diagnosis and appropriate treatment. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Research on high power intra-channel crosstalk attack in optical networks

NASA Astrophysics Data System (ADS)

Ren, Shuai; Zhang, Yinfa; Wang, Jingyu; Zhang, Jumei; Rao, Xuejun; Fang, Yuanyuan

2017-02-01

The mechanism of high power intra-channel crosstalk attack is analyzed theoretically and the conclusion that power of attack signal and crosstalk coefficient of optical switch are the main factors for which high power intra-channel have destructive effect on quality of legitimate signals is drawn. Effects of high power intra-channel crosstalk attack on quality of legitimate signals and its capability of attack propagation are investigated quantitatively by building the simulation system in VPI software. The results show that legitimate signals through the first and the second stage optical switch are affected by attack and legitimate signal through the third stage optical switch is almost unaffected by attack when power of original attack signal (OAS) is above 20dB more than that of legitimate signals and crosstalk coefficient of optical switch is -20dB at optical cross connect 1 (OXC1). High power intra-channel crosstalk attack has a certain capability of attack propagation. Attack capability of OAS can be propagated to OXC3 when power of OAS is 27dB more than that of legitimate signals and crosstalk coefficient of optical switch is -20dB. We also find that the secondary attack signal (SAS) does not have capability of attack propagation.

The role of intra-NAPL diffusion on mass transfer from MGP residuals

NASA Astrophysics Data System (ADS)

Shafieiyoun, Saeid; Thomson, Neil R.

2018-06-01

An experimental and computational study was performed to investigate the role of multi-component intra-NAPL diffusion on NAPL-water mass transfer. Molecular weight and the NAPL component concentrations were determined to be the most important parameters affecting intra-NAPL diffusion coefficients. Four NAPLs with different viscosities but the same quantified mass were simulated. For a spherical NAPL body, a combination of NAPL properties and interphase mass transfer rate can result in internal diffusion limitations. When the main intra-NAPL diffusion coefficients are in the range of self-diffusion coefficients (10-5 to 10-6 cm2/s), dissolution is not limited by internal diffusion except for high mass transfer rate coefficients (>180 cm/day). For a complex and relatively high viscous NAPL (>50 g/(cm s)), smaller intra-NAPL diffusion coefficients (<10-8) are expected and even low mass transfer rate coefficients ( 6 cm/day) can result in diffusion-limited dissolution.

A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets

PubMed Central

Jia, Dongyu; Liu, Zhenqiu; Deng, Nan; Tan, Tuan Zea; Huang, Ruby Yun-Ju; Taylor-Harding, Barbie; Cheon, Dong-Joo; Lawrenson, Kate; Wiedemeyer, Wolf R.; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra

2016-01-01

Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs. Our analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs. Using COL11A1 as a ‘seed’, we identified co-expressed genes in 13 types of primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular signature of activated CAFs is conserved in epithelial cancers regardless of organ site and transforming events within cancer cells, suggesting that targeting fibroblast activation should be effective in multiple cancers. We prioritized several potential pan-cancer therapeutic targets that are likely to have high specificity for activated CAFs and minimal toxicity in normal tissues. PMID:27609069

Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis.

PubMed

Wang, Lina; Tu, Zhaowei; Liu, Chao; Liu, Hongbin; Kaldis, Philipp; Chen, Zijiang; Li, Wei

2018-06-01

Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.

Molecular mapping of QTLs for plant type and earliness traits in pigeonpea (Cajanus cajan L. Millsp.)

PubMed Central

2012-01-01

Background Pigeonpea is an important grain legume of the semi-arid tropics and sub-tropical regions where it plays a crucial role in the food and nutritional security of the people. The average productivity of pigeonpea has remained very low and stagnant for over five decades due to lack of genomic information and intensive breeding efforts. Previous SSR-based linkage maps of pigeonpea used inter-specific crosses due to low inter-varietal polymorphism. Here our aim was to construct a high density intra-specific linkage map using genic-SNP markers for mapping of major quantitative trait loci (QTLs) for key agronomic traits, including plant height, number of primary and secondary branches, number of pods, days to flowering and days to maturity in pigeonpea. Results A population of 186 F2:3 lines derived from an intra-specific cross between inbred lines ‘Pusa Dwarf’ and ‘HDM04-1’ was used to construct a dense molecular linkage map of 296 genic SNP and SSR markers covering a total adjusted map length of 1520.22 cM for the 11 chromosomes of the pigeonpea genome. This is the first dense intra-specific linkage map of pigeonpea with the highest genome length coverage. Phenotypic data from the F2:3 families were used to identify thirteen QTLs for the six agronomic traits. The proportion of phenotypic variance explained by the individual QTLs ranged from 3.18% to 51.4%. Ten of these QTLs were clustered in just two genomic regions, indicating pleiotropic effects or close genetic linkage. In addition to the main effects, significant epistatic interaction effects were detected between the QTLs for number of pods per plant. Conclusions A large amount of information on transcript sequences, SSR markers and draft genome sequence is now available for pigeonpea. However, there is need to develop high density linkage maps and identify genes/QTLs for important agronomic traits for practical breeding applications. This is the first report on identification of QTLs for plant type and maturity traits in pigeonpea. The QTLs identified in this study provide a strong foundation for further validation and fine mapping for utilization in the pigeonpea improvement. PMID:23043321

Empowered women, social networks and the contribution of qualitative research: broadening our understanding of underlying causes for food and nutrition insecurity.

PubMed

Lemke, S; Vorster, H H; van Rensburg, N S Jansen; Ziche, J

2003-12-01

To investigate underlying causes for food and nutrition insecurity in black South African households and to gain understanding of the factors contributing to better nutrition security, with emphasis on household organisation, gender and intra-household dynamics and social networks. Within a larger cross-sectional survey that investigated the impact of urbanisation on the health of black South Africans, 166 people, mostly women, were interviewed on household food security. Methods used were structured face-to-face interviews, in-depth interviews, observation, interviews with key informants and a sociodemographic questionnaire. Information was collected from 1998 to 2000 in 15 rural and urban areas of the North West Province, South Africa. Three-quarters of households in this sample are chronically food-insecure. Families are disrupted, due to migrant work, poverty and increasing societal violence, and half of households are female-headed. Certain categories of female-headed households and households based on partnership relationships, despite more limited resources, achieve a better or an equal economic status and better nutrition security than those households led by men, with the latter often being considered an economic liability. The reliance on and fostering of social ties and networks appear to be of central significance. Gender and intra-household relations, as well as social networks and income from informal sector activities, are often not uncovered by conventional statistical methods. Qualitative research can reveal the unexpected and furthermore empowers people, as their voices are heard.

Inter- and intra-observer reliability of clinical movement-control tests for marines

PubMed Central

2012-01-01

Background Musculoskeletal disorders particularly in the back and lower extremities are common among marines. Here, movement-control tests are considered clinically useful for screening and follow-up evaluation. However, few studies have addressed the reliability of clinical tests, and no such published data exists for marines. The present aim was therefore to determine the inter- and intra-observer reliability of clinically convenient tests emphasizing movement control of the back and hip among marines. A secondary aim was to investigate the sensitivity and specificity of these clinical tests for discriminating musculoskeletal pain disorders in this group of military personnel. Methods This inter- and intra-observer reliability study used a test-retest approach with six standardized clinical tests focusing on movement control for back and hip. Thirty-three marines (age 28.7 yrs, SD 5.9) on active duty volunteered and were recruited. They followed an in-vivo observation test procedure that covered both low- and high-load (threshold) tasks relevant for marines on operational duty. Two independent observers simultaneously rated performance as “correct” or “incorrect” following a standardized assessment protocol. Re-testing followed 7–10 days thereafter. Reliability was analysed using kappa (κ) coefficients, while discriminative power of the best-fitting tests for back- and lower-extremity pain was assessed using a multiple-variable regression model. Results Inter-observer reliability for the six tests was moderate to almost perfect with κ-coefficients ranging between 0.56-0.95. Three tests reached almost perfect inter-observer reliability with mean κ-coefficients > 0.81. However, intra-observer reliability was fair-to-moderate with mean κ-coefficients between 0.22-0.58. Three tests achieved moderate intra-observer reliability with κ-coefficients > 0.41. Combinations of one low- and one high-threshold test best discriminated prior back pain, but results were inconsistent for lower-extremity pain. Conclusions Our results suggest that clinical tests of movement control of back and hip are reliable for use in screening protocols using several observers with marines. However, test-retest reproducibility was less accurate, which should be considered in follow-up evaluations. The results also indicate that combinations of low- and high-threshold tests have discriminative validity for prior back pain, but were inconclusive for lower-extremity pain. PMID:23273285

Technology transfer in the NASA Ames Advanced Life Support Division

NASA Technical Reports Server (NTRS)

Connell, Kathleen; Schlater, Nelson; Bilardo, Vincent; Masson, Paul

1992-01-01

This paper summarizes a representative set of technology transfer activities which are currently underway in the Advanced Life Support Division of the Ames Research Center. Five specific NASA-funded research or technology development projects are synopsized that are resulting in transfer of technology in one or more of four main 'arenas:' (1) intra-NASA, (2) intra-Federal, (3) NASA - aerospace industry, and (4) aerospace industry - broader economy. Each project is summarized as a case history, specific issues are identified, and recommendations are formulated based on the lessons learned as a result of each project.

An exploratory comparison of name generator content: Data from rural India

PubMed Central

Shakya, Holly B.; Christakis, Nicholas A.; Fowler, James H.

2017-01-01

Since the 1970s sociologists have explored the best means for measuring social networks, although few name generator analyses have used sociocentric data or data from developing countries, partly because sociocentric studies in developing countries have been scant. Here, we analyze 12 different name generators used in a sociocentric network study conducted in 75 villages in rural Karnataka, India. Having unusual sociocentric data from a non-Western context allowed us to extend previous name generator research through the unique analyses of network structural measures, an extensive consideration of homophily, and investigation of status difference between egos and alters. We found that domestic interaction questions generated networks that were highly clustered and highly centralized. Similarity between respondents and their nominated contacts was strongest for gender, caste, and religion. We also found that domestic interaction name generators yielded the most homogeneous ties, while advice questions yielded the most heterogeneous. Participants were generally more likely to nominate those of higher social status, although certain questions, such as who participants talk to uncovered more egalitarian relationships, while other name generators elicited the names of social contacts distinctly higher or lower in status than the respondent. Some questions also seemed to uncover networks that were specific to the cultural context, suggesting that network researchers should balance local relevance with global generalizability when choosing name generators. PMID:28845086

Highly sensitive and quantitative detection of rare pathogens through agarose droplet microfluidic emulsion PCR at the single-cell level.

PubMed

Zhu, Zhi; Zhang, Wenhua; Leng, Xuefei; Zhang, Mingxia; Guan, Zhichao; Lu, Jiangquan; Yang, Chaoyong James

2012-10-21

Genetic alternations can serve as highly specific biomarkers to distinguish fatal bacteria or cancer cells from their normal counterparts. However, these mutations normally exist in very rare amount in the presence of a large excess of non-mutated analogs. Taking the notorious pathogen E. coli O157:H7 as the target analyte, we have developed an agarose droplet-based microfluidic ePCR method for highly sensitive, specific and quantitative detection of rare pathogens in the high background of normal bacteria. Massively parallel singleplex and multiplex PCR at the single-cell level in agarose droplets have been successfully established. Moreover, we challenged the system with rare pathogen detection and realized the sensitive and quantitative analysis of a single E. coli O157:H7 cell in the high background of 100,000 excess normal K12 cells. For the first time, we demonstrated rare pathogen detection through agarose droplet microfluidic ePCR. Such a multiplex single-cell agarose droplet amplification method enables ultra-high throughput and multi-parameter genetic analysis of large population of cells at the single-cell level to uncover the stochastic variations in biological systems.

Intra-arterial Methylprednisolone Infusion in Treatment-Resistant Graft-Versus-Host Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weintraub, Joshua L., E-mail: Joshua.Weintraub@mssm.edu; Belanger, Adam R.; Sung, Chris C.

Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality. There is no generally accepted secondary therapy for acute GVHD. Although few data on localized therapy for GVHD have been published, intra-arterial injection of high-dose corticosteroids may be a viable option. We treated 11 patients with steroid-resistant GVHD using a single administration of intra-arterial high-dose methylprednisolone. Three patients (27%) died periprocedurally. Four patients (36%) had a partial response tomore » intra-arterial treatment and were discharged on total parenteral nutrition and oral medication. Four patients (36%) had a complete response and were discharged on oral diet and oral medication. No immediate treatment or procedure-related complications were noted. Twenty-seven percent of patients survived long-term. Our preliminary results suggest that regional intra-arterial treatment of steroid-resistant GVHD is a safe and potentially viable secondary therapy in primary treatment-resistant GVHD.« less

The association between Chance fractures and intra-abdominal injuries revisited: a multicenter review.

PubMed

Tyroch, Alan H; McGuire, Emmett L; McLean, Susan F; Kozar, Rosemary A; Gates, Keith A; Kaups, Krista L; Cook, Charles; Cowgill, Sarah M; Griswold, John A; Sue, Larry A; Craun, Michael L; Price, Jan

2005-05-01

The association between Chance fractures and intra-abdominal injuries is reported to be as high as 89 per cent. Because prior studies were small series or case reports, we conducted a multicenter review to learn the true association between Chance fractures and intra-abdominal injuries as well as diagnostic trends. Trauma registry data, medical records, and radiology reports from 7 trauma centers were used to characterize 79 trauma patients with Chance fractures. Initial methods of abdominal assessment were computed tomography (CT) scan (79%), clinical examination (16%), and diagnostic peritoneal lavage (DPL) (5%). Twenty-six (33%) patients had intraabdominal injuries of which hollow viscus injuries predominated (22%). Twenty patients (25%) underwent laparotomy. The presence of an abdominal wall contusion and automobile restraint use were highly predictive of intra-abdominal injury and the need for laparotomy. The association between a Chance fracture and intra-abdominal injury is not as high as previously reported. CT scan has become the primary modality to assess the abdominal cavity of patients with Chance fractures, whereas the role of DPL has diminished.

Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

PubMed

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2009-01-01

In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/-3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan-Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. According to evidence obtained from the routine documentation of 778 renal transplantations, ATG-F induction therapy administered as a part of immunosuppressive therapy significantly improves patient survival and reduces the risk of graft failure and transplant rejections.

Local network assessment

NASA Astrophysics Data System (ADS)

Glen, D. V.

1985-04-01

Local networks, related standards activities of the Institute of Electrical and Electronics Engineers the American National Standards Institute and other elements are presented. These elements include: (1) technology choices such as topology, transmission media, and access protocols; (2) descriptions of standards for the 802 local area networks (LAN's); high speed local networks (HSLN's) and military specification local networks; and (3) intra- and internetworking using bridges and gateways with protocols Interconnection (OSI) reference model. The convergence of LAN/PBX technology is also described.

Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

PubMed Central

Vaiman, Daniel; Mondon, Françoise; Garcès-Duran, Alexandra; Mignot, Thérèse-Marie; Robert, Brigitte; Rebourcet, Régis; Jammes, Hélène; Chelbi, Sonia T; Quetin, Frédérique; Marceau, Geoffrey; Sapin, Vincent; Piumi, François; Danan, Jean-Louis; Rigourd, Virginie; Carbonne, Bruno; Ferré, Françoise

2005-01-01

Background As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes. Results Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR). Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the maintenance of such clusters is requested for achieving a normal placental physiology in eutherian mammals. PMID:16129025

Interactive relationship between the mechanical properties of food and the human response during the first bite.

PubMed

Dan, Haruka; Kohyama, Kaoru

2007-05-01

Biting is an action that results from interplay between food properties and the masticatory system. The mechanical factors of food that cause biting adaptation and the recursive effects of modified biting on the mechanical phenomena of food are largely unknown. We examined the complex interaction between the bite system and the mechanical properties. Nine subjects were each given a cheese sample and instructed to bite it once with their molar teeth. An intra-oral bite force-time profile was measured using a tactile pressure-measurement system with a sheet sensor inserted between the molars. Time, force, and impulse for the first peak were specified as intra-oral parameters of the sample fracture. Mechanical properties of the samples were also examined using a universal testing machine at various test speeds. Besides fracture parameters, initial slope was also determined as a mechanical property possibly sensed shortly after bite onset. The bite profile was then examined based on the mechanical parameters. Sample-specific bite velocities were identified as characteristic responses of a human bite. A negative correlation was found between bite velocity and initial slope of the sample, suggesting that the initial slope is the mechanical factor that modifies the consequent bite velocity. The sample-specific bite velocity had recursive effects on the following fracture event, such that a slow velocity induced a low bite force and high impulse for the intra-oral fracture event. We demonstrated that examination of the physiological and mechanical factors during the first bite can provide valuable information about the food-oral interaction.

Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut Microbiota

PubMed Central

Ellegaard, Kirsten M.; Engel, Philipp

2016-01-01

Interactions with microbes affect many aspects of animal biology, including immune system development, nutrition and health. In vertebrates, the gut microbiota is dominated by a small subset of phyla, but the species composition within these phyla is typically not conserved. Moreover, several recent studies have shown that bacterial species in the gut are composed of a multitude of strains, which frequently co-exist in their host, and may be host-specific. However, since the study of intra-species diversity is challenging, particularly in the setting of complex, host-associated microbial communities, our current understanding of the distribution, evolution and functional relevance of intra-species diversity in the gut is scarce. In order to unravel how genomic diversity translates into phenotypic diversity, community analyses going beyond 16S rRNA profiling, in combination with experimental approaches, are needed. Recently, the honeybee has emerged as a promising model for studying gut bacterial communities, particularly in terms of strain-level diversity. Unlike most other invertebrates, the honeybee gut is colonized by a remarkably consistent and specific core microbiota, which is dominated by only eight bacterial species. As for the vertebrate gut microbiota, these species are composed of highly diverse strains suggesting that similar evolutionary forces shape gut community structures in vertebrates and social insects. In this review, we outline current knowledge on the evolution and functional relevance of strain diversity within the gut microbiota, including recent insights gained from mammals and other animals such as the honeybee. We discuss methodological approaches and propose possible future avenues for studying strain diversity in complex bacterial communities. PMID:27708630

Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut Microbiota.

PubMed

Ellegaard, Kirsten M; Engel, Philipp

2016-01-01

Interactions with microbes affect many aspects of animal biology, including immune system development, nutrition and health. In vertebrates, the gut microbiota is dominated by a small subset of phyla, but the species composition within these phyla is typically not conserved. Moreover, several recent studies have shown that bacterial species in the gut are composed of a multitude of strains, which frequently co-exist in their host, and may be host-specific. However, since the study of intra-species diversity is challenging, particularly in the setting of complex, host-associated microbial communities, our current understanding of the distribution, evolution and functional relevance of intra-species diversity in the gut is scarce. In order to unravel how genomic diversity translates into phenotypic diversity, community analyses going beyond 16S rRNA profiling, in combination with experimental approaches, are needed. Recently, the honeybee has emerged as a promising model for studying gut bacterial communities, particularly in terms of strain-level diversity. Unlike most other invertebrates, the honeybee gut is colonized by a remarkably consistent and specific core microbiota, which is dominated by only eight bacterial species. As for the vertebrate gut microbiota, these species are composed of highly diverse strains suggesting that similar evolutionary forces shape gut community structures in vertebrates and social insects. In this review, we outline current knowledge on the evolution and functional relevance of strain diversity within the gut microbiota, including recent insights gained from mammals and other animals such as the honeybee. We discuss methodological approaches and propose possible future avenues for studying strain diversity in complex bacterial communities.

Testing of tactical performance in youth elite soccer.

PubMed

Memmert, Daniel

2010-01-01

This is a twofold study with the goals of evaluating tactical oriented game test situations for 12-13-year old highly-talented soccer players and to analyze dynamic, intra-individual developments of the players. A cross-sectional design was carried in study 1, using game test situations to measure specific tactics and creative performance for 195 expert players. The results from five evaluation criteria show that both diagnostic instruments can be used for recording football-specific creativity and game intelligence in talented young players. They produced tactical indicators that can be described as objective and valid, exhibit a sufficient degree of differentiation and are easy to record. Study 2 uses a longitudinal design to present a dynamic performance diagnostic tool for analyzing intra-individual improvements of German Soccer Foundation talents according to football-specific creativity and game intelligence. The results with respect to divergent tactical thinking clearly show that very different change processes were observed in the German Soccer Foundation players. Finally, the practical implications for the training process are discussed on the basis of both studies. Key pointsWith game test situations it is possible to assess tactical performance as game intelligence and creativity objective, valid, with a sufficient degree of differentiation, and economically.The results with respect to game intelligence and creativity show that very different change processes were observed in the German Soccer Foundation players dependend on the bases (trainers).Current literature on tactics for school sports as well as for children's, youth and high performance soccer at the club level should place much more emphasis on individual and group-tactical requirements in soccer.

Wing Shape as an Indicator of Larval Rearing Conditions for Aedes albopictus and Ae. aegypti (Diptera: Culicidae)

PubMed Central

Stephens, C. R.; Juliano, S. A.

2012-01-01

Estimating a mosquito’s vector competence, or likelihood of transmitting disease, if it takes an infectious blood meal, is an important aspect of predicting when and where outbreaks of infectious diseases will occur. Vector competence can be affected by rearing temperature and inter- and intraspecific competition experienced by the individual mosquito during its larval development. This research investigates whether a new morphological indicator of larval rearing conditions, wing shape, can be used to distinguish reliably temperature and competitive conditions experienced during larval stages. Aedes albopictus and Aedes aegypti larvae were reared in low intra-specific, high intra-specific, or high inter-specific competition treatments at either 22°C or 32°C. The right wing of each dried female was removed and photographed. Nineteen landmarks and twenty semilandmarks were digitized on each wing. Shape variables were calculated using geometric morphometric software. Canonical variate analysis, randomization multivariate analysis of variance, and visualization of landmark movement using deformation grids provided evidence that although semilandmark position was significantly affected by larval competition and temperature for both species, the differences in position did not translate into differences in wing shape, as shown in deformation grids. Two classification procedures yielded success rates of 26–49%. Accounting for wing size produced no increase in classification success. There appeared to be a significant relationship between shape and size. These results, particularly the low success rate of classification based on wing shape, show that shape is unlikely to be a reliable indicator of larval rearing competition and temperature conditions for Aedes albopictus and Aedes aegypti. PMID:22897054

Testing of Tactical Performance in Youth Elite Soccer

PubMed Central

2010-01-01

This is a twofold study with the goals of evaluating tactical oriented game test situations for 12-13-year old highly-talented soccer players and to analyze dynamic, intra-individual developments of the players. A cross-sectional design was carried in study 1, using game test situations to measure specific tactics and creative performance for 195 expert players. The results from five evaluation criteria show that both diagnostic instruments can be used for recording football-specific creativity and game intelligence in talented young players. They produced tactical indicators that can be described as objective and valid, exhibit a sufficient degree of differentiation and are easy to record. Study 2 uses a longitudinal design to present a dynamic performance diagnostic tool for analyzing intra-individual improvements of German Soccer Foundation talents according to football-specific creativity and game intelligence. The results with respect to divergent tactical thinking clearly show that very different change processes were observed in the German Soccer Foundation players. Finally, the practical implications for the training process are discussed on the basis of both studies. Key points With game test situations it is possible to assess tactical performance as game intelligence and creativity objective, valid, with a sufficient degree of differentiation, and economically. The results with respect to game intelligence and creativity show that very different change processes were observed in the German Soccer Foundation players dependend on the bases (trainers). Current literature on tactics for school sports as well as for children’s, youth and high performance soccer at the club level should place much more emphasis on individual and group-tactical requirements in soccer. PMID:24149686

Does bone debris in anterior cruciate ligament reconstruction really matter? A cohort study of a protocol for bone debris debridement

PubMed Central

Imam, Mohamed A.; Abdelkafy, Ashraf; Dinah, Feroz; Adhikari, Ajeya

2015-01-01

Background: The purpose of the current study was to determine whether a systematic five-step protocol for debridement and evacuation of bone debris during anterior cruciate ligament reconstruction (ACLR) reduces the presence of such debris on post-operative radiographs. Methods: A five-step protocol for removal of bone debris during arthroscopic assisted ACLR was designed. It was applied to 60 patients undergoing ACLR (Group 1), and high-quality digital radiographs were taken post-operatively in each case to assess for the presence of intra-articular bone debris. A control group of 60 consecutive patients in whom no specific bone debris protocol was applied (Group 2) and their post-operative radiographs were also checked for the presence of intra-articular bone debris. Results: In Group 1, only 15% of post-operative radiographs showed residual bone debris, compared to 69% in Group 2 (p < 0.001). Conclusion: A five-step systematic protocol for bone debris removal during arthroscopic assisted ACLR resulted in a significant decrease in residual bone debris seen on high-quality post-operative radiographs. PMID:27163060

Commentary.

ERIC Educational Resources Information Center

Molenaar, Peter C. M.; van der Maas, Han L. J.

1994-01-01

Comments on Lewis's ideas about reconciling stage and specificity in neo-Piagetian theory in this issue. Focuses on whether general stages, domain specificity, and individual diversity are compatible from a nonlinear, dynamic perspective. Suggests that, by using catastrophe theory, intra- and interindividual diversity and domain specificity can be…

Intra-abdominal pedicled rectus abdominis muscle flap for treatment of high-output enterocutaneous fistulae: case reports and review of literature.

PubMed

Carey, Joseph N; Sheckter, Clifford C; Watt, Andrew J; Lee, Gordon K

2013-08-01

Despite advances in nutritional supplementation, sepsis management, percutaneous drainage and surgical technique, enterocutaneous fistulae remain a considerable source of morbidity and mortality. Use of adjunctive modalities including negative pressure wound therapy and fibrin glue have been shown to improve the rapidity of fistula closure; however, the overall rate of closure remains poor. The challenge of managing chronic, high-output proximal enterocutaneous fistulae can be successfully achieved with appropriate medical management and intra-abdominal placement of pedicled rectus abdominis muscle flaps. We report two cases of recalcitrant high output enterocutaneous fistulae that were treated successfully with pedicled intra-abdominal rectus muscle flaps. Indications for pedicled intra-abdominal rectus muscle flaps include persistent patency despite a reasonable trial of non-operative intervention, failure of traditional operative interventions (serosal patch, Graham patch), and persistent electrolyte and nutritional abnormalities in the setting of a high-output fistula. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Maternal androgens in avian brood parasites and their hosts: responses to parasitism and competition?

USGS Publications Warehouse

Hahn, Caldwell; Wingfield, John C.; Fox, David M.; Walker, Brian G.; Thomley, Jill E

2017-01-01

In the coevolutionary dynamic of avian brood parasites and their hosts, maternal (or transgenerational) effects have rarely been investigated. We examined the potential role of elevated yolk testosterone in eggs of the principal brood parasite in North America, the brown-headed cowbird, and three of its frequent host species. Elevated maternal androgens in eggs are a common maternal effect observed in many avian species when breeding conditions are unfavorable. These steroids accelerate embryo development, shorten incubation period, increase nestling growth rate, and enhance begging vigor, all traits that can increase the survival of offspring. We hypothesized that elevated maternal androgens in host eggs are a defense against brood parasitism. Our second hypothesis was that elevated maternal androgens in cowbird eggs are a defense against intra-specific competition. For host species, we found that elevated yolk testosterone was correlated with parasitized nests of small species, those whose nest success is most reduced by cowbird parasitism. For cowbirds, we found that elevated yolk testosterone was correlated with eggs in multiply-parasitized nests, which indicate intra-specific competition for nests due to high cowbird density. We propose experimental work to further examine the use of maternal effects by cowbirds and their hosts.

The use of MALDI-TOF ICMS as an alternative tool for Trichophyton rubrum identification and typing.

PubMed

Pereira, Leonel; Dias, Nicolina; Santos, Cledir; Lima, Nelson

2014-01-01

In this study, the potential of matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry (MALDI-TOF ICMS) was investigated for the identification of clinical isolates. The isolates were analyzed at the species and strain level. Spectral identification by MALDI-TOF ICMS was performed for all strains, and compared with the results of sequencing of the internal transcribed spacers (ITS1 and ITS2), and the 5.8S rDNA region. PCR fingerprinting analysis using primers M13, (GACA)4, and (AC)10 was performed in order to assess the intra-specific variability of Trichophyton rubrum strains. The identification of strains at species level by MALDI-TOF ICMS was in agreement with the previously performed morphological and biochemical analysis. Sequence data confirmed spectral mass identification at species level. Intra-specific variability was assessed. Within the T. rubrum cluster, strains were distributed into smaller highly related sub-groups with a similarity values above 85%. MALDI-TOF ICMS was shown to be a rapid, low-cost and accurate alternative tool for the identification and strain typing of T. rubrum. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Reliability of externally fixed dynamometry hamstring strength testing in elite youth football players.

PubMed

Wollin, Martin; Purdam, Craig; Drew, Michael K

2016-01-01

To investigate inter and intra-tester reliability of an externally fixed dynamometry unilateral hamstring strength test, in the elite sports setting. Reliability study. Sixteen, injury-free, elite male youth football players (age=16.81±0.54 years, height=180.22±5.29cm, weight 73.88±6.54kg, BMI=22.57±1.42) gave written informed consent. Unilateral maximum isometric peak hamstring force was evaluated by externally fixed dynamometry for inter-tester, intra-day and intra-tester, inter-week reliability. The test position was standardised to correlate with the terminal swing phase of the gait running cycle. Inter and intra-tester values demonstrated good to high levels of reliability. The intra-class coefficient (ICC) for inter-tester, intra-day reliability was 0.87 (95% CI=0.75-0.93) with standard error of measure percentage (SEM%) 4.7 and minimal detectable change percentage (MDC%) 12.9. Intra-tester, inter-week reliability results were ICC 0.86 (95% CI, 0.74-0.93), SEM% 5.0 and MDC% 14.0. This study demonstrates good to high inter and intra-tester reliability of isometric externally fixed dynamometry unilateral hamstring strength testing in the regular elite sport setting involving elite male youth football players. The intra-class coefficient in association with the low standard error of measure and minimal detectable change percentages suggest that this procedure is appropriate for clinical and academic use as well as monitoring hamstring strength in the elite sport setting. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The developmental proteome of Drosophila melanogaster

PubMed Central

Casas-Vila, Nuria; Bluhm, Alina; Sayols, Sergi; Dinges, Nadja; Dejung, Mario; Altenhein, Tina; Kappei, Dennis; Altenhein, Benjamin; Roignant, Jean-Yves; Butter, Falk

2017-01-01

Drosophila melanogaster is a widely used genetic model organism in developmental biology. While this model organism has been intensively studied at the RNA level, a comprehensive proteomic study covering the complete life cycle is still missing. Here, we apply label-free quantitative proteomics to explore proteome remodeling across Drosophila’s life cycle, resulting in 7952 proteins, and provide a high temporal-resolved embryogenesis proteome of 5458 proteins. Our proteome data enabled us to monitor isoform-specific expression of 34 genes during development, to identify the pseudogene Cyp9f3Ψ as a protein-coding gene, and to obtain evidence of 268 small proteins. Moreover, the comparison with available transcriptomic data uncovered examples of poor correlation between mRNA and protein, underscoring the importance of proteomics to study developmental progression. Data integration of our embryogenesis proteome with tissue-specific data revealed spatial and temporal information for further functional studies of yet uncharacterized proteins. Overall, our high resolution proteomes provide a powerful resource and can be explored in detail in our interactive web interface. PMID:28381612

Rich structure in the correlation matrix spectra in non-equilibrium steady states

NASA Astrophysics Data System (ADS)

Biswas, Soham; Leyvraz, Francois; Monroy Castillero, Paulino; Seligman, Thomas H.

2017-01-01

It has been shown that, if a model displays long-range (power-law) spatial correlations, its equal-time correlation matrix will also have a power law tail in the distribution of its high-lying eigenvalues. The purpose of this paper is to show that the converse is generally incorrect: a power-law tail in the high-lying eigenvalues of the correlation matrix may exist even in the absence of equal-time power law correlations in the initial model. We may therefore view the study of the eigenvalue distribution of the correlation matrix as a more powerful tool than the study of spatial Correlations, one which may in fact uncover structure, that would otherwise not be apparent. Specifically, we show that in the Totally Asymmetric Simple Exclusion Process, whereas there are no clearly visible correlations in the steady state, the eigenvalues of its correlation matrix exhibit a rich structure which we describe in detail.

Rich structure in the correlation matrix spectra in non-equilibrium steady states.

PubMed

Biswas, Soham; Leyvraz, Francois; Monroy Castillero, Paulino; Seligman, Thomas H

2017-01-17

It has been shown that, if a model displays long-range (power-law) spatial correlations, its equal-time correlation matrix will also have a power law tail in the distribution of its high-lying eigenvalues. The purpose of this paper is to show that the converse is generally incorrect: a power-law tail in the high-lying eigenvalues of the correlation matrix may exist even in the absence of equal-time power law correlations in the initial model. We may therefore view the study of the eigenvalue distribution of the correlation matrix as a more powerful tool than the study of spatial Correlations, one which may in fact uncover structure, that would otherwise not be apparent. Specifically, we show that in the Totally Asymmetric Simple Exclusion Process, whereas there are no clearly visible correlations in the steady state, the eigenvalues of its correlation matrix exhibit a rich structure which we describe in detail.

High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1.

PubMed

Maya Miles, Douglas; Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian; Geli, Vincent

2018-03-27

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1 WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28 CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. © 2018, Maya Miles et al.

High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1

PubMed Central

Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian

2018-01-01

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. PMID:29580382

Does cervical lordosis change after spinal manipulation for non-specific neck pain? A prospective cohort study.

PubMed

Shilton, Michael; Branney, Jonathan; de Vries, Bas Penning; Breen, Alan C

2015-01-01

The association between cervical lordosis (sagittal alignment) and neck pain is controversial. Further, it is unclear whether spinal manipulative therapy can change cervical lordosis. This study aimed to determine whether cervical lordosis changes after a course of spinal manipulation for non-specific neck pain. Posterior tangents of C2 and C6 were drawn on the lateral cervical fluoroscopic images of 29 patients with subacute/chronic non-specific neck pain and 30 healthy volunteers matched for age and gender, recruited August 2011 to April 2013. The resultant angle was measured using 'Image J' digital geometric software. The intra-observer repeatability (measurement error and reliability) and intra-subject repeatability (minimum detectable change (MDC) over 4 weeks) were determined in healthy volunteers. A comparison of cervical lordosis was made between patients and healthy volunteers at baseline. Change in lordosis between baseline and 4-week follow-up was determined in patients receiving spinal manipulation. Intra-observer measurement error for cervical lordosis was acceptable (SEM 3.6°) and reliability was substantial ICC 0.98, 95 % CI 0.962-0991). The intra-subject MDC however, was large (13.5°). There was no significant difference between lordotic angles in patients and healthy volunteers (p = 0.16). The mean cervical lordotic increase over 4 weeks in patients was 2.1° (9.2) which was not significant (p = 0.12). This study found no difference in cervical lordosis (sagittal alignment) between patients with mild non-specific neck pain and matched healthy volunteers. Furthermore, there was no significant change in cervical lordosis in patients after 4 weeks of cervical spinal manipulation.

Genetic variability and molecular identification of Brazilian Biomphalaria species (Mollusca: Planorbidae).

