Photoinduced electron transfer in singly labeled thiouredopyrenetrisulfonate azurin derivatives

DEFF Research Database (Denmark)

Borovok, N; Kotlyar, A B; Pecht, I

1999-01-01

efficiency. TUPS derivatives of azurin, singly labeled at specific lysine residues, were prepared and purified to homogeneity by ion exchange HPLC. Transient absorption spectroscopy was used to directly monitor the rates of the electron transfer reaction from the photoexcited triplet state of TUPS to Cu......A novel method for the initiation of intramolecular electron transfer reactions in azurin is reported. The method is based on laser photoexcitation of covalently attached thiouredopyrenetrisulfonate (TUPS), the reaction that generates the low potential triplet state of the dye with high quantum......(II) and the back reaction from Cu(I) to the oxidized dye. For all singly labeled derivatives, the rate constants of copper ion reduction were one or two orders of magnitude larger than for its reoxidation, consistent with the larger thermodynamic driving force for the former process. Using 3-D coordinates...

Single-Labeled Oligonucleotides Showing Fluorescence Changes upon Hybridization with Target Nucleic Acids

Directory of Open Access Journals (Sweden)

Gil Tae Hwang

2018-01-01

Full Text Available Sequence-specific detection of nucleic acids has been intensively studied in the field of molecular diagnostics. In particular, the detection and analysis of single-nucleotide polymorphisms (SNPs is crucial for the identification of disease-causing genes and diagnosis of diseases. Sequence-specific hybridization probes, such as molecular beacons bearing the fluorophore and quencher at both ends of the stem, have been developed to enable DNA mutation detection. Interestingly, DNA mutations can be detected using fluorescently labeled oligonucleotide probes with only one fluorophore. This review summarizes recent research on single-labeled oligonucleotide probes that exhibit fluorescence changes after encountering target nucleic acids, such as guanine-quenching probes, cyanine-containing probes, probes containing a fluorophore-labeled base, and microenvironment-sensitive probes.

Automatic single- and multi-label enzymatic function prediction by machine learning

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Shervine Amidi

2017-03-01

Full Text Available The number of protein structures in the PDB database has been increasing more than 15-fold since 1999. The creation of computational models predicting enzymatic function is of major importance since such models provide the means to better understand the behavior of newly discovered enzymes when catalyzing chemical reactions. Until now, single-label classification has been widely performed for predicting enzymatic function limiting the application to enzymes performing unique reactions and introducing errors when multi-functional enzymes are examined. Indeed, some enzymes may be performing different reactions and can hence be directly associated with multiple enzymatic functions. In the present work, we propose a multi-label enzymatic function classification scheme that combines structural and amino acid sequence information. We investigate two fusion approaches (in the feature level and decision level and assess the methodology for general enzymatic function prediction indicated by the first digit of the enzyme commission (EC code (six main classes on 40,034 enzymes from the PDB database. The proposed single-label and multi-label models predict correctly the actual functional activities in 97.8% and 95.5% (based on Hamming-loss of the cases, respectively. Also the multi-label model predicts all possible enzymatic reactions in 85.4% of the multi-labeled enzymes when the number of reactions is unknown. Code and datasets are available at https://figshare.com/s/a63e0bafa9b71fc7cbd7.

Safety of a new compact catheter for men with neurogenic bladder dysfunction: a randomised, crossover and open-labelled study

DEFF Research Database (Denmark)

Chartier-Kastler, E; Lauge, I; Ruffion, A

2011-01-01

Self-catheterising males aged =18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial.......Self-catheterising males aged =18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial....

A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

Science.gov (United States)

Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

2017-02-01

The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
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Safety of a new compact catheter for men with neurogenic bladder dysfunction: a randomised, crossover and open-labelled study

DEFF Research Database (Denmark)

Chartier-Kastler, E; Lauge, I; Ruffion, A

2011-01-01

Self-catheterising males aged ≥18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial.......Self-catheterising males aged ≥18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial....

Safety of telmisartan in patients with arterial hypertension - An open-label observational study

NARCIS (Netherlands)

Michel, Martin C.; Bohner, Herbert; Köster, Jürgen; Schäfers, Rafael; Heemann, Uwe

2004-01-01

Objective: To determine whether age, gender, concomitant disease and/or previous or present antihypertensive medication affect the safety or antihypertensive efficacy of telmisartan in the treatment of arterial hypertension. Study Design and Methods: In this large-scale, open-label postmarketing

Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study

Science.gov (United States)

Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

2008-01-01

Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

Science.gov (United States)

Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford J

2017-12-01

Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect

Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid for the treatment of osteoarthritis of the thumb

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Velasco E

2017-03-01

Full Text Available Eloisa Velasco,1 Mª Victoria Ribera,2 Joan Pi3 1Department of Orthopedic Surgery, Hospital de Sant Joan Despí Moisés Broggi, Barcelona, Spain; 2Department of Anesthesiology, Vall d’Hebron University Hospital, Barcelona, Spain; 3Department of Orthopedics and Traumatology, Parc Taulí University Hospital, Sabadell, Barcelona, Spain Introduction: Osteoarthritis of the trapeziometacarpal (TMC joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid in rhizarthrosis.Patients and methods: This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS pain score ≥4 (scale: 0–10. A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score.Results: Thirty-five patients (mean age 60.8 years; 85.7% female received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was –2.00, a reduction of 27.8% (p<0.001. The reduction in pain exceeded 25% as early as month 1 (26.5%, and gradual improvement was observed throughout the 6-month follow-up period. Secondary effectiveness parameters included QuickDASH (shortened version of Disabilities of the Arm, Shoulder, and Hand [DASH], Kapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP joint flexion, and pinch (clamp strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five

Effectiveness of a single application of 0·25% fipronil solution for the treatment of hirstiellosis in captive green iguanas (Iguana iguana): an open-label study.

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Farmaki, Rania; Simou, Chrisa; Papadopoulos, Elias; Koutinas, Alexander F; Saridomichelakis, Manolis N

2013-08-01

Hirstiella spp. are common ectoparasites of captive green iguanas (Iguana iguana). Suggested treatments are empirical and some of them are of low efficacy and potentially toxic. The objective of this open-label study was to investigate the short-term efficacy and safety of a single application of 0·25% fipronil solution for the treatment of hirstiellosis. The skin of 50 green iguanas was thoroughly examined with the aid of bright light and magnifying lenses. A total of 21 iguanas were found to be infested, harbouring 1-24 mites (median: 5). All 35 mites collected from 17 iguanas were identified as Hirstiella sp. Both infested and non-infested lizards, sharing the same enclosure, were carefully wiped with 0·25% fipronil solution. The safety and the efficacy of the treatment were evaluated after 2 days in 47/50 (94%) and 7 days in 29/50 (58%) iguanas. Compared with pre-treatment levels, the parasitic load did not changed significantly on the second day but was significantly lower on day 7 (P = 0·006). No adverse reactions were noticed. Based on these results a single whole-body application of 0·25% fipronil solution can be considered a safe and effective treatment for the reduction of parasitic burden in captive green iguanas infested by Hirstiella sp. mites.

Mobility and height detection of particle labels in an optical evanescent wave biosensor with single-label resolution

Energy Technology Data Exchange (ETDEWEB)

Van Ommering, Kim; Koets, Marjo; Schleipen, Jean J H B; Prins, Menno W J [Philips Research Laboratories, 5656 AE Eindhoven (Netherlands); Somers, Philip A; Van IJzendoorn, Leo J, E-mail: menno.prins@philips.co [Department of Applied Physics, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands)

2010-04-21

Particle labels are used in biosensors to detect the presence and concentration of analyte molecules. In this paper we demonstrate an optical technique to measure the mobility and height of bound particle labels on a biosensor surface with single-label resolution. The technique is based on the detection of the particle-induced light scattering in an optical evanescent field. We show that the thermal particle motion in the optical evanescent field leads to intensity fluctuations that can accurately be detected. The technique is demonstrated using 290 bp (99 nm) DNA as an analyte and using polystyrene particles and magnetic particles with diameters between 500 and 1000 nm as labels. The particle intensity histograms show that quantitative height measurements are obtained for particles with uniform optical properties, and the intensity versus position plots reflect the analyte-antibody orientation and the analyte flexibility. The novel optical detection technique will lead to biosensors with very high sensitivity and specificity.

Single-larger-portion-size and dual-column nutrition labeling may help consumers make more healthful food choices.

Science.gov (United States)

Lando, Amy M; Lo, Serena C

2013-02-01

The Food and Drug Administration is considering changes to the Nutrition Facts label to help consumers make more healthful choices. To examine the effects of modifications to the Nutrition Facts label on foods that can be listed as having 1 or 2 servings per container, but are reasonably consumed at a single eating occasion. Participants were randomly assigned to study conditions that varied on label format, product, and nutrition profile. Data were collected via an online consumer panel. Adults aged 18 years and older were recruited from Synovate's online household panel. Data were collected during August 2011. A total of 32,897 invitations were sent for a final sample of 9,493 interviews. Participants were randomly assigned to one of 10 label formats classified into three groups: listing 2 servings per container with a single column, listing 2 servings per container with a dual column, and listing a single serving per container. Within these groups there were versions that enlarged the font size for "calories," removed "calories from fat," and changed the wording for serving size declaration. The single product task measured product healthfulness, the amount of calories and various nutrients per serving and per container, and label perceptions. The product comparison task measured ability to identify the healthier product and the product with fewer calories per container and per serving. Analysis of covariance models with Tukey-Kramer tests were used. Covariates included general label use, age, sex, level of education, and race/ethnicity. Single-serving and dual-column formats performed better and scored higher on most outcome measures. For products that contain 2 servings but are customarily consumed at a single eating occasion, using a single-serving or dual-column labeling approach may help consumers make healthier food choices. Published by Elsevier Inc.

Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

Science.gov (United States)

McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

2011-01-01

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

Science.gov (United States)

Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

2015-05-01

Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

Science.gov (United States)

Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

2015-10-01

As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

Shelf Life of Food Products: From Open Labeling to Real-Time Measurements.

Science.gov (United States)

Corradini, Maria G

2018-03-25

The labels currently used on food and beverage products only provide consumers with a rough guide to their expected shelf lives because they assume that a product only experiences a limited range of predefined handling and storage conditions. These static labels do not take into consideration conditions that might shorten a product's shelf life (such as temperature abuse), which can lead to problems associated with food safety and waste. Advances in shelf-life estimation have the potential to improve the safety, reliability, and sustainability of the food supply. Selection of appropriate kinetic models and data-analysis techniques is essential to predict shelf life, to account for variability in environmental conditions, and to allow real-time monitoring. Novel analytical tools to determine safety and quality attributes in situ coupled with modern tracking technologies and appropriate predictive tools have the potential to provide accurate estimations of the remaining shelf life of a food product in real time. This review summarizes the necessary steps to attain a transition from open labeling to real-time shelf-life measurements.

An open-label study of sodium oxybate in Spasmodic dysphonia.

Science.gov (United States)

Rumbach, Anna F; Blitzer, Andrew; Frucht, Steven J; Simonyan, Kristina

2017-06-01

Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Open-label study. We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Sodium oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours. Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol, and as such, sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. 4 Laryngoscope, 127:1402-1407, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia--an open label study

NARCIS (Netherlands)

Kho, K. H.; Blansjaar, B. A.; de Vries, S.; Babuskova, D.; Zwinderman, A. H.; Linszen, D. H.

2004-01-01

OBJECTIVE: This open label study describes the efficacy of electroconvulsive therapy (ECT) as adjunctive treatment in clozapine nonresponders suffering from schizophrenia. METHOD: The results of clozapine and ECT treatment in 11 clozapine nonresponders suffering from schizophrenia are reported in

Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

Science.gov (United States)

Vogel, Moritz; Bayi, Pierre F; Ruf, Marie-Thérèse; Bratschi, Martin W; Bolz, Miriam; Um Boock, Alphonse; Zwahlen, Marcel; Pluschke, Gerd; Junghanss, Thomas

2016-02-01

Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. ISRCT 72102977. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Mechanics of single-walled carbon nanotubes inside open single-walled carbon nanocones

International Nuclear Information System (INIS)

Ansari, R.; Hosseinzadeh, M.

2013-01-01

This study investigates the mechanical characteristics of single-walled carbon nanotubes (CNTs) inside open single-walled carbon nanocones (CNCs). New semi-analytical expressions are presented to evaluate van der Waals (vdW) interactions between CNTs and open CNCs. Continuum approximation, along with the the Lennard-Jones (LJ) potential function, is used in this study. The effects of geometrical parameters on alterations in vdW potential energy and the interaction force are extensively examined for the concentric CNT-open CNC configuration. The CNT is assumed to enter the nanocone either through the small end or the wide end of the cone. The preferred position of the CNT with respect to the nanocone axis is fully investigated for various geometrical parameters. The optimum nanotube radius minimizing the total potential energy of the concentric configuration is determined for different radii of the small end of the cone. The examined configuration generates asymmetric oscillation; thus, the system constitutes a nano-oscillator.

Open-Access Single Balloon Enteroscopy: A Tertiary Care Experience.

Science.gov (United States)

Holman, Nathan; Wallace, Kristin; Moore, J Matthew; Brock, Andrew S

2015-12-01

To compare single balloon enteroscopy (SBE) between patients seen in consultation by a member of our gastroenterology team with those performed as open-access cases. Retrospective study of all patients who underwent SBE at a single tertiary care center from April 2008 to January 2012. Open- and closed-access procedures were compared in terms of diagnostic and therapeutic yield, adverse events, and procedural success. A total of 125 SBEs were performed on 125 patients. The mean age was 63.1 (53% men) years. In all, 43 procedures were performed open access and 82 after face-to-face consultation. Indications included anemia/gastrointestinal bleeding (110), abdominal pain (8), and other (7). Diagnostic yield for open- and closed-access procedures was 53% and 60%, respectively (P = 0.501) and therapeutic yield was 37% and 52%, respectively (P = 0.11). Overall technical success was 91% with no difference between the groups (P = 0.27). There were no major adverse events in either group. SBE can be performed as an open-access procedure without compromise to safety or diagnostic yield.

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Directory of Open Access Journals (Sweden)

Ariza de Schellenberger A

2016-04-01

Full Text Available Angela Ariza de Schellenberger,1 Harald Kratz,1 Tracy D Farr,2,3 Norbert Löwa,4 Ralf Hauptmann,1 Susanne Wagner,1 Matthias Taupitz,1 Jörg Schnorr,1 Eyk A Schellenberger1 1Department of Radiology, 2Department of Experimental Neurology, Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3School of Life Sciences, University of Nottingham, Medical School, Nottingham, UK; 4Department of Biomagnetic Signals, Physikalisch-Technische Bundesanstalt Berlin, Berlin, Germany Abstract: Sensitive cell detection by magnetic resonance imaging (MRI is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP designed by our department for magnetic particle imaging (MPI with discontinued Resovist® regarding their suitability for detection of single mesenchymal stem cells (MSC by MRI. We achieved an average intracellular nanoparticle (NP load of >10 pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist® in conjunction with high-resolution T2*-weighted imaging at 7 T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP

Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy

NARCIS (Netherlands)

van Manen, H.J.; Lenferink, Aufrid T.M.; Otto, Cornelis

2008-01-01

We have combined nonresonant Raman microspectroscopy and spectral imaging with stable isotope labeling by amino acids in cell culture (SILAC) to selectively detect the incorporation of deuterium-labeled phenylalanine, tyrosine, and methionine into proteins in intact, single HeLa cells. The C−D

Open-Label Single-Sequence Crossover Study Evaluating Pharmacokinetics, Efficacy, and Safety of Once-Daily Dosing of Nitisinone in Patients with Hereditary Tyrosinemia Type 1.

Science.gov (United States)

Guffon, Nathalie; Bröijersén, Anders; Palmgren, Ingrid; Rudebeck, Mattias; Olsson, Birgitta

2018-01-01

Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529). Well-controlled patients of dry blood spots by tandem mass spectrometry. The primary endpoint was C min of nitisinone after ≥4 weeks of treatment on each dosing regimen. Secondary objectives were evaluation of efficacy and safety during each dosing regimen. In total, 19 patients were enrolled and 17 included in the per-protocol analysis set. The mean (SD) nitisinone C min decreased by 23%, from 26.4 (10.2) to 21.2 (9.9) μmol/L in dry blood spot samples (not equivalent to plasma concentrations), when patients switched from twice- to once-daily dosing. There was no apparent age- or bodyweight-related trend in the degree of C min decrease. No patient had quantifiable succinylacetone levels during the once-daily treatment period, indicating efficacious treatment. All adverse events were mild or moderate and judged unrelated to nitisinone. The switch to once-daily treatment with nitisinone appeared efficacious and safe in the treatment of patients with HT-1.

Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

NARCIS (Netherlands)

Leonardi, C.; Strober, B.; Gottlieb, A.B.; Elewski, B.E.; Ortonne, J.P.; Kerkhof, P.C.M. van de; Chiou, C.F.; Dunn, M.; Jahreis, A.

2010-01-01

BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

Science.gov (United States)

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

2011-11-01

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

Science.gov (United States)

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

2011-11-01

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after intracardial injection in mice

International Nuclear Information System (INIS)

Salamon, J.; Adam, G.; Peldschus, K.; Wicklein, D.; Schumacher, U.; Didie, M.; Lange, C.

2014-01-01

Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ± 1.2 (n1), 9.0 ± 3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ± 3.1 (n1), 22.0 ± 6.1 (n2) and 89.8 ± 6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. Conclusion: The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. (orig.)

An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

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Pandina Gahan

2012-06-01

Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

Single-molecule mechanics of protein-labelled DNA handles

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Vivek S. Jadhav

2016-01-01

Full Text Available DNA handles are often used as spacers and linkers in single-molecule experiments to isolate and tether RNAs, proteins, enzymes and ribozymes, amongst other biomolecules, between surface-modified beads for nanomechanical investigations. Custom DNA handles with varying lengths and chemical end-modifications are readily and reliably synthesized en masse, enabling force spectroscopic measurements with well-defined and long-lasting mechanical characteristics under physiological conditions over a large range of applied forces. Although these chemically tagged DNA handles are widely used, their further individual modification with protein receptors is less common and would allow for additional flexibility in grabbing biomolecules for mechanical measurements. In-depth information on reliable protocols for the synthesis of these DNA–protein hybrids and on their mechanical characteristics under varying physiological conditions are lacking in literature. Here, optical tweezers are used to investigate different protein-labelled DNA handles in a microfluidic environment under different physiological conditions. Digoxigenin (DIG-dsDNA-biotin handles of varying sizes (1000, 3034 and 4056 bp were conjugated with streptavidin or neutravidin proteins. The DIG-modified ends of these hybrids were bound to surface-modified polystyrene (anti-DIG beads. Using different physiological buffers, optical force measurements showed consistent mechanical characteristics with long dissociation times. These protein-modified DNA hybrids were also interconnected in situ with other tethered biotinylated DNA molecules. Electron-multiplying CCD (EMCCD imaging control experiments revealed that quantum dot–streptavidin conjugates at the end of DNA handles remain freely accessible. The experiments presented here demonstrate that handles produced with our protein–DNA labelling procedure are excellent candidates for grasping single molecules exposing tags suitable for molecular

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

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Eunice Kazue Kano

2015-03-01

Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects.

Science.gov (United States)

Ruane, P J; Brinson, C; Ramgopal, M; Ryan, R; Coate, B; Cho, M; Kakuda, T N; Anderson, D

2015-05-01

Following antiretroviral therapy failure, patients are often treated with a three-drug regimen that includes two nucleoside/tide reverse transcriptase inhibitors [N(t)RTIs]. An alternative two-drug nucleoside-sparing regimen may decrease the pill burden and drug toxicities associated with the use of N(t)RTIs. The Intelence aNd pRezista Once A Day Study (INROADS; NCT01199939) evaluated the nucleoside-sparing regimen of etravirine 400 mg with darunavir/ritonavir 800/100 mg once-daily in HIV-1-infected treatment-experienced subjects or treatment-naïve subjects with transmitted resistance. In this exploratory phase 2b, single-arm, open-label, multicentre, 48-week study, the primary endpoint was the proportion of subjects who achieved HIV-1 RNA treatment-experienced subjects or treatment-naïve subjects with transmitted resistance was virologically efficacious and well tolerated. © 2014 British HIV Association.

Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

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Shadi Baniasadi

Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

Directory of Open Access Journals (Sweden)

Shadi Baniasadi

2013-02-01

Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

Influence of quantum dot labels on single molecule movement in the plasma membrane

DEFF Research Database (Denmark)

Clausen, Mathias P.; Lagerholm, B. Christoffer

2011-01-01

Single particle tracking results are very dependent on the probe that is used. In this study we have investigated the influence that functionalized quantum dots (QDs) have on the recorded movement in single molecule tracking experiments of plasma membrane species in live cells. Potential issues...... for simultaneous investigations of different plasma membrane species in order to discriminate the effect of the label from differences in movement of the target molecules....

The Effects of Individual Upper Alpha Neurofeedback in ADHD: An Open-Label Pilot Study

OpenAIRE

Escolano , Carlos; Navarro-Gil , Mayte; Garcia-Campayo , Javier; Congedo , Marco; Minguez , Javier

2014-01-01

International audience; Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individual...

Label Space Reduction in MPLS Networks: How Much Can A Single Stacked Label Do?

DEFF Research Database (Denmark)

Solano, Fernando; Stidsen, Thomas K.; Fabregat, Ramon

2008-01-01

Most network operators have considered reducing LSR label spaces (number of labels used) as a way of simplifying management of underlaying virtual private networks (VPNs) and therefore reducing operational expenditure (OPEX). The IETF outlined the label merging feature in MPLS-allowing the config......Most network operators have considered reducing LSR label spaces (number of labels used) as a way of simplifying management of underlaying virtual private networks (VPNs) and therefore reducing operational expenditure (OPEX). The IETF outlined the label merging feature in MPLS...

A toy model for single field open inflation

International Nuclear Information System (INIS)

Vaudrevange, Pascal M.; Westphal, Alexander

2012-05-01

Inflation in an open universe produced by Coleman-De Luccia (CDL) tunneling induces a friction term that is strong enough to allow for successful small-field inflation in models that would otherwise suffer from a severe overshoot problem. In this paper, we present a polynomial scalar potential which allows for a full analysis. This provides a simple model of single-field open inflation on a small-field inflection point after tunneling. We present numerical results and compare them with analytic approximations.

Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system

DEFF Research Database (Denmark)

Antfolk, Maria; Kim, Soo Hyeon; Koizumi, Saori

2017-01-01

, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood...... a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice....

Armodafinil for fatigue associated with menopause: an open-label trial.

Science.gov (United States)

Meyer, Fremonta; Freeman, Marlene P; Petrillo, Laura; Barsky, Maria; Galvan, Thania; Kim, Semmie; Cohen, Lee; Joffe, Hadine

2016-02-01

This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

Integrated MRSA-Management (IMM with prolonged decolonization treatment after hospital discharge is effective: a single centre, non-randomised open-label trial

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Bernhard Jahn

2016-06-01

Full Text Available Abstract Background Guidelines for the control of hospital-acquired MRSA include decolonization measures to end MRSA carrier status in colonized and infected patients. Successful decolonization typically requires up to 22 days of treatment, which is longer than the average hospital length of stay (LOS. Incomplete decolonization is therefore common, with long-term MRSA carriage as a consequence. To overcome this, we developed an integrated MRSA Management (IMM by extending MRSA decolonization to the outpatient and domestic setting. The protocol makes use of polyhexanide-based products, in view of reported qac-mediated resistance to chlorhexidine in S. aureus and MRSA. Methods This is a prospective, single centre, controlled, non-randomized, open-label study to evaluate the efficiency of the IMM concept. The outcome of guideline-approved decolonization during hospital stay only (control group; n = 201 was compared to the outcome following IMM treatment whereby decolonization was continued after discharge in the domestic setting or in a long-term care facility (study group; n = 99. As a secondary outcome, the effect of MRSA-status of skin alterations was assessed. Results The overall decolonization rate was 47 % in the IMM patient group compared to 12 % in the control group (p  0.05. For patients with skin alterations (e.g. wounds and entry sites, decolonization success was 50 % if the skin alterations were MRSA-negative at baseline, compared to 22 % success for patients entering the study with MRSA-positive skin alterations (p < 0.01. Conclusions The IMM strategy offers an MRSA decolonization protocol that is feasible in the domestic setting and is equally effective compared with inpatient decolonization treatment when hospital LOS is long enough to complete the treatment. Moreover, for patients with average LOS, decolonization rates obtained with IMM are significantly higher than for in-hospital treatment. IMM is a promising

Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

Science.gov (United States)

Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-09-08

MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical and instrumental evaluation of a cross-linked hyaluronic acid filler dermal injection: effects on nasolabial folds skin biophysical parameters and augmentation from a single-dose, monocentric, open-label trial.

Science.gov (United States)

Cameli, Norma; Mariano, Maria; Serio, Mirko; Berardesca, Enzo

2016-10-01

When a hyaluronic acid dermal device to fill soft tissues is chosen, efficacy, safety and durability are key concerns. This is an open-label prospective study to instrumentally evaluate the effects of HA filler dermal injection on nasolabial folds skin biophysical parameters and augmentation. A single Italian site treated female subjects aged 40-55, for nasolabial folds, with a single standardized injection. The outcome was evaluated with objective quantitative measurements after 90 (T1) and 180 days (T2) from the injection comparing to baseline (T0) by means of Corneometer (skin hydration measurement), Cutometer (skin elasticity measurement), and Visioface devices for digital and UV computerized image analysis. Secondary endpoints were safety assessment, subject investigator satisfaction with the intervention. Assessment of aesthetic results included photographic documentation. The computerized image analysis confirmed the clinical assessment showing statistically significant reduction in nasolabial folds both at T1 and T2. Visioface® indexes showed a marked and statistical significant response. An excellent profile of satisfaction of the product at T2 from investigators and patients was recorded. Skin hydration and elasticity did not show significant changes. In our study, a standardized HA filler dermal injection on nasolabial folds did not influence skin biophysical parameters such as skin hydration and elasticity. Nasolabial folds showed a persistent and significative response at T2 confirmed by instrumental evaluation. The tolerability and safety profile of the product was excellent.

The Effect of a Novel form of Extended-Release Gabapentin on Pain and Sleep in Fibromyalgia Subjects: An Open-Label Pilot Study.

Science.gov (United States)

North, James M; Hong, Kyung-Soo J; Rauck, Richard L

2016-07-01

We assessed the efficacy and safety of extended-release gabapentin in a 15-week, open-label, single-arm, single-center study in patients with fibromyalgia (FM). Subjects with documented diagnosis of FM were allowed to participate in the study. We opened enrollment to those who have tried and failed gabapentinoids such as gabapentin or pregabalin due to side effects. Subjects with autoimmune conditions, and or taking opioids for management of their FM pain, were excluded from the study. Subjects were given an extended-release gabapentin starter pack and treated for total of 12 weeks. The primary study endpoint of pain relief was measured using Numeric Pain Rating System (NPRS) scores, and secondary study endpoints were measured with Fibromyalgia Impact Questionnaire (FIQ), Patient's Global Impression of Change (PGIC), and Medical Outcome Sleep questionnaires (MOS). A total of 34 subjects were enrolled and 29 subjects completed the starter pack (85%). Patients reported significant pain relief on NPRS by end of 4 weeks (P life by end of 4 weeks on FIQ (P quality. Improvements in primary and secondary measurements were reflected in PGIC, with significant improvement in patient's impression of FM by week 8. Small sample size, geographical bias, relatively short duration of treatment, and single-arm study without control group. Extended-release gabapentin relieved FM pain symptoms and improved quality-of-life for the FM subjects studied. Subjects reported improvements in both quantity and quality of sleep. © 2015 World Institute of Pain.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study

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Caio Abujadi

2017-12-01

Full Text Available Objective: Theta-burst stimulation (TBS modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD. At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study.

Science.gov (United States)

Abujadi, Caio; Croarkin, Paul E; Bellini, Bianca B; Brentani, Helena; Marcolin, Marco A

2017-12-11

Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases.

Science.gov (United States)

Forbes, Jessica L; Kim, Regina E Y; Paulsen, Jane S; Johnson, Hans J

2016-01-01

The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%.

Open-label placebo treatment in chronic low back pain: a randomized controlled trial.

Science.gov (United States)

Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J; Kirsch, Irving

2016-12-01

This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

Label-free, single-object sensing with a microring resonator: FDTD simulation.

Science.gov (United States)

Nguyen, Dan T; Norwood, Robert A

2013-01-14

Label-free, single-object sensing with a microring resonator is investigated numerically using the finite difference time-domain (FDTD) method. A pulse with ultra-wide bandwidth that spans over several resonant modes of the ring and of the sensing object is used for simulation, enabling a single-shot simulation of the microring sensing. The FDTD simulation not only can describe the circulation of the light in a whispering-gallery-mode (WGM) microring and multiple interactions between the light and the sensing object, but also other important factors of the sensing system, such as scattering and radiation losses. The FDTD results show that the simulation can yield a resonant shift of the WGM cavity modes. Furthermore, it can also extract eigenmodes of the sensing object, and therefore information from deep inside the object. The simulation method is not only suitable for a single object (single molecule, nano-, micro-scale particle) but can be extended to the problem of multiple objects as well.

A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

Directory of Open Access Journals (Sweden)

Nalamachu S

2014-11-01

Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

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Wang, Michael L; Lee, Hun; Chuang, Hubert; Wagner-Bartak, Nicolaus; Hagemeister, Frederick; Westin, Jason; Fayad, Luis; Samaniego, Felipe; Turturro, Francesco; Oki, Yasuhiro; Chen, Wendy; Badillo, Maria; Nomie, Krystle; DeLa Rosa, Maria; Zhao, Donglu; Lam, Laura; Addison, Alicia; Zhang, Hui; Young, Ken H; Li, Shaoying; Santos, David; Medeiros, L Jeffrey; Champlin, Richard; Romaguera, Jorge; Zhang, Leo

2016-01-01

Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one

Laserlight cues for gait freezing in Parkinson's disease: an open-label study.

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Donovan, S; Lim, C; Diaz, N; Browner, N; Rose, P; Sudarsky, L R; Tarsy, D; Fahn, S; Simon, D K

2011-05-01

Freezing of gait (FOG) and falls are major sources of disability for Parkinson's disease (PD) patients, and show limited responsiveness to medications. We assessed the efficacy of visual cues for overcoming FOG in an open-label study of 26 patients with PD. The change in the frequency of falls was a secondary outcome measure. Subjects underwent a 1-2 month baseline period of use of a cane or walker without visual cues, followed by 1 month using the same device with the laserlight visual cue. The laserlight visual cue was associated with a modest but significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 ± 0.48 (p = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was 39.5 ± 9.3% with the laserlight visual cue among subjects experiencing at least one fall during the baseline and subsequent study periods (p = 0.002; two-tailed one-sample t-test with hypothesized mean of 0). Though some individual subjects may have benefited, the overall mean performance on the timed gait test (TGT) across all subjects did not significantly change. However, among the 4 subjects who underwent repeated testing of the TGT, one showed a 50% mean improvement in TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t-test). This open-label study provides evidence for modest efficacy of a laserlight visual cue in overcoming FOG and reducing falls in PD patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

High-dose nifuratel for simple and mixed aerobic vaginitis: A single-center prospective open-label cohort study.

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Liang, Qian; Li, Nan; Song, Shurong; Zhang, Aihua; Li, Ni; Duan, Ying

2016-10-01

The efficacy and safety of two nifuratel dosages for the treatment of aerobic vaginitis (AV) were compared. This was a prospective open-label cohort study of patients diagnosed and treated at the Tianjin Third Central Hospital between January 2012 and December 2013. The co-presence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or/and trichomonal vaginitis (TV; mixed AV) was determined. Patients were randomized to nifuratel-500 (500 mg nifuratel, intravaginal, 10 days) or nifuratel-250 (250 mg nifuratel, intravaginal, 10 days), and followed-up for three to seven days after treatment completion. Primary and secondary outcomes were recovery rate and adverse events, respectively. The study included 142 patients with AV. Age was not significantly different between the groups (n = 71 each), and disease distribution was identical: 29 (40.85%) simple AV and 42 (59.15%) mixed AV (AV + BV, 42.86 %; AV + VVC, 30.95%; AV + TV, 26.19%). In patients with simple AV, the recovery rate did not differ significantly between the nifuratel-500 (26/29, 89.66%) and nifuratel-250 (22/29, 75.86%) groups. In patients with mixed AV, recovery rates were significantly higher in the nifuratel-500 than in the nifuratel-250 group (AV + BV, 88.89% vs 50.00 %; AV + VVC, 76.92 % vs 30.77 %; AV + TV, 90.91 % vs 36.36%; all P < 0.05). Only one patient (nifuratel-500) reported an adverse event (mild anaphylactic reaction). Nifuratel 500 mg showed good clinical efficacy for the treatment of AV, particularly mixed AV, and is superior to the 250 mg dosage in the treatment of mixed AV. © 2016 Japan Society of Obstetrics and Gynecology.

Bioavailability of two single-dose oral formulations of omeprazole 20 mg: an open-label, randomized sequence, two-period crossover comparison in healthy Mexican adult volunteers.

Science.gov (United States)

Poo, Jorge Luis; Galán, Juan Francisco; Rosete, Alejandra; de Lago, Alberto; Oliva, Iván; González-de la Parra, Mario; Jiménez, Patricia; Burke-Fraga, Victoria; Namur, Salvador

2008-04-01

Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P disability, or required intervention to prevent permanent impairment or damage. Thirty-four subjects were enrolled and completed the study (25 men and 9

Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

DEFF Research Database (Denmark)

Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

2017-01-01

vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

Science.gov (United States)

Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

2014-01-01

The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

Science.gov (United States)

Sugimoto, Shinya; Naganuma, Makoto; Kiyohara, Hiroki; Arai, Mari; Ono, Keiko; Mori, Kiyoto; Saigusa, Keiichiro; Nanki, Kosaku; Takeshita, Kozue; Takeshita, Tatsuya; Mutaguchi, Makoto; Mizuno, Shinta; Bessho, Rieko; Nakazato, Yoshihiro; Hisamatsu, Tadakazu; Inoue, Nagamu; Ogata, Haruhiko; Iwao, Yasushi; Kanai, Takanori

2016-01-01

Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted. © 2016 S. Karger AG, Basel.

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, C; Thomsen, L L; Norgaard, A

2017-01-01

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

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Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

2013-11-01

To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor.

Science.gov (United States)

Zhang, Bailin; Tamez-Vela, Juan Manuel; Solis, Steven; Bustamante, Gilbert; Peterson, Ralph; Rahman, Shafiqur; Morales, Andres; Tang, Liang; Ye, Jing Yong

2013-01-01

The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC-TIR) is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects.

Comparative fasting bioavailability of 2 bepotastine formulations in healthy male Chinese volunteers: an open-label, randomized, single-dose, 2-way crossover study.

Science.gov (United States)

Shentu, Jianzhong; Zhou, Huili; Hu, Xingjiang; Wu, Guolan; Wu, Lihua; Zhu, Meixiang; Zhai, You; Zheng, Yunliang; Liu, Jian

2014-04-01

Bepotastine is a second-generation histamine1 receptor antagonist that is used in the treatment of allergic rhinitis, urticaria, and pruritus associated with skin disease. A new generic formulation of bepotastine has been developed in China, and information concerning bioavailability and pharmacokinetic properties in the Chinese population has not been reported. The aim of the present study was to compare the bioavailability and pharmacokinetic properties of 2 tablet formulations of bepotastine, the 10-mg generic formulation (test) and a branded formulation (reference), in healthy male Chinese volunteers to obtain registration approval of the test formulation. A single-center, open-label, randomized, 2-way crossover study with a 1-week washout period was conducted in 24 healthy male volunteers. Blood samples were collected for 16 hours after a single dose of the 10-mg bepotastine test formulation or the reference formulation. Plasma bepotastine concentrations were determined using a validated LC-MS/MS method. Cmax, Tmax, AUC₀-t, AUC₀-∞, and t½ were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for the log-transformed Cmax and AUC values were within the predetermined interval of 75% to 133% and 80% to 125%, respectively, according to the guidelines of the China Food and Drug Administration. No significant differences were found in mean (SD) pharmacokinetic parameters between the test and reference drugs, including Cmax (74.81 [9.91] ng/mL vs 78.60 [29.58] ng/mL), AUC₀-t (295.55[115.29] ng·h/mL vs 299.17[109.29] ng·h/mL), and AUC0-∞ (305.28 [118.50] ng·h/mL vs 310.90 [112.20] ng·h/mL). The mean (SD) t½ values of the test and reference formulations were 2.53 (0.50) hours and 2.62 (0.41) hours, respectively. The 90% CIs of the treatment ratios for the logarithmic transformed values of Cmax, AUC₀-t, and AUC₀-∞ were 86.96% to 101.80%, 93.22% to 104.13%, and 92.66% to 103.30%, respectively

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

Science.gov (United States)

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P 1). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Science.gov (United States)

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

76 FR 76890 - Nutrition Labeling of Single-Ingredient Products and Ground or Chopped Meat and Poultry Products...

Science.gov (United States)

2011-12-09

.... FSIS-2005-0018] Nutrition Labeling of Single-Ingredient Products and Ground or Chopped Meat and Poultry... major cuts of single-ingredient, raw meat and poultry products and ground or chopped meat and poultry... Ground or Chopped Meat and Poultry Products'' in the Federal Register (75 FR 82148) that, among other...

Synthesis of 13N and/or 11C single or doubly labelled urea

International Nuclear Information System (INIS)

Emran, A.M.

1989-01-01

Utilization of nitrogen by plants encounters two important problems which are denitrification and deficiency or inactivation of certain enzyme. In the first process the fertilizer is affected by certain bacteria to produce nitrogen or its oxides which cannot be utilized by plants. In the second process, transformation of urea nitrogen into forms usable by plants depends on abundance and activity of the enzyme urease. Study of inorganic nitrogen transport has been underway using 13 N-nitrate as a tracer. Behavior of organic nitrogen can be studied using labelled urea. [ 13 N] and/or [ 11 C] single or doubly labelled urea are good tracers for this purpose. Reaction of trace amounts of potassium cyanate with 13 N-ammonium sulfate produced 13 N-ammonium cyanate which was thermally transformed into [ 13 N]-urea with no added carrier. Similarly, [ 11 C]-potassium cyanate reacted with 13 N-ammonium sulfate to produce 13 N/ 11 C-doubly labelled urea. Thin layer and high performance liquid chromatography were used to identify the products and determine the yields

An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics.

Science.gov (United States)

Li, Yan; Wang, Xiaomin; Liu, Liangang; Zhang, Chengyue; Gomez, Diana; Reyes, Josephine; Palmisano, Maria; Zhou, Simon

2018-05-10

Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C max ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction). © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

Directory of Open Access Journals (Sweden)

Berlant Jeffrey L

2004-08-01

Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

Science.gov (United States)

Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

2016-08-01

To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

DEFF Research Database (Denmark)

Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

2016-01-01

Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retrea...

15N incorporation into organ proteins of newborn rats following single pulse-labelling with different tracers

International Nuclear Information System (INIS)

Wutzke, K.D.; Plath, C.; Richter, I.; Heine, W.; Zhukova, T.P.; Sorokina, E.G.; Friedrich, M.

1987-01-01

A short-chain 15 N-peptide mixture characterized by an average chain length of 2.3 was obtained when 15 N-labelled yeast protein was hydrolyzed enzymatically by thermitase from Thermoactinomyces vulgaris. Fifteen newborn Wistar rats were given a single pulse of [ 15 N]glycine. [ 15 N]H 4 Cl and [ 15 N]yeast protein thermitasehydrolysate (YPTH) in a dosage of 50 mg 15 N excess kg -1 by gastric tube. In comparison with [ 15 N]glycine the 15 N incorporation rates of brain, muscle and liver were approximately 150% higher after [ 15 N]YPTH application. Uniform labelling, high 15 N enrichment, almost complete absorption, avoidance of imbalances and the low price make this tracer substance superior to other tracers conventionally used for organ labelling. (author)

Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers.

