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Sample records for combined multiple intraluminal

  1. Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH

    PubMed Central

    Del Buono, R; Wenzl, T; Ball, G; Keady, S; Thomson, M

    2005-01-01

    Background: Gaviscon Infant (GI) has been recommended for gastro-oesophageal reflux (GOR) in infants. Its efficacy has not been examined with a physiologically appropriate denominator to define the degree of GOR. Aim: To investigate the influence of Gaviscon Infant on GOR in infants using combined pH and intraluminal impedance measurement. Methods: Twenty infants (mean age 163.5 days, range 34–319 days) exclusively bottle fed, with symptoms clinically suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel impedance and dual channel pH monitoring, during which six random administrations (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH reflux data were recorded and analysed blind by one observer. Results: The median number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v 0.43), minimum distal or proximal pH, total acid clearance time per hour (time with pH below pH 4), and total reflux duration per hour were not significantly different after GI than after placebo. Reflux height was marginally lower after GI (median 66.6% v 77.3% oesophageal length) compared with placebo. Conclusions: Results showed a marginal but significant difference between Gaviscon Infant and placebo in average reflux height, and raises questions regarding any perceived clinical benefit of its use. PMID:15851425

  2. Combining multiple altimeter missions

    NASA Astrophysics Data System (ADS)

    Jacobs, G. A.; Mitchell, J. L.

    1997-10-01

    Viewing altimeter data only at the points where separate altimeter missions' ground tracks cross provides a method to observe long time period sea surface height (SSH) variations and avoids many of the problems inherent in combining separate altimeter data sets through an independently determined geoid. TOPEX/POSEIDON (T/P) data over the time period from January 1, 1993, to December 31, 1995, form a mean SSH that is used as a reference by other altimeter data sets. A least squares analysis of the mean T/P SSH determines the portion of the Geographically Correlated Orbit Error (GCOE) that may be observed through crossover differences and removes this portion of the GCOE. The analysis removes errors of 0.86 cm RMS at 1 cycle per orbit revolution (cpr) and indicates negligible errors at higher frequencies. After the GCOE removal, the accuracy of the T/P reference mean is better than 1 cm RMS as measured by crossover differences. The GCOE contained in the Geosat-Exact Repeat Mission (ERM) and ERS 1 data with orbit solutions using the Joint Gravity Model (JGM) 3 is evaluated through an adjustment to the T/P reference mean surface. The Geosat-ERM data indicate a bias of about 28 cm averaged over the globe, and the ERS 1 bias is 44 cm. The T/P data used here is not corrected for the oscillator drift correction error so that the actual bias is less by about 13 cm. Both the Geosat-ERM and ERS 1 GCOE are mainly 1 cpr. GCOE estimates at frequencies above 1 cpr indicate little actual orbit error but are more correlated to instrument correction errors (particularly water vapor). Simultaneous T/P and ERS 1 SSH anomalies to the T/P mean indicate good correlation.

  3. Evaluation of Gastroesophageal Reflux by Combined Multichannel Intraluminal Impedance and pH Monitoring and Esophageal Motility Patterns in Children with Esophageal Atresia.

    PubMed

    Tong, Stanley; Mallitt, Kylie-Ann; Krishnan, Usha

    2016-08-01

    Background Gastroesophageal reflux disease (GERD) and esophageal dysmotility are common in patients with esophageal atresia (EA). The aim of this study was to evaluate GERD and esophageal motility patterns in children with EA using combined multichannel intraluminal impedance and pH (MII-pH) monitoring and high-resolution esophageal manometry (HREM), respectively. The reflux patterns seen in EA patients were also compared with a control group of normal children with suspected GERD. Methods A retrospective chart review was done on 35 patients with EA and 35 age- and sex-matched normal controls with suspected GERD, who had undergone 24-hour MII-pH monitoring. Impedance data were compared between both cohorts. Eight of the EA patients also underwent HREM. Results In the EA cohort, the median age was 53 months, with 21 males, and 71.4% had Type C EA. A total of 85.7% of the EA cohort and 40% of the control group were on proton-pump inhibitor (PPI) therapy during the MII-pH study. There was no significant difference in the total retrograde bolus movements (RBMs) between the EA cohort (1,457) and the control group (1,482). Acidic RBMs was significantly lower in the EA group (208) compared with the control group (689), p = 0.0008. Nonacid reflux index (NARI) was significantly higher in EA children (1.1; 0.0-7.8) compared with controls (0.6; 0.0-5.7), p = 0.0046. In EA patients, only 335/1,183 (28%) total symptom occurrences were associated with RBM. The mean distal baseline impedance (DBI) was significantly lower in EA (1,029.6 [410.9 SD] Ω) compared with controls (2,998.2 [1028.8 SD] Ω) with suspected GERD, p < 0.0001. By logistic regression, only PPI use had a significant effect on DBI, p < 0.0001. HREM was abnormal in all eight EA patients. Four out of eight EA patients had a different peristaltic pattern for their solid swallows compared with their liquid swallows in HREM. Conclusions MII-pH testing allowed increased detection of nonacid

  4. Intra- and inter-observer reliability of combined segmental measurement techniques for predicting immediate post-deployment intraluminal tracheal stent length in dogs.

    PubMed

    Monaco, Thomas A; Taylor, Jim A; Langenbach, Anke; Gordon, Sebastian; Vance, Eric

    2014-05-01

    This study evaluated segmental measurement techniques for predicting immediate post-deployment intraluminal tracheal stent length in dogs with naturally occurring tracheal collapse. Radiographs of 12 client-owned dogs that underwent intraluminal tracheal stent placement were retrospectively reviewed. Tracheal lengths were divided into 1, 2, 3, or 4 equal segments. Stent lengths were predicted using the widest dorsoventral height of each segment, with and without the addition of 10%, and an accompanying foreshortening chart. Techniques were compared for intra- and inter-observer reliability, and post-deployment stent length predictability. There was good to high intra- and inter-observer reliability for all segmental measurements; median intra-class correlation coefficients were 0.98 and 0.92, respectively. Measuring 2 segments without the addition of 10% to the widths was significantly more accurate in predicting immediate post-deployment stent length in terms of percent (P = 0.03) and absolute difference (P = 0.02). Segmental measuring techniques are repeatable amongst observers and may help guide stent selection. PMID:24790228

  5. Relation between gastric emptying rate and rate of intraluminal lipolysis.

    PubMed

    Maes, B D; Ghoos, Y F; Geypens, B J; Hiele, M I; Rutgeerts, P J

    1996-01-01

    The variable gastric emptying rate of a test meal is one of the major problems in evaluating accurately gastrointestinal physiological functions beyond the stomach. The aim of this study was to evaluate the effect of the gastric emptying rate on the rate of intraluminal lipolysis. Thirty four subjects without pancreatic disease (21 with a normal gastric emptying and 13 with a known slow gastric emptying) and 14 subjects with pancreatic disease (four without and 10 with pancreatic insufficiency) were studied using a dual labelled breath test. The test meal consisted of one egg, 60 grams of white bread, 10 grams of margarine, and 150 ml of water (350 kcal). The egg yolk was labelled with 91 mg of 13C-octanoic acid, the margarine was labelled with 296 kBq of distearyl-2-14C-octanoyl-glycerol. Breath samples were taken every 15 minutes during six hours and analysed for 13CO2 and 14CO2 content. The gastric emptying rate of the meal was evaluated by the gastric emptying coefficient, the half emptying time, and the lag phase; the rate of intraluminal lipolysis was evaluated by the six hours cumulative 14CO2 excretion. Despite a clear distinction in the rate of intraluminal lipolysis, no difference could be detected in gastric emptying rate of the test meal between subjects without and with pancreatic disease. In subjects with pancreatic insufficiency, intraluminal hydrolysis was the rate limiting process in fat assimilation; in patients without pancreatic insufficiency, however, gastric emptying could be rate limiting. Therefore, patients with known slow gastric emptying, displayed a significantly decreased rate of intraluminal lipolysis compared with normal controls. This decrease could be corrected for accurately using a correction factor based on the gastric emptying coefficient. In conclusion, the combined 13C-octanoic acid and 14C-mixed triglyceride breath test permits the measurement of gastric emptying rate and intraluminal lipolysis simultaneously in a minimally

  6. Intraluminal tissue welding for anastomosis

    DOEpatents

    Glinsky, M.; London, R.; Zimmerman, G.; Jacques, S.

    1998-10-27

    A method and device are provided for performing intraluminal tissue welding for anastomosis of a hollow organ. A retractable catheter assembly is delivered through the hollow organ and consists of a catheter connected to an optical fiber, an inflatable balloon, and a biocompatible patch mounted on the balloon. The disconnected ends of the hollow organ are brought together on the catheter assembly, and upon inflation of the balloon, the free ends are held together on the balloon to form a continuous channel while the patch is deployed against the inner wall of the hollow organ. The ends are joined or ``welded`` using laser radiation transmitted through the optical fiber to the patch. A thin layer of a light-absorbing dye on the patch can provide a target for welding. The patch may also contain a bonding agent to strengthen the bond. The laser radiation delivered has a pulse profile to minimize tissue damage. 8 figs.

  7. Intraluminal tissue welding for anastomosis

    DOEpatents

    Glinsky, Michael; London, Richard; Zimmerman, George; Jacques, Steven

    1998-10-27

    A method and device are provided for performing intraluminal tissue welding for anastomosis of a hollow organ. A retractable catheter assembly is delivered through the hollow organ and consists of a catheter connected to an optical fiber, an inflatable balloon, and a biocompatible patch mounted on the balloon. The disconnected ends of the hollow organ are brought together on the catheter assembly, and upon inflation of the balloon, the free ends are held together on the balloon to form a continuous channel while the patch is deployed against the inner wall of the hollow organ. The ends are joined or "welded" using laser radiation transmitted through the optical fiber to the patch. A thin layer of a light-absorbing dye on the patch can provide a target for welding. The patch may also contain a bonding agent to strengthen the bond. The laser radiation delivered has a pulse profile to minimize tissue damage.

  8. Regulation of intestinal ontogeny by intraluminal nutrients.

    PubMed

    Castillo, R O; Feng, J J; Stevenson, D K; Kerner, J A; Kwong, L K

    1990-02-01

    Major events in gastrointestinal ontogeny occur in the infant rat in association with weaning, resulting in striking alterations in small intestinal structure and function. Although the dietary changes attendant to weaning are not essential for the initiation of these events, dietary nutrients have been shown to participate in the maturation of some intestinal parameters. In order to define more precisely the role of intraluminal nutrients in the regulation of small intestinal ontogeny, a longitudinal study was conducted using a unique animal model in which intraluminal nutrients were excluded from the intact maturing intestine in vivo throughout the entire weaning period without major compromise in nutritional status. The absence of intraluminal nutrients over the weaning period resulted in diminished lengthening and accretion of mucosal mass, suggesting a slower rate of intestinal growth. Lower mucosal DNA, protein, and mitotic indices in intestines of animals receiving no intraluminal nutrients suggested that the lack of intraluminal nutrients resulted in the blunting of the striking increases in cellular proliferation normally exhibited by the developing intestinal mucosa at this time. Maturation of intestinal lactase-phlorizin hydrolase and maltase-glucoamylase was not affected by the absence of intraluminal nutrients. Although the appearance of sucrase-isomaltase was not altered by the absence of intraluminal nutrients, activity levels rose to only 50% of control levels. These data suggest that during this period of rapid intestinal maturation, intestinal growth is more dependent upon intraluminal nutrients than are the characteristic enzymic alterations normally expressed during this period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2303970

  9. Intraluminal fibrosis in interstitial lung disorders.

    PubMed Central

    Basset, F.; Ferrans, V. J.; Soler, P.; Takemura, T.; Fukuda, Y.; Crystal, R. G.

    1986-01-01

    The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are

  10. Novel Combination Treatments in Multiple Myeloma.

    PubMed

    Nooka, Ajay K; Lonial, Sagar

    2016-05-01

    The last decade has witnessed the identification of several novel druggable targets in multiple myeloma, leading to identification of novel therapies with clinically proven efficacy, both in the newly diagnosed and relapsed setting. More importantly, a common theme of good outcomes was observed among prospective randomized studies that have utilized combinations of agents with different mechanisms of action. The correlation between achieving a deeper response and the improvement in progression-free survival and overall survival has never been so clear. In this article, we elucidate the rationale for use of novel drug combinations in patients with myeloma, and review current evidence-based data supporting the use of specific combinations in various settings. We also attempt to craft a framework to guide clinicians in optimizing the use of combination therapies, to enable patients to derive maximal benefit. PMID:27188677

  11. Combining Multiple Gyroscope Outputs for Increased Accuracy

    NASA Technical Reports Server (NTRS)

    Bayard, David S.

    2003-01-01

    A proposed method of processing the outputs of multiple gyroscopes to increase the accuracy of rate (that is, angular-velocity) readings has been developed theoretically and demonstrated by computer simulation. Although the method is applicable, in principle, to any gyroscopes, it is intended especially for application to gyroscopes that are parts of microelectromechanical systems (MEMS). The method is based on the concept that the collective performance of multiple, relatively inexpensive, nominally identical devices can be better than that of one of the devices considered by itself. The method would make it possible to synthesize the readings of a single, more accurate gyroscope (a virtual gyroscope) from the outputs of a large number of microscopic gyroscopes fabricated together on a single MEMS chip. The big advantage would be that the combination of the MEMS gyroscope array and the processing circuitry needed to implement the method would be smaller, lighter in weight, and less power-hungry, relative to a conventional gyroscope of equal accuracy. The method (see figure) is one of combining and filtering the digitized outputs of multiple gyroscopes to obtain minimum-variance estimates of rate. In the combining-and-filtering operations, measurement data from the gyroscopes would be weighted and smoothed with respect to each other according to the gain matrix of a minimum- variance filter. According to Kalman-filter theory, the gain matrix of the minimum-variance filter is uniquely specified by the filter covariance, which propagates according to a matrix Riccati equation. The present method incorporates an exact analytical solution of this equation.

  12. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  13. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  14. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  15. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  16. 21 CFR 870.4875 - Intraluminal artery stripper.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Intraluminal artery stripper. 870.4875 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4875 Intraluminal artery stripper. (a) Identification. An intraluminal artery stripper is a device used to perform an...

  17. Three allele combinations associated with Multiple Sclerosis

    PubMed Central

    Favorova, Olga O; Favorov, Alexander V; Boiko, Alexey N; Andreewski, Timofey V; Sudomoina, Marina A; Alekseenkov, Alexey D; Kulakova, Olga G; Gusev, Eugenyi I; Parmigiani, Giovanni; Ochs, Michael F

    2006-01-01

    Background Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles. PMID:16872485

  18. Combining Multiple Pairwise Structure-based Alignments

    SciTech Connect

    2014-11-12

    CombAlign is a new Python code that generates a gapped, one-to-many, multiple structure-based sequence alignment(MSSA) given a set of pairwise structure-based alignments. In order to better define regions of similarity among related protein structures, it is useful to detect the residue-residue correspondences among a set of pairwise structure alignments. Few codes exist for constructing a one-to-many, multiple sequence alignment derived from a set of structure alignments, and we perceived a need for creating a new tool for combing pairwise structure alignments that would allow for insertion of gaps in the reference structure.

  19. Combining Multiple Pairwise Structure-based Alignments

    Energy Science and Technology Software Center (ESTSC)

    2014-11-12

    CombAlign is a new Python code that generates a gapped, one-to-many, multiple structure-based sequence alignment(MSSA) given a set of pairwise structure-based alignments. In order to better define regions of similarity among related protein structures, it is useful to detect the residue-residue correspondences among a set of pairwise structure alignments. Few codes exist for constructing a one-to-many, multiple sequence alignment derived from a set of structure alignments, and we perceived a need for creating a newmore » tool for combing pairwise structure alignments that would allow for insertion of gaps in the reference structure.« less

  20. Endophthalmitis associated with Glaucoma Shunt Intraluminal Stent Exposure

    PubMed Central

    Kerr, Nathan M; Ruddle, Jonathan B; Ang, Ghee Soon

    2016-01-01

    ABSTRACT Endophthalmitis post glaucoma drainage implant (GDI) surgery is rare, often associated with tube or plate exposure. We report a case of endophthalmitis following glaucoma shunt intraluminal stent exposure in a patient who underwent Baerveldt glaucoma implant surgery. Endophthalmitis following manipulation of intraluminal stents is a rare complication of GDIs but potentially vision threatening condition that needs to be carefully screened for and treated immediately. How to cite this article: Kwon HJ, Kerr NM, Ruddle JB, Ang GS. Endophthalmitis associated with Glaucoma Shunt Intraluminal Stent Exposure. J Curr Glaucoma Pract 2016;10(1):36-37. PMID:27231417

  1. Combining Results of Multiple Search Engines in Proteomics*

    PubMed Central

    Shteynberg, David; Nesvizhskii, Alexey I.; Moritz, Robert L.; Deutsch, Eric W.

    2013-01-01

    A crucial component of the analysis of shotgun proteomics datasets is the search engine, an algorithm that attempts to identify the peptide sequence from the parent molecular ion that produced each fragment ion spectrum in the dataset. There are many different search engines, both commercial and open source, each employing a somewhat different technique for spectrum identification. The set of high-scoring peptide-spectrum matches for a defined set of input spectra differs markedly among the various search engine results; individual engines each provide unique correct identifications among a core set of correlative identifications. This has led to the approach of combining the results from multiple search engines to achieve improved analysis of each dataset. Here we review the techniques and available software for combining the results of multiple search engines and briefly compare the relative performance of these techniques. PMID:23720762

  2. Combining results of multiple search engines in proteomics.

    PubMed

    Shteynberg, David; Nesvizhskii, Alexey I; Moritz, Robert L; Deutsch, Eric W

    2013-09-01

    A crucial component of the analysis of shotgun proteomics datasets is the search engine, an algorithm that attempts to identify the peptide sequence from the parent molecular ion that produced each fragment ion spectrum in the dataset. There are many different search engines, both commercial and open source, each employing a somewhat different technique for spectrum identification. The set of high-scoring peptide-spectrum matches for a defined set of input spectra differs markedly among the various search engine results; individual engines each provide unique correct identifications among a core set of correlative identifications. This has led to the approach of combining the results from multiple search engines to achieve improved analysis of each dataset. Here we review the techniques and available software for combining the results of multiple search engines and briefly compare the relative performance of these techniques. PMID:23720762

  3. Ant Colony Optimization With Combining Gaussian Eliminations for Matrix Multiplication.

    PubMed

    Zhou, Yuren; Lai, Xinsheng; Li, Yuanxiang; Dong, Wenyong

    2013-02-01

    One of the main unsolved problems in computer algebra is to determine the minimal number of multiplications which is necessary to compute the product of two matrices. For practical value, the small format is of special interest. This leads to a combinatorial optimization problem which is unlikely solved in polynomial time. In this paper, we present a method called combining Gaussian eliminations to reduce the number of variables in this optimization problem and use heuristic ant colony algorithm to solve the problem. The results of experiments on 2 × 2 case show that our algorithm achieves significant performance gains. Extending this algorithm from 2 × 2 case to 3 × 3 case is also discussed. Index Terms—Ant colony optimization (ACO), evolutionary algorithms, Gaussian eliminations, matrix multiplication, multiplicative complexity, Strassen's algorithm. PMID:22835561

  4. Recurrent Giant Cell Tumor of Skull Combined with Multiple Aneurysms

    PubMed Central

    Kim, Dae Hwan

    2016-01-01

    Giant cell tumors are benign but locally invasive and frequently recur. Giant cell tumors of the skull are extremely rare. A patient underwent a surgery to remove a tumor, but the tumor recurred. Additionally, the patient developed multiple aneurysms. The patient underwent total tumor resection and trapping for the aneurysms, followed by radiotherapy. We report this rare case and suggest some possibilities for treating tumor growth combined with aneurysm development. PMID:27195256

  5. Nanoparticle Based Combination Treatments for Targeting Multiple Hallmarks of Cancer

    PubMed Central

    VanDyke, D; Kyriacopulos, P; Yassini, B; Wright, A; Burkhart, E; Jacek, S; Pratt, M; Peterson, CR; Rai, P

    2016-01-01

    Treatment of cancer remains one of the most challenging tasks facing the healthcare system. Cancer affects the lives of millions of people and is often fatal. Current treatment methods include surgery, chemotherapy, radiation therapies or some combinations of these. However, recurrence is a major problem. These treatments can be invasive with severe side effects. Inefficacies in treatments are a result of the complex and variable biology of cancerous cells. Malignant tumor cells and normal functioning cells share many of the same biological characteristics but the main difference is that in cancer cells there is in an overuse and over expression of these biological characteristics. These pertinent characteristics can be grouped into eight hallmarks, as illustrated by Hanahan and Weinberg. These characteristics include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. In order to provide a noninvasive, effective treatment, delivery methods must be explored in order to transport cytotoxic agents used for targeting the hallmarks of cancer in a safer and more effective fashion. The use of nanoparticles as drug delivery carriers provides an effective method in which multiple cytotoxic agents can be safely delivered to cancer tissue to simultaneously target multiple hallmarks. By targeting multiple hallmarks of cancer at once, the efficacy of cancer treatments could be improved drastically. This review explores the uses and efficacy of combination therapies using nanoparticles that can simultaneously target multiple hallmarks of cancer. PMID:27547592

  6. Randomized Study Combining Interferon & Glatiramer Acetate in Multiple Sclerosis

    PubMed Central

    Lublin, Fred D.; Cofield, Stacey S.; Cutter, Gary R.; Conwit, Robin; Narayana, Ponnada A.; Nelson, Flavia; Salter, Amber R.; Gustafson, Tarah; Wolinsky, Jerry S.

    2013-01-01

    Objective A double-blind, randomized, controlled study to determine if combined use of interferon beta-1a (IFN) 30ug IM weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis (RRMS). Methods 1008 participants were randomized and followed until the last participant enrolled completed 3 yrs. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score and MRI metrics. Results Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The Combination was not better than either agent alone in lessening confirmed EDSS progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity free status (DAFS) compared to either single arm; driven by the MRI results. Interpretation Combining the two most commonly prescribed therapies for MS did not produce a significant clinical benefit over three years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address if the observed differences in MRI and DAFS findings predict later clinical differences. PMID:23424159

  7. Intraluminal tracheal stent fracture in a Yorkshire terrier.

    PubMed

    Woo, Heung-Myong; Kim, Mi-Jeong; Lee, Seung-Gon; Nam, Hyun-Sook; Kwak, Ho-Hyun; Lee, Joon-Seok; Park, In-Chul; Hyun, Changbaig

    2007-10-01

    An 8-year-old Yorkshire terrier was presented with tracheal collapse. Two intraluminal nitinol stents were implanted. The implanted stents were found to be fractured 4 weeks after implantation. The fractured stents were removed. To restore the collapsed trachea, ring prostheses were applied. However, the dog was euthanized because of a bad outcome following surgery. PMID:17987968

  8. Consensus gene regulatory networks: combining multiple microarray gene expression datasets

    NASA Astrophysics Data System (ADS)

    Peeling, Emma; Tucker, Allan

    2007-09-01

    In this paper we present a method for modelling gene regulatory networks by forming a consensus Bayesian network model from multiple microarray gene expression datasets. Our method is based on combining Bayesian network graph topologies and does not require any special pre-processing of the datasets, such as re-normalisation. We evaluate our method on a synthetic regulatory network and part of the yeast heat-shock response regulatory network using publicly available yeast microarray datasets. Results are promising; the consensus networks formed provide a broader view of the potential underlying network, obtaining an increased true positive rate over networks constructed from a single data source.

  9. Combining multiple anatomical MRI measures improves Alzheimer's disease classification.

    PubMed

    de Vos, Frank; Schouten, Tijn M; Hafkemeijer, Anne; Dopper, Elise G P; van Swieten, John C; de Rooij, Mark; van der Grond, Jeroen; Rombouts, Serge A R B

    2016-05-01

    Several anatomical MRI markers for Alzheimer's disease (AD) have been identified. Hippocampal volume, cortical thickness, and grey matter density have been used successfully to discriminate AD patients from controls. These anatomical MRI measures have so far mainly been used separately. The full potential of anatomical MRI scans for AD diagnosis might thus not yet have been used optimally. In this study, we therefore combined multiple anatomical MRI measures to improve diagnostic classification of AD. For 21 clinically diagnosed AD patients and 21 cognitively normal controls, we calculated (i) cortical thickness, (ii) cortical area, (iii) cortical curvature, (iv) grey matter density, (v) subcortical volumes, and (vi) hippocampal shape. These six measures were used separately and combined as predictors in an elastic net logistic regression. We made receiver operating curve plots and calculated the area under the curve (AUC) to determine classification performance. AUC values for the single measures ranged from 0.67 (cortical thickness) to 0.94 (grey matter density). The combination of all six measures resulted in an AUC of 0.98. Our results demonstrate that the different anatomical MRI measures contain complementary information. A combination of these measures may therefore improve accuracy of AD diagnosis in clinical practice. Hum Brain Mapp 37:1920-1929, 2016. © 2016 Wiley Periodicals, Inc. PMID:26915458

  10. Knowing the crowd within: Metacognitive limits on combining multiple judgments

    PubMed Central

    Fraundorf, Scott H.; Benjamin, Aaron S.

    2013-01-01

    We investigated how decision-makers use multiple opportunities to judge a quantity. Decision-makers undervalue the benefit of combining their own judgment with an advisor’s, but theories disagree about whether this bias would apply to combining several of one’s own judgments. Participants estimated percentage answers to general knowledge questions (e.g., What percent of the world’s population uses the Internet?) on two occasions. In a final decision phase, they selected their first, second, or average estimate to report for each question. We manipulated the cues available for this final decision. Given cues to general theories (the labels first guess, second guess, average), participants mostly averaged, but no more frequently on trials where the average was most accurate. Given item-specific cues (numerical values of the options), metacognitive accuracy was at chance. Given both cues, participants mostly averaged and switched strategies based on whichever yielded the most accurate value on a given trial. These results indicate that underappreciation of averaging estimates does not stem only from social differences between the self and an advisor and that combining general and item-specific cues benefits metacognition. PMID:24511178

  11. Combining multiple thresholding binarization values to improve OCR output

    NASA Astrophysics Data System (ADS)

    Lund, William B.; Kennard, Douglas J.; Ringger, Eric K.

    2013-01-01

    For noisy, historical documents, a high optical character recognition (OCR) word error rate (WER) can render the OCR text unusable. Since image binarization is often the method used to identify foreground pixels, a body of research seeks to improve image-wide binarization directly. Instead of relying on any one imperfect binarization technique, our method incorporates information from multiple simple thresholding binarizations of the same image to improve text output. Using a new corpus of 19th century newspaper grayscale images for which the text transcription is known, we observe WERs of 13.8% and higher using current binarization techniques and a state-of-the-art OCR engine. Our novel approach combines the OCR outputs from multiple thresholded images by aligning the text output and producing a lattice of word alternatives from which a lattice word error rate (LWER) is calculated. Our results show a LWER of 7.6% when aligning two threshold images and a LWER of 6.8% when aligning five. From the word lattice we commit to one hypothesis by applying the methods of Lund et al. (2011) achieving an improvement over the original OCR output and a 8.41% WER result on this data set.

  12. Missed appendicitis: did unexpected intraluminal densities play a role?

    PubMed

    Harper, Rachel; Friedman, Benjamin T; Strote, Jared

    2016-01-01

    A healthy 19-year-old boy presented to our emergency department with abdominal pain. His history, examination and laboratory evaluation raised concern for appendicitis. A CT study of the abdomen and pelvis was carried out by the radiologist and emergency physician and was notable only for a large amount of unexpected high-attenuation intraluminal material. With further history, this was thought to be most likely retained bismuth from over-the-counter medicine ingestion. The patient was discharged home without a diagnosis. Further review of the CT scan by a second radiologist revealed a concern for appendiceal enlargement and associated free fluid. The patient was called back for further evaluation and treatment and ultimately an appendectomy was performed. Physicians should be aware of the causes and impact of unexpected radiopaque intraluminal contents on radiological studies. Most commonly from ingested medicine, such findings can obscure mucosal details, mimic active bleeding or create a distraction from other abnormalities. PMID:27605197

  13. Combining fractional polynomial model building with multiple imputation

    PubMed Central

    Morris, Tim P.; White, Ian R.; Carpenter, James R.; Stanworth, Simon J.; Royston, Patrick

    2016-01-01

    Multivariable fractional polynomial (MFP) models are commonly used in medical research. The datasets in which MFP models are applied often contain covariates with missing values. To handle the missing values, we describe methods for combining multiple imputation with MFP modelling, considering in turn three issues: first, how to impute so that the imputation model does not favour certain fractional polynomial (FP) models over others; second, how to estimate the FP exponents in multiply imputed data; and third, how to choose between models of differing complexity. Two imputation methods are outlined for different settings. For model selection, methods based on Wald-type statistics and weighted likelihood-ratio tests are proposed and evaluated in simulation studies. The Wald-based method is very slightly better at estimating FP exponents. Type I error rates are very similar for both methods, although slightly less well controlled than analysis of complete records; however, there is potential for substantial gains in power over the analysis of complete records. We illustrate the two methods in a dataset from five trauma registries for which a prognostic model has previously been published, contrasting the selected models with that obtained by analysing the complete records only. PMID:26095614

  14. Combining fractional polynomial model building with multiple imputation.

    PubMed

    Morris, Tim P; White, Ian R; Carpenter, James R; Stanworth, Simon J; Royston, Patrick

    2015-11-10

    Multivariable fractional polynomial (MFP) models are commonly used in medical research. The datasets in which MFP models are applied often contain covariates with missing values. To handle the missing values, we describe methods for combining multiple imputation with MFP modelling, considering in turn three issues: first, how to impute so that the imputation model does not favour certain fractional polynomial (FP) models over others; second, how to estimate the FP exponents in multiply imputed data; and third, how to choose between models of differing complexity. Two imputation methods are outlined for different settings. For model selection, methods based on Wald-type statistics and weighted likelihood-ratio tests are proposed and evaluated in simulation studies. The Wald-based method is very slightly better at estimating FP exponents. Type I error rates are very similar for both methods, although slightly less well controlled than analysis of complete records; however, there is potential for substantial gains in power over the analysis of complete records. We illustrate the two methods in a dataset from five trauma registries for which a prognostic model has previously been published, contrasting the selected models with that obtained by analysing the complete records only. PMID:26095614

  15. [Placement of intraluminal stents for treating tracheal collapse in dogs].

    PubMed

    Glaus, T M; Matos, J M; Baloi, P; Wenger, M

    2011-11-01

    Tracheal collapse is a progressive disease particularly of small breed dogs. In the terminal stage, when dyspnea becomes the dominating sign and is no longer manageable with medical treatment, a surgical procedure is necessary. With increasing frequency intraluminal tracheal stents are implanted minimal-invasively. In individual animals this is a lifesaving procedure, leading to immediate elimination of dyspnea. In most dogs cough for some time has to be anticipated as the stent acts as a foreign body, but severe complications like excessive formation of granulation tissue, stent migration or stent fracture are rare. Stents represent an attractive treatment modality for tracheal collapse in dogs with dyspnea. PMID:22045455

  16. A Case of Aerophagia Diagnosed by Multichannel Intraluminal Impedance Monitoring.

    PubMed

    Sohn, Ki Chang; Jeong, Young Hoon; Jo, Dong Ho; Heo, Won Gak; Yeom, Dong Han; Choi, Suck Chei; Ryu, Han Seung

    2015-11-01

    Aerophagia is a disorder caused by abnormal accumulation of air in the gastrointestinal tract as a result of repetitive and frequent inflow of air through the mouth. For the diagnosis of this condition, it is difficult to objectively measure the air swallowing. However, multichannel intraluminal impedance monitoring facilitates the differential diagnosis between normal air swallowing and pathologic aerophagia, and can aid in the determination of the frequency and amount of air swallowed. In this report, in addition to a literature review, we describe a case of 36-year-old man with abdominal distension who was diagnosed with aerophagia using esophageal impedance monitoring and was treated with clonazepam. PMID:26586352

  17. Three-Drug Combination for Relapsed Multiple Myeloma

    Cancer.gov

    A summary of Interim results from an international, randomized phase III trial that suggest that adding carfilzomib (Kyprolis®) to a standard treatment improves outcomes for patients with multiple myeloma whose cancer has relapsed.

  18. Commercial Shot Classification Based on Multiple Features Combination

    NASA Astrophysics Data System (ADS)

    Liu, Nan; Zhao, Yao; Zhu, Zhenfeng; Ni, Rongrong

    This paper presents a commercial shot classification scheme combining well-designed visual and textual features to automatically detect TV commercials. To identify the inherent difference between commercials and general programs, a special mid-level textual descriptor is proposed, aiming to capture the spatio-temporal properties of the video texts typical of commercials. In addition, we introduce an ensemble-learning based combination method, named Co-AdaBoost, to interactively exploit the intrinsic relations between the visual and textual features employed.