PubMed

Carvalho, S; Caldeira, R L; Simpson, A J; Vidigal, T H

2001-01-01

Freshwater snails belonging to the genus Biomphalaria are intermediate hosts of the trematode Schistosoma mansoni in the Neotropical region and Africa. In Brazil, one subspecies and ten species of Biomphalaria have been identified: B. glabrata, B. tenagophila, B. straminea, B. occidentalis, B. peregrina, B. kuhniana, B. schrammi, B. amazonica, B. oligoza, B. intermedia and B.t. guaibensis. However, only the first three species are found naturally infected with S. mansoni. The classical identification of these planorbids is based on comparison of morphological characteristics of the shell and male and female reproductive organs, which is greatly complicated by the extensive intra-specific variation. Several molecular techniques have been used in studies on the identification, genetic structure as well as phylogenetic relationships between these groups of organisms. Using the randomly amplified polymorphic DNAs (RAPD) analysis we demonstrated that B. glabrata exhibits a remarkable degree of intra-specific polymorphism. Thus, the genetics of the snail host may be more important to the epidemiology of schistosomiasis than those of the parasite itself. Using the simple sequence repeat anchored polymerase chain reaction (SSR-PCR) in intra-populational and intra-specific studies we have demonstrated that snails belonging to the B. straminea complex (B. straminea, B. kuhniana and B. intermedia) clearly presented higher heterogeneity. Using the low stringency polymerase chain reaction (LS-PCR) technique we were able to separate B. glabrata from B. tenagophila and B. tenagophila from B. occidentalis. To separate all Brazilian Biomphalaria species we used the restriction fragment length polymorphism (PCR-RFLP) of the internal transcribed spacer region (ITS) of the DNA gene. The method also proved to be efficient for the specific identification of DNA extracted from snail eggs. Recently we have sequenced the ITS2 region for phylogenetic studies of all Biomphalaria snails from Brazil.

Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

PubMed

Widhalm, Georg

2014-01-01

Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that optimizes the patient management and improves the patient prognosis by maximizing the extent of tumor resection and enabling a precise histopathological tumor diagnosis.

Microbial Lifestyle and Genome Signatures

PubMed Central

Dutta, Chitra; Paul, Sandip

2012-01-01

Microbes are known for their unique ability to adapt to varying lifestyle and environment, even to the extreme or adverse ones. The genomic architecture of a microbe may bear the signatures not only of its phylogenetic position, but also of the kind of lifestyle to which it is adapted. The present review aims to provide an account of the specific genome signatures observed in microbes acclimatized to distinct lifestyles or ecological niches. Niche-specific signatures identified at different levels of microbial genome organization like base composition, GC-skew, purine-pyrimidine ratio, dinucleotide abundance, codon bias, oligonucleotide composition etc. have been discussed. Among the specific cases highlighted in the review are the phenomena of genome shrinkage in obligatory host-restricted microbes, genome expansion in strictly intra-amoebal pathogens, strand-specific codon usage in intracellular species, acquisition of genome islands in pathogenic or symbiotic organisms, discriminatory genomic traits of marine microbes with distinct trophic strategies, and conspicuous sequence features of certain extremophiles like those adapted to high temperature or high salinity. PMID:23024607

Teacher Leadership: Federal Policy Recommendations

ERIC Educational Resources Information Center

Gran, Jackie; Young, Margaret; Broin, Alexandra

2015-01-01

This policy brief was developed specifically for federal policymakers, and builds upon the policy recommendations included in "Leading from Every Seat: Empowering Principals to Cultivate Teacher Leadership for School Improvement." The recommendations in this report include the following: (1) Uncover New Leadership Ideas and Seed…

Ecological Inventory Exemplars.

ERIC Educational Resources Information Center

Sobsey, Dick, Ed.

The document contains 20 ecological inventories (developed at the University of Minnesota and the University of Alberta) to help severely disabled students learn functional living skills. The ecological approach is designed to uncover the functions critical for success in specific environments which the student frequently encounters. Matching the…

Household Energy Conservation from Elementary Science Teacher Candidates' Perspective

ERIC Educational Resources Information Center

Sahin, Elvan

2016-01-01

This study was conducted to understand the complex nature of gender differentiation in household energy consumption, and uncover the factors characterizing Turkish female university students' contribution on household energy conservation. Specifically, the study hypothesized that energy-related attributes would significantly differentiate female…

GIANT API: an application programming interface for functional genomics.

PubMed

Roberts, Andrew M; Wong, Aaron K; Fisk, Ian; Troyanskaya, Olga G

2016-07-08

GIANT API provides biomedical researchers programmatic access to tissue-specific and global networks in humans and model organisms, and associated tools, which includes functional re-prioritization of existing genome-wide association study (GWAS) data. Using tissue-specific interaction networks, researchers are able to predict relationships between genes specific to a tissue or cell lineage, identify the changing roles of genes across tissues and uncover disease-gene associations. Additionally, GIANT API enables computational tools like NetWAS, which leverages tissue-specific networks for re-prioritization of GWAS results. The web services covered by the API include 144 tissue-specific functional gene networks in human, global functional networks for human and six common model organisms and the NetWAS method. GIANT API conforms to the REST architecture, which makes it stateless, cacheable and highly scalable. It can be used by a diverse range of clients including web browsers, command terminals, programming languages and standalone apps for data analysis and visualization. The API is freely available for use at http://giant-api.princeton.edu. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

PubMed Central

Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J.; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R.; Johnsen, Steven A.

2017-01-01

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4. PMID:27651452

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire.

PubMed

Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R; Johnsen, Steven A

2017-01-09

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Red laser based on intra-cavity Nd:YAG/CH4 frequency doubled Raman lasers

NASA Astrophysics Data System (ADS)

Wang, Yanchao; Wang, Pengyuan; Liu, Jinbo; Liu, Wanfa; Guo, Jingwei

2017-01-01

Stimulated Raman scattering (SRS) is a powerful tool for the extension of the spectral range of lasers. To obtain efficient Raman conversion in SRS, many researchers have studied different types of Raman laser configurations. Among these configurations, the intra-cavity type is particularly attractive. Intra-cavity SRS has the advantages of high intra-cavity laser intensity, low-SRS threshold, and high Raman conversion efficiency. In this paper, An Q-switched intra-cavity Nd: YAG/CH4 frequency-doubled Raman lasers is reported. A negative branch confocal resonator with M= 1.25 is used for the frequency-doubling of Nd: YAG laser. The consequent 532nm light is confined in intra- cavity SRS with travelling wave resonator, and the focal of one mirror of cavity is overlap with the center of the other mirror of the cavity. We found this design is especially efficient to reduce the threshold of SRS, and increase conversion efficiency. The threshold is measured to be 0.62 MW, and at the pump energy of 16.1 mJ, the conversion efficiency is 34%. With the smaller magnification M, the threshold could further decrease, and the conversion efficiency could be improved further. This is a successful try to extend the spectral range of a laser to the shorter wavelength by SRS, and this design may play an important role in the fulfillment of high power red lasers.

A Modularity-Based Method Reveals Mixed Modules from Chemical-Gene Heterogeneous Network

PubMed Central

Song, Jianglong; Tang, Shihuan; Liu, Xi; Gao, Yibo; Yang, Hongjun; Lu, Peng

2015-01-01

For a multicomponent therapy, molecular network is essential to uncover its specific mode of action from a holistic perspective. The molecular system of a Traditional Chinese Medicine (TCM) formula can be represented by a 2-class heterogeneous network (2-HN), which typically includes chemical similarities, chemical-target interactions and gene interactions. An important premise of uncovering the molecular mechanism is to identify mixed modules from complex chemical-gene heterogeneous network of a TCM formula. We thus proposed a novel method (MixMod) based on mixed modularity to detect accurate mixed modules from 2-HNs. At first, we compared MixMod with Clauset-Newman-Moore algorithm (CNM), Markov Cluster algorithm (MCL), Infomap and Louvain on benchmark 2-HNs with known module structure. Results showed that MixMod was superior to other methods when 2-HNs had promiscuous module structure. Then these methods were tested on a real drug-target network, in which 88 disease clusters were regarded as real modules. MixMod could identify the most accurate mixed modules from the drug-target 2-HN (normalized mutual information 0.62 and classification accuracy 0.4524). In the end, MixMod was applied to the 2-HN of Buchang naoxintong capsule (BNC) and detected 49 mixed modules. By using enrichment analysis, we investigated five mixed modules that contained primary constituents of BNC intestinal absorption liquid. As a matter of fact, the findings of in vitro experiments using BNC intestinal absorption liquid were found to highly accord with previous analysis. Therefore, MixMod is an effective method to detect accurate mixed modules from chemical-gene heterogeneous networks and further uncover the molecular mechanism of multicomponent therapies, especially TCM formulae. PMID:25927435

Fluctuating selection across years and phenotypic variation in food-deceptive orchids.

PubMed

Scopece, Giovanni; Juillet, Nicolas; Lexer, Christian; Cozzolino, Salvatore

2017-01-01

Nectarless flowers that deceive pollinators offer an opportunity to study asymmetric plant-insect interactions. Orchids are a widely used model for studying these interactions because they encompass several thousand species adopting deceptive pollination systems. High levels of intra-specific phenotypic variation have been reported in deceptive orchids, suggesting a reduced consistency of pollinator-mediated selection on their floral traits. Nevertheless, several studies report on widespread directional selection mediated by pollinators even in these deceptive orchids. In this study we test the hypothesis that the observed selection can fluctuate across years in strength and direction thus likely contributing to the phenotypic variability of this orchid group. We performed a three-year study estimating selection differentials and selection gradients for nine phenotypic traits involved in insect attraction in two Mediterranean orchid species, namely Orchis mascula and O. pauciflora , both relying on a well-described food-deceptive pollination strategy. We found weak directional selection and marginally significant selection gradients in the two investigated species with significant intra-specific differences in selection differentials across years. Our data do not link this variation with a specific environmental cause, but our results suggest that pollinator-mediated selection in food-deceptive orchids can change in strength and in direction over time. In perennial plants, such as orchids, different selection differentials in the same populations in different flowering seasons can contribute to the maintenance of phenotypic variation often reported in deceptive orchids.

Rapid cell separation with minimal manipulation for autologous cell therapies

NASA Astrophysics Data System (ADS)

Smith, Alban J.; O'Rorke, Richard D.; Kale, Akshay; Rimsa, Roberts; Tomlinson, Matthew J.; Kirkham, Jennifer; Davies, A. Giles; Wälti, Christoph; Wood, Christopher D.

2017-02-01

The ability to isolate specific, viable cell populations from mixed ensembles with minimal manipulation and within intra-operative time would provide significant advantages for autologous, cell-based therapies in regenerative medicine. Current cell-enrichment technologies are either slow, lack specificity and/or require labelling. Thus a rapid, label-free separation technology that does not affect cell functionality, viability or phenotype is highly desirable. Here, we demonstrate separation of viable from non-viable human stromal cells using remote dielectrophoresis, in which an electric field is coupled into a microfluidic channel using shear-horizontal surface acoustic waves, producing an array of virtual electrodes within the channel. This allows high-throughput dielectrophoretic cell separation in high conductivity, physiological-like fluids, overcoming the limitations of conventional dielectrophoresis. We demonstrate viable/non-viable separation efficacy of >98% in pre-purified mesenchymal stromal cells, extracted from human dental pulp, with no adverse effects on cell viability, or on their subsequent osteogenic capabilities.

Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats).

PubMed

Miller, Marion G

2007-02-01

Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively explored. This review will use a SWOT analysis model to discuss some of the strengths, weaknesses, opportunities, and threats that are apparent to an investigator venturing into this relatively new field. SWOT has been used extensively in business settings to uncover new outlooks and identify problems that would impede progress. The field of environmental metabolomics provides great opportunities for discovery, and this is recognized by a high level of interest in potential applications. However, understanding the biological consequence of environmental exposures can be confounded by inter- and intra-individual differences. Metabolomic profiles can yield a plethora of data, the interpretation of which is complex and still being evaluated and researched. The development of the field will depend on the availability of technologies for data handling and that permit ready access metabolomic databases. Understanding the relevance of metabolomic endpoints to organism health vs adaptation vs variation is an important step in understanding what constitutes a substantive environmental threat. Metabolomic applications in reproductive research are discussed. Overall, the development of a comprehensive mechanistic-based interpretation of metabolomic changes offers the possibility of providing information that will significantly contribute to the protection of human health and the environment.

[Visual acuity in anti-VEGF therapy for AMD : Can specific characteristics in the SD-OCT help?

PubMed

Book, B; Ziegler, M; Heimes, B; Gutfleisch, M; Spital, G; Pauleikhoff, D; Lommatzsch, A

2017-01-01

The efficacy of anti-VEGF therapy in exudative AMD has been established in several large clinical trials using a fixed injection regimen as well as a SD-OCT-based PRN regimen. In these studies, after the first three injections, an increase of the mean visual acuity was observed, which could be stabilized with constant treatment for up to 24 months. However, the specific course of the visual acuity is very different between individuals. The aim of the present study was to correlate specific initial SD-OCT parameters with the course of visual acuity in order to characterize factors that may be important for the individual visual prognosis. In a prospective case study, the visual course and SD-OCT changes of 156 patients with minimum follow-up of 12 months (mean 80.1 months) were analysed. Visual acuity (LogMar) was investigated at regular intervals and correlated with specific SD-OCT parameters (foveal thickness, height of sub-retinal fluid or presence of associated PED, presence of intra-retinal cysts, length of IS/OS break, choroidal thickness). The initial increase in visual acuity could be stabilized over time. This effect was associated with a decrease in foveal retinal thickness, which also persisted over time. While sub-retinal fluid, presence of PED, and choroidal thickness showed no prognostic relevance for the change in visual acuity, the presence of more advanced central retinal thickness, of intra-retinal cysts or a longer break in the IS/OS junction were associated with a less favourable development of visual acuity. In the present study, the presence of more advanced central retinal thickness, of intra-retinal cysts or a larger IS/OS break correlated significantly with a worse visual prognosis. These might be clinical signs for more extensive pre-existing intra-retinal changes. Further analysis and new diagnostic tools may prove this and may result in specific additive neuroprotective or regenerative therapeutic approaches in exudative AMD.

Intra-tumor Genetic Heterogeneity and Mortality in Head and Neck Cancer: Analysis of Data from The Cancer Genome Atlas

PubMed Central

Mroz, Edmund A.; Tward, Aaron M.; Hammon, Rebecca J.; Ren, Yin; Rocco, James W.

2015-01-01

Background Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Methods and Findings Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity’s associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having oral-cavity or laryngeal cancers even when standard disease staging was taken into account. Prospective studies, however, will be required before MATH can be used prognostically in clinical trials or practice. Such studies will need to examine homogeneously treated HNSCC at specific head and neck subsites, and determine the influence of cancer therapy on MATH values. Analysis of MATH and outcome in human-papillomavirus-positive oropharyngeal squamous cell carcinoma is particularly needed. Conclusions To our knowledge this study is the first to combine data from hundreds of patients, treated at multiple institutions, to document a relation between intra-tumor heterogeneity and overall survival in any type of cancer. We suggest applying the simply calculated MATH metric of heterogeneity to prospective studies of HNSCC and other tumor types. PMID:25668320

Comparative proteomics of matrix fractions between pimpled and normal chicken eggshells.

PubMed

Liu, Zhangguo; Song, Lingzi; Lu, Lizhi; Zhang, Xianfu; Zhang, Fuming; Wang, Kehua; Linhardt, Robert J

2017-09-07

Eggshell matrix can be dissociated into three matrix fractions: acid-insoluble matrix (M1), water-insoluble matrix (M2) and acid-water facultative-soluble matrix (M3). Matrix fractions from pimpled and normal eggshells were compared using label-free proteomic method to understand the differences among three matrix fractions and the proteins involved with eggshell quality. A total of 738 and 600 proteins were identified in the pimpled and normal calcified eggshells, respectively. Both eggshells showed a combined proteomic inventory of 769 proteins. In the same type of eggshell, a high similarity was present in the proteomes of three matrix fractions. These triply overlapped common proteins formed the predominant contributor to proteomic abundance in the matrix fractions. In each matrix fraction and between both eggshell models, normal and pimpled eggshells, a majority of the proteomes of the fractions were commonly observed. Forty-two common major proteins (iBAQ-derived abundance ≥0.095% of proteomic abundance) were identified throughout the three matrix fractions and these proteins might act as backbone constituents in chicken eggshell matrix. Finally, using 1.75-fold as up-regulated and using 0.57-fold as down-regulated cutoff values, twenty-five differential major proteins were screened and they all negatively influence and none showed any effect on eggshell quality. Overall, we uncovered the characteristics of proteomics of three eggshell matrix fractions and identified candidate proteins influencing eggshell quality. The next research on differential proteins will uncover the potential mechanisms underlying how proteins affect eggshell quality. It was reported that the proteins in an eggshell can be divided into insoluble and soluble proteins. The insoluble proteins are thought to be an inter-mineral matrix and acts as a structural framework, while the soluble proteins are thought as intra-mineral matrix that are embedded within the crystal during calcification. However, the difference between matrix fractions is unknown. Cross-analysis of proteomic data of three matrix fractions from the same type of eggshell, uncovered triply overlapped common proteins formed the predominant contributor to proteomic abundance of any matrix fraction, and we suggested that abundance variance of some common proteins between the three matrix fractions might be an important cause of their solubility differences. Moreover, eggshell is formed in hen's uterus, and uterus tend to be considered as unique organ determining eggshell quality. By cross-analysis on proteomic data of three matrix fractions between two eggshell models, normal and pimpled eggshells, the differential proteins were screened as candidates influencing eggshell quality. And we suggested that the liver and spleen or lymphocytes might be the major organs influencing eggshell quality, because the most promising candidates are almost blood and non-collagenous proteins, and originated from above organs. Copyright © 2017 Elsevier B.V. All rights reserved.

Three-dimensional endoanal ultrasound is accurate and reproducible in determining type and height of anal fistulas.

PubMed

Kołodziejczak, M; Santoro, G A; Obcowska, A; Lorenc, Z; Mańczak, M; Sudoł-Szopińska, I

2017-04-01

Surgical treatment of high anal fistulas is associated with the potential risk of faecal incontinence and recurrence. The primary aim of this study was to determine the accuracy of three-dimensional endoanal ultrasound (3D-EAUS) in the assessment of height and type of anal fistulas, compared to the intra-operative findings (gold standard). The secondary aim was to evaluate the inter-observer reproducibility of 3D-EAUS. The study design was a prospective analysis of retrospective data. 299 patients (202 men), mean age 45.3 years, who underwent surgery for anal fistulas, were included. All patients were preoperatively assessed by 3D-EAUS. Two readers independently reviewed the volumes to determine the type and height of fistulas. Sensitivity, specificity, positive and negative predictive values, proportion of agreements and Cohen's kappa coefficient (κ) were calculated for both examiners. Ultrasound findings were compared with intra-operative data (reference standard), evaluated blindly by the surgeons. At surgery, 201 (67%) were transsphincteric, 49 (16%) suprasphincteric, 47 (16%) intersphincteric and two (1%) extrasphincteric fistulas. Intra-operatively, 177 (59%) were low and 122 (41%) high fistulas. The overall accuracy of 3D-EAUS was 91% for fistula type (271/299 fistulas: 97% transsphincteric, 100% intersphincteric, 57% suprasphincteric, 0% extrasphincteric) and 92% for fistula height (275/299 fistulas: 80% high and 100% low). Both readers reported very good agreement with surgery in the assessment of fistula type (proportion of agreement 0.88, κ = 0.89) and height (proportion of agreement 0.90, κ = 0.91). 3D-EAUS is an accurate and reproducible modality for the assessment of type and height of anal fistulas. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Subchondral impaction fractures of the non-weight-bearing portion of the lateral femoral condyle.

PubMed

Depasquale, Ruben; Fotiadou, Anastasia; Kumar, Dalavaye Suresh; Lalam, Radhesh; Tins, Bernhard; Tyrrell, Prudencia N M; Singh, Jaspreet; Cassar-Pullicino, Victor N

2013-02-01

To document the first report of intra-articular, non-weight-bearing, impaction fractures of the lateral femoral condyle. Institutional Review Board and Regional Ethics Committee approval for this study was obtained and patient informed consent deemed unnecessary. We prospectively documented all potential cases of non-weight-bearing posterior subchondral impaction fractures of the femoral condyles diagnosed on magnetic resonance imaging (MRI) of the knee performed at our institution between January 2006 and December 2011. The cases were reviewed and discussed by three experienced musculoskeletal radiologists and only cases satisfying pre-defined MRI criteria were included. Sixteen cases of intra-articular impaction fractures in a posterior, non-weight-bearing area of the lateral femoral condyle were diagnosed in patients with a mean age of 40. Eight were associated with recreational sports activities and 4 with repeated kneeling. There were no fractures documented in the non-weight-bearing aspect of the medial femoral condyles. Proposed underlying mechanisms for development of this type of fracture are presented. Awareness, along with a high level of suspicion, that non-specific knee pain, especially in patients involved in athletic activities, could be due to intra-articular impaction fractures of the non-weight-bearing posterior aspect of the lateral femoral condyle is essential and MRI is the mainstay of diagnosis.

Short stop mediates axonal compartmentalization of mucin-type core 1 glycans

PubMed Central

Kinoshita, Takaaki; Sato, Chikara; Fuwa, Takashi J.; Nishihara, Shoko

2017-01-01

T antigen, mucin-type core 1 O-glycan, is highly expressed in the embryonic central nervous system (CNS) and co-localizes with a Drosophila CNS marker, BP102 antigen. BP102 antigen and Derailed, an axon guidance receptor, are localized specifically in the proximal axon segment of isolated primary cultured neurons, and their mobility is restricted at the intra-axonal boundary by a diffusion barrier. However, the preferred trafficking mechanism remains unknown. In this study, the major O-glycan T antigen was found to localize within the proximal compartments of primary cultured Drosophila neurons, whereas the N-glycan HRP antigen was not. Ultrastructural analysis by atmospheric scanning electron microscopy revealed that microtubule bundles cross one another at the intra-axonal boundary, and that T antigens form circular pattern before the boundary. We then identified Short stop (Shot), a crosslinker protein between F-actin and microtubules, as a mediator for the proximal localization of T antigens; null mutation of shot cancelled preferential localization of T antigens. Moreover, F-actin binding domain of Shot was required for their proximal localization. Together, our results allow us to propose a novel trafficking pathway where Shot crosslinks F-actin and microtubules around the intra-axonal boundary, directing T antigen-carrying vesicles toward the proximal plasma membrane. PMID:28150729

Formation of intra-island grain boundaries in pentacene monolayers.

PubMed

Zhang, Jian; Wu, Yu; Duhm, Steffen; Rabe, Jürgen P; Rudolf, Petra; Koch, Norbert

2011-12-21

To assess the formation of intra-island grain boundaries during the early stages of pentacene film growth, we studied sub-monolayers of pentacene on pristine silicon oxide and silicon oxide with high pinning centre density (induced by UV/O(3) treatment). We investigated the influence of the kinetic energy of the impinging molecules on the sub-monolayer growth by comparing organic molecular beam deposition (OMBD) and supersonic molecular beam deposition (SuMBD). For pentacene films fabricated by OMBD, higher pentacene island-density and higher polycrystalline island density were observed on UV/O(3)-treated silicon oxide as compared to pristine silicon oxide. Pentacene films deposited by SuMBD exhibited about one order of magnitude lower island- and polycrystalline island densities compared to OMBD, on both types of substrates. Our results suggest that polycrystalline growth of single islands on amorphous silicon oxide is facilitated by structural/chemical surface pinning centres, which act as nucleation centres for multiple grain formation in a single island. Furthermore, the overall lower intra-island grain boundary density in pentacene films fabricated by SuMBD reduces the number of charge carrier trapping sites specific to grain boundaries and should thus help achieving higher charge carrier mobilities, which are advantageous for their use in organic thin-film transistors.

Novel inter and intra prediction tools under consideration for the emerging AV1 video codec

NASA Astrophysics Data System (ADS)

Joshi, Urvang; Mukherjee, Debargha; Han, Jingning; Chen, Yue; Parker, Sarah; Su, Hui; Chiang, Angie; Xu, Yaowu; Liu, Zoe; Wang, Yunqing; Bankoski, Jim; Wang, Chen; Keyder, Emil

2017-09-01

Google started the WebM Project in 2010 to develop open source, royalty- free video codecs designed specifically for media on the Web. The second generation codec released by the WebM project, VP9, is currently served by YouTube, and enjoys billions of views per day. Realizing the need for even greater compression efficiency to cope with the growing demand for video on the web, the WebM team embarked on an ambitious project to develop a next edition codec AV1, in a consortium of major tech companies called the Alliance for Open Media, that achieves at least a generational improvement in coding efficiency over VP9. In this paper, we focus primarily on new tools in AV1 that improve the prediction of pixel blocks before transforms, quantization and entropy coding are invoked. Specifically, we describe tools and coding modes that improve intra, inter and combined inter-intra prediction. Results are presented on standard test sets.

The dissolution kinetics of major elements in municipal solid waste incineration bottom ash particles

NASA Astrophysics Data System (ADS)

Bendz, David; Tüchsen, Peter L.; Christensen, Thomas H.

2007-12-01

Leaching and tracer experiments in batches at L/S 20 were performed with 3-month-old MSWI bottom ash separated into eight different particle sizes. The time-dependent leaching of major elements (Ca 2+, K +, Na +, Cl - and SO 4- 2 ) was monitored for up to 747 h. Physical properties of the particles, the specific surface (BET), pore volume and pore volume distribution over pore sizes (BJH) were determined for all particle classes by N 2 adsorption/desorption experiments. Some common features of physical pore structure for all particles were revealed. The specific surface and the particle pore volume were found to be negatively correlated with particle size, ranging from 3.2 m 2/g to 25.7 m 2/g for the surface area and from 0.0086 cm 3/g to 0.091 cm 3/g for the pore volume. Not surprisingly, the specific surface area was found to be the major material parameter that governed the leaching behavior for all elements (Ca 2+, K +, Na +, Cl - and SO 4- 2 ) and particle sizes. The diffusion resistance was determined independently by separate tracer (tritium) experiments. Diffusion gave a significant contribution to the apparent leaching kinetics for all elements during the first 10-40 h (depending on the particle size) of leaching and surface reaction was the overall rate controlling mechanism at late times for all particle sizes. For Ca 2+ and SO 4- 2 , the coupled effect of diffusion resistance and the degree of undersaturation in the intra particle pore volume was found to be a major rate limiting dissolution mechanism for both early and late times. The solubility control in the intra particulate porosity may undermine any attempt to treat bottom ash by washing out the sulfate. Even for high liquid/solid ratios, the solubility in the intra-particular porosity will limit the release rate.

Optimization of inclusive fitness.

PubMed

Grafen, Alan

2006-02-07

The first fully explicit argument is given that broadly supports a widespread belief among whole-organism biologists that natural selection tends to lead to organisms acting as if maximizing their inclusive fitness. The use of optimization programs permits a clear statement of what this belief should be understood to mean, in contradistinction to the common mathematical presumption that it should be formalized as some kind of Lyapunov or even potential function. The argument reveals new details and uncovers latent assumptions. A very general genetic architecture is allowed, and there is arbitrary uncertainty. However, frequency dependence of fitnesses is not permitted. The logic of inclusive fitness immediately draws together various kinds of intra-genomic conflict, and the concept of 'p-family' is introduced. Inclusive fitness is thus incorporated into the formal Darwinism project, which aims to link the mathematics of motion (difference and differential equations) used to describe gene frequency trajectories with the mathematics of optimization used to describe purpose and design. Important questions remain to be answered in the fundamental theory of inclusive fitness.

The globalization of the nursing workforce: Pulling the pieces together.

PubMed

Jones, Cheryl B; Sherwood, Gwen D

2014-01-01

The "globalization" of health care creates an increasingly interconnected workforce spanning international boundaries, systems, structures, and processes to provide care to and improve the health of peoples around the world. Because nurses comprise a large sector of the global health workforce, they are called upon to provide a significant portion of nursing and health care and thus play an integral role in the global health care economy. To meet global health care needs, nurses often move within and among countries, creating challenges and opportunities for the profession, health care organizations, communities, and nations. Researchers, policy makers, and industry and academic leaders must, in turn, grapple with the impacts of globalization on the nursing and health care workforce. Through this special issue, several key areas for discussion are raised. Although far from exhaustive, our intent is to expand and stimulate intra- and interprofessional conversations raising awareness of the issues, uncover unanticipated consequences, and offer solutions for shaping the nursing and health care workforce of the future. Copyright © 2014 Elsevier Inc. All rights reserved.

Uncovering Patterns of Inter-Urban Trip and Spatial Interaction from Social Media Check-In Data

PubMed Central

Liu, Yu; Sui, Zhengwei; Kang, Chaogui; Gao, Yong

2014-01-01

The article revisits spatial interaction and distance decay from the perspective of human mobility patterns and spatially-embedded networks based on an empirical data set. We extract nationwide inter-urban movements in China from a check-in data set that covers half a million individuals within 370 cities to analyze the underlying patterns of trips and spatial interactions. By fitting the gravity model, we find that the observed spatial interactions are governed by a power law distance decay effect. The obtained gravity model also closely reproduces the exponential trip displacement distribution. The movement of an individual, however, may not obey the same distance decay effect, leading to an ecological fallacy. We also construct a spatial network where the edge weights denote the interaction strengths. The communities detected from the network are spatially cohesive and roughly consistent with province boundaries. We attribute this pattern to different distance decay parameters between intra-province and inter-province trips. PMID:24465849

Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia

PubMed Central

Wang, Lili; Fan, Jean; Francis, Joshua M.; Georghiou, George; Hergert, Sarah; Li, Shuqiang; Gambe, Rutendo; Zhou, Chensheng W.; Yang, Chunxiao; Xiao, Sheng; Cin, Paola Dal; Bowden, Michaela; Kotliar, Dylan; Shukla, Sachet A.; Brown, Jennifer R.; Neuberg, Donna; Alessi, Dario R.; Zhang, Cheng-Zhong; Kharchenko, Peter V.; Livak, Kenneth J.; Wu, Catherine J.

2017-01-01

Intra-tumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype–phenotype relationships, we developed methods for targeted mutation detection in DNA and RNA isolated from thousands of single cells from five CLL samples. By clearly resolving phylogenic relationships, we uncovered mutated LCP1 and WNK1 as novel CLL drivers, supported by functional evidence demonstrating their impact on CLL pathways. Integrative analysis of somatic mutations with transcriptional states prompts the idea that convergent evolution generates phenotypically similar cells in distinct genetic branches, thus creating a cohesive expression profile in each CLL sample despite the presence of genetic heterogeneity. Our study highlights the potential for single-cell RNA-based targeted analysis to sensitively determine transcriptional and mutational profiles of individual cancer cells, leading to increased understanding of driving events in malignancy. PMID:28679620

Uncovering patterns of inter-urban trip and spatial interaction from social media check-in data.

PubMed

Liu, Yu; Sui, Zhengwei; Kang, Chaogui; Gao, Yong

2014-01-01

The article revisits spatial interaction and distance decay from the perspective of human mobility patterns and spatially-embedded networks based on an empirical data set. We extract nationwide inter-urban movements in China from a check-in data set that covers half a million individuals within 370 cities to analyze the underlying patterns of trips and spatial interactions. By fitting the gravity model, we find that the observed spatial interactions are governed by a power law distance decay effect. The obtained gravity model also closely reproduces the exponential trip displacement distribution. The movement of an individual, however, may not obey the same distance decay effect, leading to an ecological fallacy. We also construct a spatial network where the edge weights denote the interaction strengths. The communities detected from the network are spatially cohesive and roughly consistent with province boundaries. We attribute this pattern to different distance decay parameters between intra-province and inter-province trips.

Intra-individual cognitive imbalance in ASD between perceptual reasoning and ambiguity-solving related to tool use: Comparison among children exhibiting ASD, AD/HD, and typical development.

PubMed

Wakusawa, Keisuke; Nara, Chieko; Kubota, Yuki; Tomizawa, Yayoi; Taki, Yasuyuki; Sassa, Yuko; Kobayashi, Satoru; Suzuki-Muromoto, Sato; Hirose, Mieko; Yokoyama, Hiroyuki; Nara, Takahiro; Kure, Shigeo; Mori, Norio; Takei, Noriyoshi; Kawashima, Ryuta

2018-01-01

Several studies have suggested that objective deficits in the processing of abstract information in conjunction with an enhanced ability to process concrete information is a definitive characteristic of autism spectrum disorder (ASD). However, this cognitive imbalance is not necessarily clear in high-functioning autistic individuals who do not display absolute differences relative to typically developing (TD) populations. Thus, the purpose of this study was to identify this cognitive tendency in high-functioning autistic individuals using intra-individual cognitive comparisons. The reaction times (RTs) of TD children, children with ASD, and children with attention deficit hyperactivity disorder (AD/HD) (n=17 in each group, mean age=11.9years, age range=9.8-15.8years) were compared using the Which/How-to-Apply Tools (W/HAT) test, which consists of tasks requiring the adaptive use of novel tools and familiar tools in atypical and typical situations. Differences in RTs between the atypical and typical trials ([A-T]) were used to assess intra-individual cognitive imbalances. As predicted, the [A-T] scores of the ASD group were significantly higher than those of the TD group even though the RTs in the atypical and typical trials did not differ. Additionally, the [A-T] values were significantly higher in the ASD group than in the AD/HD group, which indicates that the cognitive imbalance was specific to ASD individuals. No significant interaction was detected between the trial and subject group. The findings of this study demonstrate that a cognitive imbalance in ASD individuals may enhance the current understanding of the pathophysiology of this disorder, which is found in a range of individuals, including those with obvious cortical dysfunction to those with only intra-individual imbalances. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Intra-peritoneal chronic loculation in peritoneal dialysis patients - a new medical management approach.

PubMed

Mitoiu, Dan; David, Cristiana; Peride, Ileana; Niculae, Andrei; Mureşan, Alin; Ciocâlteu, Alexandru; Geavlete, Bogdan Florin; Checheriţă, Ionel Alexandru

2014-01-01

Peritoneal dialysis (PD) limitation as renal replacement therapy is mostly due to peritonitis and complications. Formation and persistence of intra-abdominal loculations is often under-diagnosed. Encapsulated peritoneal sclerosis (EPS) is a life-threatening complication, but malnutrition, recurrent peritonitis and early membrane failure are insidious enemies that need to be emphasized. It is important to highlight the persistence of intra-abdominal fluid collection after clinical resolution of peritonitis in PD patients and to indicate a new medical management approach for an early diagnosis. During five years, we selected PD peritonitis cases followed by a six months interval free of infections. Ninety-seven subjects were followed at six months and one year after the first peritonitis. Tomography had been performed to patients presenting a positive inflammatory state without a specific infectious cause. Subjects presenting documented localized fluid collection (31 cases) were divided into: drug-treated group and those undergoing laparoscopy by a new surgery technique (seven patients); a comparison regarding the clinical state and biohumoral parameters was assessed in both groups. The prevalence of intra-abdominal loculation following an apparent resolved peritonitis was high (31.9%). The cases undergoing laparoscopy presented a better evolution - improved clinical status (p=0.001), higher hemoglobin values (p=0.06), significant lower doses of erythropoietin requirement (p=0.03), improved dialysis adequacy (p=0.005) and inflammatory state. In cases with confirmed fluid encapsulated loculation, an active attitude (screening imaging protocol and laparoscopic exploration) appears to be mandatory, decreasing the risk of EPS, a serious complication which pathology and treatment are incompletely understood.

