A microneedle patch containing measles vaccine is immunogenic in non-human primates.

Science.gov (United States)

Edens, Chris; Collins, Marcus L; Goodson, James L; Rota, Paul A; Prausnitz, Mark R

2015-09-08

Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Nucleosome Acidic Patch Regulates the H2B K123 Monoubiquitylation Cascade and Transcription Elongation in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Christine E Cucinotta

2015-08-01

Full Text Available Eukaryotes regulate gene expression and other nuclear processes through the posttranslational modification of histones. In S. cerevisiae, the mono-ubiquitylation of histone H2B on lysine 123 (H2B K123ub affects nucleosome stability, broadly influences gene expression and other DNA-templated processes, and is a prerequisite for additional conserved histone modifications that are associated with active transcription, namely the methylation of lysine residues in H3. While the enzymes that promote these chromatin marks are known, regions of the nucleosome required for the recruitment of these enzymes are undefined. To identify histone residues required for H2B K123ub, we exploited a functional interaction between the ubiquitin-protein ligase, Rkr1/Ltn1, and H2B K123ub in S. cerevisiae. Specifically, we performed a synthetic lethal screen with cells lacking RKR1 and a comprehensive library of H2A and H2B residue substitutions, and identified H2A residues that are required for H2B K123ub. Many of these residues map to the nucleosome acidic patch. The substitutions in the acidic patch confer varying histone modification defects downstream of H2B K123ub, indicating that this region contributes differentially to multiple histone modifications. Interestingly, substitutions in the acidic patch result in decreased recruitment of H2B K123ub machinery to active genes and defects in transcription elongation and termination. Together, our findings reveal a role for the nucleosome acidic patch in recruitment of histone modification machinery and maintenance of transcriptional integrity.

Design and in vivo evaluation of a patch system based on thiolated polymers.

Science.gov (United States)

Hoyer, Herbert; Greindl, Melanie; Bernkop-Schnürch, Andreas

2009-02-01

A new oral patch delivery system has been designed to increase the overall oral bioavailability of drugs within the gastrointestinal tract. The patch system consists of four layered films: a mucoadhesive matrix layer, a water insoluble backing layer, a middle layer and an enteric surface layer. The separation layer between the two matrix layers contained lactose, starch and confectioners' sugar. The matrix layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, comprised Polycarbophil-cysteine conjugate (49%), fluoresceine isothiocyanate-dextran (26%), glutathione (5%), and mannitol (20%). A standard tablet formulation consisting of the same matrix served as control. Entire fluoresceine isothiocyanate-dextran (FD(4)) was released from the delivery system within 2 h. For in vivo studies patch systems were administered orally to male Sprague-Dawley rats. Maximum FD(4) concentration in blood of the patch system was 46.1 +/- 8.9 ng/mL and was reached 3 h after administration. In contrast c(max) of control tablets displayed 50.5 +/- 14.9 ng/mL after 2 h and the absorption of FD(4) after administration in oral solution was negligible. The absolute bioavailability of orally administered patch systems and control tablets was 0.54% and 0.32% respectively. Results of this study indicate that a prolonged and higher oral bioavailability of FD(4) is obtained with patches than with tablets.

Heterologous, Fresh, Human Donor Sclera as Patch Graft Material in Glaucoma Drainage Device Surgery.

Science.gov (United States)

Tsoukanas, Dimitrios; Xanthopoulou, Paraskevi; Charonis, Alexandros C; Theodossiadis, Panagiotis; Kopsinis, Gerasimos; Filippopoulos, Theodoros

2016-07-01

To determine the safety and efficacy of fresh, human sclera allografts as a patch graft material in glaucoma drainage device (GDD) surgery. Retrospective, noncomparative, interventional, consecutive case series. All GDD cases operated between 2008 and 2013 in which fresh human corneoscleral rims were used immediately after the central corneal button was used for penetrating or endothelial keratoplasty. Surgery was performed by 2 surgeons at 2 facilities. The Ahmed Glaucoma Valve (FP-7) was used exclusively in this cohort. Sixty-four eyes of 60 patients were identified; demographic data were recorded along with intraocular pressure (IOP), medication requirements, visual acuity, complications, and subsequent interventions. Incidence of complications. IOP and medication requirements at the last follow-up. Quilified success utilizing Tube Versus Trabeculectomy study criteria. The mean age of the cohort was 66.2±19.1 years; the average preoperative IOP was 33.2±11.1 mm Hg on 4.2±1.3 IOP-lowering agents before GDD surgery. IOP decreased significantly to 14.1±4.7 mm Hg (Pendophthalmitis, and there was 1 case of conjunctival erosion and tube/plate exposure (1.6%) occurring 30 days after surgery. Qualified success was estimated as 90.5% and 81% at 1 and 2 years, respectively, using Tube Versus Trabeculectomy study criteria. Heterologous, fresh, human donor sclera appears to be a safe material for GDD tube coverage. It provides a cost-efficient alternative compared with traditional patch graft materials associated with a low risk of pathogen transmission.

Immunophenotyping of the cutaneous cellular infiltrate after atopy patch testing in cats with atopic dermatitis.

Science.gov (United States)

Roosje, P J; Thepen, T; Rutten, V P M G; van den Brom, W E; Bruijnzeel-Koomen, C A F M; Willemse, T

2004-10-01

Cats with spontaneously occurring atopic dermatitis have clinical and immunocytochemical characteristics compatible with these in humans with atopic dermatitis (AD). The atopy patch test (APT) has proven to be a valuable tool in elucidating the disease process in humans. Additionally, the APT is very specific and bypasses the problem of conflicting results due to differences in chronicity of lesions of AD patients. We adapted the APT for use in cats to explore the suitability of the APT as a tool to study the onset of allergic inflammation in cats with atopic dermatitis. APT were performed in AD cats (n = 6) and healthy cats (n = 10). All cats were patch tested with two allergens in three different dilutions and a diluent control. The allergens for the APT were selected from positive intradermal test and /or prick test results and consisted of: Dermatophagoides farinae, D. pteronyssinus, Tyrophagus putrescentiae, and a grass pollen mixture. APT were read after 10, 24 and 48 h, and punch biopsies for immunohistochemical evaluation were collected at these time points. Macroscopically positive APT reactions were observed in three out of six cats at 24 and/or 48 h with allergen concentrations of 25,000 and 100,000 NU/ml. Reactions were not observed at negative control sites and neither in control animals. A significantly increased number of IL-4+, CD4+, CD3+, MHC class II+ and CD1a+ cells was found in one AD cat with positive APT reactions. Five out of six AD cats had significantly increased IL-4+ T cell numbers at 24 and/or 48 h. Our data indicate that in cats, macroscopically positive patch test reactions can be induced, which have a cellular infiltrate similar to that in lesional skin. We found a high specificity and a macroscopically positive APT reaction in half of the cats, which is similar to what is seen in humans. Hence, the APT in cats might be a useful tool in studying the immunopathogenesis of feline atopic dermatitis.