  19. Using Robust Standard Errors to Combine Multiple Regression Estimates with Meta-Analysis

    ERIC Educational Resources Information Center

    Williams, Ryan T.

    2012-01-01

    Combining multiple regression estimates with meta-analysis has continued to be a difficult task. A variety of methods have been proposed and used to combine multiple regression slope estimates with meta-analysis, however, most of these methods have serious methodological and practical limitations. The purpose of this study was to explore the use…

  20. Toward an Information Visualization Workspace: Combining Multiple Means of Expression.

    ERIC Educational Resources Information Center

    Roth, Steven F.; Chuah, Mei C.; Kerpedjiev, Stephan; Kolojejchick, John A.; Lucas, Peter

    1997-01-01

    Presents an information visualization workspace in which users are able to explore data presented in diverse but coordinated formats using related systems called Visage, SAGE, and selective dynamic manipulation (SDM). Discusses four dimensions for analyzing user interfaces that reveal the combination of design approaches needed for visualizations…

  1. Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury

    PubMed Central

    Duthie, Karolina M; Hadoke, Patrick W F; Kirkby, Nicholas S; Miller, Eileen; Ivy, Jessica R; McShane, John F; Lim, Win Gel; Webb, David J

    2015-01-01

    Background and Purpose Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA/B receptor antagonism at inhibiting neointimal proliferation in a mouse model of intraluminal injury. Experimental Approach Antagonism of ETA receptors by sitaxentan (1–100 nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15 mg·kg−1·day−1), A192621 (ETB antagonist; 30 mg·kg−1·day−1), the combination of both antagonists or vehicle. Treatment began 1 week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Key Results Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA/B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions. Conclusions and Implications These results suggest that ETA receptor antagonism would be more effective than combined ETA/ETB receptor antagonism at reducing neointimal lesion formation. PMID:25598351

  2. Ranking and combining multiple predictors without labeled data

    PubMed Central

    Parisi, Fabio; Strino, Francesco; Nadler, Boaz; Kluger, Yuval

    2014-01-01

    In a broad range of classification and decision-making problems, one is given the advice or predictions of several classifiers, of unknown reliability, over multiple questions or queries. This scenario is different from the standard supervised setting, where each classifier’s accuracy can be assessed using available labeled data, and raises two questions: Given only the predictions of several classifiers over a large set of unlabeled test data, is it possible to (i) reliably rank them and (ii) construct a metaclassifier more accurate than most classifiers in the ensemble? Here we present a spectral approach to address these questions. First, assuming conditional independence between classifiers, we show that the off-diagonal entries of their covariance matrix correspond to a rank-one matrix. Moreover, the classifiers can be ranked using the leading eigenvector of this covariance matrix, because its entries are proportional to their balanced accuracies. Second, via a linear approximation to the maximum likelihood estimator, we derive the Spectral Meta-Learner (SML), an unsupervised ensemble classifier whose weights are equal to these eigenvector entries. On both simulated and real data, SML typically achieves a higher accuracy than most classifiers in the ensemble and can provide a better starting point than majority voting for estimating the maximum likelihood solution. Furthermore, SML is robust to the presence of small malicious groups of classifiers designed to veer the ensemble prediction away from the (unknown) ground truth. PMID:24474744

  3. Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma.

    PubMed

    Moreau, Philippe; Facon, Thierry; Touzeau, Cyrille; Benboubker, Lotfi; Delain, Martine; Badamo-Dotzis, Julie; Phelps, Charles; Doty, Christopher; Smit, Hans; Fourneau, Nele; Forslund, Ann; Hellemans, Peter; Leleu, Xavier

    2016-07-01

    The maximum tolerated dose (MTD) of quisinostat + bortezomib + dexamethasone in patients with relapsed multiple myeloma was evaluated in a phase-1b, open-label, multicenter, '3 + 3' dose-escalation study. Patients received escalating doses of oral quisinostat (6 mg [n = 3], 8 mg [n = 3], 10 mg [n = 6], and 12 mg [n = 6] on days 1, 3, and 5/week) plus subcutaneous bortezomib (1.3 mg/m(2)) and oral dexamethasone (20 mg) in cycles of 21 (cycles 1-8) or 35 d (cycles 9-11) until MTD was determined. No dose-limiting toxicities were reported in 6/8 mg groups except ventricular fibrillation (Grade 4 cardiac arrest, n = 1 [10 mg] cycle 6) and clinically significant cardiac toxicities (Grade 3 QTc prolongation, Grade 3 atrial fibrillation, n = 2 [12 mg]). Thrombocytopenia (n = 11), asthenia (n = 10), and diarrhea (n = 12) were most common adverse events. Overall, 88.2% patients achieved treatment response, median duration of response, and median progression-free survival were 9.4 and 8.2 months, respectively. The MTD of quisinostat was established as 10 mg thrice weekly oral dose with bortezomib + dexamethasone. PMID:26758913

  4. 26 CFR 1.457-5 - Individual limitation for combined annual deferrals under multiple eligible plans

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Individual limitation for combined annual... Gross Income Included § 1.457-5 Individual limitation for combined annual deferrals under multiple... taking into account the combined annual deferral for the participant for any taxable year under...

  5. Maturation of jejunoileal gradients in rat intestine: the role of intraluminal nutrients.

    PubMed

    Castillo, R O; Feng, J J; Stevenson, D K; Kwong, L K

    1992-01-01

    Jejunoileal gradients of intestinal function are thought to be established during the third week of life in the rat when postnatal intestinal maturation occurs. In order to investigate the normal development of jejunoileal gradients and whether either the absence of intraluminal nutrients or the form in which they are provided affected the development of jejunoileal gradients, gradients for mucosal DNA, protein, lactase and sucrase were studied in suckling rats undergoing normal weaning and compared to gradients in rats receiving no intraluminal nutrients or rats receiving nutrients in elemental form. In suckling animals, preexisting jejunoileal gradients for DNA and protein persisted through the weaning period, gradients for lactase formed by rapid decline of ileal function and sucrase gradients formed by rapid increase in jejunal activities. Intraluminal nutrients in elemental form resulted in the formation of jejunoileal gradients similar to those in intestines of normally weaned rats. The lack of intraluminal nutrients resulted in no qualitative differences in the expression of jejunoileal gradients for sucrase, but provision of elemental nutrients resulted in increased jejunoileal differences for this enzyme. The lack of intraluminal nutrients resulted in no gradients for DNA, less pronounced jejunoileal differences for protein and delayed maturational decline of ileal lactase which prevented development of jejunoileal gradients for the enzyme. These studies indicate that the formation of jejunoileal gradients in the maturing rat intestine for the parameters investigated require intraluminal nutrients regardless of the form in which they are provided for their normal expression. PMID:1467373

  6. Diamagnetically stabilized levitation control of an intraluminal magnetic capsule.

    PubMed

    Lam, Michael; Mintchev, Martin

    2009-08-01

    Controlled navigation promotes full utilization of capsule endoscopy for reliable real-time diagnosis in the gastrointestinal (GI) tract, but intermittent natural peristalsis can disturb the navigational control, destabilize the capsule and take it out of levitation. The focus of the present work was to develop an economical and effective real-time magnetic capsule-guiding system that can operate in the presence of naturally existing peristalsis while retaining navigational control. A real-size magnetic navigation system that can handle peristaltic forces of up to 1.5 N was designed utilizing the computer-aided design (CAD) system Maxwell 3D (Ansoft, Pittsburg, PA) and was verified using a small-size physical experimental setup. The proposed system contains a pair of 50 cm diameter, 10,000-turn copper electromagnets with a 10 cm x 10 cm ferrous core driven by currents of up to 300 A and can successfully maintain position control over the levitating capsule during peristalsis. The addition of bismuth diamagnetic casing for stabilizing the levitating capsule was also studied. A modeled magnetic field around the diamagnetically cased permanent magnet was shown to be redistributed aligning its interaction with the external electromagnets, thus stabilizing the levitating capsule. In summary, a custom-designed diamagnetically facilitated capsule navigation system can successfully steer an intraluminal magnet-carrying capsule. PMID:19550023

  7. Symptomatic Patients with Intraluminal Carotid Thrombus: Outcome with a Strategy of Initial Anticoagulation

    PubMed Central

    Vellimana, Ananth K.; Kadkhodayan, Yasha; Rich, Keith M.; Cross, Dewitte T.; Moran, Christopher J.; Zazulia, Allyson R.; Lee, Jin-Moo; Chicoine, Michael R.; Dacey, Ralph G.; Derdeyn, Colin P.; Zipfel, Gregory J.

    2013-01-01

    Background Optimal treatment for patients with symptomatic intraluminal carotid thrombus (ICT) remains poorly defined. Methods We performed a retrospective chart review of patients presenting to our institution between 2001 and 2011 with symptomatic ICT. Results Twenty-four patients (16 males, 8 females) with ICT presented with ischemic stroke (n=18) or TIA (n=6). All were treated initially with anticoagulation ± antiplatelet drugs. Eight of these patients had no or mild carotid stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography. Of these, 10 underwent delayed revascularization (endarterectomy, n=8; angioplasty and stenting, n=2), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation, during the perioperative period or in long-term follow up; one patient died of an unrelated condition (mean follow-up = 16.4 months). Conclusion Our results suggest that initial anticoagulation of symptomatic ICT results in a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner. PMID:23061393

  8. Using Robust Variance Estimation to Combine Multiple Regression Estimates with Meta-Analysis

    ERIC Educational Resources Information Center

    Williams, Ryan

    2013-01-01

    The purpose of this study was to explore the use of robust variance estimation for combining commonly specified multiple regression models and for combining sample-dependent focal slope estimates from diversely specified models. The proposed estimator obviates traditionally required information about the covariance structure of the dependent…

  9. FPGA-based entropy neural processor for online detection of multiple combined faults on induction motors

    NASA Astrophysics Data System (ADS)

    Cabal-Yepez, E.; Valtierra-Rodriguez, M.; Romero-Troncoso, R. J.; Garcia-Perez, A.; Osornio-Rios, R. A.; Miranda-Vidales, H.; Alvarez-Salas, R.

    2012-07-01

    For industry, a faulty induction motor signifies production reduction and cost increase. Real-world induction motors can have one or more faults present at the same time that can mislead to a wrong decision about its operational condition. The detection of multiple combined faults is a demanding task, difficult to accomplish even with computing intensive techniques. This work introduces information entropy and artificial neural networks for detecting multiple combined faults by analyzing the 3-axis startup vibration signals of the rotating machine. A field programmable gate array implementation is developed for automatic online detection of single and combined faults in real time.

  10. A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

    NASA Astrophysics Data System (ADS)

    Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

    2015-12-01

    Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.

  11. Monofilament intraluminal middle cerebral artery occlusion in the mouse.

    PubMed

    Clark, W M; Lessov, N S; Dixon, M P; Eckenstein, F

    1997-12-01

    The rat middle cerebral artery (MCA) occlusion model with an intraluminal filament is well characterized with a two hour period of occlusion in widespread use. The recent availability of transgenic animals has led to an interest in adapting the MCA model in the mouse. To date the model has not been well characterized in the mouse. We performed the present study to compare different durations of MCA occlusion and to validate new functional assessments in this model. The MCA occlusion model (5-0 filament) was used. Swiss-Webster mice, 24-44 g, were randomly assigned to four groups: one hour of occlusion; two hours of occlusion; three hours of occlusion; or permanent occlusion. At 48 hours post-ischemia, the animals were rated on three neurologic function scales, and then the brains were removed for lesion size determination. Overall, there was a significant difference in lesion volume (p < 0.001) between the groups. In the permanent group of mice, the average lesion volume was 78.41 +/- 17.47 mm (n = 12); two and three hours of ischemia produced 51.29 +/- 29.82 mm3 (n = 11) and 54.85 mm3 (n = 13), respectively, significantly different than the one hour group 14.84 +/- 31.34 mm3 (n = 11). All three functional scoring systems found significant overall differences between the four groups with our detailed General and Focal scores producing more robust between group treatment differences and showing correlation coefficients of r = 0.766 and r = 0.788, respectively to infarct volume. The MCA filament occlusion model can be successfully adapted in the mouse with either two or three hour occlusions producing reliable infarcts. New functional scoring systems unique to the mouse appear to add additional information. PMID:9427967

  12. Intraluminal stents in atherosclerotic iliac artery stenosis: preliminary report of a multicenter study.

    PubMed

    Palmaz, J C; Richter, G M; Noeldge, G; Schatz, R A; Robison, P D; Gardiner, G A; Becker, G J; McLean, G K; Denny, D F; Lammer, J

    1988-09-01

    Fifteen patients with symptomatic iliac artery stenosis were treated with intraluminal placement of balloon-expandable stents. Before treatment, 14 patients had intermittent claudication, and one had a limb at risk for amputation. One patient had diabetes mellitus, nine had hypertension, and all were long-term smokers. Two patients had surgical placement of the stent; in one patient this was part of a combined revascularization procedure. All other stents were placed percutaneously. The transstenotic gradient after injection of vasodilating drugs distal to the lesion decreased from a mean of 32.3 mm Hg +/- 16.7 to 3.1 mm Hg +/- 4.2 after stent placement. Ankle-arm Doppler systolic pressure index increased from a mean of 0.68 +/- 0.22 to 0.96 +/- 0.24 after the procedure. The treatment eliminated intermittent claudication in 14 patients and increased exercise tolerance to 500 m in the patient with a limb at risk for amputation before the procedure. The improved condition persisted in all patients during the follow-up of 6-12 months. Stent placement may be a valuable adjunct in the management of iliac artery disease. PMID:2970098

  13. Multichannel intraluminal impedance and esophageal manometry data for unrestricted swallowing: establishing normal values.

    PubMed

    Wilson, J A; Mainie, I; Tutuian, R; Agrawal, A; Castell, D O

    2008-01-01

    Standard esophageal manometric testing evaluates swallowing in the supine position using small boluses, with a recovery period imposed between swallows. Manometric tests of more physiologic unrestricted swallowing have had limited practical application due to highly variable results. The purpose of this study is to apply multichannel intraluminal impedance and manometry (MII-EM) to test esophageal function during unrestricted upright meal consumption, and to assess results in a normal healthy population. Ten healthy volunteers with normal esophageal impedance and manometry by published criteria underwent MII-EM testing using a combined 5-channel catheter. After transnasal placement of the catheter, each subject sat upright and consumed a meal that consisted of two pieces of toasted bread and two ounces of Gatorade. There were no restrictions placed on chewing, swallowing, or eating time. All data assessed by the MII-EM meal test were normally distributed. Impedance results with limited variability included the meal duration, number of swallows, postprandial emptying time and the percent of bolus presence times at 15, 10, and 5 cm above the lower esophageal sphincter. Manometric results with limited variability included the number of peristaltic sequences, mean time between these sequences and their distal esophageal amplitudes. MII-EM can be used to collect data with minimal variability in healthy subjects during unrestricted upright meal consumption. This technique may be used to identify abnormal motility patterns during physiologic swallowing. PMID:18197939

  14. Research on model of combining multiple neural networks by fuzzy integral-MNNF

    NASA Astrophysics Data System (ADS)

    Fu, Yue; Chai, Bianfang

    2013-03-01

    The method of multiple neural network Fusion using Fuzzy Integral (MNNF) presented by this paper is to improve the detection performance of data mining-based intrusion detection system. The basic idea of MNNF is to mine on distinct feature training dataset by neural networks separately, and detect TCP/IP data by different neural networks, and then nonlinearly combine the results from multiple neural networks by fuzzy integral. The experiment results show that this technique is superior to single neural networks for intrusion detection in terms of classification accuracy. Compared with other combination methods such as Majority, Average, Borda count, fuzzy integral is better than one of them.

  15. Criteria for multiple noises in residential buildings using combined rating system

    NASA Astrophysics Data System (ADS)

    Jeon, Jin Yong; Ryu, Jong Kwan; Jeong, Young

    2005-04-01

    Multiple residential noises such as floor impact, air-borne, bathroom, drainage, and traffic noises were classified using a combined rating system developed from a social noise survey and auditory experiments. The effect of individual noise perception on the evaluation of the overall noise environment was investigated through a questionnaire survey on annoyance, disturbance, and noise sensitivity. In addition, auditory experiments were undertaken to determine the allowable sound pressure level for each residential noise source and the percent satisfaction for individual noise levels. From the results of the survey and the auditory experiments, a combined rating system was developed and annoyance criteria for multiple residential noises were suggested.

  16. Scintigraphic method for the assessment of intraluminal volume and motility of isolated intestinal segments. [Dogs

    SciTech Connect

    Mitchell, A.; Macey, D.J.; Collin, J.

    1983-07-01

    The isolated in vivo intestinal segment is a popular experimental preparation for the investigation of intestinal function, but its value has been limited because no method has been available for measuring changes in intraluminal volume under experimental conditions. We report a scintigraphic technique for measuring intraluminal volume and assessing intestinal motility. Between 30 and 180 ml, the volume of a 75-cm segment of canine jejunum, perfused with Tc-99m-labeled tin colloid, was found to be proportional to the recorded count rate. This method has been used to monitor the effects of the hormone vasopressin on intestinal function.

  17. 26 CFR 1.457-5 - Individual limitation for combined annual deferrals under multiple eligible plans

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Individual limitation for combined annual deferrals under multiple eligible plans 1.457-5 Section 1.457-5 Internal Revenue INTERNAL REVENUE SERVICE...-4(e). Example 2. (i) Facts. Participant E, who will turn 63 on April 1, 2006, participates in...

  18. 26 CFR 1.457-5 - Individual limitation for combined annual deferrals under multiple eligible plans

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Individual limitation for combined annual deferrals under multiple eligible plans 1.457-5 Section 1.457-5 Internal Revenue INTERNAL REVENUE SERVICE...-4(e). Example 2. (i) Facts. Participant E, who will turn 63 on April 1, 2006, participates in...

  19. 26 CFR 1.457-5 - Individual limitation for combined annual deferrals under multiple eligible plans

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Individual limitation for combined annual deferrals under multiple eligible plans 1.457-5 Section 1.457-5 Internal Revenue INTERNAL REVENUE SERVICE...-4(e). Example 2. (i) Facts. Participant E, who will turn 63 on April 1, 2006, participates in...

  20. 26 CFR 1.457-5 - Individual limitation for combined annual deferrals under multiple eligible plans

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Individual limitation for combined annual deferrals under multiple eligible plans 1.457-5 Section 1.457-5 Internal Revenue INTERNAL REVENUE SERVICE...-4(e). Example 2. (i) Facts. Participant E, who will turn 63 on April 1, 2006, participates in...

  1. Behavioral profiling in CCTV cameras by combining multiple subtle suspicious observations of different surveillance operators

    NASA Astrophysics Data System (ADS)

    Bouma, Henri; Vogels, Jack; Aarts, Olav; Kruszynski, Chris; Wijn, Remco; Burghouts, Gertjan

    2013-05-01

    Camera surveillance and recognition of deviant behavior is important for the prevention of criminal incidents. A single observation of subtle deviant behavior of an individual may sometimes be insufficient to merit a follow-up action. Therefore, we propose a method that can combine multiple weak observations to make a strong indication that an intervention is required. We analyze the effectiveness of combining multiple observations/tags of different operators, the effects of the tagging instruction these operators received (many tags for weak signals or few tags for strong signals), and the performance of using a semi-automatic system for combining the different observations. The results show that the method can be used to increase hits (detecting criminals) whilst reducing false alarms (bothering innocent passers-by).

  2. Optimal linear combinations of multiple diagnostic biomarkers based on Youden index.

    PubMed

    Yin, Jingjing; Tian, Lili

    2014-04-15

    In practice, usually multiple biomarkers are measured on the same subject for disease diagnosis. Combining these biomarkers into a single score could improve diagnostic accuracy. Many researchers have addressed the problem of finding the optimal linear combination based on maximizing the area under ROC curve (AUC). Actually, such combined score might have less than optimal property at the diagnostic threshold. In this paper, we propose the idea of using Youden index as an objective function for searching the optimal linear combination. The combined score directly achieves the maximum overall correct classification rate at the diagnostic threshold corresponding to Youden index; in other words, it is the optimal linear combination score for making the disease diagnosis. We present both empirical and numerical searching methods for the optimal linear combination. We carry out extensive simulation study to investigate the performance of the proposed methods. Additionally, we empirically compare the optimal overall classification rates between the proposed combination based on Youden index and the traditional one based on AUC and demonstrate a significant gain in diagnostic accuracy for the proposed combination. In the end, we apply the proposed methods to a real data set. PMID:24311111

  3. Esophageal Bolus Transit in Newborns with Gastroesophageal Reflux Disease Symptoms: A Multichannel Intraluminal Impedance Study

    PubMed Central

    Liguori, Stefania Alfonsina; Maggiora, Elena; Locatelli, Emanuela; Indrio, Flavia; Bertino, Enrico; Coscia, Alessandra

    2015-01-01

    Purpose The aim of this study was to evaluate bolus transit during esophageal swallow (ES) and gastroesophageal reflux (GER) events and to investigate the relationship between the characteristics of ES and GER events in a population of term and preterm newborns with symptoms of gastroesophageal reflux disease (GERD). Methods The study population consisted of term and preterm newborns referred to combined multichannel intraluminal impedance (MII) and pH monitoring for GERD symptoms. The frequency and characteristics of ES and GER events were assessed by two independent investigators. Statistical significance was set at p<0.05. Results Fifty-four newborns (23 preterm) were included in the analyses. Median bolus head advancing time corrected for esophageal length (BHATc) was shorter during mealtime than during the postprandial period (median, interquartile range): 0.20 (0.15-0.29) s/cm vs. 0.47 (0.39-0.64) s/cm, p<0.001. Median bolus presence time (BPT) was prolonged during mealtime: 4.71(3.49-6.27) s vs. 2.66 (1.82-3.73) s, p<0.001. Higher BHATc (p=0.03) and prolonged BPT (p<0.001) were observed in preterm newborns during the postprandial period. A significant positive correlation between BHATc and bolus clearance time was also observed (ρ=0.33, p=0.016). Conclusion The analysis of ES and GER events at the same time by MII provides useful information to better understand the physiopathology of GERD. In particular, the analysis of BHATc during the postprandial period could help clinicians identify newborns with prolonged esophageal clearance time due to impaired esophageal motility, which could allow for more accurate recommendations regarding further tests and treatment. PMID:26770898

  4. A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

    PubMed Central

    Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

    2015-01-01

    Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor. PMID:26631871

  5. Magnetic Retraction of Bowel by Intraluminal Injectable Cyanoacrylate-Based Magnetic Glue

    PubMed Central

    Brown, Andrew; André, Pascal; Brown, Stuart I.; Florence, Gordon J.; Cuschieri, Alfred

    2013-01-01

    Magnetic retraction offers advantages over physical retraction by graspers because of reduced tissue trauma. The objectives of this study are to investigate a novel method of magnetisation of bowel segments by intraluminal injection of magnetic glue and to demonstrate the feasibility of magnetic retraction of bowel with sufficient force during minimal access surgery. Following an initial materials characterisation study, selected microparticles of stainless steel (SS410-μPs) were mixed with chosen cyanoacrylate glue (Loctite 4014). During intraluminal injection of the magnetic glue using ex vivo porcine colonic segments, a magnetic probe placed at the injected site ensured that the SS410-μPs aggregated during glue polymerisation to form an intraluminal mucosally adherent coagulum. The magnetised colonic segments were retracted by magnetic probes (5 and 10 mm) placed external to the bowel wall. A tensiometer was used to record the retraction force. With an injected volume of 2 mL in a particle concentration of 1 g/mL, this technique produced maximal magnetic retraction forces of 2.24 ± 0.23 N and 5.11 ± 0.34 N (n = 20), with use of 5 and 10 mm probes, respectively. The results indicate that the formation of an intraluminal coagulum based on SS410-μPs and Loctite 4014 produces sufficient magnetic retraction for bowel retraction. PMID:24319684

  6. A combined neutron and gamma-ray multiplicity counter based on liquid scintillation detectors

    NASA Astrophysics Data System (ADS)

    Enqvist, Andreas; Flaska, Marek; Dolan, Jennifer L.; Chichester, David L.; Pozzi, Sara A.

    2011-10-01

    Multiplicity counters for neutron assay have been extensively used in materials control and accountability for nonproliferation and nuclear safeguards. Typically, neutron coincidence counters are utilized in these fields. In this work, we present a measurement system that makes use not only of neutron (n) multiplicity counting but also of gamma-ray ( γ) multiplicity counting and the combined higher-order multiples containing both neutrons and gamma rays. The benefit of this approach is in using both particle types available from the sample, leading to a reduction in measurement times compared with single-particle measurements. We present measurement results of n, γ, nn, nγ, γγ, nnn, nnγ, nγγ and γγγ multiples emitted by Mixed-Oxide (MOX) samples measured at Idaho National Laboratory (INL). The MOX measurement is compared to initial validation of the detection system done using a 252Cf source. The dual radiation measuring system proposed here uses extra measurables to improve the statistics when compared to a neutron-only system and allows for extended analysis and interpretation of sample parameters. New challenges such as the effect of very high intrinsic gamma-ray sources in the case of MOX samples are discussed. Successful measurements of multiple rates can be performed also when using high-Z shielding.

  7. Intraluminal acid activates esophageal nodose C fibers after mast cell activation.

    PubMed

    Zhang, Shizhong; Liu, Zhenyu; Heldsinger, Andrea; Owyang, Chung; Yu, Shaoyong

    2014-02-01

    Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2-3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acid-induced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation. PMID:24264049

  8. A new method to combine 3D reconstruction volumes for multiple parallel circular cone beam orbits

    PubMed Central

    Baek, Jongduk; Pelc, Norbert J.

    2010-01-01

    Purpose: This article presents a new reconstruction method for 3D imaging using a multiple 360° circular orbit cone beam CT system, specifically a way to combine 3D volumes reconstructed with each orbit. The main goal is to improve the noise performance in the combined image while avoiding cone beam artifacts. Methods: The cone beam projection data of each orbit are reconstructed using the FDK algorithm. When at least a portion of the total volume can be reconstructed by more than one source, the proposed combination method combines these overlap regions using weighted averaging in frequency space. The local exactness and the noise performance of the combination method were tested with computer simulations of a Defrise phantom, a FORBILD head phantom, and uniform noise in the raw data. Results: A noiseless simulation showed that the local exactness of the reconstructed volume from the source with the smallest tilt angle was preserved in the combined image. A noise simulation demonstrated that the combination method improved the noise performance compared to a single orbit reconstruction. Conclusions: In CT systems which have overlap volumes that can be reconstructed with data from more than one orbit and in which the spatial frequency content of each reconstruction can be calculated, the proposed method offers improved noise performance while keeping the local exactness of data from the source with the smallest tilt angle. PMID:21089770

  9. The SI-Combiner: Making sense of results from multiple trained programs

    SciTech Connect

    Den Hartog, B.K.; Elling, J.W.; Kieckhafer, R.

    1998-12-31

    Many problems, such as Aroclor Interpretation, are ill-conditioned problems in which trained programs, or methods, must operate in scenarios outside their training ranges because it is intractable to train them completely. Consequently, they fail in ways related to the scenarios. Importantly, when multiple trained methods fail divergently, their patterns of failures provide insights into the true results. The SI-Combiner solves this problem of Integrating Multiple learned Models (IMLM) by automatically learning and using these insights to produce a solution more accurate than any single trained program. In application, the Aroclor Interpretation SI-Combiner improved on the accuracy of the most accurate individual trained program in the suite. This paper presents a new fuzzy IMLM method called the SI-Combiner and its application to Aroclor Interpretation. Additionally, this paper shows the improvement in accuracy that the SI-Combiner`s components show against Multicategory Classification (MCC), Dempster-Shafer (DS), and the best individual trained program in the Aroclor Interpretation suite (iMLR).

  10. Optimal configuration and combination of multiple lignocellulosic biomass feedstocks delivery to a biorefinery.

    PubMed

    Sultana, Arifa; Kumar, Amit

    2011-11-01

    Biomass availability and transportation are major challenges in establishing a large-scale biorefinery. The objective of this study was to assess the delivery cost of different combinations of multiple forms of lignocellulosic feedstocks including agricultural and woody biomass. Three types of biomass i.e., wheat straw, corn stover and forest biomass were considered in different forms such as loose biomass, bales/bundles, chopped/chipped and pellets. It was found that the delivery cost of a combination of woody and agricultural biomass feedstocks is lower than that for a single type of biomass. The delivery of agricultural residues as bales and woody biomass as chips is an economically attractive option with optimal combination of 30% bales and 70% wood chips to a biorefinery of capacity 5000 dry tonnes per day. The anticipated traffic congestions resulting from biomass supply to a large facility could be significantly reduced by increasing the density of biomass. PMID:21917448

  11. Multiple mutations and mutation combinations in the sodium channel of permethrin resistant mosquitoes, Culex quinquefasciatus

    NASA Astrophysics Data System (ADS)

    Li, Ting; Zhang, Lee; Reid, William R.; Xu, Qiang; Dong, Ke; Liu, Nannan

    2012-10-01

    A previous study identified 3 nonsynonymous and 6 synonymous mutations in the entire mosquito sodium channel of Culex quinquefasciatus, the prevalence of which were strongly correlated with levels of resistance and increased dramatically following insecticide selection. However, it is unclear whether this is unique to this specific resistant population or is a common mechanism in field mosquito populations in response to insecticide pressure. The current study therefore further characterized these mutations and their combinations in other field and permethrin selected Culex mosquitoes, finding that the co-existence of all 9 mutations was indeed correlated with the high levels of permethrin resistance in mosquitoes. Comparison of mutation combinations revealed several common mutation combinations presented across different field and permethrin selected populations in response to high levels of insecticide resistance, demonstrating that the co-existence of multiple mutations is a common event in response to insecticide resistance across different Cx. quinquefasciatus mosquito populations.

  12. Multiple scales combined principle component analysis deep learning network for face recognition

    NASA Astrophysics Data System (ADS)

    Tian, Lei; Fan, Chunxiao; Ming, Yue

    2016-03-01

    It is well known that higher level features can represent the abstract semantics of original data. We propose a multiple scales combined deep learning network to learn a set of high-level feature representations through each stage of convolutional neural network for face recognition, which is named as multiscaled principle component analysis (PCA) Network (MS-PCANet). There are two main differences between our model and the traditional deep learning network. On the one hand, we get the prefixed filter kernels by learning the principal component of images' patches using PCA, nonlinearly process the convolutional results by using simple binary hashing, and pool them using spatial pyramid pooling method. On the other hand, in our model, the output features of several stages are fed to the classifier. The purpose of combining feature representations from multiple stages is to provide multiscaled features to the classifier, since the features in the latter stage are more global and invariant than those in the early stage. Therefore, our MS-PCANet feature compactly encodes both holistic abstract information and local specific information. Extensive experimental results show our MS-PCANet model can efficiently extract high-level feature presentations and outperform state-of-the-art face/expression recognition methods on multiple modalities benchmark face-related datasets.

  13. Combination of cyclophosphamide and interferon-β halts progression in patients with rapidly transitional multiple sclerosis

    PubMed Central

    Patti, F; Cataldi, M; Nicoletti, F; Reggio, E; Nicoletti, A; Reggio, A

    2001-01-01

    The effects of combined treatment with cyclophosphamide (CTX) and interferon-β (IFN-β) are described in selected patients with "rapidly transitional" multiple sclerosis. This form of multiple sclerosis is extremely active with very frequent and severe attacks which produce a dramatic increase on the expanded disability status scale (EDSS). Ten patients with rapidly transitional multiple sclerosis were previously treated with interferon-β, but none benefited by this treatment. Monthly treatment with intravenous CTX, from 500 mg/m2 to 1500 mg/m2 to obtain a chronic lymphocytopenia (600/mm3 to 900/mm3) produced a marked and significant reduction in the number of relapses (p<0.0001), disability previously accumulated (p<0.0001), and a reduction of T2 MRI burden of lesion. This particular group of patients benefited by combining cyclophosphamide and IFN-β. The possibility is considered of carrying out further studies to test the efficacy of the association between the two drugs for patients who are not responsive to IFN-β or other active disease modifying therapies.

 PMID:11511721

  14. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo

    PubMed Central

    Grenley, Marc O.; Casalini, Joseph R.; Tretyak, Ilona; Ditzler, Sally H.; Thirstrup, Derek J.; Frazier, Jason P.; Pierce, Daniel W.; Carleton, Michael; Klinghoffer, Richard A.

    2016-01-01

    While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors. This platform provides a rapid, quantitative and cost effective approach to compare and prioritize drug combinations based on evidence of synergistic tumor cell killing in the live tumor context. Using a gemcitabine resistant model of pancreatic cancer, we efficiently investigated nine rationally selected Abraxane-based combinations employing only 19 xenografted mice. Among the drugs tested, the BCL2/BCLxL inhibitor ABT-263 was identified as the one agent that synergized with Abraxane® to enhance acute induction of localized apoptosis in this model of human pancreatic cancer. Importantly, results obtained with CIVO accurately predicted the outcome of systemic dosing studies in the same model where superior tumor regression induced by the Abraxane/ABT-263 combination was observed compared to that induced by either single agent. This supports expanded use of CIVO as an in vivo platform for expedited in vivo drug combination validation and sets the stage for performing toxicity-sparing drug combination studies directly in cancer patients with solid malignancies. PMID:27359113

  15. Genetic polymorphisms, their allele combinations and IFN-β treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-β is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-β response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-β is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  16. [Combined Open and Endovascular Repair of Multiple Aortic Aneurysms due to Syphilitic Aortitis].