Personal Knowledge Management for Employee Commoditization

ERIC Educational Resources Information Center

Schild, Susie A.

2013-01-01

Knowledge management thinking has resulted in the perception that the organization is the relevant beneficiary of knowledge. Individual approaches to and experiences with personal knowledge management are not well documented in empirical studies, which uncovered the specific problem that the situatedness of knowledge worker contemporaries within…

N-acetyl-aspartate levels correlate with intra-axonal compartment parameters from diffusion MRI.

PubMed

Grossman, Elan J; Kirov, Ivan I; Gonen, Oded; Novikov, Dmitry S; Davitz, Matthew S; Lui, Yvonne W; Grossman, Robert I; Inglese, Matilde; Fieremans, Els

2015-09-01

Diffusion MRI combined with biophysical modeling allows for the description of a white matter (WM) fiber bundle in terms of compartment specific white matter tract integrity (WMTI) metrics, which include intra-axonal diffusivity (Daxon), extra-axonal axial diffusivity (De||), extra-axonal radial diffusivity (De┴), axonal water fraction (AWF), and tortuosity (α) of extra-axonal space. Here we derive these parameters from diffusion kurtosis imaging to examine their relationship to concentrations of global WM N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myo-Inositol (mI), as measured with proton MR spectroscopy ((1)H-MRS), in a cohort of 25 patients with mild traumatic brain injury (MTBI). We found statistically significant (p<0.05) positive correlations between NAA and Daxon, AWF, α, and fractional anisotropy; negative correlations between NAA and De,┴ and the overall radial diffusivity (D┴). These correlations were supported by similar findings in regional analysis of the genu and splenium of the corpus callosum. Furthermore, a positive correlation in global WM was noted between Daxon and Cr, as well as a positive correlation between De|| and Cho, and a positive trend between De|| and mI. The specific correlations between NAA, an endogenous probe of the neuronal intracellular space, and WMTI metrics related to the intra-axonal space, combined with the specific correlations of De|| with mI and Cho, both predominantly present extra-axonally, corroborate the overarching assumption of many advanced modeling approaches that diffusion imaging can disentangle between the intra- and extra-axonal compartments in WM fiber bundles. Our findings are also generally consistent with what is known about the pathophysiology of MTBI, which appears to involve both intra-axonal injury (as reflected by a positive trend between NAA and Daxon) as well as axonal shrinkage, demyelination, degeneration, and/or loss (as reflected by correlations between NAA and De┴, AWF, and α). Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.

PubMed

Goonesekere, Nalin C W; Andersen, Wyatt; Smith, Alex; Wang, Xiaosheng

2018-02-01

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines. This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC. While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.

Proteolysis-a characteristic of tumor-initiating cells in murine metastatic breast cancer

PubMed Central

Hillebrand, Larissa E.; Bengsch, Fee; Hochrein, Jochen; Hülsdünker, Jan; Bender, Julia; Follo, Marie; Busch, Hauke; Boerries, Melanie; Reinheckel, Thomas

2016-01-01

Tumor initiating cells (TICs) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potential, TICs are founder cells for metastasis formation and are involved in chemotherapy resistance. In this study we explored molecular pathways which enable this tumor initiating potential for a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45−, showed a high tumorigenicity compared to non-CD24+CD90+CD45− cancer cells in colony formation assays, as well as upon orthotopic transplantation into the mammary fat pad of mice. In addition, these orthotopically grown CD24+CD90+CD45− TICs metastasized to the lungs. The transcriptome of TICs freshly isolated from primary tumors by cell sorting was compared with that of sorted non-CD24+CD90+CD45− cancer cells by RNA-seq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in the TICs. Accordingly, TICs showed high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on colony morphology in 3D cell culture assays. We conclude that CD24+CD90+CD45− cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature which could very well represent a functional hallmark of metastatic TICs from mammary carcinomas. PMID:27542270

Severity and treatment of "occult" intra-abdominal injuries in blunt trauma victims.

PubMed

Parreira, José G; Oliari, Camilla B; Malpaga, Juliano M D; Perlingeiro, Jacqueline A G; Soldá, Silvia C; Assef, José C

2016-01-01

to assess the severity and treatment of "occult" intra-abdominal injuries in blunt trauma victims. Retrospective analysis of charts and trauma register data of adult blunt trauma victims, admitted without abdominal pain or alterations in the abdominal physical examination, but were subsequently diagnosed with intra-abdominal injuries, in a period of 2 years. The severity was stratified according to RTS, AIS, OIS and ISS. The specific treatment for abdominal injuries and the complications related to them were assessed. Intra-abdominal injuries were diagnosed in 220 (3.8%) out of the 5785 blunt trauma victims and 76 (34.5%) met the inclusion criteria. The RTS and ISS median (lower quartile, upper quartile) were 7.84 (6.05, 7.84) and 25 (16, 34). Sixty seven percent had a GCS≥13 on admission. Injuries were identified in the spleen (34), liver (33), kidneys (9), intestines (4), diaphragm (3), bladder (3) and iliac vessels (1). Abdominal injuries scored AIS≥3 in 67% of patients. Twenty-one patients (28%) underwent laparotomy, 5 of which were nontherapeutic. The surgical procedures performed were splenectomy (8), suturing of the diaphragm (3), intestines (3), bladder (2), kidneys (1), enterectomy/anastomosis (1), ligation of the common iliac vein (1), and revascularization of the common iliac artery (1). Angiography and embolization of liver and/or spleen injuries were performed in 3 cases. Three patients developed abdominal complications, all of which were operatively treated. There were no deaths directly related to the abdominal injuries. Severe "occult" intra-abdominal injuries, requiring specific treatment, may be present in adult blunt trauma patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evidence of accumulated stress in Achilles and anterior knee tendons in elite badminton players.

PubMed

Boesen, Anders Ploug; Boesen, Morten Ilum; Koenig, Merete Juhl; Bliddal, Henning; Torp-Pedersen, Soren; Langberg, Henning

2011-01-01

Tendon-related injuries are a major problem, but the aetiology of tendinopathies is unknown. In tendinopathies as well as during unaccustomed loading, intra-tendinous flow can be detected indicating that extensive loading can provoke intra-tendinous flow. The aim of present study is to evaluate the vascular response as indicated by colour Doppler (CD) activity in both the Achilles and patella tendon after loading during high-level badminton matches. The Achilles tendon was subdivided into a mid-tendon, pre-insertional, and insertional region and the anterior knee tendons into a quadriceps-, patella- and tuberositas region. Intra-tendinous flow was measured using both a semi-quantitative grading system (CD grading) and a quantitative scoring system (CF) on colour Doppler. Intra-tendinous flow in the Achilles and anterior knee tendons was examined in fourteen single players before tournament and after 1st and 2nd match, respectively on both the dominant and non-dominant side. All players had abnormal intra-tendinous flow (Colour Doppler ≥ grade 2) in at least one tendon in at least one scan during the tournament. At baseline, only two of the 14 players had normal flow in all the tendons examined. After 1st match, tendencies to higher intra-tendinous flow were observed in both the dominant patella tendon and non-dominant quadriceps tendon (P-values n.s.). After 2nd match, intra-tendinous flow was significant increased in the dominant patella tendon (P = 0.009). In all other locations, there was a trend towards a stepwise increase in intra-tendinous flow. The preliminary results indicate that high amount of intra-tendinous flow was found in elite badminton players at baseline and was increased after repetitive loading, especially in the patella tendon (dominant leg). The colour Doppler measurement can be used to determine changes in intra-tendinous flow after repetitive loading.

Developmental dyscalculia: compensatory mechanisms in left intraparietal regions in response to nonsymbolic magnitudes.

PubMed

Kaufmann, Liane; Vogel, Stephan E; Starke, Marc; Kremser, Christian; Schocke, Michael; Wood, Guilherme

2009-08-05

Functional magnetic resonance imaging (fMRI) studies investigating the neural mechanisms underlying developmental dyscalculia are scarce and results are thus far inconclusive. Main aim of the present study is to investigate the neural correlates of nonsymbolic number magnitude processing in children with and without dyscalculia. 18 children (9 with dyscalculia) were asked to solve a non-symbolic number magnitude comparison task (finger patterns) during brain scanning. For the spatial control task identical stimuli were employed, instructions varying only (judgment of palm rotation). This design enabled us to present identical stimuli with identical visual processing requirements in the experimental and the control task. Moreover, because numerical and spatial processing relies on parietal brain regions, task-specific contrasts are expected to reveal true number-specific activations. Behavioral results during scanning reveal that despite comparable (almost at ceiling) performance levels, task-specific activations were stronger in dyscalculic children in inferior parietal cortices bilaterally (intraparietal sulcus, supramarginal gyrus, extending to left angular gyrus). Interestingly, fMRI signal strengths reflected a group x task interaction: relative to baseline, controls produced significant deactivations in (intra)parietal regions bilaterally in response to number but not spatial processing, while the opposite pattern emerged in dyscalculics. Moreover, beta weights in response to number processing differed significantly between groups in left - but not right - (intra)parietal regions (becoming even positive in dyscalculic children). Overall, findings are suggestive of (a) less consistent neural activity in right (intra)parietal regions upon processing nonsymbolic number magnitudes; and (b) compensatory neural activity in left (intra)parietal regions in developmental dyscalculia.

Developmental dyscalculia: compensatory mechanisms in left intraparietal regions in response to nonsymbolic magnitudes

PubMed Central

Kaufmann, Liane; Vogel, Stephan E; Starke, Marc; Kremser, Christian; Schocke, Michael; Wood, Guilherme

2009-01-01

Background Functional magnetic resonance imaging (fMRI) studies investigating the neural mechanisms underlying developmental dyscalculia are scarce and results are thus far inconclusive. Main aim of the present study is to investigate the neural correlates of nonsymbolic number magnitude processing in children with and without dyscalculia. Methods 18 children (9 with dyscalculia) were asked to solve a non-symbolic number magnitude comparison task (finger patterns) during brain scanning. For the spatial control task identical stimuli were employed, instructions varying only (judgment of palm rotation). This design enabled us to present identical stimuli with identical visual processing requirements in the experimental and the control task. Moreover, because numerical and spatial processing relies on parietal brain regions, task-specific contrasts are expected to reveal true number-specific activations. Results Behavioral results during scanning reveal that despite comparable (almost at ceiling) performance levels, task-specific activations were stronger in dyscalculic children in inferior parietal cortices bilaterally (intraparietal sulcus, supramarginal gyrus, extending to left angular gyrus). Interestingly, fMRI signal strengths reflected a group × task interaction: relative to baseline, controls produced significant deactivations in (intra)parietal regions bilaterally in response to number but not spatial processing, while the opposite pattern emerged in dyscalculics. Moreover, beta weights in response to number processing differed significantly between groups in left – but not right – (intra)parietal regions (becoming even positive in dyscalculic children). Conclusion Overall, findings are suggestive of (a) less consistent neural activity in right (intra)parietal regions upon processing nonsymbolic number magnitudes; and (b) compensatory neural activity in left (intra)parietal regions in developmental dyscalculia. PMID:19653919

Site-specific 13C content by quantitative isotopic 13C nuclear magnetic resonance spectrometry: a pilot inter-laboratory study.

PubMed

Chaintreau, Alain; Fieber, Wolfgang; Sommer, Horst; Gilbert, Alexis; Yamada, Keita; Yoshida, Naohiro; Pagelot, Alain; Moskau, Detlef; Moreno, Aitor; Schleucher, Jürgen; Reniero, Fabiano; Holland, Margaret; Guillou, Claude; Silvestre, Virginie; Akoka, Serge; Remaud, Gérald S

2013-07-25

Isotopic (13)C NMR spectrometry, which is able to measure intra-molecular (13)C composition, is of emerging demand because of the new information provided by the (13)C site-specific content of a given molecule. A systematic evaluation of instrumental behaviour is of importance to envisage isotopic (13)C NMR as a routine tool. This paper describes the first collaborative study of intra-molecular (13)C composition by NMR. The main goals of the ring test were to establish intra- and inter-variability of the spectrometer response. Eight instruments with different configuration were retained for the exercise on the basis of a qualification test. Reproducibility at the natural abundance of isotopic (13)C NMR was then assessed on vanillin from three different origins associated with specific δ (13)Ci profiles. The standard deviation was, on average, between 0.9 and 1.2‰ for intra-variability. The highest standard deviation for inter-variability was 2.1‰. This is significantly higher than the internal precision but could be considered good in respect of a first ring test on a new analytical method. The standard deviation of δ (13)Ci in vanillin was not homogeneous over the eight carbons, with no trend either for the carbon position or for the configuration of the spectrometer. However, since the repeatability for each instrument was satisfactory, correction factors for each carbon in vanillin could be calculated to harmonize the results. Copyright © 2013 Elsevier B.V. All rights reserved.

Reliable and fast volumetry of the lumbar spinal cord using cord image analyser (Cordial).

PubMed

Tsagkas, Charidimos; Altermatt, Anna; Bonati, Ulrike; Pezold, Simon; Reinhard, Julia; Amann, Michael; Cattin, Philippe; Wuerfel, Jens; Fischer, Dirk; Parmar, Katrin; Fischmann, Arne

2018-04-30

To validate the precision and accuracy of the semi-automated cord image analyser (Cordial) for lumbar spinal cord (SC) volumetry in 3D T1w MRI data of healthy controls (HC). 40 3D T1w images of 10 HC (w/m: 6/4; age range: 18-41 years) were acquired at one 3T-scanner in two MRI sessions (time interval 14.9±6.1 days). Each subject was scanned twice per session, allowing determination of test-retest reliability both in back-to-back (intra-session) and scan-rescan images (inter-session). Cordial was applied for lumbar cord segmentation twice per image by two raters, allowing for assessment of intra- and inter-rater reliability, and compared to a manual gold standard. While manually segmented volumes were larger (mean: 2028±245 mm 3 vs. Cordial: 1636±300 mm 3 , p<0.001), accuracy assessments between manually and semi-automatically segmented images showed a mean Dice-coefficient of 0.88±0.05. Calculation of within-subject coefficients of variation (COV) demonstrated high intra-session (1.22-1.86%), inter-session (1.26-1.84%), as well as intra-rater (1.73-1.83%) reproducibility. No significant difference was shown between intra- and inter-session reproducibility or between intra-rater reliabilities. Although inter-rater reproducibility (COV: 2.87%) was slightly lower compared to all other reproducibility measures, between rater consistency was very strong (intraclass correlation coefficient: 0.974). While under-estimating the lumbar SCV, Cordial still provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. • Lumbar spinal cord segmentation using the semi-automated cord image analyser (Cordial) is feasible. • Lumbar spinal cord is 40-mm cord segment 60 mm above conus medullaris. • Cordial provides excellent inter- and intra-session reproducibility in lumbar spinal cord region. • Cordial shows high potential for application in longitudinal trials.

Bone growth, limb proportions and non-specific stress in archaeological populations from Croatia.

PubMed

Pinhasi, R; Timpson, A; Thomas, M; Slaus, M

2014-01-01

The effect of environmental factors and, in particular, non-specific stress on the growth patterns of limbs and other body dimensions of children from past populations is not well understood. This study assesses whether growth of mediaeval and post-mediaeval children aged between 0-11.5 years from Adriatic (coastal) and continental Croatia varies by region and by the prevalence and type of non-specific stress. Dental ages were estimated using the Moorrees, Fanning and Hunt (MFH) scoring method. Growth of long bone diaphyses (femur, tibia, humerus, radius and ulna) was assessed by using a composite Z-score statistic (CZS). Clavicular length was measured as a proxy for upper trunk width, distal metaphyseal width of the femur was measured as a proxy for body mass and upper and lower intra-limb indices were calculated. Differences between sub-sets sampled by (a) region and (b) active vs healed non-specific stress indicators and (c) intra-limb indices were tested by Mann--Whitney U-tests and Analysis of Covariance (ANCOVA). Adriatic children attained larger dimensions-per-age than continental children. Children with healed stress lesions had larger dimensions-per-age than those with active lesions. No inter-regional difference was found in intra-limb indices. These findings highlight the complexity of growth patterns in past populations and indicate that variation in environmental conditions such as diet and differences in the nature of non-specific stress lesions both exert a significant effect on long bone growth.

A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways

PubMed Central

Taipale, Mikko; Tucker, George; Peng, Jian; Krykbaeva, Irina; Lin, Zhen-Yuan; Larsen, Brett; Choi, Hyungwon; Berger, Bonnie; Gingras, Anne-Claude; Lindquist, Susan

2014-01-01

Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins (clients). In vivo, chaperones also associate with a large and diverse set of co-factors (co-chaperones) that regulate their specificity and function. However, how these co-chaperones regulate protein folding and whether they have chaperone-independent biological functions is largely unknown. We have combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone/co-chaperone/client interaction network in human cells. We uncover hundreds of novel chaperone clients, delineate their participation in specific co-chaperone complexes, and establish a surprisingly distinct network of protein/protein interactions for co-chaperones. As a salient example of the power of such analysis, we establish that NUDC family co-chaperones specifically associate with structurally related but evolutionarily distinct β-propeller folds. We provide a framework for deciphering the proteostasis network, its regulation in development and disease, and expand the use of chaperones as sensors for drug/target engagement. PMID:25036637

Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.

PubMed

Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed

2017-08-04

Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.

Identification and resolution of artifacts in the interpretation of imprinted gene expression.

PubMed

Proudhon, Charlotte; Bourc'his, Déborah

2010-12-01

Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has failed to uncover a significant number of new imprinted genes, probably because of the high tissue- and developmental-stage specificity of imprinted gene expression. A very large number of technical and biological artifacts can also lead to the erroneous evidence of imprinted gene expression. In this article, we focus on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoallelic expression and (iii) contamination or infiltration of embryonic tissues with maternal material. This last situation specifically applies to genes that occur as maternally expressed in the placenta. Beside the use of reciprocal crosses that are instrumental to confirm the parental specificity of expression, we provide additional methods for the detection and elimination of these situations that can be misinterpreted as cases of imprinted expression.

Differential transesophageal echocardiographic diagnosis between linear artifacts and intraluminal flap of aortic dissection or disruption.

PubMed

Vignon, P; Spencer, K T; Rambaud, G; Preux, P M; Krauss, D; Balasia, B; Lang, R M

2001-06-01

The relatively low specificity of transesophageal echocardiography (TEE) for the diagnosis of aortic dissection (AD) or traumatic disruption of the aorta (TDA) has been attributed to linear artifacts. We sought to determine the incidence of intra-aortic linear artifacts in a cohort of patients with suspected AD or TDA, to establish the differential TEE diagnostic criteria between these artifacts and true aortic flaps, and to evaluate their impact on TEE diagnostic accuracy. During an 8-year period, patients at high risk of AD (n = 261) or TDA (n = 90) who underwent a TEE study and had confirmed final diagnoses were studied. In an initial retrospective series, linear artifacts were observed within the ascending and descending aorta in 59 of 230 patients (26%) and 17 of 230 patients (7%), respectively. TEE findings associated with linear artifacts in the ascending aorta were as follows: displacement parallel to aortic walls; similar blood flow velocities on both sides; angle with the aortic wall > 85 degrees; and thickness > 2.5 mm. Diagnostic criteria of reverberant images in the descending aorta were as follows: displacement parallel to aortic walls, overimposition of blood flow, and similar blood flow velocities on both sides of the image. In a subsequent prospective series (n = 121), systematic use of these diagnostic criteria resulted in improved TEE specificity for the identification of true intra-aortic flaps. Misleading intra-aortic linear artifacts are frequently observed in patients undergoing a TEE study for suspected AD or TDA. Routine use of the herein-proposed diagnostic criteria promises to further improve TEE diagnostic accuracy in the setting of severely ill patients with potential need for prompt surgery.

Assessment of snake DNA barcodes based on mitochondrial COI and Cytb genes revealed multiple putative cryptic species in Thailand.

PubMed

Laopichienpong, Nararat; Muangmai, Narongrit; Supikamolseni, Arrjaree; Twilprawat, Panupon; Chanhome, Lawan; Suntrarachun, Sunutcha; Peyachoknagul, Surin; Srikulnath, Kornsorn

2016-12-15

DNA barcodes of mitochondrial cytochrome c oxidase I (COI), cytochrome b (Cytb) genes, and their combined data sets were constructed from 35 snake species in Thailand. No barcoding gap was detected in either of the two genes from the observed intra- and interspecific sequence divergences. Intra- and interspecific sequence divergences of the COI gene differed 14 times, with barcode cut-off scores ranging over 2%-4% for threshold values differentiated among most of the different species; the Cytb gene differed 6 times with cut-off scores ranging over 2%-6%. Thirty-five specific nucleotide mutations were also found at interspecific level in the COI gene, identifying 18 snake species, but no specific nucleotide mutation was observed for Cytb in any single species. This suggests that COI barcoding was a better marker than Cytb. Phylogenetic clustering analysis indicated that most species were represented by monophyletic clusters, suggesting that these snake species could be clearly differentiated using COI barcodes. However, the two-marker combination of both COI and Cytb was more effective, differentiating snake species by over 2%-4%, and reducing species numbers in the overlap value between intra- and interspecific divergences. Three species delimitation algorithms (general mixed Yule-coalescent, automatic barcoding gap detection, and statistical parsimony network analysis) were extensively applied to a wide range of snakes based on both barcodes. This revealed cryptic diversity for eleven snake species in Thailand. In addition, eleven accessions from the database previously grouped under the same species were represented at different species level, suggesting either high genetic diversity, or the misidentification of these sequences in the database as a consequence of cryptic species. Copyright © 2016 Elsevier B.V. All rights reserved.

The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner.

PubMed

Rea, Kieran; McGowan, Fiona; Corcoran, Louise; Roche, Michelle; Finn, David P

2018-05-30

The emotional processing and coordination of top-down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC, (infralimbic (IL), prelimbic (PrL), anterior cingulate (ACC) cortices), differentially alter the expression of contextually-induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IL, PrL and ACC in formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone. FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra-mPFC administration of AM251 (CB 1 receptor antagonist/inverse agonist), URB597 (fatty acid amide hydrolase inhibitor) or URB597 + AM251 on FCA and freezing behaviour were assessed. AM251 attenuated FCA when injected into the IL or PrL and reduced contextually induced freezing behaviour when injected intra-IL, but not intra-PrL or intra-ACC. Intra-ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and freezing behaviour when injected intra-IL, prolonged the expression of FCA when injected intra-PrL and had no effect on these behaviours when injected intra-ACC. These results suggest important and differential roles for FAAH substrates or CB 1 receptors in the PrL, IL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone. This article is protected by copyright. All rights reserved.

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord

PubMed Central

José-Edwards, Diana S.; Oda-Ishii, Izumi; Kugler, Jamie E.; Passamaneck, Yale J.; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

2015-01-01

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs. PMID:26684323

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

PubMed

José-Edwards, Diana S; Oda-Ishii, Izumi; Kugler, Jamie E; Passamaneck, Yale J; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

2015-12-01

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

Validation of an enzyme-linked immunosorbent assay for the quantification of citrullinated histone H3 as a marker for neutrophil extracellular traps in human plasma.

PubMed

Thålin, Charlotte; Daleskog, Maud; Göransson, Sophie Paues; Schatzberg, Daphne; Lasselin, Julie; Laska, Ann-Charlotte; Kallner, Anders; Helleday, Thomas; Wallén, Håkan; Demers, Mélanie

2017-06-01

There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma. A standard curve made of in vitro PAD4-citrullinated histones H3 allows for the quantification of H3Cit in plasma using an anti-histone antibody as capture antibody and an anti-histone H3 citrulline antibody for detection. The assay was evaluated for linearity, stability, specificity, and precision on plasma samples obtained from a human model of inflammation before and after lipopolysaccharide injection. The results revealed linearity and high specificity demonstrated by the inability of detecting non-citrullinated histone H3. Coefficients of variation for intra- and inter-assay variability ranged from 2.1 to 5.1% and from 5.8 to 13.5%, respectively, allowing for a high precision. Furthermore, our results support an inflammatory induction of a systemic NET burden by showing, for the first time, clear intra-individual elevations of plasma H3Cit in a human model of lipopolysaccharide-induced inflammation. Taken together, our work demonstrates the development of a new method for the quantification of H3Cit by ELISA that can reliably be used for the detection of NETs in human plasma.

The Neuroscience of Group Membership

ERIC Educational Resources Information Center

Morrison, Samantha; Decety, Jean; Molenberghs, Pascal

2012-01-01

The present study aimed to uncover the neural activity associated with specific in-group and out-group word related stimuli, to examine the neuroanatomical basis of group membership concept representation, and investigate to what extent neural processes represent "in-group" differently from "out-group". Participants' brain activity was measured…

[Spatial patterns of dominant tree species in sub-alpine Betula-Abies forest in West Sichuan of China].

PubMed

Miao, Ning; Liu, Shi-Rong; Shi, Zuo-Min; Yu, Hong; Liu, Xing-Liang

2009-06-01

Based on the investigation in a 4 hm2 Betula-Abies forest plot in sub-alpine area in West Sichuan of China, and by using point pattern analysis method in terms of O-ring statistics, the spatial patterns of dominant species Betula albo-sinensis and Abies faxoniana in different age classes in study area were analyzed, and the intra- and inter-species associations between these age classes were studied. B. albo-sinensis had a unimodal distribution of its DBH frequency, indicating a declining population, while A. faxoniana had a reverse J-shaped pattern, showing an increasing population. All the big trees of B. albo-sinensis and A. faxoniana were spatially in random at all scales, while the medium age and small trees were spatially clumped at small scales and tended to be randomly or evenly distributed with increasing spatial scale. The maximum aggregation degree decreased with increasing age class. Spatial association mainly occurred at small scales. A. faxoniana generally showed positive intra-specific association, while B. albo-sinensis generally showed negative intra-specific association. For the two populations, big and small trees had no significant spatial association, but middle age trees had negative spatial association. Negative inter-specific associations of the two populations were commonly found in different age classes. The larger the difference of age class, the stronger the negative inter-specific association.

Estuarine use and movement patterns of seven sympatric Mugilidae fishes: The Tatu Creek estuary, central western Taiwan

NASA Astrophysics Data System (ADS)

Chang, Chih-Wei; Iizuka, Yoshiyuki

2012-06-01

By combining the spatio-temporal distribution of fish abundance and their size structure, and a detailed lifetime Sr/Ca ratio analysis in their otoliths, this study delineates the estuarine use and the movement patterns of seven sympatrical occurring adult mullets in the Tatu Creek estuary, central western Taiwan. In the estuary Mugil cephalus are the most dominant species, whereas Liza subviridis, Liza macrolepis and Liza haematocheilus are common, and Liza affinis, Liza dussumieri and Valamugil seheli are rare. They have adapted a size-related salinity preference. A mean Sr/Ca ratio of (7.5-10.2) × 10-3 in the otolith cores demonstrated that all seven mullet species spawned in the sea. After recruiting to the estuary (mean ratios of (3.6-6.4) × 10-3 at the estuarine check in the otoliths), the ratios fluctuate between (0.1-3.5) × 10-3 and (9.5-19.5) × 10-3 indicating that the mullet shared a common movement between marine and brackish waters and probably even freshwater habitats. However, the profiles fluctuated substantially among individuals. There was high intra-specific variation among M. cephalus and L. subviridis, intermediate intra-specific variation among L. macrolepis and L. affinis, and relatively little among L. haematocheilus, L. dussumieri and V. seheli. Persistent residency in high or low saline environments was found to vary among species, and the extent of their catadromy is discussed.

Building a secure internal attachment: an intra-relational approach to ego strengthening and emotional processing with chronically traumatized clients.

PubMed

Lamagna, Jerry; Gleiser, Kari A

2007-01-01

In this paper, we introduce Intra-Relational AEDP (I-R) as an attachment-based experiential approach to trauma treatment. Integrating Accelerated Experiential Dynamic Psychotherapy (AEDP) (Fosha, 2000a,b, 2002, 2003) with ego-state methodology, intra-relational interventions specifically seeks to help clients by (1) fostering capacities for self-regulation through shared states of affective resonance between therapist, client, and dissociated self-states; (2) facilitating authentic, open internal dialogue between self-states which can alter engrained patterns of intra-psychic conflict and self-punishment; (3) developing abilities for self-reflection and emotional processing by co-mingling previously disowned affect and emotional memories with here and now experience; and (4) attending to positive affects evoked through experiences of transformation, self-compassion, and self-affirmation. Drawing from object relations and attachment theory, intra-relational interventions places particular emphasis on internal attachment relationships formed through interactions between the client's subjective selves (internal subjects) and reflective selves (internal objects). Through visual imagery, internal dialogue, and explicit relational techniques, intra-relational interventions aims to develop this subjective-reflective dyad's capacity for reciprocal attunement, resonance, and responsiveness. Such clinical strategies aim to foster healing and psychological integration between the client and heretofore disavowed aspects of self.

Association between infection and fever in terminations of pregnancy using misoprostol: a retrospective cohort study.

PubMed

Nijman, Tobias A J; Voogdt, Kevin G J A; Teunissen, Pim W; van der Voorn, Patrick J Jp; de Groot, Christianne J M; Bakker, Petra C A M

2017-01-05

Fever is a well-known side effect of misoprostol, but clinically difficult to distinguish from an intra uterine infection. The aim of this study was to determine the incidence of fever in terminations of pregnancy (TOP) using misoprostol and to evaluate fever as indication of intra uterine infection. A retrospective cohort study was performed. Consecutive second trimester TOP with misoprostol between January 2008 and October 2012 were selected. We included 403 cases and determined the incidence of fever. To examine intra uterine infection as plausible cause of fever, pathological examination reports of placentas were reviewed for signs of infections. The incidence of fever was 42%. Logistic regression showed a dose dependent association between dosage misoprostol and degree of fever (OR 1.86; 95% CI: 1.3-2.7). There was no association between fever and epidural analgesia. Fever has a sensitivity of 55% and a specificity of 58% as a marker of intra uterine infection. The positive predictive value of fever for an intra uterine infection is 4% and the negative predictive value is 98%. Administration of misoprostol for the indication TOP is strongly associated with fever during labor. Fever is a poor predictor of intra uterine infection in the context of TOP.

Cell-Selective Biological Activity of Rhodium Metalloinsertors Correlates with Subcellular Localization

PubMed Central

Komor, Alexis C.; Schneider, Curtis J.; Weidmann, Alyson G.; Barton, Jacqueline K.

2013-01-01

Deficiencies in the mismatch repair (MMR) pathway are associated with several types of cancers, as well as resistance to commonly used chemotherapeutics. Rhodium metalloinsertors have been found to bind DNA mismatches with high affinity and specificity in vitro, and also exhibit cell-selective cytotoxicity, targeting MMR-deficient cells over MMR-proficient cells. Ten distinct metalloinsertors with varying lipophilicities have been synthesized and their mismatch binding affinities and biological activities determined. Although DNA photocleavage experiments demonstrate that their binding affinities are quite similar, their cell-selective antiproliferative and cytotoxic activities vary significantly. Inductively coupled plasma mass spectrometry (ICP-MS) experiments have uncovered a relationship between the subcellular distribution of these metalloinsertors and their biological activities. Specifically, we find that all of our metalloinsertors localize in the nucleus at sufficient concentrations for binding to DNA mismatches. However, the metalloinsertors with high rhodium localization in the mitochondria show toxicity that is not selective for MMR-deficient cells, whereas metalloinsertors with less mitochondrial rhodium show activity that is highly selective for MMR-deficient versus proficient cells. This work supports the notion that specific targeting of the metalloinsertors to nuclear DNA gives rise to their cell-selective cytotoxic and antiproliferative activities. The selectivity in cellular targeting depends upon binding to mismatches in genomic DNA. PMID:23137296

Intra-Operative Surgical Irrigation of the Surgical Incision: What Does the Future Hold-Saline, Antibiotic Agents, or Antiseptic Agents?

PubMed

Edmiston, Charles E; Leaper, David J

2016-12-01

Intra-operative surgical site irrigation (lavage) is common practice in surgical procedures in general, with all disciplines advocating some form of irrigation before incision closure. This practice, however, has been neither standardized nor is there compelling evidence that it effectively reduces the risk of surgical site infection (SSI). This narrative review addresses the laboratory and clinical evidence that is available to support the practice of irrigation of the abdominal cavity and superficial/deep incisional tissues, using specific irrigation solutions at the end of an operative procedure to reduce the microbial burden at wound closure. Review of PubMed and OVID for pertinent, scientific, and clinical publications in the English language was performed. Incision irrigation was found to afford a three-fold benefit: First, to hydrate the bed; second, to assist in allowing better examination of the area immediately before closure; and finally, by removing superficial and deep incisional contamination and lowering the bioburden, expedite the healing process. The clinical practice of intra-operative peritoneal lavage is highly variable and is dependent solely on surgeon preference. By contrast, intra-operative irrigation after device-related procedures has become a standard of care for the prophylaxis of acute peri-prosthetic infection. The clinical evidence that supports the use of antibiotic irrigation is limited and based on retrospective analysis and few acceptable randomized controlled trials. The results of laboratory and animal studies using aqueous 0.05% chlorhexidine gluconate are favorable, suggesting that further studies are justified to determine its clinical efficacy. The adoption of appropriate and standardized intra-operative irrigation practices into peri-operative care bundles, which include other evidence-based strategies (weight-based antimicrobial prophylaxis, antimicrobial sutures, maintenance of normothermia, and glycemic control), offers an inexpensive and effective method to reduce the risk of post-operative SSI and deserves further evaluation.

Mechanistic comparisons of functional domains across pediatric and adult bipolar disorder highlight similarities, as well as differences, influenced by the developing brain.

PubMed

Wegbreit, Ezra; Pavuluri, Mani

2012-01-01

Recent neuroimaging studies have uncovered much about the specific neural deficits in adult bipolar disorder (ABD), but despite promising results, neuroimaging research for pediatric bipolar disorder (PBD) is still developing. The neuroimaging literature is highly heterogeneous, varying in the paradigms used and in participants' mood states and medication status. Despite this variability, several dominant patterns emerge. In response to emotional stimuli, both ABD and PBD show limbic hyperactivity coupled with hypoactivity in ventral prefrontal emotion regulation systems. This pattern occurred most robustly in response to negative incidental stimuli and was especially apparent in manic PBD. ABD showed more variability in ventral prefrontal activity, possibly due to maturational and medication factors. On numerous cognitive paradigms, PBD showed dorsal prefrontal hypoactivity linked to ventral dysfunction, whereas ABD showed compensatory frontal, parietal, and temporal activity with paradigm-specific variations. In emotion-cognition interaction paradigms, patients show dysregulation in regions interfacing between cognitive and emotional brain systems (e.g., ventral prefrontal and cingulate cortices), which expend extra effort to process emotional stimuli effectively and recruit additional posterior attention systems to cope with affective instability. In addition, novel functional connectivity techniques have uncovered connectivity deficits between frontal and limbic regions in ABD and PBD at rest and during active emotional and cognitive tasks. Finally, the neuroimaging literature currently lacks cross-sectional studies comparing PBD with ABD and longitudinal studies following children and adolescents with BD into adulthood. Such studies would provide important insights into patients' prognosis and would determine targets for early interventions in the evolving illness diathesis.