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Thudium, Karen; Gallo, Jorge; Bouillaud, Emmanuel; Sachs, Carolin; Eddy, Simantini; Cheung, Wing

2015-01-01

The mammalian target of rapamycin (mTOR) inhibitor everolimus has a well-established pharmacokinetics profile. We conducted a randomized, single-center, open-label, two-sequence, two-period crossover study of healthy volunteers to assess the relative bioavailability of everolimus administered as one 5 mg tablet or five 1 mg tablets. Subjects were randomized 1:1 to receive everolimus dosed as one 5 mg tablet or as five 1 mg tablets on day 1, followed by a washout period on days 8-14 and then the opposite formulation on day 15. Blood sampling for pharmacokinetic evaluation was performed at prespecified time points, with 17 samples taken for each treatment period. Primary variables for evaluation of relative bioavailability were area under the concentration-time curve from time zero to infinity (AUCinf) and maximum blood concentration (Cmax). Safety was assessed by reporting the incidence of adverse events (AEs). Twenty-two participants received everolimus as one 5 mg tablet followed by five 1 mg tablets (n=11) or the opposite sequence (n=11). The Cmax of five 1 mg tablets was 48% higher than that of one 5 mg tablet (geometric mean ratio, 1.48; 90% confidence interval [CI], 1.35-1.62). AUCinf was similar (geometric mean ratio, 1.08; 90% CI, 1.02-1.16), as were the extent of absorption and the distribution and elimination kinetics. AEs, all grade 1 or 2, were observed in 54.5% of subjects. Although the extent of absorption was similar, the Cmax of five 1 mg tablets was higher than that of one 5 mg tablet, suggesting these formulations lead to different peak blood concentrations and are not interchangeable at the dose tested.

A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State.

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Chen, Chun Lin; Desai-Krieger, Daksha; Ortiz, Stephan; Kerolous, Majid; Wright, Harold M; Ghahramani, Parviz

2015-01-01

Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose of monotherapies. The aims of this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, and valsartan, an angiotensin II receptor blocker, and to assess safety and tolerability of the combination. This was a single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45 years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-τ,ss, Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin activity, 24-hour urinary aldosterone, and adverse events. Steady-state pharmacokinetic interactions were observed but deemed not clinically significant. Systolic and diastolic BP reduction was significantly greater with nebivolol-valsartan combination than with either monotherapy. The mean pulse rate associated with nebivolol and nebivolol-valsartan treatments was consistently lower than that associated with valsartan monotherapy. A sharp increase in mean day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan-treated participants was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at day 7 was substantially decreased after combined treatment, as compared with either monotherapy. All treatments were safe and well tolerated. In conclusion, nebivolol and valsartan coadministration led to greater reductions in BP compared with either monotherapy; nebivolol and valsartan lower BP through complementary mechanisms.

Simvastatin as an Adjunct to Conventional Therapy of Non-infectious Uveitis: A Randomized, Open-Label Pilot Study.

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Shirinsky, Ivan V; Biryukova, Anastasia A; Shirinsky, Valery S

2017-12-01

Statins have been shown to reduce ocular inflammation in animal models of uveitis and to prevent development of uveitis in observational studies. There have been no experimental human studies evaluating statins' efficacy and safety in uveitis. In this study, we aimed to investigate efficacy and safety of simvastatin in patients with uveitis. For this single-center, open-label, randomized study, we enrolled patients with acute non-infectious uveitis. The patients were randomized to receive 40 mg simvastatin per day for 2 months in addition to conventional treatment or conventional treatment alone. The studied outcomes were the rate of steroid-sparing control of ocular inflammation, measures of ocular inflammation, intraocular pressure, and visual acuity. Fifty patients were enrolled in the study. Twenty-five patients were randomly assigned to receive simvastatin with conventional treatment and 25 to conventional treatment alone. Simvastatin was associated with significantly higher rates of steroid-sparing ocular inflammation control, decrease in anterior chamber inflammation, and improvement in visual acuity. The treatment was well tolerated, no serious adverse effects were observed. Our findings suggest that statins may have therapeutic potential in uveitis. These results need to be confirmed in double-blind, randomized, controlled studies.

Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.

Science.gov (United States)

Shi, Shaojun; Liu, Yani; Wu, Jianhong; Li, Zhongfang; Zhao, Yan; Zhong, Dafang; Zeng, Fandian

2010-10-01

The proprietary formulation of fluoxetine hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. Pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed to market generic fluoxetine in China. The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population. This 10-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test or reference formulation, followed by a 35-day washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0-t), AUC(0-∞), and t(½)), blood samples were obtained over a 672-hour period after dosing. Plasma concentrations of fluoxetine and its active metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The formulations were to be considered bioequivalent if the ln-transformed ratios (test/ reference) of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125%, as established by the US Food and Drug Administration, and if the P values were fasting, healthy Chinese male volunteers. Both formulations appeared to be well tolerated. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

Deuterium labeled cannabinoids

International Nuclear Information System (INIS)

Driessen, R.A.

1979-01-01

Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

Science.gov (United States)

Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

2016-10-25

To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

The efficacy of single-stage open intramedullary nailing of neglected femur fractures.

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Boopalan, P R J V C; Sait, Azad; Jepegnanam, Thilak Samuel; Matthai, Thomas; Varghese, Viju Daniel

2014-02-01

Neglected femur fractures are not rare in the developing world. Treatment options include single-stage open reduction and intramedullary nailing, or open release, skeletal traction, and then second-stage open intramedullary nailing, with bone grafting. Single-stage procedures have the potential advantage of avoiding neurovascular complications secondary to acute lengthening, but they require a second operation, with potentially increased resource use and infection risk. We sought to determine the (1) likelihood of union, (2) complications and reoperations, and (3) functional results with single-stage open intramedullary nailing without bone grafting in patients with neglected femur fractures. Between January 2003 and December 2007, 17 consecutive patients presented to our practice with neglected femoral shaft fractures. All were treated with single-stage nailing without bone grafting. There were 15 men and two women with a median age of 27 years. The average time from fracture to treatment was 13 weeks (range, 4-44 weeks). Eleven patients underwent open nailing with interlocked nails and six were treated with cloverleaf Kuntscher nails. Patients were followed for a minimum of 6 months (mean, 33 months; range, 6-72 months). The mean preoperative ROM of the knee was 28° (range, 10°-150°) and femoral length discrepancy was 3.1 cm (range, 1-5 cm). All fractures united and the mean time to union was 16 weeks (range, 7-32 weeks). There were no neurologic complications secondary to acute lengthening. The mean postoperative ROM of the knee was 130° (range, 60°-150°). All patients were able to return to preinjury work. Sixteen patients regained their original femoral length. One-stage open intramedullary nailing of neglected femoral diaphyseal fractures without bone grafting was safe and effective, and obviated the need for a two-stage approach. Although the findings need to be replicated in larger numbers of patients, we believe this technique may be useful in

Monte Carlo simulation of second-generation open-type PET ''single-ring OpenPET'' implemented with DOI detectors

International Nuclear Information System (INIS)

Tashima, Hideaki; Yamaya, Taiga; Hirano, Yoshiyuki; Yoshida, Eiji; Kinouch, Shoko; Watanabe, Mitsuo; Tanaka, Eiichi

2013-01-01

At the National Institute of Radiological Sciences, we are developing OpenPET, an open-type positron emission tomography (PET) geometry with a physically open space, which allows easy access to the patient during PET studies. Our first-generation OpenPET system, dual-ring OpenPET, which consisted of two detector rings, could provide an extended axial field of view (FOV) including the open space. However, for applications such as in-beam PET to monitor the dose distribution in situ during particle therapy, higher sensitivity concentrated on the irradiation field is required rather than a wide FOV. In this report, we propose a second-generation OpenPET geometry, single-ring OpenPET, which can efficiently improve sensitivity while providing the required open space. When the proposed geometry was realized with block detectors, position-dependent degradation of the spatial resolution was expected because it was necessary to arrange the detector blocks in ellipsoidal rings stacked and shifted relative to one another. However, we found by Monte Carlo simulation that the use of depth-of-interaction (DOI) detectors made it feasible to achieve uniform spatial resolution in the FOV. (author)

The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial.

Science.gov (United States)

Berk, Michael; Dean, Olivia; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa S; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Allwang, Christine; Cobb, Heidi; Bush, Ashley I; Schapkaitz, Ian; Dodd, Seetal; Malhi, Gin S

2011-12-01

Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (pdepression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

Science.gov (United States)

Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not

Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

Science.gov (United States)

Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

2013-01-01

Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

Directory of Open Access Journals (Sweden)

Yang FD

2017-04-01

Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

Open-label study of donepezil in traumatic brain injury.

Science.gov (United States)

Masanic, C A; Bayley, M T; VanReekum, R; Simard, M

2001-07-01

To determine preliminarily whether donepezil will improve memory, behavior, and global function after chronic traumatic brain injury (TBI). Sixteen-week open-label study. Outpatient TBI rehabilitation program. Four patients with chronic, severe TBI. Donepezil 5mg daily for 8 weeks followed by 10mg daily for 4 weeks. Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI) evaluated behavior and affect. Function was assessed by using the FIM instrument and a clinical global impression of change. On the RAVLT, the mean scores for learning and short- and long-term recall improved by 0.4, 1.04, and.83 standard deviations (SDs) above baseline, respectively. On the CFT, the mean scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs above baseline, respectively. A positive trend was observed on the RBMT and on the NPI subscales. Donepezil may improve some aspects of memory and behavior in persons with chronic TBI. Randomized clinical trials are required to support these preliminary findings. Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Ethosuximide for Essential Tremor: An Open-Label Trial

Science.gov (United States)

Gironell, Alexandre; Marin-Lahoz, Juan

2016-01-01

Background T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score. Results Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients’ subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET. PMID:27625899

Ethosuximide for Essential Tremor: An Open-Label Trial

Directory of Open Access Journals (Sweden)

Alexandre Gironell

2016-07-01

Full Text Available Background: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods: Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID. The main outcome measures were: 1 tremor clinical rating scale (TCRS score, 2 accelerometric recordings, and 3 self-reported disability scale score. Results: Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2, daily living activities (TCRS 3, or in the patients’ subjective assessment (TCRS 4 and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion: The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET.

Light-harvesting dendrimer zinc-phthalocyanines chromophores labeled single-wall carbon nanotube nanoensembles: Synthesis and photoinduced electron transfer

Energy Technology Data Exchange (ETDEWEB)

Yang, Hongqin [Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou 350007 (China); Pan, Sujuan; Ma, Dongdong; He, Dandan; Wang, Yuhua [College of Chemistry & Engineering, Fujian Provincial Key Laboratory of Polymer Materials, Fujian Normal University, Fuzhou 350007 (China); Xie, Shusen [Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou 350007 (China); Peng, Yiru, E-mail: yirupeng@fjnu.edu.cn [College of Chemistry & Engineering, Fujian Provincial Key Laboratory of Polymer Materials, Fujian Normal University, Fuzhou 350007 (China)

2016-11-15

A novel series of light-harvesting dendrimer zinc-phthalocyanines chromophores labeled-single-wall carbon nanotubes (SWNTs) nanoparticles, in which 0–2 generations dendrimer zinc phthalocyanines covalently linked with SWNTs using either ethylenediamine or hexamethylenediamine as the space linkers were prepared. The structures and morphologies of these nanoconjugates were comprehensively characterized by Raman spectroscopy, transmission electron microscopy and thermal gravimetric analysis methods. Their photophysical properties were investigated by fluorescence and time-resolved spectroscopic methods. The photoinduced intramolecular electron transfer occurred from phthalocyanines (donors) to SWNTs (acceptors). Besides, the electron transfer exchange rates and exchange efficacies between the dendritic phthalocyanines and single-wall carbon nanotubes increased as the length of spacer linker decreased, or as the dendritic generation increased. Cyclic voltammetry (CV) method further confirmed thermodynamics possibility of the electron transfer from phthalocyanines to single-wall carbon nanotubes. These new nanoconjugates are fundamentally important due to the synergy effects of both carbon nanotubes and dendrimer phthalocyanines, which may find potential applications in the fields of drug delivery, biological labeling, or others.

Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.

Science.gov (United States)

Kaufman, Howard L; Russell, Jeffery; Hamid, Omid; Bhatia, Shailender; Terheyden, Patrick; D'Angelo, Sandra P; Shih, Kent C; Lebbé, Céleste; Linette, Gerald P; Milella, Michele; Brownell, Isaac; Lewis, Karl D; Lorch, Jochen H; Chin, Kevin; Mahnke, Lisa; von Heydebreck, Anja; Cuillerot, Jean-Marie; Nghiem, Paul

2016-10-01

Merkel cell carcinoma is a rare, aggressive skin cancer with poor prognosis in patients with advanced disease. Current standard care uses various cytotoxic chemotherapy regimens, but responses are seldom durable. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. We assessed treatment with avelumab, an anti-PD-L1 monoclonal antibody, in patients with stage IV Merkel cell carcinoma that had progressed after cytotoxic chemotherapy. In this multicentre, international, prospective, single-group, open-label, phase 2 trial, patients with stage IV chemotherapy-refractory, histologically confirmed Merkel cell carcinoma (aged ≥18 years) were enrolled from 35 cancer treatment centres and academic hospitals in North America, Europe, Australia, and Asia. Key eligibility criteria were an ECOG performance status of 0 or 1, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, adequate haematological, hepatic, and renal function, and immune-competent status (patients with HIV, immunosuppression, haematological malignancies, and previous organ transplantation were excluded). Patient selection was not based on PD-L1 expression or Merkel cell polyomavirus status. Collection of biopsy material or use of archival tissue for these assessments was mandatory. Avelumab was given intravenously at a dose of 10 mg/kg every 2 weeks. The primary endpoint was confirmed objective response (complete response or partial response) assessed according to RECIST version 1.1 by an independent review committee. Safety and clinical activity were assessed in all patients who received at least one dose of study drug (the modified intention-to-treat population). This trial is registered with ClinicalTrials.gov as NCT02155647. Between July 25, 2014, and Sept 3, 2015, 88 patients were enrolled and received at

Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study.

Science.gov (United States)

Jang, Seong Bok; Lee, Yoon Jung; Lim, Lay Ahyoung; Park, Kyung-Mi; Kwon, Bong-Ju; Woo, Jong Soo; Kim, Yong-Il; Park, Min Soo; Kim, Kyung Hwan; Park, Kyungsoo

2010-01-01

A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation. The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, open-label, parallelgroup, 2-part study. Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20% of their ideal weight. In part I, each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally (20 mg x 2 tablets) after fasting. In part II, each subject received the same dose of the CR or IR formulation for 8 consecutive days. Blood samples were obtained for 48 hours after the dose in part I and after the first and the last dose in part II. Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety). An adverse event (AE) was defined as any unfavorable sign (including an abnormal laboratory finding) or symptom, regardless of whether it had a causal relationship with the study medication. Serious AEs were defined as any events that are considered life threatening, require hospitalization or prolongation of existing hospitalization, cause persistent or significant disability or incapacity, or result in congenital abnormality, birth defect, or death. AEs were determined based on patient interviews and physical examinations. Twenty-four healthy subjects (17 men, 7 women; mean [SD] age, 29 [7] years; age range, 22-50 years) were enrolled in part I, and 29 subjects (17 men, 12 women; mean age, 33 [9] years; age range, 19-55 years) were enrolled in part II. For simvastatin acid, C

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

Science.gov (United States)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a

An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

Science.gov (United States)

Erickson, Craig A; Early, Maureen; Stigler, Kimberly A; Wink, Logan K; Mullett, Jennifer E; McDougle, Christopher J

2011-12-01

To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.

Preliminary open-label clinical evaluation of the soothing and reepithelialization properties of a novel topical formulation for rosacea

Directory of Open Access Journals (Sweden)

Sparavigna A

2014-10-01

Full Text Available Adele Sparavigna, Beatrice Tenconi, Ileana De Ponti Derming Srl, Monza, Italy Background: Rosacea is a common, incurable skin barrier disorder characterized by relapses and remissions. Purpose: To evaluate the efficacy of Farmaka Rosacea Cream (FRC, a novel topical formulation for rosacea. Methods: This single-center, open-label pilot study comprised a single-dose substudy in 20 healthy subjects and a long-term, repeat-dose substudy in 22 subjects with rosacea. The 2-hour, controlled, single-dose substudy assessed the soothing and reepithelialization properties of FRC after stripping-induced erythema based on the erythema index, transepidermal water loss, skin hydration, and clinical assessments of erythema. In the long-term substudy, subjects applied FRC twice daily for 8 weeks. Clinical assessments included vascular and pigmentary homogeneity and erythema and hemoglobin indices. Subjects completed questionnaires to assess FRC efficacy and cosmetic acceptability. Results: Greater reductions were seen in FRC-treated areas compared with untreated areas for the erythema index (-16% versus -8%; P<0.001 and mean transepidermal water loss (-35.8% versus -10.1%; P<0.001 30 minutes after stripping. Significant improvements over untreated areas were maintained 2 hours after stripping. Skin hydration and clinical erythema assessments also indicated that FRC soothed rosacea symptoms and promoted skin reepithelialization. Erythema and hemoglobin indices were significantly reduced from baseline after 4 and 8 weeks of treatment. Clinically assessed parameters were significantly improved following FRC application. Subjects assessed FRC positively. Conclusion: Improvement of rosacea symptoms was noted with FRC application. The main film-forming ingredients of FRC (trehalose, cholesterol, ceramide, and fatty acids, combined with other soothing and calming ingredients and ultraviolet filters, could explain its efficacy. Keywords: rosacea, erythema, skin

A proof that Witten's open string theory gives a single cover of moduli space

International Nuclear Information System (INIS)

Zwiebach, B.; Massachusetts Inst. of Tech., Cambridge

1991-01-01

We show that Witten's open string diagrams are surfaces with metrics of minimal area under the condition that all nontrivial open Jordan curves be longer or equal to π. The minimal area property is used together with a mini-max problem to establish a new existence and uniqueness theorem for quadratic differentials in open Riemann surfaces with or without punctures on the boundaries. This theorem implies that the Feynman rules of open string theory give a single cover of the moduli of open Riemann surfaces. (orig.)

Concurrent Improvement in Both Binge Eating and Depressive Symptoms with Naltrexone/Bupropion Therapy in Overweight or Obese Subjects with Major Depressive Disorder in an Open-Label, Uncontrolled Study.

Science.gov (United States)

Guerdjikova, Anna I; Walsh, Brandon; Shan, Kevin; Halseth, Amy E; Dunayevich, Eduardo; McElroy, Susan L

2017-10-01

Binge eating disorder (BED) is associated with obesity and major depressive disorder (MDD). Naltrexone extended-release (ER)/bupropion ER (NB) is approved as an adjunct to diet and physical activity for chronic weight management. In a prospectively designed 24-week open-label, single-arm, single-site trial of 25 women with MDD and overweight/obesity, NB reduced weight and depressive symptoms. This post hoc analysis investigated the relationship between change in self-reported binge eating behavior (evaluated with the Binge Eating Scale [BES]) and changes in weight, control of eating, and depressive symptoms. At baseline, 91% of subjects had moderate or severe BES scores, suggesting BED. BES scores were significantly improved from week 4, and by week 24, 83% reported "little or no problem." Improvement in BES scores correlated with improvement in depressive symptoms and control of eating. NB may be effective in reducing binge eating symptoms associated with MDD and overweight/obesity. Evaluation of NB in BED appears warranted. Orexigen Therapeutics, Inc.

Production of single superphosphate labeled with 34S Produção de superfosfato simples marcado com 34S

Directory of Open Access Journals (Sweden)

Alexssandra Luiza Rodrigues Molina Rossete

2008-02-01

Full Text Available Single superphosphate is currently one of the mostly used fertilizers as an alternative source for phosphorus and sulphur. Sulphur presents four stable isotopes (32S, 33S, 34S, and 36S with natural abundances of 95.00; 0.76; 4.22; and 0.014% in atoms, respectively. Single superphosphate labeled with the 34S isotope was obtained from a chemical reaction in stoichiometric amounts between Ca(H2PO42 and Ca34SO4.2H2O. Calcium sulphate (Ca34SO4.2H2O was enriched with 5.85 ± 0.01 atoms % of 34S. The Ca(H2PO42 reagent was obtained from a reaction between CaCl2.2H2O and H3PO4. The reaction between the Ca(H2PO42 thus produced and the labeled Ca34SO4.2H2O compound was then performed to obtain the 34S-labeled single surperphosphate. The thermal decomposition of the labeled superphosphate for the production of gaseous 34SO2 was carried out under a vacuum line at 900ºC in the presence of NaPO3. The isotopic determination of S (atoms % of 34S was carried out on an ATLAS-MAT model CH-4 mass spectrometer. The production yield of Ca(H2PO42 and labeled single superphosphate were approximately 97 and 99% respectively, and the purity level of the labeled single superphosphate was estimated as 96%. No isotopic fractionation was observed in the production process of 34S-labeled single superphosphate.O superfosfato simples é um dos fertilizantes mais utilizados atualmente como fonte de fósforo e uma alternativa para enxofre. O enxofre apresenta quatro isótopos estáveis, 32S, 33S, 34S e 36S, com abundância natural de 95,00; 0,76; 4,22 e 0,014% em átomos, respectivamente. O superfosfato simples marcado com 34S foi obtido a partir da reação química em proporção estequiométrica entre o Ca(H2PO42 e o Ca34SO4.2H2O. O Ca34SO4.2H2O foi enriquecido com 5,85 ± 0,01% em átomos de 34S. O Ca(H2PO42 foi obtido a partir da reação entre CaCl2.2H2O com o H3PO4. A decomposição térmica do superfosfato marcado para produção do 34SO2 gasoso foi realizada em linha de

Probiotics in diverticular disease of the colon: an open label study.

Science.gov (United States)

Lamiki, Pepu; Tsuchiya, Junji; Pathak, Surajit; Okura, Ruichi; Solimene, Umberto; Jain, Shalini; Kawakita, Shichiro; Marotta, Francesco

2010-03-01

To investigate the effectiveness and safety of a symbiotic mixture in preventing recurrence of constipation-related abdominal pain in patients with uncomplicated diverticular disease of the colon. Forty-six consecutive patients (10 men, 36 women, mean age 62.5 years, range 49 to 77 years), previously affected by symptomatic uncomplicated diverticular disease of the colon, were enrolled in a 6-month follow-up study in a prospective, randomized, open-label study. The following symptoms were assessed at entry and through follow-up by using a quantitative scale: constipation, diarrhoea and abdominal pain. After recruitment, the patients were assigned to the following treatment: SCM-III symbiotic mixture, 10 ml three times a day. The colonization of ingested Lactobacillus acidophilus 145 and Bifidobacterium spp. 420 was assessed by species-specific PCR. Forty-five patients completed the study (97%). Thirty-one patients (68%) were still symptom free after the 6th month of treatment. Treatment with SCM-III was regarded as "effective" or "very effective" in more than 78% of the patients altogether (pdiverticular disease of the colon, especially in those patients with constipation-predominant features.

[Three dimensional finite element model of a modified posterior cervical single open-door laminoplasty].

Science.gov (United States)

Wang, Q; Yang, Y; Fei, Q; Li, D; Li, J J; Meng, H; Su, N; Fan, Z H; Wang, B Q

2017-06-06

Objective: To build a three-dimensional finite element models of a modified posterior cervical single open-door laminoplasty with short-segmental lateral mass screws fusion. Methods: The C(2)-C(7) segmental data were obtained from computed tomography (CT) scans of a male patient with cervical spondylotic myelopathy and spinal stenosis.Three-dimensional finite element models of a modified cervical single open-door laminoplasty (before and after surgery) were constructed by the combination of software package MIMICS, Geomagic and ABAQUS.The models were composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments.The loads of moments 1.5Nm at different directions (flexion, extension, lateral bending and axial rotation)were applied at preoperative model to calculate intersegmental ranges of motion.The results were compared with the previous studies to verify the validation of the models. Results: Three-dimensional finite element models of the modified cervical single open- door laminoplasty had 102258 elements (preoperative model) and 161 892 elements (postoperative model) respectively, including C(2-7) six bony vertebraes, C(2-3)-C(6-7) five intervertebral disc, main ligaments and lateral mass screws.The intersegmental responses at the preoperative model under the loads of moments 1.5 Nm at different directions were similar to the previous published data. Conclusion: Three-dimensional finite element models of the modified cervical single open- door laminoplasty were successfully established and had a good biological fidelity, which can be used for further study.

Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

Science.gov (United States)

Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

2007-01-01

Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial.

Science.gov (United States)

Laing, Richard W; Mergental, Hynek; Yap, Christina; Kirkham, Amanda; Whilku, Manpreet; Barton, Darren; Curbishley, Stuart; Boteon, Yuri L; Neil, Desley A; Hübscher, Stefan G; Perera, M Thamara P R; Muiesan, Paolo; Isaac, John; Roberts, Keith J; Cilliers, Hentie; Afford, Simon C; Mirza, Darius F

2017-11-28

The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres. Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival. The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. NCT02740608

3D Restoration Microscopy Improves Quantification of Enzyme-Labeled Fluorescence-Based Single-Cell Phosphatase Activity in Plankton

OpenAIRE

Diaz-de-Quijano, Daniel; Palacios, Pilar; Hornák, Karel; Felip, Marisol

2014-01-01

The ELF or fluorescence-labeled enzyme activity (FLEA) technique is a culture-independent single-cell tool for assessing plankton enzyme activity in close-to-in situ conditions. We demonstrate that single-cell FLEA quantifications based on two-dimensional (2D) image analysis were biased by up to one order of magnitude relative to deconvolved 3D. This was basically attributed to out-of-focus light, and partially to object size. Nevertheless, if sufficient cells were measured (25-40 cells), bia...

[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

Science.gov (United States)

Ershova, O B; Lesniak, O M; Belova, K Iu; Nazarova, A V; Manovitskaia, A V; Musaeva, T M; Musraev, R M; Nurlygaianov, R Z; Rozhinskaia, L Ia; Skripnikova, I A; Toroptsova, N V

2014-01-01

To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

Development of a single-ring OpenPET prototype

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Eiji, E-mail: rush@nirs.go.jp; Tashima, Hideaki; Wakizaka, Hidekatsu; Nishikido, Fumihiko; Hirano, Yoshiyuki; Inadama, Naoko; Murayama, Hideo; Ito, Hiroshi; Yamaya, Taiga

2013-11-21

One of the challenging applications of PET is implementing it for in-beam PET, which is an in situ monitoring method for charged particle therapy. For this purpose, we have previously proposed an open-type PET scanner, OpenPET. The original OpenPET had a physically opened field-of-view (FOV) between two detector rings through which irradiation beams pass. This dual-ring OpenPET (DROP) had a wide axial FOV including the gap. This geometry was not necessarily the most efficient for application to in-beam PET in which only a limited FOV around the irradiation field is required. Therefore, we have proposed a new single-ring OpenPET (SROP) geometry which can provide an accessible and observable open space with higher sensitivity and a reduced number of detectors than the DROP. The proposed geometry was a cylinder shape with its ends cut at a slant, in which the shape of each cut end became an ellipse. In this work, we developed and evaluated a small prototype of the SROP geometry for proof-of-concept. The SROP prototype was designed with 2 ellipse-shaped detector rings of 16 depth-of-interaction (DOI) detectors each. The DOI detectors consisted of 1024 GSOZ scintillator crystals which were arranged in 4 layers of 16×16 arrays, coupled to a 64-channel FP-PMT. Each ellipse-shaped detector ring had a major axis of 281.6 mm and a minor axis of 207.5 mm. For the slant mode, the rings were placed at a 45-deg slant from the axial direction and for the non-slant mode (used as a reference) they were at 90 deg from the axial direction with no gap. The system sensitivity measured from a {sup 22}Na point source was 5.0% for the slant mode. The average spatial resolutions of major and minor axis directions were calculated as 3.8 mm FWHM and 4.9 mm FWHM, respectively for the slant mode. This difference resulted from the ellipsoidal ring geometry and the spatial resolution of the minor axis direction degraded by the parallax error. Comparison between the slant mode and the non

A Randomized Study Comparing Outcomes of Stapled and Hand-Sutured Anastomoses in Patients Undergoing Open Gastrointestinal Surgery

OpenAIRE

Chandramohan, S. M.; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L.; Waggoner, Jason R.; Tatla, Daljit

2012-01-01

Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospectiv...

Live Imaging of Cellular Internalization of Single Colloidal Particle by Combined Label-Free and Fluorescence Total Internal Reflection Microscopy.

Science.gov (United States)

Byrne, Gerard D; Vllasaliu, Driton; Falcone, Franco H; Somekh, Michael G; Stolnik, Snjezana

2015-11-02

In this work we utilize the combination of label-free total internal reflection microscopy and total internal reflectance fluorescence (TIRM/TIRF) microscopy to achieve a simultaneous, live imaging of single, label-free colloidal particle endocytosis by individual cells. The TIRM arm of the microscope enables label free imaging of the colloid and cell membrane features, while the TIRF arm images the dynamics of fluorescent-labeled clathrin (protein involved in endocytosis via clathrin pathway), expressed in transfected 3T3 fibroblasts cells. Using a model polymeric colloid and cells with a fluorescently tagged clathrin endocytosis pathway, we demonstrate that wide field TIRM/TIRF coimaging enables live visualization of the process of colloidal particle interaction with the labeled cell structure, which is valuable for discerning the membrane events and route of colloid internalization by the cell. We further show that 500 nm in diameter model polystyrene colloid associates with clathrin, prior to and during its cellular internalization. This association is not apparent with larger, 1 μm in diameter colloids, indicating an upper particle size limit for clathrin-mediated endocytosis.

Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

Science.gov (United States)

Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

2003-12-01

Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

Open-Lake Experimental Investigation of Azimuth Angle Estimation Using a Single Acoustic Vector Sensor

Directory of Open Access Journals (Sweden)

Anbang Zhao

2018-01-01

Full Text Available Five well-known azimuth angle estimation methods using a single acoustic vector sensor (AVS are investigated in open-lake experiments. A single AVS can measure both the acoustic pressure and acoustic particle velocity at a signal point in space and output multichannel signals. The azimuth angle of one source can be estimated by using a single AVS in a passive sonar system. Open-lake experiments are carried out to evaluate how these different techniques perform in estimating azimuth angle of a source. The AVS that was applied in these open-lake experiments is a two-dimensional accelerometer structure sensor. It consists of two identical uniaxial velocity sensors in orthogonal orientations, plus a pressure sensor—all in spatial collocation. These experimental results indicate that all these methods can effectively realize the azimuth angle estimation using only one AVS. The results presented in this paper reveal that AVS can be applied in a wider range of application in distributed underwater acoustic systems for passive detection, localization, classification, and so on.

Single Molecule 3D Orientation in Time and Space: A 6D Dynamic Study on Fluorescently Labeled Lipid Membranes

DEFF Research Database (Denmark)

Börner, Richard; Ehrlich, Nicky; Hohlbein, Johannes

2016-01-01

Interactions between single molecules profoundly depend on their mutual three-dimensional orientation. Recently, we demonstrated a technique that allows for orientation determination of single dipole emitters using a polarization-resolved distribution of fluorescence into several detection channels...... interesting in non-isotropic environments such as lipid membranes, which are of great importance in biology. We used giant unilamellar vesicles (GUVs) labeled with fluorescent dyes down to a single molecule concentration as a model system for both, assessing the robustness of the orientation determination...

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

Science.gov (United States)

Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

2017-07-28

A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

Single-shot LIBS spectral quality for waste particles in open air

NARCIS (Netherlands)

Xia, H.; Bakker, M.C.M.

2015-01-01

This work investigates the ability of LIBS to produce quality spectra from small particles of concrete demolition waste using single-shot spectra collected in open air. The 2–8?mm materials are rounded river gravel, green glass shards, and plastic flakes. Considered are focal length, air, moisture,

50 CFR Figure 13 to Part 223 - Single Grid Hard TED Escape Opening

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Single Grid Hard TED Escape Opening 13 Figure 13 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 13 Figure 13 to Part 223—Singl...

An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects

Directory of Open Access Journals (Sweden)

Tuccillo Dianne

2011-10-01

Full Text Available Abstract Background The ability to self-inject in patients with multiple sclerosis (MS has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen, a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex in MS patients. Methods This was a Phase IIIb, open-label, single-country, multicenter trial in MS patients currently using IM IFNβ-1a prefilled syringes. Patients received weekly 30 mcg IM IFNβ-1a treatment over 4 weeks. On Day 1, patients self-administered IM IFNβ-1a using a prefilled syringe at the clinic. On Day 8, patients received training on the prefilled pen and self-administered IM IFNβ-1a using the device. On Day 15, patients self-administered IM IFNβ-1a at home using the prefilled pen. A final injection occurred at the clinic on Day 22 when patients self-administered IM IFNβ-1a using the prefilled pen while clinic staff observed and completed a detailed questionnaire documenting patients' ability to self-inject with the device. Serum neopterin levels were evaluated pre and post-injection on Days 1 and 8. Adverse events were monitored throughout. Results Seventy-one (96% patients completed the study. The overall success rate in safely and effectively using the prefilled pen was 89%. No device malfunctions occurred. One unsuccessful administration occurred at Day 22 due to patient error; no patient injury resulted. Patients gave the prefilled pen high ratings (8.7-9.3 on a 10-point scale for ease of use (0 = extremely difficult, 10 = extremely easy. Ninety-four percent of patients preferred the prefilled pen over the

Bioavailability of Lumefantrine Is Significantly Enhanced with a Novel Formulation Approach, an Outcome from a Randomized, Open-Label Pharmacokinetic Study in Healthy Volunteers.

Science.gov (United States)

Jain, Jay Prakash; Leong, F Joel; Chen, Lan; Kalluri, Sampath; Koradia, Vishal; Stein, Daniel S; Wolf, Marie-Christine; Sunkara, Gangadhar; Kota, Jagannath

2017-09-01

The artemether-lumefantrine combination requires food intake for the optimal absorption of lumefantrine. In an attempt to enhance the bioavailability of lumefantrine, new solid dispersion formulations (SDF) were developed, and the pharmacokinetics of two SDF variants were assessed in a randomized, open-label, sequential two-part study in healthy volunteers. In part 1, the relative bioavailability of the two SDF variants was compared with that of the conventional formulation after administration of a single dose of 480 mg under fasted conditions in three parallel cohorts. In part 2, the pharmacokinetics of lumefantrine from both SDF variants were evaluated after a single dose of 480 mg under fed conditions and a single dose of 960 mg under fasted conditions. The bioavailability of lumefantrine from SDF variant 1 and variant 2 increased up to ∼48-fold and ∼24-fold, respectively, relative to that of the conventional formulation. Both variants demonstrated a positive food effect and a less than proportional increase in exposure between the 480-mg and 960-mg doses. Most adverse events (AEs) were mild to moderate in severity and not suspected to be related to the study drug. All five drug-related AEs occurred in subjects taking SDF variant 2. No clinically significant treatment-emergent changes in vital signs, electrocardiograms, or laboratory blood assessments were noted. The solid dispersion formulation enhances the lumefantrine bioavailability to a significant extent, and SDF variant 1 is superior to SDF variant 2. Copyright © 2017 Jain et al.

Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.

Science.gov (United States)

Lampl, Y; Boaz, M; Gilad, R; Lorberboym, M; Dabby, R; Rapoport, A; Anca-Hershkowitz, M; Sadeh, M

2007-10-02

Ischemic animal model studies have shown a neuroprotective effect of minocycline. To analyze the effect of minocycline treatment in human acute ischemic stroke. We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo. One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group. Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.

An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

Science.gov (United States)

Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

2007-01-01

Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

Science.gov (United States)

Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

2009-11-01

Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout

Co-Labeling for Multi-View Weakly Labeled Learning.

Science.gov (United States)

Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

2016-06-01

It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

Overview of Single-Molecule Speckle (SiMS) Microscopy and Its Electroporation-Based Version with Efficient Labeling and Improved Spatiotemporal Resolution

Science.gov (United States)

Yamashiro, Sawako; Watanabe, Naoki

2017-01-01

Live-cell single-molecule imaging was introduced more than a decade ago, and has provided critical information on remodeling of the actin cytoskeleton, the motion of plasma membrane proteins, and dynamics of molecular motor proteins. Actin remodeling has been the best target for this approach because actin and its associated proteins stop diffusing when assembled, allowing visualization of single-molecules of fluorescently-labeled proteins in a state specific manner. The approach based on this simple principle is called Single-Molecule Speckle (SiMS) microscopy. For instance, spatiotemporal regulation of actin polymerization and lifetime distribution of actin filaments can be monitored directly by tracking actin SiMS. In combination with fluorescently labeled probes of various actin regulators, SiMS microscopy has contributed to clarifying the processes underlying recycling, motion and remodeling of the live-cell actin network. Recently, we introduced an electroporation-based method called eSiMS microscopy, with high efficiency, easiness and improved spatiotemporal precision. In this review, we describe the application of live-cell single-molecule imaging to cellular actin dynamics and discuss the advantages of eSiMS microscopy over previous SiMS microscopy. PMID:28684722

Overview of Single-Molecule Speckle (SiMS) Microscopy and Its Electroporation-Based Version with Efficient Labeling and Improved Spatiotemporal Resolution.

Science.gov (United States)

Yamashiro, Sawako; Watanabe, Naoki

2017-07-06

Live-cell single-molecule imaging was introduced more than a decade ago, and has provided critical information on remodeling of the actin cytoskeleton, the motion of plasma membrane proteins, and dynamics of molecular motor proteins. Actin remodeling has been the best target for this approach because actin and its associated proteins stop diffusing when assembled, allowing visualization of single-molecules of fluorescently-labeled proteins in a state specific manner. The approach based on this simple principle is called Single-Molecule Speckle (SiMS) microscopy. For instance, spatiotemporal regulation of actin polymerization and lifetime distribution of actin filaments can be monitored directly by tracking actin SiMS. In combination with fluorescently labeled probes of various actin regulators, SiMS microscopy has contributed to clarifying the processes underlying recycling, motion and remodeling of the live-cell actin network. Recently, we introduced an electroporation-based method called eSiMS microscopy, with high efficiency, easiness and improved spatiotemporal precision. In this review, we describe the application of live-cell single-molecule imaging to cellular actin dynamics and discuss the advantages of eSiMS microscopy over previous SiMS microscopy.

Open-label pilot study of memantine in the treatment of compulsive buying.

Science.gov (United States)

Grant, Jon E; Odlaug, Brian L; Mooney, Marc; O'Brien, Robert; Kim, Suck Won

2012-05-01

Although compulsive buying (CB) is relatively common, pharmacotherapy research for CB is limited. Memantine, an N-methyl-D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive behaviors, suggesting it may help individuals with CB. Nine patients (8 females) with CB were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/d). Participants were enrolled from December 2008 until May 2010. The primary outcome measure was change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (Y-BOCS-SV). Of the 9 participants, 8 (88.9%) completed the 10-week study. Y-BOCS-SV scores decreased from a mean of 22.0 ± 1.3 at baseline to 11.0 ± 5.3 at endpoint (P impulsive buying and improvements on cognitive tasks of impulsivity. In addition, the medication was well-tolerated. These findings suggest that pharmacologic manipulation of the glutamate system may target the impulsive behavior underlying CB. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

Science.gov (United States)

Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

2011-01-01

Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain: A Prospective Open-label Study.