    PubMed

    Shima, Shotaro; Okamura, Kennichi; Morizumi, Sei; Kawata, Mitsuhiro; Suematsu, Yoshihiro

    2015-06-01

    The patient was a 69-year-old man who presented with low-grade fever and appetite loss. Thoracoabdominal computed tomography revealed multiple aneurysms in the distal arch and descending thoracic and infrarenal aortic regions combined with a right common iliac artery aneurysm. After endovascular stent grafting for a right iliac artery aneurysm, he underwent total arch replacement and open stent grafting for the descending thoracic aneurysms. Pathological microscopic examination revealed an inflammatory infiltrate within the adventitia and destruction of the elastic fibers in the media, which are classical features of syphilitic aortitis. Endovascular aneurysm repair is contraindicated in mycotic infected aneurysms. However, endovascular repair is useful for treating mycotic infected aneurysm, if multiple aneurysms have the possibility of rupture and a high risk of surgery. PMID:26066872

  17. TRACHEOSTOMAPLASTY: A SURGICAL METHOD FOR IMPROVING RETENTION OF AN INTRALUMINAL STOMA BUTTON FOR HANDS-FREE TRACHEOESOPHAGEAL SPEECH

    PubMed Central

    Moreno, Mauricio A.; Lewin, Jan S.; Hutcheson, Katherine A.; Bishop Leone, Julie K.; Barringer, Denise A.

    2014-01-01

    Background We describe a minimally invasive surgical technique, tracheostomaplasty, to overcome anatomical deformities of the stoma that preclude successful retention of a stoma button for hands free tracheoesophageal (TE) speech. Methods We conducted a retrospective analysis of 21 patients who underwent tracheostomaplasty after laryngectomy to accommodate an intraluminal valve attachment for hands-free TE speech. Results Sixteen men and 5 women (median age, 65 years; median follow-up, 27.7 months) underwent tracheostomaplasty; 6 patients developed a mild cellulitis that required therapy and 5 patients required a minor revision surgery. At last follow-up, 15 (71%) patients successfully achieved hands-free TE speech using an intraluminal stoma button. Three patients only retained the intraluminal device to facilitate digital occlusion. Tracheostomaplasty failed in 3 patients because of granulation tissue formation or stomal stenosis. Conclusions Tracheostomaplasty is a successful technique to improve intraluminal retention of a stoma button for hands-free TE speech in laryngectomy patients. PMID:20848405

  18. Acute small bowel obstruction due to a large intraluminal blood clot after laparoscopic Roux-en-Y gastric bypass

    PubMed Central

    Green, Jessica; Ikuine, Tomoko; Hacker, Shoshana; Urrego, Hernan; Tuggle, Karleena

    2016-01-01

    Small bowel obstructions (SBOs) are a known perioperative complication of laparoscopic Roux-en-Y gastric bypass and common etiologies include internal hernia, port site hernia, jejunojejunostomy stricture, ileus and adhesions. Less commonly, SBO can be caused by superior mesenteric artery syndrome, intussusception and intraluminal blood clot. We present a case of SBO caused by intraluminal blood clot from jejunojejunostomy staple line bleeding in a patient with a normal coagulation profile. Computed tomography was used to elucidate the cause of perioperative SBO, and diagnostic laparoscopy was used to both diagnose and treat the complication. In this case, the intraluminal clot was evacuated laparoscopically by enterotomy, thrombectomy and primary closure without anastomotic revision since there was no evidence of continued bleeding. Administration of enoxaparin and Toradol post-operatively may have exacerbated mild intraluminal bleeding occurring at the stapled jejunojejunal anastomosis. Prompt recognition and treatment of perioperative SBO can prevent catastrophic consequences related to bowel perforation. PMID:27554828

  19. Acute small bowel obstruction due to a large intraluminal blood clot after laparoscopic Roux-en-Y gastric bypass.

    PubMed

    Green, Jessica; Ikuine, Tomoko; Hacker, Shoshana; Urrego, Hernan; Tuggle, Karleena

    2016-01-01

    Small bowel obstructions (SBOs) are a known perioperative complication of laparoscopic Roux-en-Y gastric bypass and common etiologies include internal hernia, port site hernia, jejunojejunostomy stricture, ileus and adhesions. Less commonly, SBO can be caused by superior mesenteric artery syndrome, intussusception and intraluminal blood clot. We present a case of SBO caused by intraluminal blood clot from jejunojejunostomy staple line bleeding in a patient with a normal coagulation profile. Computed tomography was used to elucidate the cause of perioperative SBO, and diagnostic laparoscopy was used to both diagnose and treat the complication. In this case, the intraluminal clot was evacuated laparoscopically by enterotomy, thrombectomy and primary closure without anastomotic revision since there was no evidence of continued bleeding. Administration of enoxaparin and Toradol post-operatively may have exacerbated mild intraluminal bleeding occurring at the stapled jejunojejunal anastomosis. Prompt recognition and treatment of perioperative SBO can prevent catastrophic consequences related to bowel perforation. PMID:27554828

  20. Use of intraluminal nitinol stents in the treatment of tracheal collapse in a dog.

    PubMed

    Gellasch, Kelly L; Dá Costa Gómez, Tamara; McAnulty, Jonathan F; Bjorling, Dale E

    2002-12-15

    Tracheal collapse is a common problem that is typically observed in middle-aged and older small-breed dogs. It is a structural, obstructive airway disease with a dynamic component that can affect the intra- and extrathoracic portions of the trachea and mainstem bronchi. Many methods of treatment have been suggested, including medical management and provision of extraluminal and intraluminal support. All techniques used to treat intrathoracic and mainstem bronchial collapse have been associated with major complications or limitations. This report describes the implantation of intraluminal nitinol stents to successfully treat intrathoracic as well as extrathoracic tracheal collapse in a dog. The stents are composed of material that has characteristics similar to those of the trachea; nitinol stents may provide a method of supporting intrathoracic tracheal and mainstem bronchial collapse in dogs. PMID:12494969

  1. Mechanical characterization of intraluminal tissue with phase-resolved photoacoustic viscoelasticity endoscopy

    PubMed Central

    Chen, Conggui; Zhao, Yue; Yang, Sihua; Xing, Da

    2015-01-01

    We developed a phase-sensitive side-scanning photoacoustic viscoelasticity endoscopy (PAVEE) for mechanical characterization of intraluminal tissues. In PAVEE, the PA phase can be extracted from the optical absorption induced ultrasonic waves and provides an index of viscoelasticity that is closely linked to tissue compositions. The transverse resolution of the PAVEE measured by carbon fiber was about 32 μm. The imaging capability of the PAVEE was verified using a vessel-mimicking phantom with different agar density. Moreover, PAVEE was investigated in processed lumen-shaped vascular tissues to evaluate the biomechanical features, which was highly consistent with the histology. The results demonstrated that the PAVEE can obtain viscoelastic properties of intraluminal tissues, which puts a new insight into the intravascular disease and holds great promise for plaque vulnerability detection. PMID:26713209

  2. Confidence intervals after multiple imputation: combining profile likelihood information from logistic regressions.

    PubMed

    Heinze, Georg; Ploner, Meinhard; Beyea, Jan

    2013-12-20

    In the logistic regression analysis of a small-sized, case-control study on Alzheimer's disease, some of the risk factors exhibited missing values, motivating the use of multiple imputation. Usually, Rubin's rules (RR) for combining point estimates and variances would then be used to estimate (symmetric) confidence intervals (CIs), on the assumption that the regression coefficients were distributed normally. Yet, rarely is this assumption tested, with or without transformation. In analyses of small, sparse, or nearly separated data sets, such symmetric CI may not be reliable. Thus, RR alternatives have been considered, for example, Bayesian sampling methods, but not yet those that combine profile likelihoods, particularly penalized profile likelihoods, which can remove first order biases and guarantee convergence of parameter estimation. To fill the gap, we consider the combination of penalized likelihood profiles (CLIP) by expressing them as posterior cumulative distribution functions (CDFs) obtained via a chi-squared approximation to the penalized likelihood ratio statistic. CDFs from multiple imputations can then easily be averaged into a combined CDF c , allowing confidence limits for a parameter β  at level 1 - α to be identified as those β* and β** that satisfy CDF c (β*) = α ∕ 2 and CDF c (β**) = 1 - α ∕ 2. We demonstrate that the CLIP method outperforms RR in analyzing both simulated data and data from our motivating example. CLIP can also be useful as a confirmatory tool, should it show that the simpler RR are adequate for extended analysis. We also compare the performance of CLIP to Bayesian sampling methods using Markov chain Monte Carlo. CLIP is available in the R package logistf. PMID:23873477

  3. Spinal Cord Infarction Caused by Non-dissected and Unruptured Thoracoabdominal Aortic Aneurysm with Intraluminal Thrombus.

    PubMed

    Ki, Young Jin; Jeon, Byoung Hyun; Bang, Heui Je

    2012-04-01

    Spinal cord infarction, especially anterior spinal artery syndrome, is a relatively rare disease. We report a case of spinal cord infarction caused by thoracoabdominal aortic aneurysm with intraluminal thrombus. A 52-year-old man presented with sudden onset paraplegia. At first, he was diagnosed with cervical myelopathy due to a C6-7 herniated intervertebral disc, and had an operation for C6-7 discetomy and anterior interbody fusion. Approximately 1 month after the operation, he was transferred to the department of rehabilitation in our hospital. Thoracoabdominal aortic aneurysm with intraluminal thrombus was found incidentally on an enhanced computed tomography scan, and high signal intensities were detected at the anterior horns of gray matter from the T8 to cauda equina level on T2-weighted magnetic resonance imaging. There was no evidence of aortic rupture, dissection, or complete occlusion of the aorta. We diagnosed his case as a spinal cord infarction caused by thoracoabdominal aortic aneurysm with intraluminal thrombus. PMID:22639759

  4. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla

    PubMed Central

    Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

    2011-01-01

    sources included oligodendrocytes in normal-appearing white matter and activated macrophages/microglia at the edges of white matter lesions. Additionally, in white matter lesions, iron precipitation in aggregates typical of microbleeds was shown by the Perl's staining. Our combined imaging and pathological study shows that multi-gradient echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may also be seen in apparently normal tissue. Iron identification by multi-gradient echo magnetic resonance imaging in diseased tissues can shed light on the pathological processes when coupled with topographical information and patient disease history. PMID:22171355

  5. Construction of a gene-gene interaction network with a combined score across multiple approaches.

    PubMed

    Zhang, A M; Song, H; Shen, Y H; Liu, Y

    2015-01-01

    Recent progress in computational methods for inves-tigating physical and functional gene interactions has provided new insights into the complexity of biological processes. An essential part of these methods is presented visually in the form of gene interaction networks that can be valuable in exploring the mechanisms of disease. Here, a combined network based on gene pairs with an extra layer of re-liability was constructed after converting and combining the gene pair scores using a novel algorithm across multiple approaches. Four groups of kidney cancer data sets from ArrayExpress were downloaded and analyzed to identify differentially expressed genes using a rank prod-ucts analysis tool. Gene co-expression network, protein-protein interac-tion, co-occurrence network and a combined network were constructed using empirical Bayesian meta-analysis approach, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, an odds ratio formula of the cBioPortal for Cancer Genomics and a novel rank algorithm with combined score, respectively. The topological features of these networks were then compared to evaluate their performances. The results indicated that the gene pairs and their relationship rank-ings were not uniform. The values of topological parameters, such as clustering coefficient and the fitting coefficient R(2) of interaction net-work constructed using our ranked based combination score, were much greater than the other networks. The combined network had a classic small world property which transferred information quickly and displayed great resilience to the dysfunction of low-degree hubs with high-clustering and short average path length. It also followed distinct-ly a scale-free network with a higher reliability. PMID:26125911

  6. Combination of Multiple Resistance Traits from Wild Relative Species in Chrysanthemum via Trigeneric Hybridization

    PubMed Central

    Deng, Yanming; Jiang, Jiafu; Chen, Sumei; Teng, Nianjun; Song, Aiping; Guan, Zhiyong; Fang, Weimin; Chen, Fadi

    2012-01-01

    Background With the objective of combining multiple resistant traits from wild relative species in florist’s chrysanthemums, trigeneric hybridization was conducted by crossing two intergeneric F1 hybrids Chrysanthemum grandiflorum × Artemisia vulgaris and Chrysanthemum crassum × Crossostephium chinense. Methodology/Principal Findings To assess post-pollination phenomena, we investigated pollen germination on the stigma and embryo development, using fluorescence and scanning electron microscopy and paraffin-embedded sections, respectively. We selected eight putative trigeneric hybrid lines that showed the greatest morphological differences from the parents from among the progeny derived via embryo rescue. The hybridity of one trigeneric hybrid was further confirmed by fluorescent genomic in situ hybridization; in addition, the aphid resistance and salt tolerance of this hybrid were higher than those of the chrysanthemum parent and the C. grandiflorum × A. vulgaris F1 hybrid, respectively. Conclusions/Significance The enhanced aphid resistance of the hybrid line reflects the inheritance of chromosomes from A. vulgaris, which carries genes that encode bioactive components. The enhanced salt tolerance of the trigeneric hybrid is attributable to inheritance of genetic materials from Chrysanthemum crassum and Crossostephium chinense, which act to maintain the compartmentation of Na+ and K+ ions and their selective transportation among different organs to avert deleterious effects and protect the photosynthetic apparatus. The results indicate that trigeneric hybridization between different bigeneric hybrids is a promising method for combination of multiple stress-resistance traits for improvement of chrysanthemum. PMID:22952958

  7. Combining morphometric evidence from multiple registration methods using dempster-shafer theory

    NASA Astrophysics Data System (ADS)

    Rajagopalan, Vidya; Wyatt, Christopher

    2010-03-01

    In tensor-based morphometry (TBM) group-wise differences in brain structure are measured using high degreeof- freedom registration and some form of statistical test. However, it is known that TBM results are sensitive to both the registration method and statistical test used. Given the lack of an objective model of group variation is it difficult to determine a best registration method for TBM. The use of statistical tests is also problematic given the corrections required for multiple testing and the notorius difficulty selecting and intepreting signigance values. This paper presents an approach to address both of these issues by combining multiple registration methods using Dempster-Shafer Evidence theory to produce belief maps of categorical changes between groups. This approach is applied to the comparison brain morphometry in aging, a typical application of TBM, using the determinant of the Jacobian as a measure of volume change. We show that the Dempster-Shafer combination produces a unique and easy to interpret belief map of regional changes between and within groups without the complications associated with hypothesis testing.

  8. Combining information from multiple flood projections in a hierarchical Bayesian framework

    NASA Astrophysics Data System (ADS)

    Le Vine, Nataliya

    2016-04-01

    This study demonstrates, in the context of flood frequency analysis, the potential of a recently proposed hierarchical Bayesian approach to combine information from multiple models. The approach explicitly accommodates shared multimodel discrepancy as well as the probabilistic nature of the flood estimates, and treats the available models as a sample from a hypothetical complete (but unobserved) set of models. The methodology is applied to flood estimates from multiple hydrological projections (the Future Flows Hydrology data set) for 135 catchments in the UK. The advantages of the approach are shown to be: (1) to ensure adequate "baseline" with which to compare future changes; (2) to reduce flood estimate uncertainty; (3) to maximize use of statistical information in circumstances where multiple weak predictions individually lack power, but collectively provide meaningful information; (4) to diminish the importance of model consistency when model biases are large; and (5) to explicitly consider the influence of the (model performance) stationarity assumption. Moreover, the analysis indicates that reducing shared model discrepancy is the key to further reduction of uncertainty in the flood frequency analysis. The findings are of value regarding how conclusions about changing exposure to flooding are drawn, and to flood frequency change attribution studies.

  9. A rare combination between familial multiple lipomatosis and extragastrointestinal stromal tumor

    PubMed Central

    Arabadzhieva, Elena; Yonkov, Atanas; Bonev, Sasho; Bulanov, Dimitar; Taneva, Ivanka; Ivanova, Vesela; Dimitrova, Violeta

    2015-01-01

    Introduction Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Rarely, GISTs can be located in mesentery, retroperitoneal space, omentum or pancreas. In these cases, the neoplasm is defined as “extra-gastrointestinal stromal tumors” (EGISTs). Presentation of case We reported a case of a 63-year-old male patient diagnosed by computer tomography with large intraabdominal tumor with vague origin, postoperatively determined as an EGIST. The diagnosis was confirmed by immunohistochemical study. The patient had multiple, subcutaneous, painless lipomas localized in the arms, forearms, thighs, abdomen and thorax. Because of the family history and the clinical presentation the disease was determined as familial multiple lipomatosis (FML). We performed radical tumor resection with distal pancreatectomy and splenectomy, and abdominoplasty, removing redundant skin and underlying subcutaneous fat tissue with multiple lipomas. Discussion FML is a rare hereditary benign disease. On the other hand, only few cases with familial GIST have been reported. In cases with extensive abdominal involvement, the primary origin of EGIST may be impossible to determine so the differential diagnosis is very difficult. Conclusion Although we could not prove correlation between the observed diseases, they are extremely rare and their combination is unusual which makes the presented case valuable and interesting. PMID:26263450

  10. Combining ecosystem service relationships and DPSIR framework to manage multiple ecosystem services.

    PubMed

    Xue, Hui; Li, Shiyu; Chang, Jie

    2015-03-01

    Ecosystem service (ES) relationship occurs due to two types of mechanisms: (1) interact directly or (2) interact through the impact of a shared factor. Identifying such mechanisms behind ES relationship within a single land-use/land-cover category and combining it with a system thinking framework is especially necessary for effective decision-making to manage multiple ESs generated by this land-use/land-cover. In this study, we use tea plantations in China to investigate mechanisms behind ES relationships. We find that tea production is positively correlated with four regulating services (i.e., carbon sequestration, soil N protection, soil P protection, and water conservation). Several regulating services, such as carbon sequestration and soil N, P, and K protection, have positive correlations with each other. Tea production, carbon sequestration, and soil retention are significantly correlated with local annual mean temperature and precipitation. We then establish driver-pressure-state-impact-response (DPSIR) framework for tea plantations, which has been widely used for environmental management issues. Integrating our findings of ES relationship into DPSIR framework, we can estimate how ES change is responding to two types of responses: response to control drivers and response to maintain or restore state. Scenario analysis showed that the responses to control drivers have a larger impact on ES. We discuss that DPSIR would favor managing multiple ES because it enables a more precise understanding of how ES interacts through the effects of factors from various hierarchies. Finally, we suggest integrating ES direct interaction into DPSIR framework. We think such integration could improve the ability of DPSIR framework to support decision-making in multiple ES management, specifically in at least three aspects: (1) favor to identify all possible response alternatives, (2) enable us to evaluate ES which cannot be assessed if without such combining, and (3) help to

  11. Combining multiple imputation and meta-analysis with individual participant data.

    PubMed

    Burgess, Stephen; White, Ian R; Resche-Rigon, Matthieu; Wood, Angela M

    2013-11-20

    Multiple imputation is a strategy for the analysis of incomplete data such that the impact of the missingness on the power and bias of estimates is mitigated. When data from multiple studies are collated, we can propose both within-study and multilevel imputation models to impute missing data on covariates. It is not clear how to choose between imputation models or how to combine imputation and inverse-variance weighted meta-analysis methods. This is especially important as often different studies measure data on different variables, meaning that we may need to impute data on a variable which is systematically missing in a particular study. In this paper, we consider a simulation analysis of sporadically missing data in a single covariate with a linear analysis model and discuss how the results would be applicable to the case of systematically missing data. We find in this context that ensuring the congeniality of the imputation and analysis models is important to give correct standard errors and confidence intervals. For example, if the analysis model allows between-study heterogeneity of a parameter, then we should incorporate this heterogeneity into the imputation model to maintain the congeniality of the two models. In an inverse-variance weighted meta-analysis, we should impute missing data and apply Rubin's rules at the study level prior to meta-analysis, rather than meta-analyzing each of the multiple imputations and then combining the meta-analysis estimates using Rubin's rules. We illustrate the results using data from the Emerging Risk Factors Collaboration. PMID:23703895

  12. Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma.

    PubMed

    Shimura, S; Andoh, Y; Haraguchi, M; Shirato, K

    1996-07-01

    The aim of this study was to elucidate the mechanism of the formation of the widespread mucous-plugging observed in autopsied lungs from patients with bronchial asthma. We performed morphometric analysis of airways of autopsied lungs from eight patients with bronchial asthma (Group BA), and compared it with those of six chronic bronchitics (Group CB) and four control patients (Control). The following parameters were measured in paraffin sections: volume proportion of bronchial glands to bronchial wall (Gland%); goblet cell granules to total epithelial layer (Goblet %); intraluminal mucus expressed as the mucus occupying ratio (MOR); volume ratio of intraluminal mucus continuous with goblet cells to total intraluminal mucus (Vc/Vtol %); and surface ratio of the contact surface of intraluminal mucus continuous with goblet cells to the total luminal surface (Sc/Stot %). Gland%, Goblet %, and MOR or inflammatory cell numbers in the airway walls both from Group BA and CB were larger than those from the Control group. However, no significant differences were observed between Group BA and CB in Gland%, Goblet %, MOR or inflammatory cell numbers, except for the eosinophil number: i.e. 23 +/- 3, 22 +/- 3 and 6 +/- 2% in Gland%; 22 +/- 9, 5 +/- 4 and 2 +/- 2% in Goblet%; 10 +/- 3, 18 +/- 3 and 0.3 +/- 0.5% in MOR; 199 +/- 68, 10 +/- 3 and 2 +/- 2 cells. mm-2 in eosinophil number of the peripheral airways from Groups BA, CB and Control, respectively. In contrast, marked and significant increases were observed both in Vc/Vtot% and Sc/Stot% in Group BA compared to Groups CB and Control both in central and peripheral airways: i.e. Vc/Vtot% in the peripheral airways was 53 +/- 5, 4 +/- 3 and 0.8 +/- 0.8% from Groups BA, CB and Control, respectively (BA vs CB or BA vs Control, p < 0.01 each). These findings suggest that the continuity of goblet cells and intraluminal mucus or lack of full release of mucus, from goblet cells, is peculiar to asthmatic airways, and may contribute to

  13. Combining Multiple Rupture Models in Real-Time for Earthquake Early Warning

    NASA Astrophysics Data System (ADS)

    Minson, S. E.; Wu, S.; Beck, J. L.; Heaton, T. H.

    2015-12-01

    The ShakeAlert earthquake early warning system for the west coast of the United States is designed to combine information from multiple independent earthquake analysis algorithms in order to provide the public with robust predictions of shaking intensity at each user's location before they are affected by strong shaking. The current contributing analyses come from algorithms that determine the origin time, epicenter, and magnitude of an earthquake (On-site, ElarmS, and Virtual Seismologist). A second generation of algorithms will provide seismic line source information (FinDer), as well as geodetically-constrained slip models (BEFORES, GPSlip, G-larmS, G-FAST). These new algorithms will provide more information about the spatial extent of the earthquake rupture and thus improve the quality of the resulting shaking forecasts.Each of the contributing algorithms exploits different features of the observed seismic and geodetic data, and thus each algorithm may perform differently for different data availability and earthquake source characteristics. Thus the ShakeAlert system requires a central mediator, called the Central Decision Module (CDM). The CDM acts to combine disparate earthquake source information into one unified shaking forecast. Here we will present a new design for the CDM that uses a Bayesian framework to combine earthquake reports from multiple analysis algorithms and compares them to observed shaking information in order to both assess the relative plausibility of each earthquake report and to create an improved unified shaking forecast complete with appropriate uncertainties. We will describe how these probabilistic shaking forecasts can be used to provide each user with a personalized decision-making tool that can help decide whether or not to take a protective action (such as opening fire house doors or stopping trains) based on that user's distance to the earthquake, vulnerability to shaking, false alarm tolerance, and time required to act.

  14. Investigation of strategies for drug delivery by combination targeting of nanocarriers to multiple epitopes or receptors

    NASA Astrophysics Data System (ADS)

    Papademetriou, Iason Titos

    Development of drug delivery systems (ie. nanocarriers) with controllable composition, architecture, and functionalities is heavily investigated in the field of drug delivery in order to improve clinical interventions. Designing drug nanocarriers which possess targeting properties is critical to enable them to reach the intended site of intervention in the body. To achieve this goal, the surface of drug nanocarriers can be modified with targeting moieties (antibodies, peptides, etc.) addressed to cell surface molecules expressed on the diseased tissues and cells. If these molecules are receptors capable of internalizing bound ligands via endocytosis, targeting can then enable drug transport into cells or across cellular barriers in the body. Yet, addressing nanocarriers to single targets presents limited control over cellular interactions and biodistribution. Since most cell-surface markers are not exclusively expressed in a precise site in vivo, high affinity of targeted nanocarriers may lead to non-desired accumulation in regions of the body associated with low expression. Modification of nanocarriers to achieve combined-targeting (binding to more than one cell-surface receptor) may help modulate binding to cells and also endocytosis, since cell receptors possess distinct functions and features affecting these parameters, such as their expression, location on the plasmalemma, activation in disease, mechanism of endocytosis, etc. Further, targeting nanocarriers to multiple epitopes of the same receptor, a strategy which has never been tested, may also modulate these parameters since they are highly epitope specific. In this dissertation, we investigate the effect of targeting model polymer nanocarriers to: (1) multiple receptors of similar function (intercellular-, platelet-endothelial-, and/or vascular-cell adhesion molecules), (2) multiple receptors of different function (intercellular adhesion molecule 1 and transferrin receptor), or (3) multiple epitopes of

  15. Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

    PubMed Central

    Salier, J P; Sesboüé, R; Martin-Mondière, C; Daveau, M; Cesaro, P; Cavelier, B; Coquerel, A; Legrand, L; Goust, J M; Degos, J D

    1986-01-01

    In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease. PMID:3461005

  16. Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

    PubMed

    Salier, J P; Sesboüé, R; Martin-Mondière, C; Daveau, M; Cesaro, P; Cavelier, B; Coquerel, A; Legrand, L; Goust, J M; Degos, J D

    1986-08-01

    In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease. PMID:3461005

  17. Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors.

    PubMed

    Whittaker, Steven R; Cowley, Glenn S; Wagner, Steve; Luo, Flora; Root, David E; Garraway, Levi A

    2015-12-01

    RAF and MEK inhibitors are effective in BRAF-mutant melanoma but not in BRAF-mutant colorectal cancer. To gain additional insights into this difference, we performed a genome-scale pooled shRNA enhancer screen in a BRAF-mutant, RAF inhibitor-resistant colorectal cancer cell line exposed to the selective RAF inhibitor PLX4720. We identified multiple genes along the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) signaling axis that, when suppressed, either genetically or pharmacologically, sensitized cells to the selective RAF inhibitor through sustained inhibition of MAPK signaling. Strikingly, CRAF was a key mediator of resistance that could be overcome by the use of pan-RAF inhibitors in combination with a MEK inhibitor. Furthermore, the combination of pan-RAF and MEK inhibitors displayed strong synergy in melanoma and colorectal cancer cell lines with RAS-activating events such as RTK activation, KRAS mutation, or NF1 loss-of-function mutations. Combinations of selective RAF inhibitors, such as PLX4720 or dabrafenib, with MEK inhibitors did not incur such profound synergy, suggesting that inhibition of CRAF by pan-RAF inhibitors plays a key role in determining cellular response. Importantly, in contrast to the modest activity seen with single-agent treatment, dual pan-RAF and MEK inhibition results in the induction of apoptosis, greatly enhancing efficacy. Notably, combined pan-RAF and MEK inhibition can overcome intrinsic and acquired resistance to single-agent RAF/MEK inhibition, supporting dual pan-RAF and MEK inhibition as a novel therapeutic strategy for BRAF- and KRAS-mutant cancers. PMID:26351322

  18. Optical compression and encryption system combining multiple measurement matrices with fractional Fourier transform.

    PubMed

    Yi, Jiawang; Tan, Guanzheng

    2015-12-20

    Optical cryptosystems combined with compressed sensing can achieve compression and encryption simultaneously. But they usually use the same measurement matrix to sample all blocks of an image, which makes it easy to estimate the measurement matrix in the chosen plaintext attack. In this paper, we propose a robust scheme adopting multiple measurement matrices to overcome this shortcoming. The matrices can be efficiently derived by applying random row exchanging to a basic one, which is also encoded into the fractional Fourier transform (FrFT) domain to improve the visual effect of wrongly decrypted images. Chaos-based pixel scrambling is added into our double FrFT cryptosystem to guarantee its nonlinearity. Simulation results have shown the security and effectiveness of our scheme. PMID:26837032

  19. Multiple sequence alignment based on combining genetic algorithm with chaotic sequences.

    PubMed

    Gao, C; Wang, B; Zhou, C J; Zhang, Q

    2016-01-01

    In bioinformatics, sequence alignment is one of the most common problems. Multiple sequence alignment is an NP (nondeterministic polynomial time) problem, which requires further study and exploration. The chaos optimization algorithm is a type of chaos theory, and a procedure for combining the genetic algorithm (GA), which uses ergodicity, and inherent randomness of chaotic iteration. It is an efficient method to solve the basic premature phenomenon of the GA. Applying the Logistic map to the GA and using chaotic sequences to carry out the chaotic perturbation can improve the convergence of the basic GA. In addition, the random tournament selection and optimal preservation strategy are used in the GA. Experimental evidence indicates good results for this process. PMID:27420977

  20. Bird viruses in multiple sclerosis: combination of viruses or Marek's alone?

    PubMed

    McHatters, G R; Scham, R G

    1995-03-24

    This is a short report confirming recent articles that birds are very likely involved as vectors of the exogenous causative agent of multiple sclerosis (MS). It also critically reviews the most recent article (MacGregor, H. and Latiwonk, Q., Neurol. Res., 15 (1993) 391-394.) in which a high percentage of serums from MS patients reacted positively with Marek's antigen and it was accidentally discovered that Epstein-Barr virus antibodies also cross-react positively with Marek's antigen. This discovery might help explain the complex epidemiology of MS (an infectious mononucleosis infection would immunize a person against future mononucleosis and a Marek's infection). A table comparing the similarities between MS and Marek's is included. Other possible avian viral candidates are entertained plus the possibility of various viral combinations within a protective chlamydial plasmid including Marek's and avian retroviruses. PMID:7792060

  1. Local Quantification of Wall Thickness and Intraluminal Thrombus Offer Insight into the Mechanical Properties of the Aneurysmal Aorta.

    PubMed

    Martufi, Giampaolo; Satriano, Alessandro; Moore, Randy D; Vorp, David A; Di Martino, Elena S

    2015-08-01

    Wall stress is a powerful tool to assist clinical decisions in rupture risk assessment of abdominal aortic aneurysms. Key modeling assumptions that influence wall stress magnitude and distribution are the inclusion or exclusion of the intraluminal thrombus in the model and the assumption of a uniform wall thickness. We employed a combined numerical-experimental approach to test the hypothesis that abdominal aortic aneurysm (AAA) wall tissues with different thickness as well as wall tissues covered by different thrombus thickness, exhibit differences in the mechanical behavior. Ultimate tissue strength was measured from in vitro tensile testing of AAA specimens and material properties of the wall were estimated by fitting the results of the tensile tests to a histo-mechanical constitutive model. Results showed a decrease in tissue strength and collagen stiffness with increasing wall thickness, supporting the hypothesis of wall thickening being mediated by accumulation of non load-bearing components. Additionally, an increase in thrombus deposition resulted in a reduction of elastin content, collagen stiffness and tissue strength. Local wall thickness and thrombus coverage may be used as surrogate measures of local mechanical properties of the tissue, and therefore, are possible candidates to improve the specificity of AAA wall stress and rupture risk evaluations. PMID:25631202

  2. Detecting Causality by Combined Use of Multiple Methods: Climate and Brain Examples

    PubMed Central

    Hirata, Yoshito; Amigó, José M.; Matsuzaka, Yoshiya; Yokota, Ryo; Mushiake, Hajime; Aihara, Kazuyuki

    2016-01-01

    Identifying causal relations from time series is the first step to understanding the behavior of complex systems. Although many methods have been proposed, few papers have applied multiple methods together to detect causal relations based on time series generated from coupled nonlinear systems with some unobserved parts. Here we propose the combined use of three methods and a majority vote to infer causality under such circumstances. Two of these methods are proposed here for the first time, and all of the three methods can be applied even if the underlying dynamics is nonlinear and there are hidden common causes. We test our methods with coupled logistic maps, coupled Rössler models, and coupled Lorenz models. In addition, we show from ice core data how the causal relations among the temperature, the CH4 level, and the CO2 level in the atmosphere changed in the last 800,000 years, a conclusion also supported by irregularly sampled data analysis. Moreover, these methods show how three regions of the brain interact with each other during the visually cued, two-choice arm reaching task. Especially, we demonstrate that this is due to bottom up influences at the beginning of the task, while there exist mutual influences between the posterior medial prefrontal cortex and the presupplementary motor area. Based on our results, we conclude that identifying causality with an appropriate ensemble of multiple methods ensures the validity of the obtained results more firmly. PMID:27380515

  3. Intraluminal ultrasound guidance of transverse laser coronary atherectomy

    NASA Astrophysics Data System (ADS)

    Aretz, H. Thomas; Martinelli, Michael A.; LeDet, Earl G.; Sedlacek, Tomas; Hatch, G. F.; Gregg, Richard E.