Structured Set Intra Prediction With Discriminative Learning in a Max-Margin Markov Network for High Efficiency Video Coding

PubMed Central

Dai, Wenrui; Xiong, Hongkai; Jiang, Xiaoqian; Chen, Chang Wen

2014-01-01

This paper proposes a novel model on intra coding for High Efficiency Video Coding (HEVC), which simultaneously predicts blocks of pixels with optimal rate distortion. It utilizes the spatial statistical correlation for the optimal prediction based on 2-D contexts, in addition to formulating the data-driven structural interdependences to make the prediction error coherent with the probability distribution, which is desirable for successful transform and coding. The structured set prediction model incorporates a max-margin Markov network (M3N) to regulate and optimize multiple block predictions. The model parameters are learned by discriminating the actual pixel value from other possible estimates to maximize the margin (i.e., decision boundary bandwidth). Compared to existing methods that focus on minimizing prediction error, the M3N-based model adaptively maintains the coherence for a set of predictions. Specifically, the proposed model concurrently optimizes a set of predictions by associating the loss for individual blocks to the joint distribution of succeeding discrete cosine transform coefficients. When the sample size grows, the prediction error is asymptotically upper bounded by the training error under the decomposable loss function. As an internal step, we optimize the underlying Markov network structure to find states that achieve the maximal energy using expectation propagation. For validation, we integrate the proposed model into HEVC for optimal mode selection on rate-distortion optimization. The proposed prediction model obtains up to 2.85% bit rate reduction and achieves better visual quality in comparison to the HEVC intra coding. PMID:25505829

Testing the Hip Abductor Muscle Strength of Older Persons Using a Handheld Dynamometer.

PubMed

Awwad, Daniel H; Buckley, Jonathan D; Thomson, Rebecca L; O'Connor, Matthew; Carbone, Tania A; Chehade, Mellick J

2017-09-01

To investigate the reliability of a clinically applicable method of dynamometry to assess and monitor hip abductor muscle strength in older persons. Bilateral isometric hip abductor muscle strength measured with a handheld dynamometer, patients supine with the contralateral hip positioned directly against a wall for stabilization. Reliability determined by comparing intra-assessor and inter-assessor results and comparison to a criterion standard (stabilized dynamometer with patients in the standing position). UniSA Nutritional Physiology Research Centre. Twenty-one patients older than 65 years were recruited from the Royal Adelaide Hospital. Intraclass correlation coefficients (ICCs), bias, and limits of agreement calculated to determine reliability. Intra-assessor and inter-assessor ICCs were high (0.94 and 0.92-0.94, respectively). There was no intra-assessor bias and narrow limits of agreement (±2.4%). There was a small inter-assessor bias but narrow limits of agreement (0.6%-0.9% and ± 2.3%, respectively). There was a wide variation comparing results to the criterion standard (±5.0%-5.2% limits of agreement), highlighting problems attributed to difficulties that the test population had with the standing position used in the criterion standard test. Testing older persons' hip abductor muscle strength while in the supine position with optimal pelvic stabilization using a handheld dynamometer is highly reliable. While further studies must be done to assess patients with specific pathologies, this test has potential application to monitor and evaluate the effects of surgical interventions and/or rehabilitation protocols for a variety of conditions affecting hip abductor function such as hip fractures and arthritis.

Intraoperative MR-guided DBS implantation for treating PD and ET

NASA Astrophysics Data System (ADS)

Liu, Haiying; Maxwell, Robert E.; Truwit, Charles L.

2001-05-01

Deep brain stimulator (DBS) implantation is a promising treatment alternative for suppressing the motor tremor symptoms in Parkinson disease (PD) patient. The main objective is to develop a minimally invasive approach using high spatial resolution and soft-tissue contrast MR imaging techniques to guide the surgical placement of DBS. In the MR-guided procedure, the high spatial resolution MR images were obtained intra-operatively and used to target stereotactically a specific deep brain location. The neurosurgery for craniotomy was performed in the front of the magnet outside of the 10 Gauss line. Aided with positional registration assembly for the stereotactic head frame, the target location (VIM or GPi or STN) in deep brain areas was identified and measured from the MR images in reference to the markers in the calibration assembly of the head frame before the burrhole prep. In 20 patients, MR- guided DBS implantations have been performed according to the new methodology. MR-guided DBS implantation at high magnetic field strength has been shown to be feasible and desirable. In addition to the improved outcome, this offers a new surgical approach in which intra-operative visualization is possible during intervention, and any complications such as bleeding can be assessed in situ immediately prior to dural closure.

Functional genomics of root growth and development in Arabidopsis

PubMed Central

Iyer-Pascuzzi, Anjali; Simpson, June; Herrera-Estrella, Luis; Benfey, Philip N.

2009-01-01

Summary Roots are vital for the uptake of water and nutrients, and for anchorage in the soil. They are highly plastic, able to adapt developmentally and physiologically to changing environmental conditions. Understanding the molecular mechanisms behind this growth and development requires knowledge of root transcriptomics, proteomics and metabolomics. Genomics approaches, including the recent publication of a root expression map, root proteome, and environment-specific root expression studies, are uncovering complex transcriptional and post-transcriptional networks underlying root development. The challenge is in further capitalizing on the information in these datasets to understand the fundamental principles of root growth and development. In this review, we highlight progress researchers have made toward this goal. PMID:19117793

Functional genomics of root growth and development in Arabidopsis.

PubMed

Iyer-Pascuzzi, Anjali; Simpson, June; Herrera-Estrella, Luis; Benfey, Philip N

2009-04-01

Roots are vital for the uptake of water and nutrients, and for anchorage in the soil. They are highly plastic, able to adapt developmentally and physiologically to changing environmental conditions. Understanding the molecular mechanisms behind this growth and development requires knowledge of root transcriptomics, proteomics, and metabolomics. Genomics approaches, including the recent publication of a root expression map, root proteome, and environment-specific root expression studies, are uncovering complex transcriptional and post-transcriptional networks underlying root development. The challenge is in further capitalizing on the information in these datasets to understand the fundamental principles of root growth and development. In this review, we highlight progress researchers have made toward this goal.

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action.

PubMed

Selleck, Ryan A; Lake, Curtis; Estrada, Viridiana; Riederer, Justin; Andrzejewski, Matthew; Sadeghian, Ken; Baldo, Brian A

2015-09-01

Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control. Intra-PFC methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats in a 'low-drive' condition (2-h food deprivation), and also after a motivational shift to a 'high-drive' condition (18-h food deprivation). Intra-PFC DAMGO (D-[Ala2,N-MePhe4, Gly-ol]-enkephalin; a μ-opioid agonist) and d-amphetamine were also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly eliminated impulsive action in DRL engendered by hunger, at a dose (1 μg) that significantly affected neither hunger-induced PR enhancement nor hyperactivity. At a higher dose (3 μg), M-NX eliminated impulsive action and returned PR breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered 'high-drive-like' effects: enhancement of PR and impairment of DRL performance. Intra-PFC d-amphetamine failed to produce effects in either task. These results establish that endogenous PFC opioid transmission is both necessary and sufficient for the expression of impulsive action in a high-arousal, high-drive appetitive state, and that PFC-based opioid systems enact functionally unique effects on food impulsivity and motivation relative to PFC-based monoamine systems. Opioid antagonists may represent effective treatments for a range of psychiatric disorders with impulsivity features.

Genetic screens for mutations affecting development of Xenopus tropicalis.

PubMed

Goda, Tadahiro; Abu-Daya, Anita; Carruthers, Samantha; Clark, Matthew D; Stemple, Derek L; Zimmerman, Lyle B

2006-06-01

We present here the results of forward and reverse genetic screens for chemically-induced mutations in Xenopus tropicalis. In our forward genetic screen, we have uncovered 77 candidate phenotypes in diverse organogenesis and differentiation processes. Using a gynogenetic screen design, which minimizes time and husbandry space expenditures, we find that if a phenotype is detected in the gynogenetic F2 of a given F1 female twice, it is highly likely to be a heritable abnormality (29/29 cases). We have also demonstrated the feasibility of reverse genetic approaches for obtaining carriers of mutations in specific genes, and have directly determined an induced mutation rate by sequencing specific exons from a mutagenized population. The Xenopus system, with its well-understood embryology, fate map, and gain-of-function approaches, can now be coupled with efficient loss-of-function genetic strategies for vertebrate functional genomics and developmental genetics.

Multiplexed Five-Color Molecular Imaging of Cancer Cells and Tumor Tissues with Carbon Nanotube Raman Tags in the Near-Infrared

PubMed Central

Liu, Zhuang; Tabakman, Scott; Sherlock, Sarah; Li, Xiaolin; Chen, Zhuo; Jiang, Kaili; Fan, Shoushan; Dai, Hongjie

2011-01-01

Single-walled carbon nanotubes (SWNTs) with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity. Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs. Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor (EGFR) on LS174T colon cancer cells from cell culture to in vivo tumor growth. This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared (NIR) region under a single laser excitation. Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low, smooth autofluorescence background of biological species. PMID:21442006

Uncovering Global SUMOylation Signaling Networks in a Site-Specific Manner

PubMed Central

Hendriks, Ivo A.; D’Souza, Rochelle C.J.; Yang, Bing; Verlaan-de Vries, Matty; Mann, Matthias; Vertegaal, Alfred C.O.

2014-01-01

SUMOylation is a reversible post-translational modification essential for genome stability. Using high-resolution mass spectrometry, we have studied global SUMOylation in human cells and in a site-specific manner, identifying a total of over 4,300 SUMOylation sites in over 1,600 proteins. Moreover, for the first time in excess of 1,000 SUMOylation sites were identified under standard growth conditions. SUMOylation dynamics were quantitatively studied in response to SUMO protease inhibition, proteasome inhibition and heat shock. A considerable amount of SUMOylated lysines have previously been reported to be ubiquitylated, acetylated or methylated, indicating crosstalk between SUMO and other post-translational modifications. We identified 70 phosphorylation and 4 acetylation events in close proximity to SUMOylation sites, and provide evidence for acetylation-dependent SUMOylation of endogenous histone H3. SUMOylation regulates target proteins involved in all nuclear processes including transcription, DNA repair, chromatin remodeling, pre-mRNA splicing and ribosome assembly. PMID:25218447

FTIR-ATR-based prediction and modelling of lignin and energy contents reveals independent intra-specific variation of these traits in bioenergy poplars

PubMed Central

2011-01-01

Background There is an increasing demand for renewable resources to replace fossil fuels. However, different applications such as the production of secondary biofuels or combustion for energy production require different wood properties. Therefore, high-throughput methods are needed for rapid screening of wood in large scale samples, e.g., to evaluate the outcome of tree breeding or genetic engineering. In this study, we investigated the intra-specific variability of lignin and energy contents in extractive-free wood of hybrid poplar progenies (Populus trichocarpa × deltoides) and tested if the range was sufficient for the development of quantitative prediction models based on Fourier transform infrared spectroscopy (FTIR). Since lignin is a major energy-bearing compound, we expected that the energy content of wood would be positively correlated with the lignin content. Results Lignin contents of extractive-free poplar wood samples determined by the acetyl bromide method ranged from 23.4% to 32.1%, and the calorific values measured with a combustion calorimeter varied from 17260 to 19767 J g-1. For the development of calibration models partial least square regression and cross validation was applied to correlate FTIR spectra determined with an attenuated total reflectance (ATR) unit to measured values of lignin or energy contents. The best models with high coefficients of determination (R2 (calibration) = 0.91 and 0.90; R2 (cross-validation) = 0.81 and 0.79) and low root mean square errors of cross validation (RMSECV = 0.77% and 62 J g-1) for lignin and energy determination, respectively, were obtained after data pre-processing and automatic wavenumber restriction. The calibration models were validated by analyses of independent sets of wood samples yielding R2 = 0.88 and 0.86 for lignin and energy contents, respectively. Conclusions These results show that FTIR-ATR spectroscopy is suitable as a high-throughput method for lignin and energy estimations in large data sets. Our study revealed that the intra-specific variations in lignin and energy contents were unrelated to each other and that the lignin content, therefore, was no predictor of the energy content. Employing principle component analyses we showed that factor loadings for the energy content were mainly associated with carbohydrate ring vibrations, whereas those for lignin were mainly related to aromatic compounds. Therefore, our analysis suggests that it may be possible to optimize the energy content of trees without concomitant increase in lignin. PMID:21477346

The role of the atrial electromechanical delay in predicting atrial fibrillation in beta-thalassemia major patients.

PubMed

Rago, Anna; Russo, Vincenzo; Papa, Andrea Antonio; Ciardiello, Carmine; Pannone, Bruno; Mayer, Maria Carolina; Cimmino, Giovanni; Nigro, Gerardo

2017-03-01

Paroxysmal atrial tachyarrhythmias frequently occur in beta-thalassemia major (β-TM) patients. The aim of the current study was to evaluate the atrial electromechanical delay (AEMD) in a large β-TM population with normal cardiac function and its relationship to atrial fibrillation (AF) onset. Eighty β-TM patients (44 men, 36 women), with a mean age of 36.2 ± 11.1 years, and 80 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of AF during a 5-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 6 months. Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead electrocardiogram (ECG). Compared to the healthy control group, the β-TM patients showed a statistically significant increase in inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD. Dividing the β-TM group into two subgroups (patients with or without AF), the inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD were significantly higher in the subgroup with AF compared to the subgroup without AF. There were significant good correlations of intra-left AEMD and inter-AEMD with PD. A cut-off value of 40.1 ms for intra-left AEMD had a sensitivity of 76.2% and a specificity of 97.5% in identifying β-TM patients with AF risk. A cut-off value of 44.8 ms for inter-AEMD had a sensitivity of 81.2% and a specificity of 98.7% in identifying this category of patients. Our results showed that the echocardiographic atrial electromechanical delay indices (intra-left and inter-AEMD) and the PD were significantly increased in β-TM subjects with normal cardiac function. PD and AEMD represent non-invasive, inexpensive, useful, and simple parameters to assess the AF risk in β-TM patients.

Intra-annual height increment of Pinus sylvestris at high latitudes in Finland.

PubMed

Salminen, Hannu; Jalkanen, Risto

2007-09-01

Intra-annual height growth of Scots pine (Pinus sylvestris L.) in four stands was followed for up to four growing seasons (2000-2003) in the northern boreal zone in Lapland. Elongation of the leader shoot correlated with temperature sum expressed as degree-days. Total length of the leader shoot correlated with growth rate but not with duration of the height-growth period. The longer the annual shoot at the end of the season, the greater the height increment per degree- and growing day. Height-growth cessation was defined as the date when 95% of the total shoot length was achieved. In all stands and all years, height growth ceased when, on average, 41% of the relative temperature sum of the site was achieved (range of variation 38-43%). The relative temperature sum was calculated by dividing the actual temperature sum by the long-term mean for the site. Our results suggest that annual height growth is finished when a location-specific temperature sum threshold is attained.

Vegetation anomalies caused by antecedent precipitation in most of the world

NASA Astrophysics Data System (ADS)

Papagiannopoulou, C.; Miralles, D. G.; Dorigo, W. A.; Verhoest, N. E. C.; Depoorter, M.; Waegeman, W.

2017-07-01

Quantifying environmental controls on vegetation is critical to predict the net effect of climate change on global ecosystems and the subsequent feedback on climate. Following a non-linear Granger causality framework based on a random forest predictive model, we exploit the current wealth of multi-decadal satellite data records to uncover the main drivers of monthly vegetation variability at the global scale. Results indicate that water availability is the most dominant factor driving vegetation globally: about 61% of the vegetated surface was primarily water-limited during 1981-2010. This included semiarid climates but also transitional ecoregions. Intra-annually, temperature controls Northern Hemisphere deciduous forests during the growing season, while antecedent precipitation largely dominates vegetation dynamics during the senescence period. The uncovered dependency of global vegetation on water availability is substantially larger than previously reported. This is owed to the ability of the framework to (1) disentangle the co-linearities between radiation/temperature and precipitation, and (2) quantify non-linear impacts of climate on vegetation. Our results reveal a prolonged effect of precipitation anomalies in dry regions: due to the long memory of soil moisture and the cumulative, non-linear, response of vegetation, water-limited regions show sensitivity to the values of precipitation occurring three months earlier. Meanwhile, the impacts of temperature and radiation anomalies are more immediate and dissipate shortly, pointing to a higher resilience of vegetation to these anomalies. Despite being infrequent by definition, hydro-climatic extremes are responsible for up to 10% of the vegetation variability during the 1981-2010 period in certain areas, particularly in water-limited ecosystems. Our approach is a first step towards a quantitative comparison of the resistance and resilience signature of different ecosystems, and can be used to benchmark Earth system models in their representations of past vegetation sensitivity to changes in climate.

Intra-Mathematical Connections Made by High School Students in Performing Calculus Tasks

ERIC Educational Resources Information Center

García-García, Javier; Dolores-Flores, Crisólogo

2018-01-01

In this article, we report the results of research that explores the intra-mathematical connections that high school students make when they solve Calculus tasks, in particular those involving the derivative and the integral. We consider mathematical connections as a cognitive process through which a person relates or associates two or more ideas,…

Teaching to the Golem: A Pedagogical Intra-Action

ERIC Educational Resources Information Center

Tanner, Samuel Jaye

2017-01-01

This article considers the pedagogical nature of an intra-action involving the author, his high school student's final project in an English class (a golem), and his school administrators. The author relies on narrative scholarship to both tell and interpret a story of his experience as a high school English and drama teacher, to illustrate the…

Aggregation and morphology control enables multiple cases of high-efficiency polymer solar cells

PubMed Central

Liu, Yuhang; Zhao, Jingbo; Li, Zhengke; Mu, Cheng; Hu, Huawei; Jiang, Kui; Lin, Haoran; Ade, Harald; Yan, He

2014-01-01

Although the field of polymer solar cell has seen much progress in device performance in the past few years, several limitations are holding back its further development. For instance, current high-efficiency (>9.0%) cells are restricted to material combinations that are based on limited donor polymers and only one specific fullerene acceptor. Here we report the achievement of high-performance (efficiencies up to 10.8%, fill factors up to 77%) thick-film polymer solar cells for multiple polymer:fullerene combinations via the formation of a near-ideal polymer:fullerene morphology that contains highly crystalline yet reasonably small polymer domains. This morphology is controlled by the temperature-dependent aggregation behaviour of the donor polymers and is insensitive to the choice of fullerenes. The uncovered aggregation and design rules yield three high-efficiency (>10%) donor polymers and will allow further synthetic advances and matching of both the polymer and fullerene materials, potentially leading to significantly improved performance and increased design flexibility. PMID:25382026

Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

PubMed

Ikegami, Keisuke; Yoshimura, Takashi

2016-02-01

Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip

PubMed Central

Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Martin, Timothy J.; Domb, Benjamin G.

2016-01-01

The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection—local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814

Culture Clash Invades Miami: Oral Histories and Ethnography Center Stage

ERIC Educational Resources Information Center

Garcia, David G.

2008-01-01

Using a critical race theory (CRT) framework, this article compares the playwriting methods of the Chicano--Latino theater trio, Culture Clash, to a counterstorytelling methodology. The author uncovers the tenets of a critical race theater in the trio's site-specific ethnographic play, "Radio Mambo: Culture Clash Invades Miami". He…

Uncovering the Dark Energy of Aging.

PubMed

Melov, Simon

2016-10-26

A medically relevant understanding of aging requires an appreciation for how time degrades specific, healthy features of individual organisms over the course of their lives. Zach Pincus and colleagues make a key step in this direction, using C. elegans as a model system. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptional control of secondary growth and wood formation.

Treesearch

Juan Du; Andrew Groover

2010-01-01

Secondary growth and wood formation are products of the vascular cambium, a lateral meristem. Although the mechanisms have only recently begun to be uncovered, transcriptional regulation appears increasingly central to the regulation of secondary growth. The importance of transcriptional regulation is illustrated by the correlation of expression of specific classes of...

Linguistic Correlates of Social Support

ERIC Educational Resources Information Center

Suppes, Alexandra

2010-01-01

The perception that support is available is central to a person's well being. Nonetheless, naturalistic studies and experimental manipulations of support visibility have uncovered that receiving specific acts of support can entail an emotional cost and that a supportive act is most effective when it is accomplished outside of the recipient's…

Learner Centered Classroom in Science Instruction: Providing Feedback with Technology Integration

ERIC Educational Resources Information Center

Yilmaz, Ozkan

2017-01-01

"Learner centered" term points out environments that attention to the learners brings to the educational setting. This term includes teaching practices: effort to uncover what learners think in a specific problem on hand, talking about their misconceptions and, giving them situations to readjust their ideas. In Learner centered…

Understanding the Manga Hype: Uncovering the Multimodality of Comic-Book Literacies

ERIC Educational Resources Information Center

Schwartz, Adam; Rubinstein-Avila, Eliane

2006-01-01

The authors introduce manga to educators, inspired by the comics' explosive entry into U.S. popular culture. The word "manga" refers specifically to printed, Japanese-style comics found in graphic-novel format--not to be confused with "anime" (animated Japanese cartoons, including moving images on television, movies, video…

(Re/Dis)assembling Learning Practices Online with Fluid Objects and Spaces

ERIC Educational Resources Information Center

Thompson, Terrie Lynn

2012-01-01

Actor network theory (ANT) is used to explore how work-learning is enacted in informal online communities and illustrates how researchers might use sociomaterial approaches to uncover complexities, uncertainties, and specificities of work-learning practices. Participants in this study were self-employed workers. The relational and material aspects…

Preparing Principals for Social Justice Leadership

ERIC Educational Resources Information Center

Baker-Martinez, Darcy

2012-01-01

The purpose of this study is to examine the experiences of social justice leaders to uncover specific leadership competencies that may inform current principal preparation programs. This study employed a qualitative multiple case study design. The three participants all shared many common strategies on how they manage the multiple forms of…

Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutzeit, Andreas, E-mail: Andreas.Gutzeit@ksw.ch; Binkert, Christoph A.; Schoch, Eric

2009-01-15

Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to toleratemore » water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.« less

Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

PubMed

Hawser, Stephen; Hoban, Daryl J; Badal, Robert E; Bouchillon, Samuel K; Biedenbach, Douglas; Hackel, Meredith; Morrissey, Ian

2015-02-01

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.

Social Contact Networks and Mixing among Students in K-12 Schools in Pittsburgh, PA

PubMed Central

Guclu, Hasan; Read, Jonathan; Vukotich, Charles J.; Galloway, David D.; Gao, Hongjiang; Rainey, Jeanette J.; Uzicanin, Amra; Zimmer, Shanta M.; Cummings, Derek A. T.

2016-01-01

Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools. PMID:26978780

Social Contact Networks and Mixing among Students in K-12 Schools in Pittsburgh, PA.

PubMed

Guclu, Hasan; Read, Jonathan; Vukotich, Charles J; Galloway, David D; Gao, Hongjiang; Rainey, Jeanette J; Uzicanin, Amra; Zimmer, Shanta M; Cummings, Derek A T

2016-01-01

Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools.

The use of simulation in healthcare: from systems issues, to team building, to task training, to education and high stakes examinations.

PubMed

Orledge, Jeffrey; Phillips, William J; Murray, W Bosseau; Lerant, Anna

2012-08-01

Simulation in healthcare is becoming increasingly used. This review will spotlight some of the uses of simulation in healthcare training. Previously, evaluation of simulation training was typically from evaluations from trainees. Recent articles, however, have linked simulation training to actual patient outcomes and demonstrated skill retention up to 1 year. Objective measurements have demonstrated positive effects on healthcare education, have been successfully used in high stakes examinations, and have uncovered systems and patient safety issues. This article will review some recent studies showing how simulation can have a positive effect on patient outcomes and skill retention, uncover systems issues related to patient safety, and how simulation can be used in credentialing, and other high stakes examinations.

The "seat belt mark" sign: a call for increased vigilance among physicians treating victims of motor vehicle accidents.

PubMed

Velmahos, G C; Tatevossian, R; Demetriades, D

1999-02-01

The use of seat belts is shown to cause a specific pattern of internal injuries. Skin bruise corresponding to the site of the seat belt is known as the "seat belt mark" (SBM) sign and is associated with a high incidence of significant organ injuries. No study has yet defined the exact incidence of injuries requiring intervention at the presence of this sign. The objective of this study was to find the incidence of surgically correctable injuries in belted car occupants with a SBM sign and to define strategies of early detection and treatment of such injuries. The prospective study included consecutive patients involved in road traffic accidents who were admitted at an academic Level I trauma center. Of 650 car occupants, 410 (63%) were restrained and 77 (12%) had a SBM across the abdomen, chest or neck. The injuries of these 77 patients were compared with the injuries of belted patients without an SBM sign. Of patients with SBMs, 9 per cent had neck bruises, 32 per cent had chest bruises, 40 per cent had abdominal bruises, and 19 per cent had bruises in multiple sites. No significant neck injuries were detected. Three patients were found to have myocardial contusion, and 10 patients had intra-abdominal injuries (predominantly bowel and mesenteric lacerations) requiring laparotomy. There was a near 4-fold increase in thoracic trauma (22.5% versus 6%; P=0.01) and a near 8-fold increase in intra-abdominal trauma (23% versus 3%; P < 0.0001) between the groups of patients with and without SBMs. The presence of the SBM sign should alert the physician to the high likelihood of specific internal injuries. Routine laparotomy or mandatory evaluation by specific diagnostic tests is not justified; rather, a high index of suspicion with a low threshold for appropriate diagnostic evaluation and/or surgical exploration should be maintained for the optimal management of such patients.

Body sway, aim point fluctuation and performance in rifle shooters: inter- and intra-individual analysis.

PubMed

Ball, Kevin A; Best, Russell J; Wrigley, Tim V

2003-07-01

In this study, we examined the relationships between body sway, aim point fluctuation and performance in rifle shooting on an inter- and intra-individual basis. Six elite shooters performed 20 shots under competition conditions. For each shot, body sway parameters and four aim point fluctuation parameters were quantified for the time periods 5 s to shot, 3 s to shot and 1 s to shot. Three parameters were used to indicate performance. An AMTI LG6-4 force plate was used to measure body sway parameters, while a SCATT shooting analysis system was used to measure aim point fluctuation and shooting performance. Multiple regression analysis indicated that body sway was related to performance for four shooters. Also, body sway was related to aim point fluctuation for all shooters. These relationships were specific to the individual, with the strength of association, parameters of importance and time period of importance different for different shooters. Correlation analysis of significant regressions indicated that, as body sway increased, performance decreased and aim point fluctuation increased for most relationships. We conclude that body sway and aim point fluctuation are important in elite rifle shooting and performance errors are highly individual-specific at this standard. Individual analysis should be a priority when examining elite sports performance.

Intra-abdominal pressure during swimming.

PubMed

Moriyama, S; Ogita, F; Huang, Z; Kurobe, K; Nagira, A; Tanaka, T; Takahashi, H; Hirano, Y

2014-02-01

The present study aimed to determine the intra-abdominal pressure during front crawl swimming at different velocities in competitive swimmers and to clarify the relationships between stroke indices and changes in intra-abdominal pressure. The subjects were 7 highly trained competitive collegiate male swimmers. Intra-abdominal pressure was measured during front crawl swimming at 1.0, 1.2 and 1.4 m · s(-1) and during the Valsalva maneuver. Intra-abdominal pressure was taken as the difference between minimum and maximum values, and the mean of 6 stable front crawl stroke cycles was used. Stroke rate and stroke length were also measured as stroke indices. There were significant differences in stroke rate among all velocities (P < 0.05). However, there was no significant difference in stroke length by velocity. Significant within-subject correlations between intra-abdominal pressure and stroke rate or stroke length (P < 0.01) were observed, although there were no significant correlations between intra-abdominal pressure and stroke indices when controlling for swimming velocity. These findings do not appear to support the effectiveness of trunk training performed by competitive swimmers aimed at increasing intra-abdominal pressure. © Georg Thieme Verlag KG Stuttgart · New York.

Microfluidics Expanding the Frontiers of Microbial Ecology

PubMed Central

Rusconi, Roberto; Garren, Melissa; Stocker, Roman

2014-01-01

The ability afforded by microfluidics to observe the behaviors of microbes in highly controlled and confined microenvironments, across scales from a single cell to mixed communities, has significantly contributed to expand the frontiers of microbial ecology over the last decade. Spatially and temporally varying distributions of organisms and chemical cues that mimic natural microbial habitats can now be established by exploiting physics at the micrometer scale and by incorporating structures with specific geometries and materials. Here we review applications of microfluidics that have resulted in highly insightful discoveries on fundamental aspects of microbial life, ranging from growth and sensing to cell-cell interactions and population dynamics. We anticipate that this flexible, multidisciplinary technology will continue to facilitate discoveries regarding the ecology of microorganisms and help uncover strategies to control phenomena such as biofilm formation and antibiotic resistance. PMID:24773019

New classes of piezoelectrics, ferroelectrics, and antiferroelectrics by first-principles high-throughput materials design

NASA Astrophysics Data System (ADS)

Bennett, Joseph

2013-03-01

Functional materials, such as piezoelectrics, ferroelectrics, and antiferroelectrics, exhibit large changes with applied fields and stresses. This behavior enables their incorporation into a wide variety of devices in technological fields such as energy conversion/storage and information processing/storage. Discovery of functional materials with improved performance or even new types of responses is thus not only a scientific challenge, but can have major impacts on society. In this talk I will review our efforts to uncover new families of functional materials using a combined crystallographic database/high-throughput first-principles approach. I will describe our work on the design and discovery of thousands of new functional materials, specifically the LiAlSi family as piezoelectrics, the LiGaGe family as ferroelectrics, and the MgSrSi family as antiferroelectrics.

A Multicenter Trial of the Proficiency of Smart Quantitative Sensation Tests

PubMed Central

Dyck, Peter J.; Argyros, Barbara; Russell, James W.; Gahnstrom, Linde E.; Nalepa, Susan; Albers, James W.; Lodermeier, Karen A.; Zafft, Andrew J.; Dyck, P. James B.; Klein, Christopher J.; Litchy, William J.; Davies, Jenny L.; Carter, Rickey E.; Melton, L. Joseph

2014-01-01

Introduction We assessed proficiency (accuracy and intra- and inter-test reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic polyneuropathy (DSPN). Methods Technologists from 3 medical centers using different but identical QSTs assessed independently 6 modalities of sensation of foot (or leg) twice in patients without (n = 6) and with (n = 6) DSPN using smart computer assisted QSTs. Results Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intra-class correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra- or inter-test differences were observed. Discussion These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra- or inter-test differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length-dependent sensorimotor polyneuropathies. PMID:23929701

Intra-Specific Latitudinal Clines in Leaf Carbon, Nitrogen, and Phosphorus and their Underlying Abiotic Correlates in Ruellia Nudiflora.

PubMed

Abdala-Roberts, Luis; Covelo, Felisa; Parra-Tabla, Víctor; Terán, Jorge C Berny Mier Y; Mooney, Kailen A; Moreira, Xoaquín

2018-01-12

While plant intra-specific variation in the stoichiometry of nutrients and carbon is well documented, clines for such traits have been less studied, despite their potential to reveal the mechanisms underlying such variation. Here we analyze latitudinal variation in the concentration of leaf nitrogen (N), phosphorus (P), carbon (C) and their ratios across 30 populations of the perennial herb Ruellia nudiflora. In addition, we further determined whether climatic and soil variables underlie any such latitudinal clines in leaf traits. The sampled transect spanned 5° latitude (ca. 900 km) and exhibited a four-fold precipitation gradient and 2 °C variation in mean annual temperature. We found that leaf P concentration increased with precipitation towards lower latitudes, whereas N and C did not exhibit latitudinal clines. In addition, N:P and C:P decreased towards lower latitudes and latitudinal variation in the former was weakly associated with soil conditions (clay content and cation exchange capacity); C:N did not exhibit a latitudinal gradient. Overall, these results emphasize the importance of addressing and disentangling the simultaneous effects of abiotic factors associated with intra-specific clines in plant stoichiometric traits, and highlight the previously underappreciated influence of abiotic factors on plant nutrients operating under sharp abiotic gradients over smaller spatial scales.

Coherent combining of pulsed fiber amplifiers in the nonlinear chirp regime with intra-pulse phase control.

PubMed

Palese, Stephen; Cheung, Eric; Goodno, Gregory; Shih, Chun-Ching; Di Teodoro, Fabio; McComb, Timothy; Weber, Mark

2012-03-26

Two high pulse contrast (> 95 dB) polarization maintaining all-fiber amplifier chains were coherently combined to generate 0.42 mJ, 1 ns 25 kHz pulses with 79% efficiency despite 38 radians of intra-pulse phase distortion. A recursive intra-pulse phase compensation method was utilized to correct for the large nonlinear chirp providing a path for improved coherent waveform control of nanosecond pulse trains.

Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

PubMed

Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

2013-01-01

Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5)-5×10(5) human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy.

Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study

PubMed Central

Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M.; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E.; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P.

2013-01-01

Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy. PMID:23533575

An intra-specific consensus genetic map of pigeonpea [Cajanus cajan (L.) Millspaugh] derived from six mapping populations.

PubMed

Bohra, Abhishek; Saxena, Rachit K; Gnanesh, B N; Saxena, Kulbhushan; Byregowda, M; Rathore, Abhishek; Kavikishor, P B; Cook, Douglas R; Varshney, Rajeev K

2012-10-01

Pigeonpea (Cajanus cajan L.) is an important food legume crop of rainfed agriculture. Owing to exposure of the crop to a number of biotic and abiotic stresses, the crop productivity has remained stagnant for almost last five decades at ca. 750 kg/ha. The availability of a cytoplasmic male sterility (CMS) system has facilitated the development and release of hybrids which are expected to enhance the productivity of pigeonpea. Recent advances in genomics and molecular breeding such as marker-assisted selection (MAS) offer the possibility to accelerate hybrid breeding. Molecular markers and genetic maps are pre-requisites for deploying MAS in breeding. However, in the case of pigeonpea, only one inter- and two intra-specific genetic maps are available so far. Here, four new intra-specific genetic maps comprising 59-140 simple sequence repeat (SSR) loci with map lengths ranging from 586.9 to 881.6 cM have been constructed. Using these four genetic maps together with two recently published intra-specific genetic maps, a consensus map was constructed, comprising of 339 SSR loci spanning a distance of 1,059 cM. Furthermore, quantitative trait loci (QTL) analysis for fertility restoration (Rf) conducted in three mapping populations identified four major QTLs explaining phenotypic variances up to 24 %. To the best of our knowledge, this is the first report on construction of a consensus genetic map in pigeonpea and on the identification of QTLs for fertility restoration. The developed consensus genetic map should serve as a reference for developing new genetic maps as well as correlating with the physical map in pigeonpea to be developed in near future. The availability of more informative markers in the bins harbouring QTLs for sterility mosaic disease (SMD) and Rf will facilitate the selection of the most suitable markers for genetic analysis and molecular breeding applications in pigeonpea.