Successful application of large microneedle patches by human volunteers

OpenAIRE

Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F.

2017-01-01

We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600??m), were prepared from aqueous blends of 15% w/w Gantrez? S97 and 7.5% w/w poly(ethyleneglycol) 10,000?Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500??m. Ten human volunteers successfully self-inserted the microneedl...

High-Content Electrophysiological Analysis of Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs).

Science.gov (United States)

Kong, Chi-Wing; Geng, Lin; Li, Ronald A

2018-01-01

Considerable interest has been raised to develop human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as a model for drug discovery and cardiotoxicity screening. High-content electrophysiological analysis of currents generated by transmembrane cell surface ion channels has been pursued to complement such emerging applications. Here we describe practical procedures and considerations for accomplishing successful assays of hPSC-CMs using an automated planar patch-clamp system.

In silico modeling techniques for predicting the tertiary structure of human H4 receptor.

Science.gov (United States)

Zaid, Hilal; Raiyn, Jamal; Osman, Midhat; Falah, Mizied; Srouji, Samer; Rayan, Anwar

2016-01-01

First cloned in 2000, the human Histamine H4 Receptor (hH4R) is the last member of the histamine receptors family discovered so far, it belongs to the GPCR super-family and is involved in a wide variety of immunological and inflammatory responses. Potential hH4R antagonists are proposed to have therapeutic potential for the treatment of allergies, inflammation, asthma and colitis. So far, no hH4R ligands have been successfully introduced to the pharmaceutical market, which creates a strong demand for new selective ligands to be developed. in silico techniques and structural based modeling are likely to facilitate the achievement of this goal. In this review paper we attempt to cover the fundamental concepts of hH4R structure modeling and its implementations in drug discovery and development, especially those that have been experimentally tested and to highlight some ideas that are currently being discussed on the dynamic nature of hH4R and GPCRs, in regards to computerized techniques for 3-D structure modeling.

Rabies vaccination in dogs using a dissolving microneedle patch.

Science.gov (United States)

Arya, Jaya M; Dewitt, Kristopher; Scott-Garrard, Maya; Chiang, Yu-Wei; Prausnitz, Mark R

2016-10-10

Because humans get rabies primarily through dog bites, stray dog population control and mass or mandatory vaccination of domestic dogs and other animals has virtually eliminated human rabies in industrialized countries. However, thousands of people in developing countries die of rabies each year due to the inability to control dog populations and implement mass vaccination because of financial, logistical and other challenges. The availability of an easier-to-administer and more cost-effective vaccine may help to address some of these issues. Here, we propose the use of dissolving microneedle patches for simple and potentially cost-effective rabies vaccination, and assess the safety and immunogenicity of microneedle patch vaccination using a rabies DNA vaccine in dogs. The vaccine was stable upon formulation and storage for at least 3weeks at 4°C in a microneedle patch. For vaccination, the patches were applied to the inner ear by hand without an applicator. Microneedle patches were well tolerated in the skin, with mild erythema, minimal wheal formation and complete resolution of skin reactions within 7days, and generated no systemic adverse events. Microneedle patches were at least as immunogenic as intramuscular injection at the same dose, as demonstrated by similar serum neutralizing antibody titers. A ten-fold lower vaccine dose administered by microneedle patch generated a weaker immune response compared to full-dose intramuscular vaccination. We conclude that dissolving microneedle patches may provide an innovative approach to mass vaccination of dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

Super-resolution reconstruction of 4D-CT lung data via patch-based low-rank matrix reconstruction

Science.gov (United States)

Fang, Shiting; Wang, Huafeng; Liu, Yueliang; Zhang, Minghui; Yang, Wei; Feng, Qianjin; Chen, Wufan; Zhang, Yu

2017-10-01

Lung 4D computed tomography (4D-CT), which is a time-resolved CT data acquisition, performs an important role in explicitly including respiratory motion in treatment planning and delivery. However, the radiation dose is usually reduced at the expense of inter-slice spatial resolution to minimize radiation-related health risk. Therefore, resolution enhancement along the superior-inferior direction is necessary. In this paper, a super-resolution (SR) reconstruction method based on a patch low-rank matrix reconstruction is proposed to improve the resolution of lung 4D-CT images. Specifically, a low-rank matrix related to every patch is constructed by using a patch searching strategy. Thereafter, the singular value shrinkage is employed to recover the high-resolution patch under the constraints of the image degradation model. The output high-resolution patches are finally assembled to output the entire image. This method is extensively evaluated using two public data sets. Quantitative analysis shows that the proposed algorithm decreases the root mean square error by 9.7%-33.4% and the edge width by 11.4%-24.3%, relative to linear interpolation, back projection (BP) and Zhang et al’s algorithm. A new algorithm has been developed to improve the resolution of 4D-CT. In all experiments, the proposed method outperforms various interpolation methods, as well as BP and Zhang et al’s method, thus indicating the effectivity and competitiveness of the proposed algorithm.

Increased expression and levels of human β defensins (hBD2 and hBD4 in adults with dental caries

Directory of Open Access Journals (Sweden)

Girolamo Jose Barrera

2013-09-01

Full Text Available Introduction: Defensins are small anti-microbial peptides produced by epithelial cells. These peptides have a broad range of actions against microorganisms, including Gram-positive and Gram-negative bacteria.Human defensins are classifi ed into two subfamilies, the α-, and β- defensins, which differ in their distribution of disulphide bonds between the six conserved cysteine residues. Defensins are found in salivaand others compartments of the body. Human β defensins 2 (hBD2, beta defensins 4 (hBD4 and alpha defensins 4 (hNP4 in saliva may contributes to vulnerability or resistance to caries. This study aimed to determine a possible correlation between caries and levels of defensins measuring the expression in gingival tissue and concentrations in saliva samples.Methods: Oral examinations were performed on 100 adults of both genders (18-30 years old, and unstimulated whole saliva was collected for immunoassays of the three peptides and for the salivary pH, buffercapacity, protein, and peroxidase activity. mRNA levels of defensins in gingival sample were assessed by semi-quantitative RT-PCR technique.Results: The median salivary levels of hBD2 and hBD4 were 1.88 μg/ml and 0.86 μg/ml respectively for the caries-free group (n=44 and 7.26 μ/ml (hBD2 and 4.25 μg/ml (hBD4 for all subjects with evidenceof caries (n=56. There was no difference in the levels of hNP4, salivary pH, and proteins between groups, however the peroxidase activity and buffer capacity (interval 6.0-5.0 were reduced in caries group. Transcriptional levels of hBD2 and hBD4 did correlate with caries experience, the mRNA expression of hBD2 and hBD4 were signifi cantly higher in patients with caries than in patients with no-caries (p Conclusion: We conclude that high salivary levels and expression of beta defensins, low peroxidase activity and buffer capacity may represent a biological response of oral tissue to caries. Our observation couldlead to new ways to prevent caries