    1990-07-01

    A coronary laser atherectomy system combining laser delivery and ultrasonic imaging capability is described. The system is being developed by Intra-Sonix, Inc. to treat severe stenoses. The imaging system provides the clinician with the guidance needed to remove substantial plaque without perforation. The ultrasound transducers and laser optics are mounted in a small (less than 4 F), flexible catheter, that is deliverable over a standard guidewire (0.016 inch). The laser and ultrasound beams are directed at the artery wall to permit debulking of lesions and ultrasonic depth profiling of the tissue structure throughout the thickness of the artery. This allows the physician to determine the level of therapy to be applied and to monitor the plaque removal as the therapy progresses. The precise location of the ultrasound and laser beams in the artery is determined by a navigation system. Navigation data are processed electronically in conjunction with ultrasound data to produce real-time cross-sectional and longitudinal images of the artery wall at selected locations, which are updated as the catheter progresses through the vessel lumen. Results of in vitro tests on human atherosclerotic arteries and early in vivo experiments in a canine-human xenograft model showing image construction and radial laser delivery are discussed.

  4. Early And Present Examples Of Intraluminal Ultrasonic Echography

    NASA Astrophysics Data System (ADS)

    Bom, Nicolaas; Ten Hoff, H.; Lancee, Charles T.; Gussenhoven, Elma J.; Serruys, Patrick W.; Slager, C. J.; Roelandt, J.

    1989-08-01

    Although one of the great merits of medical application of ultrasound is the non-invasive character of the technique, there are several examples in which an invasive or semi-invasive application can be useful. Probably due to then poor sensitivity of the piezoelectric crystals some very early invasive echo applications are based on tube-or catheter-mounted echo elements. Echo-endoscopy for the inspection of body cavities dates back to the fifties. Not much later investigators began to develop intra-esophageal probes for inspection of the heart and great vessels. Transesophageal echography has become very important in cardiology today. Intravascular echo imaging has gained much interest. Such a technique would be very helpful in the diagnosis of obstructive arterial disease and the evaluation of therapeutic intervention. This echo technique has been suggested for steering of catheter-based desobstruction methods. A few examples of combined echo and desobstruction techniques as reported in literature are mentioned. With high-frequency intravascular real-time imaging it is possible to observe detailed information on arterial wall, fibrotic proliferation and atherosclerotic plaque.

  5. Smart Sensor for Online Detection of Multiple-Combined Faults in VSD-Fed Induction Motors

    PubMed Central

    Garcia-Ramirez, Armando G.; Osornio-Rios, Roque A.; Granados-Lieberman, David; Garcia-Perez, Arturo; Romero-Troncoso, Rene J.

    2012-01-01

    Induction motors fed through variable speed drives (VSD) are widely used in different industrial processes. Nowadays, the industry demands the integration of smart sensors to improve the fault detection in order to reduce cost, maintenance and power consumption. Induction motors can develop one or more faults at the same time that can be produce severe damages. The combined fault identification in induction motors is a demanding task, but it has been rarely considered in spite of being a common situation, because it is difficult to identify two or more faults simultaneously. This work presents a smart sensor for online detection of simple and multiple-combined faults in induction motors fed through a VSD in a wide frequency range covering low frequencies from 3 Hz and high frequencies up to 60 Hz based on a primary sensor being a commercially available current clamp or a hall-effect sensor. The proposed smart sensor implements a methodology based on the fast Fourier transform (FFT), RMS calculation and artificial neural networks (ANN), which are processed online using digital hardware signal processing based on field programmable gate array (FPGA).

  6. Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma.

    PubMed

    Chauhan, Dharminder; Singh, Ajita; Brahmandam, Mohan; Podar, Klaus; Hideshima, Teru; Richardson, Paul; Munshi, Nikhil; Palladino, Michael A; Anderson, Kenneth C

    2008-02-01

    Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 triggers apoptosis in multiple myeloma (MM) cells, and importantly, that is distinct from bortezomib (Velcade) in its chemical structure, effects on proteasome activities, and mechanisms of action. Here, we demonstrate that combining NPI-0052 and bortezomb induces synergistic anti-MM activity both in vitro using MM cell lines or patient CD138(+) MM cells and in vivo in a human plasmacytoma xenograft mouse model. NPI-0052 plus bortezomib-induced synergistic apoptosis is associated with: (1) activation of caspase-8, caspase-9, caspase-3, and PARP; (2) induction of endoplasmic reticulum (ER) stress response and JNK; (3) inhibition of migration of MM cells and angiogenesis; (4) suppression of chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) proteolytic activities; and (5) blockade of NF-kappaB signaling. Studies in a xenograft model show that low dose combination of NPI-0052 and bortezomib is well tolerated and triggers synergistic inhibition of tumor growth and CT-L, C-L, and T-L proteasome activities in tumor cells. Immununostaining of MM tumors from NPI-0052 plus bortezomib-treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Taken together, our study provides the preclinical rationale for clinical protocols evaluating bortezomib together with NPI-0052 to improve patient outcome in MM. PMID:18006697

  7. Atomic Theory and Multiple Combining Proportions: The Search for Whole Number Ratios.

    PubMed

    Usselman, Melvyn C; Brown, Todd A

    2015-04-01

    John Dalton's atomic theory, with its postulate of compound formation through atom-to-atom combination, brought a new perspective to weight relationships in chemical reactions. A presumed one-to-one combination of atoms A and B to form a simple compound AB allowed Dalton to construct his first table of relative atomic weights from literature analyses of appropriate binary compounds. For such simple binary compounds, the atomic theory had little advantages over affinity theory as an explanation of fixed proportions by weight. For ternary compounds of the form AB2, however, atomic theory made quantitative predictions that were not deducible from affinity theory. Atomic theory required that the weight of B in the compound AB2 be exactly twice that in the compound AB. Dalton, Thomas Thomson and William Hyde Wollaston all published within a few years of each other experimental data that claimed to give the predicted results with the required accuracy. There are nonetheless several experimental barriers to obtaining the desired integral multiple proportions. In this paper I will discuss replication experiments which demonstrate that only Wollaston's results are experimentally reliable. It is likely that such replicability explains why Wollaston's experiments were so influential. PMID:26104162

  8. Global multiple protein-protein interaction network alignment by combining pairwise network alignments

    PubMed Central

    2015-01-01

    Background A wealth of protein interaction data has become available in recent years, creating an urgent need for powerful analysis techniques. In this context, the problem of finding biologically meaningful correspondences between different protein-protein interaction networks (PPIN) is of particular interest. The PPIN of a species can be compared with that of other species through the process of PPIN alignment. Such an alignment can provide insight into basic problems like species evolution and network component function determination, as well as translational problems such as target identification and elucidation of mechanisms of disease spread. Furthermore, multiple PPINs can be aligned simultaneously, expanding the analytical implications of the result. While there are several pairwise network alignment algorithms, few methods are capable of multiple network alignment. Results We propose SMAL, a MNA algorithm based on the philosophy of scaffold-based alignment. SMAL is capable of converting results from any global pairwise alignment algorithms into a MNA in linear time. Using this method, we have built multiple network alignments based on combining pairwise alignments from a number of publicly available (pairwise) network aligners. We tested SMAL using PPINs of eight species derived from the IntAct repository and employed a number of measures to evaluate performance. Additionally, as part of our experimental investigations, we compared the effectiveness of SMAL while aligning up to eight input PPINs, and examined the effect of scaffold network choice on the alignments. Conclusions A key advantage of SMAL lies in its ability to create MNAs through the use of pairwise network aligners for which native MNA implementations do not exist. Experiments indicate that the performance of SMAL was comparable to that of the native MNA implementation of established methods such as IsoRankN and SMETANA. However, in terms of computational time, SMAL was significantly faster

  9. Combining multiple regression and principal component analysis for accurate predictions for column ozone in Peninsular Malaysia

    NASA Astrophysics Data System (ADS)

    Rajab, Jasim M.; MatJafri, M. Z.; Lim, H. S.

    2013-06-01

    This study encompasses columnar ozone modelling in the peninsular Malaysia. Data of eight atmospheric parameters [air surface temperature (AST), carbon monoxide (CO), methane (CH4), water vapour (H2Ovapour), skin surface temperature (SSKT), atmosphere temperature (AT), relative humidity (RH), and mean surface pressure (MSP)] data set, retrieved from NASA's Atmospheric Infrared Sounder (AIRS), for the entire period (2003-2008) was employed to develop models to predict the value of columnar ozone (O3) in study area. The combined method, which is based on using both multiple regressions combined with principal component analysis (PCA) modelling, was used to predict columnar ozone. This combined approach was utilized to improve the prediction accuracy of columnar ozone. Separate analysis was carried out for north east monsoon (NEM) and south west monsoon (SWM) seasons. The O3 was negatively correlated with CH4, H2Ovapour, RH, and MSP, whereas it was positively correlated with CO, AST, SSKT, and AT during both the NEM and SWM season periods. Multiple regression analysis was used to fit the columnar ozone data using the atmospheric parameter's variables as predictors. A variable selection method based on high loading of varimax rotated principal components was used to acquire subsets of the predictor variables to be comprised in the linear regression model of the atmospheric parameter's variables. It was found that the increase in columnar O3 value is associated with an increase in the values of AST, SSKT, AT, and CO and with a drop in the levels of CH4, H2Ovapour, RH, and MSP. The result of fitting the best models for the columnar O3 value using eight of the independent variables gave about the same values of the R (≈0.93) and R2 (≈0.86) for both the NEM and SWM seasons. The common variables that appeared in both regression equations were SSKT, CH4 and RH, and the principal precursor of the columnar O3 value in both the NEM and SWM seasons was SSKT.

  10. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever

    PubMed Central

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in “attack” or “remission” was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines’ serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  11. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever.

    PubMed

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-04-01

    The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in "attack" or "remission" was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines' serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  12. Measurement of Peak Esophageal Luminal Cross Sectional Area Utilizing Nadir Intraluminal Impedance

    PubMed Central

    Zifan, Ali; Ledgerwood-Lee, Melissa; Mittal, Ravinder K

    2015-01-01

    BACKGROUND Multichannel intraluminal impedance (MII) is currently used to monitor gastroesophageal reflux and esophageal bolus clearance. We describe a novel methodology to measure maximal luminal CSA during bolus transport from MII measurements. METHODS Studies were conducted in-vitro (test tubes) and in-vivo (healthy subjects). Concurrent MII, HRM, and intraluminal ultrasound (US) were recorded 7 cm above the lower esophageal sphincter. Swallows with two concentrations of saline, 0.1N and 0.5N, of bolus volumes 5cc, 10cc and 15cc were performed. The CSA was estimated by solving two algebraic Ohm’s law equations, resulting from the two saline solutions. The CSA calculated from impedance method was compared with the CSA measured from the intraluminal US images. KEY RESULTS The CSA measured in duplicate from B-mode US images showed a mean difference between the two manual delineations to be near zero, and the repeatability coefficient was within 7.7% of the mean of the two CSA measurements. The calculated CSA from the impedance measurements strongly correlated with the US measured CSA (R2 ≅ 0.98). A detailed statistical analysis of the impedance and US measured CSA data indicated that the 95% limits of agreement between the two methods ranged from −9.1 to 13mm2. The root mean square error (RMS) of the two measurements was 4.8% of the mean US-measured CSA. CONCLUSIONS We describe a novel methodology to measure peak esophageal luminal CSA during peristalsis. Further studies are needed to determine if it is possible to measure patterns of luminal distension during peristalsis across the entire length of the esophagus. PMID:25930157

  13. Intraluminal Radioactive Stent Compared with Covered Stent Alone for the Treatment of Malignant Esophageal Stricture

    SciTech Connect

    Wang Zhongmin; Huang Xunbo; Cao Jun; Huang Gang; Chen Kemin LIu Yu; Liu Fenju

    2012-04-15

    Objective: This study was designed to compare the clinical effectiveness of intraluminal radioactive stent loaded with iodine-125 seeds implantation versus covered stent alone insertion in patients with malignant esophageal stricture. Methods: We studied two groups of patients with malignant esophageal stricture. Group A comprised 28 patients (19 men and 9 women) who underwent intraluminal radioactive stent loaded with iodine-125 seeds implantation and were followed prospectively. Group B comprised 30 patients (18 men and 12 women) who had previously received covered stent alone insertion; these patients were evaluated retrospectively. There was no crossover between the two groups during follow-up. Informed consent was obtained from each patient, and our institutional review board approved the study. The dysphagia score, overall survival rates, complication rates, and reintervention rates were compared in the two groups. Results: There were no significant differences between the two groups in terms of baseline characteristics. Stent placement was technically successful and well tolerated in all patients. The dysphagia score was improved in both groups after stent placement. The median survival was significantly longer in group A than in group B: 11 versus 4.9 months, respectively (P < 0.001). The complications of chest pain, esophageal reflux, and stent migration was more frequent in group B, but this difference did not reach statistical significance. There was no statistical difference in reintervention between two groups. Conclusions: Intraluminal radioactive stent loaded with iodine-125 seeds implantation was a feasible and practical management in treating malignant esophageal stricture and was superior to covered stent alone insertion, as measured by survival.

  14. A Novel Electrochemical Microfluidic Chip Combined with Multiple Biomarkers for Early Diagnosis of Gastric Cancer

    NASA Astrophysics Data System (ADS)

    Xie, Yao; Zhi, Xiao; Su, Haichuan; Wang, Kan; Yan, Zhen; He, Nongyue; Zhang, Jingpu; Chen, Di; Cui, Daxiang

    2015-12-01

    Early diagnosis is very important to improve the survival rate of patients with gastric cancer and to understand the biology of cancer. In order to meet the clinical demands for early diagnosis of gastric cancer, we developed a disposable easy-to-use electrochemical microfluidic chip combined with multiple antibodies against six kinds of biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), Helicobacter pylori CagA protein (H.P.), P53oncoprotein (P53), pepsinogen I (PG I), and PG-II). The six kinds of biomarkers related to gastric cancer can be detected sensitively and synchronously in a short time. The specially designed three electrodes system enables cross-contamination to be avoided effectively. The linear ranges of detection of the electrochemical microfluidic chip were as follows: 0.37-90 ng mL-1 for CEA, 10.75-172 U mL-1 for CA19-9, 10-160 U L-1 for H.P., 35-560 ng mL-1 for P53, 37.5-600 ng mL-1 for PG I, and 2.5-80 ng mL-1for PG II. This method owns better sensitivity compared with enzyme-linked immunosorbent assay (ELISA) results of 394 specimens of gastric cancer sera. Furthermore, we established a multi-index prediction model based on the six kinds of biomarkers for predicting risk of gastric cancer. In conclusion, the electrochemical microfluidic chip for detecting multiple biomarkers has great potential in applications such as early screening of gastric cancer patients, and therapeutic evaluation, and real-time dynamic monitoring the progress of gastric cancer in near future.

  15. Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study

    PubMed Central

    2011-01-01

    Background Therapeutic massage and bodywork (TMB) practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Methods Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Results Of the 5242 distributed surveys, 791 were returned (15.1%). Practitioners were predominantly female (91.7%), worked in a range of environments, primarily private (44.4%) and home clinics (35.4%), and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%), with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. Conclusions The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient's treatment through a highly

  16. Facile integration of multiple magnetite nanoparticles for theranostics combining efficient MRI and thermal therapy

    NASA Astrophysics Data System (ADS)

    Huang, Guoming; Zhu, Xianglong; Li, Hui; Wang, Lirong; Chi, Xiaoqin; Chen, Jiahe; Wang, Xiaomin; Chen, Zhong; Gao, Jinhao

    2015-01-01

    Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned that such IO/GO-COOH nanocomposites combining efficient MRI and photothermal therapy hold great promise in theranostic applications.Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned

  17. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors.

    PubMed

    Chou, T C; Talalay, P

    1984-01-01

    A generalized method for analyzing the effects of multiple drugs and for determining summation, synergism and antagonism has been proposed. The derived, generalized equations are based on kinetic principles. The method is relatively simple and is not limited by whether the dose-effect relationships are hyperbolic or sigmoidal, whether the effects of the drugs are mutually exclusive or nonexclusive, whether the ligand interactions are competitive, noncompetitive or uncompetitive, whether the drugs are agonists or antagonists, or the number of drugs involved. The equations for the two most widely used methods for analyzing synergism, antagonism and summation of effects of multiple drugs, the isobologram and fractional product concepts, have been derived and been shown to have limitations in their applications. These two methods cannot be used indiscriminately. The equations underlying these two methods can be derived from a more generalized equation previously developed by us (59). It can be shown that the isobologram is valid only for drugs whose effects are mutually exclusive, whereas the fractional product method is valid only for mutually nonexclusive drugs which have hyperbolic dose-effect curves. Furthermore, in the isobol method, it is laborious to find proper combinations of drugs that would produce an iso-effective curve, and the fractional product method tends to give indication of synergism, since it underestimates the summation of the effect of mutually nonexclusive drugs that have sigmoidal dose-effect curves. The method described herein is devoid of these deficiencies and limitations. The simplified experimental design proposed for multiple drug-effect analysis has the following advantages: It provides a simple diagnostic plot (i.e., the median-effect plot) for evaluating the applicability of the data, and provides parameters that can be directly used to obtain a general equation for the dose-effect relation; the analysis which involves logarithmic

  18. Particle acceleration by combined diffusive shock acceleration and downstream multiple magnetic island acceleration

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.

    2015-09-01

    As a consequence of the evolutionary conditions [28; 29], shock waves can generate high levels of downstream vortical turbulence. Simulations [32-34] and observations [30; 31] support the idea that downstream magnetic islands (also called plasmoids or flux ropes) result from the interaction of shocks with upstream turbulence. Zank et al. [18] speculated that a combination of diffusive shock acceleration (DSA) and downstream reconnection-related effects associated with the dynamical evolution of a “sea of magnetic islands” would result in the energization of charged particles. Here, we utilize the transport theory [18; 19] for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets to investigate a combined DSA and downstream multiple magnetic island charged particle acceleration mechanism. We consider separately the effects of the anti-reconnection electric field that is a consequence of magnetic island merging [17], and magnetic island contraction [14]. For the merging plasmoid reconnection- induced electric field only, we find i) that the particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory, and ii) that the solution is constant downstream of the shock. For downstream plasmoid contraction only, we find that i) the accelerated particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory; ii) for a given energy, the particle intensity peaks downstream of the shock, and the peak location occurs further downstream of the shock with increasing particle energy, and iii) the particle intensity amplification for a particular particle energy, f(x, c/c0)/f(0, c/c0), is not 1, as predicted by DSA theory, but increases with increasing particle energy. These predictions can be tested against observations of electrons and ions accelerated at interplanetary shocks and the heliospheric

  19. Multiple dose study of the combined radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole)

    SciTech Connect

    Bleehen, N.M.; Newman, H.F.; Maughan, T.S.; Workman, P.

    1989-04-01

    The hypoxic cell radiosensitizers Ro 03-8799 and SR 2508 have different clinical toxicities. The former produces an acute but transient central nervous system syndrome, whereas the latter produces cumulative peripheral neuropathy. Following single dose studies, an escalating multiple dose schedule using both drugs in combination showed no unexpected adverse reactions at lower doses. This study identifies the clinical tolerance and pharmacokinetics when doses in the region of the maximal tolerated dose are given to 26 patients receiving infusions of 0.75 g/m2 Ro 03-8799 and 2 g/m2 SR 2508 three times per week. At 15 doses, 3/4 patients experienced WHO grade 2 peripheral neuropathy, whereas at 12 doses 1/9 developed grade 2 and 6/9 developed grade 1 neuropathies. This represents a lower dose of SR 2508 than can be given alone suggesting that some interaction between the two drugs does exist in terms of chronic peripheral neurotoxicity. Pharmacokinetic studies show no adverse interactions between the two drugs and minimal inter-patient variation. From bivariate analysis, cumulative AUC for Ro 03-8799 has the most significant correlation with the development of peripheral neuropathy. Tumor drug concentrations normalized to the administered dose show mean values of 34 micrograms/g Ro 03-8799 and 76 micrograms/g SR 2508 30 minutes after infusion. These could be expected to produce a single dose sensitizer enhancement ratio of 1.5. The combination of the two sensitizers at the maximum tolerable dose may be expected to give an increased therapeutic efficacy over either drug alone.

  20. Imaging leukocyte adhesion to the vascular endothelium at high intraluminal pressure.

    PubMed

    Michell, Danielle L; Andrews, Karen L; Woollard, Kevin J; Chin-Dusting, Jaye P F

    2011-01-01

    Worldwide, hypertension is reported to be in approximately a quarter of the population and is the leading biomedical risk factor for mortality worldwide. In the vasculature hypertension is associated with endothelial dysfunction and increased inflammation leading to atherosclerosis and various disease states such as chronic kidney disease(2), stroke(3) and heart failure(4). An initial step in vascular inflammation leading to atherogenesis is the adhesion cascade which involves the rolling, tethering, adherence and subsequent transmigration of leukocytes through the endothelium. Recruitment and accumulation of leukocytes to the endothelium is mediated by an upregulation of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1) and E-selectin as well as increases in cytokine and chemokine release and an upregulation of reactive oxygen species(5). In vitro methods such as static adhesion assays help to determine mechanisms involved in cell-to-cell adhesion as well as the analysis of cell adhesion molecules. Methods employed in previous in vitro studies have demonstrated that acute increases in pressure on the endothelium can lead to monocyte adhesion, an upregulation of adhesion molecules and inflammatory markers(6) however, similar to many in vitro assays, these findings have not been performed in real time under physiological flow conditions, nor with whole blood. Therefore, in vivo assays are increasingly utilised in animal models to demonstrate vascular inflammation and plaque development. Intravital microscopy is now widely used to assess leukocyte adhesion, rolling, migration and transmigration(7-9). When combining the effects of pressure on leukocyte to endothelial adhesion the in vivo studies are less extensive. One such study examines the real time effects of flow and shear on arterial growth and remodelling but inflammatory markers were only assessed via immunohistochemistry(10). Here we present

  1. Combining Evidence of Preferential Gene-Tissue Relationships from Multiple Sources

    PubMed Central

    Guo, Jing; Hammar, Mårten; Öberg, Lisa; Padmanabhuni, Shanmukha S.; Bjäreland, Marcus; Dalevi, Daniel

    2013-01-01

    An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity. PMID:23950964

  2. Facile integration of multiple magnetite nanoparticles for theranostics combining efficient MRI and thermal therapy.

    PubMed

    Huang, Guoming; Zhu, Xianglong; Li, Hui; Wang, Lirong; Chi, Xiaoqin; Chen, Jiahe; Wang, Xiaomin; Chen, Zhong; Gao, Jinhao

    2015-02-14

    Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned that such IO/GO-COOH nanocomposites combining efficient MRI and photothermal therapy hold great promise in theranostic applications. PMID:25581879

  3. A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma.

    PubMed

    Hideshima, Teru; Raje, Noopur; Richardson, Paul G; Anderson, Kenneth C

    2008-02-01

    Lenalidomide (also known as Revlimid((R)), CC-5013) is an immunomodulatory derivative of thalidomide and has more potent anti-tumor and anti-inflammatory effects than thalidomide. The molecular mechanisms of anti-tumor activity of lenalidomide have been extensively studied in multiple myeloma (MM) both preclinical models and in clinical trials. Lenalidomide: directly triggers growth arrest and/or apoptosis of drug resistant MM cells; inhibits binding of MM cells to bone marrow (BM) extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the BM milieu; and augments host anti-tumor immunity. Lenalidomide achieved responses in patients with relapsed refractory MM. Moreover, lenalidomide with dexamethasone (Dex) demonstrates more potent anti-MM activities than Dex both in vitro and in randomized phase III clinical trials. Specifically, the combination improved overall and extent of response, as well as prolonged time to progression and overall survival, resulting in FDA approval of lenalidomide with Dex for therapy MM relapsing after prior therapy. PMID:18728702

  4. Combining evidence of preferential gene-tissue relationships from multiple sources.

    PubMed

    Guo, Jing; Hammar, Mårten; Oberg, Lisa; Padmanabhuni, Shanmukha S; Bjäreland, Marcus; Dalevi, Daniel

    2013-01-01

    An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity. PMID:23950964

  5. Successful Treatment of a Large Pelvic Abscess Using Intraluminal VAC: A Case Report

    PubMed Central

    Aras, Abbas; Kiziltan, Remzi; Yilmaz, Özkan; Kotan, Çetin

    2016-01-01

    The most feared complication of the surgical treatment of rectal cancer is anastomotic leakage, which is related to high rates of mortality and morbidity. Here, we present a patient who could not be treated with surgical drainage but treated by intraluminal Vacuum Associated Closure (VAC). A 34-year-old male patient was treated for rectal cancer by low anterior resection, colorectal anastomosis, and diverting ileostomy following neoadjuvant CRT. The patient reported with a postoperative anastomotic disruption and a large pelvic abscess. Due to the continuation of foul-smell drainage inspite of perianal incision and drainage, intraluminal VAC was applied and the pelvic abscess and the foul-smell were successfully treated. The presence of an adequate anal sphincter tonus is a disadvantage in anastomotic leakage, since it prevents the emptying of the intestinal content and also precludes the drainage of the pelvic abscess. The endoluminal application of VAC, similar to the results of application of VAC in open wounds, has been demonstrated to decrease fibrin and necrotic tissue in the pelvic cavity and increase granulation tissue. VAC, which has long been used in the treatment of open wounds, is a promising method in the treatment of large pelvic abscesses due to anastomotic leakage following rectum resection. PMID:27190889

  6. An Isoprenylation and Palmitoylation Motif Promotes Intraluminal Vesicle Delivery of Proteins in Cells from Distant Species

    PubMed Central

    Oeste, Clara L.; Pinar, Mario; Schink, Kay O.; Martínez-Turrión, Javier; Stenmark, Harald; Peñalva, Miguel A.; Pérez-Sala, Dolores

    2014-01-01

    The C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these selective associations is limited. Here we show, using advanced microscopy, that the isoprenylation and palmitoylation motif of human RhoB (–CINCCKVL) targets chimeric proteins to intraluminal vesicles of endolysosomes in human cells, displaying preferential co-localization with components of the late endocytic pathway. Moreover, this distribution is conserved in distant species, including cells from amphibians, insects and fungi. Blocking lipidic modifications results in accumulation of CINCCKVL chimeras in the cytosol, from where they can reach endolysosomes upon release of this block. Remarkably, CINCCKVL constructs are sorted to intraluminal vesicles in a cholesterol-dependent process. In the lower species, neither the C-terminal sequence of RhoB, nor the endosomal distribution of its homologs are conserved; in spite of this, CINCCKVL constructs also reach endolysosomes in Xenopus laevis and insect cells. Strikingly, this behavior is prominent in the filamentous ascomycete fungus Aspergillus nidulans, in which GFP-CINCCKVL is sorted into endosomes and vacuoles in a lipidation-dependent manner and allows monitoring endosomal movement in live fungi. In summary, the isoprenylated and palmitoylated CINCCKVL sequence constitutes a specific structure which delineates an endolysosomal sorting strategy operative in phylogenetically diverse organisms. PMID:25207810

  7. Intraluminal magnetisation of bowel by ferromagnetic particles for retraction and manipulation by magnetic probes.

    PubMed

    Wang, Z; André, P; McLean, D; Brown, S I; Florence, G J; Cuschieri, A

    2014-11-01

    Feasibility studies are needed to demonstrate that safe and effective manipulation of bowel during Minimal Access Surgery (MAS) can be obtained by use of magnetic force. This paper characterises two classes of magnetic particles: stainless steel microparticles (SS-μPs) and iron oxide nanoparticles (IO-nPs) in terms of their magnetisation, chemical composition, crystallinity, morphology and size distribution. Both magnetic particles were dispersed in a high viscosity biological liquid for intraluminal injection of bowel. Ex vivo porcine bowel segments were then retracted by permanent magnetic probes of 5.0 and 10mm diameter. Strong retraction forces reaching 6N maximum were obtained by magnetic fluid based on dispersion of SS-μPs. In contrast, the IO-nP-based magnetic liquid generated less attraction force, due to both lower magnetic and solution properties of the IO-nPs. The comparison of the two particles allowed the identification of the rules to engineer the next generation of particles. The results with SS-μPs provide proof on concept that intraluminal injection of magnetic fluid can generate sufficient force for efficient bowel retraction. Thereafter we shall carry out in vivo animal studies for efficacy and safety of both types of ferrofluids. PMID:25169469

  8. The Effect of Food on the Intraluminal Behavior of Abiraterone Acetate in Man.

    PubMed

    Geboers, Sophie; Stappaerts, Jef; Mols, Raf; Snoeys, Jan; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2016-09-01

    To relate the reported positive effect of food on the oral bioavailability of abiraterone to the intraluminal behavior of abiraterone acetate, an in vivo experiment was performed, in which duodenal fluids and plasma samples were collected from healthy volunteers after the administration of abiraterone acetate in fasted and postprandial conditions. The plasma concentration-time profiles confirmed the positive food effect. Nevertheless, intraduodenal concentrations of abiraterone acetate and abiraterone did not fully reflect this observation. This apparent discrepancy was explored by performing several in vitro experiments including solubility, dissolution, and transfer studies. Gastrointestinal transfer studies illustrated a positive impact of gastric processing of the abiraterone acetate formulation on the duodenal concentrations in the fasted state, which could not be observed in the postprandial condition. As the influence of gastric dissolution on the intraluminal concentrations in the small intestine declines aborally, it is most likely the superior solubility of abiraterone acetate and abiraterone in intestinal fluids of the fed state that dictates the food effect. Furthermore, N-oxide abiraterone sulfate and abiraterone sulfate appeared in the duodenum at significantly later time points than abiraterone, suggesting biliary excretion of these abiraterone metabolites; this was confirmed by in situ biliary excretion experiments in rats. PMID:27061460

  9. In vivo study of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration

    NASA Astrophysics Data System (ADS)

    Koh, H. S.; Yong, T.; Teo, W. E.; Chan, C. K.; Puhaindran, M. E.; Tan, T. C.; Lim, A.; Lim, B. H.; Ramakrishna, S.

    2010-08-01

    A novel nanofibrous construct for promoting peripheral nerve repair was fabricated and tested in a rat sciatic nerve defect model. The conduit is made out of bilayered nanofibrous membranes with the nanofibers longitudinally aligned in the lumen and randomly oriented on the outer surface. The intra-luminal guidance channel is made out of aligned nanofibrous yarns. In addition, biomolecules such as laminin and nerve growth factor were incorporated in the nanofibrous nerve construct to determine their efficacy in in vivo nerve regeneration. Muscle reinnervation, withdrawal reflex latency, histological, axon density and electrophysiology tests were carried out to compare the efficacy of nanofibrous constructs with an autograft. Our study showed mixed results when comparing the artificial constructs with an autograft. In some cases, the nanofibrous conduit with aligned nanofibrous yarn as an intra-luminal guidance channel performs better than the autograft in muscle reinnervation and withdrawal reflex latency tests. However, the axon density count is highest in the autograft at mid-graft. Functional recovery was improved with the use of the nerve construct which suggested that this nerve implant has the potential for clinical usage in reconstructing peripheral nerve defects.

  10. Quantifying the combined effects of multiple extreme floods on river channel geometry and on flood hazards

    NASA Astrophysics Data System (ADS)

    Guan, Mingfu; Carrivick, Jonathan L.; Wright, Nigel G.; Sleigh, P. Andy; Staines, Kate E. H.