Identification of Transcription Factor Genes and Their Correlation with the High Diversity of Stramenopiles

PubMed Central

Buitrago-Flórez, Francisco Javier; Restrepo, Silvia; Riaño-Pachón, Diego Mauricio

2014-01-01

The biological diversity among Stramenopiles is striking; they range from large multicellular seaweeds to tiny unicellular species, they embrace many ecologically important autothrophic (e.g., diatoms, brown algae), and heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other transcription regulators (TRs) regulate spatial and temporal gene expression. A plethora of transcriptional regulatory proteins have been identified and classified into families on the basis of sequence similarity. The purpose of this work is to identify the TF and TR complement in diverse species belonging to Stramenopiles in order to understand how these regulators may contribute to their observed diversity. We identified and classified 63 TF and TR families in 11 species of Stramenopiles. In some species we found gene families with high relative importance. Taking into account the 63 TF and TR families identified, 28 TF and TR families were established to be positively correlated with specific traits like number of predicted proteins, number of flagella and number of cell types during the life cycle. Additionally, we found gains and losses in TF and TR families specific to some species and clades, as well as, two families with high abundance specific to the autotrophic species and three families with high abundance specific to the heterotropic species. For the first time, there is a systematic search of TF and TR families in Stramenopiles. The attempts to uncover relationships between these families and the complexity of this group may be of great impact, considering that there are several important pathogens of plants and animals, as well as, important species involved in carbon cycling. Specific TF and TR families identified in this work appear to be correlated with particular traits in the Stramenopiles group and may be correlated with the high complexity and diversity in Stramenopiles. PMID:25375671

Identification of transcription factor genes and their correlation with the high diversity of stramenopiles.

PubMed

Buitrago-Flórez, Francisco Javier; Restrepo, Silvia; Riaño-Pachón, Diego Mauricio

2014-01-01

The biological diversity among Stramenopiles is striking; they range from large multicellular seaweeds to tiny unicellular species, they embrace many ecologically important autothrophic (e.g., diatoms, brown algae), and heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other transcription regulators (TRs) regulate spatial and temporal gene expression. A plethora of transcriptional regulatory proteins have been identified and classified into families on the basis of sequence similarity. The purpose of this work is to identify the TF and TR complement in diverse species belonging to Stramenopiles in order to understand how these regulators may contribute to their observed diversity. We identified and classified 63 TF and TR families in 11 species of Stramenopiles. In some species we found gene families with high relative importance. Taking into account the 63 TF and TR families identified, 28 TF and TR families were established to be positively correlated with specific traits like number of predicted proteins, number of flagella and number of cell types during the life cycle. Additionally, we found gains and losses in TF and TR families specific to some species and clades, as well as, two families with high abundance specific to the autotrophic species and three families with high abundance specific to the heterotropic species. For the first time, there is a systematic search of TF and TR families in Stramenopiles. The attempts to uncover relationships between these families and the complexity of this group may be of great impact, considering that there are several important pathogens of plants and animals, as well as, important species involved in carbon cycling. Specific TF and TR families identified in this work appear to be correlated with particular traits in the Stramenopiles group and may be correlated with the high complexity and diversity in Stramenopiles.

Genetic variability among Trichuris ovis isolates from different hosts in Guangdong Province, China revealed by sequences of three mitochondrial genes.

PubMed

Wang, Yan; Liu, Guo-Hua; Li, Jia-Yuan; Xu, Min-Jun; Ye, Yong-Gang; Zhou, Dong-Hui; Song, Hui-Qun; Lin, Rui-Qing; Zhu, Xing-Quan

2013-02-01

This study examined sequence variation in three mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 5 (nad5) and cytochrome b (cytb), among Trichuris ovis isolates from different hosts in Guangdong Province, China. A portion of the cox1 (pcox1), nad5 (pnad5) and cytb (pcytb) genes was amplified separately from individual whipworms by PCR, and was subjected to sequencing from both directions. The size of the sequences of pcox1, pnad5 and pcytb was 618, 240 and 464 bp, respectively. Although the intra-specific sequence variations within T. ovis were 0-0.8% for pcox1, 0-0.8% for pnad5 and 0-1.9% for pcytb, the inter-specific sequence differences among members of the genus Trichuris were significantly higher, being 24.3-26.5% for pcox1, 33.7-56.4% for pnad5 and 24.8-26.1% for pcytb, respectively. Phylogenetic analyses using combined sequences of pcox1, pnad5 and pcytb, with three different computational algorithms (maximum likelihood, maximum parsimony and Bayesian inference), indicated that all of the T. ovis isolates grouped together with high statistical support. These findings demonstrated the existence of intra-specific variation in mtDNA sequences among T. ovis isolates from different hosts, and have implications for studying molecular epidemiology and population genetics of T. ovis.

Fine-needle aspiration in desmoplastic small round cell tumor: a report of 10 new tumors in 8 patients with clinicopathological and molecular correlations with review of the literature.

PubMed

Klijanienko, Jerzy; Colin, Pierre; Couturier, Jérôme; Lagacé, Réal; Fréneaux, Paul; Pierron, Gaëlle; Laé, Marick; Klijanienko, Alice; Brisse, Hervé; Orbach, Daniel; Theocharis, Stamatios

2014-05-01

Desmoplastic small round cell tumor (DSRCT) is a rare round cell sarcoma entity characterized by a specific t(11;22)(p13;q12) translocation, usually intra-abdominal localization and an aggressive clinical outcome. To date, only 35 DSRCT cases diagnosed by fine-needle aspiration have been described. This study reports the cytological diagnosis of DSRCT. Ten tumors from 8 patients were sampled for diagnosis and analyzed to search the characteristic translocation using fluorescence in situ hybridization or reverse transcription polymerase chain reaction methods. Smears were always hypercellular and consisted of nonspecific round cell sarcoma. Nuclei were polymorphic round, kidney-, or heart-shaped. Nuclear molding was usually present. Paranuclear cytoplasmic densities were obvious and noted in 7 cases. Cytonuclear atypia, mitotic figures, numerous crushed nuclei, and apoptosis were frequently seen. Purple-stained stroma was present in 8 cases (ranging from few connective tissue fragments to large hyalinized deposits). Molecular studies based on cytological aspirates were performed in 8 patients. The presence of the fusion gene EWSR1-WT 1 transcript was identified in all, which confirmed the diagnosis of DSRCT. Smears showing poorly differentiated round cells associated with cytoplasmic densities and connective stoma, in a specific clinical context, young adult age, intra-abdominal localization, suggestive immunocytochemical profile, and a unique cytogenetic abnormality are highly specific and allow an accurate diagnosis of DSRCT. © 2014 American Cancer Society.

Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma.

PubMed

Wallin, Jeffrey J; Bendell, Johanna C; Funke, Roel; Sznol, Mario; Korski, Konstanty; Jones, Suzanne; Hernandez, Genevive; Mier, James; He, Xian; Hodi, F Stephen; Denker, Mitchell; Leveque, Vincent; Cañamero, Marta; Babitski, Galina; Koeppen, Hartmut; Ziai, James; Sharma, Neeraj; Gaire, Fabien; Chen, Daniel S; Waterkamp, Daniel; Hegde, Priti S; McDermott, David F

2016-08-30

Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8(+) T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8(+) T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration.

Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma

PubMed Central

Wallin, Jeffrey J.; Bendell, Johanna C.; Funke, Roel; Sznol, Mario; Korski, Konstanty; Jones, Suzanne; Hernandez, Genevive; Mier, James; He, Xian; Hodi, F. Stephen; Denker, Mitchell; Leveque, Vincent; Cañamero, Marta; Babitski, Galina; Koeppen, Hartmut; Ziai, James; Sharma, Neeraj; Gaire, Fabien; Chen, Daniel S.; Waterkamp, Daniel; Hegde, Priti S.; McDermott, David F.

2016-01-01

Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8+ T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8+ T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration. PMID:27571927

Invasive Candidiasis in Various Patient Populations: Incorporating Non-Culture Diagnostic Tests into Rational Management Strategies

PubMed Central

Clancy, Cornelius J.; Shields, Ryan K.; Nguyen, M. Hong

2016-01-01

Mortality rates due to invasive candidiasis remain unacceptably high, in part because the poor sensitivity and slow turn-around time of cultures delay the initiation of antifungal treatment. β-d-glucan (Fungitell) and polymerase chain reaction (PCR)-based (T2Candida) assays are FDA-approved adjuncts to cultures for diagnosing invasive candidiasis, but their clinical roles are unclear. We propose a Bayesian framework for interpreting non-culture test results and developing rational patient management strategies, which considers test performance and types of invasive candidiasis that are most common in various patient populations. β-d-glucan sensitivity/specificity for candidemia and intra-abdominal candidiasis is ~80%/80% and ~60%/75%, respectively. In settings with 1%–10% likelihood of candidemia, anticipated β-d-glucan positive and negative predictive values are ~4%–31% and ≥97%, respectively. Corresponding values in settings with 3%–30% likelihood of intra-abdominal candidiasis are ~7%–51% and ~78%–98%. β-d-glucan is predicted to be useful in guiding antifungal treatment for wide ranges of populations at-risk for candidemia (incidence ~5%–40%) or intra-abdominal candidiasis (~7%–20%). Validated PCR-based assays should broaden windows to include populations at lower-risk for candidemia (incidence ≥~2%) and higher-risk for intra-abdominal candidiasis (up to ~40%). In the management of individual patients, non-culture tests may also have value outside of these windows. The proposals we put forth are not definitive treatment guidelines, but rather represent starting points for clinical trial design and debate by the infectious diseases community. The principles presented here will be applicable to other assays as they enter the clinic, and to existing assays as more data become available from different populations. PMID:29376927

Intra-ventral tegmental area microinjections of urotensin II modulate the effects of cocaine.

PubMed

Mueller, L E; Kausch, M A; Markovic, T; MacLaren, D A A; Dietz, D M; Park, J; Clark, S D

2015-02-01

Although the peptide urotensin II (UII) has well studied direct actions on the cardiovascular system, the UII receptor (UIIR) is expressed by neurons of the hindbrain. Specifically, the UIIR is expressed by the cholinergic neurons of the laterodorsal tegmentum (LDTg) and the pedunculopontine tegmentum (PPTg). These neurons send axons to the ventral tegmental area (VTA), for which the PPTg and LDTg are the sole source of acetylcholine. Therefore, it was hypothesized that UIIR activation within the VTA would modulate reward-related behaviors, such as cocaine-induced drug seeking. Intra-VTA microinjections of UII at high concentrations (1 nmole) established conditioned place preference (CPP), but also blocked cocaine-mediated CPP (10 mg/kg). When rats received systemic sub-effectual doses of cocaine (7.5 mg/kg) with intra-VTA injections of 1 or 10 pmole of UII CPP was formed. Furthermore, the second endogenous ligand for the UIIR, urotensin II-related peptide, had the same effect at the 10 pmole dose. The effects of low doses of UII were blocked by pretreatment with the UIIR antagonist SB657510. Furthermore, it was found that intra-VTA UII (10 pmole) further increased cocaine-mediated (7.5 mg/kg) rises in electrically evoked dopamine in the nucleus accumbens. Our study has found that activation of VTA-resident UIIR produces observable behavioral changes in rats, and that UIIR is able to modulate the effects of cocaine. In addition, it was found that UIIR activation within the VTA can potentiate cocaine-mediated neurochemical effects. Therefore, the coincident activation of the UII-system and cocaine administration may increase the liability for drug taking behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

Cortical Brain Atrophy and Intra-Individual Variability in Neuropsychological Test Performance in HIV Disease

PubMed Central

HINES, Lindsay J.; MILLER, Eric N.; HINKIN, Charles H.; ALGER, Jeffery R.; BARKER, Peter; GOODKIN, Karl; MARTIN, Eileen M.; MARUCA, Victoria; RAGIN, Ann; SACKTOR, Ned; SANDERS, Joanne; SELNES, Ola; BECKER, James T.

2015-01-01

Objective To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Methods Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV−) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD’s) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Results Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. Conclusions IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests. PMID:26303224

Phases of match-play in professional Australian Football: Descriptive analysis and reliability assessment.

PubMed

Rennie, Michael J; Watsford, Mark L; Spurrs, Robert W; Kelly, Stephen J; Pine, Matthew J

2018-06-01

To examine the frequency and time spent in the phases of Australian Football (AF) match-play and to assess the intra-assessor reliability of coding these phases of match-play. Observational, intra-reliability assessment. Video footage of 10 random quarters of AF match-play were coded by a single researcher. Phases of offence, defence, contested play, umpire stoppage, set shot and goal reset were coded using a set of operational definitions. Descriptive statistics were provided for all phases of match-play. Following a 6-month washout period, intra-coder reliability was assessed using typical error of measurement (TEM) and intra-class correlation coefficients (ICC). A quarter of AF match-play involved 128±20 different phases of match-play. The highest proportion of match-play involved contested play (25%), followed by offence (18%), defence (18%) and umpire stoppages (18%). The mean duration of offence, defence, contested play, umpire stoppage, set shot and goal reset were 14, 14, 10, 11, 28 and 47s, respectively. No differences were found between the two coding assessments (p>0.05). ICCs for coding the phases of play demonstrated very high reliability (r=0.902-0.992). TEM of the total time spent in each phase of play represented moderate to good reliability (TEM=1.8-9.3%). Coding of offence, defence and contested play tended to display slightly poorer TEMs than umpire stoppages, set shots and goal resets (TEM=8.1 vs 4.5%). Researchers can reliably code the phases of AF match-play which may permit the analysis of specific elements of competition. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle.

PubMed

Shock, Jennifer L; Fischer, Kael F; DeRisi, Joseph L

2007-01-01

The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression. We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes. Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.

Hierarchical Discriminant Analysis.

PubMed

Lu, Di; Ding, Chuntao; Xu, Jinliang; Wang, Shangguang

2018-01-18

The Internet of Things (IoT) generates lots of high-dimensional sensor intelligent data. The processing of high-dimensional data (e.g., data visualization and data classification) is very difficult, so it requires excellent subspace learning algorithms to learn a latent subspace to preserve the intrinsic structure of the high-dimensional data, and abandon the least useful information in the subsequent processing. In this context, many subspace learning algorithms have been presented. However, in the process of transforming the high-dimensional data into the low-dimensional space, the huge difference between the sum of inter-class distance and the sum of intra-class distance for distinct data may cause a bias problem. That means that the impact of intra-class distance is overwhelmed. To address this problem, we propose a novel algorithm called Hierarchical Discriminant Analysis (HDA). It minimizes the sum of intra-class distance first, and then maximizes the sum of inter-class distance. This proposed method balances the bias from the inter-class and that from the intra-class to achieve better performance. Extensive experiments are conducted on several benchmark face datasets. The results reveal that HDA obtains better performance than other dimensionality reduction algorithms.

Inter- and intra-specific variability in δ13C and δ18O values of freshwater gastropod shells from Lake Lednica, western Poland

NASA Astrophysics Data System (ADS)

Apolinarska, Karina; Pełechaty, Mariusz

2017-09-01

This study focuses on the inter- and intra-specific variability in δ13C and δ18O values of shells and opercula of gastropods sampled live from the littoral zone of Lake Lednica, western Poland. The δ13C and δ18O values were measured in individual opercula of Bithynia tentaculata and in shells of Bithynia tentaculata, Gyraulus albus, Gyraulus crista, Lymnaea sp., Physa fontinalis, Radix auricularia, Theodoxus fluviatilis and Valvata cristata. The gastropods selected for the study are among the species most commonly found in European Quaternary lacustrine sediments. The carbon isotope composition of the gastropod shells was species-specific and the same order of species from the most to the least 13C-depleted was observed at all sites sampled. Differences in shell δ13C values between species were similar at all sampling sites, thus the factors influencing shell isotopic composition were interpreted as species-specific. The δ18O values of shells were similar in all the species investigated. Significant intra-specific variability in shell δ13C and δ18O values was observed not only within the populations of Lake Lednica, which can be explained by heterogeneity of δ13C DIC, δ18O water and water temperature between the sites where macrophytes with snails attached were sampled, but also between individuals sampled from restricted areas of the lake's bottom. The latter points to the importance of factors related to the ontogeny of individual gastropods.

Repeatability and reproducibility of corneal thickness using SOCT Copernicus HR.

PubMed

Vidal, Silvia; Viqueira, Valentín; Mas, David; Domenech, Begoña

2013-05-01

The aim of this study is to determine the reliability of corneal thickness measurements derived from SOCT Copernicus HR (Fourier domain OCT). Thirty healthy eyes of 30 subjects were evaluated. One eye of each patient was chosen randomly. Images were obtained of the central (up to 2.0 mm from the corneal apex) and paracentral (2.0 to 4.0 mm) cornea. We assessed corneal thickness (central and paracentral) and epithelium thickness. The intra-observer repeatability data were analysed using the intra-class correlation coefficient (ICC) for a range of 95 per cent within-subject standard deviation (S(W)) and the within-subject coefficient of variation (C(W)). The level of agreement by Bland-Altman analysis was also represented for the study of the reproducibility between observers and agreement between methods of measurement (automatic versus manual). The mean value of the central corneal thickness (CCT) was 542.4 ± 30.1 μm (SD). There was a high intra-observer agreement, finding the best result in the central sector with an intra-class correlation coefficient of 0.99, 95 per cent CI (0.989 to 0.997) and the worst, in the minimum corneal thickness, with an intra-class correlation coefficient of 0.672, 95 per cent CI (0.417 to 0.829). Reproducibility between observers was very high. The best result was found in the central sector thickness obtained both manually and automatically with an intra-class correlation coefficient of 0.990 in both cases and the worst result in the maximum corneal thickness with an intra-class correlation coefficient of 0.827. The agreement between measurement methods was also very high with intra-class correlation coefficient greater than 0.91. On the other hand the repeatability and reproducibility for epithelial measurements was poor. Pachymetric mapping with SOCT Copernicus HR was found to be highly repeatable and reproducible. We found that the device lacks an appropriate ergonomic design as proper focusing of the laser beam onto the cornea for anterior segment scanning required that patients were positioned slightly farther away from the machine head-rest than in the setup for retinal imaging. © 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.

Rapid and specific detection of Salmonella in water samples using real-time PCR and High Resolution Melt (HRM) curve analysis.

PubMed

van Blerk, G N; Leibach, L; Mabunda, A; Chapman, A; Louw, D

2011-01-01

A real-time PCR assay combined with a pre-enrichment step for the specific and rapid detection of Salmonella in water samples is described. Following amplification of the invA gene target, High Resolution Melt (HRM) curve analysis was used to discriminate between products formed and to positively identify invA amplification. The real-time PCR assay was evaluated for specificity and sensitivity. The assay displayed 100% specificity for Salmonella and combined with a 16-18 h non-selective pre-enrichment step, the assay proved to be highly sensitive with a detection limit of 1.0 CFU/ml for surface water samples. The detection assay also demonstrated a high intra-run and inter-run repeatability with very little variation in invA amplicon melting temperature. When applied to water samples received routinely by the laboratory, the assay showed the presence of Salmonella in particularly surface water and treated effluent samples. Using the HRM based assay, the time required for Salmonella detection was drastically shortened to less than 24 h compared to several days when using standard culturing methods. This assay provides a useful tool for routine water quality monitoring as well as for quick screening during disease outbreaks.

Implementation of molecular intra-operative assessment of sentinel lymph node in breast cancer.

PubMed

Khaddage, Abir; Berremila, Sid-Ali; Forest, Fabien; Clemenson, Alix; Bouteille, Catherine; Seffert, Pierre; Peoc'h, Michel

2011-02-01

Sentinel lymph node (SLN) biopsy is used as a staging procedure in early breast cancer, however, histology based intra-operative assessment of the SLN status has a low sensitivity. The one-step nucleic acid amplification (OSNA) method was developed to detect metastases by amplification of cytokeratin (CK) 19 mRNA. Experience with OSNA during a French multi-centric prospective study, as well as intra-operative clinical routine use, is reported. For the clinical study 80 SLNs from 46 patients were assessed. During routine use, the central slice of the SLN from 197 patients was investigated by permanent histology and the remainder was assessed by OSNA. During the clinical study, OSNA detected 15/17 metastases, including all the macrometastases, reaching a 96.3% concordance rate, 88.2% sensitivity and 98.4% specificity. During routine use, both OSNA and histology detected 25 patients with metastasis. OSNA is an accurate tool for intra-operative assessment of SLN status and could reduce the need for second surgery.

[Posttraumatic deformities of the knee joint : Intra-articular osteotomy after malreduction of tibial head fractures].

PubMed

Frosch, K-H; Krause, M; Frings, J; Drenck, T; Akoto, R; Müller, G; Madert, J

2016-10-01

Malreduction of tibial head fractures often leads to malalignment of the lower extremity, pain, limited range of motion and instability. The extent of the complaints and the degree of deformity requires an exact analysis and a standardized approach. True ligamentous instability should be distinguished from pseudoinstability of the joint. Also extra- and intra-articular deformities have to be differentiated. In intra-articular deformities the extent of articular surface displacement, defects and clefts must be accurately evaluated. A specific surgical approach is necessary, which allows adequate visualization, correct osteotomy and refixation of the fractured area of the tibial head. In the long-term course good clinical results are described for intra-articular osteotomies. If the joint is damaged to such an extent that it cannot be reconstructed or in cases of advanced posttraumatic osteoarthritis, total knee arthroplasty may be necessary; however, whenever possible and reasonable, anatomical reconstruction and preservation of the joint should be attempted.

An approach to evaluate the intra-urban thermal variability in summer using an urban indicator.

PubMed

Massetti, Luciano; Petralli, Martina; Brandani, Giada; Orlandini, Simone

2014-09-01

Urban planners and managers need tools to evaluate the performance of the present state and future development of cities in terms of comfort and quality of life. In this paper, an approach to analyse the intra-urban summer thermal variability, using an urban planning indicator, is presented. The proportion of buildings and concrete surfaces in a specific buffer area are calculated. Besides, the relationship between urban and temperature indicators is investigated and used to produce thermal maps of the city. This approach is applied to the analysis of intra-urban variability in Florence (Italy), of two thermal indices (heat index and cooling degree days) used to evaluate impacts on thermal comfort and energy consumption for indoor cooling. Our results suggest that urban planning indicators can describe intra-urban thermal variability in a way that can easily be used by urban planners for evaluating the effects of future urbanization scenarios on human health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Ixekizumab Treatment on Work Productivity for Patients With Moderate-to-Severe Plaque Psoriasis: Analysis of Results From 3 Randomized Phase 3 Clinical Trials.

PubMed

Armstrong, April W; Lynde, Charles W; McBride, Sandy R; Ståhle, Mona; Edson-Heredia, Emily; Zhu, Baojin; Amato, David; Nikaï, Enkeleida; Yang, Fan Emily; Gordon, Kenneth B

2016-06-01

Therapies that reduce psoriasis symptoms may improve work productivity. To assess the effect of ixekizumab therapy on work productivity, measured by the Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO). Three multicenter, randomized double-blind phase 3 trials conducted during the following periods: December 2011 through August 2014 (UNCOVER-1), May 2012 through April 2015 (UNCOVER-2), and August 2012 through July 2014 (UNCOVER-3). Adult outpatients with moderate-to-severe chronic plaque psoriasis were included. In UNCOVER-1, patients were randomized 1:1:1 to subcutaneous placebo or 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 12 weeks; UNCOVER-2 and UNCOVER-3 also had an etanercept arm (50 mg twice weekly). Maintenance of initial ixekizumab response was evaluated in UNCOVER-1 and UNCOVER-2 during a randomized withdrawal period following week 12 through week 60. The WPAI-PSO questionnaire was administered at baseline and week 12 for all patients and at weeks 24, 36, 52, and 60 for patients in UNCOVER-1 and UNCOVER-2. Change in work productivity from baseline as measured by WPAI-PSO scores. Across trials, 5101 patients consented; 3866 were randomized (mean [SD] age, UNCOVER-1, 45.7 [12.9] y, 68.1% male; UNCOVER-2: 45.0 [13.0] y, 67.1% male; UNCOVER-3: 45.8 [13.1] y, 68.2% male). At week 12 in UNCOVER-1, the ixekizumab Q4W and ixekizumab Q2W groups showed significantly greater improvements in WPAI-PSO scores (least squares mean change from baseline [SE]) relative to placebo: absenteeism (-3.5 [0.87], P < .001; -2.6 [0.84], P = .003, respectively, vs 0.2 [0.88]), presenteeism (-18.8 [1.28], P < .001; -18.3 [1.24], P < .001, vs 0.5 [1.30]), work productivity loss (-20.6 [1.38], P < .001; -19.8 [1.33], P < .001, vs -0.8 [1.40]), and activity impairment (-24.5 [1.18], P < .001; -25.2 [1.15], P < .001, vs 0.8 [1.18]). Similar results were obtained for UNCOVER-2 and UNCOVER-3, with the exception of absenteeism with ixekizumab Q4W in UNCOVER-2. Additionally, ixekizumab-treated patients showed significantly greater improvements in WPAI-PSO scores vs etanercept-treated patients: UNCOVER-2: presenteeism, work productivity loss, activity impairment (P < .001 both doses), UNCOVER-3: activity impairment (ie, regular activities outside of work) (ixekizumab Q2W; P = .009). Improvements in WPAI-PSO scores at week 12 were sustained to at least week 60. Ixekizumab-treated patients reported short- and long-term improvements in work productivity, which could lead to reduced productivity-related cost burden in patients with psoriasis. clinicaltrials.gov Identifiers: NCT01474512, NCT01597245, NCT01646177.

Using peptide array to identify binding motifs and interaction networks for modular domains.

PubMed

Li, Shawn S-C; Wu, Chenggang

2009-01-01

Specific protein-protein interactions underlie all essential biological processes and form the basis of cellular signal transduction. The recognition of a short, linear peptide sequence in one protein by a modular domain in another represents a common theme of macromolecular recognition in cells, and the importance of this mode of protein-protein interaction is highlighted by the large number of peptide-binding domains encoded by the human genome. This phenomenon also provides a unique opportunity to identify protein-protein binding events using peptide arrays and complementary biochemical assays. Accordingly, high-density peptide array has emerged as a useful tool by which to map domain-mediated protein-protein interaction networks at the proteome level. Using the Src-homology 2 (SH2) and 3 (SH3) domains as examples, we describe the application of oriented peptide array libraries in uncovering specific motifs recognized by an SH2 domain and the use of high-density peptide arrays in identifying interaction networks mediated by the SH3 domain. Methods reviewed here could also be applied to other modular domains, including catalytic domains, that recognize linear peptide sequences.

Depth-specific optogenetic control in vivo with a scalable, high-density μLED neural probe

NASA Astrophysics Data System (ADS)

Scharf, Robert; Tsunematsu, Tomomi; McAlinden, Niall; Dawson, Martin D.; Sakata, Shuzo; Mathieson, Keith

2016-06-01

Controlling neural circuits is a powerful approach to uncover a causal link between neural activity and behaviour. Optogenetics has been widely adopted by the neuroscience community as it offers cell-type-specific perturbation with millisecond precision. However, these studies require light delivery in complex patterns with cellular-scale resolution, while covering a large volume of tissue at depth in vivo. Here we describe a novel high-density silicon-based microscale light-emitting diode (μLED) array, consisting of up to ninety-six 25 μm-diameter μLEDs emitting at a wavelength of 450 nm with a peak irradiance of 400 mW/mm2. A width of 100 μm, tapering to a 1 μm point, and a 40 μm thickness help minimise tissue damage during insertion. Thermal properties permit a set of optogenetic operating regimes, with ~0.5 °C average temperature increase. We demonstrate depth-dependent activation of mouse neocortical neurons in vivo, offering an inexpensive novel tool for the precise manipulation of neural activity.

Simultaneous wireless assessment of intra-oral pH and temperature.

PubMed

Farella, M; Loke, C; Sander, S; Songini, A; Allen, M; Mei, L; Cannon, R D

2016-08-01

Intra-oral pH plays an important role in the pathogenesis of tooth erosion and decay, but there is limited information about its variation in real life settings. The aims of this research were to: 1) develop a wireless device, which can be used to continuously monitor intra-oral pH and temperature in real-time; 2) test and validate the device under controlled laboratory conditions; and 3) collect data in a natural environment in a sample of healthy volunteers. A wireless device for measuring pH and temperature simultaneously was developed, calibrated and validated against the gold standard glass electrode pH meter. A smart phone was used as data logger. The wireless device was embedded in an oral appliance and worn by eleven participants (mean age 31.1±6.9years) for 24h, while conducting standardised drinking tasks and regular daily activities. The wireless device could accurately measure pH and temperature both in vitro and in vivo. The recovery time following the swallow of a standard acidic drink varied markedly among individuals (mean=1.3±0.9min). The intra-oral pH and temperature recorded in the natural environment also showed a large inter- and intra-individual variability. The average intra-oral pH when asleep (6.7±0.5) was lower (p<0.001) than when awake (7.2±0.5). The average intra-oral temperature during sleep (35.6±0.5°C) was higher (p<0.001) than when awake (34.5±0.7°C). Intra-oral pH and temperature can be continuously and wirelessly assessed in real-life settings, and show individual-specific patterns with circadian variations. Intra-oral pH becomes slightly acidic during sleep while intra-oral temperature increases and fluctuates less. We propose a wireless device that is capable of measuring intra-oral pH over a 24-h period. We found marked inter-individual variation after acidic stimuli, and day to sleep time variation of both intra-oral temperature and pH. Our approach may provide new insight into the relationship between oral pH, tooth wear and decay. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of intra- and extra-epithelial secretory IgA in chlamydial infections

PubMed Central

Armitage, Charles W; O’Meara, Connor P; Harvie, Marina C G; Timms, Peter; Wijburg, Odilia L; Beagley, Kenneth W

2014-01-01

Immunoglobulin A is an important mucosal antibody that can neutralize mucosal pathogens by either preventing attachment to epithelia (immune exclusion) or alternatively inhibit intra-epithelial replication following transcytosis by the polymeric immunoglobulin receptor (pIgR). Chlamydia trachomatis is a major human pathogen that initially targets the endocervical or urethral epithelium in women and men, respectively. As both tissues contain abundant secretory IgA (SIgA) we assessed the protection afforded by IgA targeting different chlamydial antigens expressed during the extra- and intra-epithelial stages of infection. We developed an in vitro model using polarizing cells expressing the murine pIgR together with antigen-specific mouse IgA, and an in vivo model using pIgR−/− mice. Secretory IgA targeting the extra-epithelial chlamydial antigen, the major outer membrane protein, significantly reduced infection in vitro by 24% and in vivo by 44%. Conversely, pIgR-mediated delivery of IgA targeting the intra-epithelial inclusion membrane protein A bound to the inclusion but did not reduce infection in vitro or in vivo. Similarly, intra-epithelial IgA targeting the secreted protease Chlamydia protease-like activity factor also failed to reduce infection. Together, these data suggest the importance of pIgR-mediated delivery of IgA targeting extra-epithelial, but not intra-epithelial, chlamydial antigens for protection against a genital tract infection. PMID:24827556

Steady state and transient simulation of anion exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Dekel, Dario R.; Rasin, Igal G.; Page, Miles; Brandon, Simon

2018-01-01

We present a new model for anion exchange membrane fuel cells. Validation against experimental polarization curve data is obtained for current densities ranging from zero to above 2 A cm-2. Experimental transient data is also successfully reproduced. The model is very flexible and can be used to explore the system's sensitivity to a wide range of material properties, cell design specifications, and operating parameters. We demonstrate the impact of gas inlet relative humidity (RH), operating current density, ionomer loading and ionomer ion exchange capacity (IEC) values on cell performance. In agreement with the literature, high air RH levels are shown to improve cell performance. At high current densities (>1 A cm-2) this effect is observed to be especially significant. Simulated hydration number distributions across the cell reveal the related critical dependence of cathode hydration on air RH and current density values. When exploring catalyst layer design, optimal intermediate ionomer loading values are demonstrated. The benefits of asymmetric (cathode versus anode) electrode design are revealed, showing enhanced performance using higher cathode IEC levels. Finally, electrochemical reaction profiles across the electrodes uncover inhomogeneous catalyst utilization. Specifically, at high current densities the cathodic reaction is confined to a narrow region near the membrane.

Urine test for HPV genotypes as a predictor of precancerous cervical lesions and for cervical cancer screening.

PubMed

Maged, Ahmed M; Saad, Hany; Salah, Emad; Meshaal, Hadeer; AbdElbar, Mostafa; Omran, Eman; Eldaly, Ashraf

2018-06-01

To assess the sensitivity of a urine test for high-risk HPV DNA genotypes in the detection of high-grade squamous intra-epithelial lesion (HSIL) and its correlation with pathologic precancerous lesions. The present prospective cross-sectional study included women referred to Kasr AlAiny Medical School, Cairo, Egypt, for cervical smear anomalies, a history of cervical smear anomalies, or for suspicious cervix between May 1, 2015, and April 30, 2017. Paired urine tests and cervical smears were performed. HPV DNA was detected in urine using polymerase chain reaction and cervical smears were performed with a cervical spatula and a cytobrush. Agreement between urine test results and pathology was examined. In total, 1375 women were included. Urine test for high-risk HPV DNA demonstrated 97.8% (95% confidence interval [CI] 92.1%-99.7%) sensitivity and 100% (95% CI 99.7%-100.0%) specificity for HSIL. Overall, 87 women had a positive urine test for high-risk HPV; of these, 82 (94.3%, 95% CI 87.1%-98.1%) had pathologic findings of cervical intra-epithelial neoplasia 2 or 3 (CIN2/3). Similarly, 89 women had HSIL cytology; again, 82 had CIN2/3 (92.1%; 95% CI, 84.3%-96.4%). There was good agreement between a positive urine test for high-risk HPV DNA genotypes and pathologic findings of CIN2/3. © 2018 International Federation of Gynecology and Obstetrics.