Increased expression and levels of human β defensins (hBD2 and hBD4 in adults with dental caries

Directory of Open Access Journals (Sweden)

Girolamo Jose Barrera

2013-09-01

Full Text Available Introduction: Defensins are small anti-microbial peptides produced by epithelial cells. These peptides have a broad range of actions against microorganisms, including Gram-positive and Gram-negative bacteria.Human defensins are classifi ed into two subfamilies, the α-, and β- defensins, which differ in their distribution of disulphide bonds between the six conserved cysteine residues. Defensins are found in salivaand others compartments of the body. Human β defensins 2 (hBD2, beta defensins 4 (hBD4 and alpha defensins 4 (hNP4 in saliva may contributes to vulnerability or resistance to caries. This study aimed to determine a possible correlation between caries and levels of defensins measuring the expression in gingival tissue and concentrations in saliva samples.Methods: Oral examinations were performed on 100 adults of both genders (18-30 years old, and unstimulated whole saliva was collected for immunoassays of the three peptides and for the salivary pH, buffercapacity, protein, and peroxidase activity. mRNA levels of defensins in gingival sample were assessed by semi-quantitative RT-PCR technique.Results: The median salivary levels of hBD2 and hBD4 were 1.88 μg/ml and 0.86 μg/ml respectively for the caries-free group (n=44 and 7.26 μ/ml (hBD2 and 4.25 μg/ml (hBD4 for all subjects with evidenceof caries (n=56. There was no difference in the levels of hNP4, salivary pH, and proteins between groups, however the peroxidase activity and buffer capacity (interval 6.0-5.0 were reduced in caries group. Transcriptional levels of hBD2 and hBD4 did correlate with caries experience, the mRNA expression of hBD2 and hBD4 were signifi cantly higher in patients with caries than in patients with no-caries (p < 0.01.Conclusion: We conclude that high salivary levels and expression of beta defensins, low peroxidase activity and buffer capacity may represent a biological response of oral tissue to caries. Our observation couldlead to new ways to prevent

Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions.

Science.gov (United States)

McCarron, Paul A; Donnelly, Ryan F; Zawislak, Agnieszka; Woolfson, A David; Price, John H; McClelland, Raymond

2005-04-11

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 Ncm(-2). Patient evaluation demonstrated comfort and firm attachment for up to 4h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

Adaptive patch-based POCS approach for super resolution reconstruction of 4D-CT lung data

International Nuclear Information System (INIS)

Wang, Tingting; Cao, Lei; Yang, Wei; Feng, Qianjin; Chen, Wufan; Zhang, Yu

2015-01-01

Image enhancement of lung four-dimensional computed tomography (4D-CT) data is highly important because image resolution remains a crucial point in lung cancer radiotherapy. In this paper, we proposed a method for lung 4D-CT super resolution (SR) by using an adaptive-patch-based projection onto convex sets (POCS) approach, which is in contrast with the global POCS SR algorithm, to recover fine details with lesser artifacts in images. The main contribution of this patch-based approach is that the interfering local structure from other phases can be rejected by employing a similar patch adaptive selection strategy. The effectiveness of our approach is demonstrated through experiments on simulated images and real lung 4D-CT datasets. A comparison with previously published SR reconstruction methods highlights the favorable characteristics of the proposed method. (paper)

Sensitivity to the visual field origin of natural image patches in human low-level visual cortex

Directory of Open Access Journals (Sweden)

Damien J. Mannion

2015-06-01

Full Text Available Asymmetries in the response to visual patterns in the upper and lower visual fields (above and below the centre of gaze have been associated with ecological factors relating to the structure of typical visual environments. Here, we investigated whether the content of the upper and lower visual field representations in low-level regions of human visual cortex are specialised for visual patterns that arise from the upper and lower visual fields in natural images. We presented image patches, drawn from above or below the centre of gaze of an observer navigating a natural environment, to either the upper or lower visual fields of human participants (n = 7 while we used functional magnetic resonance imaging (fMRI to measure the magnitude of evoked activity in the visual areas V1, V2, and V3. We found a significant interaction between the presentation location (upper or lower visual field and the image patch source location (above or below fixation; the responses to lower visual field presentation were significantly greater for image patches sourced from below than above fixation, while the responses in the upper visual field were not significantly different for image patches sourced from above and below fixation. This finding demonstrates an association between the representation of the lower visual field in human visual cortex and the structure of the visual input that is likely to be encountered below the centre of gaze.

Delirium due to Scopolamine Patch in a 4-Year-Old Boy

Directory of Open Access Journals (Sweden)

Yang-Guang Lin

2011-03-01

Full Text Available The scopolamine patch is usually used to reduce postoperative nausea and vomiting associated with anesthesia and/or surgery. It is also commonly used for the prevention of motion sickness. Transdermal scopolamine patches have been used for decades and there are few reports in the literature of toxic psychosis associated with the product. Most documented cases of acute psychosis following administration of scopolamine or other anticholinergic agents have been from the adult population. Here we present a 4-year-old boy with deteriorated cognitive function and changed mental status acutely. Besides flushing skin and psychotic behaviors including bizarre actions, hallucinations, aggressive behavior, hyperactivity, and incoherent speech were also noticed. Symptoms and signs were resolved after removal of scopolamine patch and conservative management. This case is possibly one of the youngest patients to exhibit such toxic effects. We hope to relay information about common agents with anticholinergic effects to clinical practitioners and remind that drug-induced psychosis should be considered in children with acute changes in behavior.

FuncPatch: a web server for the fast Bayesian inference of conserved functional patches in protein 3D structures.