    2016-07-01

    Effects of flood-induced bed elevation and channel geometry changes on flood hazards are largely unexplored, especially in the case of multiple floods from the same site. This study quantified the evolution of river channel and floodplain geometry during a repeated series of hypothetical extreme floods using a 2D full hydro-morphodynamic model (LHMM). These experiments were designed to examine the consequences of channel geometry changes on channel conveyance capacity and subsequent flood dynamics. Our results revealed that extreme floods play an important role in adjusting a river channel to become more efficient for subsequent propagation of floods, and that in-channel scour and sediment re-distribution can greatly improve the conveyance capacity of a channel for subsequent floods. In our hypothetical sequence of floods the response of bed elevation was of net degradation, and sediment transport successively weakened even with floods of the same magnitude. Changes in river channel geometry led to significant impact on flood hydraulics and thereby flood hazards. We found that flood-induced in-channel erosion can disconnect the channel from its floodplain resulting in a reduction of floodwater storage. Thus, the frequency and extent of subsequent overbank flows and floodplain inundation decreased, which reduced downstream flood attenuation and increased downstream flood hazard. In combination and in summary, these results suggest that changes in channel capacity due to extreme floods may drive changes in flood hazard. The assumption of unchanging of river morphology during inundation modelling should therefore be open to question for flood risk management.

  11. Combining Multiple Performance Measures: Do Common Approaches Undermine Districts' Personnel Evaluation Systems? CALDER Working Paper No. 118

    ERIC Educational Resources Information Center

    Hansen, Michael; Lemke, Mariann; Sorensen, Nicholas

    2014-01-01

    Teacher and principal evaluation systems now emerging in response to federal, state and/or local policy initiatives typically require that a component of teacher evaluation be based on multiple performance metrics, which must be combined to produce summative ratings of teacher effectiveness. Districts have utilized three common approaches to…

  12. Assessment of Wall Elasticity Variations on Intraluminal Haemodynamics in Descending Aortic Dissections Using a Lumped-Parameter Model

    PubMed Central

    Rudenick, Paula A.; Bijnens, Bart H.; Segers, Patrick; García-Dorado, David; Evangelista, Arturo

    2015-01-01

    Descending aortic dissection (DAD) is associated with high morbidity and mortality rates. Aortic wall stiffness is a variable often altered in DAD patients and potentially involved in long-term outcome. However, its relevance is still mostly unknown. To gain more detailed knowledge of how wall elasticity (compliance) might influence intraluminal haemodynamics in DAD, a lumped-parameter model was developed based on experimental data from a pulsatile hydraulic circuit and validated for 8 clinical scenarios. Next, the variations of intraluminal pressures and flows were assessed as a function of wall elasticity. In comparison with the most rigid-wall case, an increase in elasticity to physiological values was associated with a decrease in systolic and increase in diastolic pressures of up to 33% and 63% respectively, with a subsequent decrease in the pressure wave amplitude of up to 86%. Moreover, it was related to an increase in multidirectional intraluminal flows and transition of behaviour as 2 parallel vessels towards a vessel with a side-chamber. The model supports the extremely important role of wall elasticity as determinant of intraluminal pressures and flow patterns for DAD, and thus, the relevance of considering it during clinical assessment and computational modelling of the disease. PMID:25881158

  13. Assessment of wall elasticity variations on intraluminal haemodynamics in descending aortic dissections using a lumped-parameter model.

    PubMed

    Rudenick, Paula A; Bijnens, Bart H; Segers, Patrick; García-Dorado, David; Evangelista, Arturo

    2015-01-01

    Descending aortic dissection (DAD) is associated with high morbidity and mortality rates. Aortic wall stiffness is a variable often altered in DAD patients and potentially involved in long-term outcome. However, its relevance is still mostly unknown. To gain more detailed knowledge of how wall elasticity (compliance) might influence intraluminal haemodynamics in DAD, a lumped-parameter model was developed based on experimental data from a pulsatile hydraulic circuit and validated for 8 clinical scenarios. Next, the variations of intraluminal pressures and flows were assessed as a function of wall elasticity. In comparison with the most rigid-wall case, an increase in elasticity to physiological values was associated with a decrease in systolic and increase in diastolic pressures of up to 33% and 63% respectively, with a subsequent decrease in the pressure wave amplitude of up to 86%. Moreover, it was related to an increase in multidirectional intraluminal flows and transition of behaviour as 2 parallel vessels towards a vessel with a side-chamber. The model supports the extremely important role of wall elasticity as determinant of intraluminal pressures and flow patterns for DAD, and thus, the relevance of considering it during clinical assessment and computational modelling of the disease. PMID:25881158

  14. Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response.

    PubMed

    Dong, Xiaoxian; Liao, Yuning; Liu, Ningning; Hua, Xianliang; Cai, Jianyu; Liu, Jinbao; Huang, Hongbiao

    2016-09-01

    Bortezomib (Bor), a proteasome inhibitor, has marked therapeutic effects in multiple myeloma (MM), and its synergistic effects with other anticancer agents have been widely investigated. In the present study, endoplasmic reticulum (ER) stress was the target of the treatment strategy; anacardic acid (AA) and Bor induce ER stress, resulting in apoptosis of multiple myeloma cells. AA/Bor combination therapy exhibited overt cytotoxicity in MM cells, by synergistically reducing cell growth and promoting cell death. Notably, expression levels of the stress‑associated molecules binding protein, phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4 (ATF4) and CCAAT‑enhancer binding protein homologous protein (CHOP) were increased following treatment. AA/Bor combination therapy‑induced U266 cell cytotoxicity was partially reversed by ATF4 gene silencing and slightly enhanced by CHOP knockdown. The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment. PMID:27430733

  15. Combined Acquisition Technique (CAT) for Neuroimaging of Multiple Sclerosis at Low Specific Absorption Rates (SAR)

    PubMed Central

    Biller, Armin; Choli, Morwan; Blaimer, Martin; Breuer, Felix A.; Jakob, Peter M.; Bartsch, Andreas J.

    2014-01-01

    Purpose To compare a novel combined acquisition technique (CAT) of turbo-spin-echo (TSE) and echo-planar-imaging (EPI) with conventional TSE. CAT reduces the electromagnetic energy load transmitted for spin excitation. This radiofrequency (RF) burden is limited by the specific absorption rate (SAR) for patient safety. SAR limits restrict high-field MRI applications, in particular. Material and Methods The study was approved by the local Medical Ethics Committee. Written informed consent was obtained from all participants. T2- and PD-weighted brain images of n = 40 Multiple Sclerosis (MS) patients were acquired by CAT and TSE at 3 Tesla. Lesions were recorded by two blinded, board-certificated neuroradiologists. Diagnostic equivalence of CAT and TSE to detect MS lesions was evaluated along with their SAR, sound pressure level (SPL) and sensations of acoustic noise, heating, vibration and peripheral nerve stimulation. Results Every MS lesion revealed on TSE was detected by CAT according to both raters (Cohen’s kappa of within-rater/across-CAT/TSE lesion detection κCAT = 1.00, at an inter-rater lesion detection agreement of κLES = 0.82). CAT reduced the SAR burden significantly compared to TSE (p<0.001). Mean SAR differences between TSE and CAT were 29.0 (±5.7) % for the T2-contrast and 32.7 (±21.9) % for the PD-contrast (expressed as percentages of the effective SAR limit of 3.2 W/kg for head examinations). Average SPL of CAT was no louder than during TSE. Sensations of CAT- vs. TSE-induced heating, noise and scanning vibrations did not differ. Conclusion T2−/PD-CAT is diagnostically equivalent to TSE for MS lesion detection yet substantially reduces the RF exposure. Such SAR reduction facilitates high-field MRI applications at 3 Tesla or above and corresponding protocol standardizations but CAT can also be used to scan faster, at higher resolution or with more slices. According to our data, CAT is no more uncomfortable than TSE scanning. PMID

  16. In silico identification of breast cancer genes by combined multiple high throughput analyses.

    PubMed

    Shen, Dejun; He, Jianbo; Chang, Helena R

    2005-02-01

    that the combined multiple high throughput analyses is an effective data mining strategy in cancer gene identification. This approach may improve the usage of public available genomic data through strategic data mining of high throughput analysis. PMID:15647832

  17. Management of advanced tracheal collapse in dogs using intraluminal self-expanding biliary wallstents.

    PubMed

    Moritz, Andreas; Schneider, Matthias; Bauer, Natali

    2004-01-01

    Twenty-four client-owned dogs with tracheal collapse refractory to conventional treatment underwent management with an intraluminal self-expanding stainless-steel endoprosthesis (Wallstent). Initial improvement of clinical signs was observed in 95.8% of the dogs. Two dogs (8.3%) died within a median interval of 6 days after stent implantation due to incorrect placement and size of the stent and emphysema, respectively. A dry cough occurred temporarily in most of the patients. One dog each (4.1%) suffered mild transient tracheal hemorrhage and pneumomediastinum. The results showed that the initial survival rate of intraluminal stabilization was comparable with surgical implantation of extratracheal prostheses. Clinical reevaluation was performed in 18 dogs within a median interval of 68 days after treatment. Of the dogs treated, 30.4% were reported to be asymptomatic after stent implantation, 60.9% improved markedly, and 4.3% remained symptomatic. In all patients undergoing endoscopy, the Wallstents were almost completely covered with tracheal epithelium. A median shortening of 27.3% of the endoprosthesis within a median interval of 175 days after stent implantation in 15 of 18 dogs was noted. The shortening was associated with clinical signs in 2 patients. In 5 dogs, steroid-responsive granuloma formation resulted in a severe reduction of the tracheal lumen in 3 patients. The results suggest that implantation of Wallstents was minimally invasive and provided stabilization of collapsed thoracic tracheal portions in addition to the cervical part of the trachea. This minimally invasive method for the management of severe tracheal collapse therefore provides an attractive alternative to surgery. PMID:14765729

  18. Strategies to reduce intraluminal clot formation in endoscopically harvested saphenous veins

    PubMed Central

    Brown, Emile N.; Kon, Zachary N.; Tran, Richard; Burris, Nicholas S.; Gu, Junyen; Laird, Patrick; Brazio, Philip S.; Kallam, Seeta; Schwartz, Kimberly; Bechtel, Lisa; Joshi, Ashish; Zhang, Shaosong; Poston, Robert S.

    2010-01-01

    Objective Residual clot strands within the excised saphenous vein are an increasingly recognized sequela of endoscopic vein harvest. We hypothesized that endoscopic visualization facilitated by sealed carbon dioxide insufflation causes stagnation of blood within the saphenous vein. In the absence of prior heparin administration, this stasis provokes clot formation. Methods Forty consecutive patients having coronary artery bypass grafting underwent endoscopic vein harvest using sealed (Guidant VasoView, n = 30; Guidant Corp, Minneapolis, Minn) or open (Datascope ClearGlide, n = 10; Datascope Corp, Montvale, NJ) carbon dioxide insufflation followed by ex vivo assessment of intraluminal saphenous vein clot via optical coherence tomography. In the sealed carbon dioxide insufflation groups, clot formation was compared with (preheparinized, n = 20) and without (control, n = 10) heparin administration before endoscopic vein harvest, either at a fixed dose or titrated to an activated clotting time greater than 300 seconds. Risk factors for clot formation were assessed. Results Residual saphenous vein clot was a universal finding in control veins (sealed carbon dioxide insufflation endoscopic vein harvest without preheparinization). At either dose used, heparin given before endoscopic vein harvest significantly decreased saphenous vein clot burden. A similar reduction in clot was observed when using open carbon dioxide insufflation endoscopic vein harvest without preheparinization. Intraoperative blood loss and blood product requirements were similar in all groups. Patient age and preoperative maximum amplitude of the thrombelastography tracing showed a linear correlation with saphenous vein clot volume. Conclusion By enabling the quantification of this issue as never before possible, optical coherence tomography screening revealed that intraluminal saphenous vein clot is frequently found after endoscopic vein harvest. Systemic heparinization before harvest or an open

  19. The use of intraluminal strain gauges for recording ambulant small bowel motility.

    PubMed

    Gill, R C; Kellow, J E; Browning, C; Wingate, D L

    1990-04-01

    Perfused-tube manometry has hitherto been the standard technique for recording intraluminal intestinal pressure in humans, but it is unsuitable for ambulant use. The aim of our study was to evaluate the ability of resistive strain gauge transducers attached to a fine catheter to detect pressure change. Simultaneous strain gauge and perfused-tube manometry was performed on six fasting subjects; in four, strain gauge activation was continuous and in two, the transducers were activated in a pulsed mode with data encoded as a pulse train with an approximate frequency of 20 Hz. Eight thousand eight hundred eighty-eight pressure waves were recorded by strain gauge, of which 96% were detected by perfused-tube manometry. There was good agreement in both phases II and III of the migrating motor complex. The amplitude of pressure waves recorded by strain gauge was slightly but significantly greater. A proportion (14-17%) of pressure waves recorded by strain gauge were bifid; this was not seen with the perfused tube. These differences are best explained by the greater sensitivity and more rapid rise time of the strain gauges. There was no loss of fidelity in the pulse-interval recording mode. A seventh subject underwent a continuous 72-h recording with the strain gauge catheter attached to a battery-operated encoder and magnetic tape cassette recorder and was freely ambulant during this period. The procedure was well tolerated and motility patterns could be clearly identified. We conclude that intraluminal strain gauge catheters are suitable for prolonged use in ambulant subjects and produce data that are closely comparable to the data acquired from perfused-tube manometry under laboratory conditions. PMID:2333973

  20. [Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].

    PubMed

    Ooe, Asako; Suganuma, Yasushi

    2016-03-01

    We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients. PMID:27067853

  1. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension.

    PubMed

    Chrysant, Steven G

    2011-11-01

    Hypertension (HTN) affects an estimated 76.4 million US adults. Despite improvements in blood pressure (BP) control rates and the availability of effective antihypertensive agents, only 50% of these individuals achieve BP control. It is now recognized that many patients will require ≥ 2 antihypertensive agents to achieve BP control. Both the current US and reappraisal of the 2007 European guidelines include dual-combination regimens among recommended treatments for initial HTN therapy. For patients requiring 3 drugs, the combination of agents with complementary mechanisms of action (ie, renin-angiotensin-aldosterone system blocker, calcium channel blocker, and diuretic) has been recognized as rational and effective. Three single-pill triple-drug combinations have recently been approved for use in HTN in the United States: valsartan (VAL)/amlodipine (AML)/hydrochlorothiazide (HCTZ); olmesartan medoxomil (OM)/AML/HCTZ; and aliskiren (ALI)/VAL/HCTZ. Triple-combination regimens have resulted in a greater proportion of patients achieving BP control compared with dual-combination regimens, with significantly lower BP levels documented after only 2 weeks at maximum doses. Single-pill combinations offer convenience to address barriers to BP control such as poor adherence to therapy and therapeutic inertia. Additional benefits of combining antihypertensive agents from different classes include improved efficacy, safety, and reduction of cardiovascular risk. In patients with essential HTN for whom dual therapy is inadequate, single-pill triple-drug therapy can offer a simplified and effective treatment strategy. PMID:22104451

  2. A combined limit on the neutrino mass from neutrinoless double-beta decay searches in multiple isotopes

    NASA Astrophysics Data System (ADS)

    Guzowski, P.

    2016-05-01

    We set a combined limit on the effective Majorana neutrino mass mββ from experimental searches for neutrinoless double-beta decay of multiple isotopes. The limits on mββ range between 130-310 meV, depending on the choice of nuclear matrix element calculation. The limits on mββ can also be translated into a limit on the neutrino mass and mixing parameters of a fourth sterile neutrino.

  3. Multiple resistance of horseweed to glyphosate and paraquat and its control with paraquat and metribuzin combinations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Greenhouse and field studies were conducted in 2007 and 2008 to investigate possible multiple-resistance of horseweed to paraquat and glyphosate, and to evaluate the effect of the addition of metribuzin to paraquat on control of paraquat-resistant horseweed. Results indicated that the GR50 (herbicid...

  4. Rainfall estimation by rain gauge-radar combination: A concurrent multiplicative-additive approach

    NASA Astrophysics Data System (ADS)

    GarcíA-Pintado, Javier; Barberá, Gonzalo G.; Erena, Manuel; Castillo, Victor M.

    2009-01-01

    A procedure (concurrent multiplicative-additive objective analysis scheme [CMA-OAS]) is proposed for operational rainfall estimation using rain gauges and radar data. On the basis of a concurrent multiplicative-additive (CMA) decomposition of the spatially nonuniform radar bias, within-storm variability of rainfall and fractional coverage of rainfall are taken into account. Thus both spatially nonuniform radar bias, given that rainfall is detected, and bias in radar detection of rainfall are handled. The interpolation procedure of CMA-OAS is built on Barnes' objective analysis scheme (OAS), whose purpose is to estimate a filtered spatial field of the variable of interest through a successive correction of residuals resulting from a Gaussian kernel smoother applied on spatial samples. The CMA-OAS, first, poses an optimization problem at each gauge-radar support point to obtain both a local multiplicative-additive radar bias decomposition and a regionalization parameter. Second, local biases and regionalization parameters are integrated into an OAS to estimate the multisensor rainfall at the ground level. The procedure is suited to relatively sparse rain gauge networks. To show the procedure, six storms are analyzed at hourly steps over 10,663 km2. Results generally indicated an improved quality with respect to other methods evaluated: a standard mean-field bias adjustment, a spatially variable adjustment with multiplicative factors, and ordinary cokriging.

  5. Tracking Iron in Multiple Sclerosis: A Combined Imaging and Histopathological Study at 7 Tesla

    ERIC Educational Resources Information Center

    Bagnato, Francesca; Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

    2011-01-01

    Previous authors have shown that the transverse relaxivity R[subscript 2][superscript *] and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a…

  6. INTRODUCTION TO A COMBINED MULTIPLE LINEAR REGRESSION AND ARMA MODELING APPROACH FOR BEACH BACTERIA PREDICTION

    EPA Science Inventory

    Due to the complexity of the processes contributing to beach bacteria concentrations, many researchers rely on statistical modeling, among which multiple linear regression (MLR) modeling is most widely used. Despite its ease of use and interpretation, there may be time dependence...

  7. Combining Multiple Measures of Students' Opportunities to Develop Analytic, Text-Based Writing Skills

    ERIC Educational Resources Information Center

    Correnti, Richard; Matsumura, Lindsay Clare; Hamilton, Laura S.; Wang, Elaine

    2012-01-01

    Guided by evidence that teachers contribute to student achievement outcomes, researchers have been reexamining how to study instruction and the classroom opportunities teachers create for students. We describe our experience measuring students' opportunities to develop analytic, text-based writing skills. Utilizing multiple methods of data…

  8. Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

    PubMed Central

    Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

    2015-01-01

    In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

  9. A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

    PubMed Central

    Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

    2012-01-01

    Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional

  10. Laparoscopic Management of Symptomatic Multiple Hepatic Cysts: a Combination of Deroofing and Radical Excision

    PubMed Central

    Palanivelu, Chinnusamy; Senthilkumar, Rangasamy; Madankumar, Madhupalayam Velusamy

    2007-01-01

    Background: Liver cysts have been estimated to occur in 5% of the population. Multiple liver cysts can also be part of the polycystic disease complex. Only symptomatic or complicated cysts need surgery. Traditionally, laparotomy is the procedure of choice. We present our experiences with laparoscopic management of both symptomatic multiple liver cysts and polycystic liver disease. Methods: Between 1995 and 2006, we treated 12 patients with large, multiple liver cysts, including 4 cases of polycystic liver disease. Most of the patients were elderly males. The lung and other organs were not involved in any case. Laparoscopic deroofing or radical excision with omentoplasty was successfully performed in these patients. Results: Postoperatively, 4 patients had fluid draining through the drainage tube for an average of 10 days. One patient had ascites that resolved spontaneously. Cysts recurred in 5 patients. Discussion: There are not many reports in the literature regarding large series of patients, further confirming the rarity of the disease. Liver cysts can occur as a part of polycystic renal and lung disease or isolated to the liver alone. Laparoscopic deroofing is the ideal treatment for nonpolycystic liver disease, and laparoscopic radical excision is ideal for polycystic liver disease. Simple needle aspiration or sclerotherapy is inadequate as recurrence is almost 100%. Conclusion: Currently, laparoscopy scores over laparotomy for the treatment of nonparasitic liver cysts as evidenced by this and other studies. PMID:18237512

  11. Targeting multiple dyslipidemias with fixed combinations--focus on extended release niacin and simvastatin.

    PubMed

    Pandian, Anbu; Arora, Anjali; Sperling, Laurence S; Khan, Bobby V

    2008-01-01

    Dyslipidemia is a major risk factor in the initiation and progression of cardiovascular diseases such as atherosclerosis. Several pharmacological agents have been developed over the past 50 years which target various lipid components such as low density lipoprotein (LDL) cholesterol, triglyceride, and high density lipoprotein (HDL) cholesterol. Similar to other risk factors such as hypertension and diabetes mellitus, the management of dyslipidemia can be complicated and may require combination therapy for effective treatment. This review discusses the biochemical mechanisms of action and clinical uses for simvastatin (the most widely available and commercially prescribed statin) and niacin, and the combination of these agents in the management and treatment of dyslipidemia. PMID:19183748

  12. Assessment of tissue blood flow following small artery welding with an intraluminal dissolvable stent.

    PubMed

    He, F C; Wei, L P; Lanzetta, M; Owen, E R

    1999-01-01

    Using the technique of radioactive 51Cr-labeled biological microspheres, this study evaluated arterial blood flow following small vessel anastomosis by CO2 laser welding and a dissolvable stent in the lumen. A total of 30 Sprague-Dawley rats were divided into two groups. Group A: 11 rats had their femoral arteries ligated on one side. The contralateral side served as a control, with the artery transected and repaired using conventional microsuturing. Group B: 19 rats had their femoral arteries transected and repaired using CO2 laser welding and an intraluminal dissolvable stent technique. The contralateral side was again used as a control using conventional microsuturing. At 1 hr postoperatively, 51Cr-labeled biological microspheres were injected centripetally into the left common carotid artery and the legs and thighs immediately harvested for measurement of radioactivity. All repaired arteries were patent (30/30 in the microsuturing group and 19/19 in the stented welding group), with no detectable stenosis or dilation at the repaired site. Statistical analysis showed that tissue radioactivity (cpm/g) in the ligated group (3,972 +/- 384 in thighs and 3,142 +/- 742 in legs) was significantly lower than in the microsuturing group (7,132 +/- 1,723 in thighs and 6,557 +/- 1,469 in legs) (P < 0.01). In the ligated group, a significant reduction of blood flow was seen in the legs when compared with the thighs (P < 0.05). There was no significant difference in radioactivity when comparing the microsuturing control with the stented welding group, in both thighs (7,064 +/- 2,599 and 7,006 +/- 2,406, respectively; P > 0.05) and legs (6,386 +/- 1,703 and 6,288 +/- 1,757, respectively; P > 0.05). This study provided evidence that the dissolvable stent placed intraluminally does not impair blood circulation and that when coupled with CO2 laser welding offers a high-quality alternative to conventional small vessel anastomosis. PMID:10231124

  13. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington,...

  14. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington,...

  15. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington,...

  16. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington,...

  17. 5 CFR 591.216 - How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false How does OPM combine survey data for the DC area and for COLA areas with multiple survey areas? 591.216 Section 591.216 Administrative... combine survey data for the DC area and for COLA areas with multiple survey areas? (a) Washington,...

  18. Combination therapy of Lovastatin and Rolipram Provides Neuroprotection and Promotes Neurorepair in Inflammatory Demyelination Model of Multiple Sclerosis

    PubMed Central

    Paintlia, Ajaib S; Paintlia, Manjeet K; Singh, Inderjit; Skoff, Robert B; Singh, Avtar K

    2009-01-01

    Drug combination therapies for central nervous system (CNS) demyelination diseases including multiple sclerosis (MS) are gaining momentum over monotherapy. Over the past decade, both in vitro and in vivo studies established that statins (HMG-CoA reductase inhibitors) and rolipram (phosphodiesterase-4 inhibitor; blocks the degradation of intracellular cyclic AMP) can prevent the progression of MS in affected individuals via different mechanisms of action. In the present study, we evaluated the effectiveness of lovastatin and rolipram in combination therapy to promote neurorepair in an inflammatory CNS demyelination model of MS, experimental autoimmune encephalomyelitis (EAE). Combination treatment with suboptimal doses of these drugs in an established case of EAE (clinical disease score ≥2.0) significantly attenuated the infiltration of inflammatory cells and protected myelin sheath and axonal integrity in the CNS. It was accompanied with elevated level of cyclic AMP and activation of its associated protein kinase A. Interestingly, combination treatment with these drugs impeded neurodegeneration and promoted neurorepair in established EAE animals (clinical disease score ≥3.5) as verified by quantitative real-time polymerase chain reaction, immunohistochemistry, and electron microscopic analyses. These effects of combination therapy were minimal and/or absent with either drug alone in these settings. Together, these data suggest that combination therapy with lovastatin and rolipram has the potential to provide neuroprotection and promote neurorepair in MS, and may have uses in other related CNS demyelinating diseases. PMID:18720408

  19. Combining Multiple External Representations and Refutational Text: An Intervention on Learning to Interpret Box Plots

    ERIC Educational Resources Information Center

    Lem, Stephanie; Kempen, Goya; Ceulemans, Eva; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

    2015-01-01

    Box plots are frequently misinterpreted and educational attempts to correct these misinterpretations have not been successful. In this study, we used two instructional techniques that seemed powerful to change the misinterpretation of the area of the box in box plots, both separately and in combination, leading to three experimental conditions,…

  20. Ultramini nephrostomy tract combined with flexible ureterorenoscopy for the treatment of multiple renal calculi in paediatric patients

    PubMed Central

    Yang, Wen Zeng; Zhang, Yanqiao; An, Feng; Wei, Ruojing; Li, Yu; Zhang, Haisong

    2015-01-01

    Purpose To assess the safety and efficacy of an ultramini nephrostomy tract, which we were using for the first time, combined with flexible ureterorenoscopy (URS) in the treatment of pediatric patients with multiple renal calculi. Materials and Methods Twenty pediatric patients (age, ≤6 years) underwent ultramini percutaneous nephrolithotomy (PCNL) combined with flexible URS. The group had multiple renal calculi, which were bilateral in 3 cases and were located in a total of 23 sites. The calculi were located in 2 calyces in 10 cases, scattered in more than 2 calyces in 7 cases, and limited to 1 calyx in 3 cases. The average patient age was 37.35 months (range, 14-68 months). The average stone diameter was 2.0 cm (range, 1-3.0 cm). In all patients, an ultramini nephrostomy tract was established under ultrasound guidance (dilated to F10) with simultaneous sheath placement. The flexible URS was placed into the collecting system during holmium laser lithotripsy. Results When ultramini PCNL was combined with flexible ureterorenoscopic holmium laser lithotripsy, the complete stone-free rate was 87% (20/23). The average level of hemoglobin decreased to 1.0 g/dL after the operation. No blood transfusions were needed. Levels of blood urea nitrogen, creatinine, and C-reactive protein were not significantly different before and after the operation. The average duration of hospitalization was approximately 4.85 days, and all cases were followed up for 6 to 12 months. No complications were found. Conclusions Ultramini PCNL combined with flexible ureterorenoscopic holmium laser lithotripsy is a safe and effective treatment for children with multiple renal calculi. PMID:26175871

  1. Combined heterogeneous metal/chiral amine: multiple relay catalysis for versatile eco-friendly synthesis.

    PubMed

    Deiana, Luca; Jiang, Yan; Palo-Nieto, Carlos; Afewerki, Samson; Incerti-Pradillos, Celia A; Verho, Oscar; Tai, Cheuk-Wai; Johnston, Eric V; Córdova, Armando

    2014-03-24

    Herein is described a versatile and broad synergistic strategy for expansion of chemical space and the synthesis of valuable molecules (e.g. carbocycles and heterocycles), with up to three quaternary stereocenters, in a highly enantioselective fashion from simple alcohols (31 examples, 95:5 to >99.5:0.5 e.r.) using integrated heterogeneous metal/chiral amine multiple relay catalysis and air/O₂ as the terminal oxidant. A novel highly 1,4-selective heterogeneous metal/amine co-catalyzed hydrogenation of enals was also added to the relay catalysis sequences. PMID:24677482

  2. In Vivo Experiments with Intraluminal Ultrasound Applicator Compatible with ``Real-Time'' MR Temperature Mapping, designed for Oesophagus Tumour Ablation

    NASA Astrophysics Data System (ADS)

    Melodelima, D.; Salomir, R.; Mougenot, C.; Theillère, Y.; Moonen, C.; Cathignol, D.

    2005-03-01

    High intensity ultrasound has shown considerable ability to produce precise and deep thermal coagulation necrosis. Focused, cylindrical, spherical or plane transducers have been used to induce high temperature elevation in tissues, in order to coagulate proteins and kill cells. Magnetic Resonance Imaging (MRI) has been used, with focused transducers and cylindrical interstitial applicators, to monitor temperature distribution and provide temperature feedback control during heating procedures. The active part of intraluminal applicators is positioned very close to the target region. It is therefore essential to provide accurate monitoring of heat deposition in the tissue layer near the transducer, in order to control the extension of coagulation necrosis. The purpose of this study was to develop a 10-mm diameter intraluminal ultrasound applicator, designed to treat oesophageal cancers and compatible with "real-time" MR temperature mapping. The ultrasound applicator was tested in vivo under real time, PRF based, fast MR temperature monitoring. Experiments were performed in vivo on pig oesophagus. Respiratory-gated, MR thermometry was performed with segmented EPI gradient echo sequences. Post treatment follow up was performed with MRI in oesophagus and liver. Excellent MR compatibility was demonstrated. Thermal lesions identified on post-treatment follow up showed good correlation with on line MR thermometry data. This study demonstrated the feasibility of oesophageal thermal ablation using intraluminal ultrasound and on line MR temperature monitoring.

  3. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

    PubMed Central

    Kloster, Brian O.; Lund, Lars; Lindholt, Jes S.

    2016-01-01

    Background The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. Methods The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. Results All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. Conclusion In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms. PMID:27144001

  4. Shape-based discriminative analysis of combined bilateral hippocampi using multiple object alignment

    NASA Astrophysics Data System (ADS)

    Shen, Li; Makedon, Fillia; Saykin, Andrew

    2004-05-01

    Shape analysis of hippocampi in schizophrenia has been preformed previously using the spherical harmonic SPHARM description. In these studies, the left and right hippocampi are aligned independently and the spatial relation between them is not explored. This paper presents a new SPHARM-based technique which examines not only the individual shape information of the two hippocampi but also the spatial relation between them. The left and right hippocampi are treated as a single shape configuration. A ploy-shape alignment algorithm is developed for aligning configurations of multiple SPHARM surfaces as follows: (1) the total volume is normalized; (2) the parameter space is aligned for creating the surface correspondence; (3) landmarks are created by a uniform sampling of multiple surfaces for each configuration; (4) a quaternion-based algorithm is employed to align each landmark representation to the mean configuration through the least square rotation and translation iteratively until the mean converges. After applying the poly-shape alignment algorithm, a point distribution model is applied to aligned landmarks for feature extraction. Classification is performed using Fisher's linear discriminant with an effective feature selection scheme. Applying the above procedure to our hippocampal data (14 controls versus 25 schizophrenics, all right-handed males), we achieve the best cross-validation accuracy of 92%, supporting the idea that the whole shape configuration of the two hippocampi provides valuable information in detecting schizophrenia. The results of an ROC analysis and a visualization of discriminative patterns are also included.

  5. Synergistic Combinations of Multiple Chemotherapeutic Agents in High Capacity Poly(2-oxazoline) Micelles

    PubMed Central

    Han, Yingchao; He, Zhijian; Schulz, Anita; Bronich, Tatiana K.; Jordan, Rainer; Luxenhofer, Robert; Kabanov, Alexander V.

    2012-01-01

    Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multi-drug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt.% drug per final formulation. Multi-drug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells. PMID:22681126

  6. [The diagnostic impact and limitations of 24 hour pH monitoring with multichannel intraluminal impedance].