Science.gov (United States)

Haroutounian, Simon; Ratz, Yael; Ginosar, Yehuda; Furmanov, Karina; Saifi, Fayez; Meidan, Ronit; Davidson, Elyad

2016-12-01

The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain. The primary outcome was the change in the pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey-Short Form) questionnaire at the 6-month follow-up in an intent-to-treat population. Secondary outcomes included the change in S-TOPS physical, social, and emotional disability scales, the pain severity, and pain interference on the Brief Pain Inventory, sleep problems, and the change in opioid consumption. A total of 274 participants were approved for treatment; complete baseline data were available for 206 (intent-to-treat), and complete follow-up data for 176 participants. At follow-up, the pain symptom score improved from median 83.3 (95% confidence interval [CI], 79.2-87.5) to 75.0 (95% CI, 70.8-79.2) (Pmedicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study's noncontrolled nature should be considered when extrapolating the results.

N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study.

Science.gov (United States)

Cullen, Kathryn R; Klimes-Dougan, Bonnie; Westlund Schreiner, Melinda; Carstedt, Patricia; Marka, Nicholas; Nelson, Katharine; Miller, Michael J; Reigstad, Kristina; Westervelt, Ana; Gunlicks-Stoessel, Meredith; Eberly, Lynn E

2018-03-01

Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth. Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects. We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy.

Effect of benzalkonium chloride-free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study.

Science.gov (United States)

Lopes, Joao F; Hubatsch, Douglas A; Amaris, Patricia

2015-11-12

Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005 % were transitioned to receive once-daily BAK-free travoprost 0.004 % containing polyquaternium-1 (Travatan® preserved with POLYQUAD® [PQ], Alcon Laboratories, Inc; Fort Worth, TX) for 12 weeks. Mean change in IOP from baseline (primary efficacy endpoint) and the percentage of patients who achieved a target IOP of ≤18 mmHg were evaluated at all on-therapy visits. Ocular hyperemia, patient preference, and self-projected adherence were assessed at week 12. Adverse events (AEs) were monitored throughout the study. All enrolled patients were included in the analysis (n = 191); the majority of patients (90.6 %, n = 173/191) completed the study. Mean (SD) patient age was 67.5 (11.3) years, and mean baseline IOP was 14.8 mmHg. Mean IOP was reduced by 0.94 mmHg at week 6 and by 1.09 mmHg at week 12 (P glaucoma or ocular hypertension who were intolerant of latanoprost. BAK-free travoprost 0.004 % is a viable alternative for patients who require switching their IOP-lowering medications because of tolerability issues. ClinicalTrials.gov identifier, NCT01510145.

2-Deoxyglucose autoradiography of single motor units: labelling of individual acutely active muscle fibers

International Nuclear Information System (INIS)

Toop, J.; Burke, R.E.; Dum, R.P.; O'Donovan, M.J.; Smith, C.B.

1982-01-01

2-Deoxy-D-[1- 14 C]glucose (2DG) was given intravenously during repetitive stimulation of single motor units in adult cats and autoradiographs were made of frozen sections of the target muscles in order to evaluate methods designed to improve the spatial resolution of [ 14 C]2DG autoradiography. With the modifications used, acutely active muscle fibers, independently identified by depletion of intrafiber glycogen, were associated with highly localized accumulations of silver grains over the depleted fibers. The results indicate that [ 14 C]2DG autoradiography can successfully identify individual active muscle fibers and might in principle be used to obtain quantitative data about rates of glucose metabolism in single muscle fibers of defined histochemical type. The modifications may be applicable also to other tissues to give improved spatial resolution with [ 14 C]-labeled metabolic markers. (Auth.)

Clinical outcomes of CO2-less single-port video-assisted thoracoscopic thymectomy versus open thymectomy: comparative study.

Science.gov (United States)

Aragón, Javier; Pérez Méndez, Itzell; Gutiérrez Pérez, Alexia

2016-01-01

Although video-assisted thoracoscopic surgery (VATS) for thymic disorders has been introduced, its oncological outcome and benefits over others open approaches remains unclear. Single-port VATS thymectomy using a flexible port and CO 2 has been described. However, VATS thymectomy is possible by a single incision of 3 cm without CO 2 insufflation or special port device avoiding objections related to CO 2 insufflation and allowing instruments to move more freely making procedure easier and cheaper. Our institutional experience in open and CO 2 -less VATS single-port thymectomy was retrospectively reviewed to evaluate compared to sternotomy, the clinical and oncological outcomes with this novel approach. A retrospective review consisting of 84 patients who underwent thymectomy because different thymic disorders especially thymoma was performed. Eighteen patients underwent CO 2 -less VATS single port thymectomy, while 66 underwent thymectomy through open sternotomy. Many clinical factors associated with the surgical and clinical outcomes, including tumor recurrence and clinical remission, were recorded. Non major postoperative complications were observed in any group. The median operative time and postoperative hospital stay of CO 2 -less VATS single port thymectomy were 95 min and 1 day, respectively and 120 min and 7 days for open sternotomy. The thymoma was the most common thymic disorder with 7 patients (38%) in VATS group and 28 patients (42.4%) for the open approach. The median lesion size was 2.6 cm in the VATS group and 3.2 cm in the open approach. No thymoma recurrence in patients undergoing VATS was observed during the follow-up time, while in the open surgery group 14.28% recurrence was observed, distributed as follows: loco-regional 75% and 25% at distance; free disease period of these patients was 8.3 months. Thymectomy associated with myasthenia gravis (MG) was observed in 6 (33%) patients in the VATS group and 32 (48%) patients for sternotomy; our

Link Label Prediction in Signed Citation Network

KAUST Repository

Akujuobi, Uchenna Thankgod

2016-01-01

such as using regression, trust propagation and matrix factorization. These approaches have tried to solve the problem of link label prediction by using ideas from social theories, where most of them predict a single missing label given that labels of other

Six week open-label reboxetine treatment in children and adolescents with attention deficit hyperactivity disorder

Directory of Open Access Journals (Sweden)

Arabgol F

2007-10-01

Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a common psychiatric disorder among children and adolescents. This disorder causes difficulties in academic, behavioral, emotional, social and family performance. Stimulants show robust efficacy and a good safety profile in children with this disorder, but a significant percent of ADHD children do not respond adequately or cannot tolerate the associated adverse effects with stimulants. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention deficit hyperactivity disorder (ADHD."nMethods: Fifteen child and adolescent outpatients, aged 7 to 16 (Mean± SD=9.72±2.71 years, diagnosed with ADHD were enrolled in a six open-label study with reboxetine 4-6 mg/d. The principal measure of the outcome was the teacher and parent Attention Deficit Hyperactive Disorder Rating Scale (ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks of the medication started. Side effects questionnaire was used to detect side effects of reboxetine. Repeated measures Analysis of variance (ANOVA was done for comparison of Teacher and Parent ADHD Rating Scale scores during the intervention."nResults: Twelve of 15 (80% participants completed the treatment protocol. A significant decrease in ADHD symptoms on teacher (p=0.04 and parent (p=0.003 ADHD rating scale was noted. Adverse effects were mild to moderate in severity. The most common adverse effects were drowsiness/sedation and appetite decrease."nConclusion: The results of the current study suggest the effectiveness of reboxetine in the treatment of ADHD in children and adolescents. Double-blind, placebo-controlled studies and larger sample size with long duration of intervention are indicated to rigorously

Single Cigarette Sales: State Differences in FDA Advertising and Labeling Violations, 2014, United States.

Science.gov (United States)

Baker, Hannah M; Lee, Joseph G L; Ranney, Leah M; Goldstein, Adam O

2016-02-01

Single cigarettes, which are sold without warning labels and often evade taxes, can serve as a gateway for youth smoking. The Family Smoking Prevention and Tobacco Control Act of 2009 gives the US Food and Drug Administration (FDA) authority to regulate the manufacture, distribution, and marketing of tobacco products, including prohibiting the sale of single cigarettes. To enforce these regulations, the FDA conducted over 335,661 inspections between 2010 and September 30, 2014, and allocated over $115 million toward state inspections contracts. To examine differences in single cigarette violations across states and determine if likely correlates of single cigarette sales predict single cigarette violations at the state level. Cross-sectional study of publicly available FDA warning letters from January 1 to July 31, 2014. All 50 states and the District of Columbia. Tobacco retailer inspections conducted by FDA (n = 33 543). State cigarette tax, youth smoking prevalence, poverty, and tobacco production. State proportion of FDA warning letters issued for single cigarette violations. There are striking differences in the number of single cigarette violations found by state, with 38 states producing no warning letters for selling single cigarettes even as state policymakers developed legislation to address retailer sales of single cigarettes. The state proportion of warning letters issued for single cigarettes is not predicted by state cigarette tax, youth smoking, poverty, or tobacco production, P = .12. Substantial, unexplained variation exists in violations of single cigarette sales among states. These data suggest the possibility of differences in implementation of FDA inspections and the need for stronger quality monitoring processes across states implementing FDA inspections. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

Directory of Open Access Journals (Sweden)

Ito Mikako

2011-10-01

Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

Assigning Significance in Label-Free Quantitative Proteomics to Include Single-Peptide-Hit Proteins with Low Replicates

OpenAIRE

Li, Qingbo

2010-01-01

When sample replicates are limited in a label-free proteomics experiment, selecting differentially regulated proteins with an assignment of statistical significance remains difficult for proteins with a single-peptide hit or a small fold-change. This paper aims to address this issue. An important component of the approach employed here is to utilize the rule of Minimum number of Permuted Significant Pairings (MPSP) to reduce false positives. The MPSP rule generates permuted sample pairings fr...

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

International Nuclear Information System (INIS)

Martín-Richard, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Ángel; Quindós, Maria; Maisonobe, Pascal; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta

2013-01-01

Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier http://clinicaltrials.gov/show/NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18

Randomized open-label trial of dextromethorphan in Rett syndrome.

Science.gov (United States)

Smith-Hicks, Constance L; Gupta, Siddharth; Ewen, Joshua B; Hong, Manisha; Kratz, Lisa; Kelley, Richard; Tierney, Elaine; Vaurio, Rebecca; Bibat, Genila; Sanyal, Abanti; Yenokyan, Gayane; Brereton, Nga; Johnston, Michael V; Naidu, Sakkubai

2017-10-17

To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect. © 2017 American Academy of Neurology.

Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study.

Science.gov (United States)

Huang, Fenglei; Marzin, Kristell; Koenen, Rüdiger; Kammerer, Klaus Peter; Strelkowa, Natalja; Elgadi, Mabrouk; Quinson, Anne-Marie; Haertter, Sebastian

2017-10-01

Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by 240 mg faldaprevir once daily from day 6 to day 10, with an additional single dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples for the statins were collected on days 1-3 and days 10-12. Concomitant administration with faldaprevir led to approximately 9-fold and 34-fold increases in AUC 0-∞ and C max , respectively, of atorvastatin and approximately 15-fold and 33-fold increases in AUC 0-∞ and C max , respectively, of rosuvastatin, compared with the statins given alone. Exposure to the major metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased to a similar magnitude as that of the parent compounds. The marked drug-drug interaction observed is most likely related to the inhibitory effects of faldaprevir on transporters, particularly hepatic uptake transporters such as OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in healthy volunteers, coadministration of faldaprevir with statins should be avoided. © 2017, The American College of Clinical Pharmacology.

Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.

Science.gov (United States)

Inoue, Kenichi; Kuroi, Katsumasa; Shimizu, Satoru; Rai, Yoshiaki; Aogi, Kenjiro; Masuda, Norikazu; Nakayama, Takahiro; Iwata, Hiroji; Nishimura, Yuichiro; Armour, Alison; Sasaki, Yasutsuna

2015-12-01

Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles. The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9). The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.

Single-label kinase and phosphatase assays for tyrosine phosphorylation using nanosecond time-resolved fluorescence detection.

Science.gov (United States)

Sahoo, Harekrushna; Hennig, Andreas; Florea, Mara; Roth, Doris; Enderle, Thilo; Nau, Werner M

2007-12-26

The collision-induced fluorescence quenching of a 2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine (Dbo) by hydrogen atom abstraction from the tyrosine residue in peptide substrates was introduced as a single-labeling strategy to assay the activity of tyrosine kinases and phosphatases. The assays were tested for 12 different combinations of Dbo-labeled substrates and with the enzymes p60c-Src Src kinase, EGFR kinase, YOP protein tyrosine phosphatase, as well as acid and alkaline phosphatases, thereby demonstrating a broad application potential. The steady-state fluorescence changed by a factor of up to 7 in the course of the enzymatic reaction, which allowed for a sufficient sensitivity of continuous monitoring in steady-state experiments. The fluorescence lifetimes (and intensities) were found to be rather constant for the phosphotyrosine peptides (ca. 300 ns in aerated water), while those of the unphosphorylated peptides were as short as 40 ns (at pH 7) and 7 ns (at pH 13) as a result of intramolecular quenching. Owing to the exceptionally long fluorescence lifetime of Dbo, the assays were alternatively performed by using nanosecond time-resolved fluorescence (Nano-TRF) detection, which leads to an improved discrimination of background fluorescence and an increased sensitivity. The potential for inhibitor screening was demonstrated through the inhibition of acid and alkaline phosphatases by molybdate.

Expanded HIV pre-exposure prophylaxis (PrEP) implementation in communities in New South Wales, Australia (EPIC-NSW): design of an open label, single arm implementation trial.

Science.gov (United States)

Zablotska, Iryna B; Selvey, Christine; Guy, Rebecca; Price, Karen; Holden, Jo; Schmidt, Heather-Marie; McNulty, Anna; Smith, David; Jin, Fengyi; Amin, Janaki; Cooper, David A; Grulich, Andrew E

2018-02-02

The New South Wales (NSW) HIV Strategy 2016-2020 aims for the virtual elimination of HIV transmission in NSW, Australia, by 2020. Despite high and increasing levels of HIV testing and treatment since 2012, the annual number of HIV diagnoses in NSW has remained generally unchanged. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV infection among gay and bisexual men (GBM) when taken appropriately. However, there have been no population-level studies that evaluate the impact of rapid PrEP scale-up in high-risk GBM. Expanded PrEP Implementation in Communities in NSW (EPIC-NSW) is a population-level evaluation of the rapid, targeted roll-out of PrEP to high-risk individuals. EPIC-NSW, is an open-label, single-arm, multi-centre prospective observational study of PrEP implementation and impact. Over 20 public and private clinics across urban and regional areas in NSW have participated in the rapid roll-out of PrEP, supported by strong community mobilization and PrEP promotion. The study began on 1 March 2016, aiming to enroll at least 3700 HIV negative people at high risk of HIV. This estimate took into consideration criteria for PrEP prescription in people at high risk for acquiring HIV as defined in the NSW PrEP guidelines. Study participants receive once daily co-formulated tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and are followed for up to 24 months. Follow-up includes: testing for HIV at 1 month, HIV and other sexually transmissible infections three-monthly, HCV annually and monitoring of renal function six-monthly. Optional online behavioural surveys are conducted quarterly. The co-primary endpoints are (i) HIV diagnoses and incidence in the cohort and (ii) HIV diagnoses in NSW. EPIC-NSW is a population-based PrEP implementation trial which targets the entire estimated population of GBM at high risk for HIV infection in NSW. It will provide a unique opportunity to evaluate the population impact of PrEP on a concentrated HIV

Mindboggle: Automated brain labeling with multiple atlases

International Nuclear Information System (INIS)

Klein, Arno; Mensh, Brett; Ghosh, Satrajit; Tourville, Jason; Hirsch, Joy

2005-01-01

To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data. Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently. When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions. Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images

The clinical meaningfulness of ADAS-Cog changes in Alzheimer's disease patients treated with donepezil in an open-label trial.

Science.gov (United States)

Rockwood, Kenneth; Fay, Sherri; Gorman, Mary; Carver, Daniel; Graham, Janice E

2007-08-30

In 6-month anti-dementia drug trials, a 4-point change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is held to be clinically important. We examined how this change compared with measures of clinical meaningfulness. This is a secondary analysis of a 12 month open-label study of 100 patients (71 women) diagnosed with mild to moderate AD treated with 5-10 mg of donepezil daily. We studied the observed case, 6-month change from baseline on the ADAS-Cog, the Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-Plus), patient-Goal Attainment Scaling (PGAS) and clinician-GAS (CGAS). At 6 months, donepezil-treated patients (n = 95) were more likely to show no change (+/- 3 points) on the ADAS-Cog (56%) than to improve (20%) or decline (24%) by 4-points. ADAS-Cog change scores were little correlated with other measures: from -0.09 for PGAS to 0.27 for the CIBIC-Plus. While patients who improved on the ADAS-Cog were less likely to decline on the clinical measures (26%), 43% of patients who declined on the ADAS-Cog improved on at least two of the clinical measures. The ADAS-Cog did not capture all clinically important effects. In general, ADAS-Cog improvement indicates clinical improvement, whereas many people with ADAS-Cog decline do not show clinical decline. The open-label design of this study does not allow us to know whether this is a treatment effect, which requires further investigation.

Combining EPR spectroscopy and X-ray crystallography to elucidate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals.

Science.gov (United States)

Consentius, Philipp; Gohlke, Ulrich; Loll, Bernhard; Alings, Claudia; Heinemann, Udo; Wahl, Markus C; Risse, Thomas

2017-08-09

Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling is used to investigate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals. Within a single crystal, the oriented ensemble of spin bearing moieties results in a strong angle dependence of the EPR spectra. A quantitative description of the EPR spectra requires the determination of the unit cell orientation with respect to the sample tube and the orientation of the spin bearing moieties within the crystal lattice. Angle dependent EPR spectra were analyzed by line shape simulations using the stochastic Liouville equation approach developed by Freed and co-workers and an effective Hamiltonian approach. The gain in spectral information obtained from the EPR spectra of single crystalline samples taken at different frequencies, namely the X-band and Q-band, allows us to discriminate between motional models describing the spectra of isotropic solutions similarly well. In addition, it is shown that the angle dependent single crystal spectra allow us to identify two spin label rotamers with very similar side chain dynamics. These results demonstrate the utility of single crystal EPR spectroscopy in combination with spectral line shape simulation techniques to extract valuable dynamic information not readily available from the analysis of isotropic systems. In addition, it will be shown that the loss of electron density in high resolution diffraction experiments at room temperature does not allow us to conclude that there is significant structural disorder in the system.

Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

Science.gov (United States)

Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

2010-11-01

Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

Detection of Single Pt Nanoparticle Collisions by Open-Circuit Potential Changes at Ag Ultramicroelectrode

International Nuclear Information System (INIS)

Mun, Seon Kyu; Shin, Changhwan; Kwon, Seong Jung

2016-01-01

Single platinum (Pt) nanoparticle (NP) collisions were investigated with open-circuit potential (OCP) using a silver (Ag) ultramicroelectrode (UME). The Ag UME showed higher sensitivity to single Pt NP detection by the OCP method than gold (Au) UME. The detection of ⁓2 nm radius Pt NP collisions was carried out successfully using Ag UME. The magnitude of the potential step and collision frequency for the single Pt NP collision on Ag UME was investigated and compared with those of the previous work done on Au UME.

Single molecule optical measurements of orientation and rotations of biological macromolecules.

Science.gov (United States)

Shroder, Deborah Y; Lippert, Lisa G; Goldman, Yale E

2016-11-22

Subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measurement of their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here we describe the range of single molecule optical technologies that can extract orientation information from these probes, review the relevant types of probes and labeling techniques, and highlight the advantages and disadvantages of these technologies for addressing specific inquiries.

An open-label trial of L-5-hydroxytryptophan in subjects with romantic stress.

Science.gov (United States)

Emanuele, Enzo; Bertona, Marco; Minoretti, Piercarlo; Geroldi, Diego

2010-01-01

This open-label trial assessed the clinical efficacy of L-5-hydroxytryptophan (5-HTP), a natural serotonin precursor, in nondepressed young subjects with high levels of romantic stress. Since both neurotrophins and serotonin have been linked to human romantic attachment, we sought to investigate the changes in serum brain-derived neurotrophic factor (BDNF) levels and platelet serotonin content in relation to the changes in romantic stress throughout the study. A total of 15 healthy subjects (11 females and 4 males, mean age: 23.3 ± 2.1 years) who experienced a recent romantic break-up or reported recent romantic problems took part in the study. The participants were treated openly for 6 weeks with L-5-hydroxytryptophan (60 mg Griffonia simplicifolia extract containing 12.8 mg 5-HTP b.i.d., Amorex, Coropharm, Villach, Austria). The subjects were evaluated at baseline, at 3 weeks and at the end of the 6-week trial using an adapted version of the Seiffge-Krenke's Problem Questionnaire. BDNF and platelet serotonin content were determined at baseline, at 3 weeks, and after the completion of the 6-week trial. We observed significant improvements in romantic stress scores from weeks 0 through 3 (p=0.007) but no further significant improvement was evident from weeks 3 through 6 (p=0.19). At 6 weeks, subjects had a significant increase from baseline in both BDNF and platelet serotonin values. Our data suggest that direct modulation of the serotonergic system may have use for the treatment of psychological suffering associated with unreciprocated romantic love.

Efficacy and safety of amphotericin B emulsion versus liposomal formulation in Indian patients with visceral leishmaniasis: a randomized, open-label study.

Directory of Open Access Journals (Sweden)

Shyam Sundar

2014-09-01

Full Text Available India is home to 60% of the total global visceral leishmaniasis (VL population. Use of long-term oral (e.g. miltefosine and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB lipid emulsion (ABLE in comparison with that of liposomal formulation (LAmB.In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3:1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376 or LAmB (N = 124. Initial cure (Day 30/45, clinical improvement (Day 30 and long term definitive cure (Day 180 were assessed.A total of 326 (86.7% patients in the ABLE group and 122 (98.4% patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: -0.0663, -0.0150. Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%. Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3% and chills (18.4% vs. 18.5% were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3% compared to LAmB (1.6%. Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.www.clinicaltrials.gov NCT00876824.

Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial.

Science.gov (United States)

Longo, Nicola; Harding, Cary O; Burton, Barbara K; Grange, Dorothy K; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M; Dorenbaum, Alejandro; Neuenburg, Jutta K; Musson, Donald G; Gu, Zhonghua; Sile, Saba

2014-07-05

Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. Phenylalanine ammonia lyase is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. We aimed to assess the safety, tolerability, pharmacokinetic characteristics, and efficacy of recombinant Anabaena variabilis phenylalanine ammonia lyase (produced in Escherichia coli) conjugated with polyethylene glycol (rAvPAL-PEG) in reducing phenylalanine concentrations in adult patients with phenylketonuria. In this open-label, phase 1, multicentre trial, single subcutaneous injections of rAvPAL-PEG were given in escalating doses (0·001, 0·003, 0·010, 0·030, and 0·100 mg/kg) to adults with phenylketonuria. Participants aged 18 years or older with blood phenylalanine concentrations of 600 μmol/L or higher were recruited from among patients attending metabolic disease clinics in the USA. The primary endpoints were safety and tolerability of rAvPAL-PEG. Secondary endpoints were the pharmacokinetic characteristics of the drug and its effect on concentrations of phenylalanine. Participants and investigators were not masked to assigned dose group. This study is registered with ClinicalTrials.gov, number NCT00925054. 25 participants were recruited from seven centres between May 6, 2008, and April 15, 2009, with five participants assigned to each escalating dose group. All participants were included in the safety population. The most frequently reported adverse events were injection-site reactions and dizziness, which were self-limited and without sequelae. Two participants had serious adverse reactions to intramuscular medroxyprogesterone acetate, a drug that contains polyethylene glycol as an excipient. Three of five participants given the highest dose of rAvPAL-PEG (0·100 mg/kg) developed a generalised skin rash

Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers.

Science.gov (United States)

Belotto, Karisa Cristina Rodrigues; Raposo, Nádia Rezende Barbosa; Ferreira, Aline Siqueira; Gattaz, Wagner Farid

2010-11-01

Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m

Graceful, harmonious and magic type labelings relations and techniques

CERN Document Server

López, Susana C

2017-01-01

Aimed toward upper undergraduate and graduate students in mathematics, this book examines the foremost forms of graph labelings including magic, harmonious, and graceful labelings. An overview of basic graph theory concepts and notation is provided along with the origins of graph labeling. Common methods and techniques are presented introducing readers to links between graph labels. A variety of useful techniques are presented to analyze and understand properties of graph labelings. The classical results integrated with new techniques, complete proofs, numerous exercises, and a variety of open problems, will provide readers with a solid understanding of graph labelings.

Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial.

Science.gov (United States)

Wozniak, Janet; Biederman, Joseph; Mick, Eric; Waxmonsky, James; Hantsoo, Liisa; Best, Catherine; Cluette-Brown, Joanne E; Laposata, Michael

2007-01-01

To test the effectiveness and safety of omega-3 fatty acids (Omegabrite(R) brand) in the treatment of pediatric bipolar disorder (BPD). Subjects (N=20) were outpatients of both sexes, 6 to 17 years of age, with a DSM-IV diagnosis of BPD and Young Mania Rating Scale (YMRS) score of >15 treated over an 8-week period in open-label trial with omega-3 fatty acids 1290 mg-4300 mg combined EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Subjects experienced a statistically significant but modest 8.9+/-2.9 point reduction in the YMRS scores (baseline YMRS=28.9+/-10.1; endpoint YMRS=19.1+/-2.6, pDHA increased in treated subjects. As only 35% of these subjects had a response by the usual accepted criteria of >50% decrease on the YMRS, omega-3 fatty acids treatment was associated with a very modest improvement in manic symptoms in children with BPD.

An instrument assessing satisfaction with iron chelation therapy: Psychometric testing from an open-label clinical trial.

Science.gov (United States)

Rofail, Diana; Viala, Muriel; Gater, Adam; Abetz-Webb, Linda; Baladi, Jean-Francois; Cappellini, Maria Domenica

2010-08-01

The Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument. Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4. Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach's alpha: 0.75-0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened). The SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument.

Enhanced photoluminescence from single nitrogen-vacancy defects in nanodiamonds coated with phenol-ionic complexes

Science.gov (United States)

Bray, Kerem; Previdi, Rodolfo; Gibson, Brant C.; Shimoni, Olga; Aharonovich, Igor

2015-03-01

Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing. We propose that the nanodiamond encapsulation reduces the non-radiative decay pathways of the NV color centers. Our results provide a versatile and assessable way to enhance photoluminescence from nanodiamond defects that can be used in a variety of sensing and imaging applications.Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing. We propose that the nanodiamond encapsulation reduces the non-radiative decay pathways of the NV color centers. Our results provide a versatile and assessable way to enhance photoluminescence from nanodiamond defects that can be used in a variety of sensing and imaging applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07510b

Analysis of short and long crack behavior and single overload effect by crack opening stress

International Nuclear Information System (INIS)

Song, Sam Hong; Lee, Kyeong Ro

1999-01-01

The study analyzed the behaviors of short and long crack as well as the effect of single tensile overload on the crack behaviors by using fatigue crack opening behavior. Crack opening stress is measured by an elastic compliance method which may precisely and continuously provide many data using strain gages during experiment. The unusual growth behaviors of short crack and crack after the single tensile overload applied, was explained by the variations of crack opening stress. In addition, fatigue crack growth rate was expressed as a linear form for short crack as for long crack by using effective stress intensity factor range as fracture mechanical parameter, which is based on crack closure concept. And investigation is performed with respect to the relation between plastic zone size formed at the crack tip and crack retardation, crack length and the number of cycles promoted or retarded, and the overload effect on the fatigue life

An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

Directory of Open Access Journals (Sweden)

Zhang C

2017-03-01

Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK).

Science.gov (United States)

Mueller, Ruediger B; Gengenbacher, Michael; Richter, Symi; Dudler, Jean; Möller, Burkhard; von Kempis, Johannes

2016-04-14

Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in

An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

DEFF Research Database (Denmark)

Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

2013-01-01

This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

Larmor labeling by time-gradient magnetic fields

International Nuclear Information System (INIS)

Ioffe, Alexander; Bodnarchuk, Victor; Bussmann, Klaus; Mueller, Robert

2007-01-01

The Larmor labeling of neutrons, due to the Larmor precession of neutron spin in a magnetic field, opens the unique possibility for the development of neutron spin-echo (NSE) based on neutron scattering techniques, featuring an extremely high energy (momentum) resolution. Here, we present the experimental proof of a new method of the Larmor labeling using time-gradient magnetic fields

Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study [Corrigendum

Directory of Open Access Journals (Sweden)

Wani RA

2015-03-01

Full Text Available Wani RA, Dar MA, Chandel RK, et al Title of paper should have been “Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a randomized, open-label study”.  Read the original paper 

An Open-Label Evaluator Blinded Study of the Efficacy and Safety of a New Nutritional Supplement in Androgenetic Alopecia: A Pilot Study

OpenAIRE

Nichols, Anna J.; Hughes, Olivia Bosshardt; Canazza, Agnese; Zaiac, Martin N.

2017-01-01

Objective: To evaluate the effectiveness of a novel oral supplement, Forti5?, containing green tea extract, omega 3 and 6 fatty acids, cholecalciferol, melatonin, beta-sitosterol, and soy isoflavones, and in the management of subjects with androgenetic alopecia. Design: A prospective case series of 10 subjects. Setting: Open-label, evaluator-blinded, proof-of-concept study. Participants: Ten adult subjects with androgenetic alopecia completed the study. Subjects were not allowed to use oral o...

Photon-HDF5: An Open File Format for Timestamp-Based Single-Molecule Fluorescence Experiments.

Science.gov (United States)

Ingargiola, Antonino; Laurence, Ted; Boutelle, Robert; Weiss, Shimon; Michalet, Xavier

2016-01-05

We introduce Photon-HDF5, an open and efficient file format to simplify exchange and long-term accessibility of data from single-molecule fluorescence experiments based on photon-counting detectors such as single-photon avalanche diode, photomultiplier tube, or arrays of such detectors. The format is based on HDF5, a widely used platform- and language-independent hierarchical file format for which user-friendly viewers are available. Photon-HDF5 can store raw photon data (timestamp, channel number, etc.) from any acquisition hardware, but also setup and sample description, information on provenance, authorship and other metadata, and is flexible enough to include any kind of custom data. The format specifications are hosted on a public website, which is open to contributions by the biophysics community. As an initial resource, the website provides code examples to read Photon-HDF5 files in several programming languages and a reference Python library (phconvert), to create new Photon-HDF5 files and convert several existing file formats into Photon-HDF5. To encourage adoption by the academic and commercial communities, all software is released under the MIT open source license. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

Science.gov (United States)

Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

2016-01-01

To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

Science.gov (United States)

Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

2016-01-01

Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

Isotope label-aided mass spectrometry reveals the influence of environmental factors on metabolism in single eggs of fruit fly.

Directory of Open Access Journals (Sweden)

Te-Wei Tseng

Full Text Available In order to investigate the influence of light/dark cycle on the biosynthesis of metabolites during oogenesis, here we demonstrate a simple experimental protocol which combines in-vivo isotopic labeling of primary metabolites with mass spectrometric analysis of single eggs of fruit fly (Drosophila melanogaster. First, fruit flies were adapted to light/dark cycle using artificial white light. Second, female flies were incubated with an isotopically labeled sugar ((13C(6-glucose for 12 h--either during the circadian day or the circadian night, at light or at dark. Third, eggs were obtained from the incubated female flies, and analyzed individually by matrix-assisted laser desorption/ionization (MALDI mass spectrometry (MS: this yielded information about the extent of labeling with carbon-13. Since the incorporation of carbon-13 to uridine diphosphate glucose (UDP-glucose in fruit fly eggs is very fast, the labeling of this metabolite was used as an indicator of the biosynthesis of metabolites flies/eggs during 12-h periods, which correspond to circadian day or circadian night. The results reveal that once the flies adapted to the 12-h-light/12-h-dark cycle, the incorporation of carbon-13 to UDP-glucose present in fruit fly eggs was not markedly altered by an acute perturbation to this cycle. This effect may be due to a relationship between biosynthesis of primary metabolites in developing eggs and an alteration to the intake of the labeled substrate - possibly related to the change of the feeding habit. Overall, the study shows the possibility of using MALDI-MS in conjunction with isotopic labeling of small metazoans to unravel the influence of environmental cues on primary metabolism.

Photon-HDF5: An Open File Format for Timestamp-Based Single-Molecule Fluorescence Experiments

OpenAIRE

Ingargiola, Antonino; Laurence, Ted; Boutelle, Robert; Weiss, Shimon; Michalet, Xavier

2016-01-01

We introduce Photon-HDF5, an open and efficient file format to simplify exchange and long-term accessibility of data from single-molecule fluorescence experiments based on photon-counting detectors such as single-photon avalanche diode, photomultiplier tube, or arrays of such detectors. The format is based on HDF5, a widely used platform- and language-independent hierarchical file format for which user-friendly viewers are available. Photon-HDF5 can store raw photon data (timestamp, channel n...

Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

Science.gov (United States)

Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

2016-03-01

Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

Science.gov (United States)

Bernardo-Escudero, Roberto; Alonso-Campero, Rosalba; Francisco-Doce, María Teresa de Jesús; Cortés-Fuentes, Myriam; Villa-Vargas, Miriam; Angeles-Uribe, Juan

2012-12-01

The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

Science.gov (United States)

Thyssen, An; Solanki, Bhavna; Treem, William

2012-07-01

A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable

Progressive multi-atlas label fusion by dictionary evolution.

Science.gov (United States)

Song, Yantao; Wu, Guorong; Bahrami, Khosro; Sun, Quansen; Shen, Dinggang

2017-02-01

Accurate segmentation of anatomical structures in medical images is important in recent imaging based studies. In the past years, multi-atlas patch-based label fusion methods have achieved a great success in medical image segmentation. In these methods, the appearance of each input image patch is first represented by an atlas patch dictionary (in the image domain), and then the latent label of the input image patch is predicted by applying the estimated representation coefficients to the corresponding anatomical labels of the atlas patches in the atlas label dictionary (in the label domain). However, due to the generally large gap between the patch appearance in the image domain and the patch structure in the label domain, the estimated (patch) representation coefficients from the image domain may not be optimal for the final label fusion, thus reducing the labeling accuracy. To address this issue, we propose a novel label fusion framework to seek for the suitable label fusion weights by progressively constructing a dynamic dictionary in a layer-by-layer manner, where the intermediate dictionaries act as a sequence of guidance to steer the transition of (patch) representation coefficients from the image domain to the label domain. Our proposed multi-layer label fusion framework is flexible enough to be applied to the existing labeling methods for improving their label fusion performance, i.e., by extending their single-layer static dictionary to the multi-layer dynamic dictionary. The experimental results show that our proposed progressive label fusion method achieves more accurate hippocampal segmentation results for the ADNI dataset, compared to the counterpart methods using only the single-layer static dictionary. Copyright © 2016 Elsevier B.V. All rights reserved.

An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.

Science.gov (United States)

Ratliff, Joseph C; Palmese, Laura B; Reutenauer, Erin L; Tek, Cenk

2015-01-01

A possible mechanism of antipsychotic-induced weight gain is activation of hypothalamic monophosphate-dependent kinase (AMPK) mediated by histamine 1 receptors. Alpha-lipoic acid (ALA), a potent antioxidant, counteracts this effect and may be helpful in reducing weight for patients taking antipsychotics. The objective of this open-label study was to assess the efficacy of ALA (1,200 mg) on twelve non-diabetic schizophrenia patients over ten weeks. Participants lost significant weight during the intervention (-2.2 kg±2.5 kg). ALA was well tolerated and was particularly effective for individuals taking strongly antihistaminic antipsychotics (-2.9 kg±2.6 kg vs. -0.5 kg±1.0 kg). NCT01355952.

Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

NARCIS (Netherlands)

F.W. Rozendaal (Frans); P.E. Spronk (Peter); F.F. Snellen (Ferdinand); A. Schoen (Adri); A.R.H. van Zanten (Arthur); N.A. Foudraine (Norbert); P.G.H. Mulder (Paul); J. Bakker (Jan)

2009-01-01

textabstractObjective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals.

Gap opening and tuning in single-layer graphene with combined electric and magnetic field modulation

Institute of Scientific and Technical Information of China (English)

Lin Xin; Wang Hai-Long; Pan Hui; Xu Huai-Zhe

2011-01-01

The energy band structure of single-layer graphene under one-dimensional electric and magnetic field modulation is theoretically investigated. The criterion for bandgap opening at the Dirac point is analytically derived with a two-fold degeneracy second-order perturbation method. It is shown that a direct or an indirect bandgap semiconductor could be realized in a single-layer graphene under some specific configurations of the electric and magnetic field arrangement. Due to the bandgap generated in the single-layer graphene, the Klein tunneling observed in pristine graphene is completely suppressed.

No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a Phase I Open Label Study to assess safety, tolerability and cytokine responses

Science.gov (United States)

Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed since the mid 1990s by between 2 and 5 million people daily, the scientific literature lacks rigorous clinical trials that describe the potential harms of LGG, particularly in the elderly. The primary objective of this open label...

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

Science.gov (United States)

Smith, Deidre J; Sarris, Jerome; Dowling, Nathan; O'Connor, Manjula; Ng, Chee H

2018-04-01

Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P depression.

An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder.

Science.gov (United States)

Kent, Justine M; Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

2013-12-01

The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

Single walled carbon nanotube-based electrical biosensor for the label-free detection of pathogenic bacteria

DEFF Research Database (Denmark)

Yoo, S. M.; Baek, Y. K.; Shin, S.

2016-01-01

We herein describe the development of a single-walled carbon nanotube (SWNT)-based electrical biosensor consisting of a two-terminal resistor, and report its use for the specific, label-free detection of pathogenic bacteria via changes in conductance. The ability of this biosensor to recognize...... different pathogenic bacteria was analyzed, and conditions were optimized with different probe concentrations. Using this system, the reference strains and clinical isolates of Staphylococcus aureus and Escherichia coli were successfully detected; in both cases, the sensor showed a detection limit of 10 CFU....... This SWNT-based electrical biosensor will prove useful for the development of highly sensitive and specific handheld pathogen detectors....

Canonical Labelling of Site Graphs

Directory of Open Access Journals (Sweden)

Nicolas Oury

2013-06-01

Full Text Available We investigate algorithms for canonical labelling of site graphs, i.e. graphs in which edges bind vertices on sites with locally unique names. We first show that the problem of canonical labelling of site graphs reduces to the problem of canonical labelling of graphs with edge colourings. We then present two canonical labelling algorithms based on edge enumeration, and a third based on an extension of Hopcroft's partition refinement algorithm. All run in quadratic worst case time individually. However, one of the edge enumeration algorithms runs in sub-quadratic time for graphs with "many" automorphisms, and the partition refinement algorithm runs in sub-quadratic time for graphs with "few" bisimulation equivalences. This suite of algorithms was chosen based on the expectation that graphs fall in one of those two categories. If that is the case, a combined algorithm runs in sub-quadratic worst case time. Whether this expectation is reasonable remains an interesting open problem.

The Evolution of the Appendectomy: From Open to Laparoscopic to Single Incision

Directory of Open Access Journals (Sweden)

Noah J. Switzer

2012-01-01

Full Text Available Beginning with its initial description by Fitz in the 19th century, acute appendicitis has been a significant long-standing medical challenge; today it remains the most common gastrointestinal emergency in adults. Already in 1894, McBurney advocated for the surgical removal of the inflamed appendix and is credited with the initial description of an Open Appendectomy (OA. With the introduction of minimally invasive surgery, this classic approach evolved into a procedure with multiple, smaller incisions; a technique termed Laparoscopic Appendectomy (LA. There is much literature describing the advantages of this newer approach. To name a few, patients have significantly less wound infections, reduced pain, and a reduction in ileus compared with the OA. In the past few years, Single Incision Laparoscopic Appendectomy (SILA has gained popularity as the next major evolutionary advancement in the removal of the appendix. Described as a pioneer in the era of “scarless surgery,” it involves only one transumbilical incision. Patients are postulated to have reduced post-operative complications such as infection, hernias, and hematomas, as well as a quicker recovery time and less post-operative pain scores, in comparison to its predecessors. In this review, we explore the advancement of the appendectomy from open to laparoscopic to single incision.

Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

Science.gov (United States)

Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

2011-06-08

ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

Application of single-vial ready-for-use formulation of 111In- or 177Lu-labelled somatostatin analogs.