Science.gov (United States)

Huang, Yi-Fei; Golding, G Brian

2015-02-15

A number of statistical phylogenetic methods have been developed to infer conserved functional sites or regions in proteins. Many methods, e.g. Rate4Site, apply the standard phylogenetic models to infer site-specific substitution rates and totally ignore the spatial correlation of substitution rates in protein tertiary structures, which may reduce their power to identify conserved functional patches in protein tertiary structures when the sequences used in the analysis are highly similar. The 3D sliding window method has been proposed to infer conserved functional patches in protein tertiary structures, but the window size, which reflects the strength of the spatial correlation, must be predefined and is not inferred from data. We recently developed GP4Rate to solve these problems under the Bayesian framework. Unfortunately, GP4Rate is computationally slow. Here, we present an intuitive web server, FuncPatch, to perform a fast approximate Bayesian inference of conserved functional patches in protein tertiary structures. Both simulations and four case studies based on empirical data suggest that FuncPatch is a good approximation to GP4Rate. However, FuncPatch is orders of magnitudes faster than GP4Rate. In addition, simulations suggest that FuncPatch is potentially a useful tool complementary to Rate4Site, but the 3D sliding window method is less powerful than FuncPatch and Rate4Site. The functional patches predicted by FuncPatch in the four case studies are supported by experimental evidence, which corroborates the usefulness of FuncPatch. The software FuncPatch is freely available at the web site, http://info.mcmaster.ca/yifei/FuncPatch golding@mcmaster.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Piper betle LEAVES EXTRACT PATCH: EVALUATION OF ANTIBACTERIAL ACTIVITY, RELEASE PROFILE OF EUGENOL, AND LOCAL TOLERANCE

Directory of Open Access Journals (Sweden)

Mufrod Mufrod

2016-08-01

Full Text Available Piper betle leaf in extract form is more effective than crude drug. Eugenol is a component in the extract that has antibacterial activity but irritate. Patch of piper betle leaf extract was used on the mucosa to make oral cavity hygiene. Antibacterial activity was influenced by the release of eugenol from the patch. Release enhancer substances (RES such as glycerin, propylen glicol and tween 80 were added in patch formulation to increase the release of active substances. The aim of the research was to investigate the physicochemical properties, eugenol release profiles, and local tolerance test of the patch. Extract of piper betle leaf was made using infundation method. Patch was made according to the variation concentration of extract (1, 2 and 4% and RES (glycerine, propylen glycol and tween 80 using chitosan as vehicle. Patch produced solvent casting method. Patch obtained was tested for swelling index, folding endurance, surface pH, antibacterial activity, release of eugenol, and local tolerance. Data obtained were analyzed descriptively. The result showed that the addition of RES did not affect the surface pH but increase the water absorption with in inconsistent way except patch with tween 80. The flexibility (folding endurance value increased, and the highest amount of eugenol released was achieved by patch using propylen glicol. Patch with tween 80 and glycerin for all extract concentration and patch with 1% extract concentration using propylen glycol showed medium sensation (local tolerance, and patch with 2 and 4% extract using propylen glycol showed severe sensation.

Histological distinction between early allergic and irritant patch test reactions

DEFF Research Database (Denmark)

Vestergaard, L; Clemmensen, Ole; Sørensen, Flemming Brandt

1999-01-01

Comparative light microscopic studies have revealed subtle differences between allergic and irritant reactions in the skin. In the search for specific differences, we focussed on the early inflammatory response. This pilot study was conducted to test the hypothesis that follicular spongiosis can...... differentiate between early allergic and irritant patch test reactions. 8 patients with known contact allergy to either colophony or quarternium-15 participated in the study. In each patient, allergic and irritant patch tests reactions were elicited, and 4-mm punch biopsies were taken after 6 8 h from...... clinically equipotent reactions. Paired sets of slides were assessed blindly by 2 pathologists. 1 patient showing a pityrosporum folliculitis was excluded from the study. All biopsies from allergic patch tests were characterized by follicular spongiosis, while biopsies from irritant patch tests showed...

Analyzing the Safeguarding Our Communities Act: Patch for Patch Return Policy in Ontario

Directory of Open Access Journals (Sweden)

Soo-Min Kim

2018-04-01

Full Text Available Fentanyl is prescribed to patients suffering from severe chronic pain. Transdermal patches are the best mode of delivery for patients who have developed tolerance for opioids. However, used patches still contain fentanyl that can be extracted and misused, with potentially severe consequences. To address this issue, patients who are prescribed fentanyl patches in Ontario are now required to return previously dispensed patches to receive new patches under the Safeguarding Our Communities Act: Patch for Patch (P4P Return Policy. The problem is significant in Ontario because the province has the largest annual dispense rate of high-dose prescription fentanyl (112 units per 1,000 population in Canada even though the prevalence rate of chronic pain is lower than the national reported range (16.6% in Ontario versus 19.6 to 21.9% in other provinces, according to Gomes et al. 2014. The primary goal of this reform is to instill responsible use of fentanyl patches, and to improve safety for patients and the public by having a central disposal process. The reform was modeled after a community initiative that was pioneered in North Bay after receiving great support from health professional colleges and communities that voluntarily integrated the program prior to the introduction of Bill 33. Preliminary data suggest that the P4P policy is positively received by health professionals, although ongoing evaluation is needed to assess the effectiveness of the policy in reducing misuse and abuse of prescribed fentanyl patches.

Electronic structure of homoleptic transition metal hydrides: TiH4, VH4, CrH4, MnH4, FeH4, CoH4, and NiH4

International Nuclear Information System (INIS)

Hood, D.M.; Pitzer, R.M.; Schaefer III, H.F.

1979-01-01

Ab initio molecular electronic structure theory has been applied to the family of transition metal tetrahydrides TiH 4 through NiH 4 . For the TiH 4 molecule a wide range of contracted Gaussian basis sets has been tested at the self-consistent-field (SCF) level of theory. The largest basis, labeled M(14s 11p 6d/10s 8p 3d), H(5s 1p/3s 1p), was used for all members of the series and should yield wave functions approaching true Hartree-Fock quality. Predicted SCF dissociation energies (relative to M+4H) and M--H bond distances are TiH 4 132 kcal, 1.70 A; VH 4 86 kcal, 1.64 A; CrH 4 65 kcal, 1.59 A; MnH 4 -- 36 kcal, 1.58 A; FeH 4 0 kcal, 1.58 A; CoH 4 27 kcal, 1.61 A; and NiH 4 18 kcal, 1.75 A. It should be noted immediately that each of these SCF dissociation energies will be increased by electron correlation effects by perhaps as much as 90 kcal. For all of these molecules except TiH 4 excited states have also been studied. One of the most interesting trends seen for these excited states is the shortening of the M--H bond as electrons are transferred from the antibonding 4t 2 orbital to the nonbonding 1e orbitals

Streamlining of plant patches in streams

DEFF Research Database (Denmark)

Jensen, Kaj Sand; Pedersen, Morten Lauge

2008-01-01

. Sediment elevation within patches (avg. 4.1 cm) increased significantly with patch length, but did not differ between unstable sand or more stable coarse sediment for the same patch length. Shape of canopy and root area did not change significantly with sediment type. 4. Pressure drag on the canopy...