    PubMed

    Korszun, Karolina; Dyrla, Przemysław; Wojtuń, Stanisław; Gil, Jerzy

    2014-08-01

    Gastroesophageal reflux disease (GERD) is a result of reflux of gastric contents into the esophagus. Gastroscopy is often the first examination performed in GERD diagnosis. Some patients have macroscopic lesions, namely erosions, in the esophagus above the cardia of stomach. It enables to diagnose gastroesophageal reflux disease. However, many patients have no macroscopic lesions of the esophageal mucosa in endoscopy. That is why 24-hour pH monitoring with multichannel intraluminal impedance is the gold standard in diagnosis establishing of GERD and make feasible to distinguish acid, weakly acid and nonacid reflux and its correlation with reported symptoms. Impedance-pH is used to establish diagnosis of GERD, in patient qualification to anti-reflux surgery, to find the cause of not efficient reflux disease treatment as well as the cause of extra-esophageal symptoms of reflux disease. During impedance-pH test catheter connected with the recorder is placed in patient's esophagus. Recorded data is analyzed with the computer program. The examination is safe, the only complication that can occur is nasal bleeding, which can be a result of mucosa damage caused while catheter implementation. Nowadays disposable catheters are used, that excludes the risk of catheter related infection. On the basis of pH-impedance results it is possible to divide patients into 3 groups: patients with functional heartburn, patients with esophageal hypersensitivity and abnormal esophageal acid exposure. This classification is very helpful in the choice of treatment - antireflux surgery, proton pump inhibitor or prokinetic therapy. PMID:25252438

  7. Added Value of pH Multichannel Intraluminal Impedance in Adults Operated for Esophageal Atresia.

    PubMed

    Gatzinsky, Vladimir; Andersson, Olof; Eriksson, Anders; Jönsson, Linus; Abrahamsson, Kate; Sillén, Ulla

    2016-04-01

    Background Gastroesophageal reflux (GER) and dysphagia are common following repaired esophageal atresia (EA). The risk of esophagitis and Barrett esophagus is increased compared with the general population. As yet, the causes are not fully explained. Purpose The aim of this study was to investigate how GER, measured by pH multichannel intraluminal impedance (pH-MII), is correlated to the esophageal symptoms and histological findings. Methods Twenty-nine adult subjects operated for EA in Gothenburg from 1968 to 1983 were evaluated with pH-MII, manometry, and gastroscopy. Results pH-MII was performed in 15, manometry in 19, and gastroscopy in 24 subjects. Eleven subjects displayed pathological reflux parameters of any kind, mainly nonacid reflux (10/15). Dysphagia correlated to the number of weakly acidic reflux episodes. Lower esophageal sphincter (LES) incompetence, which correlated to a pathological number of acid reflux episodes (p = 0.012), was noted in 21/24 subjects, but the majority had a normal resting pressure. Esophagitis was present in 14/24, two of whom had Barrett esophagus. Histological changes correlated to the reflux index and the number of weakly acidic reflux episodes (p = 0.028 and 0.040) and tended to correlate to dysphagia (p = 0.052). Conclusion pH-MII adds further information when it comes to explaining what causes symptoms and esophageal histological changes in adults operated for EA. PMID:25643247

  8. Impact of poroelasticity of intraluminal thrombus on wall stress of abdominal aortic aneurysms

    PubMed Central

    2012-01-01

    Background The predictions of stress fields in Abdominal Aortic Aneurysm (AAA) depend on constitutive descriptions of the aneurysm wall and the Intra-luminal Thrombus (ILT). ILT is a porous diluted structure (biphasic solid–fluid material) and its impact on AAA biomechanics is controversially discussed in the literature. Specifically, pressure measurements showed that the ILT cannot protect the wall from the arterial pressure, while other (numerical and experimental) studies showed that at the same time it reduces the stress in the wall. Method To explore this phenomenon further a poroelastic description of the ILT was integrated in Finite Element (FE) Models of the AAA. The AAA model was loaded by a pressure step and a cyclic pressure wave and their transition into wall tension was investigated. To this end ILT’s permeability was varied within a microstructurally motivated range. Results The two-phase model verified that the ILT transmits the entire mean arterial pressure to the wall while, at the same time, it significantly reduces the stress in the wall. The predicted mean stress in the AAA wall was insensitive to the permeability of the ILT and coincided with the results of AAA models using a single-phase ILT description. Conclusion At steady state, the biphasic ILT behaves like a single-phase material in an AAA model. Consequently, computational efficient FE single-phase models, as they have been exclusively used in the past, accurately predict the wall stress in AAA models. PMID:22931215

  9. Can intraluminal devices prevent or reduce colorectal anastomotic leakage: A review

    PubMed Central

    Morks, Annelien N; Havenga, Klaas; Ploeg, Rutger J

    2011-01-01

    Colorectal anastomotic leakage is a serious complication of colorectal surgery, leading to high morbidity and mortality rates. In recent decades, many strategies aimed at lowering the incidence of anastomotic leakage have been examined. The focus of this review will be on mechanical aids protecting the colonic anastomosis against leakage. A literature search was performed using MEDLINE, EMBASE, and The Cochrane Collaborative library for all papers related to prevention of anastomotic leakage by placement of a device in the colon. Devices were categorised as decompression devices, intracolonic devices, and biodegradable devices. A decompression device functions by keeping the anal sphincter open, thereby lowering the intraluminal pressure and lowering the pressure on the anastomosis. Intracolonic devices do not prevent the formation of dehiscence. However, they prevent the faecal load from contacting the anastomotic site, thereby preventing leakage of faeces into the peritoneal cavity. Many attempts have been made to find a device that decreases the incidence of AL; however, to date, none of the devices have been widely accepted. PMID:22110276

  10. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI. PMID:26726878

  11. Association of Intraluminal Thrombus, Hemodynamic Forces, and Abdominal Aortic Aneurysm Expansion Using Longitudinal CT Images.

    PubMed

    Zambrano, Byron A; Gharahi, Hamidreza; Lim, ChaeYoung; Jaberi, Farhad A; Choi, Jongeun; Lee, Whal; Baek, Seungik

    2016-05-01

    While hemodynamic forces and intraluminal thrombus (ILT) are believed to play important roles on abdominal aortic aneurysm (AAA), it has been suggested that hemodynamic forces and ILT also interact with each other, making it a complex problem. There is, however, a pressing need to understand relationships among three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA prognosis. Hence this study used longitudinal computer tomography scans from 14 patients and analyzed the relationship between them. Hemodynamic forces, represented by wall shear stress (WSS), were obtained from computational fluid dynamics; ILT accumulation was described by ILT thickness distribution changes between consecutives scans, and ILT accumulation and AAA expansion rates were estimated from changes in ILT and AAA volume. Results showed that, while low WSS was observed at regions where ILT accumulated, the rate at which ILT accumulated occurred at the same rate as the aneurysm expansion. Comparison between AAAs with and without thrombus showed that aneurysm with ILT recorded lower values of WSS and higher values of AAA expansion than those without thrombus. Findings suggest that low WSS may promote ILT accumulation and submit the idea that by increasing WSS levels ILT accumulation may be prevented. PMID:26429788

  12. A Computational Model of Biochemomechanical Effects of Intraluminal Thrombus on the Enlargement of Abdominal Aortic Aneurysms.

    PubMed

    Virag, Lana; Wilson, John S; Humphrey, Jay D; Karšaj, Igor

    2015-12-01

    Abdominal aortic aneurysms (AAAs) typically develop an intraluminal thrombus (ILT), yet most computational models of AAAs have focused on either the mechanics of the wall or the hemodynamics within the lesion, both in the absence of ILT. In the few cases wherein ILT has been modeled directly, as, for example, in static models that focus on the state of stress in the aortic wall and the associated rupture risk, thrombus has been modeled as an inert, homogeneous, load-bearing material. Given the biochemomechanical complexity of an ILT, there is a pressing need to consider its diverse effects on the evolving aneurysmal wall. Herein, we present the first growth and remodeling model that addresses together the biomechanics, mechanobiology, and biochemistry of thrombus-laden AAAs. Whereas it has been shown that aneurysmal enlargement in the absence of ILT depends primarily on the stiffness and turnover of fibrillar collagen, we show that the presence of a thrombus within lesions having otherwise the same initial wall composition and properties can lead to either arrest or rupture depending on the biochemical effects (e.g., release of proteases) and biomechanical properties (e.g., stiffness of fibrin) of the ILT. These computational results suggest that ILT should be accounted for when predicting the potential enlargement or rupture risk of AAAs and highlight specific needs for further experimental and computational research. PMID:26070724

  13. High-dose-rate intraluminal brachytherapy for paraneoplastic autoimmune multiorgan syndrome

    PubMed Central

    Lee, Sun-Young; Kim, Jong-Hyun; Cho, Dong-Hyu

    2016-01-01

    Paraneoplastic autoimmune multiorgan syndrome (PAMS), also known as paraneoplasic pemphigus, involves the skin, internal organs and mucosa. PAMS-associated mortality may occur as a result of autoantibody formation against internal tumors and their infiltration into organs other than the skin lesions that characterize PAMS. The most common symptoms of PAMS include pain associated with continuous oral ulceration and resistance to pharmacological treatment. The present study reports the case of a 42-year-old female patient who was admitted with an 8-month history of erosive skin lesions within the trunk region, oral mucosa and vaginal mucosa. The patient was diagnosed with PAMS based on computed tomography scans and histological analyses of the lesions. The lymphoid hyperplasia in the retroperitoneum and lesions in the vaginal mucosa and trunk area were improved following pharmacological treatment and resection of the lymph node showing hyperplasia. However, the oral lesion was treated with intraluminal brachytherapy due to its resistance to long-term pharmacological treatment. The majority of the lesions were improved following treatment, in the absence of any severe side effects. In addition, neither worsening nor progression of the oral lesion was observed during the 4-year follow-up period. PMID:27602070

  14. Centrifugo-pneumatic multi-liquid aliquoting - parallel aliquoting and combination of multiple liquids in centrifugal microfluidics.

    PubMed

    Schwemmer, F; Hutzenlaub, T; Buselmeier, D; Paust, N; von Stetten, F; Mark, D; Zengerle, R; Kosse, D

    2015-08-01

    The generation of mixtures with precisely metered volumes is essential for reproducible automation of laboratory workflows. Splitting a given liquid into well-defined metered sub-volumes, the so-called aliquoting, has been frequently demonstrated on centrifugal microfluidics. However, so far no solution exists for assays that require simultaneous aliquoting of multiple, different liquids and the subsequent pairwise combination of aliquots with full fluidic separation before combination. Here, we introduce the centrifugo-pneumatic multi-liquid aliquoting designed for parallel aliquoting and pairwise combination of multiple liquids. All pumping and aliquoting steps are based on a combination of centrifugal forces and pneumatic forces. The pneumatic forces are thereby provided intrinsically by centrifugal transport of the assay liquids into dead end chambers to compress the enclosed air. As an example, we demonstrate simultaneous aliquoting of 1.) a common assay reagent into twenty 5 μl aliquots and 2.) five different sample liquids, each into four aliquots of 5 μl. Subsequently, the reagent and sample aliquots are simultaneously transported and combined into twenty collection chambers. All coefficients of variation for metered volumes were between 0.4%-1.0% for intra-run variations and 0.5%-1.2% for inter-run variations. The aliquoting structure is compatible to common assay reagents with a wide range of liquid and material properties, demonstrated here for contact angles between 20° and 60°, densities between 789 and 1855 kg m(-3) and viscosities between 0.89 and 4.1 mPa s. The centrifugo-pneumatic multi-liquid aliquoting is implemented as a passive fluidic structure into a single fluidic layer. Fabrication is compatible to scalable fabrication technologies such as injection molding or thermoforming and does not require any additional fabrication steps such as hydrophilic or hydrophobic coatings or integration of active valves. PMID:26138211

  15. Waveguide Power Combiner Demonstration for Multiple High Power Millimeter Wave TWTAs

    NASA Technical Reports Server (NTRS)

    Wintucky, Edwin G.; Simons, Rainee N.; Lesny, Gary G.; Glass, Jeffrey L.

    2004-01-01

    NASA is presently developing nuclear reactor technologies, under Project Prometheus, which will provide spacecraft with greatly increased levels of sustained onboard power and thereby dramatically enhance the capability for future deep space exploration. The first mission planned for use of this high power technology is the Jupiter Icy Moons Orbiter (JIMO). In addition to electric propulsion and science, there will also be unprecedented onboard power available for deep space communications. A 32 GHz transmitter with 1 kW of RF output power is being considered to enable the required very high data transmission rates. One approach to achieving the 1 kW RF power, now being investigated at NASA GRC, is the possible power combining of a number of 100-1 50 W TWTs now under development. The work presented here is the results of a proof-of-concept demonstration of the power combining Ka-band waveguide circuit design and test procedure using two Ka- band TWTAs (Varian model VZA6902V3 and Logimetrics model A440/KA-1066), both of which were previously employed in data uplink evaluation terminals at 29.36 GHz for the NASA Advanced Communications Technology Satellite (ACTS) program. The characterization of the individual TWTAs and power combining demonstration were done over a 500 MHz bandwidth from 29.1 to 29.6 GHz to simulate the Deep Space Network (DSN) bandwidth of 3 1.8 to 32.3 GHz. Figures 1-3 show some of the power transfer and gain measurements of the TWTAs using a swept signal generator (Agilent 83640b) for the RF input. The input and output powers were corrected for circuit insertion losses due to the waveguide components. The RF saturated powers of both ACTS TWTAs were on the order of 120 W, which is comparable to the expected output powers of the 32 GHz TWTs. Additional results for the individual TWTAs will be presented (AM/AM, AM/PM conversion and gain compression), some of which were obtained from swept frequency and power measurements using a vector network

  16. Experimental study of resolution of proton chemical shifts in solids: Combined multiple pulse NMR and magic-angle spinning

    SciTech Connect

    Ryan, L.M.; Taylor, R.E.; Paff, A.J.; Gerstein, B.C.

    1980-01-01

    High-resolution nuclear magnetic resonance spectra of protons in rigid, randomly oriented solids have been measured using combined homonuclear dipolar decoupling (via multiple pulse techniques) and attenuation of chemical shift anisotropies (via magic-angle sample spinning). Under those conditions, isotropic proton chemical shifts were recorded for a variety of chemical species, with individual linewidths varying from about 55 to 110 Hz (1--2 ppm). Residual line broadening was due predominately to (i) magnetic-field instability and inhomogeneity, (ii) unresolved proton--proton spin couplings, (iii) chemical shift dispersion, (iv) residual dipolar broadening, and (v) lifetime broadening under the multiple pulse sequences used. The magnitudes of those effects and the current limits of resolution for this experiment in our spectrometer have been investigated. The compounds studied included organic solids (4, 4'-dimethylbenzophenone, 2, 6-dimethylbenzoic acid, and aspirin), polymers (polystyrene and polymethylmethacrylate), and the vitrain portion of a bituminous coal.

  17. Multiple Imputation For Combined-Survey Estimation With Incomplete Regressors In One But Not Both Surveys

    PubMed Central

    Rendall, Michael S.; Ghosh-Dastidar, Bonnie; Weden, Margaret M.; Baker, Elizabeth H.; Nazarov, Zafar

    2013-01-01

    Within-survey multiple imputation (MI) methods are adapted to pooled-survey regression estimation where one survey has more regressors, but typically fewer observations, than the other. This adaptation is achieved through: (1) larger numbers of imputations to compensate for the higher fraction of missing values; (2) model-fit statistics to check the assumption that the two surveys sample from a common universe; and (3) specificying the analysis model completely from variables present in the survey with the larger set of regressors, thereby excluding variables never jointly observed. In contrast to the typical within-survey MI context, cross-survey missingness is monotonic and easily satisfies the Missing At Random (MAR) assumption needed for unbiased MI. Large efficiency gains and substantial reduction in omitted variable bias are demonstrated in an application to sociodemographic differences in the risk of child obesity estimated from two nationally-representative cohort surveys. PMID:24223447

  18. Toward Complete Bacterial Genome Sequencing Through the Combined Use of Multiple Next-Generation Sequencing Platforms.

    PubMed

    Jeong, Haeyoung; Lee, Dae-Hee; Ryu, Choong-Min; Park, Seung-Hwan

    2016-01-01

    PacBio's long-read sequencing technologies can be successfully used for a complete bacterial genome assembly using recently developed non-hybrid assemblers in the absence of secondgeneration, high-quality short reads. However, standardized procedures that take into account multiple pre-existing second-generation sequencing platforms are scarce. In addition to Illumina HiSeq and Ion Torrent PGM-based genome sequencing results derived from previous studies, we generated further sequencing data, including from the PacBio RS II platform, and applied various bioinformatics tools to obtain complete genome assemblies for five bacterial strains. Our approach revealed that the hierarchical genome assembly process (HGAP) non-hybrid assembler resulted in nearly complete assemblies at a moderate coverage of ~75x, but that different versions produced non-compatible results requiring post processing. The other two platforms further improved the PacBio assembly through scaffolding and a final error correction. PMID:26464377

  19. Combining data from multiple sources using the CUAHSI Hydrologic Information System

    NASA Astrophysics Data System (ADS)

    Tarboton, D. G.; Ames, D. P.; Horsburgh, J. S.; Goodall, J. L.

    2012-12-01

    The Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) has developed a Hydrologic Information System (HIS) to provide better access to data by enabling the publication, cataloging, discovery, retrieval, and analysis of hydrologic data using web services. The CUAHSI HIS is an Internet based system comprised of hydrologic databases and servers connected through web services as well as software for data publication, discovery and access. The HIS metadata catalog lists close to 100 web services registered to provide data through this system, ranging from large federal agency data sets to experimental watersheds managed by University investigators. The system's flexibility in storing and enabling public access to similarly formatted data and metadata has created a community data resource from governmental and academic data that might otherwise remain private or analyzed only in isolation. Comprehensive understanding of hydrology requires integration of this information from multiple sources. HydroDesktop is the client application developed as part of HIS to support data discovery and access through this system. HydroDesktop is founded on an open source GIS client and has a plug-in architecture that has enabled the integration of modeling and analysis capability with the functionality for data discovery and access. Model integration is possible through a plug-in built on the OpenMI standard and data visualization and analysis is supported by an R plug-in. This presentation will demonstrate HydroDesktop, showing how it provides an analysis environment within which data from multiple sources can be discovered, accessed and integrated.

  20. Connectivity mapping using a combined gene signature from multiple colorectal cancer datasets identified candidate drugs including existing chemotherapies

    PubMed Central

    2015-01-01

    Background While the discovery of new drugs is a complex, lengthy and costly process, identifying new uses for existing drugs is a cost-effective approach to therapeutic discovery. Connectivity mapping integrates gene expression profiling with advanced algorithms to connect genes, diseases and small molecule compounds and has been applied in a large number of studies to identify potential drugs, particularly to facilitate drug repurposing. Colorectal cancer (CRC) is a commonly diagnosed cancer with high mortality rates, presenting a worldwide health problem. With the advancement of high throughput omics technologies, a number of large scale gene expression profiling studies have been conducted on CRCs, providing multiple datasets in gene expression data repositories. In this work, we systematically apply gene expression connectivity mapping to multiple CRC datasets to identify candidate therapeutics to this disease. Results We developed a robust method to compile a combined gene signature for colorectal cancer across multiple datasets. Connectivity mapping analysis with this signature of 148 genes identified 10 candidate compounds, including irinotecan and etoposide, which are chemotherapy drugs currently used to treat CRCs. These results indicate that we have discovered high quality connections between the CRC disease state and the candidate compounds, and that the gene signature we created may be used as a potential therapeutic target in treating the disease. The method we proposed is highly effective in generating quality gene signature through multiple datasets; the publication of the combined CRC gene signature and the list of candidate compounds from this work will benefit both cancer and systems biology research communities for further development and investigations. PMID:26356760

  1. Combining Multiple Electrode Arrays for Two-Dimensional Electrical Resistivity Imaging Using the Unsupervised Classification Technique

    NASA Astrophysics Data System (ADS)

    Ishola, K. S.; Nawawi, M. N. M.; Abdullah, K.

    2015-06-01

    This article describes the use of k-means clustering, an unsupervised image classification technique, to help interpret subsurface targets. The k-means algorithm is employed to combine and classify the two-dimensional (2D) inverse resistivity models obtained from three different electrode arrays. The algorithm is initialized through the selection of the number of clusters, number of iterations and other parameters such as stopping criteria. Automatically, it seeks to find groups of closely related resistivity values that belong to the same cluster and are more similar to each other than resistivity values belonging to other clusters. The approach is applied to both synthetic and field data. The 2D postinversions of the resistivity data were preprocessed by resampling and interpolating to the same coordinate. Following the preprocessing, the three images are combined into a single classified image. All the image preprocessing, manipulation and analysis are performed using the PCI Geomatics software package. The results of the clustering and classification are presented as classified images. An assessment of the performance of the individual and combined images for the synthetic models is carried out using an error matrix, mean absolute error and mean absolute percent error. The estimated errors show that images obtained from maximum values of the reconstructed resistivity for the different models give the best representation of the true models. Additionally, the overall accuracy and kappa values show good agreement between the combined classified images and true models. Depending on the model, the overall accuracy ranges from 86 to 99 %, while the kappa coefficient is in the range of 54-98 %. Classified images with kappa coefficients greater than 0.8 show strong agreement, while images with kappa coefficients greater than 0.5 but less than 0.8 give moderate agreement. For the field data, the k-mean classifier produces images that incorporate structural features of

  2. Isolation of Shiga Toxin-Producing Escherichia coli from Ground Beef Using Multiple Combinations of Enrichment Broths and Selective Agars.

    PubMed

    Brusa, Victoria; Piñeyro, Pablo E; Galli, Lucía; Linares, Luciano H; Ortega, Emanuel E; Padola, Nora L; Leotta, Gerardo A

    2016-03-01

    Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens, and beef cattle are recognized as the principal reservoir. The aims of this study were (1) to identify the most sensitive combination of selective enrichment broths and agars for STEC isolation in artificially inoculated ground beef samples, and (2) to evaluate the most efficient combination(s) of methods for naturally contaminated ground beef samples. A total of 192 ground beef samples were artificially inoculated with STEC and non-stx bacterial strains. A combination of four enrichment broths and three agars were evaluated for sensitivity, specificity, and positive predictive value for STEC isolation from experimentally inoculated samples. Enrichments with either modified tryptic soy broth (mTSB) containing 8 mg/L novobiocin (mTSB-8) or modified Escherichia coli (mEC) broth followed by isolation in MacConkey agar were the most sensitive combinations for STEC isolation of artificially inoculated samples. Independently, both enrichments media followed by isolation in MacConkey were used to evaluate ground beef samples from 43 retail stores, yielding 65.1% and 58.1% stx-positive samples by RT-PCR, respectively. No difference was observed in the isolate proportions between these two methods (8/25 [32%] and 8/28 [28.6%]). Identical serotypes and stx genotypes were observed in STEC strains isolated from the same samples by either method. In this study, no single enrichment protocol was sufficient to detect all STEC in artificially inoculated samples and had considerable variation in detection ability with naturally contaminated samples. Moreover, none of the single or combinations of multiple isolation agars used were capable of identifying all STEC serogroups in either artificially inoculated or naturally occurring STEC-contaminated ground beef. Therefore, it may be prudent to conclude that there is no single method or combination of isolation methods capable of identifying all STEC serogroups

  3. Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

    PubMed

    Lanzillo, Roberta; Orefice, Giuseppe; Quarantelli, Mario; Rinaldi, Carlo; Prinster, Anna; Ventrella, Gianluca; Spitaleri, Daniele; Lus, Giacomo; Vacca, Giovanni; Carotenuto, Barbara; Salvatore, Elena; Brunetti, Arturo; Tedeschi, Gioacchino; Brescia Morra, Vincenzo

    2010-04-01

    A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing-remitting multiple sclerosis patients, aged 18-50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 microg (three times weekly) for 12 months, were randomized to combination therapy (interferon + atorvastatin 20 mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n = 21) or B (n = 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p = 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone. PMID:20150398

  4. Cumulative Risk Assessment: An Overview of Methodological Approaches for Evaluating Combined Health Effects from Exposure to Multiple Environmental Stressors

    PubMed Central

    Sexton, Ken

    2012-01-01

    Systematic evaluation of cumulative health risks from the combined effects of multiple environmental stressors is becoming a vital component of risk-based decisions aimed at protecting human populations and communities. This article briefly examines the historical development of cumulative risk assessment as an analytical tool, and discusses current approaches for evaluating cumulative health effects from exposure to both chemical mixtures and combinations of chemical and nonchemical stressors. A comparison of stressor-based and effects-based assessment methods is presented, and the potential value of focusing on viable risk management options to limit the scope of cumulative evaluations is discussed. The ultimate goal of cumulative risk assessment is to provide answers to decision-relevant questions based on organized scientific analysis; even if the answers, at least for the time being, are inexact and uncertain. PMID:22470298

  5. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    PubMed Central

    Park, Yoon-Dong; Sun, Wei; Salas, Antonio; Antia, Avan; Carvajal, Cindy; Wang, Amy; Xu, Xin; Meng, Zhaojin; Zhou, Ming; Tawa, Gregory J.; Dehdashti, Jean; Zheng, Wei; Henderson, Christina M.; Zelazny, Adrian M.

    2016-01-01

    ABSTRACT Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS) screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development. PMID:27486194

  6. Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity.

    PubMed

    Oreja-Guevara, Celia

    2012-04-01

    Multiple sclerosis (MS) is associated with a wide range of disease symptoms and amongst these, spasticity is one of the most disabling and has the greatest impact on patient well-being and quality of life. Until now, available drug therapies for spasticity appear to have limited benefit and are often associated with poor tolerability. In a recent Spanish survey it was noted that multidrug therapy and a low control rate were common features for a large proportion of patients with MS-related spasticity, suggesting that currently available monotherapies lack significant activity. Sativex is a 1:1 mixture of δ-9-tetrahydrocannabinol and cannabidiol derived from Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with MS-related spasticity is steadily accumulating. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status. These are highly encouraging findings that provide some much needed optimism for the treatment of this disabling and often painful symptom of MS. PMID:22509985

  7. Comparative proteogenomics: combining mass spectrometry and comparative genomics to analyze multiple genomes

    SciTech Connect

    Gupta, Nitin; Benhamida, Jamal; Bhargava, Vipul; Goodman, Daniel; Kain , Elisabeth; Kerman, Ian; Nguyen , Ngan; Ollikainen, Noah; Rodriguez, Jesse; Wang, J.; Lipton, Mary S.; Romine, Margaret F.; Bafna, Vineet; Smith, Richard D.; Pevzner, Pavel A.

    2008-07-30

    While bacterial genome annotations have significantly improved in recent years, techniques for bacterial proteome annotation (including post-translational chemical modifications, signal peptides, proteolytic events, etc.) are still in their infancy. At the same time, the number of sequenced bacterial genomes is rising sharply, far outpacing our ability to validate the predicted genes, let alone annotate bacterial proteomes. In this study, we use tandem mass spectrometry (MS/MS) to annotate the proteome of Shewanella oneidensis MR-1, an important microbe for bioremediation. In particular, we provide the first comprehensive map of post-translational modifications in a bacterial genome, including a large number of chemical modifications, signal peptide cleavages and cleavage of N-terminal methionine residues. We also detect multiple genes that were missed or assigned incorrect start positions by gene prediction programs and suggest corrections to improve the gene annotation. This study demonstrates that complementing every genome sequencing project by an MS/MS project would significantly improve both genome and proteome annotations for a reasonable cost.

  8. Combining Multiple Data Acquisition Systems to Study Corticospinal Output and Multi-segment Biomechanics.

    PubMed

    Asmussen, Michael J; Bailey, Aaron Z; Keir, Peter J; Potvin, Jim; Bergel, Tim; Nelson, Aimee J

    2016-01-01

    Transcranial magnetic stimulation techniques allow for an in-depth investigation into the neural mechanisms that underpin human behavior. To date, the use of TMS to study human movement, has been limited by the challenges related to precisely timing the delivery of TMS to features of the unfolding movement and, also, by accurately characterizing kinematics and kinetics. To overcome these technical challenges, TMS delivery and acquisition systems should be integrated with an online motion tracking system. The present manuscript details technical innovations that integrate multiple acquisition systems to facilitate and advance the use of TMS to study human movement. Using commercially available software and hardware systems, a step-by-step approach to both the hardware assembly and the software scripts necessary to perform TMS studies triggered by specific features of a movement is provided. The approach is focused on the study of upper limb, planar, multi-joint reaching movements. However, the same integrative system is amenable to a multitude of sophisticated studies of human motor control. PMID:26780153

  9. Combined virtual and real robotic test-bed for single operator control of multiple robots

    NASA Astrophysics Data System (ADS)

    Lee, Sam Y.-S.; Hunt, Shawn; Cao, Alex; Pandya, Abhilash

    2010-04-01

    Teams of heterogeneous robots with different dynamics or capabilities could perform a variety of tasks such as multipoint surveillance, cooperative transport and explorations in hazardous environments. In this study, we work with heterogeneous robots of semi-autonomous ground and aerial robots for contaminant localization. We developed a human interface system which linked every real robot to its virtual counterpart. A novel virtual interface has been integrated with Augmented Reality that can monitor the position and sensory information from video feed of ground and aerial robots in the 3D virtual environment, and improve user situational awareness. An operator can efficiently control the real multi-robots using the Drag-to-Move method on the virtual multi-robots. This enables an operator to control groups of heterogeneous robots in a collaborative way for allowing more contaminant sources to be pursued simultaneously. The advanced feature of the virtual interface system is guarded teleoperation. This can be used to prevent operators from accidently driving multiple robots into walls and other objects. Moreover, the feature of the image guidance and tracking is able to reduce operator workload.

  10. Combining hidden Markov models for comparing the dynamics of multiple sleep electroencephalograms.

    PubMed

    Langrock, Roland; Swihart, Bruce J; Caffo, Brian S; Punjabi, Naresh M; Crainiceanu, Ciprian M

    2013-08-30

    In this manuscript, we consider methods for the analysis of populations of electroencephalogram signals during sleep for the study of sleep disorders using hidden Markov models (HMMs). Notably, we propose an easily implemented method for simultaneously modeling multiple time series that involve large amounts of data. We apply these methods to study sleep-disordered breathing (SDB) in the Sleep Heart Health Study (SHHS), a landmark study of SDB and cardiovascular consequences. We use the entire, longitudinally collected, SHHS cohort to develop HMM population parameters, which we then apply to obtain subject-specific Markovian predictions. From these predictions, we create several indices of interest, such as transition frequencies between latent states. Our HMM analysis of electroencephalogram signals uncovers interesting findings regarding differences in brain activity during sleep between those with and without SDB. These findings include stability of the percent time spent in HMM latent states across matched diseased and non-diseased groups and differences in the rate of transitioning. PMID:23348835

  11. Heart failure analysis dashboard for patient's remote monitoring combining multiple artificial intelligence technologies.

    PubMed

    Guidi, G; Pettenati, M C; Miniati, R; Iadanza, E

    2012-01-01

    In this paper we describe an Heart Failure analysis Dashboard that, combined with a handy device for the automatic acquisition of a set of patient's clinical parameters, allows to support telemonitoring functions. The Dashboard's intelligent core is a Computer Decision Support System designed to assist the clinical decision of non-specialist caring personnel, and it is based on three functional parts: Diagnosis, Prognosis, and Follow-up management. Four Artificial Intelligence-based techniques are compared for providing diagnosis function: a Neural Network, a Support Vector Machine, a Classification Tree and a Fuzzy Expert System whose rules are produced by a Genetic Algorithm. State of the art algorithms are used to support a score-based prognosis function. The patient's Follow-up is used to refine the diagnosis. PMID:23366362

  12. On Combining Multiple-Instance Learning and Active Learning for Computer-Aided Detection of Tuberculosis.

    PubMed

    Melendez, Jaime; van Ginneken, Bram; Maduskar, Pragnya; Philipsen, Rick H H M; Ayles, Helen; Sanchez, Clara I

    2016-04-01

    The major advantage of multiple-instance learning (MIL) applied to a computer-aided detection (CAD) system is that it allows optimizing the latter with case-level labels instead of accurate lesion outlines as traditionally required for a supervised approach. As shown in previous work, a MIL-based CAD system can perform comparably to its supervised counterpart considering complex tasks such as chest radiograph scoring in tuberculosis (TB) detection. However, despite this remarkable achievement, the uncertainty inherent to MIL can lead to a less satisfactory outcome if analysis at lower levels (e.g., regions or pixels) is needed. This issue may seriously compromise the applicability of MIL to tasks related to quantification or grading, or detection of highly localized lesions. In this paper, we propose to reduce uncertainty by embedding a MIL classifier within an active learning (AL) framework. To minimize the labeling effort, we develop a novel instance selection mechanism that exploits the MIL problem definition through one-class classification. We adapt this mechanism to provide meaningful regions instead of individual instances for expert labeling, which is a more appropriate strategy given the application domain. In addition, and contrary to usual AL methods, a single iteration is performed. To show the effectiveness of our approach, we compare the output of a MIL-based CAD system trained with and without the proposed AL framework. The task is to detect textural abnormalities related to TB. Both quantitative and qualitative evaluations at the pixel level are carried out. Our method significantly improves the MIL-based classification. PMID:26660889

  13. Factorial combinations of protein interactions generate a multiplicity of florigen activation complexes in wheat and barley.

    PubMed

    Li, Chengxia; Lin, Huiqiong; Dubcovsky, Jorge

    2015-10-01

    The FLOWERING LOCUS T (FT) protein is a central component of a mobile flowering signal (florigen) that is transported from leaves to the shoot apical meristem (SAM). Two FT monomers and two DNA-binding bZIP transcription factors interact with a dimeric 14-3-3 protein bridge to form a hexameric protein complex. This complex, designated as the 'florigen activation complex' (FAC), plays a critical role in flowering. The wheat homologue of FT, designated FT1 (= VRN3), activates expression of VRN1 in the leaves and the SAM, promoting flowering under inductive long days. In this study, we show that FT1, other FT-like proteins, and different FD-like proteins, can interact with multiple wheat and barley 14-3-3 proteins. We also identify the critical amino acid residues in FT1 and FD-like proteins required for their interactions, and demonstrate that 14-3-3 proteins are necessary bridges to mediate the FT1-TaFDL2 interaction. Using in vivo bimolecular fluorescent complementation (BiFC) assays, we demonstrate that the interaction between FT1 and 14-3-3 occurs in the cytoplasm, and that this complex is then translocated to the nucleus, where it interacts with TaFDL2 to form a FAC. We also demonstrate that a FAC including FT1, TaFDL2 and Ta14-3-3C can bind to the VRN1 promoter in vitro. Finally, we show that relative transcript levels of FD-like and 14-3-3 genes vary among tissues and developmental stages. Since FD-like proteins determine the DNA specificity of the FACs, variation in FD-like gene expression can result in spatial and temporal modulation of the effects of mobile FT-like signals. PMID:26252567

  14. Combinations of susceptibility genes are associated with higher risk for multiple sclerosis and imply disease course specificity.