Science.gov (United States)

de Blois, Erik; Chan, Ho Sze; de Zanger, Rory; Konijnenberg, Mark; Breeman, Wouter A P

2014-02-01

For the sake of safety it would be desirable to store and transport the ready-for-use liquid formulation (diagnostics and therapeutics) of radiolabelled peptides. The use of ethanol, in combination with a mixture of gentisic- and ascorbic acid, has superior effects on stabilizing radiolabelled somatostatin analogs. As a consequence, (111)In- and (177)Lu-labelled somatostatin analogs can be stored and transported in a single-vial ready-for-use liquid formulation up to 7 days after radiolabelling. © 2013 Published by Elsevier Ltd.

Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

NARCIS (Netherlands)

Marina, Neyssa M.; Smeland, Sigbjørn; Bielack, Stefan S.; Bernstein, Mark; Jovic, Gordana; Krailo, Mark D.; Hook, Jane M.; Arndt, Carola; van den Berg, Henk; Brennan, Bernadette; Brichard, Bénédicte; Brown, Ken L. B.; Butterfass-Bahloul, Trude; Calaminus, Gabriele; Daldrup-Link, Heike E.; Eriksson, Mikael; Gebhardt, Mark C.; Gelderblom, Hans; Gerss, Joachim; Goldsby, Robert; Goorin, Allen; Gorlick, Richard; Grier, Holcombe E.; Hale, Juliet P.; Hall, Kirsten Sundby; Hardes, Jendrik; Hawkins, Douglas S.; Helmke, Knut; Hogendoorn, Pancras C. W.; Isakoff, Michael S.; Janeway, Katherine A.; Jürgens, Heribert; Kager, Leo; Kühne, Thomas; Lau, Ching C.; Leavey, Patrick J.; Lessnick, Stephen L.; Mascarenhas, Leo; Meyers, Paul A.; Mottl, Hubert; Nathrath, Michaela; Papai, Zsuzsanna; Randall, R. Lor; Reichardt, Peter; Renard, Marleen; Safwat, Akmal Ahmed; Schwartz, Cindy L.; Stevens, Michael C. G.; Strauss, Sandra J.; Teot, Lisa; Werner, Mathias; Sydes, Matthew R.; Whelan, Jeremy S.

2016-01-01

We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. EURAMOS-1 was an open-label,

Novel Optical Labeling Scheme for Ultra-High Bit Rate Data Packets

DEFF Research Database (Denmark)

Medhin, Ashenafi Kiros; Galili, Michael; Oxenløwe, Leif Katsuo

2013-01-01

We propose and verify by simulations an optical in-band labeling scheme for ultra-fast optical switching. The scheme is able to label more than 60 different 640-Gbit/s OTDM packets with eye opening penalty <1 dB....

Multi-Label Learning via Random Label Selection for Protein Subcellular Multi-Locations Prediction.

Science.gov (United States)

Wang, Xiao; Li, Guo-Zheng

2013-03-12

Prediction of protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods are only used to deal with the single-location proteins. In the past few years, only a few methods have been proposed to tackle proteins with multiple locations. However, they only adopt a simple strategy, that is, transforming the multi-location proteins to multiple proteins with single location, which doesn't take correlations among different subcellular locations into account. In this paper, a novel method named RALS (multi-label learning via RAndom Label Selection), is proposed to learn from multi-location proteins in an effective and efficient way. Through five-fold cross validation test on a benchmark dataset, we demonstrate our proposed method with consideration of label correlations obviously outperforms the baseline BR method without consideration of label correlations, indicating correlations among different subcellular locations really exist and contribute to improvement of prediction performance. Experimental results on two benchmark datasets also show that our proposed methods achieve significantly higher performance than some other state-of-the-art methods in predicting subcellular multi-locations of proteins. The prediction web server is available at http://levis.tongji.edu.cn:8080/bioinfo/MLPred-Euk/ for the public usage.

An observational study of consumer use of fast-food restaurant drive-through lanes: implications for menu labelling policy.

Science.gov (United States)

Roberto, Christina A; Hoffnagle, Elena; Bragg, Marie A; Brownell, Kelly D

2010-11-01

Some versions of restaurant menu labelling legislation do not require energy information to be posted on menus for drive-through lanes. The present study was designed to quantify the number of customers who purchase fast food through drive-in windows as a means of informing legislative labelling efforts. This was an observational study. The study took place at two McDonald's and Burger King restaurants, and single Dairy Queen, Kentucky Fried Chicken, Taco Bell and Wendy's restaurants. The number of customers entering the chain restaurants and purchasing food via the drive-through lane were recorded. A total of 3549 patrons were observed. The percentage of customers who made their purchases at drive-throughs was fifty-seven. The overall average (57 %) is likely a conservative estimate because some fast-food restaurants have late-night hours when only the drive-throughs are open. Since nearly six in ten customers purchase food via the drive-through lanes, menu labelling legislation should mandate the inclusion of menu labels on drive-through menu boards to maximise the impact of this public health intervention.

METHOD AND MODULE FOR OPTICAL SUBCARRIER LABELLING

DEFF Research Database (Denmark)

2004-01-01

The present invention relates to optical labelling in WDM networks, in that it provides a method and a module to be used in subcarrier label generation and switching in network edge nodes and core switch nodes. The methods and modules are typically employed in Optical Subcarrier Multiplexing (OSCM......) transmitters. The payload and the label are encoded independently on optical carrier and subcarrier signals respectively, using electro-optical modulators. The invention applies single or double sideband carrier-suppressed modulation to generate subcarrier signals for encoding of the label. Thereby the payload...... encoded carrier signal and the label encoded subcarrier signal can be coupled directly without prior filtering....

Label-free cell-cycle analysis by high-throughput quantitative phase time-stretch imaging flow cytometry

Science.gov (United States)

Mok, Aaron T. Y.; Lee, Kelvin C. M.; Wong, Kenneth K. Y.; Tsia, Kevin K.

2018-02-01

Biophysical properties of cells could complement and correlate biochemical markers to characterize a multitude of cellular states. Changes in cell size, dry mass and subcellular morphology, for instance, are relevant to cell-cycle progression which is prevalently evaluated by DNA-targeted fluorescence measurements. Quantitative-phase microscopy (QPM) is among the effective biophysical phenotyping tools that can quantify cell sizes and sub-cellular dry mass density distribution of single cells at high spatial resolution. However, limited camera frame rate and thus imaging throughput makes QPM incompatible with high-throughput flow cytometry - a gold standard in multiparametric cell-based assay. Here we present a high-throughput approach for label-free analysis of cell cycle based on quantitative-phase time-stretch imaging flow cytometry at a throughput of > 10,000 cells/s. Our time-stretch QPM system enables sub-cellular resolution even at high speed, allowing us to extract a multitude (at least 24) of single-cell biophysical phenotypes (from both amplitude and phase images). Those phenotypes can be combined to track cell-cycle progression based on a t-distributed stochastic neighbor embedding (t-SNE) algorithm. Using multivariate analysis of variance (MANOVA) discriminant analysis, cell-cycle phases can also be predicted label-free with high accuracy at >90% in G1 and G2 phase, and >80% in S phase. We anticipate that high throughput label-free cell cycle characterization could open new approaches for large-scale single-cell analysis, bringing new mechanistic insights into complex biological processes including diseases pathogenesis.

Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

Directory of Open Access Journals (Sweden)

Sasaki T

2014-01-01

Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Keiko Okawada,1 Maki Ishikawa,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,3 Tetsuya Shiraishi,2 Masaomi Iyo1–31Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, JapanBackground: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0 received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS, Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS, Japanese version.Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores

The relationship among expressions, labels, and descriptions of contempt.

Science.gov (United States)

Matsumoto, David; Ekman, Paul

2004-10-01

This article reports 4 studies that demonstrate that the contempt expression is reliably associated with situations that elicit contempt and that the inability to label the contempt expression reflects a problem with its label or concept and not with the relationship between its expression and emotion. In Study I, the labeling of contempt in fixed-choice judgment tasks did not occur because of a process of elimination. In Studies 2 and 3, the contempt expression was associated with situations that elicit contempt, but participants did not label the situations in an open-ended response. In Study 3, participants also more reliably labeled the contempt expression with situations rather than with labels and did not generate contempt situations from labels. In Study 4, participants reported using, hearing, and reading about contempt the least among 7 emotions tested. (c) 2004 APA, all rights reserved

Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings

Directory of Open Access Journals (Sweden)

Muriah Dawn Wheelock

2014-07-01

Full Text Available Rationale: Varenicline, the most effective single agent for smoking cessation, is a partial agonist at α4β2 nicotinic acetylcholine receptors. Increasing evidence implicates glutamate in the pathophysiology of addiction and one of the benefits of treatment for smoking cessation is the ability to regain cognitive control. Objective: To evaluate the effects of 12 week varenicline administration on glutamate levels in the dorsal anterior cingulate cortex (dACC and functional changes within the cognitive control network.Methods: We used single-voxel proton magnetic resonance spectroscopy (1H-MRS in the dACC and functional MRI (fMRI during performance of a Stroop color-naming task before and after smoking cessation with varenicline in 11 healthy smokers (open label design. Using the dACC as a seed region, we evaluated functional connectivity changes using a psychophysiological interaction (PPI analysis. Results: We observed a significant decrease in dACC glutamate + glutamine (Glx/Cr levels as well as significant blood oxygen level-dependent signal (BOLD decreases in the rostral ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These BOLD changes are suggestive of alterations in default mode network (DMN function and are further supported by the results of the PPI analysis that revealed changes in connectivity between the dACC and regions of the DMN. Baseline measures of nicotine dependence and craving positively correlated with baseline Glx/Cr levels.Conclusions: These results suggest possible mechanisms of action for varenicline such as reduction in Glx levels in dACC and shifts in BOLD activities between large scale brain networks. They also suggest a role for ACC Glx in the modulation of behavior. Due to the preliminary nature of this study (lack of control group and small sample size, future studies are needed to replicate these findings.

Accuracy of single count methods of WL determination for open-pit uranium mines

International Nuclear Information System (INIS)

Solomon, S.B.; Kennedy, K. N.

1983-01-01

A study of single count methods of WL determination was made using a database respresentative of Australian open pit uranium mine conditions. The aim of the study was to check the existence of the optimum time delay coresponding to the Rolle method, to determine the accuracy of the conversion factor for Australian conditions and to examine any systematic use of data bases of representative radon daughter concentration

Absorption, Distribution, Metabolism, and Excretion of [14C]-Volixibat in Healthy Men: Phase 1 Open-Label Study.

Science.gov (United States)

Siebers, Nicholas; Palmer, Melissa; Silberg, Debra G; Jennings, Lee; Bliss, Caleb; Martin, Patrick T

2018-02-01

Volixibat is a potent inhibitor of the apical sodium-dependent bile acid transporter in development for the treatment of nonalcoholic steatohepatitis. This phase 1, open-label study investigated the absorption, distribution, metabolism, and excretion of [ 14 C]-volixibat in heathy men. Eligible men (n = 8) aged 18-50 years (body mass index 18.0-30.0 kg/m 2 ; weight >50 kg) received a single oral dose of [ 14 C]-volixibat 50 mg containing ~5.95 µCi radioactivity. The primary objectives were to assess the pharmacokinetics of [ 14 C]-volixibat and to determine the total radioactivity in whole blood, plasma, urine, and feces at pre-selected time points over 6 days. The secondary objectives were to characterize metabolites and to assess the safety and tolerability. Low concentrations of volixibat (range 0-0.179 ng/mL) were detected in plasma up to 8 h following administration; the pharmacokinetic parameters could not be calculated. No radioactivity was observed in plasma or whole blood. The percentage (mean ± standard deviation) of total radioactivity in urine was 0.01 ± 0.007%. The vast majority (92.3 ± 5.25%) of volixibat was recovered in feces (69.2 ± 33.1% within 24 h). Unchanged volixibat was the only radioactive component detected in feces. Adverse events were mild in severity and mostly gastrointestinal. Changes in laboratory values were not clinically meaningful. Following oral administration, [ 14 C]-volixibat was excreted unchanged from the parent compound almost exclusively via fecal excretion, indicating that the drug is minimally absorbed. Consistent with other studies, adverse events were primarily gastrointestinal in nature. ClinicalTrials.gov identifier NCT02571192.

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.

Science.gov (United States)

Tawbi, Hussein A; Burgess, Melissa; Bolejack, Vanessa; Van Tine, Brian A; Schuetze, Scott M; Hu, James; D'Angelo, Sandra; Attia, Steven; Riedel, Richard F; Priebat, Dennis A; Movva, Sujana; Davis, Lara E; Okuno, Scott H; Reed, Damon R; Crowley, John; Butterfield, Lisa H; Salazar, Ruth; Rodriguez-Canales, Jaime; Lazar, Alexander J; Wistuba, Ignacio I; Baker, Laurence H; Maki, Robert G; Reinke, Denise; Patel, Shreyaskumar

2017-11-01

Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC). Patients with soft-tissue sarcoma had to be aged 18 years or older to enrol; patients with bone sarcoma could enrol if they were aged 12 years or older. Patients had histological evidence of metastatic or surgically unresectable locally advanced sarcoma, had received up to three previous lines of systemic anticancer therapy, had at least one measurable lesion according to the Response Evaluation Criteria In Solid Tumors version 1.1, and had at least one lesion accessible for biopsy. All patients were treated with 200 mg intravenous pembrolizumab every 3 weeks. The primary endpoint was investigator-assessed objective response. Patients who received at least one dose of pembrolizumab were included in the safety analysis and patients who progressed or reached at least one scan assessment were included in the activity analysis. Accrual is ongoing in some disease cohorts. This trial is registered with ClinicalTrials.gov, number NCT02301039. Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). Median follow-up was 17·8 months (IQR 12·3-19·3). Seven (18%) of 40 patients with soft-tissue sarcoma had an objective response, including four (40%) of ten patients with undifferentiated pleomorphic sarcoma, two (20%) of ten patients with liposarcoma, and one (10%) of ten patients

Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

Science.gov (United States)

Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

2014-11-01

A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml-1 with a limit of detection of 0.16 ng ml-1.

Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

DEFF Research Database (Denmark)

Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo

2015-01-01

The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean...... age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect...... in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response....

A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

DEFF Research Database (Denmark)

Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

2008-01-01

causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...

Uncertainty Flow Facilitates Zero-Shot Multi-Label Learning in Affective Facial Analysis

Directory of Open Access Journals (Sweden)

Wenjun Bai

2018-02-01

Full Text Available Featured Application: The proposed Uncertainty Flow framework may benefit the facial analysis with its promised elevation in discriminability in multi-label affective classification tasks. Moreover, this framework also allows the efficient model training and between tasks knowledge transfer. The applications that rely heavily on continuous prediction on emotional valance, e.g., to monitor prisoners’ emotional stability in jail, can be directly benefited from our framework. Abstract: To lower the single-label dependency on affective facial analysis, it urges the fruition of multi-label affective learning. The impediment to practical implementation of existing multi-label algorithms pertains to scarcity of scalable multi-label training datasets. To resolve this, an inductive transfer learning based framework, i.e.,Uncertainty Flow, is put forward in this research to allow knowledge transfer from a single labelled emotion recognition task to a multi-label affective recognition task. I.e., the model uncertainty—which can be quantified in Uncertainty Flow—is distilled from a single-label learning task. The distilled model uncertainty ensures the later efficient zero-shot multi-label affective learning. On the theoretical perspective, within our proposed Uncertainty Flow framework, the feasibility of applying weakly informative priors, e.g., uniform and Cauchy prior, is fully explored in this research. More importantly, based on the derived weight uncertainty, three sets of prediction related uncertainty indexes, i.e., soft-max uncertainty, pure uncertainty and uncertainty plus are proposed to produce reliable and accurate multi-label predictions. Validated on our manual annotated evaluation dataset, i.e., the multi-label annotated FER2013, our proposed Uncertainty Flow in multi-label facial expression analysis exhibited superiority to conventional multi-label learning algorithms and multi-label compatible neural networks. The success of our

Exploring the Relevance of Single-Gender Group Formation: What We Learn from a Massive Open Online Course (MOOC)

Science.gov (United States)

Bayeck, Rebecca Yvonne; Hristova, Adelina; Jablokow, Kathryn W.; Bonafini, Fernanda

2018-01-01

This paper reports the results of an exploratory study on participants' perception of the importance of single-gender grouping in a massive open online course (MOOC) delivered through the Coursera platform. Findings reveal that female and male learners' perception of single-gender grouping differs. Female students more than males indicated less…

Pharmacokinetic interaction of finasteride with tamsulosin hydrochloride: an open-label, randomized, 3-period crossover study in healthy Chinese male volunteers.

Science.gov (United States)

Chu, Nannan; Xu, Hongrong; Wang, Guoqin; Wang, Jiangdian; Chen, Weili; Yuan, Fei; Yang, Mengjie; Li, Xuening

2015-02-01

The primary aim of this study was to evaluate whether there was clinically significant pharmacokinetic (PK) interaction between finasteride and tamsulosin in healthy Chinese male subjects. This was an open-label, randomized, 3-period, crossover study. Subjects received single and multiple doses of 5 mg finasteride alone, single and multiple doses of 0.2 mg tamsulosin hydrochloride sustained-release capsule alone, and single and multiple doses of 5 mg finasteride with 0.2 mg tamsulosin hydrochloride, in an order determined by a computerized randomization schedule. Blood samples were collected up to 48 hours after dosing on study day 1 and up to 24 hours after dosing on study day 9 for determination of plasma concentrations with a validated LC-MS/MS method. Pharmacokinetic parameters were estimated via noncompartmental methods. Tolerability was evaluated by monitoring adverse events, laboratory assays, vital signs, and 12-lead ECG. Fifteen subjects were enrolled, and 14 completed the study. The geometric mean ratios (GMRs) (90% CIs) of AUC(τ,ss) and C(max,ss) values of finasteride at steady state between coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.14 (1.05-1.23) and 1.06 (0.99-1.14), respectively. The GMRs (90% CIs) for AUC(0-t) and C(max) values of finasteride for a single dose of coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.02 (0.94-1.11) and 1.06 (1.01-1.11), respectively. The GMRs (90% CIs) for AUC(τ,ss) and C(max,ss) values of tamsulosin at steady-state for coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.18 (1.05-1.33) and 1.23 (1.06-1.43), respectively. The GMRs (90% CIs) for AUC(0-t) and C(max) values of tamsulosin for a single dose of coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.04 (0.97-1.10) and 1.04 (0.98-1.11), respectively. Statistical analyses

Microbial status and product labelling of 58 original tattoo inks

DEFF Research Database (Denmark)

Høgsberg, T; Saunte, D M; Frimodt-møller, Niels

2011-01-01

and labelled according to REACH as if they were plain chemicals. Objective  The objective of this study was to check the microbial product safety of unopened and opened tattoo ink stock bottles. Packaging, labelling, preservation, sterility and contamination with micro-organisms were studied. Methods  Physical......-pathogenic environmental bacteria. Yeast or moulds were detected in none of the samples. A total of 31% of the manufacturers informed only about the brand name. No information about content, sterility, risks or expiry date was indicated on the label. A total of 42% claimed sterility of their inks. A total of 54% labelled...

High-resolution Spectroscopic Observations of Single Red Giants in Three Open Clusters: NGC 2360, NGC 3680, and NGC 5822

Science.gov (United States)

Peña Suárez, V. J.; Sales Silva, J. V.; Katime Santrich, O. J.; Drake, N. A.; Pereira, C. B.

2018-02-01

Single stars in open clusters with known distances are important targets in constraining the nucleosynthesis process since their ages and luminosities are also known. In this work, we analyze a sample of 29 single red giants of the open clusters NGC 2360, NGC 3680, and NGC 5822 using high-resolution spectroscopy. We obtained atmospheric parameters, abundances of the elements C, N, O, Na, Mg, Al, Ca, Si, Ti, Ni, Cr, Y, Zr, La, Ce, and Nd, as well as radial and rotational velocities. We employed the local thermodynamic equilibrium atmospheric models of Kurucz and the spectral analysis code MOOG. Rotational velocities and light-element abundances were derived using spectral synthesis. Based on our analysis of the single red giants in these three open clusters, we could compare, for the first time, their abundance pattern with that of the binary stars of the same clusters previously studied. Our results show that the abundances of both single and binary stars of the open clusters NGC 2360, NGC 3680, and NGC 5822 do not have significant differences. For the elements created by the s-process, we observed that the open clusters NGC 2360, NGC 3680, and NGC 5822 also follow the trend already raised in the literature that young clusters have higher s-process element abundances than older clusters. Finally, we observed that the three clusters of our sample exhibit a trend in the [Y/Mg]-age relation, which may indicate the ability of the [Y/Mg] ratio to be used as a clock for the giants. Based on the observations made with the 2.2 m telescope at the European Southern Observatory (La Silla, Chile) under an agreement with Observatório Nacional and under an agreement between Observatório Nacional and Max-Planck Institute für Astronomie.

New thiol-responsive mono-cleavable block copolymer micelles labeled with single disulfides.

Science.gov (United States)

Sourkohi, Behnoush Khorsand; Schmidt, Rolf; Oh, Jung Kwon

2011-10-18

Thiol-responsive symmetric triblock copolymers having single disulfide linkages in the middle blocks (called mono-cleavable block copolymers, ss-ABP(2)) were synthesized by atom transfer radical polymerization in the presence of a disulfide-labeled difunctional Br-initiator. These brush-like triblock copolymers consist of a hydrophobic polyacrylate block having pendent oligo(propylene oxide) and a hydrophilic polymethacrylate block having pendent oligo(ethylene oxide). Gel permeation chromatography and (1)H NMR results confirmed the synthesis of well-defined mono-cleavable block copolymers and revealed that polymerizations were well controlled. Because of amphiphilic nature, these copolymers self-assembled to form colloidally stable micelles above critical micellar concentration of 0.032 mg · mL(-1). In response to reductive reactions, disulfides in thiol-responsive micelles were cleaved. Atomic force microscopy and dynamic light scattering analysis suggested that the cleavage of disulfides caused dissociation of micelles to smaller-sized assembled structures in water. Moreover, in a biomedical perspective, the mono-cleavable block copolymer micelles are not cytotoxic and thus biocompatible. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interval prediction for graded multi-label classification

CERN Document Server

Lastra, Gerardo; Bahamonde, Antonio

2014-01-01

Multi-label was introduced as an extension of multi-class classification. The aim is to predict a set of classes (called labels in this context) instead of a single one, namely the set of relevant labels. If membership to the set of relevant labels is defined to a certain degree, the learning task is called graded multi-label classification. These learning tasks can be seen as a set of ordinal classifications. Hence, recommender systems can be considered as multi-label classification tasks. In this paper, we present a new type of nondeterministic learner that, for each instance, tries to predict at the same time the true grade for each label. When the classification is uncertain for a label, however, the hypotheses predict a set of consecutive grades, i.e., an interval. The goal is to keep the set of predicted grades as small as possible; while still containing the true grade. We shall see that these classifiers take advantage of the interrelations of labels. The result is that, with quite narrow intervals, i...

A Bayesian analysis of the mixed labelling phenomenon in two-target tracking

NARCIS (Netherlands)

Aoki, E.H.; Boers, Y.; Svensson, L.; Mandal, Pranab K.; Bagchi, Arunabha

In mulit-target tracking and labelling (MTTL), mixed labelling corresponds to a situation where there is ambiguity in labelling, i.e. in the assignment of labels to locations (where a "location" here means simply an unlabelled single-target state. The phenomenon is well-known in literature, and

The effects of individual upper alpha neurofeedback in ADHD: an open-label pilot study.

Science.gov (United States)

Escolano, C; Navarro-Gil, M; Garcia-Campayo, J; Congedo, M; Minguez, J

2014-12-01

Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individually determined using the alpha peak frequency as an anchor point. 20 ADHD children underwent 18 training sessions. Clinical and neurophysiological variables were measured pre- and post-training. EEG was recorded pre- and post-training, and pre- and post-training trials within each session, in both eyes closed resting state and eyes open task-related activity. A power EEG analysis assessed long-term and within-session effects, in the trained parameter and in all the sensors in the (1-30) Hz spectral range. Learning curves over sessions were assessed as well. Parents rated a clinical improvement in children regarding inattention and hyperactivity/impulsivity. Neurophysiological tests showed an improvement in working memory, concentration and impulsivity (decreased number of commission errors in a continuous performance test). Relative and absolute upper alpha power showed long-term enhancement in task-related activity, and a positive learning curve over sessions. The analysis of within-session effects showed a power decrease ("rebound" effect) in task-related activity, with no significant effects during training trials. We conclude that the enhancement of the individual upper alpha power is effective in improving several measures of clinical outcome and cognitive performance in ADHD. This is the first NF study evaluating such a protocol in ADHD. A controlled evaluation seems warranted due to the positive results obtained in the current study.

48-spot single-molecule FRET setup with periodic acceptor excitation

Science.gov (United States)

Ingargiola, Antonino; Segal, Maya; Gulinatti, Angelo; Rech, Ivan; Labanca, Ivan; Maccagnani, Piera; Ghioni, Massimo; Weiss, Shimon; Michalet, Xavier

2018-03-01

Single-molecule Förster resonance energy transfer (smFRET) allows measuring distances between donor and acceptor fluorophores on the 3-10 nm range. Solution-based smFRET allows measurement of binding-unbinding events or conformational changes of dye-labeled biomolecules without ensemble averaging and free from surface perturbations. When employing dual (or multi) laser excitation, smFRET allows resolving the number of fluorescent labels on each molecule, greatly enhancing the ability to study heterogeneous samples. A major drawback to solution-based smFRET is the low throughput, which renders repetitive measurements expensive and hinders the ability to study kinetic phenomena in real-time. Here we demonstrate a high-throughput smFRET system that multiplexes acquisition by using 48 excitation spots and two 48-pixel single-photon avalanche diode array detectors. The system employs two excitation lasers allowing separation of species with one or two active fluorophores. The performance of the system is demonstrated on a set of doubly labeled double-stranded DNA oligonucleotides with different distances between donor and acceptor dyes along the DNA duplex. We show that the acquisition time for accurate subpopulation identification is reduced from several minutes to seconds, opening the way to high-throughput screening applications and real-time kinetics studies of enzymatic reactions such as DNA transcription by bacterial RNA polymerase.

Direct single-molecule dynamic detection of chemical reactions.

Science.gov (United States)

Guan, Jianxin; Jia, Chuancheng; Li, Yanwei; Liu, Zitong; Wang, Jinying; Yang, Zhongyue; Gu, Chunhui; Su, Dingkai; Houk, Kendall N; Zhang, Deqing; Guo, Xuefeng

2018-02-01

Single-molecule detection can reveal time trajectories and reaction pathways of individual intermediates/transition states in chemical reactions and biological processes, which is of fundamental importance to elucidate their intrinsic mechanisms. We present a reliable, label-free single-molecule approach that allows us to directly explore the dynamic process of basic chemical reactions at the single-event level by using stable graphene-molecule single-molecule junctions. These junctions are constructed by covalently connecting a single molecule with a 9-fluorenone center to nanogapped graphene electrodes. For the first time, real-time single-molecule electrical measurements unambiguously show reproducible large-amplitude two-level fluctuations that are highly dependent on solvent environments in a nucleophilic addition reaction of hydroxylamine to a carbonyl group. Both theoretical simulations and ensemble experiments prove that this observation originates from the reversible transition between the reactant and a new intermediate state within a time scale of a few microseconds. These investigations open up a new route that is able to be immediately applied to probe fast single-molecule physics or biophysics with high time resolution, making an important contribution to broad fields beyond reaction chemistry.

Bisimulation and open maps

DEFF Research Database (Denmark)

Joyal, André; Nielsen, Mogens; Winskel, Glynn

1993-01-01

Petri nets), and labeled event structures are considered. On transition systems, the abstract definition readily specialises to Milner's (1989) strong bisimulation. On event structures, it explains and leads to a revision of the history-preserving bisimulation of Rabinovitch and Traktenbrot (1988......), and Goltz and van Glabeek (1989). A tie-up with open maps in a (pre)topos brings to light a promising new model, presheaves on categories of pomsets, into which the usual category of labeled event structures embeds fully and faithfully. As an indication of its promise, this new presheaf model has refinement...

Label-Driven Learning Framework: Towards More Accurate Bayesian Network Classifiers through Discrimination of High-Confidence Labels

Directory of Open Access Journals (Sweden)

Yi Sun

2017-12-01

Full Text Available Bayesian network classifiers (BNCs have demonstrated competitive classification accuracy in a variety of real-world applications. However, it is error-prone for BNCs to discriminate among high-confidence labels. To address this issue, we propose the label-driven learning framework, which incorporates instance-based learning and ensemble learning. For each testing instance, high-confidence labels are first selected by a generalist classifier, e.g., the tree-augmented naive Bayes (TAN classifier. Then, by focusing on these labels, conditional mutual information is redefined to more precisely measure mutual dependence between attributes, thus leading to a refined generalist with a more reasonable network structure. To enable finer discrimination, an expert classifier is tailored for each high-confidence label. Finally, the predictions of the refined generalist and the experts are aggregated. We extend TAN to LTAN (Label-driven TAN by applying the proposed framework. Extensive experimental results demonstrate that LTAN delivers superior classification accuracy to not only several state-of-the-art single-structure BNCs but also some established ensemble BNCs at the expense of reasonable computation overhead.

Label-free tracking of single extracellular vesicles in a nano-fluidic optical fiber (Conference Presentation)

Science.gov (United States)

van der Pol, Edwin; Weidlich, Stefan; Lahini, Yoav; Coumans, Frank A. W.; Sturk, Auguste; Nieuwland, Rienk; Schmidt, Markus A.; Faez, Sanli; van Leeuwen, Ton G.

2016-03-01

Background: Extracellular vesicles, such as exosomes, are abundantly present in human body fluids. Since the size, concentration and composition of these vesicles change during disease, vesicles have promising clinical applications, including cancer diagnosis. However, since ~70% of the vesicles have a diameter <70 nm, detection of single vesicles remains challenging. Thus far, vesicles <70 nm have only be studied by techniques that require the vesicles to be adhered to a surface. Consequently, the majority of vesicles have never been studied in their physiological environment. We present a novel label-free optical technique to track single vesicles <70 nm in suspension. Method: Urinary vesicles were contained within a single-mode light-guiding silica fiber containing a 600 nm nano-fluidic channel. Light from a diode laser (660 nm wavelength) was coupled to the fiber, resulting in a strongly confined optical mode in the nano-fluidic channel, which continuously illuminated the freely diffusing vesicles inside the channel. The elastic light scattering from the vesicles, in the direction orthogonal to the fiber axis, was collected using a microscope objective (NA=0.95) and imaged with a home-built microscope. Results: We have tracked single urinary vesicles as small as 35 nm by elastic light scattering. Please note that vesicles are low-refractive index (n<1.4) particles, which we confirmed by combining data on thermal diffusion and light scattering cross section. Conclusions: For the first time, we have studied vesicles <70 nm freely diffusing in suspension. The ease-of-use and performance of this technique support its potential for vesicle-based clinical applications.

Aripiprazole for Irritability in Asian Children and Adolescents with Autistic Disorder: A 12-Week, Multinational, Multicenter, Prospective Open-Label Study.

Science.gov (United States)

Kim, Hyo-Won; Park, Eun-Jin; Kim, Ji-Hoon; Boon-Yasidhi, Vitharon; Tarugsa, Jariya; Reyes, Alexis; Manalo, Stella; Joung, Yoo-Sook

2018-04-24

We investigated the effectiveness and tolerability of aripiprazole in the treatment of irritability in Asian children and adolescents (6-17 years) with autistic disorder in a 12-week, multinational, multicenter, open-label study. Sixty-seven subjects (10.0 ± 3.1 years old, 52 boys) were enrolled and treated with flexibly dosed aripiprazole for 12 weeks (mean dose, 5.1 ± 2.5 mg; range 2-15 mg). Aripiprazole significantly reduced the mean caregiver-rated scores for the Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech subscales of the Aberrant Behavior Checklist from baseline to week 12 (p autistic disorder. Further studies with larger sample sizes and longer treatment durations are required.

Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome.

Science.gov (United States)

Erickson, Craig A; Wink, Logan K; Ray, Balmiki; Early, Maureen C; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; Lahiri, Debomoy K; McDougle, Christopher J

2013-07-01

Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism. As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts. Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission. We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11.9 years) with FXS. Acamprosate use (mean dose: 1,054  ±  422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of "very much improved" or "much improved") in nine of 12 (75 %) subjects. Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures. No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate. Additionally, pre- and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment. In our pilot sample, treatment response did not correlate with change in BDNF with treatment. Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity. The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies. Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted.

Link Label Prediction in Signed Citation Network

KAUST Repository

Akujuobi, Uchenna

2016-04-12

Link label prediction is the problem of predicting the missing labels or signs of all the unlabeled edges in a network. For signed networks, these labels can either be positive or negative. In recent years, different algorithms have been proposed such as using regression, trust propagation and matrix factorization. These approaches have tried to solve the problem of link label prediction by using ideas from social theories, where most of them predict a single missing label given that labels of other edges are known. However, in most real-world social graphs, the number of labeled edges is usually less than that of unlabeled edges. Therefore, predicting a single edge label at a time would require multiple runs and is more computationally demanding. In this thesis, we look at link label prediction problem on a signed citation network with missing edge labels. Our citation network consists of papers from three major machine learning and data mining conferences together with their references, and edges showing the relationship between them. An edge in our network is labeled either positive (dataset relevant) if the reference is based on the dataset used in the paper or negative otherwise. We present three approaches to predict the missing labels. The first approach converts the label prediction problem into a standard classification problem. We then, generate a set of features for each edge and then adopt Support Vector Machines in solving the classification problem. For the second approach, we formalize the graph such that the edges are represented as nodes with links showing similarities between them. We then adopt a label propagation method to propagate the labels on known nodes to those with unknown labels. In the third approach, we adopt a PageRank approach where we rank the nodes according to the number of incoming positive and negative edges, after which we set a threshold. Based on the ranks, we can infer an edge would be positive if it goes a node above the

Crystallographic and single-particle analyses of native- and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein.

Science.gov (United States)

Awayn, N H; Rosenberg, M F; Kamis, A B; Aleksandrov, L A; Riordan, J R; Ford, R C

2005-11-01

Cystic fibrosis, one of the major human inherited diseases, is caused by defects in the CFTR (cystic fibrosis transmembrane conductance regulator), a cell-membrane protein. CFTR acts as a chloride channel which can be opened by ATP. Low-resolution structural studies of purified recombinant human CFTR are described in the present paper. Localization of the C-terminal decahistidine tag in CFTR was achieved by Ni2+-nitriloacetate nanogold labelling, followed by electron microscopy and single-particle analysis. The presence of the gold label appears to improve the single-particle-alignment procedure. Projection structures of CFTR from two-dimensional crystals analysed by electron crystallography displayed two alternative conformational states in the presence of nucleotide and nanogold, but only one form of the protein was observed in the quiescent (nucleotide-free) state.

Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications

Science.gov (United States)

Harrer, S.; Kim, S. C.; Schieber, C.; Kannam, S.; Gunn, N.; Moore, S.; Scott, D.; Bathgate, R.; Skafidas, S.; Wagner, J. M.

2015-05-01

Employing integrated nano- and microfluidic circuits for detecting and characterizing biological compounds through resistive pulse sensing technology is a vibrant area of research at the interface of biotechnology and nanotechnology. Resistive pulse sensing platforms can be customized to study virtually any particle of choice which can be threaded through a fluidic channel and enable label-free single-particle interrogation with the primary read-out signal being an electric current fingerprint. The ability to perform label-free molecular screening with single-molecule and even single binding site resolution makes resistive pulse sensing technology a powerful tool for analyzing the smallest units of biological systems and how they interact with each other on a molecular level. This task is at the core of experimental systems biology and in particular ‘omics research which in combination with next-generation DNA-sequencing and next-generation drug discovery and design forms the foundation of a novel disruptive medical paradigm commonly referred to as personalized medicine or precision medicine. DNA-sequencing has approached the 1000-Dollar-Genome milestone allowing for decoding a complete human genome with unmatched speed and at low cost. Increased sequencing efficiency yields massive amounts of genomic data. Analyzing this data in combination with medical and biometric health data eventually enables understanding the pathways from individual genes to physiological functions. Access to this information triggers fundamental questions for doctors and patients alike: what are the chances of an outbreak for a specific disease? Can individual risks be managed and if so how? Which drugs are available and how should they be applied? Could a new drug be tailored to an individual’s genetic predisposition fast and in an affordable way? In order to provide answers and real-life value to patients, the rapid evolvement of novel computing approaches for analyzing big data in

Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications.

Science.gov (United States)

Harrer, S; Kim, S C; Schieber, C; Kannam, S; Gunn, N; Moore, S; Scott, D; Bathgate, R; Skafidas, S; Wagner, J M

2015-05-08

Employing integrated nano- and microfluidic circuits for detecting and characterizing biological compounds through resistive pulse sensing technology is a vibrant area of research at the interface of biotechnology and nanotechnology. Resistive pulse sensing platforms can be customized to study virtually any particle of choice which can be threaded through a fluidic channel and enable label-free single-particle interrogation with the primary read-out signal being an electric current fingerprint. The ability to perform label-free molecular screening with single-molecule and even single binding site resolution makes resistive pulse sensing technology a powerful tool for analyzing the smallest units of biological systems and how they interact with each other on a molecular level. This task is at the core of experimental systems biology and in particular 'omics research which in combination with next-generation DNA-sequencing and next-generation drug discovery and design forms the foundation of a novel disruptive medical paradigm commonly referred to as personalized medicine or precision medicine. DNA-sequencing has approached the 1000-Dollar-Genome milestone allowing for decoding a complete human genome with unmatched speed and at low cost. Increased sequencing efficiency yields massive amounts of genomic data. Analyzing this data in combination with medical and biometric health data eventually enables understanding the pathways from individual genes to physiological functions. Access to this information triggers fundamental questions for doctors and patients alike: what are the chances of an outbreak for a specific disease? Can individual risks be managed and if so how? Which drugs are available and how should they be applied? Could a new drug be tailored to an individual's genetic predisposition fast and in an affordable way? In order to provide answers and real-life value to patients, the rapid evolvement of novel computing approaches for analyzing big data in

Energy and traffic light labelling have no impact on parent and child fast food selection.

Science.gov (United States)

Dodds, Pennie; Wolfenden, Luke; Chapman, Kathy; Wellard, Lyndal; Hughes, Clare; Wiggers, John

2013-10-25

Labelling of food from fast food restaurants at point-of-purchase has been suggested as one strategy to reduce population energy consumption and contribute to reductions in obesity prevalence. The aim of this study was to examine the effects of energy and single traffic light labelling systems on the energy content of child and adult intended food purchases. The study employed a randomised controlled trial design. English speaking parents of children aged between three and 12 years were recruited from an existing research cohort. Participants were mailed one of three hypothetical fast food menus. Menus differed in their labelling technique- either energy labels, single traffic light labels, or a no-label control. Participants then completed a telephone survey which assessed intended food purchases for both adult and child. The primary trial outcome was total energy of intended food purchase. A total of 329 participants completed the follow-up telephone interview. Eighty-two percent of the energy labelling group and 96% of the single traffic light labelling group reported noticing labelling information on their menu. There were no significant differences in total energy of intended purchases of parents, or intended purchases made by parents for children, between the menu labelling groups, or between menu labelling groups by socio-demographic subgroups. This study provided no evidence to suggest that energy labelling or single traffic light labelling alone were effective in reducing the energy of fast food items selected from hypothetical fast food menus for purchase. Additional complementary public health initiatives promoting the consumption of healthier foods identified by labelling, and which target other key drivers of menu item selection in this setting may be required. Copyright © 2013. Published by Elsevier Ltd.