Immunoisolation Patch System for Cellular Transplantation

Science.gov (United States)

Wang, Taylor G. (Inventor)

2014-01-01

An immunoisolation patch system, and particularly a patch system comprising multiple immunoisolation microcapsules, each encapsulating biological material such as cells for transplantation, which can be used in the prophylactic and therapeutic treatment of disease in large animals and humans without the need for immunosuppression.

Miniaturization of Multiple-Layer Folded Patch Antennas

DEFF Research Database (Denmark)

Zhang, Jiaying; Breinbjerg, Olav

2009-01-01

A new folded patch antenna with multiple layers was developed in this paper, by folding the patch in a proper way, and a highly miniaturized antenna can be realized. The multiple layer patch with 4-layer and 6-layer are designed and evaluated at 2.4 GHz, 915 MHz, and 415 MHz respectively. Then a 4...... layer patch is fabricated and measured to validate the design method. The theoretical analysis, design and simulations, fabrications, as well as the measurements are presented in this paper. All the results show that the folded patch antenna is a good candidate in making a highly miniaturized compact...

Human Sodium Phosphate Transporter 4 (hNPT4/SLC17A3) as a Common Renal Secretory Pathway for Drugs and Urate*

Science.gov (United States)

Jutabha, Promsuk; Anzai, Naohiko; Kitamura, Kenichiro; Taniguchi, Atsuo; Kaneko, Shuji; Yan, Kunimasa; Yamada, Hideomi; Shimada, Hidetaka; Kimura, Toru; Katada, Tomohisa; Fukutomi, Toshiyuki; Tomita, Kimio; Urano, Wako; Yamanaka, Hisashi; Seki, George; Fujita, Toshiro; Moriyama, Yoshinori; Yamada, Akira; Uchida, Shunya; Wempe, Michael F.; Endou, Hitoshi; Sakurai, Hiroyuki

2010-01-01

The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4. PMID:20810651

Transdermal patches: history, development and pharmacology

Science.gov (United States)

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

Cell-Detection Technique for Automated Patch Clamping

Science.gov (United States)

McDowell, Mark; Gray, Elizabeth

2008-01-01

data are analyzed by software that implements the present machine-vision technique. This analysis results in the identification of cells that are "good" candidates for patch clamping (see figure). Once a "good" cell is identified, a patch clamp can be effected by an automated patchclamping apparatus or by a human operator. This technique has been shown to enable reliable identification of "good" and "bad" candidate cells for patch clamping. The ultimate goal in further development of this technique is to combine artificial-intelligence processing with instrumentation and controls in order to produce a complete "turnkey" automated patch-clamping system capable of accurately and reliably patch clamping cells with a minimum intervention by a human operator. Moreover, this technique can be adapted to virtually any cellular-analysis procedure that includes repetitive operation of microscope hardware by a human.

Pancreatic Transdifferentiation and Glucose-Regulated Production of Human Insulin in the H4IIE Rat Liver Cell Line

Directory of Open Access Journals (Sweden)

Binhai Ren

2016-04-01

Full Text Available Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone, H4IIE/ND (NeuroD1 gene alone, and H4IIEins/ND (insulin and NeuroD1 genes. The H4IIEins cells did not store insulin; however, H4IIE/ND and H4IIEins/ND cells stored 65.5 ± 5.6 and 1475.4 ± 171.8 pmol/insulin/5 × 106 cells, respectively. Additionally, several β cell transcription factors and pancreatic hormones were expressed in both H4IIE/ND and H4IIEins/ND cells. Electron microscopy revealed insulin storage vesicles in the H4IIE/ND and H4IIEins/ND cell lines. Regulated secretion of insulin to glucose (0–20 mmol/L was seen in the H4IIEins/ND cell line. The H4IIEins/ND cells were transplanted into diabetic immunoincompetent mice, resulting in normalization of blood glucose. This data shows that the expression of NeuroD1 and insulin in liver cells may be a useful strategy for inducing islet neogenesis and reversing diabetes.

A specialized face-processing model inspired by the organization of monkey face patches explains several face-specific phenomena observed in humans.

Science.gov (United States)

Farzmahdi, Amirhossein; Rajaei, Karim; Ghodrati, Masoud; Ebrahimpour, Reza; Khaligh-Razavi, Seyed-Mahdi

2016-04-26

Converging reports indicate that face images are processed through specialized neural networks in the brain -i.e. face patches in monkeys and the fusiform face area (FFA) in humans. These studies were designed to find out how faces are processed in visual system compared to other objects. Yet, the underlying mechanism of face processing is not completely revealed. Here, we show that a hierarchical computational model, inspired by electrophysiological evidence on face processing in primates, is able to generate representational properties similar to those observed in monkey face patches (posterior, middle and anterior patches). Since the most important goal of sensory neuroscience is linking the neural responses with behavioral outputs, we test whether the proposed model, which is designed to account for neural responses in monkey face patches, is also able to predict well-documented behavioral face phenomena observed in humans. We show that the proposed model satisfies several cognitive face effects such as: composite face effect and the idea of canonical face views. Our model provides insights about the underlying computations that transfer visual information from posterior to anterior face patches.

Regions of mid-level human visual cortex sensitive to the global coherence of local image patches.

Science.gov (United States)

Mannion, Damien J; Kersten, Daniel J; Olman, Cheryl A

2014-08-01

The global structural arrangement and spatial layout of the visual environment must be derived from the integration of local signals represented in the lower tiers of the visual system. This interaction between the spatially local and global properties of visual stimulation underlies many of our visual capacities, and how this is achieved in the brain is a central question for visual and cognitive neuroscience. Here, we examine the sensitivity of regions of the posterior human brain to the global coordination of spatially displaced naturalistic image patches. We presented observers with image patches in two circular apertures to the left and right of central fixation, with the patches drawn from either the same (coherent condition) or different (noncoherent condition) extended image. Using fMRI at 7T (n = 5), we find that global coherence affected signal amplitude in regions of dorsal mid-level cortex. Furthermore, we find that extensive regions of mid-level visual cortex contained information in their local activity pattern that could discriminate coherent and noncoherent stimuli. These findings indicate that the global coordination of local naturalistic image information has important consequences for the processing in human mid-level visual cortex.