TH-CD-207A-12: Impacts of Inter- and Intra-Fractional Organ Motion for High-Risk Prostate Cancer Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hassan Rezaeian, N; Chi, Y; Zhou, Y

2016-06-15

Purpose: We are conducting a clinical trial on stereotactic body radiation therapy (SBRT) for high-risk prostate cancer. Doses to three targets, prostate, intra-prostatic lesion, and pelvic lymph node (PLN) region, are escalated to three different levels via simultaneous integrated boost technique. Inter-/intra-fractional organ motions deteriorate planned dose distribution. This study aims at developing a dose reconstruction system to comprehensively understand the impacts of organ motion in our clinical trial. Methods: A 4D dose reconstruction system has been developed for this study. Using a GPU-based Monte-Carlo dose engine and delivery log file, the system is able to reconstruct dose on staticmore » or dynamic anatomy. For prostate and intra-prostatic targets, intra-fractional motion is the main concern. Motion trajectory acquired from Calypso in previously treated SBRT patients were used to perform 4D dose reconstructions. For pelvic target, inter-fractional motion is one concern. Eight patients, each with four cone beam CTs, were used to derive fractional motion. The delivered dose was reconstructed on the deformed anatomy. Dosimetric parameters for delivered dose distributions of the three targets were extracted and compared with planned levels. Results: For prostate intra-fractional motion, the mean 3D motion amplitude during beam delivery ranged from 1.5mm to 5.0mm and the average among all patients was 2.61mm. Inter-fractional motion for the PLN target was more significant. The average amplitude among patients was 4mm with the largest amplitude up to 9.6mm. The D95% deviation from planned level for prostate PTVs and GTVs are on average less than<0.1% and this deviation for intra-prostatic lesion PTVs and GTVs were more prominent. The dose at PLN was significantly affected with D{sub 95}% reduced by up to 44%. Conclusion: Intra-/inter-fractional organ motion is a concern for high-risk prostate SBRT, particularly for the PLN target. Our dose reconstruction approach can also serve as the basis to guide treatment adaptation.« less

White Paper: Recommendations on the Conduct of Superiority and Organism-Specific Clinical Trials of Antibacterial Agents for the Treatment of Infections Caused by Drug-Resistant Bacterial Pathogens

PubMed Central

2012-01-01

There is a critical need for new pathways to develop antibacterial agents to treat life-threatening infections caused by highly resistant bacteria. Traditionally, antibacterial agents have been studied in noninferiority clinical trials that focus on one site of infection (eg, pneumonia, intra-abdominal infection). Conduct of superiority trials for infections caused by highly antibiotic-resistant bacteria represents a new, and as yet, untested paradigm for antibacterial drug development. We sought to define feasible trial designs of antibacterial agents that could enable conduct of superiority and organism-specific clinical trials. These recommendations are the results of several years of active dialogue among the white paper's drafters as well as external collaborators and regulatory officials. Our goal is to facilitate conduct of new types of antibacterial clinical trials to enable development and ultimately approval of critically needed new antibacterial agents. PMID:22891041

Relevance of the Axis Spermidine/eIF5A for Plant Growth and Development

PubMed Central

Belda-Palazón, Borja; Almendáriz, Carla; Martí, Esmeralda; Carbonell, Juan; Ferrando, Alejandro

2016-01-01

One key role of the essential polyamine spermidine in eukaryotes is to provide the 4-aminobutyl moiety group destined to the post-translational modification of a lysine in the highly conserved translation factor eIF5A. This modification is catalyzed by two sequential enzymatic steps leading to the activation of eIF5A by the conversion of one conserved lysine to the unusual amino acid hypusine. The active translation factor facilitates the sequence-specific translation of polyproline sequences that otherwise cause ribosome stalling. In spite of the well-characterized involvement of active eIF5A in the translation of proline repeat-rich proteins, its biological role has been recently elucidated only in mammals, and it is poorly described at the functional level in plants. Here we describe the alterations in plant growth and development caused by RNAi-mediated conditional genetic inactivation of the hypusination pathway in Arabidopsis thaliana by knocking-down the enzyme deoxyhypusine synthase. We have uncovered that spermidine-mediated activation of eIF5A by hypusination is involved in several aspects of plant biology such as the control of flowering time, the aerial and root architecture, and root hair growth. In addition this pathway is required for adaptation to challenging growth conditions such as high salt and high glucose medium and to elevated concentrations of the plant hormone ABA. We have also performed a bioinformatic analysis of polyproline-rich containing proteins as putative eIF5A targets to uncover their organization in clusters of protein networks to find molecular culprits for the disclosed phenotypes. This study represents a first attempt to provide a holistic view of the biological relevance of the spermidine-dependent hypusination pathway for plant growth and development. PMID:26973686

Plant hydraulic strategies and their variability at high latitudes: insights from a southern Canadian boreal forest site

NASA Astrophysics Data System (ADS)

Pappas, C.; Matheny, A. M.; Maillet, J.; Baltzer, J. L.; Stephens, J.; Barr, A.; Black, T. A.; Sonnentag, O.

2016-12-01

Boreal forests cover about one third of the world's forested area with a large part of the boreal zone located in Canada. These high-latitude ecosystems respond rapidly to environmental changes. Plant water stress and the resulting drought-induced mortality has been recently hypothesised as a major driver of forest changes in western Canada. Although boreal forests often exhibit low floristic complexity, local scale abiotic heterogeneities may lead to highly variable plant functional traits and thus to diverging plant responses to environmental changes. However, detailed measurements of plant hydraulic strategies and their inter- and intra-specific variability are still lacking for these ecosystems. Here, we quantify plant water use and hydraulic strategies of black spruce (Picea mariana) and larch (Larix laricina), that are widespread in the boreal zone, at a long-term monitoring site located in central Saskatchewan (53.99° N, 105.12° W; elevation 628.94 m a.s.l.). The site is characterized by a mature black spruce overstorey that dominates the landscape with few larch individuals. The ground cover consists mainly of mosses with some peat moss and lichens over a rich soil organic layer. Tree-level sap flux density, measured with Granier-style thermal dissipation probes (N=39), and concurrently recorded radial stem dynamics, measured with high frequency dendrometers (N=13), are used to quantify plant hydraulic functioning during the 2016 growing season. Hydrometeorological measurements, including soil moisture and micrometeorological data, are used to describe environmental constraints in plant water use. Tree-level dynamics are then integrated to the landscape and compared with ecosystem-level evapotranspiration measurements from an adjacent eddy-covariance flux tower. This experimental design allows us to quantify the main environmental drivers that shape plant hydraulic strategies in this southern boreal zone and to provide new insights into the inter- and intra-specific variability in plant hydraulic functioning in high-latitude ecosystems.

Application of point-process statistical tools to stable isotopes in xylem water for the study of inter- and intra-specific interactions in water uptake patterns in a mixed stand of Pinus halepensis Mill. and Quercus ilex L.

NASA Astrophysics Data System (ADS)

Comas, Carles; del Castillo, Jorge; Voltas, Jordi; Ferrio, Juan Pedro

2013-04-01

The stable isotope composition of xylem water reflects has been used to assess inter-specific differences in uptake patterns, revealing synergistic and competition processes in the use of water resources (see e.g. Dawson et al. 1993). However, there is a lack of detailed studies on spatial and temporal variability of inter- and intra-specific competition within forest stands. In this context, the aim of this work was to compare the isotope composition of xylem water (δ18O , δ2H) in two common Mediterranean tree species, Quercus ilex L. and Pinus halepensis Mill, in order to understand their water uptake patterns throughout the growing season. In addition, we analyze the spatial variability of xylem water, to get insight into inter-specific strategies employed to cope with drought and the interaction between the individuals. Our first hypothesis was that both species used different strategies to cope with drought by uptaking water at different depths; and our second hypothesis was that individual trees would behave in different manner according to the distance to their neighbours as well as to whether the neighbour is from one species or the other. The study was performed in a mixed stand where both species are nearly co-dominant, adding up to a total of 33 oaks and 77 pines (plot area= 893 m2). We sampled sun-exposed branches of each tree six times over the growing season, and extracted the xylem water with a cryogenic trap. The isotopic composition of the water was determined using a Picarro Water Analizer L2130-i. Tree mapping for spatial analysis was done using a high resolution GPS technology (Trimble GeoExplorer 6000). For the spatial analysis, we used the pair-correlation function to study intra-specific tree configuration and the bivariate pair correlation function to analyse the inter-specific spatial configurations (Stoyan et al 1995). Moreover, the isotopic composition of xylem water was assumed to be a mark associated to each tree and analysed as a marked point pattern. Preliminary results showed significant differences between species, but only during drought periods, confirming our first hypothesis. For example, in late-summer and early-autumn, the values for Q. Ilex (δ18O= -4.9 ±0.3 permille, δ2H=-53.5±1.2 permille) were significantly lower than for P. halepensis (δ18O= -1.1±0.2 permille, δ2H = -27.8±0.8 permille), pointing to the use of deeper soil layers by Q. ilex. On the other hand, point process analyses showed intra-specific interactions, whereas inter-specific interactions were not detected. Acknowledgements: This work was funded by MC-ERG-246725 (FP7, EU) and AGL 2012-40039-C02-02 (MINECO, Spain). JdC and JPF are supported by FPI fellowship (MCINN) and Ramón y Cajal programme (RYC-2008-02050, MINECO), respectively. References Dawson TE et al. 1993. In: Ehleringer JR, Hall AE, Farquhar GD (eds) Stable isotopes and plant carbon-water relations. Academic Press, Inc. IPCC. 2007 Climate Change 2007: The Physical Science Basis. Cambridge UP. Stoyan D et al. 1995. Stochastic Geometry and its Applications. Wiley&Sons.

Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

PubMed

Spiroski, A M; Oliver, M H; Jaquiery, A L; Prickett, T C R; Espiner, E A; Harding, J E; Bloomfield, F H

2017-12-12

Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 μg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter at birth and demonstrated accelerated postnatal growth velocity. IGF1 treatment did not alter perinatal mortality, partially abrogated the reduction in newborn size in females, but not males, and reduced accelerated growth in both sexes. IGF1-mediated upregulation of somatotrophic genes in males during the early postnatal period could suggest that treatment effects are associated with delayed axis maturation, whilst treatment outcomes in females may rely on the reprogramming of nutrient-dependent mechanisms of growth. These data suggest that the growth-restricted fetus is responsive to intra-amniotic intervention with IGF1, and that sex-specific somatotrophic effects persist in the early postnatal period. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

[Molecular identification of Hibiscus syriacus and its adulterants using ITS2 barcode].

PubMed

Liu, Yi-Mei; Jin, Li-Na; Xiong, Yong-Xin; Wu, Lan; Chen, Ke-Li

2014-03-01

To identify Hibiscus syriacus and its adulterants using DNA barcoding technique. Nine samples of five species were PCR amplified and sequenced, and twelve samples were downloaded from the GenBank. The intra-specific and interspecific K2P distances were calculated, and neighbor-joining( NJ) tree was constructed by MEGA 5.0. The results showed the intra-specific genetic distances of Hibiscus syriacus were ranged from 0.009 to 0.056, which were far lower than inter-specific genetic distances between Hibiscus syriacus and its adulterants (0.236 - 0.301). Variable sites within Hibiscus syriacus ranged from 2 to 9 which were far less than the adulterants (45 - 52); Different samples of Hibiscus syriacus were gathered together and could be distinguished from its adulterants by NJ tree. ITS2 can discriminate Hibiscus syriacus from its adulterants correctly. The ITS2 region is an efficient barcode for authentication of Hibiscus syriacus and its adulterants.

Using small RNA (sRNA) deep sequencing to understand global virus distribution in plants

USDA-ARS?s Scientific Manuscript database

Small RNAs (sRNAs), a class of regulatory RNAs, have been used to serve as the specificity determinants of suppressing gene expression in plants and animals. Next generation sequencing (NGS) uncovered the sRNA landscape in most organisms including their associated microbes. In the current study, w...

Examining the Anatomy of a Screencast: Uncovering Common Elements and Instructional Strategies

ERIC Educational Resources Information Center

Sugar, William; Brown, Abbie; Luterbach, Kenneth

2010-01-01

The researchers engaged in cooperative inquiry in order to explore screencasts as online instructional tools. In total, each researcher analyzed 37 screencasts, which provided over two hours of instruction. The content area of these screencasts concentrated on teaching specific computing procedures (e.g., how to install web server software or how…

Discursive Hierarchical Patterning in Economics Cases

ERIC Educational Resources Information Center

Lung, Jane

2011-01-01

This paper attempts to apply Lung's (2008) model of the discursive hierarchical patterning of cases to a closer and more specific study of Economics cases and proposes a model of the distinct discursive hierarchical patterning of the same. It examines a corpus of 150 Economics cases with a view to uncovering the patterns of discourse construction.…

Power Relations in Creating and Distributing Official Knowledge in Children's Literature: "Historical Picture of Taiwan"

ERIC Educational Resources Information Center

Lu, Lin-Miao

2014-01-01

With a specific focus on power relations in creating and distributing knowledge in society, this study examines the government-published children's series "Historical Picture of Taiwan" produced in Taiwan in the Martial Law era (1949-1987) to uncover ideological assumptions and persuasions permeating both linguistic and visual…

Impact of Professional Development on Teacher Practice: Uncovering Connections

ERIC Educational Resources Information Center

Buczynski, Sandy; Hansen, C. Bobbi

2010-01-01

An Inquiry Learning Partnership (ILP) for professional development (PD) was formed between a university, science centre, and two urban school districts to offer 4-6th grade teachers specific science content and pedagogical techniques intended to integrate inquiry-based instruction in elementary classrooms. From pre/post content exams, PD surveys,…

Text Analysis of Chemistry Thesis and Dissertation Titles

ERIC Educational Resources Information Center

Scalfani, Vincent F.

2017-01-01

Programmatic text analysis can be used to understand patterns and reveal trends in data that would otherwise be difficult or impossible to uncover with manual coding methods. This work uses programmatic text analysis, specifically term frequency counts, to study nearly 10,000 chemistry thesis and dissertation titles from 1911-2015. The thesis and…

Creativity and the Brain: Uncovering the Neural Signature of Conceptual Expansion

ERIC Educational Resources Information Center

Abraham, Anna; Pieritz, Karoline; Thybusch, Kristin; Rutter, Barbara; Kroger, Soren; Schweckendiek, Jan; Stark, Rudolf; Windmann, Sabine; Hermann, Christiane

2012-01-01

Neurophysiological studies of creativity thus far have not allowed for clear conclusions to be made regarding the specific neural underpinnings of such complex cognition due to overgeneralizations concerning the creativity construct, heterogeneity in the type of creativity tasks used, and the questionable efficacy of the employed comparison tasks.…

Going beyond Input Quantity: "Wh"-Questions Matter for Toddlers' Language and Cognitive Development

ERIC Educational Resources Information Center

Rowe, Meredith L.; Leech, Kathryn A.; Cabrera, Natasha

2017-01-01

There are clear associations between the overall quantity of input children are exposed to and their vocabulary acquisition. However, by uncovering specific features of the input that matter, we can better understand the mechanisms involved in vocabulary learning. We examine whether exposure to "wh"-questions, a challenging quality of…

Seeking a Balance: Online Safety for Our Children

ERIC Educational Resources Information Center

Endicott-Popovsky, Barbara

2009-01-01

Without specific education in online safety and security issues, putting any limitations on access could seem counter to what a librarian is trained to do. At a cybersecurity workshop sponsored by Washington Library Media Association (WLMA) last October, an informal show of hands from attending teacher-librarians uncovered a range of motivations…

Identifying the Camouflage: Uncovering and Supporting the Transition Experiences of Military and Veteran Students

ERIC Educational Resources Information Center

Williams-Klotz, Denise N.; Gansemer-Topf, Ann M.

2017-01-01

This study summarizes the qualitative findings from a multi-institutional study about the college transition experiences of military and veteran students, specifically students' articulation of their needs. Findings reveal (a) a lack of inprocessing, (b) need for community, and (c) institutional invisibility. Using the Student Veteran Transition…

How to Show One-Fourth? Uncovering Hidden Context through Reciprocal Learning

ERIC Educational Resources Information Center

Abramovich, S.; Brouwer, P.

2007-01-01

This paper suggests that mathematics teacher educators should listen carefully to what their students are saying. More specifically, it demonstrates how from one pre-teacher's non-traditional geometric representation of a unit fraction, a variety of learning environments that lead to the enrichment of mathematics for teaching can be developed. The…

The Learning Pyramid: Does It Point Teachers in the Right Direction?

ERIC Educational Resources Information Center

Lalley, James P.; Miller, Robert H.

2007-01-01

This paper raises serious questions about the reliability of the learning pyramid as a guide to retention among students. The pyramid suggests that certain teaching methods are connected with a corresponding hierarchy of student retention. No specific credible research was uncovered to support the pyramid, which is loosely associated with the…

Of Texts AND Translations And Rhizomes: Postcolonial Anxieties and Deracinations and Knowledge Constructions

ERIC Educational Resources Information Center

Ramanathan, Vaidehi

2006-01-01

This article uncovers some problems involved in culling and translating non-western texts--written in other languages, at particular times, for specific audiences, and rooted in particular local milieus--before assembling them into academic arguments in English in the west. Based on my longterm, evolving endeavour regarding English- and…

The Profile of Misconceptions among Science Subject Student-Teachers in Primary Schools

ERIC Educational Resources Information Center

Subayani, Nataria Wahyuning

2016-01-01

Students' different background knowledge determines their quality of conceptions towards a specific subject in college. This research sought to uncover the profile of misconceptions experienced by 48 students of Primary School Teaching Major, studying Science in University of Muhammadiyah Gresik. The educational background of the students in high…

Cultures in Dialogue: Perceptions and Experiences of Finnish Teachers of Transnational Dances

ERIC Educational Resources Information Center

Siljamäki, Mariana Elisabet; Anttila, Eeva; Sääkslahti, Arja

2014-01-01

This article is based on a phenomenographic study that focuses on identifying the pedagogical conceptions of Finnish teachers of transnational dances. The purpose is to uncover and understand teachers' conceptions concerning the implications of the cultural contexts of their specific dance forms for their pedagogical practices. Through a process…

In the Minds of OSCE Examiners: Uncovering Hidden Assumptions

ERIC Educational Resources Information Center

Chahine, Saad; Holmes, Bruce; Kowalewski, Zbigniew

2016-01-01

The Objective Structured Clinical Exam (OSCE) is a widely used method of assessment in medical education. Rater cognition has become an important area of inquiry in the medical education assessment literature generally, and in the OSCE literature specifically, because of concerns about potential compromises of validity. In this study, a novel…

A Critical Quantitative Examination of the Relationship between Constructs of Engagement and Latino College Completion

ERIC Educational Resources Information Center

Raynor, Samantha L.

2017-01-01

Investigating the validity and applicability of student success theories for minority students uncovers the nuance and context of student experiences. This study examines the validity and applicability of student engagement and involvement for Latino students. Specifically, this study employs a critical quantitative lens to question current…

Distributed Instructional Leadership in High Schools

ERIC Educational Resources Information Center

Halverson, Richard; Clifford, Matthew

2013-01-01

This article explores the idea of distributed instructional leadership as a way to understand instructional leadership practice in comprehensive high schools. Our argument is that distributed leadership analyses allow researchers to uncover and explain how instructional improvement in high schools occurs through the efforts of multiple individuals…

Sustained response with ixekizumab treatment of moderate-to-severe psoriasis with scalp involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2, UNCOVER-3).

PubMed

Reich, Kristian; Leonardi, Craig; Lebwohl, Mark; Kerdel, Francisco; Okubo, Yukari; Romiti, Ricardo; Goldblum, Orin; Dennehy, Ellen B; Kerr, Lisa; Sofen, Howard

2017-06-01

Scalp is a frequently affected and difficult-to-treat area in psoriasis patients. We assessed the efficacy of ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI). In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg bi-weekly etanercept through Week 12. Patients entering the open-label long-term extension (LTE) (UNCOVER-3) received ixekizumab Q4W; UNCOVER-1 and UNCOVER-2 included a blinded maintenance period in which static physician global assessment (sPGA) 0/1 responders were re-randomized to placebo, ixekizumab Q4W, or 80 mg ixekizumab every 12 weeks (Q12W) through Week 60. In patients with moderate-to-severe psoriasis with baseline scalp involvement, PSSI 90 and 100 were achieved at Week 12 in higher percentages of patients treated with ixekizumab Q2W (81.7% and 74.6%) or ixekizumab Q4W (75.6% and 68.9%) compared with patients treated with placebo (7.6% and 6.7%; p < .001 each ixekizumab arm versus placebo) or etanercept (55.5% and 48.1%; p < .001 each ixekizumab arm versus etanercept). These outcomes were maintained through Week 60 of the maintenance (UNCOVER-1 and UNCOVER-2) and LTE (UNCOVER-3) period in patients who continued on ixekizumab Q4W. Ixekizumab was efficacious in treating scalp psoriasis in patients with moderate-to-severe psoriasis, with most patients achieving complete or near-complete resolution of scalp psoriasis and maintaining this response over 60 weeks.

High Frequency Cut-off Characteristics of Strong Ground Motion Records at Hard Sites, Subduction and Intra-Slab Earthquakes

NASA Astrophysics Data System (ADS)

Kagawa, T.; Tsurugi, M.; Irikura, K.

2006-12-01

A study on high frequency cut-off characteristics of strong ground motion is presented for subduction and intra- slab earthquakes in Japan. In the latest decade, observed records at hard sites are published by NIED, National Research Institute for Earth Science and Disaster Prevention, and JCOLD, Japan Commission on Large Dams. Especially, KiK-net and K-NET maintained by NIED have been providing high quality data to study high-frequency characteristics. Kagawa et al.(2003) studied the characteristics for crustal earthquakes. We apply the same methodology to the recently observed Japanese records due to subduction and intra-slab earthquakes. We assume a Butterworth type high-cut filter with limit frequency (fmax) and its power factor. These two parameters were derived from Fourier spectrum of observed records fitting the theoretical filter shape. After analyzing the result from view points of site, path, or source effects, an averaged filter model is proposed with its standard deviation. Kagawa et al.(2003) derived average as 8.3 Hz with power factor of 1.92. It is used for strong ground motion simulation. We will propose parameters for the high-cut filters of subduction and intra-slab earthquakes and compare them with the results by Kagawa et al.(2003). REFERENCES: Kagawa et al. (2003), 27JEES (in Japanese with English Abstract).

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction.

PubMed

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-05-15

Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction

PubMed Central

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-01-01

Background/Aims Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. Methods A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. Results The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Conclusions Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs. PMID:28208003

The use of anti-gravity suits for the control of critical intra-abdominal hemmorhage

NASA Technical Reports Server (NTRS)

Kravik, S.; Landmark, K.

1980-01-01

The history and use as well as the physiology of the use of antigravity suits for the control of critical intra-abdominal hemorrhages is reviewed. The use of this suit is highly recommended, especially for first aid.

77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental... review of the uncovered finished water reservoir requirement in the Long Term 2 Enhanced Surface Water... uncovered finished water reservoir requirement and the agency's Six Year Review process. EPA also plans to...

Validation of tablet-based evaluation of color fundus images

PubMed Central

Christopher, Mark; Moga, Daniela C.; Russell, Stephen R.; Folk, James C.; Scheetz, Todd; Abràmoff, Michael D.

2012-01-01

Purpose To compare diabetic retinopathy (DR) referral recommendations made by viewing fundus images using a tablet computer to recommendations made using a standard desktop display. Methods A tablet computer (iPad) and a desktop PC with a high-definition color display were compared. For each platform, two retinal specialists independently rated 1200 color fundus images from patients at risk for DR using an annotation program, Truthseeker. The specialists determined whether each image had referable DR, and also how urgently each patient should be referred for medical examination. Graders viewed and rated the randomly presented images independently and were masked to their ratings on the alternative platform. Tablet- and desktop display-based referral ratings were compared using cross-platform, intra-observer kappa as the primary outcome measure. Additionally, inter-observer kappa, sensitivity, specificity, and area under ROC (AUC) were determined. Results A high level of cross-platform, intra-observer agreement was found for the DR referral ratings between the platforms (κ=0.778), and for the two graders, (κ=0.812). Inter-observer agreement was similar for the two platforms (κ=0.544 and κ=0.625 for tablet and desktop, respectively). The tablet-based ratings achieved a sensitivity of 0.848, a specificity of 0.987, and an AUC of 0.950 compared to desktop display-based ratings. Conclusions In this pilot study, tablet-based rating of color fundus images for subjects at risk for DR was consistent with desktop display-based rating. These results indicate that tablet computers can be reliably used for clinical evaluation of fundus images for DR. PMID:22495326

Diagnostic accuracy of clinical tests of the hip: a systematic review with meta-analysis.

PubMed

Reiman, Michael P; Goode, Adam P; Hegedus, Eric J; Cook, Chad E; Wright, Alexis A

2013-09-01

Hip Physical Examination (HPE) tests have long been used to diagnose a myriad of intra-and extra-articular pathologies of the hip joint. Useful clinical utility is necessary to support diagnostic imaging and subsequent surgical decision making. Summarise and evaluate the current research and utility on the diagnostic accuracy of HPE tests for the hip joint germane to sports related injuries and pathology. A computer-assisted literature search of MEDLINE, CINHAL and EMBASE databases (January 1966 to January 2012) using keywords related to diagnostic accuracy of the hip joint. This systematic review with meta-analysis utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the search and reporting phases of the study. Der-Simonian and Laird random effects models were used to summarise sensitivities (SN), specificities (SP), likelihood ratios and diagnostic OR. The employed search strategy revealed 25 potential articles, with 10 demonstrating high quality. Fourteen articles qualified for meta-analysis. The meta-analysis demonstrated that most tests possess weak diagnostic properties with the exception of the patellar-pubic percussion test, which had excellent pooled SN 95 (95% CI 92 to 97%) and good specificity 86 (95% CI 78 to 92%). Several studies have investigated pathology in the hip. Few of the current studies are of substantial quality to dictate clinical decision-making. Currently, only the patellar-pubic percussion test is supported by the data as a stand-alone HPE test. Further studies involving high quality designs are needed to fully assess the value of HPE tests for patients with intra- and extra-articular hip dysfunction.

Laser ablation of iron-rich black films from exposed granite surfaces

NASA Astrophysics Data System (ADS)

Delgado Rodrigues, J.; Costa, D.; Mascalchi, M.; Osticioli, I.; Siano, S.

2014-10-01

Here, we investigated the potential of laser removal of iron-rich dark films from weathered granite substrates, which represents a very difficult conservation problem because of the polymineralic nature of the stone and of its complex deterioration mechanisms. As often occurs, biotite was the most critical component because of its high optical absorption, low melting temperature, and pronounced cleavage, which required a careful control of the photothermal and photomechanical effects to optimize the selective ablation of the mentioned unwanted dark film. Different pulse durations and wavelengths Nd:YAG lasers were tested and optimal irradiation conditions were determined through thorough analytical characterisations. Besides addressing a specific conservation problem, the present work provides information of general valence in laser uncovering of encrusted granite.

The evolutionary ecology of the Lygaeidae

PubMed Central

Burdfield-Steel, Emily R; Shuker, David M

2014-01-01

The Lygaeidae (sensu lato) are a highly successful family of true bugs found worldwide, yet many aspects of their ecology and evolution remain obscure or unknown. While a few species have attracted considerable attention as model species for the study of insect physiology, it is only relatively recently that biologists have begun to explore aspects of their behavior, life history evolution, and patterns of intra- and interspecific ecological interactions across more species. As a result though, a range of new phenotypes and opportunities for addressing current questions in evolutionary ecology has been uncovered. For example, researchers have revealed hitherto unexpectedly rich patterns of bacterial symbiosis, begun to explore the evolutionary function of the family's complex genitalia, and also found evidence of parthenogenesis. Here we review our current understanding of the biology and ecology of the group as a whole, focusing on several of the best-studied characteristics of the group, including aposematism (i.e., the evolution of warning coloration), chemical communication, sexual selection (especially, postcopulatory sexual selection), sexual conflict, and patterns of host-endosymbiont coevolution. Importantly, many of these aspects of lygaeid biology are likely to interact, offering new avenues for research, for instance into how the evolution of aposematism influences sexual selection. With the growing availability of genomic tools for previously “non-model” organisms, combined with the relative ease of keeping many of the polyphagous species in the laboratory, we argue that these bugs offer many opportunities for behavioral and evolutionary ecologists. PMID:25360267

THE INTRA- AND INTER-RATER RELIABILITY OF THE SOCCER INJURY MOVEMENT SCREEN (SIMS).

PubMed

McCunn, Robert; Aus der Fünten, Karen; Govus, Andrew; Julian, Ross; Schimpchen, Jan; Meyer, Tim

2017-02-01

The growing volume of movement screening research reveals a belief among practitioners and researchers alike that movement quality may have an association with injury risk. However, existing movement screening tools have not considered the sport-specific movement and injury patterns relevant to soccer. The present study introduces the Soccer Injury Movement Screen (SIMS), which has been designed specifically for use within soccer. Furthermore, the purpose of the present study was to assess the intra- and inter-rater reliability of the SIMS and determine its suitability for use in further research. The study utilized a test-retest design to discern reliablility. Twenty-five (11 males, 14 females) healthy, recreationally active university students (age 25.5 ± 4.0 years, height 171 ± 9 cm, weight 64.7 ± 12.6 kg) agreed to participate. The SIMS contains five sub-tests: the anterior reach, single-leg deadlift, in-line lunge, single-leg hop for distance and tuck jump. Each movement was scored out of 10 points and summed to produce a composite score out of 50. The anterior reach and single-leg hop for distance were scored in real-time while the remaining tests were filmed and scored retrospectively. Three raters conducted the SIMS with each participant on three occasions separated by an average of three and a half days (minimum one day, maximum seven days). Rater 1 re-scored the filmed movements for all participants on all occasions six months later to establish the 'pure' intra-rater (intra-occasion) reliability for those movements. Intraclass correlation coefficient (ICC) values for intra- and inter-rater composite score reliability ranged from 0.66-0.72 and 0.79-0.86 respectively. Weighted kappa values representing the intra- and inter-rater reliability of the individual sub-tests ranged from 0.35-0.91 indicating fair to almost perfect agreement. Establishing the reliability of the SIMS is a prerequisite for further research seeking to investigate the relationship between test score and subsequent injury. The present results indicate acceptable reliability for this purpose; however, room for further development of the intra-rater reliability exists for some of the individual sub-tests. 2b.

THE INTRA- AND INTER-RATER RELIABILITY OF THE SOCCER INJURY MOVEMENT SCREEN (SIMS)

PubMed Central

aus der Fünten, Karen; Govus, Andrew; Julian, Ross; Schimpchen, Jan; Meyer, Tim

2017-01-01

Background/purpose The growing volume of movement screening research reveals a belief among practitioners and researchers alike that movement quality may have an association with injury risk. However, existing movement screening tools have not considered the sport-specific movement and injury patterns relevant to soccer. The present study introduces the Soccer Injury Movement Screen (SIMS), which has been designed specifically for use within soccer. Furthermore, the purpose of the present study was to assess the intra- and inter-rater reliability of the SIMS and determine its suitability for use in further research. Methods The study utilized a test-retest design to discern reliablility. Twenty-five (11 males, 14 females) healthy, recreationally active university students (age 25.5 ± 4.0 years, height 171 ± 9 cm, weight 64.7 ± 12.6 kg) agreed to participate. The SIMS contains five sub-tests: the anterior reach, single-leg deadlift, in-line lunge, single-leg hop for distance and tuck jump. Each movement was scored out of 10 points and summed to produce a composite score out of 50. The anterior reach and single-leg hop for distance were scored in real-time while the remaining tests were filmed and scored retrospectively. Three raters conducted the SIMS with each participant on three occasions separated by an average of three and a half days (minimum one day, maximum seven days). Rater 1 re-scored the filmed movements for all participants on all occasions six months later to establish the ‘pure’ intra-rater (intra-occasion) reliability for those movements. Results Intraclass correlation coefficient (ICC) values for intra- and inter-rater composite score reliability ranged from 0.66-0.72 and 0.79-0.86 respectively. Weighted kappa values representing the intra- and inter-rater reliability of the individual sub-tests ranged from 0.35-0.91 indicating fair to almost perfect agreement. Conclusions Establishing the reliability of the SIMS is a prerequisite for further research seeking to investigate the relationship between test score and subsequent injury. The present results indicate acceptable reliability for this purpose; however, room for further development of the intra-rater reliability exists for some of the individual sub-tests. Level of evidence 2b PMID:28217416

A CCR2+ myeloid cell niche required for pancreatic β cell growth

PubMed Central

Mussar, Kristin; Pardike, Stephanie; Hohl, Tobias M.; Hardiman, Gary; Cirulli, Vincenzo

2017-01-01

Organ-specific patterns of myeloid cells may contribute tissue-specific growth and/or regenerative potentials. The perinatal stage of pancreas development marks a time characterized by maximal proliferation of pancreatic islets, ensuring the maintenance of glucose homeostasis throughout life. Ontogenically distinct CX3CR1+ and CCR2+ macrophage populations have been reported in the adult pancreas, but their functional contribution to islet cell growth at birth remains unknown. Here, we uncovered a temporally restricted requirement for CCR2+ myeloid cells in the perinatal proliferation of the endocrine pancreatic epithelium. CCR2+ macrophages are transiently enriched over CX3CR1+ subsets in the neonatal pancreas through both local expansion and recruitment of immature precursors. Using CCR2-specific depletion models, we show that loss of this myeloid population leads to a striking reduction in β cell proliferation, dysfunctional islet phenotypes, and glucose intolerance in newborns. Replenishment of pancreatic CCR2+ myeloid compartments by adoptive transfer rescues these defects. Gene profiling identifies pancreatic CCR2+ myeloid cells as a prominent source of IGF2, which contributes to IGF1R-mediated islet proliferation. These findings uncover proproliferative functions of CCR2+ myeloid subsets and identify myeloid-dependent regulation of IGF signaling as a local cue supporting pancreatic proliferation. PMID:28768911

De novo transcriptomic analysis during Lentinula edodes fruiting body growth.

PubMed

Wang, Yingzhu; Zeng, Xianlu; Liu, Wenguang

2018-01-30

The fruiting body of Lentinula edodes is a popular edible mushroom, and extracts from the mycelium and the fruiting body of this species have diverse therapeutic potential. To gain insights into the molecular mechanisms underlying the fruiting body growth of L. edodes from the early bud stage (EBS), through the intermediate developing stage (IDS), to the fully developed stage (FDS), we performed de novo transcriptomic analysis using high-throughput Illumina RNA-sequencing. First, we generated three cDNA libraries representative of the three respective stages. We then obtained 38,933,148, 44,594,472, and 37,905,646 high-quality reads from the respective libraries and assembled the reads into 25,104 transcriptional contigs, containing 15,199 unigenes. We found that only 9331 of the unigenes had been annotated in the NCBI non-redundant protein database, and we functionally annotated 4758 of them through Gene Ontology (GO) analysis and 2921 of them through Clusters of Orthologous Groups of proteins (COGs) analysis. We also assigned 3995 unigenes to metabolic pathways by using the Kyoto Encyclopedia of Genes and Genomes (KEGG). We further identified 399 differentially expressed genes (DEGs) between EBS and IDS, 1428 between IDS and FDS, and 1830 between EBS and FDS, uncovering 769 DEGs in multiple metabolic and signaling pathways. Interestingly, there were a limited number of DEGs whose expression was dramatically associated with FDS. Finally, genes, whose expression was either highly up-regulated in FDS or remained at a high level during fruiting body growth, were annotated specifically in the pathways of purine metabolism, unsaturated fatty acid metabolism and meiosis, suggesting that these key molecular events were actively occurring in the fruiting body. Our work is the first high-throughput transcriptome study on the growth of L. edodes fruiting bodies, and the results uncovered candidate genes for future gene identification and utilization of this commercially and medically important mushroom. Copyright © 2017 Elsevier B.V. All rights reserved.

Time-Gating Processes in Intra-Cavity Mode-Locking Devices Like Saturable Absorbers and Kerr Cells

NASA Technical Reports Server (NTRS)

Prasad, Narasimha; Roychoudhuri, Chandrasekhar

2010-01-01

Photons are non-interacting entities. Light beams do not interfere by themselves. Light beams constituting different laser modes (frequencies) are not capable of re-arranging their energies from extended time-domain to ultra-short time-domain by themselves without the aid of light-matter interactions with suitable intra-cavity devices. In this paper we will discuss the time-gating properties of intra-cavity "mode-locking" devices that actually help generate a regular train of high energy wave packets.