Homoeopathic management of Schizophrenia: A prospective, non-comparative, open-label observational study

Directory of Open Access Journals (Sweden)

Praveen Oberai

2016-01-01

Full Text Available Objectives: To evaluate the usefulness of homoeopathic intervention in Schizophrenia, in untreated cases and antipsychotic treatment resistant cases, to verify indications of medicines, and to assess relapse, if any. Materials and Methods: A prospective, non-comparative, open-label observational study was carried out from October 2005-September 2010 by CCRH at Central Research Institute (H, Kottayam, Kerala, India. Patients between 20 and 60 years of age, presenting with symptoms of Schizophrenia were screened for inclusion and exclusion criteria. The patients who were on antipsychotic drugs were allowed to continue the same along with homoeopathic medicine, the dose of antipsychotics was monitored by the Psychiatrist. The symptoms of each patient were repertorized, and medicine was initially prescribed in 30C potency after consulting Materia Medica. Patients were followed up for 12 months. Outcome of treatment was assessed with Brief Psychiatric Rating Scales (BPRS. Analysis was done using Statistical Package for the Social Sciences  SPSS Version 20.0. Results: Out of 188 enrolled patients, 17 cases did not complete the baseline information. Total 171 patients were analysed as per modified Intention to Treat Principle. Significant difference (P = 0.0001, P < 0.05 in the mean scores of BPRS, using paired t test was observed at end of the study. Sulphur, Lycopodium, Natrum muriaticum, Pulsatilla and Phosphorus were found to be the most useful medicines in treating schizophrenic patients. Conclusion: The study reflects the positive role of homoeopathic medicines in the management of patients suffering from schizophrenia as measured by BPRS.

An open-label study of sodium oxybate (Xyrem®) in spasmodic dysphonia

Science.gov (United States)

Rumbach, Anna F.; Blitzer, Andrew; Frucht, Steven J.; Simonyan, Kristina

2016-01-01

Objective Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Study Design and Methods We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem®), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Results Sodium oxybate significantly improved voice symptoms (p = 0.001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (p = 0.03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug’s effects were observed approximately 30–40 min after its intake and lasted about 3.5–4 hours. Conclusion Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol and as such sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. PMID:27808415

Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

International Nuclear Information System (INIS)

Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

2014-01-01

A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml −1 with a limit of detection of 0.16 ng ml −1

Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

Energy Technology Data Exchange (ETDEWEB)

Singh, Swati; Kumar, Ashok, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007 (India); Academy of Scientific and Innovative Research (AcSIR), New Delhi (India); Khare, Shashi [National Centre for Disease Control, Sham Nath Marg, Delhi 110054 (India); Mulchandani, Ashok [Department of Chemical and Environmental Engineering, University of California, Riverside, California 92521 (United States); Rajesh, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012 (India)

2014-11-24

A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml{sup −1} with a limit of detection of 0.16 ng ml{sup −1}.

Aziridines in the synthesis of 11C- and 18F-labelled compounds

International Nuclear Information System (INIS)

Gillings, N.M.

1998-01-01

Racemic [4- 11 C]aspartic acid, [4- 11 C]asparagine and 2,4-diamino[4- 11 C]butyric acid were synthesised by the ring-opening of an N-activated aziridine-2-carboxylate with 11 C]cyanide, followed by preparative HPLC and hydrolysis/reduction. These labelled amino acids arise from nucleophilic attack at the β-carbon of the aziridine ring. A radioactive by-product of ca. 25% was attributed to the product of α-attack. Several N-activated 2-aryl aziridines were synthesised for the attempted synthesis of β-[ 18 F] fluorophenylalanine and β-[ 18 F]fluorodopa. Ring-opening with [ 18 F]fluoride showed no evidence of β-fluorinated products and it is proposed that attack occurs exclusively at the α-carbon, giving the corresponding α-[ 18 F]fluoro-β-amino acids. Further evidence for this was the reaction of the β-unsubstituted N-activated aziridine-2-carboxylate with [ 18 F]fluoride. This reaction was totally regiospecific and afforded exclusively the α-substituted product, α-[ 18 F]fluoro-β-alanine. Aziridine precursors were resolved by chiral HPLC. On labelling the chiral aziridines, however, racemic 11 C- and 18 F-labelled amino acids were obtained. This was attributed to racemisation of the initially formed ring-opened products. The use of [ 11 C]methyl lithium as a nucleophile for aziridine ring-opening was investigated. Reaction was expected to occur at low temperature, thus potentially avoiding racemisation. No products corresponding to aziridine ring-opening with [ 11 C]methyl lithium were, however, observed. A difluorinated analogue of amphetamine was synthesised by fluorination of an azirine (via an aziridine). This racemic compound was resolved as its chiral tartarate salts and subsequently labelled by methylation with [ 11 C]methyl iodide, giving the novel compound β, β-difluoro[N-methyl- 11 C]methamphetamine in high specific activity for in vivo binding studies using positron emission tomography. The non-radioactive reference compound was also

Label inspection of approximate cylinder based on adverse cylinder panorama

Science.gov (United States)

Lin, Jianping; Liao, Qingmin; He, Bei; Shi, Chenbo

2013-12-01

This paper presents a machine vision system for automated label inspection, with the goal to reduce labor cost and ensure consistent product quality. Firstly, the images captured from each single-camera are distorted, since the inspection object is approximate cylindrical. Therefore, this paper proposes an algorithm based on adverse cylinder projection, where label images are rectified by distortion compensation. Secondly, to overcome the limited field of viewing for each single-camera, our method novelly combines images of all single-cameras and build a panorama for label inspection. Thirdly, considering the shake of production lines and error of electronic signal, we design the real-time image registration to calculate offsets between the template and inspected images. Experimental results demonstrate that our system is accurate, real-time and can be applied for numerous real- time inspections of approximate cylinders.

Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: a randomized, open-label pilot study.

Science.gov (United States)

Iha, Kosaku; Suzuki, Nao; Yoneda, Masahiro; Takeshita, Toru; Hirofuji, Takao

2013-10-01

The aim of the study was to evaluate the effect of mouth cleaning with hinokitiol-containing gel on oral malodor. An open-label, randomized, controlled trial was conducted to assess oral malodor and clinical parameters related to oral malodor before and after mouth cleaning with hinokitiol-containing gel (n = 9) or with gel not including hinokitiol (n = 9). Mouth cleaning included the teeth, gingiva, and tongue and was carried out 3 times per day for 4 weeks. Organoleptic test (OLT) scores (P = .021), levels of hydrogen sulfide (P = .008) and methyl mercaptan (P = .020), frequency of bleeding on probing, average probing pocket depth, and plaque index significantly improved in the group using hinokitiol. In contrast, only the OLT score (P = .031) significantly improved in the control group after the treatment regimen. Mouth cleaning with hinokitiol-containing gel may be effective for reduction of oral malodor. Copyright © 2013 Elsevier Inc. All rights reserved.

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

Science.gov (United States)

Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

2016-01-01

Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

Multiple tag labeling method for DNA sequencing

Science.gov (United States)

Mathies, R.A.; Huang, X.C.; Quesada, M.A.

1995-07-25

A DNA sequencing method is described which uses single lane or channel electrophoresis. Sequencing fragments are separated in the lane and detected using a laser-excited, confocal fluorescence scanner. Each set of DNA sequencing fragments is separated in the same lane and then distinguished using a binary coding scheme employing only two different fluorescent labels. Also described is a method of using radioisotope labels. 5 figs.

Enhanced photoluminescence from single nitrogen-vacancy defects in nanodiamonds coated with phenol-ionic complexes.

Science.gov (United States)

Bray, Kerem; Previdi, Rodolfo; Gibson, Brant C; Shimoni, Olga; Aharonovich, Igor

2015-03-21

Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing. We propose that the nanodiamond encapsulation reduces the non-radiative decay pathways of the NV color centers. Our results provide a versatile and assessable way to enhance photoluminescence from nanodiamond defects that can be used in a variety of sensing and imaging applications.

Two-dimensional single fluid MHD simulations of plasma opening switches

International Nuclear Information System (INIS)

Roderick, N.F.; Payne, S.S.; Peterkin, R.E. Jr.; Frese, M.H.; Hussey, T.W.

1989-01-01

Simulations of plasma opening switch have been made using two-dimensional, single fluid, magnetohydrodynamic codes HAM and MACH2. A variety of mechanisms for magnetic field penetration have been investigated. These include plasma convection, classical and microturbulent resistive diffusion, and Hall effect transport. We find that plasma microturbulent models are necessary to explain the broad current channels observed in experiments. Both heuristic and consistent microturbulent models are able to explain observed channel widths and penetration features. The best results are obtained for a consistent model that includes the Buneman, ion acoustic, and lower hybrid microturbulent collision frequencies and threshold conditions. Maximum microturbulent collision frequencies of 5 ω p , are typical. Field transport and current channel profiles are in excellent agreement with experimental observations for GAMBLE I, GAMBLE II, and SUPERMITE experiments. Dominant field penetration mechanisms and center of mass plasma motion are current and density dependent. Including the Hall effect enhanced field penetration. Center of mass motion is negligible for the GAMBLE I experiments but significant for the GAMBLE II conditions. Scaling of plasma opening time with switch length and density can be fit by linear representations for lengths from 0.03 m to 0.24 m and ion densities from 10 18 m -3 to 1.5 times 10 19 m -3 . 15 refs., 7 figs., 1 tab

Compound list: carboplatin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available carboplatin CBP 00133 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vitro/carboplatin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo.../Liver/Single/carboplatin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...T/Rat/in_vivo/Liver/Repeat/carboplatin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bio...sciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/carboplatin.Rat.in_vivo.Kidney.Single.zip ftp:

Compound list: cephalothin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available cephalothin CLT 00141 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vitro/cephalothin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo.../Liver/Single/cephalothin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...T/Rat/in_vivo/Liver/Repeat/cephalothin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bio...sciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/cephalothin.Rat.in_vivo.Kidney.Single.zip ftp:

Compound list: triamterene [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available triamterene TRI 00101 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vitro/triamterene.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo.../Liver/Single/triamterene.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...T/Rat/in_vivo/Liver/Repeat/triamterene.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bio...sciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/triamterene.Rat.in_vivo.Kidney.Single.zip ftp:

Evaluation of the Single-precision Floatingpoint Vector Add Kernel Using the Intel FPGA SDK for OpenCL

Energy Technology Data Exchange (ETDEWEB)

Jin, Zheming [Argonne National Lab. (ANL), Argonne, IL (United States); Yoshii, Kazutomo [Argonne National Lab. (ANL), Argonne, IL (United States); Finkel, Hal [Argonne National Lab. (ANL), Argonne, IL (United States); Cappello, Franck [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-04-20

Open Computing Language (OpenCL) is a high-level language that enables software programmers to explore Field Programmable Gate Arrays (FPGAs) for application acceleration. The Intel FPGA software development kit (SDK) for OpenCL allows a user to specify applications at a high level and explore the performance of low-level hardware acceleration. In this report, we present the FPGA performance and power consumption results of the single-precision floating-point vector add OpenCL kernel using the Intel FPGA SDK for OpenCL on the Nallatech 385A FPGA board. The board features an Arria 10 FPGA. We evaluate the FPGA implementations using the compute unit duplication and kernel vectorization optimization techniques. On the Nallatech 385A FPGA board, the maximum compute kernel bandwidth we achieve is 25.8 GB/s, approximately 76% of the peak memory bandwidth. The power consumption of the FPGA device when running the kernels ranges from 29W to 42W.

Quantitative monitoring of two simultaneously binding species using Label-Enhanced surface plasmon resonance.

Science.gov (United States)

Eng, Lars; Garcia, Brandon L; Geisbrecht, Brian V; Hanning, Anders

2018-02-26

Surface plasmon resonance (SPR) is a well-established method for biomolecular interaction studies. SPR monitors the binding of molecules to a solid surface, embodied as refractive index changes close to the surface. One limitation of conventional SPR is the universal nature of the detection that results in an inability to qualitatively discriminate between different binding species. Furthermore, it is impossible to directly discriminate two species simultaneously binding to different sites on a protein, which limits the utility of SPR, for example, in the study of allosteric binders or bi-specific molecules. It is also impossible in principle to discriminate protein conformation changes from actual binding events. Here we demonstrate how Label-Enhanced SPR can be utilized to discriminate and quantitatively monitor the simultaneous binding of two different species - one dye-labeled and one unlabeled - on a standard, single-wavelength SPR instrument. This new technique increases the versatility of SPR technology by opening up application areas where the usefulness of the approach has previously been limited. Copyright © 2018 Elsevier Inc. All rights reserved.

More or less-On the influence of labelling strategies to infer cell population dynamics.

Science.gov (United States)

Gabel, Michael; Regoes, Roland R; Graw, Frederik

2017-01-01

The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

More or less-On the influence of labelling strategies to infer cell population dynamics.

Directory of Open Access Journals (Sweden)

Michael Gabel

Full Text Available The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

Science.gov (United States)

Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

2016-04-01

Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

Science.gov (United States)

Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

2016-01-01

As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation.

Topical Coconut Oil in Very Preterm Infants: An Open-Label Randomised Controlled Trial.

Science.gov (United States)

Strunk, Tobias; Pupala, Sameer; Hibbert, Julie; Doherty, Dorota; Patole, Sanjay

2018-01-01

The immature fragile skin of preterm infants represents an inadequate protective barrier. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. Our aim was to evaluate feasibility, safety, and the effects of topical coconut oil on skin condition in very preterm infants. An open-label randomised controlled trial in preterm infants coconut oil (5 mL/kg) twice daily for 21 days, starting within 24 h of birth. The neonatal skin condition was the primary outcome, and was assessed using the Neonatal Skin Condition Score (NSCS) on days 1, 7, 14, and 21. The number of coconut oil applications was recorded to assess clinical feasibility and all enrolled infants were monitored for adverse effects of topical coconut application, such as skin irritation. A total of 72 infants born coconut oil was feasible and without adverse effects. The NSCS was maintained in the coconut oil group throughout the intervention period, but deteriorated from a median (IQR) of 3 (3-4) on day 1 to 4 (4-4) on day 21 in the control group (p = 0.01). There were no differences in common neonatal outcomes, including sepsis, necrotising enterocolitis, retinopathy of prematurity, chronic lung disease, and mortality. Topical coconut oil maintained a better skin condition in very preterm infants without adverse effects. This simple, safe, and affordable intervention warrants further investigation. © 2017 S. Karger AG, Basel.

Compound list: cisplatin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available cisplatin CSP 00132 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_v...itro/cisplatin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/cisplatin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/...in_vivo/Liver/Repeat/cisplatin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscienced...bc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/cisplatin.Rat.in_vivo.Kidney.Single.zip ftp://ft

Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

Science.gov (United States)

Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

2011-12-01

A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

Strategic Decision-Making Learning from Label Distributions: An Approach for Facial Age Estimation.

Science.gov (United States)

Zhao, Wei; Wang, Han

2016-06-28

Nowadays, label distribution learning is among the state-of-the-art methodologies in facial age estimation. It takes the age of each facial image instance as a label distribution with a series of age labels rather than the single chronological age label that is commonly used. However, this methodology is deficient in its simple decision-making criterion: the final predicted age is only selected at the one with maximum description degree. In many cases, different age labels may have very similar description degrees. Consequently, blindly deciding the estimated age by virtue of the highest description degree would miss or neglect other valuable age labels that may contribute a lot to the final predicted age. In this paper, we propose a strategic decision-making label distribution learning algorithm (SDM-LDL) with a series of strategies specialized for different types of age label distribution. Experimental results from the most popular aging face database, FG-NET, show the superiority and validity of all the proposed strategic decision-making learning algorithms over the existing label distribution learning and other single-label learning algorithms for facial age estimation. The inner properties of SDM-LDL are further explored with more advantages.

Label-free imaging of gold nanoparticles in single live cells by photoacoustic microscopy

Science.gov (United States)

Tian, Chao; Qian, Wei; Shao, Xia; Xie, Zhixing; Cheng, Xu; Liu, Shengchun; Cheng, Qian; Liu, Bing; Wang, Xueding

2016-03-01

Gold nanoparticles (AuNPs) have been extensively explored as a model nanostructure in nanomedicine and have been widely used to provide advanced biomedical research tools in diagnostic imaging and therapy. Due to the necessity of targeting AuNPs to individual cells, evaluation and visualization of AuNPs in the cellular level is critical to fully understand their interaction with cellular environment. Currently imaging technologies, such as fluorescence microscopy and transmission electron microscopy all have advantages and disadvantages. In this paper, we synthesized AuNPs by femtosecond pulsed laser ablation, modified their surface chemistry through sequential bioconjugation, and targeted the functionalized AuNPs with individual cancer cells. Based on their high optical absorption contrast, we developed a novel, label-free imaging method to evaluate and visualize intracellular AuNPs using photoacoustic microscopy (PAM). Preliminary study shows that the PAM imaging technique is capable of imaging cellular uptake of AuNPs in vivo at single-cell resolution, which provide an important tool for the study of AuNPs in nanomedicine.

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial

Directory of Open Access Journals (Sweden)

Subha V. Raman

2017-02-01

Full Text Available Abstract Background Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD. We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. Results Eleven subjects (phase 1 baseline median [range] age: 13 [7 – 25] years from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045. During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE with preserved ejection fraction (EF. The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9% in younger subjects whereas older subjects’ strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%. EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. Conclusions Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. Trial registration http://ClinicalTrials.gov identifier NCT01521546

Rectified-Linear-Unit-Based Deep Learning for Biomedical Multi-label Data.

Science.gov (United States)

Wang, Pu; Ge, Ruiquan; Xiao, Xuan; Cai, Yunpeng; Wang, Guoqing; Zhou, Fengfeng

2017-09-01

Disease diagnosis is one of the major data mining questions by the clinicians. The current diagnosis models usually have a strong assumption that one patient has only one disease, i.e. a single-label data mining problem. But the patients, especially when at the late stages, may have more than one disease and require a multi-label diagnosis. The multi-label data mining is much more difficult than a single-label one, and very few algorithms have been developed for this situation. Deep learning is a data mining algorithm with highly dense inner structure and has achieved many successful applications in the other areas. We propose a hypothesis that rectified-linear-unit-based deep learning algorithm may also be good at the clinical questions, by revising the last layer as a multi-label output. The proof-of-concept experimental data support the hypothesis, and the community may be interested in trying more applications.

Compound list: ketoconazole [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ketoconazole KC 00047 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/ketoco...nazole.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/ketoco...nazole.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/ketoco...jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/ketoconazole.Rat.in_vivo.Liver.Repeat.zip ftp://ftp....biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/ketoconazole.Rat.in_vivo.Kidney.Singl

Tritiated bovine fibrinogen labelled in fibrinopeptide A region

International Nuclear Information System (INIS)

Wegrzynowicz, Z.; Kloczewiak, M.; Kopec, M.

1974-01-01

The method is described for labelling of bovine fibrinogen with 3 H-AcOAc. Preparations labelled at pH 7.8 with 10 to 40 molar excess of 3 H-AcOAc were found to contain 8 to 13 moles of acetyl residues per mole of fibrinogen. The content of clottable protein and UV spectra were unchanged as compared with control unlabelled preprations. The rate of clotting with thrombin was only slightly affected. The investigations on distribution of 3 H in products of proteolysis of 3 H-fibrinogen by thrombin and plasmin demonstrated a preferential labelling of fibrinopeptide A, absence of radioactive tracer in fibrinopeptide B, significantly higher specific radioactivity of fragment E than that of fragment D. Incorporation of the label into fibrinopeptide A opens the possibility for application of 3 H-fibrinogen as a convenient substrate for selective investigations on the enzymatic phase of clotting. (author)

Does energy labelling on residential housing cause energy savings? Working paper

Energy Technology Data Exchange (ETDEWEB)

Kjaerbye, V.H.

2008-12-15

More than 80% of energy used in households is dedicated to space heating. Large potential energy savings have been identified in the existing housing stock. Energy labelling of single-family houses is seen as an important instrument to provide new house owners with information on efficient energy saving investments that can be made on the house. This paper evaluates the effects of the Danish Energy Labelling Scheme on energy consumption in existing single-family houses with propensity score matching using actual consumption of energy and register data describing the houses and households. We do not find significant energy savings due to the Danish Energy Labelling Scheme. (Author)

Label-free characterization of vitrification-induced morphology changes in single-cell embryos with full-field optical coherence tomography

Science.gov (United States)

Zarnescu, Livia; Leung, Michael C.; Abeyta, Michael; Sudkamp, Helge; Baer, Thomas; Behr, Barry; Ellerbee, Audrey K.

2015-09-01

Vitrification is an increasingly popular method of embryo cryopreservation that is used in assisted reproductive technology. Although vitrification has high post-thaw survival rates compared to other freezing techniques, its long-term effects on embryo development are still poorly understood. We demonstrate an application of full-field optical coherence tomography (FF-OCT) to visualize the effects of vitrification on live single-cell (2 pronuclear) mouse embryos without harmful labels. Using FF-OCT, we observed that vitrification causes a significant increase in the aggregation of structures within the embryo cytoplasm, consistent with reports in literature based on fluorescence techniques. We quantify the degree of aggregation with an objective metric, the cytoplasmic aggregation (CA) score, and observe a high degree of correlation between the CA scores of FF-OCT images of embryos and of fluorescence images of their mitochondria. Our results indicate that FF-OCT shows promise as a label-free assessment of the effects of vitrification on embryo mitochondria distribution. The CA score provides a quantitative metric to describe the degree to which embryos have been affected by vitrification and could aid clinicians in selecting embryos for transfer.

Observing Protein & Energy Nutrition (OPEN) Study

Science.gov (United States)

The Observing Protein and Energy Nutrition (OPEN) Study was designed to assess dietary measurement error by comparing results from self-reported dietary intake data with four dietary biomarkers: doubly labeled water and urinary nitrogen, sodium, and potassium.

Evaluation Of Open, Wedge Filtered And Half Block Profile For Single And Plan Parallel Field For 60Co Teletherapy Unit

International Nuclear Information System (INIS)

Heru-Prasetio; Nasukha; Soejoko, Djarwani S

2003-01-01

TPS shall be evaluated with experimental data before it is used for patient treatment. This experiment was performed using small water phantom, at the depth of 10 cm, SSD technique for single beam and 16 cm, SAD technique for plan parallel beam. Measuring device used in this experiment is Farmer 2571 detector. It was found differences between experiment and TPS iSis are not significant. Single field experiment and TPS differences of 0.6%, 3.6% and 0.1% for open, wedge filter and half-blocked field, for plan parallel experiment and TPS differences are 2.1%, 2% and 2.4% for open, wedge filter and half-blocked field. (author)

The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1 year, open-label, prospective study.

Science.gov (United States)

Chue, Pierre; Mandel, Francine S; Therrien, François

2014-06-01

Metabolic syndrome (MetS) is prevalent in subjects with schizophrenia-related psychotic disorders and contributes to increased rates of premature death due to cardiovascular disease. This study examined the impact of switching from another antipsychotic to ziprasidone on the distribution of the number of risk factors for MetS in subjects with schizophrenia or related psychotic disorders. In this 1 year, open-label, prospective study, all subjects received ziprasidone 40-160 mg/day. Standard exclusion criteria included treatment resistance, physical health disorders, and substance abuse. The primary end point was the percentage of subjects achieving a reduction from baseline of at least one risk factor for MetS at end point (week 52 or premature discontinuation) in the per-protocol population (treated for at least 16 weeks). Secondary end points included the mean change from baseline in number of MetS risk factors, the prevalence of MetS, individual MetS risk factors (waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and glucose), and 10 year coronary heart disease (Framingham score) risk. www.clinicaltrials.gov: NCT00748566. Of 114 evaluable subjects, 58.77% demonstrated one less MetS risk factor at week 52 (last observation carried forward) compared with baseline. Secondary end points also improved, with reductions in other metabolic parameters (fasting low-density lipoprotein cholesterol, total cholesterol and serum insulin, weight, body mass index and glycosylated hemoglobin [HbA1c]). The 10 year coronary heart disease risk decreased continually over time. The open-label and uncontrolled design is a limitation of the study. Ziprasidone treatment reduced both the rate of MetS and its individual risk factors in subjects with schizophrenia and related psychotic disorders. The results have implications for the selection of first-line treatments in schizophrenia and related psychotic disorders, and provide treatment

An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women.

Science.gov (United States)

Kious, Brent M; Sabic, Hana; Sung, Young-Hoon; Kondo, Douglas G; Renshaw, Perry

2017-10-01

Many women with major depressive disorder (MDD) respond inadequately to standard treatments. Augmentation of conventional antidepressants with creatine monohydrate and 5-hydroxytryptophan (5-HTP) could correct deficits in serotonin production and brain bioenergetics associated with depression in women, yielding synergistic benefit. We describe an open-label study of 5-HTP and creatine augmentation in women with MDD who had failed selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) monotherapy. Fifteen women who were adequately adherent to an SSRI or SNRI and currently experiencing MDD, with a 17-item Hamilton Depression Rating Scale (HAM-D) score of 16 or higher, were treated with 5 g of creatine monohydrate daily and 100 mg of 5-HTP twice daily for 8 weeks, with 4 weeks of posttreatment follow-up. The primary outcome was change in mean HAM-D scores. Mean HAM-D scores declined from 18.9 (SD, 2.5) at pretreatment visits to 7.5 (SD, 4.4) (P creatine and 5-HTP may represent an effective augmentation strategy for women with SSRI- or SNRI-resistant depression. Given the limitations of this small, open-label trial, future study in randomized, placebo-controlled trials is warranted.

Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies

Directory of Open Access Journals (Sweden)

Kevin J Ruff

2009-05-01

Full Text Available Kevin J Ruff1, Dale P DeVore2, Michael D Leu3, Mark A Robinson41ESM Technologies, LLC, Carthage, MO, USA; 2Membrell, LLC, Carthage, MO, USA; 3Private Practice, Jenks, OK, USA; 4Robinson Family Health Center, Carthage, MO, USABackground: Natural Eggshell Membrane (NEM® is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and inflexibility associated with joint and connective tissue disorders. Methods: Eleven (single-arm trial and 28 (double-arm trial patients received oral NEM® 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies. In the single-arm trial, range of motion (ROM and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT population within each study.Results: Single-arm trial: Supplementation with NEM® produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038 and at 30 days for general pain (72.5% reduction; P = 0.007, flexibility (43.7% increase; P = 0.006, and ROM-associated pain (75.9% reduction; P = 0.021. Double-arm trial: Supplementation with NEM® produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014. There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001. There were no adverse events reported during either

LFQProfiler and RNP(xl): Open-Source Tools for Label-Free Quantification and Protein-RNA Cross-Linking Integrated into Proteome Discoverer.

Science.gov (United States)

Veit, Johannes; Sachsenberg, Timo; Chernev, Aleksandar; Aicheler, Fabian; Urlaub, Henning; Kohlbacher, Oliver

2016-09-02

Modern mass spectrometry setups used in today's proteomics studies generate vast amounts of raw data, calling for highly efficient data processing and analysis tools. Software for analyzing these data is either monolithic (easy to use, but sometimes too rigid) or workflow-driven (easy to customize, but sometimes complex). Thermo Proteome Discoverer (PD) is a powerful software for workflow-driven data analysis in proteomics which, in our eyes, achieves a good trade-off between flexibility and usability. Here, we present two open-source plugins for PD providing additional functionality: LFQProfiler for label-free quantification of peptides and proteins, and RNP(xl) for UV-induced peptide-RNA cross-linking data analysis. LFQProfiler interacts with existing PD nodes for peptide identification and validation and takes care of the entire quantitative part of the workflow. We show that it performs at least on par with other state-of-the-art software solutions for label-free quantification in a recently published benchmark ( Ramus, C.; J. Proteomics 2016 , 132 , 51 - 62 ). The second workflow, RNP(xl), represents the first software solution to date for identification of peptide-RNA cross-links including automatic localization of the cross-links at amino acid resolution and localization scoring. It comes with a customized integrated cross-link fragment spectrum viewer for convenient manual inspection and validation of the results.

Compound list: bromoethylamine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available bromoethylamine BEA 00134 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/bromoethylam...ine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST...Rat/in_vivo/Liver/Single/bromoethylamine.Rat.in_vivo.Liver.Single.zip ftp://ftp.b...iosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/bromoethylamine.Rat.in_vivo.Liver.Repea...t.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/bromoethylamine.Rat.i

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings

OpenAIRE

Dittmann, Ralf W.; Wehmeier, Peter M.; Schacht, Alexander; Lehmann, Martin; Lehmkuhl, Gerd

2009-01-01

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12?17?years), treated in an open-label study for 24?weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous stru...

Other origins for the fluorescence modulation of single dye molecules in open-circuit and short-circuit devices.

Science.gov (United States)

Teguh, Jefri S; Kurniawan, Michael; Wu, Xiangyang; Sum, Tze Chien; Yeow, Edwin K L

2013-01-07

Fluorescence intensity modulation of single Atto647N dye molecules in a short-circuit device and a defective device, caused by damaging an open-circuit device, is due to a variation in the excitation light focus as a result of the formation of an alternating electric current.

An open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder.

Science.gov (United States)

Kuperman, Samuel; Calarge, Chadi; Kolar, Anne; Holman, Timothy; Barnett, Mitchell; Perry, Paul

2011-11-01

The adverse effect profiles of typical and atypical antipsychotics are problematic because of their extrapyramidal and endocrine adverse effects, respectively. Ten adolescent male patients diagnosed with conduct disorder received aripiprazole in doses of ≤20 mg/d in an open-label, intent-to-treat design to establish and characterize the efficacy of the drug in reducing aggressive behavior. Based on clinician and parent observations, aripiprazole was effective in reducing aggressive behavior in adolescent boys. The change in clinician-observed aggression ratings appears to have been driven by a decrease in physical aggression, whereas the change in parent-observed aggression ratings appears to have been driven by a decrease in verbal aggression and aggression against objects and animals. Aripiprazole was an effective and relatively well-tolerated treatment for overall aggression in adolescent males with conduct disorder, in the view of both clinicians and parents. Depending on the observer, aripiprazole improved aggression categorized as physical aggression, verbal aggression, and aggression against objects and animals.

Apparent discrepancy between single-unit activity and [14C]deoxyglucose labeling in optic tectum of the rattlesnake

International Nuclear Information System (INIS)

Auker, C.R.; Meszler, R.M.; Carpenter, D.O.

1983-01-01

Autoradiographic analysis of [1- 14 C]2-deoxy-D-glucose-6-phosphate ([ 14 C]2-DG-P) accumulation in the rattlesnake brain stem and optic tectum was used in an effort to map infrared and visual neuronal pathways. Visual stimulation with a standard stimulus (a heat lamp) resulted in dense labeling of the superficial layers of the optic tectum. Infrared stimulation resulted in labeling at the first synaptic relay, the lateral descending nucleus of the trigeminal tract, but not at higher levels. Responses of infrared units in one hemitectum and visual units in the other were analyzed. There were no clear differences in the number, maximal density, spread, or rates of accommodation of visual units and infrared units, although the locus of maximal density was more superficial for visual units. In general, infrared units generated a greater number of action potentials. All infrared units responded to onset but they varied greatly in their ability to maintain discharge for the duration of the stimulus. Infrared stimuli generated single, large, triphasic on-responses, whereas visual stimulation generated complex multiphasic and long-lasting on- and off-responses. The major infrared-on peak reached maximal amplitude at greater depths and was larger than the major visual-on peak. Amplitude of the infrared peak fell off more rapidly with distance than did amplitude of the visual peak. These observations are consistent with the view that infrared stimulation is effective in discharging neurons but is not associated with intense synaptic excitation. Our observations suggest that 2-deoxy-D-glucose uptake is not necessarily correlated with the degree of action potential activation of specific neuronal pathways. The amount of [ 14 C]2-DG-P labeling may reflect the metabolic requirements for support of synaptic depolarization as well as that supporting action potentials

Labeled factor IX kinetics in patients with hemophilia-B

International Nuclear Information System (INIS)

Smith, K.J.; Thompson, A.R.

1981-01-01

Labeled factor IX was infused five time into four patients with hemophilia-B. Ten-minute plasma recovery average 35% (SD +/- 2) and the mean T 1/2 beta-phase elimination was 23 hr (+/- 5). No alteration in the postinfusion 125I-factor-IX could be detected by radioautography of plasma samples run on polyacrylamide gels or on crossed-immunoelectrophoresis. Label was excreted into the urine as free 125I-iodide. Kinetics were similar when the labeled preparation was infused alone or with a commercial concentrate containing unlabeled factor IX. Infusion of factor IX in man is best described by a two-compartment open pharmacokinetic model where factor IX is distributed in a space larger than the plasma volume

Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

Science.gov (United States)

Gurulingappa, Harsha; Toldo, Luca; Rajput, Abdul Mateen; Kors, Jan A; Taweel, Adel; Tayrouz, Yorki

2013-11-01

The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks. Copyright © 2013 John Wiley & Sons, Ltd.

Single- and central-diffractive production of open charm and bottom mesons at the LHC

CERN Document Server

Łuszczak, Marta; Szczurek, Antoni

2015-01-01

We discuss diffractive production of open charm and bottom mesons at the LHC. The differential cross sections for single- and central-diffractive mechanisms for $c\\bar c$ and $b\\bar b$ pair production are calculated in the framework of the Ingelman-Schlein model corrected for absorption effects. The LO gluon-gluon fusion and quark-antiquark anihilation partonic subprocesses are taken into consideration, which are calculated within standard collinear approximation. The extra corrections from reggeon exchanges are taken into account. The hadronization of charm and bottom quarks is taken into account by means of fragmentation functions. Predictions for single- and central-diffractive production in the case of $D$ and $B$ mesons, as well as $D\\bar D$ pairs are presented, including detector acceptance of the ATLAS, CMS and LHCb Collaborations.

Compound list: methyltestosterone [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available methyltestosterone MTS 00041 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/methyltes...LATEST/Rat/in_vitro/methyltestosterone.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggate...s/LATEST/Rat/in_vivo/Liver/Single/methyltestosterone.Rat.in_vivo.Liver.Single.zip... ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/methyltestosterone.Rat.in_v...ivo.Liver.Repeat.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/methyltest

Compound list: thioacetamide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available thioacetamide TAA 00017 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/thioacetamide.Human.in_vitro.Liver.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/thioacetam..._vivo/Liver/Single/thioacetamide.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/thioacetamide.Rat.in_vivo.Liver.Repeat.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/thioacetamide.Rat.in_vivo.Kidne

Compound list: acetazolamide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available acetazolamide ACZ 00108 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/acetazolam...ide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/acetazolam..._vivo/Liver/Single/acetazolamide.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/acetazolamide.Rat.in_vivo.Liver.Repeat.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/acetazolamide.Rat.in_vivo.Kidne

Achieving transparency in carbon labelling for construction materials – Lessons from current assessment standards and carbon labels

International Nuclear Information System (INIS)

Wu, Peng; Low, Sui Pheng; Xia, Bo; Zuo, Jian

2014-01-01

Highlights: • The evolution of international GHG standards is reviewed. • The evolution of international carbon labelling schemes is reviewed. • The transparency requirements in carbon labelling schemes are revealed. • Key recommendations are provided to improve transparency in carbon labelling. - Abstract: The construction industry is one of the largest sources of carbon emissions. Manufacturing of raw materials, such as cement, steel and aluminium, is energy intensive and has considerable impact on carbon emissions level. Due to the rising recognition of global climate change, the industry is under pressure to reduce carbon emissions. Carbon labelling schemes are therefore developed as meaningful yardsticks to measure and compare carbon emissions. Carbon labelling schemes can help switch consumer-purchasing habits to low-carbon alternatives. However, such switch is dependent on a transparent scheme. The principle of transparency is highlighted in all international greenhouse gas (GHG) standards, including the newly published ISO 14067: Carbon footprint of products – requirements and guidelines for quantification and communication. However, there are few studies which systematically investigate the transparency requirements in carbon labelling schemes. A comparison of five established carbon labelling schemes, namely the Singapore Green Labelling Scheme, the CarbonFree (the U.S.), the CO 2 Measured Label and the Reducing CO 2 Label (UK), the CarbonCounted (Canada), and the Hong Kong Carbon Labelling Scheme is therefore conducted to identify and investigate the transparency requirements. The results suggest that the design of current carbon labels have transparency issues relating but not limited to the use of a single sign to represent the comprehensiveness of the carbon footprint. These transparency issues are partially caused by the flexibility given to select system boundary in the life cycle assessment (LCA) methodology to measure GHG emissions. The

Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

Institute of Scientific and Technical Information of China (English)

ZHENG Yi; GONG Mei-en; YIN Qing-yun; MAI Jian-ning; JING Jin; LUO Xiang-yang; MA Hong-wei; LI Hai-bo; XIE Ling; LI Yan; Kuang Gui-fang; WANG Yu-feng; YI Ming-ji; WANG Feng; ZHU Xiao-hua; YAO Yah-bin; QIN Jiong; WANG Li-wen; ZOU Li-ping; JIN Xing-ming; XU Tong; WANG Yi; QI Yuan-li

2011-01-01

Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood,characterized by the core symptoms of hyperactivity,impulsivity and inattention and puts great burden on children themselves,their families and the society.Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH).It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles.The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.Methods This 6-week,multi-center,prospective,open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg,36 mg or 54 mg) treatment.The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales,physician-rated CGI-I and parent-rated global efficacy assessment scale.Blood pressure,pulse rate measurement,adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial.Totally 96.8％children received an OROS-MPH modal dose of 18 mg,3.1％ with 36 mg and 0.1％ with 54 mg at the endpoint of study.The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P ＜0.001) improvement with OROS-MPH (mean:6.95±2.71) versus the score at baseline (10.45±2.72).The change in the parent IOWA Conners O/D subscale,CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment.Fewer than half of 1447 patients (511 (35.3％)) reported AEs,and the majority of the events reported were mild (68.2�

Leukemic cell labeling with indium-111-oxine

International Nuclear Information System (INIS)

Uchida, T.; Takagi, Y.; Matsuda, S.; Yui, T.; Ishibashi, T.; Kimura, H.; Kariyone, S.

1984-01-01

Leukemic cells were labeled with In-111-oxine in patients with acute leukemia. In vitro labeling studies revealed that labeling efficiency reached maximum 80.8 +- 3.6% (mean +- 1SD) by 2 times washes after 20 minutes incubation time. Cell viability was assessed by trypan blue exclusion test and in vitro culture of leukemic cells, which showed no cellular damage during labeling procedure. Elution of In-111 from the labeled cells was 10.0 +- 1.2% at 12 hours after labeling. For in vivo leukemic cell kinetic studies, more than 10/sup 8/ leukemic cells separated from Ficoll-Hypacque sedimentation were labeled by 30 minutes of In-111-oxine incubation and two times washes at 37 0 C. In vivo studies were performed in 7 patients with acute myeloblastic, lymphoblastic leukemia and blastic crisis of chronic myelocytic leukemia. Labeled leukemic cells disappeared in single exponential fashion with half life of 9.6 to 31.8 hours. Total leukemic cell pool in peripheral circulation was calculated, which correlated well with peripheral leukemic cell counts (r=0.99). No relationship was observed between total leukemic cell pool and leukemic cell turnover rate. Migration patterns of labeled leukemic cells showed that pulmonary uptake was evident within 15 minutes after the infusion and returned to base-line. Splenic and hepatic uptake showed gradual increase up to 24 hours. Bone marrow accumulation was shown only in 2 cases. Presently, there are no suitable radionuclides for leukemic cell labeling. In-111-oxine labeled leukemic cells would overcome this difficulty

Insertion of a single double-J stent for bilateral open ureteral reimplantation: introducing a novel technique and assessment of feasibility.