Preparation and evaluation of cosmetic patches containing lactic and glycolic acids

Directory of Open Access Journals (Sweden)

Mahdavi H

2006-01-01

Full Text Available Background: Alpha-hydroxy acids such as glycolic acid (GA and lactic acid (LA, are used in cosmetic patches. The important fact in cosmetic patches is its suitable adhesion and peel properties. Aim: The objective of this study was to prepare LA- and GA-containing cosmetic patches and evaluate in-vitro/in-vivo correlation of adhesion properties. Methods: Pressure-sensitive adhesives with different concentrations of GA and LA were cast on a polyethylene terephthalate film. The patches were evaluated for peel adhesive strength. On the basis of in vitro adhesion properties the patches were selected for wear performance tests and skin irritation potential. Results: The adhesion properties (adhesion to steel plate and skin and cohesive strength tests indicated the substantial influence of GA and LA concentrations. Based on in vitro adhesion studies the patches containing 3% (w/w GA were selected for in vivo studies. In vivo studies show that a formulation containing 3% GA displays good adhesion on the skin, but it leaves little residues on the skin. Skin Irritation studies on healthy human volunteers showed negligible erythema at the site of application after 48h. Conclusion: The noninvasive patch test model was found useful for detecting irritant skin reactions to the cosmetic patch containing GA. Our results demonstrated a strong correlation between the adhesion to steel plate and adhesion to skin. But a weak correlation between the degree of adhesive residue on the skin in in vitro and in vivo tests was observed for the formulation containing 3% (w/w GA.

Stability of fragrance patch test preparations applied in test chambers.

Science.gov (United States)

Mowitz, M; Zimerson, E; Svedman, C; Bruze, M

2012-10-01

Petrolatum patch test preparations are for practical reasons often applied in test chambers in advance, several hours or even days before the patient is tested. As many fragrance compounds are volatile it may be suspected that petrolatum preparations applied in test chambers are not stable over time. To investigate the stability of petrolatum preparations of the seven chemically defined components in the fragrance mix (FM I) when stored in test chambers. Samples of petrolatum preparations applied in test chambers stored at room temperature and in a refrigerator for between 4 and 144 h were analysed using liquid chromatographic methods. The concentration decreased by ≥ 20% within 8 h in four of seven preparations stored in Finn chambers at room temperature. When stored in a refrigerator only the preparation of cinnamal had decreased by ≥ 20% within 24 h. The stability of preparations of cinnamal stored in IQ chambers with a plastic cover was slightly better, but like the preparations applied in Finn chambers, the concentration decreased by ≥ 20% within 4 h at room temperature and within 24 h in a refrigerator. Cinnamal and cinnamyl alcohol were found to be more stable when analysed as ingredients in FM I compared with when analysed in individual preparations. Within a couple of hours several fragrance allergens evaporate from test chambers to an extent that may affect the outcome of the patch test. Application to the test chambers should be performed as close to the patch test occasion as possible and storage in a refrigerator is recommended. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination.

Directory of Open Access Journals (Sweden)

Yoshie Kametani

Full Text Available Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD, which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg. After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2 cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP or keyhole limpet hemocyanin (KLH successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.

Method optimization of ocular patches

Directory of Open Access Journals (Sweden)

Kamalesh Upreti

2012-01-01

Full Text Available The intraocular patches were prepared using gelatin as the polymer. Ocular patch were prepared by solvent casting method. The patches were prepared for six formulations GP1, GP2, GP3, GP4, GP5 and GP6. Petri dishes were used for formulation of ocular patch. Gelatin was used as a polymer of choice. Glutaraldehyde used as cross linking agent and (DMSO dimethylsulfoxide used as solubility enhancer. The elasticity depends upon the concentration of gelatin. 400 mg amount of polymer i.e gelatin gave the required elasticity for the formulation.

H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

Directory of Open Access Journals (Sweden)

Anne-France Petit-Bertron

Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

Use of rivastigmine transdermal patch in the treatment of Alzheimer's disease.

Science.gov (United States)

Winblad, Bengt; Machado, João Carlos

2008-12-01

Cholinesterase inhibitors such as rivastigmine and donepezil exhibit a dose-response relationship, with higher doses of the drugs demonstrating greater efficacy. Transdermal patches provide smooth continuous drug delivery, with the potential to offer efficacious levels of drug exposure while avoiding the peaks and troughs associated with side effects. As a small, lipophilic and hydrophilic molecule, rivastigmine (C14H22N2O2) is chemically well-suited to transdermal delivery. The technology underlying the rivastigmine patch allows it to be discreetly small and thin. The target dose 9.5 mg/24 h rivastigmine patch has a diameter of just 3.5 cm and a surface area of 10 cm2. A large randomized controlled trial has demonstrated that the target dose 9.5 mg/24 h rivastigmine patch provided similar efficacy to the highest rivastigmine capsule doses, yet with three times fewer reports of nausea and vomiting. Thus, the rivastigmine patch enables quick and easy access to high dose efficacy. The skin tolerability profile is good, and the patch has demonstrated excellent adhesion. The apparent success of rivastigmine patch, in terms of clinical utility and patient acceptability, suggests that it may mark the next generation of dementia treatment.

Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice.

Science.gov (United States)

van der Maaden, Koen; Varypataki, Eleni Maria; Romeijn, Stefan; Ossendorp, Ferry; Jiskoot, Wim; Bouwstra, Joke

2014-10-01

The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the coated arrays onto ex vivo human skin, and by conducting a dermal immunization study in mice. The release of antigen into ex vivo human skin from the coated microneedles was determined by using radioactively labeled ovalbumin. To investigate the induction of antigen-specific IgG, and CD4(+) and CD8(+) T-cell responses, BALB/c mice were immunized with antigen-coated pH-sensitive microneedles by the 'coat and poke' approach. These responses were compared to responses induced by the 'poke and patch' approach, and subcutaneous and intradermal vaccination with classic hypodermic needles. The pH-sensitive microneedle arrays were efficiently coated with ovalbumin (95% coating efficiency) and upon application of six microneedle arrays 4.27 of 7 μg ovalbumin was delivered into the skin, showing a release efficiency of 70%. In contrast, the 'poke and patch' approach led to a delivery of only 6.91 of 100 μg ovalbumin (7% delivery efficiency). Immunization by means of ovalbumin-coated microneedles resulted in robust CD4(+) and CD8(+) T-cell responses comparable to those obtained after subcutaneous or intradermal immunization with conventional needles. Moreover, it effectively induced IgG responses; however, it required prime-boost immunizations before antibodies were produced. In conclusion, antigen delivery into ex vivo human skin by antigen-coated pH-sensitive microneedle arrays is more efficient than the 'poke-and-patch' approach and in vivo vaccination studies show the applicability of pH-sensitive microneedles for the induction of both T cell and B cell responses. Copyright © 2014 Elsevier B.V. All rights reserved.