    PubMed

    Akkad, Denis A; Olischewsky, Alexandra; Reiner, Franziska; Hellwig, Kerstin; Esser, Sarika; Epplen, Jörg T; Curk, Tomaz; Gold, Ralf; Haghikia, Aiden

    2015-01-01

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by a genome wide association study (GWAS) conducted by the International Multiple Sclerosis Genetic Consortium in a multinational cohort prompting the discovery of 57 non-MHC MS-associated common genetic variants. Hitherto, few of these newly reported variants have been replicated in larger independent patient cohorts. We genotyped a cohort of 1033 MS patients and 644 healthy controls with a consistent genetic background for the 57 non-MHC variants reported to be associated with MS by the first large GWAS as well as the HLA DRB1*1501 tagging SNP rs3135388. We robustly replicated three of the 57 non-MHC reported MS-associated single nucleotide polymorphisms (SNPs). In addition, our study revealed several genotype-genotype combinations with an evidently higher degree of disease association than the genotypes of the single SNPs. We further correlated well-defined clinical phenotypes, i.e. ataxia, visual impairment due to optic neuritis and paresis with single SNPs and genotype combinations, and identified several associations. The results may open new avenues for clinical implications of the MS associated genetic variants reported from large GWAS. PMID:26011527

  15. Phase I study of pegylated liposomal doxorubicin in combination with bortezomib for Japanese patients with relapsed or refractory multiple myeloma.

    PubMed

    Kusumoto, Shigeru; Sunami, Kazutaka; Inagaki, Mitsuo; Iida, Shinsuke

    2015-06-01

    This phase I open-label study evaluated the tolerability of pegylated liposomal doxorubicin (PLD) and bortezomib combination in Japanese patients with relapsed or refractory multiple myeloma. Eligible patients (≥20 years) who had ≥1 line of prior chemotherapy received bortezomib 1.3 mg/m(2) rapid intravenous infusion on days 1, 4, 8 and 11 (each 21-day cycle), followed by PLD 30 mg/m(2) intravenous infusion on day 4 (each cycle), up to 6 cycles. Dose-limiting toxicity (DLT), defined as Grade 4 hematologic or Grade ≥3 non-hematologic, was evaluated through end of day 21. All three patients enrolled in the study developed DLTs [Grade 4 thrombocytopenia (n = 2) and Grade 3 ileus (n = 1)]. The study was, therefore, terminated without adding new patients, as per protocol-specified criteria. The most common Grade 3-4 adverse events (AEs) were hematologic, including thrombocytopenia, leucopenia, and neutropenia. The treatment was prematurely discontinued in all three patients due to AEs: Grade 3 bronchiolitis (serious AE), Grade 3 peripheral sensory neuropathy, and Grade 2 stomatitis. All patients achieved partial response (efficacy, secondary endpoint). In conclusion, the tolerability of PLD and bortezomib combination at dose levels approved in various countries was not confirmed in relapsed or refractory multiple myeloma patients from Japan. PMID:25749662

  16. Combinations of Susceptibility Genes Are Associated with Higher Risk for Multiple Sclerosis and Imply Disease Course Specificity

    PubMed Central

    Akkad, Denis A.; Olischewsky, Alexandra; Reiner, Franziska; Hellwig, Kerstin; Esser, Sarika; Epplen, Jörg T.; Curk, Tomaz; Gold, Ralf; Haghikia, Aiden

    2015-01-01

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by a genome wide association study (GWAS) conducted by the International Multiple Sclerosis Genetic Consortium in a multinational cohort prompting the discovery of 57 non-MHC MS-associated common genetic variants. Hitherto, few of these newly reported variants have been replicated in larger independent patient cohorts. We genotyped a cohort of 1033 MS patients and 644 healthy controls with a consistent genetic background for the 57 non-MHC variants reported to be associated with MS by the first large GWAS as well as the HLA DRB1*1501 tagging SNP rs3135388. We robustly replicated three of the 57 non-MHC reported MS-associated single nucleotide polymorphisms (SNPs). In addition, our study revealed several genotype-genotype combinations with an evidently higher degree of disease association than the genotypes of the single SNPs. We further correlated well-defined clinical phenotypes, i.e. ataxia, visual impairment due to optic neuritis and paresis with single SNPs and genotype combinations, and identified several associations. The results may open new avenues for clinical implications of the MS associated genetic variants reported from large GWAS. PMID:26011527

  17. Striking multiple synergies created by combining reduced graphene oxides and carbon nanotubes for polymer nanocomposites.

    PubMed

    Song, Ping'an; Liu, Lina; Fu, Shenyuan; Yu, Youming; Jin, Chunde; Wu, Qiang; Zhang, Yan; Li, Qian

    2013-03-29

    The extraordinary properties of carbon nanotubes (CNTs) and graphene stimulate the development of advanced composites. Recently, several studies have reported significant synergies in the mechanical, electrical and thermal conductivity properties of polymer nanocomposites by incorporating their nanohybrids. In this work, we created polypropylene nanocomposites with homogeneous dispersion of CNTs and reduced graphene oxides via a facile polymer-latex-coating plus melt-mixing strategy, and investigated their synergistic effects in their viscoelastic, gas barrier, and flammability properties. Interestingly, the results show remarkable synergies, enhancing their melt modulus and viscosity, O2 barrier, and flame retardancy properties and respectively exhibiting a synergy percentage of 15.9%, 45.3%, and 20.3%. As previously reported, we also observed remarkable synergistic effects in their tensile strength (14.3%) and Young's modulus (27.1%), electrical conductivity (32.3%) and thermal conductivity (34.6%). These impressive results clearly point towards a new strategy to create advanced materials by adding binary combinations of different types of nanofillers. PMID:23459335

  18. IPeak: An open source tool to combine results from multiple MS/MS search engines.

    PubMed

    Wen, Bo; Du, Chaoqin; Li, Guilin; Ghali, Fawaz; Jones, Andrew R; Käll, Lukas; Xu, Shaohang; Zhou, Ruo; Ren, Zhe; Feng, Qiang; Xu, Xun; Wang, Jun

    2015-09-01

    Liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) is an important technique for detecting peptides in proteomics studies. Here, we present an open source software tool, termed IPeak, a peptide identification pipeline that is designed to combine the Percolator post-processing algorithm and multi-search strategy to enhance the sensitivity of peptide identifications without compromising accuracy. IPeak provides a graphical user interface (GUI) as well as a command-line interface, which is implemented in JAVA and can work on all three major operating system platforms: Windows, Linux/Unix and OS X. IPeak has been designed to work with the mzIdentML standard from the Proteomics Standards Initiative (PSI) as an input and output, and also been fully integrated into the associated mzidLibrary project, providing access to the overall pipeline, as well as modules for calling Percolator on individual search engine result files. The integration thus enables IPeak (and Percolator) to be used in conjunction with any software packages implementing the mzIdentML data standard. IPeak is freely available and can be downloaded under an Apache 2.0 license at https://code.google.com/p/mzidentml-lib/. PMID:25951428

  19. Formalized Conflicts Detection Based on the Analysis of Multiple Emails: An Approach Combining Statistics and Ontologies

    NASA Astrophysics Data System (ADS)

    Zakaria, Chahnez; Curé, Olivier; Salzano, Gabriella; Smaïli, Kamel

    In Computer Supported Cooperative Work (CSCW), it is crucial for project leaders to detect conflicting situations as early as possible. Generally, this task is performed manually by studying a set of documents exchanged between team members. In this paper, we propose a full-fledged automatic solution that identifies documents, subjects and actors involved in relational conflicts. Our approach detects conflicts in emails, probably the most popular type of documents in CSCW, but the methods used can handle other text-based documents. These methods rely on the combination of statistical and ontological operations. The proposed solution is decomposed in several steps: (i) we enrich a simple negative emotion ontology with terms occuring in the corpus of emails, (ii) we categorize each conflicting email according to the concepts of this ontology and (iii) we identify emails, subjects and team members involved in conflicting emails using possibilistic description logic and a set of proposed measures. Each of these steps are evaluated and validated on concrete examples. Moreover, this approach's framework is generic and can be easily adapted to domains other than conflicts, e.g. security issues, and extended with operations making use of our proposed set of measures.

  20. Striking multiple synergies created by combining reduced graphene oxides and carbon nanotubes for polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Song, Ping'an; Liu, Lina; Fu, Shenyuan; Yu, Youming; Jin, Chunde; Wu, Qiang; Zhang, Yan; Li, Qian

    2013-03-01

    The extraordinary properties of carbon nanotubes (CNTs) and graphene stimulate the development of advanced composites. Recently, several studies have reported significant synergies in the mechanical, electrical and thermal conductivity properties of polymer nanocomposites by incorporating their nanohybrids. In this work, we created polypropylene nanocomposites with homogeneous dispersion of CNTs and reduced graphene oxides via a facile polymer-latex-coating plus melt-mixing strategy, and investigated their synergistic effects in their viscoelastic, gas barrier, and flammability properties. Interestingly, the results show remarkable synergies, enhancing their melt modulus and viscosity, O2 barrier, and flame retardancy properties and respectively exhibiting a synergy percentage of 15.9%, 45.3%, and 20.3%. As previously reported, we also observed remarkable synergistic effects in their tensile strength (14.3%) and Young’s modulus (27.1%), electrical conductivity (32.3%) and thermal conductivity (34.6%). These impressive results clearly point towards a new strategy to create advanced materials by adding binary combinations of different types of nanofillers.

  1. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers.

    PubMed

    Pope, Laura E; Khalil, M H; Berg, James E; Stiles, Mark; Yakatan, Gerald J; Sellers, Edward M

    2004-10-01

    Dextromethorphan (DM) pharmacological properties predict that the widely used cough suppressant could be used to treat several neuronal disorders, but it is rapidly metabolized after oral dosing. To find out whether quinidine (Q), a CYP2D6 inhibitor, could elevate and prolong DM plasma profiles, 2 multiple-dose studies identified the lowest oral dose of Q that could be used in a fixed combination with 3 doses of DM. A multiple-dose study in healthy subjects with an extensive or a poor enzyme metabolizer phenotype evaluated the safety and pharmacokinetic profile of a selected fixed-dose combination (AVP-923). Study 1 randomized 46 healthy subjects, who were extensive CYP2D6 metabolizers, to receive 0, 2.5, 10, 25, 50, or 75 mg Q twice daily in combination with 30 mg DM for 7 days. Plasma and urine samples were collected after the first and last doses for the assay of DM, dextrorphan (DX), and Q. Study 2 randomized 65 healthy extensive CYP2D6 metabolizers to 8 groups given twice-daily 45- or 60-mg DM doses combined with 0, 30, 45, or 60 mg Q for 7 days. The effects of increasing Q were not different with doses greater than 25 mg, whereas lower doses showed a dose-related increase in plasma DM concentrations. Urinary ratios of DM/DX showed a Q dose- and time-related increase in the number of subjects converted to the poor metabolizer phenotype that reached 100% on day 3 of dosing with 25 mg Q. Results from both studies indicated that 25 to 30 mg Q is adequate to maximally suppress O-demethylation of DM. Study 3 evaluated 7 extensive metabolizers and 2 poor metabolizers given an oral capsule every 12 hours containing 30 mg Q combined with 30 mg DM. DM plasma AUC values increased in both groups of subjects during the 8-day study. The mean urinary metabolic ratio (DM/DX) increased at least 27-fold in extensive metabolizers by day 8. There was no effect of Q on urinary metabolic ratios in poor metabolizers. Safety evaluations, including electrocardiograms, indicated that

  2. The combined SOHO-STEREO dataset: Simultaneous observations of comets from multiple vantage points

    NASA Astrophysics Data System (ADS)

    Knight, M.; Begun, J.; Kelley, M.; Battams, K.; A'Hearn, M.

    2014-07-01

    The set of comets observed by Solar and Heliospheric Observatory (SOHO) and Solar-TErrestrial RElations Observatory (STEREO) provides a large (>2500 comets) and unique database for studying cometary properties. Sungrazing comets are discovered in SOHO or STEREO images on average every few days, with individual comets typically observable for up to a few days. We compiled photometry of more than 20 comets observed simultaneously by the same telescope and filter on both STEREO spacecraft to construct the first dust scattering phase function ever directly computed from simultaneous observations of the same object from two vantage points, thus removing uncertainty caused by changing heliocentric distance between observations. The collective dust scattering phase function spans phase angles from 28--153 deg and agrees reasonably well with the theoretical curve from [1]. However, individual comets deviate from the predicted curve by varying amounts during their apparition. This may suggest that the dust properties of individual comets change on the timescale of hours due to the dramatically different heliocentric distance or that the number of dust grains in the coma is changing due to nucleus activity, rotation, and/or erosion. We have also begun a study of the dust tails of selected well-observed comets in our database. This project utilizes the 3-D aspects of the combined SOHO and STEREO dataset to constrain the dust properties and time of release better than is possible with observations from a single location. We will present ongoing results of these investigations and place them into the wider context of sungrazing comet studies, notably by comparison with SOHO and STEREO observations of comet C/2012 S1 ISON [2], the most extensively observed sungrazing comet in history.

  3. Massive Stellar Outflows From the Combined Action of Multiple Stellar Jets

    NASA Astrophysics Data System (ADS)

    Mac Low, Mordecai-Mark; Peters, T.; Klaassen, P.; Schrön, M.; Klessen, R.

    2014-01-01

    The formation of high-mass stars is usually accompanied by powerful protostellar outflows. Such high-mass outflows are not simply scaled-up versions of their lower-mass counterparts, since observations seem to suggest that the collimation degree degrades with stellar mass. Theoretically, the origins of massive outflows are not well understood because radiative feedback and gravitational fragmentation of the accretion flow around the high-mass star impede the driving of magnetic disk winds. We here present the first 3D simulation of massive star formation that simultaneously includes feedback by non-ionizing and ionizing radiation as well as a subgrid-scale model for protostellar outflows. We ran this model with the Flash adaptive mesh refinement hydrocode. We find that stars that form in a common accretion flow have aligned outflow axes, so that the individual jets of lower-mass companion stars combine to form a collective outflow. We compare our simulation to observations with synthetic H2 and CO observations and find that the morphology and kinematics of this collective outflow is very similar to observed massive outflows, such as Cepheus A and DR 21. The properties of high-mass outflows are therefore generally consistent with the formation of massive stars in gravitationally unstable accretion flows. We acknowledge support from SNF grant 200020 137896, U. Zurich grant FK-13-112, NSF grant AST11-09395, and DFG grant KL 1358/14-1, as well as SBB 811, and computing time at the LRZ (project h1343), the CSCS (Project 364), and the Juelich Supercomputing Center (project HHD14).

  4. Real-time gastric motility monitoring using transcutaneous intraluminal impedance measurements (TIIM).

    PubMed

    Poscente, M D; Wang, G; Filip, D; Ninova, P; Yadid-Pecht, O; Andrews, C N; Mintchev, M P

    2014-02-01

    The stomach plays a critical role in digestion, processing ingested food mechanically and breaking it up into particles, which can be effectively and efficiently processed by the intestines. When the motility of the stomach is compromised, digestion is adversely affected. This can lead to a variety of disorders. Current diagnostic techniques for gastric motility disorders are seriously lacking, and are based more on eliminating other possibilities rather than on specific tests. Presently, gastric motility can be assessed by monitoring gastric emptying, food transit, intragastric pressures, etc. The associated tests are usually stationary and of relatively short duration. The present study proposes a new method of measuring gastric motility, utilizing the attenuation of an oscillator-induced electrical signal across the gastric tissue, which is modulated by gastric contractions. The induced high-frequency oscillator signal is generated within the stomach, and is picked up transluminally by cutaneous electrodes positioned on the abdominal area connected to a custom-designed data acquisition instrument. The proposed method was implemented in two different designs: first a transoral catheter was modified to emit the signal inside the stomach; and second, a gastric retentive pill was designed to emit the signal. Both implementations were applied in vivo on two mongrel dogs (25.50 kg and 25.75 kg). Gastric contractions were registered and quantitatively compared to recordings from force transducers sutured onto the serosa of the stomach. Gastric motility indices were calculated for each minute, with transluminal impedance measurements and the measurements from the force transducers showing statistically significant (p < 0.05) Pearson correlation coefficients (0.65 ± 0.08 for the catheter-based design and 0.77 ± 0.03 for the gastric retentive pill design). These results show that transcutaneous intraluminal impedance measurement has the potential with further research

  5. Flow residence time and regions of intraluminal thrombus deposition in intracranial aneurysms.

    PubMed

    Rayz, V L; Boussel, L; Ge, L; Leach, J R; Martin, A J; Lawton, M T; McCulloch, C; Saloner, D

    2010-10-01

    Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as "virtual ink" and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone. PMID:20499185

  6. Intraluminal superior vena cava metastasis from adenosquamous carcinoma of the duodenum: A case report

    PubMed Central

    TAKAYOSHI, KOTOE; ARIYAMA, HIROSHI; TAMURA, SHINGO; YODA, SHUNSUKE; ARITA, TAKESHI; YAMAGUCHI, TOSHIHIRO; OZONO, KEIGO; YAMAMOTO, HIDETAKA; INADOMI, KYOKO; KUMAGAI, HOZUMI; TANAKA, MAMORU; OKUMURA, YUTA; SAGARA, KOSUKE; NIO, KENTA; NAKANO, MICHITAKA; ARITA, SHUJI; KUSABA, HITOSHI; ODASHIRO, KEITA; ODA, YOSHINAO; AKASHI, KOICHI; BABA, EISHI

    2016-01-01

    In 2013, a 76-year-old male with a cardiac pacemaker was diagnosed with adenosquamous carcinoma of the duodenum. Subsequently, a pancreatoduodenectomy and lymph node dissection were performed, and 12 cycles of adjuvant chemotherapy (modified FOLFOX6 regimen), which consisted of fluorouracil, leucovorin and oxaliplatin, were administered via a central venous catheter. At 5 months after the completion of adjuvant chemotherapy, the patient experienced the sudden onset of severe pain at the back right of the ear, edema of the right side of the face and right jugular vein dilatation. Computed tomography (CT) revealed filling defects in the superior vena cava (SVC) and right brachiocephalic vein, indicating catheter-induced venous thrombosis. Although the catheter was removed and anti-coagulation therapy, aspiration of the thrombosis and ballooning dilatation were performed immediately, the patient's symptoms were not ameliorated. Notably, histological examination following thrombus aspiration revealed metastatic cancer cells, and fluorodeoxyglucose-positron emission tomography/CT identified metabolically active nodules in the SVC at locations consistent with the initial duodenal tumors detected by CT and in the first thoracic vertebrae. The tumor thrombus rapidly increased in size and resulted in worsening dyspnea. Subsequently, radiotherapy was performed, followed by chemotherapy, which relieved the systemic symptoms and suppressed the tumor growth. Adenosquamous carcinoma of the duodenum is extremely rare, and to the best of our knowledge, intraluminal SVC metastasis as a result of adenosquamous carcinoma of the duodenum has not been reported previously. The placement of a cardiac pacemaker, central venous catheter and tumor cells possessing high metastatic potential are hypothesized to have contributed to this rare case of metastasis. PMID:26870254

  7. Management of delayed intrathoracic esophageal perforation with modified intraluminal esophageal stent.

    PubMed

    Zhou, J-H; Gong, T-Q; Jiang, Y-G; Wang, R-W; Zhao, Y-P; Tan, Q-Y; Ma, Z; Lin, Y-D; Deng, B

    2009-01-01

    In this article, we reviewed our experience of treatment of the delayed intrathoracic nonmalignant esophageal perforation employing modified intraluminal esophageal stent. Between February 1990 and August 2006, eight patients were included in this study. Five patients experienced sepsis. The interval time between perforation and stent placement ranged from 36 h to 27 days (average, 8.6 days). Esophageal stenting and throracotomy for foreign body removal were performed in four patients. The remaining four patients underwent stent placement and thoracostomy. Nutrition was initiated through gastrostomy after 7 to 10 days after the stenting. The stent was removed after the patients resumed oral intake of food and the esophagogram showed that perforation was closed. There was no death in this group. Signs of sepsis remitted 1 week after stent placement. Complications included stress ulcer, stimulative cough, and pneumonia each. Stent removal ranged 32 to 120 days (average 66.7) after its placement. The stent was kept in place for 4 months to prevent formation of esophageal stricture in one patient with caustic esophageal burns. The follow-up was completed in all the patients. The mean follow-up period was 59 months (range 12-180). One patient with caustic esophageal burn underwent cicatricial esophagectomy and gastric transposition 3 years later due to the esophageal stricture. Barium swallow demonstrated that there was a diverticulum-like outpouching in one patient and slight esophageal stricture at T2 and T3 level in another. One patient developed reflux esophagitis 5 years after stent removal. All the patients finally had a normal intake of food. Modified esophageal stenting is an effective method to manage the delayed intrathoracic esophageal perforation. Prevention of stent migration and its convenient adjustment might be the major advantages of this method. PMID:19191858

  8. Combining different functions to describe milk, fat, and protein yield in goats using Bayesian multiple-trait random regression models.

    PubMed

    Oliveira, H R; Silva, F F; Siqueira, O H G B D; Souza, N O; Junqueira, V S; Resende, M D V; Borquis, R R A; Rodrigues, M T

    2016-05-01

    We proposed multiple-trait random regression models (MTRRM) combining different functions to describe milk yield (MY) and fat (FP) and protein (PP) percentage in dairy goat genetic evaluation by using Bayesian inference. A total of 3,856 MY, FP, and PP test-day records, measured between 2000 and 2014, from 535 first lactations of Saanen and Alpine goats, including their cross, were used in this study. The initial analyses were performed using the following single-trait random regression models (STRRM): third- and fifth-order Legendre polynomials (Leg3 and Leg5), linear B-splines with 3 and 5 knots, the Ali and Schaeffer function (Ali), and Wilmink function. Heterogeneity of residual variances was modeled considering 3 classes. After the selection of the best STRRM to describe each trait on the basis of the deviance information criterion (DIC) and posterior model probabilities (PMP), the functions were combined to compose the MTRRM. All combined MTRRM presented lower DIC values and higher PMP, showing the superiority of these models when compared to other MTRRM based only on the same function assumed for all traits. Among the combined MTRRM, those considering Ali to describe MY and PP and Leg5 to describe FP (Ali_Leg5_Ali model) presented the best fit. From the Ali_Leg5_Ali model, heritability estimates over time for MY, FP. and PP ranged from 0.25 to 0.54, 0.27 to 0.48, and 0.35 to 0.51, respectively. Genetic correlation between MY and FP, MY and PP, and FP and PP ranged from -0.58 to 0.03, -0.46 to 0.12, and 0.37 to 0.64, respectively. We concluded that combining different functions under a MTRRM approach can be a plausible alternative for joint genetic evaluation of milk yield and milk constituents in goats. PMID:27285684

  9. Considerations when combining data from multiple nutrition experiments to estimate genetic parameters for feed efficiency.

    PubMed

    Hardie, L C; Armentano, L E; Shaver, R D; VandeHaar, M J; Spurlock, D M; Yao, C; Bertics, S J; Contreras-Govea, F E; Weigel, K A

    2015-04-01

    Prior to genomic selection on a trait, a reference population needs to be established to link marker genotypes with phenotypes. For costly and difficult-to-measure traits, international collaboration and sharing of data between disciplines may be necessary. Our aim was to characterize the combining of data from nutrition studies carried out under similar climate and management conditions to estimate genetic parameters for feed efficiency. Furthermore, we postulated that data from the experimental cohorts within these studies can be used to estimate the net energy of lactation (NE(L)) densities of diets, which can provide estimates of energy intakes for use in the calculation of the feed efficiency metric, residual feed intake (RFI), and potentially reduce the effect of variation in energy density of diets. Individual feed intakes and corresponding production and body measurements were obtained from 13 Midwestern nutrition experiments. Two measures of RFI were considered, RFI(Mcal) and RFI(kg), which involved the regression of NE(L )intake (Mcal/d) or dry matter intake (DMI; kg/d) on 3 expenditures: milk energy, energy gained or lost in body weight change, and energy for maintenance. In total, 677 records from 600 lactating cows between 50 and 275 d in milk were used. Cows were divided into 46 cohorts based on dietary or nondietary treatments as dictated by the nutrition experiments. The realized NE(L) densities of the diets (Mcal/kg of DMI) were estimated for each cohort by totaling the average daily energy used in the 3 expenditures for cohort members and dividing by the cohort's total average daily DMI. The NE(L) intake for each cow was then calculated by multiplying her DMI by her cohort's realized energy density. Mean energy density was 1.58 Mcal/kg. Heritability estimates for RFI(kg), and RFI(Mcal) in a single-trait animal model did not differ at 0.04 for both measures. Information about realized energy density could be useful in standardizing intake data from

  10. Outage Performance and Average Symbol Error Rate of M-QAM for Maximum Ratio Combining with Multiple Interferers

    NASA Astrophysics Data System (ADS)

    Ahn, Kyung Seung

    In this paper, we investigate the performance of maximum ratio combining (MRC) in the presence of multiple cochannel interferences over a flat Rayleigh fading channel. Closed-form expressions of signal-to-interference-plus-noise ratio (SINK), outage probability, and average symbol error rate (SER) of quadrature amplitude modulation (QAM) with Mary signaling are obtained for unequal-power interference-to-noise ratio (INR). We also provide an upper-bound for the average SER using moment generating function (MGF) of the SINR. Moreover, we quantify the array gain loss between pure MRC (MRC system in the absence of CCI) and MRC system in the presence of CCI. Finally, we verify our analytical results by numerical simulations.

  11. Managing multiple myeloma: the emerging role of novel therapies and adapting combination treatment for higher risk settings.

    PubMed

    Richardson, Paul G; Laubach, Jacob; Mitsiades, Constantine S; Schlossman, Robert; Hideshima, Teru; Redman, Katherine; Chauhan, Dharminder; Ghobrial, Irene M; Munshi, Nikhil; Anderson, Kenneth C

    2011-09-01

    Novel therapies have transformed the treatment paradigm for multiple myeloma with significant improvements in survival now seen in both younger and older patients. Nonetheless, the disease is heterogeneous and high-risk patients in particular continue to have poor outcome. Moreover, the disease remains incurable. Efforts to refine risk stratification and disease characteristics continue with the use of cytogenetics, enhanced imaging techniques and other new technologies, such as genomics. The integration of novel therapies into induction therapy, consolidation and maintenance continues to evolve, and the appropriate use of combination strategies including proteasome inhibition and immunomodulatory treatment is emerging as a platform with application across the disease spectrum. Despite these advances, resistance to novel agents occurs and so the identification of new targets and the recognition of clonal heterogeneity are especially important as improvements to current treatment strategies are developed, with the goal of further improving patient outcome. PMID:21732930

  12. Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods.

    PubMed

    Burgess, Stephen; Dudbridge, Frank; Thompson, Simon G

    2016-05-20

    Mendelian randomization is the use of genetic instrumental variables to obtain causal inferences from observational data. Two recent developments for combining information on multiple uncorrelated instrumental variables (IVs) into a single causal estimate are as follows: (i) allele scores, in which individual-level data on the IVs are aggregated into a univariate score, which is used as a single IV, and (ii) a summary statistic method, in which causal estimates calculated from each IV using summarized data are combined in an inverse-variance weighted meta-analysis. To avoid bias from weak instruments, unweighted and externally weighted allele scores have been recommended. Here, we propose equivalent approaches using summarized data and also provide extensions of the methods for use with correlated IVs. We investigate the impact of different choices of weights on the bias and precision of estimates in simulation studies. We show that allele score estimates can be reproduced using summarized data on genetic associations with the risk factor and the outcome. Estimates from the summary statistic method using external weights are biased towards the null when the weights are imprecisely estimated; in contrast, allele score estimates are unbiased. With equal or external weights, both methods provide appropriate tests of the null hypothesis of no causal effect even with large numbers of potentially weak instruments. We illustrate these methods using summarized data on the causal effect of low-density lipoprotein cholesterol on coronary heart disease risk. It is shown that a more precise causal estimate can be obtained using multiple genetic variants from a single gene region, even if the variants are correlated. © 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:26661904

  13. ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches.

    PubMed

    Wang, Shuangquan; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

    2016-08-01

    Blockade of human ether-à-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability. PMID:27379394

  14. Combining non selective gas sensors on a mobile robot for identification and mapping of multiple chemical compounds.

    PubMed

    Bennetts, Victor Hernandez; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources. PMID:25232911

  15. Combining Non Selective Gas Sensors on a Mobile Robot for Identification and Mapping of Multiple Chemical Compounds

    PubMed Central

    Victor Hernandez, Bennetts; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J.; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources. PMID:25232911

  16. Isotope ratio measurements of pg-size plutonium samples using TIMS in combination with "multiple ion counting" and filament carburization

    NASA Astrophysics Data System (ADS)

    Jakopic, Rozle; Richter, Stephan; Kühn, Heinz; Benedik, Ljudmila; Pihlar, Boris; Aregbe, Yetunde

    2009-01-01

    A sample preparation procedure for isotopic measurements using thermal ionization mass spectrometry (TIMS) was developed which employs the technique of carburization of rhenium filaments. Carburized filaments were prepared in a special vacuum chamber in which the filaments were exposed to benzene vapour as a carbon supply and carburized electrothermally. To find the optimal conditions for the carburization and isotopic measurements using TIMS, the influence of various parameters such as benzene pressure, carburization current and the exposure time were tested. As a result, carburization of the filaments improved the overall efficiency by one order of magnitude. Additionally, a new "multi-dynamic" measurement technique was developed for Pu isotope ratio measurements using a "multiple ion counting" (MIC) system. This technique was combined with filament carburization and applied to the NBL-137 isotopic standard and samples of the NUSIMEP 5 inter-laboratory comparison campaign, which included certified plutonium materials at the ppt-level. The multi-dynamic measurement technique for plutonium, in combination with filament carburization, has been shown to significantly improve the precision and accuracy for isotopic analysis of environmental samples with low-levels of plutonium.

  17. Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma.

    PubMed

    Chauhan, Dharminder; Singh, Ajita V; Ciccarelli, Bryan; Richardson, Paul G; Palladino, Michael A; Anderson, Kenneth C

    2010-01-28

    Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib (Velcade) and, importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib. Here we demonstrate that combining NPI-0052 and lenalidomide (Revlimid) induces synergistic anti-MM activity in vitro using MM-cell lines or patient MM cells. NPI-0052 plus lenalidomide-induced apoptosis is associated with (1) activation of caspase-8, caspase-9, caspase-12, caspase-3, and poly(ADP) ribose polymerase; (2) activation of BH-3 protein BIM; (3) translocation of BIM to endoplasmic reticulum; (4) inhibition of migration of MM cells and angiogenesis; and (5) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. Importantly, blockade of BIM using siRNA significantly abrogates NPI-0052 plus lenalidomide-induced apoptosis. Furthermore, studies using biochemical inhibitors of caspase-8 versus caspase-9 demonstrate that NPI-0052 plus lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling. In animal tumor model studies, low-dose combination of NPI-0052 and lenalidomide is well tolerated, significantly inhibits tumor growth, and prolongs survival. Taken together, our study provides the preclinical rationale for clinical protocols evaluating lenalidomide together with NPI-0052 to improve patient outcome in MM. PMID:19965674

  18. Genotype to Phenotype Maps: Multiple Input Abiotic Signals Combine to Produce Growth Effects via Attenuating Signaling Interactions in Maize

    PubMed Central

    Makumburage, G. Buddhika; Richbourg, H. Lee; LaTorre, Kalindi D.; Capps, Andrew; Chen, Cuixen; Stapleton, Ann E.

    2013-01-01

    The complexity of allele interactions constrains crop improvement and the prediction of disease susceptibility. Additive allele effects are the foundation for selection in animal and plant breeding, and complex genetic and environmental interactions contribute to inefficient detection of desirable loci. Manipulation and modeling of other sources of variation, such as environmental variables, have the potential to improve our prediction of phenotype from genotype. As an example of our approach to analysis of the network linking environmental input to alleles, we mapped the genetic architecture of single and combined abiotic stress responses in two maize mapping populations and compared the observed genetic architecture patterns to simple theoretical predictions. Comparisons of single and combined stress effects on growth and biomass traits exhibit patterns of allele effects that suggest attenuating interactions among physiological signaling steps in drought and ultraviolet radiation stress responses. The presence of attenuating interactions implies that shared QTL found in sets of environments could be used to group environment types and identify underlying environmental similarities, and that patterns of stress-dependent genetic architecture should be studied as a way to prioritize prebreeding populations. A better understanding of whole-plant interactor pathways and genetic architecture of multiple-input environmental signaling has the potential to improve the prediction of genomic value in plant breeding and crop modeling. PMID:24142926

  19. Concurrent combined verification: reducing false positives in automated NMR structure verification through the evaluation of multiple challenge control structures.