Science.gov (United States)

Nabavizadeh, Behnam; Keihani, Sorena; Hosseini Sharifi, Seyed Hossein; Kajbafzadeh, Abdol-Mohammad

2016-07-01

To propose a novel technique for bilateral placement of a single double-J stent during bilateral open ureteral reimplantation in order to reduce the intravesical length of stent and potentially minimize the irritative symptoms. A retrospective chart review was performed to find patients who underwent bilateral open ureteral reimplantation. According to the patient's age, an appropriate single double-J stent is used for stenting both ureters after open reimplantation using the Politano-Leadbetter technique. The stent is fixed to the bladder wall with a 4-0 chromic absorbable suture in the midline, superior to the intertrigonal ridge. A non-absorbable suture is also fixed to the stent in the midline as an extraction string. From June 2009 to July 2013, 20 patients underwent bilateral ureteric surgery. Twelve (60 %) were female. Patients' age ranged from 3 months to 2 years. Double-J stents were successfully removed within 2 weeks postoperatively in all patients. This technique might reduce the stent-related symptoms after open bladder surgery for bilateral ureteral surgery. Using this technique will reduce the redundant mass of ureteral stents in bladder and potentially minimize the trigonal irritation and subsequent pain and discomfort.

Aziridines in the synthesis of {sup 11}C- and {sup 18}F-labelled compounds

Energy Technology Data Exchange (ETDEWEB)

Gillings, N.M

1998-07-01

Racemic [4-{sup 11}C]aspartic acid, [4-{sup 11}C]asparagine and 2,4-diamino[4-{sup 11}C]butyric acid were synthesised by the ring-opening of an N-activated aziridine-2-carboxylate with [{sup 11}C]cyanide, followed by preparative HPLC and hydrolysis/reduction. These labelled amino acids arise from nucleophilic attack at the {beta}-carbon of the aziridine ring. A radioactive by-product of ca. 25% was attributed to the product of {alpha}-attack. Several N-activated 2-aryl aziridines were synthesised for the attempted synthesis of {beta}-[{sup 18}F] fluorophenylalanine and {beta}-[{sup 18}F]fluorodopa. Ring-opening with [{sup 18}F]fluoride showed no evidence of {beta}-fluorinated products and it is proposed that attack occurs exclusively at the {alpha}-carbon, giving the corresponding {alpha}-[{sup 18}F]fluoro-{beta}-amino acids. Further evidence for this was the reaction of the {beta}-unsubstituted N-activated aziridine-2-carboxylate with [{sup 18}F]fluoride. This reaction was totally regiospecific and afforded exclusively the {alpha}-substituted product, {alpha}-[{sup 18}F]fluoro-{beta}-alanine. Aziridine precursors were resolved by chiral HPLC. On labelling the chiral aziridines, however, racemic {sup 11}C- and {sup 18}F-labelled amino acids were obtained. This was attributed to racemisation of the initially formed ring-opened products. The use of [{sup 11}C]methyl lithium as a nucleophile for aziridine ring-opening was investigated. Reaction was expected to occur at low temperature, thus potentially avoiding racemisation. No products corresponding to aziridine ring-opening with [{sup 11}C]methyl lithium were, however, observed. A difluorinated analogue of amphetamine was synthesised by fluorination of an azirine (via an aziridine). This racemic compound was resolved as its chiral tartarate salts and subsequently labelled by methylation with [{sup 11}C]methyl iodide, giving the novel compound {beta}, {beta}-difluoro[N-methyl-{sup 11}C]methamphetamine in high

Compound list: amphotericin B [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available amphotericin B AMB 00157 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/amphotericin_B.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vivo/Liver/Single/amphotericin_B.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-...tggates/LATEST/Rat/in_vivo/Liver/Repeat/amphotericin_B.Rat.in_vivo.Liver.Repeat.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/amphotericin_B.Rat.in_vivo.Kidney.Single.zip ftp:

Compound list: caffeine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available caffeine CAF 00097 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/caffeine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/caffeine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/caffeine...-tggates/LATEST/Rat/in_vivo/Liver/Repeat/caffeine.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.biosciencedbc.jp/ar...chive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/caffeine.Rat.in_vivo.Kidney.Single.zip ftp://ftp.bioscie

Compound list: gentamicin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available gentamicin GMC 00147 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/gentam...icin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/gentam...at/in_vivo/Liver/Repeat/gentamicin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscie...ncedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/gentamicin.Rat.in_vivo.Kidney.Single.zip ftp...://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/gentamicin.Rat.in_vivo.Kidney.Repeat.zip ...

Compound list: lomustine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available lomustine LS 00049 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/lomustine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/lomustine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/lomustine...pen-tggates/LATEST/Rat/in_vivo/Liver/Repeat/lomustine.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.biosciencedbc.j...p/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/lomustine.Rat.in_vivo.Kidney.Single.zip ftp://ftp.bi

Compound list: ethionine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ethionine ET 00013 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/ethionine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/ethionine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/ethionine...pen-tggates/LATEST/Rat/in_vivo/Liver/Repeat/ethionine.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.biosciencedbc.j...p/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/ethionine.Rat.in_vivo.Kidney.Single.zip ftp://ftp.bi

Ultrasensitive Single Fluorescence-Labeled Probe-Mediated Single Universal Primer-Multiplex-Droplet Digital Polymerase Chain Reaction for High-Throughput Genetically Modified Organism Screening.

Science.gov (United States)

Niu, Chenqi; Xu, Yuancong; Zhang, Chao; Zhu, Pengyu; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

2018-05-01

As genetically modified (GM) technology develops and genetically modified organisms (GMOs) become more available, GMOs face increasing regulations and pressure to adhere to strict labeling guidelines. A singleplex detection method cannot perform the high-throughput analysis necessary for optimal GMO detection. Combining the advantages of multiplex detection and droplet digital polymerase chain reaction (ddPCR), a single universal primer-multiplex-ddPCR (SUP-M-ddPCR) strategy was proposed for accurate broad-spectrum screening and quantification. The SUP increases efficiency of the primers in PCR and plays an important role in establishing a high-throughput, multiplex detection method. Emerging ddPCR technology has been used for accurate quantification of nucleic acid molecules without a standard curve. Using maize as a reference point, four heterologous sequences ( 35S, NOS, NPTII, and PAT) were selected to evaluate the feasibility and applicability of this strategy. Surprisingly, these four genes cover more than 93% of the transgenic maize lines and serve as preliminary screening sequences. All screening probes were labeled with FAM fluorescence, which allows the signals from the samples with GMO content and those without to be easily differentiated. This fiveplex screening method is a new development in GMO screening. Utilizing an optimal amplification assay, the specificity, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The LOD and LOQ of this GMO screening method were 0.1% and 0.01%, respectively, with a relative standard deviation (RSD) < 25%. This method could serve as an important tool for the detection of GM maize from different processed, commercially available products. Further, this screening method could be applied to other fields that require reliable and sensitive detection of DNA targets.

Efficacy of Modified Atkins Ketogenic Diet in Chronic Cluster Headache: An Open-Label, Single-Arm, Clinical Trial

Directory of Open Access Journals (Sweden)

Cherubino Di Lorenzo

2018-02-01

Full Text Available IntroductionDrug-resistant cluster headache (CH is still an open clinical challenge. Recently, our group observed the clinical efficacy of a ketogenic diet (KD, usually adopted to treat drug-resistant epilepsies, on migraine.AimHere, we aim to detect the effect of KD in a group of drug-resistant chronic CH (CCH patients.Materials and methodsEighteen drug-resistant CCH patients underwent a 12-week KD (Modified Atkins Diet, MAD, and the clinical response was evaluated in terms of response (≥50% attack reduction.ResultsOf the 18 CCH patients, 15 were considered responders to the diet (11 experienced a full resolution of headache, and 4 had a headache reduction of at least 50% in terms of mean monthly number of attacks during the diet. The mean monthly number of attacks for each patient at the baseline was 108.71 (SD = 81.71; at the end of the third month of diet, it was reduced to 31.44 (SD = 84.61.ConclusionWe observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03244735.

A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Greten, Tim F; Bruix, Jordi; Forner, Alejandro; Korangy, Firouzeh; N'Kontchou, Gisele; Barget, Nathalie; Ayuso, Carmen; Ormandy, Lars A; Manns, Michael P; Beaugrand, Michel

2010-01-01

The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. 40 patients with advanced HCC were treated with 300 mg/m 2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4 + CD25 + Foxp3 + regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. NCT00444782

A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Ayuso Carmen

2010-05-01

Full Text Available Abstract Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001 vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9% demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782

On-target labeling of intracellular metabolites combined with chemical mapping of individual hyphae revealing cytoplasmic relocation of isotopologues.

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Hu, Jie-Bi; Chen, Yu-Chie; Urban, Pawel L

2012-06-05

A microscale analytical platform integrating microbial cell culture, isotopic labeling, along with visual and mass spectrometric imaging with single-cell resolution has been developed and applied in the monitoring of cellular metabolism in fungal mycelium. The method implements open chips with a two-dimensional surface pattern composed of hydrophobic and hydrophilic zones. Two hydrophilic islands are used as medium reservoirs, while the hydrophobic area constitutes the support for the growing aerial hyphae, which do not have direct contact with the medium. The first island, containing (12)C(6)-glucose medium, was initially inoculated with the mycelium (Neurospora crassa), and following the initial incubation period, the hyphae progressed toward the second medium island, containing an isotopically labeled substrate ((13)C(6)-glucose). The (13)C atoms were gradually incorporated into cellular metabolites, which was revealed by MALDI-MS. The fate of the chitin-biosynthesis precursor, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), was monitored by recording mass spectra with characteristic isotopic patterns, which indicated the presence of various (12)C/(13)C isotopologues. The method enabled mapping the (13)C-labeled UDP-GlcNAc in fungal mycelium and recording its redistribution in hyphae, directly on the chip.

Effects of a single inhalative exposure to formaldehyde on the open field behavior of mice.

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Malek, Fathi A; Möritz, Klaus-Uwe; Fanghänel, Jochen

2004-02-01

The effects of formaldehyde on the explorative behavior and locomotor activity of mice after a single inhalative exposure were examined in an open field. Adult male mice were exposed to approximately 1.1 ppm, 2.3 ppm, or 5.2 ppm formaldehyde vapour for 2 hours and the open field test was carried out two hours after the end of exposure (trial 1) and repeated 24 hours thereafter (trial 2). The following behavioral parameters were quantitatively examined: numbers of crossed floor squares (inner, peripheral, total), sniffing, grooming, rearing, climbing, and incidence of fecal boli. The results of the first trial revealed that the motion activity was significantly reduced in all exposed groups. In the 1.1 ppm group, the frequency of rearing was reduced and that of floor sniffing increased. The exposure to the two higher formaldehyde concentrations caused a significant decrease in total numbers of floor squares crossed by the subjects, air sniffing, and rearing. The open field test on the next day (trial 2) showed that the frequencies of floor sniffing, grooming, and rearing in all formaldehyde groups were significantly altered. In the 2.5 ppm group, an increased incidence of fecal boli was observed. From the results obtained, we conclude that the exposure of male mice to formaldehyde vapour affects their locomotor and explorative activity in the open field, and that some open field parameters are still altered in the exposed animals even after 24 hours.

Quantitative localization microscopy: effects of photophysics and labeling stoichiometry.

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Robert P J Nieuwenhuizen

Full Text Available Quantification in localization microscopy with reversibly switchable fluorophores is severely hampered by the unknown number of switching cycles a fluorophore undergoes and the unknown stoichiometry of fluorophores on a marker such as an antibody. We overcome this problem by measuring the average number of localizations per fluorophore, or generally per fluorescently labeled site from the build-up of spatial image correlation during acquisition. To this end we employ a model for the interplay between the statistics of activation, bleaching, and labeling stoichiometry. We validated our method using single fluorophore labeled DNA oligomers and multiple-labeled neutravidin tetramers where we find a counting error of less than 17% without any calibration of transition rates. Furthermore, we demonstrated our quantification method on nanobody- and antibody-labeled biological specimens.

The effect of energy and traffic light labelling on parent and child fast food selection: a randomised controlled trial.

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Dodds, Pennie; Wolfenden, Luke; Chapman, Kathy; Wellard, Lyndal; Hughes, Clare; Wiggers, John

2014-02-01

Labelling of food from fast food restaurants at point-of-purchase has been suggested as one strategy to reduce population energy consumption and contribute to reductions in obesity prevalence. The aim of this study was to examine the effects of energy and single traffic light labelling systems on the energy content of child and adult intended food purchases. The study employed a randomised controlled trial design. English speaking parents of children aged between three and 12 years were recruited from an existing research cohort. Participants were mailed one of three hypothetical fast food menus. Menus differed in their labelling technique – either energy labels, single traffic light labels, or a no-label control. Participants then completed a telephone survey which assessed intended food purchases for both adult and child. The primary trial outcome was total energy of intended food purchase. A total of 329 participants completed the follow-up telephone interview. Eighty-two percent of the energy labelling group and 96% of the single traffic light labelling group reported noticing labelling information on their menu. There were no significant differences in total energy of intended purchases of parents, or intended purchases made by parents for children, between the menu labelling groups, or between menu labelling groups by socio-demographic subgroups. This study provided no evidence to suggest that energy labelling or single traffic light labelling alone were effective in reducing the energy of fast food items selected from hypothetical fast food menus for purchase. Additional complementary public health initiatives promoting the consumption of healthier foods identified by labelling, and which target other key drivers of menu item selection in this setting may be required.

Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA.

Science.gov (United States)

Valantin, Marc-Antoine; Aubron-Olivier, Camille; Ghosn, Jade; Laglenne, Elisabeth; Pauchard, Michelle; Schoen, Hélène; Bousquet, Raymond; Katz, Philippe; Costagliola, Dominique; Katlama, Christine

2003-11-21

In the absence of currently available therapy to manage facial lipoatrophy, strategies used to compensate for facial fat loss warrant clinical evaluation. The goal of this open-label, single-arm, pilot study was to evaluate the efficacy and safety of facial injections of poly-L-lactic acid (PLA) (New-Fill) in HIV-infected patients with severe facial lipoatrophy. Patients received four sets of injection at day 0 and then every 2 weeks for 6 weeks. Patients were evaluated by clinical examination, facial ultrasonography, and photography at screening and at weeks 6, 24, 48, 72, and 96. Fifty patients were enrolled. At entry, the median facial fat thickness was equal to zero (range, 0.0-2.1 mm). The median total cutaneous thickness (TCT) increased significantly from baseline : +5.1 mm (range, 2.2-8.6 mm) at week 6, +6.4 mm (range, 3.1-9.1 mm) at week 24, +7.2 mm (range, 4.2-9.6 mm) at week 48, +7.2 mm (range, 3.5-9.6 mm) at week 72 and +6.8 mm (range, 3.9-10.1 mm) at week 96 (P 10 mm was observed in 19% at week 6, 41% at week 24, 61% at week 48, 52% at week 72 and 43% at week 96. In 22 (44%) patients, palpable but non-visible subcutaneous micronodules were observed with a spontaneous resolution in six patients at week 96. The benefit of PLA for the correction of the facial lipoatrophy in HIV-infected patients was clearly demonstrated, with an evident aesthetic and quality of life improvement. The efficacy, safety profile, and the simplicity of the injection schedule of PLA make this filling material a potentially attractive treatment.

Label triangulation

International Nuclear Information System (INIS)

May, R.P.

1983-01-01

Label Triangulation (LT) with neutrons allows the investigation of the quaternary structure of biological multicomponent complexes under native conditions. Provided that the complex can be fully separated into and reconstituted from its single - protonated and deuterated - components, small angle neutron scattering (SANS) can give selective information on shapes and pair distances of these components. Following basic geometrical rules, the spatial arrangement of the components can be reconstructed from these data. LT has so far been successfully applied to the small and large ribosomal subunits and the transcriptase of E. coli. (author)

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

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Nativ Ofer

2012-11-01

Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer’s Disease

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Marc L. Gordon

2012-08-01

Full Text Available Aim: To characterize progression of Alzheimer’s disease (AD using proton magnetic resonance spectroscopy (1H MRS. Methods: Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel 1H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA, myo-inositol (mI, choline (Cho, and creatine (Cr] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. Results: AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. Conclusion: Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL. There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor.

SALP, a new single-stranded DNA library preparation method especially useful for the high-throughput characterization of chromatin openness states.

Science.gov (United States)

Wu, Jian; Dai, Wei; Wu, Lin; Wang, Jinke

2018-02-13

Next-generation sequencing (NGS) is fundamental to the current biological and biomedical research. Construction of sequencing library is a key step of NGS. Therefore, various library construction methods have been explored. However, the current methods are still limited by some shortcomings. This study developed a new NGS library construction method, Single strand Adaptor Library Preparation (SALP), by using a novel single strand adaptor (SSA). SSA is a double-stranded oligonucleotide with a 3' overhang of 3 random nucleotides, which can be efficiently ligated to the 3' end of single strand DNA by T4 DNA ligase. SALP can be started with any denatured DNA fragments such as those sheared by Tn5 tagmentation, enzyme digestion and sonication. When started with Tn5-tagmented chromatin, SALP can overcome a key limitation of ATAC-seq and become a high-throughput NGS library construction method, SALP-seq, which can be used to comparatively characterize the chromatin openness state of multiple cells unbiasly. In this way, this study successfully characterized the comparative chromatin openness states of four different cell lines, including GM12878, HepG2, HeLa and 293T, with SALP-seq. Similarly, this study also successfully characterized the chromatin openness states of HepG2 cells with SALP-seq by using 10 5 to 500 cells. This study developed a new NGS library construction method, SALP, by using a novel kind of single strand adaptor (SSA), which should has wide applications in the future due to its unique performance.

Synthesis and pharmacokinetics of thiacoccide labeled with tritium

International Nuclear Information System (INIS)

Shestakov, A.D.; Kaminskii, Yu.L.; Nurova, I.M.; Nikitina, V.N.; Zaionts, V.I.; Maksimova, O.V.; Mikhailov, G.A.

1986-01-01

To obtain information on the pharmacokinetics of thiacoccide, the authors effect the synthesis of an analog of thiacoccide, viz., the hydrochloride of 2-methyl-N-(2'-n-propyl-4'-aminopyrimid-5'-ylmethyl)pyridinium chloride (I) labeled with tritium. The simplest way to introduce a tritium label into (I) is by isotopic exchange of hydrogen of (I) with H 3 HO. Typical material obtained from isotopic exchange with water labeled with tritium is shown. The dynamics of 3 H distribution in the organism of the chick and the rate of its elimination on single administration of thiacoccide containing isotope in both the methyl group and in the pyridine ring are shown

Open areas and open access

International Nuclear Information System (INIS)

Thorndike, A.M.

1978-01-01

One objective of the two open areas in the present ISABELLE design is to provide flexibility with respect to the size and shape of experimental equipment that would eventually be installed there. No permanent building would be installed initially. A second objective of the design of open areas is to keep initial costs as low as practicable. Another objective is open access. This note explores this idea and some design concepts based on it. It would permit inserting large pieces of experimental equipment quickly and removing them with equal ease and speed. Entire experiments would be moved in a single piece (or a few) by building them on movable platforms with capacities of up to about 1000 tons per platform. Most experiments could be built on a single platform or on a few. The shielding must also be moved. It must also be organized into a small number of large units. A scheme using large tanks filled with water is described. It is important to make the equipment on a given platform as complete and self-contained as possible, with a minimum of interconnections for power, coolant, controls, data transmission, etc. 5 figures

Single-organelle tracking by two-photon conversion

Science.gov (United States)

Watanabe, Wataru; Shimada, Tomoko; Matsunaga, Sachihiro; Kurihara, Daisuke; Fukui, Kiichi; Shin-Ichi Arimura, Shin-Ichi; Tsutsumi, Nobuhiro; Isobe, Keisuke; Itoh, Kazuyoshi

2007-03-01

Spatial and temporal information about intracellular objects and their dynamics within a living cell are essential for dynamic analysis of such objects in cell biology. A specific intracellular object can be discriminated by photoactivatable fluorescent proteins that exhibit pronounced light-induced spectral changes. Here, we report on selective labeling and tracking of a single organelle by using two-photon conversion of a photoconvertible fluorescent protein with near-infrared femtosecond laser pulses. We performed selective labeling of a single mitochondrion in a living tobacco BY-2 cell using two-photon photoconversion of Kaede. Using this technique, we demonstrated that, in plants, the directed movement of individual mitochondria along the cytoskeletons was mediated by actin filaments, whereas microtubules were not required for the movement of mitochondria. This single-organelle labeling technique enabled us to track the dynamics of a single organelle, revealing the mechanisms involved in organelle dynamics. The technique has potential application in direct tracking of selective cellular and intracellular structures.

Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

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Alok Sharma

2013-01-01

Full Text Available Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7. Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT scan recorded objective changes. Out of 32 patients, a total of 29 (91% patients improved on total ISAA scores and 20 patients (62% showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P<0.001 on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

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Sriram Ramaswamy

2015-01-01

Full Text Available Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS. RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS, Hamilton Depression Scale (HAM-D, Hamilton Anxiety Scale (HAM-A, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q, and Sheehan Disability Scale (SDS were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P<0.05, over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C and hyperarousal symptoms (CAPS-D, HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations.

Energy momentum tensor and marginal deformations in open string field theory

International Nuclear Information System (INIS)

Sen, Ashoke

2004-01-01

Marginal boundary deformations in a two dimensional conformal field theory correspond to a family of classical solutions of the equations of motion of open string field theory. In this paper we develop a systematic method for relating the parameter labelling the marginal boundary deformation in the conformal field theory to the parameter labelling the classical solution in open string field theory. This is done by first constructing the energy-momentum tensor associated with the classical solution in open string field theory using Noether method, and then comparing this to the answer obtained in the conformal field theory by analysing the boundary state. We also use this method to demonstrate that in open string field theory the tachyon lump solution on a circle of radius larger than one has vanishing pressure along the circle direction, as is expected for a co-dimension one D-brane. (author)

Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema - An open-label randomized controlled trial of efficacy

NARCIS (Netherlands)

van Coevorden, AM; Kamphof, WG; van Sonderen, E; Bruynzeel, DP; Coenraads, PJ

2004-01-01

Objective: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. Design: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. Setting:

Effects of risperidone on core symptoms of autistic disorder based on childhood autism rating scale: an open label study.

Science.gov (United States)

Ghaeli, Padideh; Nikvarz, Naemeh; Alaghband-Rad, Javad; Alimadadi, Abbas; Tehrani-Doost, Mehdi

2014-01-01

The aim of the present study was to evaluate the effect of risperidone in patients afflicted by autistic disorder especially with regards to its three core symptoms, including "relating to others", "communication skills", and "stereotyped behaviors" based on Childhood Autism Rating Scale (CARS). An 8-week open-label study of risperidone for treatment of autistic disorder in children 4-17 years old was designed. Risperidone dose titration was as follow: 0.02 mg/kg/day at the first week, 0.04 mg/kg/day at the second week, and 0.06 mg/kg/day at the third week and thereafter. The outcome measures were scores obtained by CARS, Aberrant Behavior Checklist (ABC), and Clinical Global Impression-Improvement (CGI-I) scale. Fifteen patients completed this study. After 8 weeks, CARS total score decreased significantly, (P=0.001). At the end of the study, social interactions and verbal communication skills of the patients were significantly improved (Pautistic disorder.

Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study.

Science.gov (United States)

Nakao, Atsunori; Toyoda, Yoshiya; Sharma, Prachi; Evans, Malkanthi; Guthrie, Najla

2010-03-01

Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55-0.65 mM), by the following chemical reaction; Mg + 2H(2)O --> Mg (OH)(2) + H(2). The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (pfasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.

Reduction of renal uptake of 111In-DOTA-labeled and A700-labeled RAFT-RGD during integrin αvβ3 targeting using single photon emission computed tomography and optical imaging.

Science.gov (United States)

Briat, Arnaud; Wenk, Christiane H F; Ahmadi, Mitra; Claron, Michael; Boturyn, Didier; Josserand, Véronique; Dumy, Pascal; Fagret, Daniel; Coll, Jean-Luc; Ghezzi, Catherine; Sancey, Lucie; Vuillez, Jean-Philippe

2012-06-01

Integrin α(v)β(3) expression is upregulated during tumor growth and invasion in newly formed endothelial cells in tumor neovasculature and in some tumor cells. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin α(v)β(3) in vitro and in vivo. When labeled with indium-111, the RAFT-RGD is partially reabsorbed and trapped in the kidneys, limiting its use for further internal targeted radiotherapy and imaging investigations. We studied the effect of Gelofusine on RAFT-RGD renal retention in tumor-bearing mice. Mice were imaged using single photon emission computed tomography and optical imaging 1 and 24 h following tracer injection. Distribution of RAFT-RGD was further investigated by tissue removal and direct counting of the tracer. Kidney sections were analyzed by confocal microscopy. Gelofusine significantly induced a >50% reduction of the renal reabsorption of (111)In-DOTA-RAFT-RGD and A700-RAFT-RGD, without affecting tumor uptake. Injection of Gelofusine significantly reduced the renal retention of labeled RAFT-RGD, while increasing the tumor over healthy tissue ratio. These results will lead to the development of future therapeutic approaches. © 2012 Japanese Cancer Association.

Open quantum systems and the two-level atom interacting with a single mode of the electromagnetic field

International Nuclear Information System (INIS)

Sandulescu, A.; Stefanescu, E.

1987-07-01

On the basis of Lindblad theory of open quantum systems we obtain new optical equations for the system of two-level atom interacting with a single mode of the electromagnetic field. The conventional Block equations in a generalized form with field phases are obtained in the hypothesis that all the terms are slowly varying in the rotating frame.(authors)

Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

Directory of Open Access Journals (Sweden)

Kim YH

2015-02-01

Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

Science.gov (United States)

Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

2016-06-07

Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study.

Science.gov (United States)

Lotan, Itay; Treves, Therese A; Roditi, Yaniv; Djaldetti, Ruth

2014-01-01

The use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of PD. Twenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. Mean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.

Continuing weight-loss effect after topiramate discontinuation in obese persons with schizophrenia: a pilot open-label study.

Science.gov (United States)

Liang, C-S; Yang, F-W; Huang, S-Y; Ho, P-S

2014-07-01

Few studies have investigated the likelihood of weight maintenance in obese persons with schizophrenia after their initial successful weight loss. This pilot open-label study examined the efficacy of topiramate in weight loss and the trajectory of weight changes after topiramate discontinuation. This study enrolled 10 obese persons with schizophrenia. A 4-month treatment phase was started, followed by a 12-month discontinuation phase. Body weight was measured as the primary outcome every month. Secondary outcomes included leptin levels, fasting glucose, lipid profiles, and insulin resistance index. After the 4-month addition of topiramate, participants lost 1.79 kg of their body weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32 kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41 to -2.24, p<0.001). The continuing weight-loss effect after topiramate discontinuation might have resulted from topiramate's potential to improve leptin functioning. These findings demonstrate that topiramate's weight-loss effect could not only persist during its administration, but also continue to improve after its discontinuation. © Georg Thieme Verlag KG Stuttgart · New York.

Measuring chess experts' single-use sequence knowledge: an archival study of departure from 'theoretical' openings.

Directory of Open Access Journals (Sweden)

Philippe Chassy

Full Text Available The respective roles of knowledge and search have received considerable attention in the literature on expertise. However, most of the evidence on knowledge has been indirect--e.g., by inferring the presence of chunks in long-term memory from performance in memory recall tasks. Here we provide direct estimates of the amount of monochrestic (single use and rote knowledge held by chess players of varying skill levels. From a large chess database, we analyzed 76,562 games played in 2008 by individuals ranging from Class B players (average players to Masters to measure the extent to which players deviate from previously known initial sequences of moves ("openings". Substantial differences were found in the number of moves known by players of different skill levels, with more expert players knowing more moves. Combined with assumptions independently made about the branching factor in master games, we estimate that masters have memorized about 100,000 opening moves. Our results support the hypothesis that monochrestic knowledge is essential for reaching high levels of expertise in chess. They provide a direct, quantitative estimate of the number of opening moves that players have to know to reach master level.

Ringer's lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial.

Science.gov (United States)

Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert G

2015-05-06

The infusion of large amounts of Ringer's lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringer's lactate exerts these adverse effects when the surgery is performed by laparoscopy. Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid treatment with 9 ml/kg of either 6% hydroxyethyl starch 130/0.4 (Voluven) or Ringer's lactate, just after induction of anaesthesia; this was followed by a second-line infusion with 12 ml/kg of either starch or Ringer's lactate over 1 hour. Further therapy was managed at the discretion of the attending anaesthetist. Outcome data consisted of postoperative gastrointestinal recovery time, complications and length of hospital stay. The order of the infusions had no impact on the outcome. Both the administration of ≥ 2 L of Ringer's lactate and the development of a surgical complication were associated with a longer time period of paralytic ileus and food intolerance (two-way ANOVA, P food intolerance time amounted to 2 days each. The infusion of ≥ 1 L of hydroxyethyl starch did not adversely affect gastrointestinal recovery. Ringer's lactate, but not hydroxyethyl starch, prolonged the gastrointestinal recovery time in patients undergoing laparoscopic cancer surgery. Surgical complications prolonged the hospital stay.

Compound list: cyclosporine A [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available cyclosporine A CSA 00142 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/cyclosporine..._A.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/cyclosporine.../in_vivo/Liver/Single/cyclosporine_A.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc...iencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/cyclosporine_A.Rat.in_vivo.Liver.Repeat.zip... ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/cyclosporine_A.Rat.in_vivo

Influence of label information on dark chocolate acceptability.

Science.gov (United States)

Torres-Moreno, M; Tarrega, A; Torrescasana, E; Blanch, C

2012-04-01

The aim of the present work was to study how the information on product labels influences consumer expectations and their acceptance and purchase intention of dark chocolate. Six samples of dark chocolate, varying in brand (premium and store brand) and in type of product (regular dark chocolate, single cocoa origin dark chocolate and high percentage of cocoa dark chocolate), were evaluated by 109 consumers who scored their liking and purchase intention under three conditions: blind (only tasting the products), expected (observing product label information) and informed (tasting the products together with provision of the label information). In the expected condition, consumer liking was mainly affected by the brand. In the blind condition, differences in liking were due to the type of product; the samples with a high percentage of cocoa were those less preferred by consumers. Under the informed condition, liking of dark chocolates varied depending on both brand and type of product. Premium brand chocolates generated high consumer expectations of chocolate acceptability, which were fulfilled by the sensory characteristics of the products. Store brand chocolates created lower expectations, but when they were tasted they were as acceptable as premium chocolates. Claims of a high percentage of cocoa and single cocoa origin on labels did not generate higher expectations than regular dark chocolates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Compound list: TNFα [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available TNFα TNF 00A08 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitr...o/TNFa.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/TNFa.Rat....in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/TNFa.Rat.in_vivo.Liver.Single.zip ...

Compound list: LPS [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available LPS LPS 00A07 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro.../LPS.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/LPS.Rat.in..._vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/LPS.Rat.in_vivo.Liver.Single.zip ...

Compound list: phenobarbital [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available phenobarbital PB 00004 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/phenobarbital.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/...in_vitro/phenobarbital.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vivo/Liver/Single/phenobarbital.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscience

Compound list: sulfasalazine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available sulfasalazine SS 00034 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/sulfasalazine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/...in_vitro/sulfasalazine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vivo/Liver/Single/sulfasalazine.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscience

Compound list: methapyrilene [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available methapyrilene MP 00025 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/methapyrilene.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/...in_vitro/methapyrilene.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vivo/Liver/Single/methapyrilene.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscience

Compound list: galactosamine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available galactosamine GaN 00A06 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/galactosamine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/galactosamine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/galactosamine.Rat.in_vivo.Liver.Single.zip ...

Direct isotope determination of isotopically labelled lipids by field desorption mass spectrometry

International Nuclear Information System (INIS)

Lehmann, W.D.; Kessler, M.

1982-01-01

Lipids labelled with deuterium or carbon-14 have been investigated by field desorption mass spectrometry for determination of their degree of labelling. This application is demonstrated for free fatty acids, cholesterol, cholesteryl esters, triglycerides, and L-α-phosphatidylcholines. Comparison of the molecular ion groups of the non-labelled and of the labelled compounds enables a fast and reliable determination of the degree of labelling. For multiply labelled compounds the label distribution is also obtained from the molecular ion group. In addition, for cholesteryl esters and for phosphatidylcholines structurally significant fragment ions provide information about the position of the label. Several hundred nanograms of the compound are typically required for a single analysis with a relative standard error of 0.5-2% in the value calculated for atom% hydrogen-2 or for the specific carbon-14 activity. (orig.) [de

Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

Science.gov (United States)

2017-10-01

We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores ≥2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-R], forced vital capacity ≥80%, definite or probable ALS, and disease duration ≤2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean ± standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was -4.1 ± 3.4 and -6.9 ± 5.1 in the E-E group and P-E group, respectively, while it was -8.0 ± 5.6 in the E-E group and -10.9 ± 6.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.

A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease.

Science.gov (United States)

Friedman, Neil J; Butron, Karla; Robledo, Nora; Loudin, James; Baba, Stephanie N; Chayet, Arturo

2016-01-01

Dry eye disease (DED), a chronic disorder affecting the tear film and lacrimal functional unit, is a widely prevalent condition associated with significant burden and unmet treatment needs. Since specific neural circuits play an important role in maintaining ocular surface health, microelectrical stimulation of these pathways could present a promising new approach to treating DED. This study evaluated the efficacy and safety of nasal electrical stimulation in patients with DED. This prospective, open-label, single-arm, nonrandomized pilot study included 40 patients with mild to severe DED. After undergoing two screening visits, enrolled subjects were provided with a nasal stimulation device and instructed to use it at home four times daily (or more often as needed). Follow-up assessments were conducted up to day 180. The primary efficacy endpoint was the difference between unstimulated and stimulated tear production quantified by Schirmer scores. Additional efficacy endpoints included change from baseline in corneal and conjunctival staining, symptoms evaluated on a Visual Analog Scale, and Ocular Surface Disease Index scores. Safety parameters included adverse event (AE) rates, visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, and endoscopic nasal examinations. Mean stimulated Schirmer scores were significantly higher than the unstimulated scores at all visits, and corneal and conjunctival staining and symptom scores from baseline to day 180 were significantly reduced. No serious device-related AEs and nine nonserious AEs (three device-related) were reported. Intraocular pressure remained stable and most subjects showed little or no change in visual acuity at days 30 and 180. No significant findings from other clinical examinations were noted. Neurostimulation of the nasolacrimal pathway is a safe and effective means of increasing tear production and reducing symptoms of dry eye in patients with DED.

Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

Directory of Open Access Journals (Sweden)

Kasper S

2017-03-01

Full Text Available Siegfried Kasper,1 Angelika Dienel2 1Universitätsklinik für Psychiatrie und Psychotherapie, Medizinische Universität Wien, Wien, Austria; 2Dr Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany Purpose: This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group.Methods: The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results: The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to

Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer's disease in an open-label pilot study.

Science.gov (United States)

Remington, Ruth; Chan, Amy; Lepore, Alicia; Kotlya, Elizabeth; Shea, Thomas B

2010-06-01

Preclinical studies demonstrate that apple juice exerts multiple beneficial effects including reduction of central nervous system oxidative damage, suppression of Alzheimer's disease (AD) hallmarks, improved cognitive performance, and organized synaptic signaling. Herein, we initiated an open-label clinical trial in which 21 institutionalized individuals with moderate-to-severe AD consumed 2 4-oz glasses of apple juice daily for 1 month. Participants demonstrated no change in the Dementia Rating Scale, and institutional caregivers reported no change in Alzheimer's Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) in this brief study. However, caregivers reported an approximate 27% (P Inventory, with the largest changes in anxiety, agitation, and delusion. This pilot study suggests that apple juice may be a useful supplement, perhaps to augment pharmacological approaches, for attenuating the decline in mood that accompanies progression of AD, which may also reduce caregiver burden.

Single-tier city logistics model for single product

Science.gov (United States)

Saragih, N. I.; Nur Bahagia, S.; Suprayogi; Syabri, I.

2017-11-01

This research develops single-tier city logistics model which consists of suppliers, UCCs, and retailers. The problem that will be answered in this research is how to determine the location of UCCs, to allocate retailers to opened UCCs, to assign suppliers to opened UCCs, to control inventory in the three entities involved, and to determine the route of the vehicles from opened UCCs to retailers. This model has never been developed before. All the decisions will be simultaneously optimized. Characteristic of the demand is probabilistic following a normal distribution, and the number of product is single.

pyOpenMS: a Python-based interface to the OpenMS mass-spectrometry algorithm library.

Science.gov (United States)

Röst, Hannes L; Schmitt, Uwe; Aebersold, Ruedi; Malmström, Lars

2014-01-01

pyOpenMS is an open-source, Python-based interface to the C++ OpenMS library, providing facile access to a feature-rich, open-source algorithm library for MS-based proteomics analysis. It contains Python bindings that allow raw access to the data structures and algorithms implemented in OpenMS, specifically those for file access (mzXML, mzML, TraML, mzIdentML among others), basic signal processing (smoothing, filtering, de-isotoping, and peak-picking) and complex data analysis (including label-free, SILAC, iTRAQ, and SWATH analysis tools). pyOpenMS thus allows fast prototyping and efficient workflow development in a fully interactive manner (using the interactive Python interpreter) and is also ideally suited for researchers not proficient in C++. In addition, our code to wrap a complex C++ library is completely open-source, allowing other projects to create similar bindings with ease. The pyOpenMS framework is freely available at https://pypi.python.org/pypi/pyopenms while the autowrap tool to create Cython code automatically is available at https://pypi.python.org/pypi/autowrap (both released under the 3-clause BSD licence). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Labeled Data Set For Flow-based Intrusion Detection

NARCIS (Netherlands)

Sperotto, Anna; Sadre, R.; van Vliet, Frank; Pras, Aiko; Nunzi, Giorgio; Scoglio, Caterina; Li, Xing

2009-01-01

Flow-based intrusion detection has recently become a promising security mechanism in high speed networks (1-10 Gbps). Despite the richness in contributions in this field, benchmarking of flow-based IDS is still an open issue. In this paper, we propose the first publicly available, labeled data set

Photon-HDF5: Open Data Format and Computational Tools for Timestamp-based Single-Molecule Experiments.

Science.gov (United States)

Ingargiola, Antonino; Laurence, Ted; Boutelle, Robert; Weiss, Shimon; Michalet, Xavier

2016-02-13

Archival of experimental data in public databases has increasingly become a requirement for most funding agencies and journals. These data-sharing policies have the potential to maximize data reuse, and to enable confirmatory as well as novel studies. However, the lack of standard data formats can severely hinder data reuse. In photon-counting-based single-molecule fluorescence experiments, data is stored in a variety of vendor-specific or even setup-specific (custom) file formats, making data interchange prohibitively laborious, unless the same hardware-software combination is used. Moreover, the number of available techniques and setup configurations make it difficult to find a common standard. To address this problem, we developed Photon-HDF5 (www.photon-hdf5.org), an open data format for timestamp-based single-molecule fluorescence experiments. Building on the solid foundation of HDF5, Photon-HDF5 provides a platform- and language-independent, easy-to-use file format that is self-describing and supports rich metadata. Photon-HDF5 supports different types of measurements by separating raw data (e.g. photon-timestamps, detectors, etc) from measurement metadata. This approach allows representing several measurement types and setup configurations within the same core structure and makes possible extending the format in backward-compatible way. Complementing the format specifications, we provide open source software to create and convert Photon-HDF5 files, together with code examples in multiple languages showing how to read Photon-HDF5 files. Photon-HDF5 allows sharing data in a format suitable for long term archival, avoiding the effort to document custom binary formats and increasing interoperability with different analysis software. We encourage participation of the single-molecule community to extend interoperability and to help defining future versions of Photon-HDF5.