Composite GPS Patch Antenna for the AR Bandwidth Enhancement

Directory of Open Access Journals (Sweden)

Minkil Park

2016-01-01

Full Text Available A composite Global Positioning System (GPS patch antenna with a quadrature 3 dB hybrid coupler was designed and implemented for working RHCP and had a broadband axial ratio (AR bandwidth. We designed two patches as a FR-4 patch and 1.5 mm thickness thin ceramic patch with a quadrature 3 dB hybrid coupler. A CP radiation pattern was achieved, and the AR bandwidth improved by incorporating a quadrature 3 dB hybrid coupler feed structure in a micro-strip patch antenna. SMD by chip elements was applied to the quadrature 3 dB hybrid coupler. For the composite FR-4 and ceramic patch antennas, the VSWR measurement showed a 2 : 1 ratio over the entire design band, and the 3 dB AR bandwidth was 295 and 580 MHz for the FR-4 patch and ceramic patch antennas, respectively. The antenna gains for the composite FR-4 and ceramic patch antennas were measured as 1.36–2.75 and 1.47–2.71 dBi with 15.11–25.3% and 19.25–28.45% efficiency, respectively.

Edge of polar cap patches

Science.gov (United States)

Hosokawa, K.; Taguchi, S.; Ogawa, Y.

2016-04-01

On the night of 4 December 2013, a sequence of polar cap patches was captured by an all-sky airglow imager (ASI) in Longyearbyen, Norway (78.1°N, 15.5°E). The 630.0 nm airglow images from the ASI of 4 second exposure time, oversampled the emission of natural lifetime (with quenching) of at least ˜30 sec, introduce no observational blurring effects. By using such high-quality ASI images, we succeeded in visualizing an asymmetry in the gradients between the leading/trailing edges of the patches in a 2-D fashion. The gradient in the leading edge was found to be 2-3 times steeper than that in the trailing edge. We also identified fingerlike structures, appearing only along the trailing edge of the patches, whose horizontal scale size ranged from 55 to 210 km. These fingers are considered to be manifestations of plasma structuring through the gradient-drift instability (GDI), which is known to occur only along the trailing edge of patches. That is, the current 2-D observations visualized, for the first time, how GDI stirs the patch plasma and such a mixing process makes the trailing edge more gradual. This result strongly implies a close connection between the GDI-driven plasma stirring and the asymmetry in the large-scale shape of patches and then suggests that the fingerlike structures can be used as markers to estimate the fine-scale structure in the plasma flow within patches.

Exploring Potential Foreshocks on Highly Compressed Patches in a Rate-and-State Fault Model

Science.gov (United States)

Higgins, N.; Lapusta, N.

2015-12-01

On both natural and laboratory faults, some mainshocks are preceded by foreshocks. Such foreshocks may be triggered by aseismic processes of the mainshock nucleation at fault heterogeneities such as bumps, as inferred in some laboratory experiments. We explore a rate-and-state fault model in which potential foreshocks occur on patches of elevated normal compression (by a factor of 5 to 10) within a larger velocity-weakening (VW) region, using 3D numerical simulations of long-term earthquake sequences and aseismic slip. We find that this model produces isolated microseismicity during the nucleation of a larger-scale seismic event, under the following conditions: (i) Patch diameter D is comparable to or larger than the patch nucleation size h*patch; (ii) D is much smaller than the nucleation size h*main for the larger-scale VW region; otherwise, a patch-hosted event simply starts the larger-scale event; (iii) the patches are sufficiently separated to prevent them triggering each other nearly instantaneously. Hence the nucleation sizes h*main and h*patch need to be substantially different, by a factor of around 10 in our simulations so far, and potentially much more. The aforementioned separation of scales can be achieved by assigning high levels of compression on the patches. However, one would expect unrealistically large stress drops for events on such patches. Remarkably, in this model, we find that the stress drops of the patch-hosted events are reasonable and roughly constant, despite a wide variation in the patch compression, due to patch ruptures extending into the surrounding VW region. Furthermore, for D close to h*patch, a substantial part of the stress change on the patch occurs aseismically. Our current work is directed towards quantifying and explaining these trends, as well as exploring whether the microseismicity occurring on highly compressed patches due to nucleation-induced creep has any observable differences from other events.

Characterization of novel non-clonal intrachromosomal rearrangements between the H4 and PTEN genes (H4/PTEN) in human thyroid cell lines and papillary thyroid cancer specimens

International Nuclear Information System (INIS)

Puxeddu, Efisio; Zhao Guisheng; Stringer, James R.; Medvedovic, Mario; Moretti, Sonia; Fagin, James A.

2005-01-01

The two main forms of RET rearrangement in papillary thyroid carcinomas (PTC) arise from intrachromosomal inversions fusing the tyrosine kinase domain of RET with either the H4 (RET/PTC1) or the ELE1/RFG genes (RET/PTC3). PTEN codes for a dual-specificity phosphatase and maps to chromosome 10q22-23. Germline mutations confer susceptibility to Cowden syndrome whereas somatic mutations or deletions are common in several sporadic human tumors. Decreased PTEN expression has been implicated in thyroid cancer development. We report the characterization of a new chromosome 10 rearrangement involving H4 and PTEN. The initial H4/PTEN rearrangement was discovered as a non-specific product of RT-PCR for RET/PTC1 in irradiated thyroid cell lines. Sequencing revealed a transcript consisting of exon 1 and 2 of H4 fused with exons 3-6 of PTEN. Nested RT-PCR with specific primers bracketing the breakpoints confirmed the H4/PTEN rearrangements in irradiated KAT-1 and KAT-50 cells. Additional H4/PTEN variants, generated by recombination of either exon 1 or exon 2 of H4 with exon 6 of PTEN, were found in non-irradiated KAK-1, KAT-50, ARO and NPA cells. Their origin through chromosomal recombination was confirmed by detection of the reciprocal PTEN/H4 product. H4/PTEN recombination was not a clonal event in any of the cell lines, as Southern blots with appropriate probes failed to demonstrate aberrant bands, and multicolor FISH of KAK1 cells with BAC probes for H4 and PTEN did not show a signal overlap in all cells. Based on PCR of serially diluted samples, the minimal frequency of spontaneous recombination between these loci was estimated to be approximately 1/10 6 cells. H4/PTEN products were found by nested RT-PCR in 4/14 normal thyroid tissues (28%) and 14/18 PTC (78%) (P < 0.01). H4/PTEN is another example of recombination involving the H4 locus, and points to the high susceptibility of thyroid cells to intrachromosomal gene rearrangements. As this also represents a plausible