    PubMed

    Golotvin, Sergey S; Pol, Rostislav; Sasaki, Ryan R; Nikitina, Asya; Keyes, Philip

    2012-06-01

    Automated structure verification using (1)H NMR data or a combination of (1)H and heteronuclear single-quantum correlation (HSQC) data is gaining more interest as a routine application for qualitative evaluation of large compound libraries produced by synthetic chemistry. The goal of this automated software method is to identify a manageable subset of compounds and data that require human review. In practice, the automated method will flag structure and data combinations that exhibit some inconsistency (i.e. strange chemical shifts, conflicts in multiplicity, or overestimated and underestimated integration values) and validate those that appear consistent. One drawback of this approach is that no automated system can guarantee that all passing structures are indeed correct structures. The major reason for this is that approaches using only (1)H or even (1)H and HSQC spectra often do not provide sufficient information to properly distinguish between similar structures. Therefore, current implementations of automated structure verification systems allow, in principle, false positive results. Presented in this work is a method that greatly reduces the probability of an automated validation system passing incorrect structures (i.e. false positives). This novel method was applied to automatically validate 127 non-proprietary compounds from several commercial sources. Presented also is the impact of this approach on false positive and false negative results. PMID:22549844

  20. COMPARISON OF FLUOROSCOPY AND COMPUTED TOMOGRAPHY FOR TRACHEAL LUMEN DIAMETER MEASUREMENT AND DETERMINATION OF INTRALUMINAL STENT SIZE IN HEALTHY DOGS.

    PubMed

    Williams, Jackie M; Krebs, Ingar A; Riedesel, Elizabeth A; Zhao, Qianqian

    2016-05-01

    Tracheal collapse is a progressive airway disease that can ultimately result in complete airway obstruction. Intraluminal tracheal stents are a minimally invasive and viable treatment for tracheal collapse once the disease becomes refractory to medical management. Intraluminal stent size is chosen based on the maximum measured tracheal diameter during maximum inflation. The purpose of this prospective, cross-sectional study was to compare tracheal lumen diameter measurements and subsequent selected stent size using both fluoroscopy and CT and to evaluate inter- and intraobserver variability of the measurements. Seventeen healthy Beagles were anesthetized and imaged with fluoroscopy and CT with positive pressure ventilation to 20 cm H2 O. Fluoroscopic and CT maximum tracheal diameters were measured by three readers. Three individual measurements were made at eight predetermined tracheal sites for dorsoventral (height) and laterolateral (width) dimensions. Tracheal diameters and stent sizes (based on the maximum tracheal diameter + 10%) were analyzed using a linear mixed model. CT tracheal lumen diameters were larger compared to fluoroscopy at all locations (P-value < 0.0001). When comparing modalities, fluoroscopic and CT stent sizes were statistically different. Greater overall variation in tracheal diameter measurement (height or width) existed for fluoroscopy compared to CT, both within and among observers. The greater tracheal diameter measured with CT and lower measurement variability has clinical significance, as this may be the imaging modality of choice for appropriate stent selection to minimize complications in veterinary patients. PMID:26784924

  1. Intraluminal measurement of papillary duct urine pH, in vivo: a pilot study in the swine kidney.

    PubMed

    Handa, Rajash K; Lingeman, James E; Bledsoe, Sharon B; Evan, Andrew P; Connors, Bret A; Johnson, Cynthia D

    2016-06-01

    We describe the in vivo use of an optic-chemo microsensor to measure intraluminal papillary duct urine pH in a large mammal. Fiber-optic pH microsensors have a tip diameter of 140-µm that allows insertion into papillary Bellini ducts to measure tubule urine proton concentration. Anesthetized adult pigs underwent percutaneous nephrolithotomy to access the lower pole of the urinary collecting system. A flexible nephroscope was advanced towards an upper pole papilla with the fiber-optic microsensor contained within the working channel. The microsensor was then carefully inserted into Bellini ducts to measure tubule urine pH in real time. We successfully recorded tubule urine pH values in five papillary ducts from three pigs (1 farm pig and 2 metabolic syndrome Ossabaw pigs). Our results demonstrate that optical microsensor technology can be used to measure intraluminal urine pH in real time in a living large mammal. This opens the possibility for application of this optical pH sensing technology in nephrolithiasis. PMID:26526044

  2. Detrimental influences of intraluminally-administered sclerotic agents on surrounding tissues and peripheral nerves: An experimental study

    PubMed Central

    Fujiki, Masahide; Kurita, Masakazu; Ozaki, Mine; Kawakami, Hayato; Kaji, Nobuyuki; Takushima, Akihiko; Harii, Kiyonori

    2012-01-01

    The minimally-invasive nature of sclerotherapy makes it one of the first treatment options for venous malformations, although treatment-related complications, such as peripheral nerve paralysis, have been reported in some clinical cases. However, no studies of the aetiology of the detrimental effects of intraluminally-administered sclerotic agents on the surrounding tissues, including the peripheral nerves, have yet been published. This study therefore investigated the influences of intraluminally-administered sclerotic agents on the tissues surrounding the injection site using a newly-developed rat femoral vein model. Using this model, the effects of absolute ethanol, 5% ethanolamine oleate, and 1% polidocanol were compared histologically with those of normal saline controls. Fluorescein isothiocyanate-conjugated agents were administered and the leakage of sclerotic agents through the venous wall was evaluated by fluorescence microscopy. Damage to the adjacent femoral nerve was quantitatively evaluated by counting the numbers of axons in cross-sections. All the sclerotic agents caused vascular wall injuries and leakage into the surrounding tissues. The number of axons in the femoral nerve was significantly reduced following administration of absolute ethanol or 5% ethanolamine oleate, compared with normal saline. The results of this study suggest that sclerotic agents commonly leak out the vascular lumen, and some agents can cause adjacent nerve injury. It is important to be aware of this type of complication of sclerotherapy for venous malformations when selecting appropriate therapeutic interventions. PMID:22686430

  3. Biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus: a patient-specific modelling study.

    PubMed

    Wang, Xiaohong; Li, Xiaoyang

    2013-01-01

    Cerebral aneurysm is an irreversible dilatation causing intracranial haemorrhage with severe complications. It is assumed that the biomechanical factor plays a significant role in the development of cerebral aneurysm. However, reports on the correlations between the formation of intraluminal thrombus and the flow pattern, wall shear stress (WSS) distribution of the cerebral aneurysm as well as wall compliance are still limited. In this research, patient-specific numerical simulation was carried out for three cerebral aneurysms based on magnetic resonance imaging (MRI) data-sets. The interaction between pulsatile blood and aneurysm wall was taken into account. The biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus was studied systematically. The results of the numerical simulation indicated that the region of low blood flow velocity and the region of swirling recirculation were nearly coincident with each other. Besides, there was a significant correlation between the slow swirling flow and the location of thrombus deposition. Excessively low WSS was also found to have strong association with the regions of thrombus formation. Moreover, the relationship between cerebral aneurysm compliance and thrombus deposition was discovered. The patient-specific modelling study based on fluid-structure interaction) may provide a basis for future investigation on the prediction of thrombus formation in cerebral aneurysm. PMID:22292428

  4. Feasibility of Catheter-Directed Intraluminal Irreversible Electroporation of Porcine Ureter and Acute Outcomes in Response to Increasing Energy Delivery

    PubMed Central

    Srimathveeravalli, Govindarajan; Silk, Mikhail; Wimmer, Thomas; Monette, Sebastien; Kimm, Simon; Maybody, Majid; Solomon, Stephen B.; Coleman, Jonathan; Durack, Jeremy C.

    2015-01-01

    Purpose To evaluate the feasibility of focal intraluminal irreversible electroporation (IRE) in the ureter with a novel electrode catheter and to study the treatment effects in response to increasing pulse strength. Material and Methods Five IRE treatment settings were each evaluated twice for the ablation of normal ureter in five Yorkshire pigs (1–4 ablations/animal, total of 10 ablations) using a prototype device under ultrasound and fluoroscopic guidance. Animals received either unilateral or bilateral treatment, limited to a maximum of two ablations in any one ureter. Treatment was delivered with increasing pulse strength (1000V–3000V; increments of 500V) while keeping the pulse duration (100 µseconds) and number of pulses (90) constant. Ureter patency was assessed immediately following treatment with an antegrade ureteropyelography. Animals were sacrificed within 4 hours following treatment, and treated urinary tract was harvested for histopathologic analysis using hematoxylin and eosin (H&E) and Masson’s Trichrome (MT) stains. Results IRE was successfully performed in all animals without evidence of ureteral perforation. H&E analysis of IRE treatments demonstrated full thickness ablation at higher field strengths (mucosa to the adventitia). MT stains showed preservation of connective tissue at all field strengths. Conclusion Intraluminal catheter directed IRE ablation is feasible and produces full thickness ablation of normal ureters. There was no evidence of lumen perforation even at the maximum voltages evaluated in the study. PMID:25769212

  5. Combining Seismic Arrays to Image Detailed Rupture Properties of Large Earthquakes: Evidence for Frequent Triggering of Multiple Faults

    NASA Astrophysics Data System (ADS)

    Ishii, M.; Kiser, E.

    2010-12-01

    Imaging detailed rupture characteristics using the back-projection method, which time-reverses waveforms to their source, has become feasible in recent years due to the availability of data from large aperture arrays with dense station coverage. In contrast to conventional techniques, this method can quickly and indiscriminately provide the spatio-temporal details of rupture propagation. Though many studies have utilized the back-projection method with a single regional array, the limited azimuthal coverage often leads to skewed resolution. In this study, we enhance the imaging power by combining data from two arrays, i.e., the Transportable Array (TA) in the United States and the High Sensitivity Seismographic Network (Hi-net) in Japan. This approach suppresses artifacts and achieves good lateral resolution by improving distance and azimuthal coverage while maintaining waveform coherence. We investigate four large events using this method: the August 15, 2007 Pisco, Peru earthquake, the September 12, 2007 Southern Sumatra earthquake, the September 29, 2009 Samoa Islands earthquake, and the February 27, 2010 Maule, Chile earthquake. In every case, except the Samoa Islands event, the distance of one of the arrays from the epicenter requires us to use the direct P wave and core phases in the back-projection. One of the common features of the rupture characteristics obtained from the back-projection analysis is spatio-temporal rupture discontinuities, or discrete subevents. Both the size of the gaps and the timing between subevents suggest that multiple segments are involved during giant earthquakes, and that they trigger slip on other faults. For example, the 2009 Samoa Islands event began with a rupture propagating north for about 15 seconds followed by a much larger rupture that originated 30 km northwest of the terminus of the first event and propagated back toward the southeast. The involvement of multiple rupture segments with different slip characteristics

  6. Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation

    PubMed Central

    Biasetti, Jacopo; Hussain, Fazle; Gasser, T. Christian

    2011-01-01

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear–stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ2-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau–Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth. PMID:21471188

  7. A method to detect single and multiple delamination problems using a combined neural network technique and genetic algorithm optimization

    NASA Astrophysics Data System (ADS)

    Le, Hieu The

    This thesis develops a new method to detect delaminations in composite laminates using a combination of finite element method, artificial neural networks, and genetic algorithms. Next, this newly developed method is applied to successfully solve delamination detection problems. Delaminations in a composite laminate with various sizes and locations are considered in the present studies. The improved layerwise shear deformation theory is implemented into the finite element method and used to calculate responses of laminates with single and multiple delaminations. Mappings between the natural frequencies and delamination characteristics are first determined from the developed models. These data are then used to train artificial neural networks of multiplayer perceptron using back-propagation. These trained artificial neural networks are in turn used as an approximate tool to calculate the responses of the delaminated laminates and to feed the data to the delamination detection process. Two different approaches for handling the neural network models are applied in the work and are presented for comparison. The delamination detection problem is formulated as an optimization problem with mixed type design variables. A genetic algorithm, which is a guided probabilistic search technique based on the simulation of Darwin's principle of evolution and natural selection, is developed to solve this optimization problem. Single through-the-width delamination, single internal delamination, and multiple through-the-width delaminations are separately considered for detection study. At last, the application is extended to the most challenging problem, which is the detection of general delamination. Various factors affecting the detection process such as the finite element convergence factor and the laminate geometry factor are also examined. Case studies are made and the findings are summarized in detail in each chapter of the dissertation. It is found that the newly developed

  8. Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods

    SciTech Connect

    McGurk, Ross J.; Bowsher, James; Das, Shiva K.; Lee, John A

    2013-04-15

    different between 128 Multiplication-Sign 128 and 256 Multiplication-Sign 256 grid sizes for either method (MJV, p= 0.0519; STAPLE, p= 0.5672) but was for SMASD values (MJV, p < 0.0001; STAPLE, p= 0.0164). The best individual method varied depending on object characteristics. However, both MJV and STAPLE provided essentially equivalent accuracy to using the best independent method in every situation, with mean differences in DSC of 0.01-0.03, and 0.05-0.12 mm for SMASD. Conclusions: Combining segmentations offers a robust approach to object segmentation in PET. Both MJV and STAPLE improved accuracy and were robust against the widely varying performance of individual segmentation methods. Differences between MJV and STAPLE are such that either offers good performance when combining volumes. Neither method requires a training dataset but MJV is simpler to interpret, easy to implement and fast.

  9. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    PubMed

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs. PMID:26985781

  10. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: A combined experimental and theoretical study

    SciTech Connect

    Ghosh, R.; Samajdar, R. N.; Bhattacharyya, Aninda Jiban; Bagchi, B.

    2015-07-07

    Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at x{sub EtOH} ∼ 0.05 and the other at x{sub EtOH} ∼ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at x{sub EtOH} ∼ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at x{sub EtOH} ∼ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition.

  11. X-ray solution scattering combined with computation characterizing protein folds and multiple conformational states : computation and application.

    SciTech Connect

    Yang, S.; Park, S.; Makowski, L.; Roux, B.

    2009-02-01

    Small angle X-ray scattering (SAXS) is an increasingly powerful technique to characterize the structure of biomolecules in solution. We present a computational method for accurately and efficiently computing the solution scattering curve from a protein with dynamical fluctuations. The method is built upon a coarse-grained (CG) representation of the protein. This CG approach takes advantage of the low-resolution character of solution scattering. It allows rapid determination of the scattering pattern from conformations extracted from CG simulations to obtain scattering characterization of the protein conformational landscapes. Important elements incorporated in the method include an effective residue-based structure factor for each amino acid, an explicit treatment of the hydration layer at the surface of the protein, and an ensemble average of scattering from all accessible conformations to account for macromolecular flexibility. The CG model is calibrated and illustrated to accurately reproduce the experimental scattering curve of Hen egg white lysozyme. We then illustrate the computational method by calculating the solution scattering pattern of several representative protein folds and multiple conformational states. The results suggest that solution scattering data, when combined with a reliable computational method, have great potential for a better structural description of multi-domain complexes in different functional states, and for recognizing structural folds when sequence similarity to a protein of known structure is low. Possible applications of the method are discussed.

  12. Inversion of the haze aerosol sky columnar AVSD in central China by combining multiple ground observation equipment.

    PubMed

    Ma, Yingying; Gong, Wei; Wang, Lunche; Zhang, Ming; Chen, Zhongyong; Li, Jun; Yang, Jian

    2016-04-18

    Wuhan is the biggest city in China that has been facing an increasingly serious problem of air pollution in the recent years. In order to understand the mechanism of haze formation and diffusion, it is very important to obtain multiple atmospheric parameters. Columnar aerosol volume size distribution (AVSD) is an important atmospheric parameter in this regard, and utilizing CIMEL sun-photometer data to obtain this parameter has become the most popular method. However, currently, the widely used retrieval algorithms cannot be accessed using an open source code, and thus the retrieval of columnar AVSD is still a challenging task.. In this article, we introduce a new method that combines partial least squares (PLS) and genetic algorithm (GA) for the retrieval of columnar AVSD. By using this new method, we could obtain credible results even during hazy periods, despite the fact that our sun-photometer did not participate in the AERONET program and we did not use an official data processing method. First, it was assumed that columnar AVSD obeys the double logarithmic normal distribution function. Second, the relationship between the columnar AVSD and the AVSD on earth's surface was established using the partial least squares (PLS) method. Finally, the initial distribution parameters were adjusted through GA to obtain an optimal solution. This new method can improve the accuracy and reduce the computational difficulties faced in the retrieval of columnar AVSD in the absence of AREONET-based algorithm. PMID:27137256

  13. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: a combined experimental and theoretical study.

    PubMed

    Ghosh, R; Samajdar, R N; Bhattacharyya, Aninda Jiban; Bagchi, B

    2015-07-01

    Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at xEtOH ∼ 0.05 and the other at xEtOH ∼ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at xEtOH ∼ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at xEtOH ∼ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition. PMID:26156494

  14. Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: A combined experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Ghosh, R.; Samajdar, R. N.; Bhattacharyya, Aninda Jiban; Bagchi, B.

    2015-07-01

    Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at xEtOH ˜ 0.05 and the other at xEtOH ˜ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at xEtOH ˜ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at xEtOH ˜ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition.

  15. Solution of the structure of Aspergillus niger acid alpha-amylase by combined molecular replacement and multiple isomorphous replacement methods.

    PubMed

    Brady, R L; Brzozowski, A M; Derewenda, Z S; Dodson, E J; Dodson, G G

    1991-08-01

    The crystal structure of Aspergillus niger acid alpha-amylase was solved by a combination of multiple isomorphous replacement and molecular replacement methods. The atomic coordinates of Aspergillus oryzae (TAKA) alpha-amylase (entry 2TAA in the Protein Data Bank) and experimental diffraction data from a new monoclinic crystal form of TAKA alpha-amylase, were used during the procedure. Sequence identity between the two proteins is approximately 80%. The atomic parameters derived from the molecular replacement solution were too inaccurate to initiate least-squares crystallographic refinement. The molecular model was extensively revised against the experimental electron density map calculated at 3 A resolution. Subsequent crystallographic refinement of this model using synchrotron data to 2.1 A resolution led to a conventional R factor of 16.8%. The structure conforms well to expected stereochemistry with bond lengths deviating from target values by 0.031 A, and planar groups showing a root-mean-square deviation from ideal planes of 0.025 A. PMID:1930834

  16. Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

    PubMed Central

    2012-01-01

    Background Many marine meiofaunal species are reported to have wide distributions, which creates a paradox considering their hypothesized low dispersal abilities. Correlated with this paradox is an especially high taxonomic deficit for meiofauna, partly related to a lower taxonomic effort and partly to a high number of putative cryptic species. Molecular-based species delineation and barcoding approaches have been advocated for meiofaunal biodiversity assessments to speed up description processes and uncover cryptic lineages. However, these approaches show sensitivity to sampling coverage (taxonomic and geographic) and the success rate has never been explored on mesopsammic Mollusca. Results We collected the meiofaunal sea-slug Pontohedyle (Acochlidia, Heterobranchia) from 28 localities worldwide. With a traditional morphological approach, all specimens fall into two morphospecies. However, with a multi-marker genetic approach, we reveal multiple lineages that are reciprocally monophyletic on single and concatenated gene trees in phylogenetic analyses. These lineages are largely concordant with geographical and oceanographic parameters, leading to our primary species hypothesis (PSH). In parallel, we apply four independent methods of molecular based species delineation: General Mixed Yule Coalescent model (GMYC), statistical parsimony, Bayesian Species Delineation (BPP) and Automatic Barcode Gap Discovery (ABGD). The secondary species hypothesis (SSH) is gained by relying only on uncontradicted results of the different approaches (‘minimum consensus approach’), resulting in the discovery of a radiation of (at least) 12 mainly cryptic species, 9 of them new to science, some sympatric and some allopatric with respect to ocean boundaries. However, the meiofaunal paradox still persists in some Pontohedyle species identified here with wide coastal and trans-archipelago distributions. Conclusions Our study confirms extensive, morphologically cryptic diversity among

  17. Combined phase I/II study of imexon (AOP99.0001) for treatment of relapsed or refractory multiple myeloma.

    PubMed

    Moehler, Thomas M; Feneberg, Reinhard; Ho, Anthony Dick; Golenkov, Anatoly K; Ludwig, Heinz; Kropff, Martin; Khuageva, Nuriet K; Hajda, Jacek; von Broen, Ingo; Goldschmidt, Hartmut

    2010-08-01

    its known synergistic activity in combination with approved agents for myeloma treatment, AOP99.0001 is recommended for future clinical studies in combination regimens in multiple myeloma. PMID:20571355

  18. Combining multiple data sources for the quantification of snow and glacier melt contributions to streamflow over the last 100 years

    NASA Astrophysics Data System (ADS)

    Stahl, Kerstin; Freudiger, Daphné S.; Kohn, Irene; Seibert, Jan; Weiler, Markus

    2015-04-01

    High alpine headwater catchments are important source areas for many large rivers. There is considerable interest in understanding and predicting the changing hydrological processes in these catchments due to climatic changes. At the same time, high elevation regions tend to be data scarce. The aim of the study is a re-analysis of the changing contributions of snow and glacier melt to streamflow in the river Rhine over the entire 20th Century. The success of quantifying these contributions across scales and over such a long time period depends on the use of all available information. We present the challenges and benefits of combining multiple regional data sources (i) to analyze these changes empirically and (ii) to constrain hydrological modeling in the headwater basins. The reconstruction of gridded meteorological variables for the period 1901-1950 based on an analogue resampling technique created a consistent meteorological forcing over the entire period. Glacier extents from maps of the early 20th Century defined the starting conditions to bridge the time to existing glacier volume and area change data. The analysis of the co-variability and trends in a set of long time series of climate variables and streamflow in unregulated headwaters provided insight into different phases of changing climate-hydrology relations. These signatures, together with the snow water equivalent maps for the last 30 years produced by the SLF and the collection of all available streamflow records provided important benchmarks for model calibration and validation. This work improves the understanding of climate sensitivity in high mountain environments and demonstrates important challenges when modeling partly compensating effects of a changing climate.

  19. Lenalidomide in Combination with Dexamethasone in Elderly Patients with Advanced, Relapsed or Refractory Multiple Myeloma and Renal Failure

    PubMed Central

    Tosi, Patrizia; Gamberi, Barbara; Castagnari, Barbara; Molinari, Anna Lia; Savini, Paolo; Ceccolini, Michela; Tani, Monica; Merli, Anna; Imola, Manuela; Mianulli, Anna Maria; Cellini, Claudia; Tomassetti, Simona; Merli, Francesco; Fattori, Pierpaolo; Zaccaria, Alfonso

    2013-01-01

    Salvage therapy of elderly patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this can potentially limit the therapeutic options. Both thalidomide and bortezomib have proven effective in these patients, with an acceptable toxicity, while, in clinical practice, lenalidomide is generally not considered a first-choice drug for MM patients with renal failure as early reports showed an increased hematological toxicity unless appropriate dose reduction is applied. Aim of this study was a retrospective evaluation of the efficacy of the combination Lenalidomide + Dexamethasone in a population of elderly MM patients treated in 5 Italian Centers. The study included 20 consecutive MM patients (9 M, 11 F, median age 76.5 years) with relapsed (N= 6) or refractory (N=13) MM and moderate to severe renal failure, defined as creatinine clearance (Cr Cl) < 50ml/min. Four patients were undergoing hemodyalisis at study entry. 85 % of the patients had been previously treated with bortezomib-containing regimens. Lenalidomide dose was adjusted according to renal function and patients clinical conditions Median treatment duration was 16 months (1–22), therapy was interrupted after 1 21-day cycle in 2 patients. Grade III–IV neutropenia was observed in 7 patients (35%); grade III–IV non hematological toxicity was recorded in 3 cases (28%). A > partial response was observed in 8 patients (40%), 1 of whom obtained a VGPR; 4 additional patients achieved a minor response. Median response duration was 16 months (range 2–19+ months). A complete and partial renal response was obtained in 4 and 3 patients, respectively, all of them were responsive to Lenalidomide-dexamethasone According to our data, LEN+DEX has shown efficacy and acceptable toxicity in this population of elderly patients with advanced MM and renal failure PMID:23795275

  20. Intraluminal occlusion of the seminal duct by laser and Histoacryl: Two non-invasive alternatives for vasectomy

    NASA Astrophysics Data System (ADS)

    Freitag, B.; Sroka, R.; Koelle, S.; Becker, A. J.; Khoder, W.; Pongratz, T.; Stief, C. G.; Trottmann, M.

    2014-03-01

    Introduction and objective: Vasectomy is a well-established method in family control. Even though it is a safe and low risk operation, this surgery is invasive and difficult to reverse. Therefore the aim of this study was to investigate new non-invasive methods for occlusion of the seminal duct. Material and Methods: Seminal duct tissue was obtained from patients (n=30) suffering from prostate cancer and therefore undergoing prostatectomy. In a first set of experiments, the seminal duct was occluded by intraluminal application of Histoacryl® (Braun Aesculap AG, Tuttlingen, Germany). In a 2nd set of experiments, endoluminal laser induced occlusion was performed. Four different laser wavelengths (1940nm, 1470nm, 1064nm, 940nm) and different sets of laser parameters (e.g. power, exposure duration, fibre diameter, energy applied) were compared. Effectiveness of occlusion of the seminal duct was proven by post-treatment irrigation flow measurement, as well as by morphological analyses. To evaluate a potential damage of the surrounding tissue, external temperature was measured using a thermometer during laser application. Results: Intraluminal application of Histoacryl® induced an immediate and complete occlusion of the seminal duct. The underlying connective tissue maintained its functional integrity after this treatment. By laser light application to a Histoacryl® block, a hole could be created into the block thus indicating the possibility of recanalization. Treatment with laser energy resulted in shrinkage of the ductal lumen. The laser application generally caused necrosis in the epithelium and induced formation of vacuoles in the underlying connective tissue. As described for endoluminal varicose treatment, this distinct local reaction might result in an intense inflammation leading to a functional occlusion of the vas deferens. Conclusions: Both laser-induced occlusion and application of Histoacryl® are fast and simple techniques which may be able to achieve a

  1. Influences of Item Content and Format on the Dimensionality of Tests Combining Multiple-Choice and Open-Response Items: An Application of the Poly-DIMTEST Procedure.

    ERIC Educational Resources Information Center

    Perkhounkova, Yelena; Dunbar, Stephen B.

    The DIMTEST statistical procedure was used in a confirmatory manner to explore the dimensionality structures of three kinds of achievement tests: multiple-choice tests, constructed-response tests, and tests combining both formats. The DIMTEST procedure is based on estimating conditional covariances of the responses to the item pairs. The analysis…

  2. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells.

    PubMed

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3',4',5'-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development. PMID:27525972

  3. A Hybrid Chalcone Combining the Trimethoxyphenyl and Isatinyl Groups Targets Multiple Oncogenic Proteins and Pathways in Hepatocellular Carcinoma Cells

    PubMed Central

    Cao, Lili; Zhang, Lijun; Zhao, Xiang; Zhang, Ye

    2016-01-01

    Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3’,4’,5’-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development. PMID:27525972

  4. Exploring multiple feature combination strategies with a recurrent neural network architecture for off-line handwriting recognition

    NASA Astrophysics Data System (ADS)

    Mioulet, L.; Bideault, G.; Chatelain, C.; Paquet, T.; Brunessaux, S.

    2015-01-01

    The BLSTM-CTC is a novel recurrent neural network architecture that has outperformed previous state of the art algorithms in tasks such as speech recognition or handwriting recognition. It has the ability to process long term dependencies in temporal signals in order to label unsegmented data. This paper describes different ways of combining features using a BLSTM-CTC architecture. Not only do we explore the low level combination (feature space combination) but we also explore high level combination (decoding combination) and mid-level (internal system representation combination). The results are compared on the RIMES word database. Our results show that the low level combination works best, thanks to the powerful data modeling of the LSTM neurons.

  5. Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1.

    PubMed

    Kumar, Tarun; Gupta, Brijnandan; Das, Prasenjit; Jain, Deepali; Jain, Hemant Ashok; Madhusudhan, Kumble S; Dash, Nihar Ranjan; Gupta, Siddhartha Datta

    2016-01-01

    Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient. PMID:27510677

  6. Timing Treatment of a Giant Intracranial Aneurysm by the Use of Magnetic Resonance Imaging for the Determination of Intraluminal Clot Stability

    PubMed Central

    Jungreis, Charles A.; Jannetta, Peter J.; Yonas, Howard

    1993-01-01

    A 44-year-old man presented with a giant intracranial carotid artery aneurysm. Magnetic resonance (MR) images demonstrated a large amount of fresh intraluminal thrombus in the aneurysm. During test occlusion of the internal carotid artery using an endovascular balloon positioned in the cervical portion of the internal carotid, the patient sustained an apparent embolic episode. The patient was followed for several weeks with serial MR imaging until the thrombus had lysed. Repeat test occlusion followed by permanent carotid occlusion was uneventful. Serial MR evaluations of intraluminal thrombus in large aneurysms might help to determine an optimal time for institution of intervention. ImagesFigure 1Figure 2Figure 3p34-bFigure 4Figure 5 PMID:17170887

  7. Combined exercise training reduces IFN-γ and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis.

    PubMed

    Golzari, Zahra; Shabkhiz, Fatemeh; Soudi, Sara; Kordi, Mohammad Reza; Hashemi, Seyed Mahmoud

    2010-11-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder in which lymphocytic infiltration mediated mainly by pro-inflammatory cytokines. In this study, we examined the effect of combined exercise training on the levels of IFN-γ, IL-4 and IL-17 in the plasma and the supernatant of peripheral blood lymphocytes in women with multiple sclerosis. Expanded Disability Status Scale (EDSS), VO(2)max, muscle strength, and balance tests were obtained at baseline and post-treatment follow-up. Combined exercises training was designed for 24 sessions during 8 weeks. Each session was started with 5 min warm-up and was followed by 10 min stretch training, 20 min aerobic exercises and 20 min resistance-endurance training. The disability score was significantly decreased in test MS subjects after 8 weeks combined exercise training. Muscle strength and balance were increased significantly after the training program in test group. In this study, plasma, and peripheral blood mononuclear cell (PBMC) IL-17 and IFN-γ production was significantly decreased after 8 weeks combined training. Our findings suggest that combined training has useful anti-inflammatory effects by decrease in PBMC and plasma IL-17 production. PMID:20797460

  8. Multiple Channel Exposure Therapy: Combining Cognitive-Behavioral Therapies for the Treatment of Posttraumatic Stress Disorder with Panic Attacks

    ERIC Educational Resources Information Center

    Falsetti, Sherry A.; Resnick, Heidi S.; Davis, Joanne

    2005-01-01

    A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic…

  9. Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow†

    PubMed Central

    Caro, Colin Gerald; Seneviratne, Anusha; Heraty, Kevin B.; Monaco, Claudia; Burke, Martin G.; Krams, Rob; Chang, Carlos C.; Coppola, Gianfilippo; Gilson, Paul

    2013-01-01

    Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels. PMID:24132200

  10. Suppression of large intraluminal bubble expansion in shock wave lithotripsy without compromising stone comminution: Refinement of reflector geometry

    NASA Astrophysics Data System (ADS)

    Zhou, Yufeng; Zhong, Pei

    2003-01-01

    Using the Hamilton model [Hamilton, J. Acoust. Soc. Am. 93, 1256-1266 (1993)], the effects of reflector geometry on the pulse profile and sequence of the shock waves produced by the original and upgraded reflector of an HM-3 lithotripter were evaluated qualitatively. Guided by this analysis, we have refined the geometry of the upgraded reflector to enhance its suppressive effect on intraluminal bubble expansion without compromising stone comminution in shock wave lithotripsy. Using the original HM-3 reflector at 20 kV, rupture of a standard vessel phantom made of cellulose hollow fiber (i.d.=0.2 mm), in which degassed water seeded with ultrasound contrast agents was circulated, was produced at the lithotripter focus after about 30 shocks. In contrast, using the upgraded reflector at 24 kV no rupture of the vessel phantom could be produced within a 20-mm diameter around the lithotripter focus even after 200 shocks. On the other hand, stone comminution was comparable between the two reflector configurations, although slightly larger fragments were produced by the upgraded reflector. After 2000 shocks, stone comminution efficiency produced by the original HM-3 reflector at 20 kV is 97.15+/-1.92% (mean+/-SD), compared to 90.35+/-1.96% produced by the upgraded reflector at 24 kV (p<0.02). All together, it was found that the upgraded reflector could significantly reduce the propensity for vessel rupture in shock wave lithotripsy while maintaining satisfactory stone comminution.