Compound list: nitrosodiethylamine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nitrosodiethylamine DEN 00145 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...s/LATEST/Rat/in_vitro/nitrosodiethylamine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tgg...ates/LATEST/Rat/in_vivo/Liver/Single/nitrosodiethylamine.Rat.in_vivo.Liver.Single....zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/nitrosodiethylamine.Rat.in_vivo.Liver.Repeat.zip ... ...T/Human/in_vitro/nitrosodiethylamine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggate

Compound list: hexachlorobenzene [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available hexachlorobenzene HCB 00022 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/...Human/in_vitro/hexachlorobenzene.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LA...TEST/Rat/in_vitro/hexachlorobenzene.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/L...ATEST/Rat/in_vivo/Liver/Single/hexachlorobenzene.Rat.in_vivo.Liver.Single.zip ftp...://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/hexachlorobenzene.Rat.in_vivo.L

Compound list: cyclophosphamide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available cyclophosphamide CPA 00024 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/H...uman/in_vitro/cyclophosphamide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...ST/Rat/in_vitro/cyclophosphamide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...ST/Rat/in_vivo/Liver/Single/cyclophosphamide.Rat.in_vivo.Liver.Single.zip ftp://f...tp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/cyclophosphamide.Rat.in_vivo.Liver.

Compound list: aspirin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available aspirin ASA 00014 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/aspirin....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/aspirin....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/aspirin....Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/aspirin.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: doxorubicin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available doxorubicin DOX 00149 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/doxorubicin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/doxorubicin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/doxorubicin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/...archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/doxorubicin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bios

Compound list: ethanol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ethanol ETN 00137 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_v...itro/ethanol.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/et...hanol.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single.../ethanol.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/ethanol.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: adapin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available adapin ADP 00039 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vi...tro/adapin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/adap...in.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/ad...apin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/adapin.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: danazol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available danazol DNZ 00127 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_v...itro/danazol.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/da...nazol.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single.../danazol.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/danazol.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: allopurinol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available allopurinol APL 00028 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/allopurinol.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/allopurinol.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/allopurinol.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/...archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/allopurinol.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bios

Compound list: ciprofloxacin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ciprofloxacin CPX 00050 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/ciprofloxacin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/ciprofloxacin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/ciprofloxacin.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/ciprofloxacin.Rat.in_vivo.Liver.Repeat.zip ftp:

Compound list: tacrine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available tacrine TAC 00060 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_v...itro/tacrine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/ta...crine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single.../tacrine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/tacrine.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: monocrotaline [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available monocrotaline MCT 00058 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/monocrotaline.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/monocrotaline.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/monocrotaline.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/monocrotaline.Rat.in_vivo.Liver.Repeat.zip ftp:

Phase II open label study of valproic acid in spinal muscular atrophy.

Directory of Open Access Journals (Sweden)

Kathryn J Swoboda

Full Text Available Preliminary in vitro and in vivo studies with valproic acid (VPA in cell lines and patients with spinal muscular atrophy (SMA demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS, electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP amplitudes and motor unit number estimation (MUNE, body composition and bone density via dual-energy X-ray absorptiometry (DEXA, and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p

Foliar absorption of 15N labeled urea by tea plant

International Nuclear Information System (INIS)

Hoshina, Tsuguo; Kozai, Shuji; Ishigaki, Kozo

1978-01-01

The effect of foliar application on the nitrogen nutrient status of tea shoots has been studied using 15 N labelled urea. Furthermore, the difference in nitrogen utilization by tea plant between foliar applied and top dressed nitrogen was investigated using 15 N labelled urea and ammonium sulfate. The foliar application of urea increased the amount of chlorophyll and total nitrogen in the new shoot, and the foliar application was more effective under shading condition. The urea sprayed upon old leaves prior to the opening of new leaf translocated to the new shoots. However, the foliar application after the opening of new leaf was more effective on nitrogen absorption by new shoots than one prior to that, and rather than top dressing for new shoots. It could be recognized that the foliar application of urea raises the nitrogen nutrient status of tea leaves in summer. (author)

PySeqLab: an open source Python package for sequence labeling and segmentation.

Science.gov (United States)

Allam, Ahmed; Krauthammer, Michael

2017-11-01

Text and genomic data are composed of sequential tokens, such as words and nucleotides that give rise to higher order syntactic constructs. In this work, we aim at providing a comprehensive Python library implementing conditional random fields (CRFs), a class of probabilistic graphical models, for robust prediction of these constructs from sequential data. Python Sequence Labeling (PySeqLab) is an open source package for performing supervised learning in structured prediction tasks. It implements CRFs models, that is discriminative models from (i) first-order to higher-order linear-chain CRFs, and from (ii) first-order to higher-order semi-Markov CRFs (semi-CRFs). Moreover, it provides multiple learning algorithms for estimating model parameters such as (i) stochastic gradient descent (SGD) and its multiple variations, (ii) structured perceptron with multiple averaging schemes supporting exact and inexact search using 'violation-fixing' framework, (iii) search-based probabilistic online learning algorithm (SAPO) and (iv) an interface for Broyden-Fletcher-Goldfarb-Shanno (BFGS) and the limited-memory BFGS algorithms. Viterbi and Viterbi A* are used for inference and decoding of sequences. Using PySeqLab, we built models (classifiers) and evaluated their performance in three different domains: (i) biomedical Natural language processing (NLP), (ii) predictive DNA sequence analysis and (iii) Human activity recognition (HAR). State-of-the-art performance comparable to machine-learning based systems was achieved in the three domains without feature engineering or the use of knowledge sources. PySeqLab is available through https://bitbucket.org/A_2/pyseqlab with tutorials and documentation. ahmed.allam@yale.edu or michael.krauthammer@yale.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects

Science.gov (United States)

Moore, Kenneth Todd; Byra, William; Vaidyanathan, Seema; Natarajan, Jaya; Ariyawansa, Jay; Salih, Hiba; Turner, Kenneth C

2015-01-01

Aims The primary objective was to explore the pharmacodynamic changes during transition from rivaroxaban to warfarin in healthy subjects. Safety, tolerability and pharmacokinetics were assessed as secondary objectives. Methods An open label, non-randomized, sequential two period study. In treatment period 1 (TP1), subjects received rivaroxaban 20 mg once daily (5 days), followed by co-administration with a warfarin loading dose regimen of 5 or 10 mg (for the 10 mg regimen, the dose could be uptitrated to attain target international normalized ratio [INR] ≥2.0) once daily (2–4 days). When trough INR values ≥2.0 were attained, rivaroxaban was discontinued and warfarin treatment continued as monotherapy (INR 2.0–3.0). During treatment period 2, subjects received the same warfarin regimen as in TP1, but without rivaroxaban. Results During co-administration, maximum INR and prothrombin time (PT) values were higher than with rivaroxaban or warfarin monotherapy. The mean maximum effect (Emax) for INR after co-administration was 2.79–4.15 (mean PT Emax 41.0–62.7 s), compared with 1.41–1.74 (mean PT Emax 20.1–25.2 s) for warfarin alone. However, rivaroxaban had the smallest effect on INR at trough rivaroxaban concentrations. Neither rivaroxaban nor warfarin significantly affected maximum plasma concentrations of the other drug. Conclusions The combined pharmacodynamic effects during co-administration of rivaroxaban and warfarin were greater than additive, but the pharmacokinetics of both drugs were unaffected. Co-administration was well tolerated. When transitioning from rivaroxaban to warfarin, INR monitoring during co-administration should be performed at the trough rivaroxaban concentration to minimize the effect of rivaroxaban on INR. PMID:25475601

Single step 18F-labeling of dimeric cycloRGD for functional PET imaging of tumors in mice

International Nuclear Information System (INIS)

Li, Ying; Liu, Zhibo; Lozada, Jerome; Wong, May Q.; Lin, Kuo-Shyan; Yapp, Donald; Perrin, David M.

2013-01-01

Introduction: Arylboronates afford rapid aqueous 18 F-labeling via the creation of a highly polar 18 F-aryltrifluoroborate anion ( 18 F-ArBF 3 − ). Hypothesis: Radiosynthesis of an 18 F-ArBF 3 − can be successfully applied to a clinically relevant peptide. To test this hypothesis, we labeled dimeric-cylcoRGD, [c(RGDfK)] 2 E because a) it is molecularly complex and provides a challenging substrate to test the application of this technique, and b) [c(RGDfK)] 2 E has already been labeled via several 18 F-labeling methods which provide for a preliminary comparison. Goal: To validate this labeling method in the context of a complex and clinically relevant tracer to show tumor-specific uptake ex vivo with representative PET images in vivo. Methods: An arylborimidine was conjugated to [c(RGDfK)] 2 E to give the precursor [c(RGDfK)] 2 E-ArB(dan), which was aliquoted and stored at − 20 °C. Aliquots of 10 or 25 nmol, containing only micrograms of precursor, were labeled using relatively low levels of 18 F-activity. Following purification eight mice (pre-blocked/unblocked) with U87M xenograft tumors were injected with [c(RGDfK)] 2 E- 18 F-ArBF 3 − (n = 4) for ex vivo tissue dissection. Two sets of mice (pre-blocked/unblocked) were also imaged with PET–CT (n = 2). Results: The [c(RGDfK)] 2 E-ArB(dan) is converted within 15 min to [c(RGDfK)] 2 E- 18 F-ArBF 3 − in isolated radiochemical yields of ∼ 10% (n = 3) at a minimum effective specific activity of 0.3 Ci/μmol. Biodistribution shows rapid clearance to the bladder via the kidney resulting in high tumor-to-blood and tumor-to-muscle ratios of > 9 and > 6 respectively while pre-blocking with [c(RGDfK)] 2 E showed high tumor specificity. PET imaging showed good contrast between tumor and non-target tissues confirming the biodistribution data. Conclusion: An arylborimidine-RGD peptide is rapidly 18 F-labeled in one step, in good yield, at useful specific activity. Biodistribution studies with blocking controls

High-energy intermediates in protein unfolding characterized by thiol labeling under nativelike conditions.

Science.gov (United States)

Malhotra, Pooja; Udgaonkar, Jayant B

2014-06-10

A protein unfolding reaction usually appears to be so dominated by a large free energy barrier that identifying and characterizing high-energy intermediates and, hence, dissecting the unfolding reaction into multiple structural transitions have proven to be a challenge. In particular, it has been difficult to identify any detected high-energy intermediate with the dry (DMG) and wet (WMG) molten globules that have been implicated in the unfolding reactions of at least some proteins. In this study, a native-state thiol labeling methodology was used to identify high-energy intermediates, as well as to delineate the barriers to the disruption of side chain packing interactions and to site-specific solvent exposure in different regions of the small protein, single-chain monellin (MNEI). Labeling studies of four single-cysteine-containing variants of MNEI have identified three high-energy intermediates, populated to very low extents under nativelike conditions. A significant dispersion in the opening rates of the cysteine side chains has allowed multiple steps, leading to the loss of side chain packing, to be resolved temporally. A detailed structural analysis of the positions of the four cysteine residue positions, which are buried to different depths within the protein, has suggested a direct correlation with the structure of a DMG, detected in previous studies. It is observed that side chain packing within the core of the protein is maintained, while that at the surface is disrupted, in the DMG. The core of the protein becomes solvent-exposed only in a WMG populated after the rate-limiting step of unfolding at high denaturant concentrations.

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

Science.gov (United States)

Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

2016-07-01

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

Compound list: chlorpheniramine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available chlorpheniramine CHL 00090 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/chlorpheni...ramine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...ST/Rat/in_vivo/Liver/Single/chlorpheniramine.Rat.in_vivo.Liver.Single.zip ftp://f...tp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/chlorpheniramine.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: chloramphenicol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available chloramphenicol CMP 00064 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/chlorampheni...col.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST...Rat/in_vivo/Liver/Single/chloramphenicol.Rat.in_vivo.Liver.Single.zip ftp://ftp.b...iosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/chloramphenicol.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: meloxicam [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available meloxicam MLX 00124 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/meloxicam.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/meloxicam.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/meloxicam.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: disopyramide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available disopyramide DIS 00102 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/disopyramide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/i...n_vitro/disopyramide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...vo/Liver/Single/disopyramide.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc

Compound list: ethionamide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ethionamide ETH 00135 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/ethionamide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/ethionamide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/ethionamide.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: tetracycline [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available tetracycline TC 00048 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/tetracycline.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vitro/tetracycline.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_viv...o/Liver/Single/tetracycline.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.

Compound list: diclofenac [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available diclofenac DFNa 00019 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/diclofenac.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_v...itro/diclofenac.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Li...ver/Single/diclofenac.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arc

Compound list: theophylline [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available theophylline TEO 00096 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/theophylline.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/i...n_vitro/theophylline.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...vo/Liver/Single/theophylline.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc

Compound list: griseofulvin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available griseofulvin GF 00043 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/griseofulvin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vitro/griseofulvin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_viv...o/Liver/Single/griseofulvin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.

Compound list: propylthiouracil [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available propylthiouracil PTU 00029 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/H...uman/in_vitro/propylthiouracil.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...ST/Rat/in_vitro/propylthiouracil.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...ST/Rat/in_vivo/Liver/Single/propylthiouracil.Rat.in_vivo.Liver.Single.zip ftp://f

Compound list: carbamazepine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available carbamazepine CBZ 00018 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/carbamazepine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/carbamazepine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/carbamazepine.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc

Compound list: benziodarone [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available benziodarone BZD 00130 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/benziodarone.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/i...n_vitro/benziodarone.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...vo/Liver/Single/benziodarone.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc

Compound list: quinidine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available quinidine QND 00074 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/quinidine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/quinidine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/quinidine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: nitrofurazone [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nitrofurazone NFZ 00065 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/nitrofurazone.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/nitrofurazone.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/nitrofurazone.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc

Compound list: trimethadione [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available trimethadione TMD 00122 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/trimethadione.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/trimethadione.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/trimethadione.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc

Compound list: ticlopidine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ticlopidine TCP 00146 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/ticlopidine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/ticlopidine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/ticlopidine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: hydroxyzine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available hydroxyzine HYZ 00071 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/hydroxyzine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/hydroxyzine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/hydroxyzine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: ibuprofen [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ibuprofen IBU 00072 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/ibuprofen.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/ibuprofen.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/ibuprofen.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: chlormezanone [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available chlormezanone CMN 00052 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/chlormezanone.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/chlormezanone.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/chlormezanone.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc

Compound list: chlorpropamide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available chlorpropamide CPP 00080 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/chlorpropamide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/chlorpropamide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/chlorpropamide.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc

Compound list: azathioprine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available azathioprine AZP 00046 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/azathioprine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/i...n_vitro/azathioprine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...vo/Liver/Single/azathioprine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc

Compound list: simvastatin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available simvastatin SST 00117 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/simvastatin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/simvastatin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/simvastatin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: phenytoin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available phenytoin PHE 00026 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/phenytoin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/phenytoin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/phenytoin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: metformin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available metformin MFM 00053 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/metformin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/metformin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/metformin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: methimazole [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available methimazole MTZ 00057 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/methimazole.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/methimazole.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/methimazole.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: sulpiride [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available sulpiride SLP 00115 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/sulpiride.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/sulpiride.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/sulpiride.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: fenofibrate [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available fenofibrate FFB 00079 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/fenofibrate.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/fenofibrate.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/fenofibrate.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: thioridazine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available thioridazine TRZ 00038 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/thioridazine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/i...n_vitro/thioridazine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...vo/Liver/Single/thioridazine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc

Compound list: isoniazid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available isoniazid INAH 00002 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/isoniazid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vit...ro/isoniazid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver.../Single/isoniazid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive

Compound list: labetalol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available labetalol LBT 00040 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/labetalol.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/labetalol.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/labetalol.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

Compound list: chlorpromazine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available chlorpromazine CPZ 00016 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/chlorpromazine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R.../in_vivo/Liver/Single/chlorpromazine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc...iencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/chlorpromazine.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: clomipramine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available clomipramine CPM 00121 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/clomipramine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/clomipramine...vo/Liver/Single/clomipramine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc....jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/clomipramine.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: promethazine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available promethazine PMZ 00110 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/promethazine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/promethazine...vo/Liver/Single/promethazine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc....jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/promethazine.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: penicillamine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available penicillamine PEN 00099 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/penicillamine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/penicillamine..._vivo/Liver/Single/penicillamine.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/penicillamine.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: glibenclamide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available glibenclamide GBC 00042 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/glibenclam...ide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/glibenclam..._vivo/Liver/Single/glibenclamide.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/glibenclamide.Rat.in_vivo.Liver.Repeat.zip ...

Enzymatic production of single-molecule FISH and RNA capture probes.

Science.gov (United States)

Gaspar, Imre; Wippich, Frank; Ephrussi, Anne

2017-10-01

Arrays of singly labeled short oligonucleotides that hybridize to a specific target revolutionized RNA biology, enabling quantitative, single-molecule microscopy analysis and high-efficiency RNA/RNP capture. Here, we describe a simple and efficient method that allows flexible functionalization of inexpensive DNA oligonucleotides by different fluorescent dyes or biotin using terminal deoxynucleotidyl transferase and custom-made functional group conjugated dideoxy-UTP. We show that (i) all steps of the oligonucleotide labeling-including conjugation, enzymatic synthesis, and product purification-can be performed in a standard biology laboratory, (ii) the process yields >90%, often >95% labeled product with minimal carryover of impurities, and (iii) the oligonucleotides can be labeled with different dyes or biotin, allowing single-molecule FISH, RNA affinity purification, and Northern blot analysis to be performed. © 2017 Gaspar et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

New Developments in Spin Labels for Pulsed Dipolar EPR

Directory of Open Access Journals (Sweden)

Alistair J. Fielding

2014-10-01

Full Text Available Spin labelling is a chemical technique that enables the integration of a molecule containing an unpaired electron into another framework for study. Given the need to understand the structure, dynamics, and conformational changes of biomacromolecules, spin labelling provides a relatively non-intrusive technique and has certain advantages over X-ray crystallography; which requires high quality crystals. The technique relies on the design of binding probes that target a functional group, for example, the thiol group of a cysteine residue within a protein. The unpaired electron is typically supplied through a nitroxide radical and sterically shielded to preserve stability. Pulsed electron paramagnetic resonance (EPR techniques allow small magnetic couplings to be measured (e.g., <50 MHz providing information on single label probes or the dipolar coupling between multiple labels. In particular, distances between spin labels pairs can be derived which has led to many protein/enzymes and nucleotides being studied. Here, we summarise recent examples of spin labels used for pulse EPR that serve to illustrate the contribution of chemistry to advancing discoveries in this field.

Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

DEFF Research Database (Denmark)

Bousser, M.G.; Bouthier, J.; Buller, H.R.

2008-01-01

5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; pvitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0......BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim...... of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. METHODS: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K...

Raman-Activated Droplet Sorting (RADS) for Label-Free High-Throughput Screening of Microalgal Single-Cells.

Science.gov (United States)

Wang, Xixian; Ren, Lihui; Su, Yetian; Ji, Yuetong; Liu, Yaoping; Li, Chunyu; Li, Xunrong; Zhang, Yi; Wang, Wei; Hu, Qiang; Han, Danxiang; Xu, Jian; Ma, Bo

2017-11-21

Raman-activated cell sorting (RACS) has attracted increasing interest, yet throughput remains one major factor limiting its broader application. Here we present an integrated Raman-activated droplet sorting (RADS) microfluidic system for functional screening of live cells in a label-free and high-throughput manner, by employing AXT-synthetic industrial microalga Haematococcus pluvialis (H. pluvialis) as a model. Raman microspectroscopy analysis of individual cells is carried out prior to their microdroplet encapsulation, which is then directly coupled to DEP-based droplet sorting. To validate the system, H. pluvialis cells containing different levels of AXT were mixed and underwent RADS. Those AXT-hyperproducing cells were sorted with an accuracy of 98.3%, an enrichment ratio of eight folds, and a throughput of ∼260 cells/min. Of the RADS-sorted cells, 92.7% remained alive and able to proliferate, which is equivalent to the unsorted cells. Thus, the RADS achieves a much higher throughput than existing RACS systems, preserves the vitality of cells, and facilitates seamless coupling with downstream manipulations such as single-cell sequencing and cultivation.

The fluorodediazonation - a method for n.c.a.-18F-labelling of aromatic substrates

International Nuclear Information System (INIS)

Zwernemann, O.

1991-06-01

For the positron emission tomography (PET) applications, radiopharmaceuticals are required that are labelled with short-lived positron emitters. Fluorine-18 has become the leading radionuclide used for PET, due to its favourable physical properties. However, the labelling of aromatic substances with fluorine-18 with the methods available presents problems not encountered with aliphatic compounds. The decomposition of aromatic diazonium salts opens up feasible ways of preparing a broad range of labelled compounds. The dissertation investigated the possibilities of labelling with fluorine-18 by way of dediazonation on the standard substrate p-Toluidyl diazonium ion. The results reported show that the method of fluorodediazonation is an interesting further method for F-18 labelling of aromatic substrates in addition to the hitherto applied techniques. It allows carrier-free labelling of a large group of substances which cannot be fluorinated via direct nucleophilicity. (BBR) [de

Effect of omega-3 polyunsaturated fatty acids on the cytoskeleton: an open-label intervention study.

Science.gov (United States)

Schmidt, Simone; Willers, Janina; Riecker, Sabine; Möller, Katharina; Schuchardt, Jan Philipp; Hahn, Andreas

2015-02-14

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) show beneficial effects on cardiovascular health and cognitive functions, but the underlying molecular mechanisms are not completely understood. Because of the fact that cytoskeleton dynamics affect almost every cellular process, the regulation of cytoskeletal dynamics could be a new pathway by which n-3 PUFAs exert their effects on cellular level. A 12-week open-label intervention study with 12 healthy men was conducted to determine the effects of 2.7 g/d n-3 PUFA on changes in mRNA expression of cytoskeleton-associated genes by quantitative real-time PCR in whole blood. Furthermore, the actin content in red blood cells was analyzed by immunofluorescence imaging. N-3 PUFA supplementation resulted in a significant down-regulation of cytoskeleton-associated genes, in particular three GTPases (RAC1, RHOA, CDC42), three kinases (ROCK1, PAK2, LIMK), two Wiskott-Aldrich syndrome proteins (WASL, WASF2) as well as actin related protein 2/3 complex (ARPC2, ARPC3) and cofilin (CFL1). Variability in F-actin content between subjects was high; reduced actin content was only reduced within group evaluation. Reduced cytoskeleton-associated gene expression after n-3 PUFA supplementation suggests that regulation of cytoskeleton dynamics might be an additional way by which n-3 PUFAs exert their cellular effects. Concerning F-actin, this analysis did not reveal unmistakable results impeding a generalized conclusion.

All-atom molecular dynamics simulations of spin labelled double and single-strand DNA for EPR studies.

Science.gov (United States)

Prior, C; Danilāne, L; Oganesyan, V S

2018-05-16

We report the first application of fully atomistic molecular dynamics (MD) simulations to the prediction of electron paramagnetic resonance (EPR) spectra of spin labelled DNA. Models for two structurally different DNA spin probes with either the rigid or flexible position of the nitroxide group in the base pair, employed in experimental studies previously, have been developed. By the application of the combined MD-EPR simulation methodology we aimed at the following. Firstly, to provide a test bed against a sensitive spectroscopic technique for the recently developed improved version of the parmbsc1 force field for MD modelling of DNA. The predicted EPR spectra show good agreement with the experimental ones available from the literature, thus confirming the accuracy of the currently employed DNA force fields. Secondly, to provide a quantitative interpretation of the motional contributions into the dynamics of spin probes in both duplex and single-strand DNA fragments and to analyse their perturbing effects on the local DNA structure. Finally, a combination of MD and EPR allowed us to test the validity of the application of the Model-Free (M-F) approach coupled with the partial averaging of magnetic tensors to the simulation of EPR spectra of DNA systems by comparing the resultant EPR spectra with those simulated directly from MD trajectories. The advantage of the M-F based EPR simulation approach over the direct propagation techniques is that it requires motional and order parameters that can be calculated from shorter MD trajectories. The reported MD-EPR methodology is transferable to the prediction and interpretation of EPR spectra of higher order DNA structures with novel types of spin labels.

Buoyancy Driven Natural Ventilation through Horizontal Openings

OpenAIRE

Heiselberg, Per

2009-01-01

An experimental study of the phenomenon of buoyancy driven natural ventilation through single-sided horizontal openings was performed in a full-scale laboratory test rig. The measurements were made for opening ratios L/D ranging from 0.027 to 4.455, where L and D are the length of the opening and the diameter of the opening, respectively. The basic nature of airflow through single-sided openings, including airflow rate, air velocity, temperature difference between the rooms and the dimensions...

Compound list: phenacetin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available phenacetin PCT 00138 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/phenacetin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/phenacetin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/phenacetin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/phenacetin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscienc

Compound list: imipramine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available imipramine IMI 00069 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/imipramine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/imipramine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/imipramine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/imipramine.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscienc

Compound list: ethinylestradiol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ethinylestradiol EE 00055 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hu...man/in_vitro/ethinylestradiol.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...T/Rat/in_vitro/ethinylestradiol.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...T/Rat/in_vivo/Liver/Single/ethinylestradiol.Rat.in_vivo.Liver.Single.zip ftp://ft...p.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/ethinylestradiol.Rat.in_vivo.Liver.Repeat.zip ftp:

Compound list: omeprazole [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available omeprazole OPZ 00012 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/omeprazole.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/omeprazole.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/omeprazole.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/omeprazole.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscienc

Compound list: nitrofurantoin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nitrofurantoin NFT 00020 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/nitrofurantoin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/nitrofurantoin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/nitrofurantoin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc...iencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/nitrofurantoin.Rat.in_vivo.Liver.Repeat.zip ftp:

Evidence-based severity assessment: Impact of repeated versus single open-field testing on welfare in C57BL/6J mice.

Science.gov (United States)

Bodden, Carina; Siestrup, Sophie; Palme, Rupert; Kaiser, Sylvia; Sachser, Norbert; Richter, S Helene

2018-01-15

According to current guidelines on animal experiments, a prospective assessment of the severity of each procedure is mandatory. However, so far, the classification of procedures into different severity categories mainly relies on theoretic considerations, since it is not entirely clear which of the various procedures compromise the welfare of animals, or, to what extent. Against this background, a systematic empirical investigation of the impact of each procedure, including behavioral testing, seems essential. Therefore, the present study was designed to elucidate the effects of repeated versus single testing on mouse welfare, using one of the most commonly used paradigms for behavioral phenotyping in behavioral neuroscience, the open-field test. In an independent groups design, laboratory mice (Mus musculus f. domestica) experienced either repeated, single, or no open-field testing - procedures that are assigned to different severity categories. Interestingly, testing experiences did not affect fecal corticosterone metabolites, body weights, elevated plus-maze or home cage behavior differentially. Thus, with respect to the assessed endocrinological, physical, and behavioral outcome measures, no signs of compromised welfare could be detected in mice that were tested in the open-field repeatedly, once, or, not at all. These findings challenge current classification guidelines and may, furthermore, stimulate systematic research on the severity of single procedures involving living animals. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel single fluorophore-labeled double-stranded oligonucleotide probe for fluorescence-enhanced nucleic acid detection based on the inherent quenching ability of deoxyguanosine bases and competitive strand-displacement reaction.

Science.gov (United States)

Zhang, Yingwei; Tian, Jingqi; Li, Hailong; Wang, Lei; Sun, Xuping

2012-01-01

We develop a novel single fluorophore-labeled double-stranded oligonucleotide (OND) probe for rapid, nanostructure-free, fluorescence-enhanced nucleic acid detection for the first time. We further demonstrate such probe is able to well discriminate single-base mutation in nucleic acid. The design takes advantage of an inherent quenching ability of guanine bases. The short strand of the probe is designed with an end-labeled fluorophore that is placed adjacent to two guanines as the quencher located on the long opposite strand, resulting in great quenching of dye fluorescence. In the presence of a target complementary to the long strand of the probe, a competitive strand-displacement reaction occurs and the long strand forms a more stable duplex with the target, resulting in the two strands of the probe being separated from each other. As a consequence of this displacement, the fluorophore and the quencher are no longer in close proximity and dye fluorescence increases, signaling the presence of target.

Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

Science.gov (United States)

Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

2017-02-09

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

Synthesis of a fluorine-18 labeled hypoxic cell sensitizer

International Nuclear Information System (INIS)

Jerabek, P.A.; Dischino, D.D.; Kilbourn, M.R.; Welch, M.J.

1984-01-01

The objective of this work was to synthesize a positron emitting radiosensitizing agent as a potential in vivo marker of hypoxic regions within tumors, and ischemic areas of the heart and brain. The method involved radiochemical synthesis of fluorine-18 labeled 1-(2-nitro-imidazolyl)-3-fluoro-2-propanol via nucleophilic ring opening of 1-(2,3-epoxypropyl)2-nitro-imidzole by fluorine-18 labeled tetrabutylammonium fluoride (TBAF). Fluroine-18 TBAF was prepared by the exchange reaction of TBAF with aqueous flourine-18 produced by proton bombardment of enriched oxygen-18 water. The aqueous solution was evaporated carefully by azeotropic distillation with acetonitrile. The fluorine-18 labeled TBAF was taken up in N,N-dimethylacetamide or dimethysulfoxide, then reacted with the episode at 60C for 30 minutes. Separation and identification of the fluorine-18 labeled products by high performance liquid chromatography showed a radioactive peak with a retention time identical to that of 1-(2-nitro-1-imidazolyl)-3-fluoro-2-propanol and a second radioactive peak with a retention time three minutes longer in addition to unreacted fluorine-18 labeled TBAF. The second radioactive peak may represent fluorine-18 labeled 1-2-nitro-1-imidazolyl)-2-fluoro-3-propanol. The average radiochemical yield from reactions run in N,N-dimethylacetamide using 20 micromoles of TBAF and 1-2 mg of the epoxide was l7% in a synthesis time of about 40 minutes. The synthesis of fluorohydrins by the reaction of fluorine-18 labeled TBAF on epoxides represents a new method for the preparation of fluorine-18 labeled fluorohydrins

Compound list: acetamidofluorene [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available acetamidofluorene AAF 00144 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/acetam...idofluorene.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/acetam...ATEST/Rat/in_vivo/Liver/Single/acetamidofluorene.Rat.in_vivo.Liver.Single.zip ftp...://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/acetamidofluorene.Rat.in_vivo.Liver.Repeat.zip ...

Compound list: famotidine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available famotidine FAM 00085 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/famotidine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/famotidine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/famotidine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: nifedipine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nifedipine NIF 00091 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/nifedipine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/nifedipine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/nifedipine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: perhexiline [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available perhexiline PH 00045 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/perhexiline.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_v...itro/perhexiline.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/L...iver/Single/perhexiline.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/a

Compound list: colchicine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available colchicine COL 00113 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/colchicine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/colchicine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/colchicine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: ranitidine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ranitidine RAN 00086 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/ranitidine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/ranitidine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/ranitidine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: nimesulide [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nimesulide NIM 00136 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/nimesulide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/nimesulide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/nimesulide.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: dantrolene [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available dantrolene DTL 00119 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/dantrolene.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/dantrolene.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/dantrolene.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: moxisylyte [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available moxisylyte MXS 00061 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/moxisylyte.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/moxisylyte.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/moxisylyte.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: iproniazid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available iproniazid IPA 00062 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/iproniazid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/iproniazid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/iproniazid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: methyldopa [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available methyldopa MDP 00056 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/methyldopa.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/methyldopa.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/methyldopa.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: mexiletine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available mexiletine MEX 00103 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/mexiletine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/mexiletine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/mexiletine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: lornoxicam [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available lornoxicam LNX 00125 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/lornoxicam.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/lornoxicam.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/lornoxicam.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: phalloidin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available phalloidin PHA 00A11 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/phalloidin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/phalloidin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/phalloidin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Compound list: cimetidine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available cimetidine CIM 00035 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/cimetidine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/cimetidine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/cimetidine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch

Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial.

Science.gov (United States)

Shaw, Alice T; Felip, Enriqueta; Bauer, Todd M; Besse, Benjamin; Navarro, Alejandro; Postel-Vinay, Sophie; Gainor, Justin F; Johnson, Melissa; Dietrich, Jorg; James, Leonard P; Clancy, Jill S; Chen, Joseph; Martini, Jean-François; Abbattista, Antonello; Solomon, Benjamin J

2017-12-01

Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, commonly within the CNS. This study aimed to analyse the safety, efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resistance mutations, in patients with advanced ALK-positive or ROS1-positive NSCLC. In this international multicentre, open-label, single-arm, first-in-man phase 1 dose-escalation study, eligible patients had advanced ALK-positive or ROS1-positive NSCLC and were older than 18 years, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate end-organ function. Lorlatinib was administered orally to patients at doses ranging from 10 mg to 200 mg once daily or 35 mg to 100 mg twice daily, with a minimum of three patients receiving each dose. For some patients, tumour biopsy was done before lorlatinib treatment to identify ALK resistance mutations. Safety was assessed in patients who received at least one dose of lorlatinib; efficacy was assessed in the intention-to-treat population (patients who received at least one dose of study treatment and had either ALK or ROS1 rearrangement). The primary endpoint was dose-limiting toxicities during cycle 1 according to investigator assessment; secondary endpoints included safety, pharmacokinetics, and overall response. This study is ongoing and is registered with ClinicalTrials.gov, number NCT01970865. Between Jan 22, 2014, and July 10, 2015, 54 patients received at least one dose of lorlatinib, including 41 (77%) with ALK-positive and 12 (23%) with ROS1-positive NSCLC; one patient had unconfirmed ALK and ROS1 status. 28 (52%) patients had received two or more TKIs, and 39 (72%) patients had CNS metastases. The most common treatment

Compound list: bucetin [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available bucetin BCT 00139 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_v...itro/bucetin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/bu...cetin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single.../bucetin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tgg...ates/LATEST/Rat/in_vivo/Liver/Repeat/bucetin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.biosciencedbc.jp/archive

The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study.

Science.gov (United States)

Dannon, P N; Iancu, I; Grunhaus, L

2002-10-01

Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line treatment for panic disorder, although up to 30% of patients either do not respond to SSRIs or withdraw due to adverse events. Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is effective in treating depression and may alleviate depression-related anxiety. This study aimed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs. In this 6-week, open-label study, 29 adult outpatients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day, titrated to a maximum of 8 mg/day over the first 10 days. Efficacy was assessed using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety (HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment of Functioning (GAF) Scale. The 24 patients who completed the study responded well to reboxetine treatment. Significant improvement (p < 0.001) was observed in the number of daily panic attacks, and on the scales measuring anxiety, depression and functioning. Reboxetine was generally well tolerated. Five patients withdrew due to adverse events. Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation. Copyright 2002 John Wiley & Sons, Ltd.

Use of Vitex agnus-castus in migrainous women with premenstrual syndrome: an open-label clinical observation.

Science.gov (United States)

Ambrosini, Anna; Di Lorenzo, Cherubino; Coppola, Gianluca; Pierelli, Francesco

2013-03-01

Premenstrual syndrome (PMS) affects most women during their reproductive life. Headache is regarded as a typical symptom of PMS and, close to menses, migrainous women could experience their worst migraine attacks. Vitex agnus-castus (VAC) is a phytopharmaceutical compound, considered worldwide to be a valid tool to treat PMS. Aim of this study is to explore if headache is ameliorate in migrainous women treated with VAC for PMS by an open-label clinical observation. Migrainous women with PMS were enrolled in the study and advised to assume a treatment with VAC (40 mg/day) for PMS for a 3-month period. Effects both on PMS and headache were assessed. Out of 107 women, 100 completed the 3-month treatment for PMS. Out of them, 66 women reported a dramatic reduction of PMS symptoms, 26 a mild reduction, and 8 no effect. Concerning migraine, 42 % of patients experienced a reduction higher than 50 % in frequency of monthly attacks, and 57 % of patients experienced a reduction higher than 50 % in monthly days with headache. No patients reported remarkable side effects. Pending a placebo-controlled trial to confirm our results, we observed that the use of VAC in migrainous women affected by PMS resulted to be safe and well tolerated, and may positively influence the frequency and duration of migraine attacks.

Optimal induced universal graphs and adjacency labeling for trees

DEFF Research Database (Denmark)

Alstrup, Stephen; Dahlgaard, Søren; Knudsen, Mathias Bæk Tejs

2015-01-01

bound. The lower bound and previously best upper bounds were presented in Alstrup and Rauhe (FOCS'02). Our upper bounds are obtained through a log2 n + O(1) labeling scheme for adjacency queries in forests. We hereby solve an open problem being raised repeatedly over decades, e.g. in Kannan, Naor...

An Open-Label, Multicenter Observational Study for Patients with Alzheimer’s Disease Treated with Memantine in the Clinical Practice

Directory of Open Access Journals (Sweden)

S.S. Stamouli

2011-01-01

Full Text Available Background/Aims: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer’s disease (AD. Methods: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE and the Instrumental Activities of Daily Living (IADL scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs were also recorded to evaluate the safety profile of memantine. Results: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≧1 ADRs, and treatment was discontinued due to ADR in 0.7%. Conclusion: Memantine was well tolerated and had a positive effect on the patient’s cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.

Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

Science.gov (United States)

Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

2017-08-01

Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

HaloTag protein-mediated specific labeling of living cells with quantum dots

International Nuclear Information System (INIS)

So, Min-kyung; Yao Hequan; Rao Jianghong

2008-01-01

Quantum dots emerge as an attractive alternative to small molecule fluorophores as fluorescent tags for in vivo cell labeling and imaging. This communication presents a method for specific labeling of live cells using quantum dots. The labeling is mediated by HaloTag protein expressed at the cell surface which forms a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be performed in one single step with quantum dot conjugates that are functionalized with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and followed by streptavidin coated quantum dots. Live cell fluorescence imaging indicates that the labeling is specific and takes place at the cell surface. This HaloTag protein-mediated cell labeling method should facilitate the application of quantum dots for live cell imaging

Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension.

Science.gov (United States)

Richeldi, Luca; Kreuter, Michael; Selman, Moisés; Crestani, Bruno; Kirsten, Anne-Marie; Wuyts, Wim A; Xu, Zuojun; Bernois, Katell; Stowasser, Susanne; Quaresma, Manuel; Costabel, Ulrich

2017-10-09

The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was -125.4 mL/year (95% CI -168.1 to -82.7) in the nintedanib group and -189.7 mL/year (95% CI -229.8 to -149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of self-citation by peer reviewers in a journal with single-blind peer review versus a journal with open peer review.

Science.gov (United States)

Levis, Alexander W; Leentjens, Albert F G; Levenson, James L; Lumley, Mark A; Thombs, Brett D

2015-12-01

Some peer reviewers may inappropriately, or coercively request that authors include references to the reviewers' own work. The objective of this study was to evaluate whether, compared to reviews for a journal with single-blind peer review, reviews for a journal with open peer review included (1) fewer self-citations; (2) a lower proportion of self-citations without a rationale; and (3) a lower ratio of proportions of citations without a rationale in self-citations versus citations to others' work. Peer reviews for published manuscripts submitted in 2012 to a single-blind peer review journal, the Journal of Psychosomatic Research, were previously evaluated (Thombs et al., 2015). These were compared to publically available peer reviews of manuscripts published in 2012 in an open review journal, BMC Psychiatry. Two investigators independently extracted data for both journals. There were no significant differences between journals in the proportion of all reviewer citations that were self-citations (Journal of Psychosomatic Research: 71/225, 32%; BMC Psychiatry: 90/315, 29%; p=.50), or in the proportion of self-citations without a rationale (Journal of Psychosomatic Research: 15/71, 21%; BMC Psychiatry: 12/90, 13%; p=.21). There was no significant difference between journals in the proportion of self-citations versus citations to others' work without a rationale (p=.31). Blind and open peer review methodologies have distinct advantages and disadvantages. The present study found that, in reasonably similar journals that use single-blind and open review, there were no substantive differences in the pattern of peer reviewer self-citations. Copyright © 2015 Elsevier Inc. All rights reserved.