Genetic monitoring detects an overlooked cryptic species and reveals the diversity and distribution of three invasive Rattus congeners in south Africa

PubMed Central

2011-01-01

Background South Africa's long and extensive trade activity has ensured ample opportunities for exotic species introduction. Whereas the rich biodiversity of endemic southern African fauna has been the focus of many studies, invasive vertebrates are generally overlooked despite potential impacts on biodiversity, health and agriculture. Genetic monitoring of commensal rodents in South Africa which uncovered the presence of Rattus tanezumi, a South-East Asian endemic not previously known to occur in Africa, provided the impetus for expanded studies on all invasive Rattus species present. Results To this end, intensified sampling at 28 South African localities and at one site in Swaziland, identified 149 Rattus specimens. Cytochrome b gene sequencing revealed the presence of two R. tanezumi, seven Rattus rattus and five Rattus norvegicus haplotypes in south Africa. Phylogenetic results were consistent with a single, recent R. tanezumi introduction and indicated that R. norvegicus and R. rattus probably became established following at least two and three independent introductions, respectively. Intra- and inter-specific diversity was highest in informal human settlements, with all three species occurring at a single metropolitan township site. Rattus norvegicus and R. rattus each occurred sympatrically with Rattus tanezumi at one and five sites, respectively. Karyotyping of selected R. rattus and R. tanezumi individuals identified diploid numbers consistent with those reported previously for these cryptic species. Ordination of bioclimatic variables and MaxEnt ecological niche modelling confirmed that the bioclimatic niche occupied by R. tanezumi in south Africa was distinct from that occupied in its naturalised range in south-east Asia suggesting that factors other than climate may influence the distribution of this species. Conclusions This study has highlighted the value of genetic typing for detecting cryptic invasive species, providing historical insights into introductions and for directing future sampling. The apparent ease with which a cryptic species can become established signals the need for broader implementation of genetic monitoring programmes. In addition to providing baseline data and potentially identifying high-risk introduction routes, the predictive power of ecological niche modelling is enhanced when species records are genetically verified. PMID:21324204

Effect of biotin supplementation on meat quality of F1 Wagyu/Black Angus feedlot steers of known genotype.

PubMed

Lawrence, R J; Doyle, J C; Elliott, R; Norton, B W; Loxton, I

2007-10-01

Biotin (D-biotin) was supplemented to F1 Wagyu/Black Angus steers fed a wheat-based ration to evaluate the effect on meat quality. One hundred and eight steers of known Wagyu sire lines were assigned to three biotin treatments (0, 10 and 20mg/head/day) with each treatment replicated four times using an unfasted liveweight of 410.5kg (±24.42 SD). Biotin supplementation had no effect (P>0.05) on beef marbling standard at either the 5/6th or 10/11th rib quartering site, 10/11th rib intra-muscular fat percentage, intra-muscular fat fatty acid composition or adipose melting points. Wagyu genotype had an effect (P<0.05) on beef marbling standard and intra-muscular fat percentage at the 10/11th rib, inter-muscular and intra-muscular melting point and fatty acid composition of intra-muscular fat. A significant (P<0.001) but poor correlation existed between beef marbling standard and intra-muscular fat percentage (R(2)=0.198). Total conjugated linoleic acid had a highly significantly (P<0.0001) positive correlation to intra-muscular fat percentage (R(2)=0.446).

Identification of Novel Synthetic Toll-like Receptor 2 Agonists by High Throughput Screening*

PubMed Central

Guan, Yue; Omueti-Ayoade, Katherine; Mutha, Sarita K.; Hergenrother, Paul J.; Tapping, Richard I.

2010-01-01

Toll-like receptors (TLRs) play a central role in host defense by inducing inflammatory and adaptive immune responses following infection. Drugs that target TLRs are of considerable interest as potential inflammatory regulators, vaccine adjuvants, and novel immunotherapeutics. TLR2, in cooperation with either TLR1 or TLR6, mediates responses to a wide variety of microbial products as well as products of host tissue damage. In an effort to understand the structural basis of TLR2 recognition and uncover novel TLR2 agonists, a synthetic chemical library of 24,000 compounds was screened using an IL-8-driven luciferase reporter in cells expressing these human receptors. The screening yielded several novel TLR2-dependent activators that utilize TLR1, TLR6, or both as co-receptors. These novel small molecule compounds are aromatic in nature and structurally unrelated to any known TLR2 agonists. The three most potent compounds do not exhibit synergistic activity, nor do they act as pseudoantagonists toward natural TLR2 activators. Interestingly, two of the compounds exhibit species specificity and are inactive toward murine peritoneal macrophages. Mutational analysis reveals that although the central extracellular region of TLR1 is required for stimulation, there are subtle differences in the mechanism of stimulation mediated by the synthetic compounds in comparison with natural lipoprotein agonists. The three most potent compounds activate cells in the nanomolar range and stimulate cytokine production from human peripheral blood monocytes. Our results confirm the utility of high throughput screens to uncover novel synthetic TLR2 agonists that may be of therapeutic benefit. PMID:20504771

Thoracic injury rule out criteria and NEXUS chest in predicting the risk of traumatic intra-thoracic injuries: A diagnostic accuracy study.

PubMed

Safari, Saeed; Radfar, Fatemeh; Baratloo, Alireza

2018-05-01

This study aimed to compare the diagnostic accuracy of NEXUS chest and Thoracic Injury Rule out criteria (TIRC) models in predicting the risk of intra-thoracic injuries following blunt multiple trauma. In this diagnostic accuracy study, using the 2 mentioned models, blunt multiple trauma patients over the age of 15 years presenting to emergency department were screened regarding the presence of intra-thoracic injuries that are detectable via chest x-ray and screening performance characteristics of the models were compared. In this study, 3118 patients with the mean (SD) age of 37.4 (16.9) years were studied (57.4% male). Based on TIRC and NEXUS chest, respectively, 1340 (43%) and 1417 (45.4%) patients were deemed in need of radiography performance. Sensitivity, specificity, and positive and negative predictive values of TIRC were 98.95%, 62.70%, 21.19% and 99.83%. These values were 98.61%, 59.94%, 19.97% and 99.76%, for NEXUS chest, respectively. Accuracy of TIRC and NEXUS chest models were 66.04 (95% CI: 64.34-67.70) and 63.50 (95% CI: 61.78-65.19), respectively. TIRC and NEXUS chest models have proper and similar sensitivity in prediction of blunt traumatic intra-thoracic injuries that are detectable via chest x-ray. However, TIRC had a significantly higher specificity in this regard. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparison of phase-contrast MR imaging and endovascular sonography for intracranial blood flow velocity measurements.

PubMed

Schneiders, J J; Ferns, S P; van Ooij, P; Siebes, M; Nederveen, A J; van den Berg, R; van Lieshout, J; Jansen, G; vanBavel, E; Majoie, C B

2012-10-01

Local hemodynamic information may help to stratify rupture risk of cerebral aneurysms. Patient-specific modeling of cerebral hemodynamics requires accurate data on BFV in perianeurysmal arteries as boundary conditions for CFD. The aim was to compare the BFV measured with PC-MR imaging with that obtained by using intra-arterial Doppler sonography and to determine interpatient variation in intracranial BFV. In 10 patients with unruptured intracranial aneurysms, BFV was measured in the cavernous ICA with PC-MR imaging in conscious patients before treatment, and measured by using an intra-arterial Doppler sonography wire when the patient was anesthetized with either propofol (6 patients) or sevoflurane (4 patients). Both techniques identified a pulsatile blood flow pattern in cerebral arteries. PSV differed >50 cm/s between patients. A mean velocity of 41.3 cm/s (95% CI, 39.3-43.3) was measured with PC-MR imaging. With intra-arterial Doppler sonography, a mean velocity of 29.3 cm/s (95% CI, 25.8-32.8) was measured with the patient under propofol-based intravenous anesthesia. In patients under sevoflurane-based inhaled anesthesia, a mean velocity of 44.9 cm/s (95% CI, 40.6-49.3) was measured. We showed large differences in BFV between patients, emphasizing the importance of using patient-specific hemodynamic boundary conditions in CFD. PC-MR imaging measurements of BFV in conscious patients were comparable with those obtained with the intra-arterial Doppler sonography when the patient was anesthetized with a sevoflurane-based inhaled anesthetic.

Intra-seasonal variation in foraging behavior among Adélie penguins (Pygocelis adeliae) breeding at Cape Hallett, Ross Sea, Antarctica

USGS Publications Warehouse

Lyver, P.O.B.; MacLeod, C.J.; Ballard, G.; Karl, B.J.; Barton, K.J.; Adams, J.; Ainley, D.G.; Wilson, P.R.

2011-01-01

We investigated intra-seasonal variation in foraging behavior of chick-rearing Adélie penguins,Pygoscelis adeliae, during two consecutive summers at Cape Hallett, northwestern Ross Sea. Although foraging behavior of this species has been extensively studied throughout the broad continental shelf region of the Ross Sea, this is the first study to report foraging behaviors and habitat affiliations among birds occupying continental slope waters. Continental slope habitat supports the greatest abundances of this species throughout its range, but we lack information about how intra-specific competition for prey might affect foraging and at-sea distribution and how these attributes compare with previous Ross Sea studies. Foraging trips increased in both distance and duration as breeding advanced from guard to crèche stage, but foraging dive depth, dive rates, and vertical dive distances travelled per hour decreased. Consistent with previous studies within slope habitats elsewhere in Antarctic waters, Antarctic krill (Euphausia superba) dominated chick meal composition, but fish increased four-fold from guard to crèche stages. Foraging-, focal-, and core areas all doubled during the crèche stage as individuals shifted distribution in a southeasterly direction away from the coast while simultaneously becoming more widely dispersed (i.e., less spatial overlap among individuals). Intra-specific competition for prey among Adélie penguins appears to influence foraging behavior of this species, even in food webs dominated by Antarctic krill.

Intra-seasonal variation in foraging behavior among Adélie penguins (Pygocelis adeliae) breeding at Cape Hallett, Ross Sea, Antarctica

USGS Publications Warehouse

Lyver, P.O.B.; MacLeod, C.J.; Ballard, G.; Karl, B.J.; Barton, K.J.; Adams, J.; Ainley, D.G.; Wilson, P.R.

2011-01-01

We investigated intra-seasonal variation in foraging behavior of chick-rearing Adélie penguins, Pygoscelis adeliae, during two consecutive summers at Cape Hallett, northwestern Ross Sea. Although foraging behavior of this species has been extensively studied throughout the broad continental shelf region of the Ross Sea, this is the first study to report foraging behaviors and habitat affiliations among birds occupying continental slope waters. Continental slope habitat supports the greatest abundances of this species throughout its range, but we lack information about how intra-specific competition for prey might affect foraging and at-sea distribution and how these attributes compare with previous Ross Sea studies. Foraging trips increased in both distance and duration as breeding advanced from guard to crèche stage, but foraging dive depth, dive rates, and vertical dive distances travelled per hour decreased. Consistent with previous studies within slope habitats elsewhere in Antarctic waters, Antarctic krill (Euphausia superba) dominated chick meal composition, but fish increased four-fold from guard to crèche stages. Foraging-, focal-, and core areas all doubled during the crèche stage as individuals shifted distribution in a southeasterly direction away from the coast while simultaneously becoming more widely dispersed (i.e., less spatial overlap among individuals). Intra-specific competition for prey among Adélie penguins appears to influence foraging behavior of this species, even in food webs dominated by Antarctic krill.

Development and Function of the Drosophila Tracheal System.

PubMed

Hayashi, Shigeo; Kondo, Takefumi

2018-06-01

The tracheal system of insects is a network of epithelial tubules that functions as a respiratory organ to supply oxygen to various target organs. Target-derived signaling inputs regulate stereotyped modes of cell specification, branching morphogenesis, and collective cell migration in the embryonic stage. In the postembryonic stages, the same set of signaling pathways controls highly plastic regulation of size increase and pattern elaboration during larval stages, and cell proliferation and reprograming during metamorphosis. Tracheal tube morphogenesis is also regulated by physicochemical interaction of the cell and apical extracellular matrix to regulate optimal geometry suitable for air flow. The trachea system senses both the external oxygen level and the metabolic activity of internal organs, and helps organismal adaptation to changes in environmental oxygen level. Cellular and molecular mechanisms underlying the high plasticity of tracheal development and physiology uncovered through research on Drosophila are discussed. Copyright © 2018 by the Genetics Society of America.

Angiocrine functions of organ-specific endothelial cells

PubMed Central

Rafii, Shahin; Butler, Jason M; Ding, Bi-Sen

2016-01-01

Preface Endothelial cells lining blood vessel capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establish specialized vascular niches that deploy specific sets of growth factors, known as angiocrine factors, which actively participate in inducing, specifying, patterning, and guiding organ regeneration and maintaining homeostasis and metabolism. Angiocrine factors upregulated in response to injury orchestrates self-renewal and differentiation of tissue-specific repopulating resident stem and progenitor cells into functional organs. Uncovering the precise mechanisms whereby physiological-levels of angiocrine factors are spatially and temporally produced, and distributed by organotypic endothelium to repopulating cells, will lay the foundation for driving organ repair without scarring. PMID:26791722

Covered versus uncovered self-expandable metal stents for malignant biliary strictures: A meta-analysis and systematic review.

PubMed

Moole, Harsha; Bechtold, Matthew L; Cashman, Micheal; Volmar, Fritz H; Dhillon, Sonu; Forcione, David; Taneja, Deepak; Puli, Srinivas R

2016-09-01

Self-expandable metal stents (SEMS) are used for palliating inoperable malignant biliary strictures. It is unclear if covered metal stents are superior to uncovered metal stents in these patients. We compared clinical outcomes in patients with covered and uncovered stents. Studies using covered and uncovered metallic stents for palliation in patients with malignant biliary stricture were reviewed. Articles were searched in MEDLINE, PubMed, and Ovid journals. Fixed and random effects models were used to calculate the pooled proportions. Initial search identified 1436 reference articles, of which 132 were selected and reviewed. Thirteen studies (n = 2239) for covered and uncovered metallic stents which met the inclusion criteria were included in this analysis. Odds ratio for stent occlusion rates in covered vs. uncovered stents was 0.79 (95 % CI = 0.65 to 0.96). Survival benefit in patients with covered vs. uncovered stents showed the odds ratio to be 1.29 (95 % CI = 0.95 to 1.74). Pooled odds ratio for migration of covered vs. uncovered stents was 9.9 (95 % CI = 4.5 to 22.3). Covered stents seemed to have significantly lesser occlusion rates, increased odds of migration, and increased odds of pancreatitis compared to uncovered stents. There was no statistically significant difference in the survival benefit, overall adverse event rate, and patency period of covered vs. uncovered metal stents in patients with malignant biliary strictures.

Intra-individual variability in information processing speed reflects white matter microstructure in multiple sclerosis.

PubMed

Mazerolle, Erin L; Wojtowicz, Magdalena A; Omisade, Antonina; Fisk, John D

2013-01-01

Slowed information processing speed is commonly reported in persons with multiple sclerosis (MS), and is typically investigated using clinical neuropsychological tests, which provide sensitive indices of mean-level information processing speed. However, recent studies have demonstrated that within-person variability or intra-individual variability (IIV) in information processing speed may be a more sensitive indicator of neurologic status than mean-level performance on clinical tests. We evaluated the neural basis of increased IIV in mildly affected relapsing-remitting MS patients by characterizing the relation between IIV (controlling for mean-level performance) and white matter integrity using diffusion tensor imaging (DTI). Twenty women with relapsing-remitting MS and 20 matched control participants completed the Computerized Test of Information Processing (CTIP), from which both mean response time and IIV were calculated. Other clinical measures of information processing speed were also collected. Relations between IIV on the CTIP and DTI metrics of white matter microstructure were evaluated using tract-based spatial statistics. We observed slower and more variable responses on the CTIP in MS patients relative to controls. Significant relations between white matter microstructure and IIV were observed for MS patients. Increased IIV was associated with reduced integrity in more white matter tracts than was slowed information processing speed as measured by either mean CTIP response time or other neuropsychological test scores. Thus, despite the common use of mean-level performance as an index of cognitive dysfunction in MS, IIV may be more sensitive to the overall burden of white matter disease at the microstructural level. Furthermore, our study highlights the potential value of considering within-person fluctuations, in addition to mean-level performance, for uncovering brain-behavior relationships in neurologic disorders with widespread white matter pathology.

7 CFR 1170.8 - Price reporting specifications.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Specifications for Dry Whey Prices: (1) Variety: Edible nonhygroscopic. (2) Age: No more than 180 days. (3) Grade..., or tanker. (5) Exclude: Sales of Grade A dry whey, intra-company sales, resales of purchased dry whey... transaction was completed), dry whey produced under faith-based close supervision and marketed at a higher...

Preliminary analysis of loss-of-coolant accident in Fukushima nuclear accident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su'ud, Zaki; Anshari, Rio

Loss-of-Coolant Accident (LOCA) in Boiling Water Reactor (BWR) especially on Fukushima Nuclear Accident will be discussed in this paper. The Tohoku earthquake triggered the shutdown of nuclear power reactors at Fukushima Nuclear Power station. Though shutdown process has been completely performed, cooling process, at much smaller level than in normal operation, is needed to remove decay heat from the reactor core until the reactor reach cold-shutdown condition. If LOCA happen at this condition, it will cause the increase of reactor fuel and other core temperatures and can lead to reactor core meltdown and exposure of radioactive material to the environmentmore » such as in the Fukushima Dai Ichi nuclear accident case. In this study numerical simulation has been performed to calculate pressure composition, water level and temperature distribution on reactor during this accident. There are two coolant regulating system that operational on reactor unit 1 at this accident, Isolation Condensers (IC) system and Safety Relief Valves (SRV) system. Average mass flow of steam to the IC system in this event is 10 kg/s and could keep reactor core from uncovered about 3,2 hours and fully uncovered in 4,7 hours later. There are two coolant regulating system at operational on reactor unit 2, Reactor Core Isolation Condenser (RCIC) System and Safety Relief Valves (SRV). Average mass flow of coolant that correspond this event is 20 kg/s and could keep reactor core from uncovered about 73 hours and fully uncovered in 75 hours later. There are three coolant regulating system at operational on reactor unit 3, Reactor Core Isolation Condenser (RCIC) system, High Pressure Coolant Injection (HPCI) system and Safety Relief Valves (SRV). Average mass flow of water that correspond this event is 15 kg/s and could keep reactor core from uncovered about 37 hours and fully uncovered in 40 hours later.« less

Preliminary analysis of loss-of-coolant accident in Fukushima nuclear accident

NASA Astrophysics Data System (ADS)

Su'ud, Zaki; Anshari, Rio

2012-06-01

Loss-of-Coolant Accident (LOCA) in Boiling Water Reactor (BWR) especially on Fukushima Nuclear Accident will be discussed in this paper. The Tohoku earthquake triggered the shutdown of nuclear power reactors at Fukushima Nuclear Power station. Though shutdown process has been completely performed, cooling process, at much smaller level than in normal operation, is needed to remove decay heat from the reactor core until the reactor reach cold-shutdown condition. If LOCA happen at this condition, it will cause the increase of reactor fuel and other core temperatures and can lead to reactor core meltdown and exposure of radioactive material to the environment such as in the Fukushima Dai Ichi nuclear accident case. In this study numerical simulation has been performed to calculate pressure composition, water level and temperature distribution on reactor during this accident. There are two coolant regulating system that operational on reactor unit 1 at this accident, Isolation Condensers (IC) system and Safety Relief Valves (SRV) system. Average mass flow of steam to the IC system in this event is 10 kg/s and could keep reactor core from uncovered about 3,2 hours and fully uncovered in 4,7 hours later. There are two coolant regulating system at operational on reactor unit 2, Reactor Core Isolation Condenser (RCIC) System and Safety Relief Valves (SRV). Average mass flow of coolant that correspond this event is 20 kg/s and could keep reactor core from uncovered about 73 hours and fully uncovered in 75 hours later. There are three coolant regulating system at operational on reactor unit 3, Reactor Core Isolation Condenser (RCIC) system, High Pressure Coolant Injection (HPCI) system and Safety Relief Valves (SRV). Average mass flow of water that correspond this event is 15 kg/s and could keep reactor core from uncovered about 37 hours and fully uncovered in 40 hours later.

The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET.

PubMed

Yang, Mengyi; Peng, Sijia; Sun, Ruirui; Lin, Jingdi; Wang, Nan; Chen, Chunlai

2018-01-09

Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: metals.

PubMed

Smolders, Roel; Koch, Holger M; Moos, Rebecca K; Cocker, John; Jones, Kate; Warren, Nick; Levy, Len; Bevan, Ruth; Hays, Sean M; Aylward, Lesa L

2014-12-01

The aim of the current HBM-study is to further the understanding of the impact of inter- and intra-individual variability in HBM surveys as it may have implications for the design and interpretation of the study outcomes. As spot samples only provide a snapshot in time of the concentrations of chemicals in an individual, it remains unclear to what extent intra-individual variability plays a role in the overall variability of population-wide HBM surveys. The current paper describes the results of an intensive biomonitoring study, in which all individual urine samples of 8 individuals were collected over a 6-day sampling period (a total of 352 unique samples). By analyzing different metals (As, Cd, Mn, Ni) in each individual sample, inter- and intra-individual variability for these four metals could be determined, and the relationships between exposure, internal dose, and sampling protocol assessed. Although the range of biomarker values for different metals was well within the normal range reported in large-scale population surveys, large intra-individual differences over a 6-day period could also be observed. Typically, measured biomarker values span at least an order of magnitude within an individual, and more if specific exposure episodes could be identified. Fish consumption for example caused a twenty- to thirty-fold increase in urinary As-levels over a period of 2-6h. Intra-class correlation coefficients (ICC) were typically low for uncorrected biomarker values (between 0.104 and 0.460 for the 4 metals), but improved when corrected for creatinine or specific gravity (SG). The results show that even though urine is a preferred matrix for HBM studies, there are certain methodological issues that need to be taken into account in the interpretation of urinary biomarker data, related to the intrinsic variability of the urination process itself, the relationship between exposure events and biomarker quantification, and the timing of sampling. When setting up HBM-projects, this expected relationship between individual exposure episode and urinary biomarker concentration needs to be taken into account. Copyright © 2014. Published by Elsevier Ireland Ltd.

Stage-Specific Human Induced Pluripotent Stem Cells Map the Progression of Myeloid Transformation to Transplantable Leukemia.

PubMed

Kotini, Andriana G; Chang, Chan-Jung; Chow, Arthur; Yuan, Han; Ho, Tzu-Chieh; Wang, Tiansu; Vora, Shailee; Solovyov, Alexander; Husser, Chrystel; Olszewska, Malgorzata; Teruya-Feldstein, Julie; Perumal, Deepak; Klimek, Virginia M; Spyridonidis, Alexandros; Rampal, Raajit K; Silverman, Lewis; Reddy, E Premkumar; Papaemmanuil, Elli; Parekh, Samir; Greenbaum, Benjamin D; Leslie, Christina S; Kharas, Michael G; Papapetrou, Eirini P

2017-03-02

Myeloid malignancy is increasingly viewed as a disease spectrum, comprising hematopoietic disorders that extend across a phenotypic continuum ranging from clonal hematopoiesis to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we derived a collection of induced pluripotent stem cell (iPSC) lines capturing a range of disease stages encompassing preleukemia, low-risk MDS, high-risk MDS, and secondary AML. Upon their differentiation, we found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia. We also show that disease stage transitions, both reversal and progression, can be modeled in this system using genetic correction or introduction of mutations via CRISPR/Cas9 and that this iPSC-based approach can be used to uncover disease-stage-specific responses to drugs. Our study therefore provides insight into the cellular events demarcating the initiation and progression of myeloid transformation and a new platform for testing genetic and pharmacological interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification and resolution of artifacts in the interpretation of imprinted gene expression

PubMed Central

Proudhon, Charlotte

2010-01-01

Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has failed to uncover a significant number of new imprinted genes, probably because of the high tissue- and developmental-stage specificity of imprinted gene expression. A very large number of technical and biological artifacts can also lead to the erroneous evidence of imprinted gene expression. In this article, we focus on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoallelic expression and (iii) contamination or infiltration of embryonic tissues with maternal material. This last situation specifically applies to genes that occur as maternally expressed in the placenta. Beside the use of reciprocal crosses that are instrumental to confirm the parental specificity of expression, we provide additional methods for the detection and elimination of these situations that can be misinterpreted as cases of imprinted expression. PMID:20829207

Uncovering the Internal Structure of the Indian Financial Market: Large Cross-correlation Behavior in the NSE

NASA Astrophysics Data System (ADS)

Sinha, Sitabhra; Pan, Raj Kumar

The cross-correlations between price fluctuations of 201 frequently traded stocks in the National Stock Exchange (NSE) of India are analyzed in this paper. We use daily closing prices for the period 1996-2006, which coincides with the period of rapid transformation of the market following liberalization. The eigenvalue distribution of the cross-correlation matrix, C, of NSE is found to be similar to that of developed markets, such as the New York Stock Exchange (NYSE): the majority of eigenvalues fall within the bounds expected for a random matrix constructed from mutually uncorrelated time series. Of the few largest eigenvalues that deviate from the bulk, the largest is identified with market-wide movements. The intermediate eigenvalues that occur between the largest and the bulk have been associated in NYSE with specific business sectors with strong intra-group interactions. However, in the Indian market, these deviating eigenvalues are comparatively very few and lie much closer to the bulk. We propose that this is because of the relative lack of distinct sector identity in the market, with the movement of stocks dominantly influenced by the overall market trend. This is shown by explicit construction of the interaction network in the market, first by generating the minimum spanning tree from the unfiltered correlation matrix, and later, using an improved method of generating the graph after filtering out the market mode and random effects from the data. Both methods show, compared to developed markets, the relative absence of clusters of co-moving stocks that belong to the same business sector. This is consistent with the general belief that emerging markets tend to be more correlated than developed markets.

Dimensions of Social Capital among High School Mathematics Teachers

ERIC Educational Resources Information Center

Koebley, Sarah Cotton

2013-01-01

This study sought to uncover teacher perceptions of social capital within a high school mathematics department utilizing a research design that acknowledged the complex environment faced by high school teachers and their subsequent interpretations of how and from whom they sought access to professional resources. Through an analysis of narratives…

Beat-to-beat agreement of noninvasive tonometric and intra-radial arterial blood pressure during microgravity and hypergravity generated by parabolic flights.

PubMed

Normand, Hervé; Lemarchand, Erick; Arbeille, Philippe; Quarck, Gaëlle; Vaïda, Pierre; Duretete, Arnaud; Denise, Pierre

2007-12-01

Accurate measurement of beat-to-beat arterial blood pressure is essential for understanding the cardiovascular adaptation to weightlessness; however, the intra-arterial standard of beat-to-beat blood pressure measurement has never been used during space flight because of its invasive nature. The aim of the present study was to compare noninvasive radial artery tonometry blood pressure measurement with intra-radial pressure measurement during microgravity and hypergravity generated by parabolic flights. Two study participants, equipped with an intra-radial pressure line on the left arm and a Colin CBM-7000 (Colin Corp., Komaki City, Japan) beat-to-beat pressure measurement apparatus on the right arm, were studied in a supine position, during parabolic flights on board of the Airbus A300 OG of the Centre National d'Etudes Spatiales. The mean and standard deviations of the beat-to-beat difference between tonometric and intra-radial blood pressure were calculated for systolic and diastolic arterial pressure in the three gravity conditions (1g, 0 g and 1.8 g) experienced during parabolic flight. The Colin CBM-7000 met the specifications required by the Association for the Advancement of Medical Instrumentation in the 0 g environment. Gravity, however, significantly affected the difference between tonometric and intra-arterial blood pressure, possibly owing to the effect of gravity on the apparent weight of the device and the corresponding calibration factor. We conclude that the Colin CBM-7000 can be used with confidence during space flight.

High Resolution Live Cell Raman Imaging Using Subcellular Organelle-Targeting SERS-Sensitive Gold Nanoparticles with Highly Narrow Intra-Nanogap

PubMed Central

Kang, Jeon Woong; So, Peter T. C.; Dasari, Ramachandra R.; Lim, Dong-Kwon

2015-01-01

We report a method to achieve high speed and high resolution live cell Raman images using small spherical gold nanoparticles with highly narrow intra-nanogap structures responding to NIR excitation (785 nm) and high-speed confocal Raman microscopy. The three different Raman-active molecules placed in the narrow intra-nanogap showed a strong and uniform Raman intensity in solution even under transient exposure time (10 ms) and low input power of incident laser (200 μW), which lead to obtain high-resolution single cell image within 30 s without inducing significant cell damage. The high resolution Raman image showed the distributions of gold nanoparticles for their targeted sites such as cytoplasm, mitochondria, or nucleus. The high speed Raman-based live cell imaging allowed us to monitor rapidly changing cell morphologies during cell death induced by the addition of highly toxic KCN solution to cells. These results strongly suggest that the use of SERS-active nanoparticle can greatly improve the current temporal resolution and image quality of Raman-based cell images enough to obtain the detailed cell dynamics and/or the responses of cells to potential drug molecules. PMID:25646716

Intra-operative mapping of the atria: the first step towards individualization of atrial fibrillation therapy?

PubMed

Kik, Charles; Mouws, Elisabeth M J P; Bogers, Ad J J C; de Groot, Natasja M S

2017-07-01

Atrial fibrillation (AF), an age-related progressive disease, is becoming a worldwide epidemic with a prevalence rate of 33 million. Areas covered: In this expert review, an overview of important results obtained from previous intra-operative mapping studies is provided. In addition, our novel intra-operative high resolution mapping studies, its surgical considerations and data analyses are discussed. Furthermore, the importance of high resolution mapping studies of both sinus rhythm and AF for the development of future AF therapy is underlined by our most recent results. Expert commentary: Progression of AF is determined by the extensiveness of electropathology which is defined as conduction disorders caused by structural damage of atrial tissue. The severity of electropathology is a major determinant of therapy failure. At present, we do not have any diagnostic tool to determine the degree of electropathology in the individual patient and we can thus not select the most optimal treatment modality for the individual patient. An intra-operative, high resolution scale, epicardial mapping approach combined with quantification of electrical parameters may serve as a diagnostic tool to stage AF in the individual patient and to provide patient tailored therapy.

Micro-Doppler Ambiguity Resolution for Wideband Terahertz Radar Using Intra-Pulse Interference

PubMed Central

Yang, Qi; Qin, Yuliang; Deng, Bin; Wang, Hongqiang; You, Peng

2017-01-01

Micro-Doppler, induced by micro-motion of targets, is an important characteristic of target recognition once extracted via parameter estimation methods. However, micro-Doppler is usually too significant to result in ambiguity in the terahertz band because of its relatively high carrier frequency. Thus, a micro-Doppler ambiguity resolution method for wideband terahertz radar using intra-pulse interference is proposed in this paper. The micro-Doppler can be reduced several dozen times its true value to avoid ambiguity through intra-pulse interference processing. The effectiveness of this method is proved by experiments based on a 0.22 THz wideband radar system, and its high estimation precision and excellent noise immunity are verified by Monte Carlo simulation. PMID:28468257

Somatostatin Receptor SPECT/CT using 99mTc Labeled HYNIC-TOC Aids in Diagnosis of Primary Optic Nerve Sheath Meningioma.

PubMed

Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

2017-01-01

Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99m Tc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

Micro-Doppler Ambiguity Resolution for Wideband Terahertz Radar Using Intra-Pulse Interference.

PubMed

Yang, Qi; Qin, Yuliang; Deng, Bin; Wang, Hongqiang; You, Peng

2017-04-29

Micro-Doppler, induced by micro-motion of targets, is an important characteristic of target recognition once extracted via parameter estimation methods. However, micro-Doppler is usually too significant to result in ambiguity in the terahertz band because of its relatively high carrier frequency. Thus, a micro-Doppler ambiguity resolution method for wideband terahertz radar using intra-pulse interference is proposed in this paper. The micro-Doppler can be reduced several dozen times its true value to avoid ambiguity through intra-pulse interference processing. The effectiveness of this method is proved by experiments based on a 0.22 THz wideband radar system, and its high estimation precision and excellent noise immunity are verified by Monte Carlo simulation.

A Model-Based Investigation of Learner Attitude towards Recently Introduced Classroom Technology

ERIC Educational Resources Information Center

Manochehri, Nick-Naser; Sharif, Khurram

2010-01-01

The major aim of this study was to uncover the influence of recently introduced classroom technology on a student's learning attitude. Research was conducted in a Gulf Cooperation Council (GCC) region university where classroom technology was being implemented for the first time. Hence specific attention was being given to the careful management…

An English Teacher's Developing Self-Efficacy Beliefs in Using Groupwork

ERIC Educational Resources Information Center

Wyatt, Mark

2010-01-01

In this article, I explore how an English teacher's self-efficacy beliefs in using groupwork developed, specifically with regard to his work with young learners, while he was engaged part-time on an in-service BA TESOL programme in the Middle East. Using qualitative case study methodology, I uncover various aspects of his self-efficacy growth,…

Revealing List-Level Control in the Stroop Task by Uncovering Its Benefits and a Cost

ERIC Educational Resources Information Center

Bugg, Julie M.; McDaniel, Mark A.; Scullin, Michael K.; Braver, Todd S.

2011-01-01

Interference is reduced in mostly incongruent relative to mostly congruent lists. Classic accounts of this list-wide proportion congruence effect assume that list-level control processes strategically modulate word reading. Contemporary accounts posit that reliance on the word is modulated poststimulus onset by item-specific information (e.g.,…

Developing Guidance Material To Uncover a Mathematics Profile of Adult Participants on a Crane Course.

ERIC Educational Resources Information Center

Lindenskov, Lena

This paper reports on a pilot study in the Danish "Profile in Mathematics" project implemented by the Directorate General for Employment, Placement and Vocational Training and the Ministry of Education. The pilot study develops and tests specific guidance materials to guide participants and teachers through a course for crane workers…

Non-Muslim Schooling in Kosovo during the Abdulhamit II Era and the Policy of Ottoman Government

ERIC Educational Resources Information Center

Nurdogan, Arzu M.

2013-01-01

The purpose of this study was to uncover real importance and volume of schooling interlaced with political practices through placing the education in a pragmatic position in forming national epistemologies and political ambitions by non-Muslims who desire to establish a geography by virtue of having specific national histories, cultures,…

Language-General Biases and Language-Specific Experience Contribute to Phonological Detail in Toddlers' Word Representations

ERIC Educational Resources Information Center

Tsuji, Sho; Fikkert, Paula; Yamane, Naoto; Mazuka, Reiko

2016-01-01

Although toddlers in their 2nd year of life generally have phonologically detailed representations of words, a consistent lack of sensitivity to certain kinds of phonological changes has been reported. The origin of these insensitivities is poorly understood, and uncovering their cause is crucial for obtaining a complete picture of early…

Stress and Deep Structure: A Measure of Language Acquisition, Grades K-6.

ERIC Educational Resources Information Center

Milner, Joseph O.

A study was undertaken to see whether developmental patterns of language acquisition could be discovered in children beyond age five. Specifically, the study attempted to uncover a pattern in the development of the skill of stress interpretation, or the understanding of the effect of emphasis of a particular word on the deep structure of the…

Morphological Awareness in Vocabulary Acquisition among Chinese-Speaking Children: Testing Partial Mediation via Lexical Inference Ability

ERIC Educational Resources Information Center

Zhang, Haomin

2015-01-01

The goal of this study was to investigate the effect of Chinese-specific morphological awareness on vocabulary acquisition among young Chinese-speaking students. The participants were 288 Chinese-speaking second graders from three different cities in China. Multiple regression analysis and mediation analysis were used to uncover the mediated and…

Intra-abdominal fat measurement by ultrasonography: association with anthropometry and metabolic syndrome in adolescents.

PubMed

Novais, Rommel L R; Café, Ana Carolina C; Morais, Aisha A; Bila, Wendell C; Santos, Gilson D da S; Lopes, Carlos Alexandre de O; Belo, Vinícius S; Romano, Márcia Christina C; Lamounier, Joel A

2018-04-27

To associate intra-abdominal fat thickness measured by ultrasonography to the factors related to metabolic syndrome and to determine cutoff points of intra-abdominal fat measurement associated with a greater chance of metabolic syndrome in adolescents. This was a cross-sectional study, with 423 adolescents from public schools. Intra-abdominal fat was measured by ultrasonography. Anthropometric data were collected, and biochemical analyses were performed. Intra-abdominal fat was measured by ultrasonography, showing a statistically significant association with the diagnosis of metabolic syndrome (p=0.037), body mass index (p<0.001), elevated triglyceride levels (p=0.012), decreased plasma HDL levels (p=0.034), and increased systemic blood pressure values (p=0.023). Cutoff values of intra-abdominal fat thickness measurements were calculated by ultrasound to estimate the individuals most likely to develop metabolic syndrome. In the logistic regression models, the cutoff values that showed the highest association with metabolic syndrome in males were 4.50, 5.35, 5.46, 6.24, and 6.50cm for the ages of 14, 15, 16, 17, and 18/19 years, respectively. In the female gender, the cutoff values defined for the same age groups were 4.46, 4.55, 4.45, 4.90, and 6.46cm. In an overall analysis using the ROC curve, without gender and age stratification, the cut-off of 3.67cm showed good sensitivity, but low specificity. Ultrasonography is a useful method to estimate intra-abdominal adipose tissue in adolescents, which is associated with the main factors related to obesity and metabolic syndrome. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.

PubMed

De Jaeger, Xavier; Bishop, Stephanie F; Ahmad, Tasha; Lyons, Danika; Ng, Garye Ami; Laviolette, Steven R

2013-02-01

The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function. The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning. Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl). We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade. These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

Potential impact of climate change on the Intra-Americas Sea: Part 2. Implications for Atlantic bluefin tuna and skipjack tuna adult and larval habitats

NASA Astrophysics Data System (ADS)

Muhling, Barbara A.; Liu, Yanyun; Lee, Sang-Ki; Lamkin, John T.; Roffer, Mitchell A.; Muller-Karger, Frank; Walter, John F., III

2015-08-01

Increasing water temperatures due to climate change will likely have significant impacts on distributions and life histories of Atlantic tunas. In this study, we combined predictive habitat models with a downscaled climate model to examine potential impacts on adults and larvae of Atlantic bluefin tuna (Thunnus thynnus) and skipjack tuna (Katsuwonus pelamis) in the Intra-Americas Sea (IAS). An additional downscaled model covering the 20th century was used to compare habitat fluctuations from natural variability to predicted future changes under two climate change scenarios: Representative Concentration Pathway (RCP) 4.5 (medium-low) and RCP 8.5 (high). Results showed marked temperature-induced habitat losses for both adult and larval bluefin tuna on their northern Gulf of Mexico spawning grounds. In contrast, habitat suitability for skipjack tuna increased as temperatures warmed. Model error was highest for the two skipjack tuna models, particularly at higher temperatures. This work suggests that influences of climate change on highly migratory Atlantic tuna species are likely to be substantial, but strongly species-specific. While impacts on fish populations remain uncertain, these changes in habitat suitability will likely alter the spatial and temporal availability of species to fishing fleets, and challenge equilibrium assumptions of environmental stability, upon which fisheries management benchmarks are based.

Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds.

PubMed

Chang, Chenchen; Huang, Rong; Yan, Yan; Ma, Hongmin; Dai, Zheng; Zhang, Benying; Deng, Zixin; Liu, Wen; Qu, Xudong

2015-04-01

Selective modification of carbon scaffolds via biosynthetic engineering is important for polyketide structural diversification. Yet, this scope is currently restricted to simple aliphatic groups due to (1) limited variety of CoA-linked extender units, which lack aromatic structures and chemical reactivity, and (2) narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked extender units. In this report, we uncovered and characterized the first aromatic CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a deamination/reductive carboxylation strategy to convert phenylalanine into benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender unit synthesis. By characterization of its selection, we further validated that AT domains of splenocin, and antimycin polyketide synthases are able to select this extender unit to introduce the phenyl group into their dilactone scaffolds. The biosynthetic machinery involved in the formation of this extender unit is highly versatile and can be potentially tailored for tyrosine, histidine and aspartic acid. The disclosed aromatic extender unit, amino acid-oriented synthetic pathway, and aromatic-selective AT domains provides a systematic breakthrough toward current knowledge of polyketide extender unit formation and selection, and also opens a route for further engineering of polyketide carbon scaffolds using amino acids.

Construction and Comparative Analyses of Highly Dense Linkage Maps of Two Sweet Cherry Intra-Specific Progenies of Commercial Cultivars

PubMed Central

Quero-García, José; Guzmán, Alejandra; Mansur, Levi; Gratacós, Eduardo; Silva, Herman; Rosyara, Umesh R.; Iezzoni, Amy; Meisel, Lee A.; Dirlewanger, Elisabeth

2013-01-01

Despite the agronomical importance and high synteny with other Prunus species, breeding improvements for cherry have been slow compared to other temperate fruits, such as apple or peach. However, the recent release of the peach genome v1.0 by the International Peach Genome Initiative and the sequencing of cherry accessions to identify Single Nucleotide Polymorphisms (SNPs) provide an excellent basis for the advancement of cherry genetic and genomic studies. The availability of dense genetic linkage maps in phenotyped segregating progenies would be a valuable tool for breeders and geneticists. Using two sweet cherry (Prunus avium L.) intra-specific progenies derived from crosses between ‘Black Tartarian’ × ‘Kordia’ (BT×K) and ‘Regina’ × ‘Lapins’(R×L), high-density genetic maps of the four parental lines and the two segregating populations were constructed. For BT×K and R×L, 89 and 121 F1 plants were used for linkage mapping, respectively. A total of 5,696 SNP markers were tested in each progeny. As a result of these analyses, 723 and 687 markers were mapped into eight linkage groups (LGs) in BT×K and R×L, respectively. The resulting maps spanned 752.9 and 639.9 cM with an average distance of 1.1 and 0.9 cM between adjacent markers in BT×K and R×L, respectively. The maps displayed high synteny and co-linearity between each other, with the Prunus bin map, and with the peach genome v1.0 for all eight LGs (LG1–LG8). These maps provide a useful tool for investigating traits of interest in sweet cherry and represent a qualitative advance in the understanding of the cherry genome and its synteny with other members of the Rosaceae family. PMID:23382953

Lipids in the cell: organisation regulates function.

PubMed

Santos, Ana L; Preta, Giulio

2018-06-01

Lipids are fundamental building blocks of all cells and play important roles in the pathogenesis of different diseases, including inflammation, autoimmune disease, cancer, and neurodegeneration. The lipid composition of different organelles can vary substantially from cell to cell, but increasing evidence demonstrates that lipids become organised specifically in each compartment, and this organisation is essential for regulating cell function. For example, lipid microdomains in the plasma membrane, known as lipid rafts, are platforms for concentrating protein receptors and can influence intra-cellular signalling. Lipid organisation is tightly regulated and can be observed across different model organisms, including bacteria, yeast, Drosophila, and Caenorhabditis elegans, suggesting that lipid organisation is evolutionarily conserved. In this review, we summarise the importance and function of specific lipid domains in main cellular organelles and discuss recent advances that investigate how these specific and highly regulated structures contribute to diverse biological processes.

Inter-observer and intra-observer agreement on interpretation of uroflowmetry curves of kindergarten children.

PubMed

Chang, Shang-Jen; Yang, Stephen S D

2008-12-01

To evaluate the inter-observer and intra-observer agreement on the interpretation of uroflowmetry curves of children. Healthy kindergarten children were enrolled for evaluation of uroflowmetry. Uroflowmetry curves were classified as bell-shaped, tower, plateau, staccato and interrupted. Only the bell-shaped curves were regarded as normal. Two urodynamists evaluated the curves independently after reviewing the definitions of the different types of uroflowmetry curve. The senior urodynamist evaluated the curves twice 3 months apart. The final conclusion was made when consensus was reached. Agreement among observers was analyzed using kappa statistics. Of 190 uroflowmetry curves eligible for analysis, the intra-observer agreement in interpreting each type of curve and interpreting normalcy vs abnormality was good (kappa=0.71 and 0.68, respectively). Very good inter-observer agreement (kappa=0.81) on normalcy and good inter-observer agreement (kappa=0.73) on types of uroflowmetry were observed. Poor inter-observer agreement existed on the classification of specific types of abnormal uroflowmetry curves (kappa=0.07). Uroflowmetry is a good screening tool for normalcy of kindergarten children, while not a good tool to define the specific types of abnormal uroflowmetry.

Phenylpropanoids are key players in the antioxidant defense to ozone of European ash, Fraxinus excelsior.

PubMed

Cotrozzi, Lorenzo; Campanella, Alessandra; Pellegrini, Elisa; Lorenzini, Giacomo; Nali, Cristina; Paoletti, Elena

2018-03-01

Physiological and biochemical responses to ozone (O 3 ) (150 ppb, 8 h day -1 , 35 consecutive days) of two Italian provenances (Piedmont and Tuscany) of Fraxinus excelsior L. were evaluated, with special attention to the role of phenylpropanoids. Our results indicate (i) the high O 3 sensitivity especially of Piedmont provenance (in terms of visible injury, water status, and photosynthetic apparatus); (ii) although the intra-specific sensitivity to O 3 between provenances differs (mainly due to different stomatal behaviors since only Tuscany plants partially avoided the uptake of the pollutant gas), both provenances showed detoxification and defense mechanisms; (iii) the crucial participation of phenylpropanoids, with a key role played by flavonoids (especially quercitrin): among this class of metabolites, isoquercitrin is the principal player in the lower O 3 sensitivity of Tuscany plants, together with lignins; (iv) although coumarins (typical compounds of Fraxinus) were severely depressed by O 3 , isofraxidin was triggered suggesting a key role in reactive oxygen species (ROS) detoxification, as well as trans-chalcone. Furthermore, the different behavior of verbascoside and oleuropein among provenances lead us to speculate on their influence in the tentatively repair or acclimation shown by Piedmont plants at the end of the exposure. Finally, the intra-specific O 3 sensitivity may be also due to de novo peaks triggered by O 3 not yet associated to some chemicals.

Malassezia intra-specific diversity and potentially new species in the skin microbiota from Brazilian healthy subjects and seborrheic dermatitis patients.

PubMed

Soares, Renan Cardoso; Zani, Marcelo Bergamin; Arruda, Ana Carolina Belini Bazán; Arruda, Lucia Helena Fávaro de; Paulino, Luciana Campos

2015-01-01

Malassezia yeasts are part of the resident cutaneous microbiota, and are also associated with skin diseases such as seborrheic dermatitis (SD). The role these fungi play in skin diseases and why they are pathogenic for only some individuals remain unclear. This study aimed to characterize Malassezia microbiota from different body sites in healthy and SD subjects from Brazil. Scalp and forehead samples from healthy, mild SD and severe SD subjects were collected. Non-scalp lesions from severe SD patients were also sampled. 5.8S rDNA/ITS2 amplicons from Malassezia sp. were analyzed by RFLP and sequencing. Results indicate that Malassezia microbiota did not group according to health condition or body area. Phylogenetic analysis revealed that three groups of sequences did not cluster together with any formally described species, suggesting that they might belong to potential new species. One of them was found in high proportions in scalp samples. A large variety of Malassezia subtypes were detected, indicating intra-specific diversity. Higher M. globosa proportions were found in non-scalp lesions from severe SD subjects compared with other areas, suggesting closer association of this species with SD lesions from areas other than scalp. Our results show the first panorama of Malassezia microbiota in Brazilian subjects using molecular techniques and provide new perspectives for further studies to elucidate the association between Malassezia microbiota and skin diseases.

Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery

PubMed Central

Valdés, Pablo A.; Kim, Anthony; Leblond, Frederic; Conde, Olga M.; Harris, Brent T.; Paulsen, Keith D.; Wilson, Brian C.; Roberts, David W.

2011-01-01

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin concentration, oxygen saturation, and optical scattering parameters. We developed a diagnostic algorithm for intra-operative tissue delineation that accounts for the combined tumor-specific predictive capabilities of these quantitative biomarkers. Tumor tissue delineation achieved accuracies of up to 94% (specificity = 94%, sensitivity = 94%) across a range of glioma histologies beyond current state-of-the-art optical approaches, including state-of-the-art fluorescence image guidance. This multiple biomarker strategy opens the door to optical methods for surgical guidance that use quantification of well-established neoplastic processes. Future work would seek to validate the predictive power of this proof-of-concept study in a separate larger cohort of patients. PMID:22112112

Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery

NASA Astrophysics Data System (ADS)

Valdés, Pablo A.; Kim, Anthony; Leblond, Frederic; Conde, Olga M.; Harris, Brent T.; Paulsen, Keith D.; Wilson, Brian C.; Roberts, David W.

2011-11-01

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin concentration, oxygen saturation, and optical scattering parameters. We developed a diagnostic algorithm for intra-operative tissue delineation that accounts for the combined tumor-specific predictive capabilities of these quantitative biomarkers. Tumor tissue delineation achieved accuracies of up to 94% (specificity = 94%, sensitivity = 94%) across a range of glioma histologies beyond current state-of-the-art optical approaches, including state-of-the-art fluorescence image guidance. This multiple biomarker strategy opens the door to optical methods for surgical guidance that use quantification of well-established neoplastic processes. Future work would seek to validate the predictive power of this proof-of-concept study in a separate larger cohort of patients.

TMS uncovers details about sub-regional language-specific processing networks in early bilinguals.

PubMed

Hämäläinen, Sini; Mäkelä, Niko; Sairanen, Viljami; Lehtonen, Minna; Kujala, Teija; Leminen, Alina

2018-05-01

Despite numerous functional neuroimaging and intraoperative electrical cortical mapping studies aimed at investigating the cortical organisation of native (L1) and second (L2) language processing, the neural underpinnings of bilingualism remain elusive. We investigated whether the neural network engaged in speech production over the bilateral posterior inferior frontal gyrus (pIFG) is the same (i.e., shared) or different (i.e., language-specific) for the two languages of bilingual speakers. Navigated transcranial magnetic stimulation (TMS) was applied over the left and right posterior inferior gyrus (pIFG), while early simultaneous bilinguals performed a picture naming task with their native languages. An ex-Gaussian distribution was fitted to the naming latencies and the resulting parameters were compared between languages and across stimulation conditions. The results showed that although the naming performance in general was highly comparable between the languages, TMS produced a language-specific effect when the pulses were delivered to the left pIFG at 200 ms poststimulus. We argue that this result causally demonstrates, for the first time, that even within common language-processing areas, there are distinct language-specific neural populations for the different languages in early simultaneous bilinguals. Copyright © 2018 Elsevier Inc. All rights reserved.

Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver

PubMed Central

2018-01-01

CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that intra-TAD loops form by the same loop extrusion mechanism as the larger TAD loops, and that their shorter length enables finer regulatory control in restricting enhancer-promoter interactions, which enables selective, high-level expression of gene targets of super-enhancers and genes located within repressive nuclear compartments. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. PMID:29757144

Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver.

PubMed

Matthews, Bryan J; Waxman, David J

2018-05-14

CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that intra-TAD loops form by the same loop extrusion mechanism as the larger TAD loops, and that their shorter length enables finer regulatory control in restricting enhancer-promoter interactions, which enables selective, high-level expression of gene targets of super-enhancers and genes located within repressive nuclear compartments. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. © 2018, Matthews et al.

Plasmonic Nanobubbles Rapidly Detect and Destroy Drug-Resistant Tumors

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Townley, Debra; Wu, Xiangwei; Kupferman, Michael E.; Lapotko, Dmitri O.

2012-01-01

The resistance of residual cancer cells after oncological resection to adjuvant chemoradiotherapies results in both high recurrence rates and high non-specific tissue toxicity, thus preventing the successful treatment of such cancers as head and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality of life therefore depend upon the efficacy, selectivity and low non-specific toxicity of the adjuvant treatment. We report a novel, theranostic in vivo technology that unites both the acoustic diagnostics and guided intracellular delivery of anti-tumor drug (liposome-encapsulated doxorubicin, Doxil) in one rapid process, namely a pulsed laser-activated plasmonic nanobubble (PNB). HNSCC-bearing mice were treated with gold nanoparticle conjugates, Doxil, and single near-infrared laser pulses of low energy. Tumor-specific clusters of gold nanoparticles (solid gold spheres) converted the optical pulses into localized PNBs. The acoustic signals of the PNB detected the tumor with high specificity and sensitivity. The mechanical impact of the PNB, co-localized with Doxil liposomes, selectively ejected the drug into the cytoplasm of cancer cells. Cancer cell-specific generation of PNBs and their intracellular co-localization with Doxil improved the in vivo therapeutic efficacy from 5-7% for administration of only Doxil or PNBs alone to 90% thus demonstrating the synergistic therapeutic effect of the PNB-based intracellular drug release. This mechanism also reduced the non-specific toxicity of Doxil below a detectable level and the treatment time to less than one minute. Thus PNBs combine highly sensitive diagnosis, overcome drug resistance and minimize non-specific toxicity in a single rapid theranostic procedure for intra-operative treatment. PMID:23139725

Juvenile granulosa cell tumor arising from intra-abdominal testis in newborn: case report and review of the literature.

PubMed

Partalis, Nikolaos; Tzardi, Maria; Barbagadakis, Sophia; Sakellaris, George

2012-05-01

In the present case, the neonate presented with a left-sided abdominal mass and an empty left scrotum. Abdominal ultrasonography showed well-defined cystic formation, and laparotomy revealed a tumor arising from an intra-abdominal left testis. The carcinoembryonic antigen and neuron-specific enolase levels were within normal limits, and the serum β-human chorionic gonadotropin and α-fetoprotein levels were within age-related normal values. The findings from the immunochemistry tests confirmed the diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Insights into Ventilatory Inhomogeneity from Respiratory Measurements on Spacelab Mission D-2

NASA Technical Reports Server (NTRS)

Paiva, Manuel; Verbanck, Sylvia; Linnarsson, Dag; Prisk, Kim; West, John B.

1996-01-01

The relative contributions of inter-regional and intra-regional ventilation inhomogeneities of Spacelab astronauts are studied. The classical theory of ventilation distribution in the lung is that the top-to-bottom (inter-regional) ventilation inhomogeneities are primarily gravity dependent, whereas the peripheral (intra-regional) ventilation distribution is gravity independent. Argon rebreathing tests showed that gravity independent specific ventilation (ventilation per unit volume) inhomogeneities are at least as large as gravity dependent ones. Single breath tests with helium and sulfur hexafluoride showed the different sensitivity of these gases to microgravity.

Development and validation of a computational model of the knee joint for the evaluation of surgical treatments for osteoarthritis

PubMed Central

Mootanah, R.; Imhauser, C.W.; Reisse, F.; Carpanen, D.; Walker, R.W.; Koff, M.F.; Lenhoff, M.W.; Rozbruch, S.R.; Fragomen, A.T.; Dewan, Z.; Kirane, Y.M.; Cheah, Pamela A.; Dowell, J.K.; Hillstrom, H.J.

2014-01-01

A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between EE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning. PMID:24786914

Development and validation of a computational model of the knee joint for the evaluation of surgical treatments for osteoarthritis.

PubMed

Mootanah, R; Imhauser, C W; Reisse, F; Carpanen, D; Walker, R W; Koff, M F; Lenhoff, M W; Rozbruch, S R; Fragomen, A T; Dewan, Z; Kirane, Y M; Cheah, K; Dowell, J K; Hillstrom, H J

2014-01-01

A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between FE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning.

Validation of 2 commercially available enzyme-linked immunosorbent assays for adiponectin determination in canine serum samples.

PubMed

Tvarijonaviciute, Asta; Martínez-Subiela, Silvia; Ceron, José J

2010-10-01

The aim of this study was to validate 2 commercially available enzyme-linked immunosorbent assays (ELISAs) for adiponectin in dogs, 1 canine-specific and 1 originally designed for measurements in humans. Intra-assay and interassay precision was evaluated by multiple measurements in canine serum samples, and assay accuracy was indirectly determined by linearity under dilution. Interference caused by hemolysis and lipemia was also studied. Both assays were subsequently used for measuring adiponectin concentrations in clinically healthy dogs and those with different grades of obesity. The intra-assay and inter-assay precision was less than 7.5% and 13.5% in serum samples with low and high adiponectin concentrations, respectively. Lipemia and hemolysis did not affect the results of any of the assays. Both assays were able to differentiate lean dogs from those that were overweight or obese on the basis of the measured adiponectin concentrations. From these results it can be concluded that canine adiponectin concentrations can be measured reliably by means of the 2 ELISAs evaluated in this study.

Validation of 2 commercially available enzyme-linked immunosorbent assays for adiponectin determination in canine serum samples

PubMed Central

Tvarijonaviciute, Asta; Martínez-Subiela, Silvia; Ceron, José J.

2010-01-01

The aim of this study was to validate 2 commercially available enzyme-linked immunosorbent assays (ELISAs) for adiponectin in dogs, 1 canine-specific and 1 originally designed for measurements in humans. Intra-assay and interassay precision was evaluated by multiple measurements in canine serum samples, and assay accuracy was indirectly determined by linearity under dilution. Interference caused by hemolysis and lipemia was also studied. Both assays were subsequently used for measuring adiponectin concentrations in clinically healthy dogs and those with different grades of obesity. The intra-assay and inter-assay precision was less than 7.5% and 13.5% in serum samples with low and high adiponectin concentrations, respectively. Lipemia and hemolysis did not affect the results of any of the assays. Both assays were able to differentiate lean dogs from those that were overweight or obese on the basis of the measured adiponectin concentrations. From these results it can be concluded that canine adiponectin concentrations can be measured reliably by means of the 2 ELISAs evaluated in this study. PMID:21197228

Biogeomorphic feedbacks within riparian corridors: the role of positive interactions between riparian plants

NASA Astrophysics Data System (ADS)

Corenblit, Dov; Steiger, Johannes; Till-Bottraud, Irène

2017-04-01

Riparian vegetation affects hydrogeomorphic processes and leads to the construction of wooded fluvial landforms within riparian corridors. Multiple plants form dense multi- and mono-specific stands that enhance plant resistance as grouped plants are less prone to be uprooted than free-standing individuals. Riparian plants which grow in dense stands also enhance their role as ecosystem engineers through the trapping of sediment, organic matter and nutrients. The wooded biogeomorphic landforms which originate from the effect of vegetation on geomorphology lead in return to an improved capacity of the plants to survive, exploit resources, and reach sexual maturity in the intervals between destructive floods. Thus, these vegetated biogeomorphic landforms likely represent a positive niche construction of riparian plants. The nature and intensity of biotic interactions between riparian plants of different species (inter-specific) or the same species (intra-specific) which form dense stands and construct together the niche remain unclear. We strongly suspect that indirect inter-specific positive interactions (facilitation) occur between plants but that more direct intra-specific interactions, such as cooperation and altruism, also operate during the niche construction process. Our aim is to propose an original theoretical framework of inter and intra-specific positive interactions between riparian plants. We suggest that positive interactions between riparian plants are maximized in river reaches with an intermediate level of hydrogeomorphic disturbance. During establishment, plants that grow within dense stands improve their survival and growth because individuals protect each other from shear stress. In addition to the improved capacity to trap mineral and organic matter, individuals which constitute the dense stand can cooperate to mutually support a mycorrhizal fungi network that will connect plants, soil and ground water and influence nutrient transfer, cycling and storage within the shared constructed niche. During post-establishment, the probability of finding functional natural root grafting between neighbour trees increases, which could represent a biomechanical and physiological advantage for anchorage and nutrient acquisition and exchange. These stands remain dense on alluvial bars until a threshold of landform construction and hydrogeomorphic disconnection is reached. We suggest that intra-specific competition for resources then increases and induces a density reduction in the stand (i.e. self-thinning), linked not only to competition but potentially also to altruism. This may be due to a grafted root system and the death of aboveground stems of some of the grafted individuals, resulting in more space for the development of the tall competitive individuals, whereas the initial riparian biogeomorphic landform turns more and more into a terrestrial biogeomorphic landform.

Usefulness of magnifying endoscopy with narrow-band imaging for diagnosis of depressed gastric lesions

PubMed Central

SUMIE, HIROAKI; SUMIE, SHUJI; NAKAHARA, KEITA; WATANABE, YASUTOMO; MATSUO, KEN; MUKASA, MICHITA; SAKAI, TAKESHI; YOSHIDA, HIKARU; TSURUTA, OSAMU; SATA, MICHIO

2014-01-01

The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) for the diagnosis of early gastric cancer is well known, however, there are no evaluation criteria. The aim of this study was to devise and evaluate a novel diagnostic algorithm for ME-NBI in depressed early gastric cancer. Between August, 2007 and May, 2011, 90 patients with a total of 110 depressed gastric lesions were enrolled in the study. A diagnostic algorithm was devised based on ME-NBI microvascular findings: microvascular irregularity and abnormal microvascular patterns (fine network, corkscrew and unclassified patterns). The diagnostic efficiency of the algorithm for gastric cancer and histological grade was assessed by measuring its mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Furthermore, inter- and intra-observer variation were measured. In the differential diagnosis of gastric cancer from non-cancerous lesions, the mean sensitivity, specificity, PPV, NPV, and accuracy of the diagnostic algorithm were 86.7, 48.0, 94.4, 26.7, and 83.2%, respectively. Furthermore, in the differential diagnosis of undifferentiated adenocarcinoma from differentiated adenocarcinoma, the mean sensitivity, specificity, PPV, NPV, and accuracy of the diagnostic algorithm were 61.6, 86.3, 69.0, 84.8, and 79.1%, respectively. For the ME-NBI final diagnosis using this algorithm, the mean κ values for inter- and intra-observer agreement were 0.50 and 0.77, respectively. In conclusion, the diagnostic algorithm based on ME-NBI microvascular findings was convenient and had high diagnostic accuracy, reliability and reproducibility in the differential diagnosis of depressed gastric lesions. PMID:24649321

Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering.

PubMed

Peurois, François; Veyron, Simon; Ferrandez, Yann; Ladid, Ilham; Benabdi, Sarah; Zeghouf, Mahel; Peyroche, Gérald; Cherfils, Jacqueline

2017-03-23

Active, GTP-bound small GTPases need to be attached to membranes by post-translational lipid modifications in order to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by guanine nucleotide exchange factors (GEFs) and their termination by GTPase-activating proteins. Here, we replaced the lipid modification by a histidine tag in 11 full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid-containing membranes and characterize the kinetics of their activation by GEFs. Remarkably, this strategy uncovered large effects of membranes on the efficiency and/or specificity in all systems studied. Notably, it recapitulated the release of autoinhibition of Arf1, Arf3, Arf4, Arf5 and Arf6 GTPases by membranes and revealed that all isoforms are efficiently activated by two GEFs with different regulatory regimes, ARNO and Brag2. It demonstrated that membranes stimulate the GEF activity of Trio toward RhoG by ∼30 fold and Rac1 by ∼10 fold, and uncovered a previously unknown broader specificity toward RhoA and Cdc42 that was undetectable in solution. Finally, it demonstrated that the exceptional affinity of the bacterial RabGEF DrrA for the phosphoinositide PI(4)P delimits the activation of Rab1 to the immediate vicinity of the membrane-bound GEF. Our study thus validates the histidine-tag strategy as a potent and simple means to mimic small GTPase lipidation, which opens a variety of applications to uncover regulations brought about by membranes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Inhibition of intra-Golgi transport in vitro by mitotic kinase.

PubMed

Stuart, R A; Mackay, D; Adamczewski, J; Warren, G

1993-02-25

It has previously been shown that exocytic and endocytic membrane traffic are inhibited in mitotic mammalian cells. Here we have used a cell-free intra-Golgi transport assay supplemented with heterologous cytosols to mimic this effect in vitro. Cytosols with high histone kinase activity, made either from mitotic cells or by cyclin A treatment of interphase cells, inhibited intra-Golgi transport by up to 75%. Inhibition of transport was reversed by the kinase inhibitor staurosporine or by reduction in ATP levels leading to inactivation of histone kinase. The data indicate that cell cycle control of intra-Golgi transport is due to a reversible modification of cytosol, and this assay system may be used to study the molecular mechanism of mitotic transport inhibition in mammalian cells.

Translation into Brazilian Portuguese, cross-cultural adaptation and validation of the Stanford presenteeism scale-6 and work instability scale for ankylosing spondylitis.

PubMed

Frauendorf, Renata; de Medeiros Pinheiro, Marcelo; Ciconelli, Rozana Mesquita

2014-12-01

Loss of productivity at work, as a result of health problems, is becoming an issue of interest due to the high burden it represents in society. The measurement of such phenomenon can be made using generic and specific scales for certain diseases such as the Stanford Presenteeism Scale (SPS-6) and the Work Instability Scale for Ankylosing Spondylitis (AS-WIS), specific for patients with ankylosing spondylitis (AS). The aim of this study was to translate and perform a cross-cultural adaptation of SPS-6 and AS-WIS into Portuguese and check their psychometric properties. The study also aimed to evaluate the relationship between the general scores of the scales and the main sociodemographic and clinical data, lifestyles, and absenteeism in patients with AS and correlate these variables with SPS-6 and AS-WIS scales. A sample of 120 patients with AS and 80 workers at a university hospital was evaluated. The processes for the translation and cross-cultural adaptation of the instruments followed preestablished steps and rules presented in the literature. For the evaluation of measurement properties and correlations between scales, intra-class correlation coefficient (reproducibility analysis), Cronbach alpha (internal consistency), and Pearson correlation coefficient (validity) were employed. The inter-observer (0.986) and intra-observer (0.992) reproducibilities of the AS-WIS were shown to be high as well as the internal consistency (0.995). Similarly, the inter-observer reliability of SPS-6 was considered good (0.890), although it showed a poorer performance when considering the same observer (Pearson correlation coefficient = 0.675 and intra-class correlation = 0.656). Internal consistency, for the total number of items, as measured by Cronbach alpha, was 0.889. The validity of the scales was evaluated thru the comparison of the achieved scores with the results of the WLQ, SF-36, ASQoL, BASFI, BASDAI, HAQ-S, and SRQ-20 instruments. Correlations between loss of productivity at work, worse quality of life, presence of emotional disturbances, and worse health conditions were positive. The process of translation, cross-cultural adaptation, and validation of the SPS-6 as a generic measurement for the loss of productivity at work and of the AS-WIS as a specific measurement for patients with AS are valid, reproducible, and specific instruments to be used in Brazil. In both scales, productivity at work was associated to advanced age, higher rate of absenteeism in the last month and year, presence of peripheral arthritis, and a larger number of comorbidities in patients with AS. The AS-WIS and SPS-6 showed a good correlation among them although they are not mutually exclusive but supplementary.

A multiplex branched DNA assay for parallel quantitative gene expression profiling.

PubMed

Flagella, Michael; Bui, Son; Zheng, Zhi; Nguyen, Cung Tuong; Zhang, Aiguo; Pastor, Larry; Ma, Yunqing; Yang, Wen; Crawford, Kimberly L; McMaster, Gary K; Witney, Frank; Luo, Yuling

2006-05-01

We describe a novel method to quantitatively measure messenger RNA (mRNA) expression of multiple genes directly from crude cell lysates and tissue homogenates without the need for RNA purification or target amplification. The multiplex branched DNA (bDNA) assay adapts the bDNA technology to the Luminex fluorescent bead-based platform through the use of cooperative hybridization, which ensures an exceptionally high degree of assay specificity. Using in vitro transcribed RNA as reference standards, we demonstrated that the assay is highly specific, with cross-reactivity less than 0.2%. We also determined that the assay detection sensitivity is 25,000 RNA transcripts with intra- and interplate coefficients of variance of less than 10% and less than 15%, respectively. Using three 10-gene panels designed to measure proinflammatory and apoptosis responses, we demonstrated sensitive and specific multiplex gene expression profiling directly from cell lysates. The gene expression change data demonstrate a high correlation coefficient (R(2)=0.94) compared with measurements obtained using the single-plex bDNA assay. Thus, the multiplex bDNA assay provides a powerful means to quantify the gene expression profile of a defined set of target genes in large sample populations.

Inter and intra-observer reliability in assessment of the position of the lateral sesamoid in determining the severity of hallux valgus.

PubMed

Panchani, Sunil; Reading, Jonathan; Mehta, Jaysheel

2016-06-01

The position of the lateral sesamoid on standard dorso-plantar weight bearing radiographs, with respect to the lateral cortex of the first metatarsal, has been shown to correlate well with the degree of the hallux valgus angle. This study aimed to assess the inter- and intra-observer error of this new classification system. Five orthopaedic consultants and five trainee orthopaedic surgeons were recruited to assess and document the degree of displacement of the lateral sesamoid on 144 weight-bearing dorso-plantar radiographs on two separate occasions. The severity of hallux valgus was defined as normal (0%), mild (≤50%), moderate (51-≤99%) or severe (≥100%) depending on the percentage displacement of the lateral sesamoid body from the lateral cortical border of the first metatarsal. Consultant intra-observer variability showed good agreement between repeated assessment of the radiographs (mean Kappa=0.75). Intra-observer variability for trainee orthopaedic surgeons also showed good agreement with a mean Kappa=0.73. Intraclass correlations for consultants and trainee surgeons was also high. The new classification system of assessing the severity of hallux valgus shows high inter- and intra-observer variability with good agreement and reproducibility between surgeons of consultant and trainee grades. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intra-arterial Ultra-low-Dose CT Angiography of Lower Extremity in Diabetic Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Özgen, Ali, E-mail: draliozgen@hotmail.com; Sanioğlu, Soner; Bingöl, Uğur Anıl

2016-08-15

PurposeTo image lower extremity arteries by CT angiography using a very low-dose intra-arterial contrast medium in patients with high risk of developing contrast-induced nephropathy (CIN).Materials and MethodsThree cases with long-standing diabetes mellitus and signs of lower extremity atherosclerotic disease were evaluated by CT angiography using 0.1 ml/kg of the body weight of contrast medium given via 10-cm-long 4F introducer by puncturing the CFA. Images were evaluated by an interventional radiologist and a cardiovascular surgeon. Density values of the lower extremity arteries were also calculated. Findings in two cases were compared with digital subtraction angiography images performed for percutaneous revascularization. Blood creatininemore » levels were followed for possible CIN.ResultsIntra-arterial CT angiography images were considered diagnostic in all patients and optimal in one patient. No patient developed CIN after intra-arterial CT angiography, while one patient developed CIN after percutaneous intervention.ConclusionIntra-arterial CT angiography of lower extremity might be performed in selected patients with high risk of developing CIN. Our limited experience suggests that as low as of 0.1 ml/kg of the body weight of contrast medium may result in adequate diagnostic imaging.« less