Ultra-sensitive DNA assay based on single-molecule detection coupled with fluorescent quantum dot-labeling and its application to determination of messenger RNA

International Nuclear Information System (INIS)

Li Li; Li Xincang; Li Lu; Wang Jinxing; Jin Wenrui

2011-01-01

An ultra-sensitive single-molecule detection (SMD) method for quantification of DNA using total internal reflection fluorescence microscopy (TIRFM) coupled with fluorescent quantum dot (QD)-labeling was developed. In this method, the target DNA (tDNA) was captured by the capture DNA immobilized on the silanized coverslip blocked with ethanolamine and bovine serum albumin. Then, the QD-labeled probe DNA was hybridized to the tDNA. Ten fluorescent images of the QD-labeled sandwich DNA hybrids on the coverslip were taken by a high-sensitive CCD. The tDNA was quantified by counting the bright spots on the images using a calibration curve. The LOD of the method was 1 x 10 -14 mol L -1 . Several key factors, including image acquirement, fluorescence probe, substrate preparation, noise elimination from solutions and glass coverslips, and nonspecific adsorption and binding of solution-phase detection probes were discussed in detail. The method could be applied to quantify messenger RNA (mRNA) in cells. In order to determine mRNA, double-stranded RNA-DNA hybrids consisting of mRNA and corresponding cDNA were synthesized from the cellular mRNA template using reverse transcription in the presence of reverse transcriptase. After removing the mRNA in the double-stranded hybrids using ribonuclease, cDNA was quantified using the SMD-based TIRFM. Osteopontin mRNA in decidual stromal cells was chosen as the model analyte.

Double-labeled donor probe can enhance the signal of fluorescence resonance energy transfer (FRET) in detection of nucleic acid hybridization

Science.gov (United States)

Okamura, Yukio; Kondo, Satoshi; Sase, Ichiro; Suga, Takayuki; Mise, Kazuyuki; Furusawa, Iwao; Kawakami, Shigeki; Watanabe, Yuichiro

2000-01-01

A set of fluorescently-labeled DNA probes that hybridize with the target RNA and produce fluorescence resonance energy transfer (FRET) signals can be utilized for the detection of specific RNA. We have developed probe sets to detect and discriminate single-strand RNA molecules of plant viral genome, and sought a method to improve the FRET signals to handle in vivo applications. Consequently, we found that a double-labeled donor probe labeled with Bodipy dye yielded a remarkable increase in fluorescence intensity compared to a single-labeled donor probe used in an ordinary FRET. This double-labeled donor system can be easily applied to improve various FRET probes since the dependence upon sequence and label position in enhancement is not as strict. Furthermore this method could be applied to other nucleic acid substances, such as oligo RNA and phosphorothioate oligonucleotides (S-oligos) to enhance FRET signal. Although the double-labeled donor probes labeled with a variety of fluorophores had unexpected properties (strange UV-visible absorption spectra, decrease of intensity and decay of donor fluorescence) compared with single-labeled ones, they had no relation to FRET enhancement. This signal amplification mechanism cannot be explained simply based on our current results and knowledge of FRET. Yet it is possible to utilize this double-labeled donor system in various applications of FRET as a simple signal-enhancement method. PMID:11121494

40 Gbit/s NRZ Packet-Length Insensitive Header Extraction for Optical Label Switching Networks

DEFF Research Database (Denmark)

Seoane, Jorge; Kehayas, E; Avramopoulos, H.

2006-01-01

A simple method for 40 Gbit/s NRZ header extraction based on envelope detection for optical label switching networks is presented. The scheme is insensitive to packet length and spacing and can be single-chip integrated cost-effectively......A simple method for 40 Gbit/s NRZ header extraction based on envelope detection for optical label switching networks is presented. The scheme is insensitive to packet length and spacing and can be single-chip integrated cost-effectively...

Structure-guided approach to site-specific fluorophore labeling of the lac repressor LacI.

Directory of Open Access Journals (Sweden)

Kalle Kipper

Full Text Available The lactose operon repressor protein LacI has long served as a paradigm of the bacterial transcription factors. However, the mechanisms whereby LacI rapidly locates its cognate binding site on the bacterial chromosome are still elusive. Single-molecule fluorescence imaging approaches are well suited for the study of these mechanisms but rely on a functionally compatible fluorescence labeling of LacI. Particularly attractive for protein fluorescence labeling are synthetic fluorophores due to their small size and favorable photophysical characteristics. Synthetic fluorophores are often conjugated to natively occurring cysteine residues using maleimide chemistry. For a site-specific and functionally compatible labeling with maleimide fluorophores, the target protein often needs to be redesigned to remove unwanted native cysteines and to introduce cysteines at locations better suited for fluorophore attachment. Biochemical screens can then be employed to probe for the functional activity of the redesigned protein both before and after dye labeling. Here, we report a mutagenesis-based redesign of LacI to enable a functionally compatible labeling with maleimide fluorophores. To provide an easily accessible labeling site in LacI, we introduced a single cysteine residue at position 28 in the DNA-binding headpiece of LacI and replaced two native cysteines with alanines where derivatization with bulky substituents is known to compromise the protein's activity. We find that the redesigned LacI retains a robust activity in vitro and in vivo, provided that the third native cysteine at position 281 is retained in LacI. In a total internal reflection microscopy assay, we observed individual Cy3-labeled LacI molecules bound to immobilized DNA harboring the cognate O1 operator sequence, indicating that the dye-labeled LacI is functionally active. We have thus been able to generate a functional fluorescently labeled LacI that can be used to unravel mechanistic

Compound list: ajmaline [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available ajmaline AJM 00118 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/ajmaline....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/ajmaline....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/ajmaline.Rat.in_vivo.Liver.Single.zip ftp://ftp.bi...-tggates/LATEST/Rat/in_vivo/Liver/Repeat/ajmaline.Rat.in_vivo.Liver.Repeat.zip ...

LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia.

Science.gov (United States)

Magno, S; Ceccarini, G; Pelosini, C; Jaccheri, R; Vitti, J; Fierabracci, P; Salvetti, G; Airoldi, G; Minale, M; Saponati, G; Santini, F

2018-05-24

Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. LDL-C decreased by 23.3% during treatment with N (p ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. ClinicalTrials.gov ID: NCT03425630 .

An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

Directory of Open Access Journals (Sweden)

Si TM

2015-01-01

Full Text Available TianMei Si,1 QingRong Tan,2 KeRang Zhang,3 Yang Wang,4 Qing Rui4 1Peking University Institute of Mental health, Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, 2Fourth Military Medical University, First Hospital, Xi’an, 3Shanxi Medical University, First Hospital, Shanxi, 4Janssen Research and Development, Beijing, People’s Republic of China Background: Antipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER, an atypical anti­psychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis. Methods: In this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a Positive and Negative Syndrome Scale (PANSS total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day. The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP score from baseline to day 56 (8 weeks. Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.Results: Overall, 283 of 294 patients (96% achieved a ≥8-point increase in PSP (primary endpoint, analysis set. For the secondary efficacy endpoints, 284/306 patients (93% had a ≥30% reduction in PANSS total score; 266/306 patients (87% achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74% had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a

Label-free probing of genes by time-domain terahertz sensing

International Nuclear Information System (INIS)

Bolivar, P Haring; Brucherseifer, M; Nagel, M; Kurz, H; Bosserhoff, A; Buettner, R

2002-01-01

A label-free sensing approach for the label-free characterization of genetic material with terahertz (THz) electromagnetic waves is presented. Time-resolved THz analysis of polynucleotides demonstrates a strong dependence of the complex refractive index of DNA molecules in the THz frequency range on their hybridization state. By monitoring THz signals one can thus infer the binding state (hybridized or denatured) of oligo- and polynucleotides, enabling the label-free determination the genetic composition of unknown DNA sequences. A broadband experimental proof-of-principle in a free-space analytic configuration, as well as a higher-sensitivity approach using integrated THz sensors reaching femtomol detection levels and demonstrating the capability to detect single-base mutations, are presented. The potential application for next generation high-throughput label-free genetic analytic systems is discussed

Label-free probing of genes by time-domain terahertz sensing

Energy Technology Data Exchange (ETDEWEB)

Bolivar, P Haring [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Brucherseifer, M [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Nagel, M [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Kurz, H [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Bosserhoff, A [Institut fuer Pathologie, Universitaet Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg (Germany); Buettner, R [Institut fuer Pathologie, Universitaetsklinikum Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn (Germany)

2002-11-07

A label-free sensing approach for the label-free characterization of genetic material with terahertz (THz) electromagnetic waves is presented. Time-resolved THz analysis of polynucleotides demonstrates a strong dependence of the complex refractive index of DNA molecules in the THz frequency range on their hybridization state. By monitoring THz signals one can thus infer the binding state (hybridized or denatured) of oligo- and polynucleotides, enabling the label-free determination the genetic composition of unknown DNA sequences. A broadband experimental proof-of-principle in a free-space analytic configuration, as well as a higher-sensitivity approach using integrated THz sensors reaching femtomol detection levels and demonstrating the capability to detect single-base mutations, are presented. The potential application for next generation high-throughput label-free genetic analytic systems is discussed.

Label Review Training: Module 1: Label Basics, Page 21

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about types of labels.

Effects of rasagiline on freezing of gait in Parkinson's disease - an open-label, multicenter study.

Science.gov (United States)

Cibulcik, Frantisek; Benetin, Jan; Kurca, Egon; Grofik, Milan; Dvorak, Miloslav; Richter, Denis; Donath, Vladimir; Kothaj, Jan; Minar, Michal; Valkovic, Peter

2016-12-01

Freezing of gait is a disabling symptom in advanced Parkinson's disease. Positive effects have been suggested with MAO-B inhibitors. We report on an open label clinical study on the efficacy of rasagiline as add-on therapy on freezing of gait and quality of life in patients with Parkinson's disease. Forty two patients with freezing of gait were treated with 1 mg rasagiline daily as an add-on therapy. Patients were assessed at baseline and after 1, 2 and 3 months of treatment. Freezing of gait severity was assessed using the Freezing of Gait Questionnaire, motor impairment by the modified MDS UPDRS part III, and quality of life using the PDQ-39 questionnaire. Patients treated with rasagiline had a statistically significant decrease in FoG-Q score and modified MDS UPDRS score after 1, 2 and 3 months of therapy. A moderately strong (r = 0.686, P = 0.002) correlation between the effects on mobility and freezing of gait was found. We also observed a statistically significant improvement in global QoL and in the subscales mobility, ADL, stigma and bodily discomfort in patients after 3 months of rasagiline therapy. A significant correlation (r = 0.570, P = 0.02) between baseline FoG-Q score and the baseline score for the PDQ Mobility subscale was found. In our study rasagiline as add-on antiparkinsonian therapy significantly improved mobility, freezing of gait and quality of life. The positive effect on freezing of gait appears to be related to improvement of mobility.

Topical Ketamine 10% for Neuropathic Pain in Spinal Cord Injury Patients: An Open-Label Trial.

Science.gov (United States)

Rabi, Joseph; Minori, Joshua; Abad, Hasan; Lee, Ray; Gittler, Michelle

2016-01-01

Topical ketamine, an N-methyl-D-aspartate antagonist, has been shown to be effective in certain neuropathic pain syndromes. The objective of this study was to determine the efficacy of topical ketamine in spinal cord injury patients with neuropathic pain. An open label trial enrolled five subjects at an outpatient rehabilitation hospital with traumatic spinal cord injuries who had neuropathic pain at or below the level of injury. Subjects applied topical ketamine 10% three times a day for a two-week duration. Subjects recorded their numerical pain score-ranging from 0 to 10, with 0 representing "no pain, 5 representing "moderate pain," and 10 being described as "worst possible pain"-in a journal at the time of application of topical ketamine and one hour after application. Using a numerical pain scale allows for something as subjective as pain to be given an objective quantification. Subjects also recorded any occurrence of adverse events and level of satisfaction. All five subjects had a decrease in their numerical pain scale by the end of two weeks, ranging from 14% to 63%. The duration ranged from one hour in one subject to the next application in other subjects. There were no adverse effects. Overall, four out of the five subjects stated they were satisfied. Topical ketamine 10% is an effective neuropathic pain medicine in patients with spinal cord injuries; however, further studies need to be done with a placebo and larger sample size. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Thermodynamics of single polyethylene and polybutylene glycols with hydrogen-bonding ends: A transition from looped to open conformations

Science.gov (United States)

Lee, Eunsang; Paul, Wolfgang

2018-02-01

A variety of linear polymer precursors with hydrogen bonding motifs at both ends enable us to design supramolecular polymer systems with tailored macroscopic properties including self-healing. In this study, we investigate thermodynamic properties of single polyethylene and polybutylene glycols with hydrogen bonding motifs. In this context, we first build a coarse-grained model of building blocks of the supramolecular polymer system based on all-atom molecular structures. The density of states of the single precursor is obtained using the stochastic approximation Monte Carlo method. Constructing canonical partition functions from the density of states, we find the transition from looped to open conformations at transition temperatures which are non-monotonously changing with an increasing degree of polymerization due to the competition between chain stiffness and loop-forming entropy penalty. In the complete range of chain length under investigation, a coexistence of the looped and open morphologies at the transition temperature is shown regardless of whether the transition is first-order-like or continuous. Polyethylene and polybutylene glycols show similar behavior in all the thermodynamic properties but the transition temperature of the more flexible polybutylene glycol is shown to change more gradually.

Compound list: diethyl maleate [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available diethyl maleate DEM 00A05 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/diethyl_male.../Rat/in_vitro/diethyl_maleate.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/diethyl_maleate.Rat.in_vivo.Liver.Single.zip ... ...ate.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST

Compound list: buthionine sulfoximine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available buthionine sulfoximine BSO 00A04 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LA...TEST/Human/in_vitro/buthionine_sulfoximine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-...tggates/LATEST/Rat/in_vitro/buthionine_sulfoximine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive.../open-tggates/LATEST/Rat/in_vivo/Liver/Single/buthionine_sulfoximine.Rat.in_vivo.Liver.Single.zip ...

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about what labels require review.

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section covers supplemental distributor labeling.

Compound list: valproic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available valproic acid VPA 00005 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/valpr...oic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/valpr...oic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/valpr...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/valproic_acid.Rat.in_vivo.Liver.Repeat.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/valproic_acid.Rat.in_vivo.Kidne

Compound list: allyl alcohol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available allyl alcohol AA 00010 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/allyl_alcohol....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/allyl_alcohol...dbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/allyl_alcohol.Rat.in_vivo.Liver.Repeat.zip ftp:/.../ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/allyl_alcohol.Rat.in_vivo.Kidney....Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/allyl_alcohol.Rat.in_vivo.Kidney.Repeat.zip ...

Label Review Training: Module 1: Label Basics, Page 15

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the consequences of improper labeling.

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about positive effects from proper labeling.

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section discusses the types of labels.

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about mandatory and advisory label statements.

Scalable In-Band Optical Notch-Filter Labeling for Ultrahigh Bit Rate Optical Packet Switching

DEFF Research Database (Denmark)

Medhin, Ashenafi Kiros; Galili, Michael; Oxenløwe, Leif Katsuo

2014-01-01

We propose a scalable in-band optical notch-filter labeling scheme for optical packet switching of high-bit-rate data packets. A detailed characterization of the notch-filter labeling scheme and its effect on the quality of the data packet is carried out in simulation and verified by experimental...... demonstrations. The scheme is able to generate more than 91 different labels that can be applied to 640-Gb/s optical time division multiplexed packets causing an eye opening penalty of $1.2-dB. Experimental demonstration shows that up to 256 packets can be uniquely labeled by employing up to eight notch filters...... with only 0.9-dB power penalty to achieve BER of 1E-9. Using the proposed labeling scheme, optical packet switching of 640 Gb/s data packets is experimentally demonstrated in which two data packets are labeled by making none and one spectral hole using a notch filter and are switched using a LiNbO$_3...

The success of opening single chronic total occlusion lesions to improve myocardialviabilitytrial (SOS-COMEDY)

Science.gov (United States)

Huang, Rongchong; Song, Xiantao; Zhang, Haishan; Tian, Wen; Huang, Zheng; Zhang, Xingwei; Yang, Junqing; Zhang, Dongfeng; Wu, Jian; Zhong, Lei; Ting, Henry H.

2018-01-01

Abstract Aims: Success of opening single (SOS)-comedy is a prospective multicenter study to compare the improvement in the decrease of myocardial viability by percutaneous coronary intervention (PCI) with that by optimal medical therapy (OMT) alone in patients with chronic total occlusion (CTO) of a single coronary artery. Methods and results: The risks and the benefits of both options (PCI and OMT) were listed in a CTO decision aid (DA). Eligible participants detected by invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) were divided into PCI or OMT groups according to patients’ choice after shared-decision making process with DA. Participants will undergo positron emission tomography/computed tomography (PET/CT), cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE), and proceed to ICA and revascularization if possible. Blinded core laboratory interpretation will be performed for ICA, CCTA, PET/CT, CMR, and TTE. All participants will be followed up for 12 months. The primary endpoint is the improvement to the decrease of myocardial viability from baseline assessed with the use of PET/CT after 12-month follow-up. Conclusions: All of the patients are appropriately consented before enrolling in this study, which has been approved by the Ethics Committee. Results of SOS-COMEDY will be helpful to develop a strategy for single CTO patients. PMID:29668609

Label Review Training: Module 1: Label Basics, Page 24

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is about which labels require review.

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See examples of mandatory and advisory label statements.

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See an overview of the importance of labels.

A 6-week, multicenter, randomized, double-masked, parallel-group study comparing travoprost 0.004% to latanoprost 0.005% followed by 6-week, open-label treatment with travoprost 0.004%.

Science.gov (United States)

Maul, Eugenio; Carrasco, Félix Gil; Costa, Vital Paulino; Casiraghi, Javier F; Vargas, Enrique; Sarmina, Judith S; Mayol, Renato

2007-09-01

The aim of this study was to compare the tolerability and efficacy of once-daily travoprost 0.004% versus latanoprost 0.005% for 6 weeks followed by 6 weeks of once-daily travoprost 0.004% in decreasing intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). This multicenter, randomized, doublemasked, active-controlled, parallel-group trial was conducted at 32 centers across Latin America. Patients aged > or =18 years with OAG or OH were randomly assigned to receive topical travoprost 0.004% or latanoprost 0.005% 1 drop QD (9 PM) for 6 weeks (masked phase). At 6 weeks, all patients were assigned to receive open-label travoprost 0.004% 1 drop QD (9 PM) for 6 additional weeks (open-label phase). Study visits were scheduled at weeks 1, 2, 4, 6, 8, and 12. At each study visit, IOP was measured at 5 PM (+/-1 hour; approximately 20 hours after study drug administration). IOP changes from baseline were combined (pooled) from the 1-, 2-, 4-, and 6-week data to provide a comparison between the 2 treatment groups. Ocular adverse events (AEs) were monitored using slit-lamp examination. A total of 302 patients were enrolled (travoprost group, 155 patients; latanoprost group, 147 patients). The mean (SD) age of the travoprost group was 61.9 (10.6) years; 60.6% were female; and 47.1% were white. The mean (SD) age of the latanoprost group was 60.5 (12.4) years; 62.6% were female; and 49.0% were white. Mean IOP values were not significantly different between the travoprost and latanoprost groups at baseline (24.7 vs 24.2 mm Hg) or 6 weeks; however, the between-group difference in reductions from baseline in pooled IOP during the masked phase of the study was statistically significant (-8.3 vs -7.5 mm Hg; P = 0.009). At weeks 6 and 12, mean lOP levels were 16.1 and 16.2 mm Hg, respectively, in the travoprost group and 16.4 and 16.1 mm Hg in the group that was switched from latanoprost to travoprost (all, P = NS). The most common ocular AEs

Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics

Science.gov (United States)

Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C.; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

2017-03-01

Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

Label Review Training: Module 1: Label Basics, Page 23

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Lists types of labels that do not require review.

Calorie-labelling in catering outlets: acceptability and impacts on food sales.

Science.gov (United States)

Nikolaou, Charoula K; Lean, Michael E J; Hankey, Catherine R

2014-10-01

Obesity is the biggest challenge facing preventive medicine. Calorie-labelling has been suggested as a way of changing the architecture of an 'obesogenic' environment without limiting consumer choice. This study examined the effect of calorie-labelling on sales of food items at catering outlets on a city-centre university campus. Sales data were collected for two consecutive months in 2013 on three UK university sites (two with calorie-labelling during second month, one control) and analysed with chi-square 'Goodness-of-Fit' tests. A questionnaire seeking consumers' views and use of the calorie-labelling was administered and analysed at group-level with chi-square tests. In intervention vs control sites, total sales of all labelled items fell significantly (-17% vs -2%, p<0.001) for the month with calorie-labelling. Calorie-labelling was associated with substantially reduced sales of high-calorie labelled items, without any compensatory changes in unlabelled alternative items. Among 1166 student- and 646 staff-respondents, 56% reported using the calorie-labels, 97% of them to make lower-calorie choices. More females (63%) than males (40%) reported being influenced by calorie-labels when choosing foods (p=0.01). This study provides evidence, beyond that from single-meal exposures, for the acceptability of meal calorie-labelling and its potential as an effective low-cost anti-obesity measure. Copyright © 2014 Elsevier Inc. All rights reserved.

Technetium-99m-HMPAO labeled leukocyte single photon emission computerized tomography (SPECT) for assessing Crohn's disease extent and intestinal infiltration.

Science.gov (United States)

Biancone, L; Schillaci, O; Capoccetti, F; Bozzi, R M; Fina, D; Petruzziello, C; Geremia, A; Simonetti, G; Pallone, F

2005-02-01

Scintigraphy using radiolabeled leukocytes is a useful technique for assessing intestinal infiltration in Crohn's disease (CD). However, limits of planar images include overlapping activity in other organs and low specificity. To investigate the usefulness of (99m)Tc-HMPAO (hexametyl propylene amine oxime) labeled leukocyte single photon emission computerized tomography (SPECT) for assessing CD lesions, in comparison with planar images. Twenty-two inflammatory bowel disease patients (19 CD; 2 ulcerative colitis, UC; 1 ileal pouch) assessed by conventional endoscopy or radiology were enrolled. Leukocytes were labeled with (99m)Tc-HMPAO. SPECT images were acquired at 2 h and planar images at 30 min and 2 h. Bowel uptake was quantitated in nine regions (score 0-3). Both SPECT and planar images detected a negative scintigraphy (score 0) in the UC patient with no pouchitis and a positive scintigraphy (score 1-3) in the 21 patients showing active inflammation by conventional techniques. SPECT showed a higher global score than planar images (0.71 +/- 0.09 vs 0.30 +/- 0.05; p < 0.001), and in particular in the right iliac fossa (p= 0.003), right and left flank (p < 0.001; p= 0.02), hypogastrium (p= 0.002), and mesogastrium (p < 0.001). SPECT provided a better visualization and a higher uptake than planar images in patients with ileal and ileocolonic CD (6.45 +/- 0.82 vs 2.8 +/- 0.55, p < 0.001; 5.5 +/- 1.6 vs 2.6 +/- 0.7, p= 0.03), and with perianal CD (6.6 +/- 1.6 vs 3.4 +/- 1.2; p= 0.03). (99m)Tc-HMPAO labeled leukocyte SPECT provides a more detailed visualization of CD lesions than planar images. This technique may better discriminate between intestinal and bone marrow uptake, thus being useful for assessing CD lesions within the pelvis, including perianal disease.

Enzymatically Generated CRISPR Libraries for Genome Labeling and Screening.

Science.gov (United States)

Lane, Andrew B; Strzelecka, Magdalena; Ettinger, Andreas; Grenfell, Andrew W; Wittmann, Torsten; Heald, Rebecca

2015-08-10

CRISPR-based technologies have emerged as powerful tools to alter genomes and mark chromosomal loci, but an inexpensive method for generating large numbers of RNA guides for whole genome screening and labeling is lacking. Using a method that permits library construction from any source of DNA, we generated guide libraries that label repetitive loci or a single chromosomal locus in Xenopus egg extracts and show that a complex library can target the E. coli genome at high frequency. Copyright © 2015 Elsevier Inc. All rights reserved.

Label Review Training: Module 1: Label Basics, Page 16

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This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the importance of labels and the role in enforcement.

Single-Molecule Plasmon Sensing: Current Status and Future Prospects.

Science.gov (United States)

Taylor, Adam B; Zijlstra, Peter

2017-08-25

Single-molecule detection has long relied on fluorescent labeling with high quantum-yield fluorophores. Plasmon-enhanced detection circumvents the need for labeling by allowing direct optical detection of weakly emitting and completely nonfluorescent species. This review focuses on recent advances in single molecule detection using plasmonic metal nanostructures as a sensing platform, particularly using a single particle-single molecule approach. In the past decade two mechanisms for plasmon-enhanced single-molecule detection have been demonstrated: (1) by plasmonically enhancing the emission of weakly fluorescent biomolecules, or (2) by monitoring shifts of the plasmon resonance induced by single-molecule interactions. We begin with a motivation regarding the importance of single molecule detection, and advantages plasmonic detection offers. We describe both detection mechanisms and discuss challenges and potential solutions. We finalize by highlighting the exciting possibilities in analytical chemistry and medical diagnostics.

Feasibility study of a single-element transcranial focused ultrasound system for blood-brain barrier opening

Science.gov (United States)

Marquet, Fabrice; Tung, Yao-Sheng; Teichert, Tobias; Ferrera, Vincent P.; Konofagou, Elisa E.

2012-10-01

The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent CNS disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. The study addresses the focusing properties of single-element transducers at intermediate frequencies (500 kHz) through primate and human skulls, targeting clinically relevant targets extracted from 3D brain atlases such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. A preliminary in vivo study was performed to study the frequency dependence of BBB opening parameters in mice. Then, feasibility of transcranial ME-FUS BBB opening in non-human primates was demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (custom made 4-5 μm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage.

Efficient Multi-Label Feature Selection Using Entropy-Based Label Selection

Directory of Open Access Journals (Sweden)

Jaesung Lee

2016-11-01

Full Text Available Multi-label feature selection is designed to select a subset of features according to their importance to multiple labels. This task can be achieved by ranking the dependencies of features and selecting the features with the highest rankings. In a multi-label feature selection problem, the algorithm may be faced with a dataset containing a large number of labels. Because the computational cost of multi-label feature selection increases according to the number of labels, the algorithm may suffer from a degradation in performance when processing very large datasets. In this study, we propose an efficient multi-label feature selection method based on an information-theoretic label selection strategy. By identifying a subset of labels that significantly influence the importance of features, the proposed method efficiently outputs a feature subset. Experimental results demonstrate that the proposed method can identify a feature subset much faster than conventional multi-label feature selection methods for large multi-label datasets.

Compound list: methylene dianiline [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available methylene dianiline DAPM 00155 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/methyle...es/LATEST/Rat/in_vivo/Liver/Single/methylene_dianiline.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc....jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/methylene_dianiline.Rat.in_vivo.Liver.Repeat.zip ... ...ne_dianiline.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggat

Compound list: tannic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available tannic acid TAN 00093 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/tannic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/tannic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/tannic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/

Compound list: mefenamic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available mefenamic acid MEF 00084 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/mefenamic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/mefenamic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/mefenamic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc

Compound list: nicotinic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nicotinic acid NIC 00081 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/nicotinic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/nicotinic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/nicotinic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc

Single-base resolution and long-coverage sequencing based on single-molecule nanomanipulation

International Nuclear Information System (INIS)

An Hongjie; Huang Jiehuan; Lue Ming; Li Xueling; Lue Junhong; Li Haikuo; Zhang Yi; Li Minqian; Hu Jun

2007-01-01

We show new approaches towards a novel single-molecule sequencing strategy which consists of high-resolution positioning isolation of overlapping DNA fragments with atomic force microscopy (AFM), subsequent single-molecule PCR amplification and conventional Sanger sequencing. In this study, a DNA labelling technique was used to guarantee the accuracy in positioning the target DNA. Single-molecule multiplex PCR was carried out to test the contamination. The results showed that the two overlapping DNA fragments isolated by AFM could be successfully sequenced with high quality and perfect contiguity, indicating that single-base resolution and long-coverage sequencing have been achieved simultaneously

EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

Science.gov (United States)

Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

2016-11-01

Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

Multi-label Learning with Missing Labels Using Mixed Dependency Graphs

KAUST Repository

Wu, Baoyuan; Jia, Fan; Liu, Wei; Ghanem, Bernard; Lyu, Siwei

2018-01-01

This work focuses on the problem of multi-label learning with missing labels (MLML), which aims to label each test instance with multiple class labels given training instances that have an incomplete/partial set of these labels (i.e., some

Synthesis of specifically labelled L-phenylalanines using phenylalanine ammonia lyase activity

International Nuclear Information System (INIS)

Haedener, A.; Tamm, Ch.

1987-01-01

Specifically labelled L-phenylalanines have been prepared using a variety of classical synthetic methods in combination with phenylalanine ammonia lyase (PAL) enzyme activity of the yeast Rhodosporidium toruloides ATCC 10788 or Rhodotorula glutinis IFO 0559, respectively. Thus, L-[2- 2 H]phenyl-[2- 2 H]alanine was formed from (E) -[2,2'- 2 H 2 ]cinnamic acid and ammonia in 46% yield, whereas L-phenyl-[2- 13 C, 15 N]alanine was obtained from (E)-[2- 13 C]cinnamic acid in 45% overall yield. Generally, labelled cinnamic acids were recovered in pure form from the reaction mixture, with a loss of 6-8%. Likewise, unchanged 15 NH 3 was reisolated as 15 NH 4 Cl after steam distillation with overall losses of less than 4%. Labelled cinnamic acids were prepared by Knoevenagel condensations between appropriately labelled benzaldehydes and malonic acids. [2- 2 H]Benzaldehyde was obtained from 2-bromotoluene by decomposition of the corresponding Grignard reagent with 2 H 2 O and subsequent oxidation. Since simple molecules, most of them commercially available in labelled form or otherwise easily accessible, may serve as starting material, and due to its defined stereochemistry, the reaction catalysed by PAL opens a short and attractive route to specifically labelled L-phenylalanines. (author)

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings.

Science.gov (United States)

Dittmann, Ralf W; Wehmeier, Peter M; Schacht, Alexander; Lehmann, Martin; Lehmkuhl, Gerd

2009-12-01

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12-17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD. © The Author(s) 2009. This article is published with open access at Springerlink.com

Electron Paramagnetic Resonance of a Single NV Nanodiamond Attached to an Individual Biomolecule.

Science.gov (United States)

Teeling-Smith, Richelle M; Jung, Young Woo; Scozzaro, Nicolas; Cardellino, Jeremy; Rampersaud, Isaac; North, Justin A; Šimon, Marek; Bhallamudi, Vidya P; Rampersaud, Arfaan; Johnston-Halperin, Ezekiel; Poirier, Michael G; Hammel, P Chris

2016-05-10

Electron paramagnetic resonance (EPR), an established and powerful methodology for studying atomic-scale biomolecular structure and dynamics, typically requires in excess of 10(12) labeled biomolecules. Single-molecule measurements provide improved insights into heterogeneous behaviors that can be masked in ensemble measurements and are often essential for illuminating the molecular mechanisms behind the function of a biomolecule. Here, we report EPR measurements of a single labeled biomolecule. We selectively label an individual double-stranded DNA molecule with a single nanodiamond containing nitrogen-vacancy centers, and optically detect the paramagnetic resonance of nitrogen-vacancy spins in the nanodiamond probe. Analysis of the spectrum reveals that the nanodiamond probe has complete rotational freedom and that the characteristic timescale for reorientation of the nanodiamond probe is slow compared with the transverse spin relaxation time. This demonstration of EPR spectroscopy of a single nanodiamond-labeled DNA provides the foundation for the development of single-molecule magnetic resonance studies of complex biomolecular systems. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Long-term changes in open field behaviour following a single social defeat in rats can be reversed by sleep deprivation

NARCIS (Netherlands)

Meerlo, P; Overkamp, GJF; Benning, MA; Koolhaas, JM; vandenHoofdakker, RH

1996-01-01

The long-term consequences of a single social defeat on open field behaviour in rats were studied, with special emphasis on the time course of stress-induced changes. Animals were subjected to social defeat by placing them into the territory of an aggressive male conspecific for 1 h. After the

Tritium labeling of detonation nanodiamonds.

Science.gov (United States)

Girard, Hugues A; El-Kharbachi, Abdelouahab; Garcia-Argote, Sébastien; Petit, Tristan; Bergonzo, Philippe; Rousseau, Bernard; Arnault, Jean-Charles

2014-03-18

For the first time, the radioactive labeling of detonation nanodiamonds was efficiently achieved using a tritium microwave plasma. According to our measurements, the total radioactivity reaches 9120 ± 120 μCi mg(-1), with 93% of (3)H atoms tightly bonded to the surface and up to 7% embedded into the diamond core. Such (3)H doping will ensure highly stable radiolabeled nanodiamonds, on which surface functionalization is still allowed. This breakthrough opens the way to biodistribution and pharmacokinetics studies of nanodiamonds, while this approach can be scalable to easily treat bulk quantities of nanodiamonds at low cost.

Ultra-sensitive DNA assay based on single-molecule detection coupled with fluorescent quantum dot-labeling and its application to determination of messenger RNA

Energy Technology Data Exchange (ETDEWEB)

Li Li [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Li Xincang [School of Life Sciences, Shandong University, Jinan 250100 (China); Li Lu [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Wang Jinxing [School of Life Sciences, Shandong University, Jinan 250100 (China); Jin Wenrui, E-mail: jwr@sdu.edu.cn [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China)

2011-01-24

An ultra-sensitive single-molecule detection (SMD) method for quantification of DNA using total internal reflection fluorescence microscopy (TIRFM) coupled with fluorescent quantum dot (QD)-labeling was developed. In this method, the target DNA (tDNA) was captured by the capture DNA immobilized on the silanized coverslip blocked with ethanolamine and bovine serum albumin. Then, the QD-labeled probe DNA was hybridized to the tDNA. Ten fluorescent images of the QD-labeled sandwich DNA hybrids on the coverslip were taken by a high-sensitive CCD. The tDNA was quantified by counting the bright spots on the images using a calibration curve. The LOD of the method was 1 x 10{sup -14} mol L{sup -1}. Several key factors, including image acquirement, fluorescence probe, substrate preparation, noise elimination from solutions and glass coverslips, and nonspecific adsorption and binding of solution-phase detection probes were discussed in detail. The method could be applied to quantify messenger RNA (mRNA) in cells. In order to determine mRNA, double-stranded RNA-DNA hybrids consisting of mRNA and corresponding cDNA were synthesized from the cellular mRNA template using reverse transcription in the presence of reverse transcriptase. After removing the mRNA in the double-stranded hybrids using ribonuclease, cDNA was quantified using the SMD-based TIRFM. Osteopontin mRNA in decidual stromal cells was chosen as the model analyte.

Selective labeling of a single organelle by using two-photon conversion of a photoconvertible fluorescent protein

Science.gov (United States)

Watanabe, Wataru; Shimada, Tomoko; Matsunaga, Sachihiro; Kurihara, Daisuke; Arimura, Shin-ichi; Tsutsumi, Nobuhiro; Fukui, Kiichi; Itoh, Kazuyoshi

2008-02-01

We present space-selective labeling of organelles by using two-photon conversion of a photoconvertible fluorescent protein with near-infrared femtosecond laser pulses. Two-photon excitation of photoconvertible fluorescent-protein, Kaede, enables space-selective labeling of organelles. We alter the fluorescence of target mitochondria in a tobacco BY-2 cell from green to red by focusing femtosecond laser pulses with a wavelength of 750 nm.

Detection of myocardial ischemia before infarction, based on accumulation of labeled pyruvate

International Nuclear Information System (INIS)

Goldstein, R.A.; Klein, M.S.; Sobel, B.E.

1980-01-01

To determine whether ischemic, but not irreversibly injured myocardium, can be differentiated from normal tissue based on accumulation of labeled pyruvate, isolated hearts were perfused with buffer containing [ 14 C]pyruvate under conditions of normal or low flow. Fifteen minutes after the hearts were exposed to labeled material, myocardial radioactivity was fourfold greater in ischemic compared to control hearts, due to accumulation of label in sequestered lactate produced from the pyruvate. Open-chest rabbits subjected to coronary occlusion exhibited a 1.73:1 ratio of radioactivity in ischemic compared with normal myocardium 15 min after systemic injection of [ 14 C]pyruvate. The results obtained suggest that zones of myocardial ischemia should be detectable in vivo by positron tomography after systemic administration of [ 11 C]pyruvate as well

Multi-label Learning with Missing Labels Using Mixed Dependency Graphs

KAUST Repository

Wu, Baoyuan

2018-04-06

This work focuses on the problem of multi-label learning with missing labels (MLML), which aims to label each test instance with multiple class labels given training instances that have an incomplete/partial set of these labels (i.e., some of their labels are missing). The key point to handle missing labels is propagating the label information from the provided labels to missing labels, through a dependency graph that each label of each instance is treated as a node. We build this graph by utilizing different types of label dependencies. Specifically, the instance-level similarity is served as undirected edges to connect the label nodes across different instances and the semantic label hierarchy is used as directed edges to connect different classes. This base graph is referred to as the mixed dependency graph, as it includes both undirected and directed edges. Furthermore, we present another two types of label dependencies to connect the label nodes across different classes. One is the class co-occurrence, which is also encoded as undirected edges. Combining with the above base graph, we obtain a new mixed graph, called mixed graph with co-occurrence (MG-CO). The other is the sparse and low rank decomposition of the whole label matrix, to embed high-order dependencies over all labels. Combining with the base graph, the new mixed graph is called as MG-SL (mixed graph with sparse and low rank decomposition). Based on MG-CO and MG-SL, we further propose two convex transductive formulations of the MLML problem, denoted as MLMG-CO and MLMG-SL respectively. In both formulations, the instance-level similarity is embedded through a quadratic smoothness term, while the semantic label hierarchy is used as a linear constraint. In MLMG-CO, the class co-occurrence is also formulated as a quadratic smoothness term, while the sparse and low rank decomposition is incorporated into MLMG-SL, through two additional matrices (one is assumed as sparse, and the other is assumed as low

9 CFR 381.125 - Special handling label requirements.

Science.gov (United States)

2010-01-01

... AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY.... The safe handling information shall be set off by a border and shall be one color type printed on a single color contrasting background whenever practical. (2) (i) The labels of the poultry products...

Label-free detection of DNA hybridization using carbon nanotube network field-effect transistors

Science.gov (United States)

Star, Alexander; Tu, Eugene; Niemann, Joseph; Gabriel, Jean-Christophe P.; Joiner, C. Steve; Valcke, Christian

2006-01-01

We report carbon nanotube network field-effect transistors (NTNFETs) that function as selective detectors of DNA immobilization and hybridization. NTNFETs with immobilized synthetic oligonucleotides have been shown to specifically recognize target DNA sequences, including H63D single-nucleotide polymorphism (SNP) discrimination in the HFE gene, responsible for hereditary hemochromatosis. The electronic responses of NTNFETs upon single-stranded DNA immobilization and subsequent DNA hybridization events were confirmed by using fluorescence-labeled oligonucleotides and then were further explored for label-free DNA detection at picomolar to micromolar concentrations. We have also observed a strong effect of DNA counterions on the electronic response, thus suggesting a charge-based mechanism of DNA detection using NTNFET devices. Implementation of label-free electronic detection assays using NTNFETs constitutes an important step toward low-cost, low-complexity, highly sensitive and accurate molecular diagnostics. hemochromatosis | SNP | biosensor

Compound list: 2-nitrofluorene [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available 2-nitrofluorene 2NF 00160 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/2-nitroflu...orene.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/2-nitrofluorene.Rat.in_vivo.Liver.Single.zip ...

Compound list: N-nitrosomorpholine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available N-nitrosomorpholine NMOR 00163 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...es/LATEST/Rat/in_vivo/Liver/Single/N-nitrosomorpholine.Rat.in_vivo.Liver.Single.zip ... ...ST/Human/in_vitro/N-nitrosomorpholine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggat

A universal and label-free impedimetric biosensing platform for discrimination of single nucleotide substitutions in long nucleic acid strands.