Characterization of novel non-clonal intrachromosomal rearrangements between the H4 and PTEN genes (H4/PTEN) in human thyroid cell lines and papillary thyroid cancer specimens

Energy Technology Data Exchange (ETDEWEB)

Puxeddu, Efisio [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Zhao Guisheng [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Stringer, James R. [Department of Molecular Genetics, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Medvedovic, Mario [Center for Biostatistic Service, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States); Moretti, Sonia [Dipartimento di Medicina Interna, Universita degli Studi di Perugia, Via E. dal Pozzo, Perugia 06126, (Italy); Fagin, James A. [Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, PO Box 670547, Cincinnati, OH 45267-0547 (United States)]. E-mail: james.fagin@uc.edu

2005-02-15

The two main forms of RET rearrangement in papillary thyroid carcinomas (PTC) arise from intrachromosomal inversions fusing the tyrosine kinase domain of RET with either the H4 (RET/PTC1) or the ELE1/RFG genes (RET/PTC3). PTEN codes for a dual-specificity phosphatase and maps to chromosome 10q22-23. Germline mutations confer susceptibility to Cowden syndrome whereas somatic mutations or deletions are common in several sporadic human tumors. Decreased PTEN expression has been implicated in thyroid cancer development. We report the characterization of a new chromosome 10 rearrangement involving H4 and PTEN. The initial H4/PTEN rearrangement was discovered as a non-specific product of RT-PCR for RET/PTC1 in irradiated thyroid cell lines. Sequencing revealed a transcript consisting of exon 1 and 2 of H4 fused with exons 3-6 of PTEN. Nested RT-PCR with specific primers bracketing the breakpoints confirmed the H4/PTEN rearrangements in irradiated KAT-1 and KAT-50 cells. Additional H4/PTEN variants, generated by recombination of either exon 1 or exon 2 of H4 with exon 6 of PTEN, were found in non-irradiated KAK-1, KAT-50, ARO and NPA cells. Their origin through chromosomal recombination was confirmed by detection of the reciprocal PTEN/H4 product. H4/PTEN recombination was not a clonal event in any of the cell lines, as Southern blots with appropriate probes failed to demonstrate aberrant bands, and multicolor FISH of KAK1 cells with BAC probes for H4 and PTEN did not show a signal overlap in all cells. Based on PCR of serially diluted samples, the minimal frequency of spontaneous recombination between these loci was estimated to be approximately 1/10{sup 6} cells. H4/PTEN products were found by nested RT-PCR in 4/14 normal thyroid tissues (28%) and 14/18 PTC (78%) (P < 0.01). H4/PTEN is another example of recombination involving the H4 locus, and points to the high susceptibility of thyroid cells to intrachromosomal gene rearrangements. As this also represents a

IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification

Directory of Open Access Journals (Sweden)

Yu L

2018-01-01

Full Text Available Lei Yu,1 Na Li,1 Jisheng Zhang,2 Yan Jiang1 1Department of Otorhinolaryngology, 2Key Laboratory of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, China Introduction: Epigenetic regulation has been shown to play an important role in the development of inflammatory diseases, including chronic rhinosinusitis and nasal polyps. The latter are characterized by epithelial mis-differentiation and infiltration of inflammatory cytokines. H3K4me3 has been shown to be involved in regulating lineage commitment. However, the underlying mechanisms, especially in human nasal epithelial cells (HNEpC, remain underexplored. The objective of this study was to investigate the role of H3K4me3 in HNEpC differentiation treated with the Th2 cytokine IL-13. Patients and methods: The expression levels of mRNA and proteins were investigated using reverse transcription-polymerase chain reaction (RT-PCR assays and Western blot in nasal polyp tissues and human nasal epithelial cells respectively. We measured these levels of H3K4me3, MLL1 and targeted genes compared with control subjects.Results: We demonstrate that expression of H3K4me3 and its methyltransferase MLL1 was significantly upregulated in IL-13-treated HNEpC. This elevation was also observed in nasal polyps. Expression of cilia-related transcription factors FOXJ1 and DNAI2 decreased, while goblet cell-derived genes CLCA1 and MUC5a increased upon IL-13 treatment. Mechanistically, knockdown of MLL1 restored expression of these four genes induced by IL-13. Conclusion: These findings suggest that H3K4me3 is a critical regulator in control of nasal epithelial cell differentiation. MLL1 may be a potential therapeutic target for nasal inflammatory diseases. Keywords: IL-13, H3K4me3 modification, nasal epithelial cell, differentiation 

Desain Antena Hexagonal Patch Array Berbasis Sistem Transfer Daya Wireless pada Frekuensi 2,4 GHz

Directory of Open Access Journals (Sweden)

Herma Nugroho R. A. K.

2016-06-01

Full Text Available Pada penelitian ini telah didesain antena hexagonal patch array yang dapat digunakan sebagai perangkat catu daya wireless. Antena hexagonal patch array ini didesain untuk menangkap gelombang radio (RF pada frekuensi 2,4 GHz yang dapat diaplikasikan sebagai antena pada Wireless Local Area Network (WLAN. Desain antena dilakukan menggunakan software CST Microwave studio, kemudian dilakukan pabrikasi dan pengukuran secara riil. Parameter pengujian antena hexagonal patch array meliputi return loss, Voltage Standing Wave Ratio (VSWR, gain, bandwidth, dan daya. Metode yang digunakan adalah pemodelan transmission line dan corporate feed line untuk pengaturan perubahan jarak antar patch antena. Perubahan variabel juga diteliti pengaruhnya terhadap parameter antena khususnya daya terima antena yang kemudian ditransmisikan ke rangkaian power harvester. Nilai parameter antena hasil simulasi menunjukkan nilai return loss adalah -33,38 dB, VSWR sebesar 1,041, gain sebesar 8,81 dBi, bandwidth adalah 0,084 GHz, daya sebesar 0,499 W (-3 dBm. Sedangkan parameter hasil pengukuran dari antena yang telah dipabrikasi adalah nilai return loss sebesar -33,21 dB, VSWR sebesar 1,048, gain sebesar 5 dBi, bandwidth adalah 0,145 GHz, daya sebesar -33 dBm.

The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4α

International Nuclear Information System (INIS)

Klapper, Maja; Boehme, Mike; Nitz, Inke; Doering, Frank

2007-01-01

The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4α (HNF-4α), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4α binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4α by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4α, that are both candidate genes for diabetes type 2, may be a powerful approach

The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4{alpha}

Energy Technology Data Exchange (ETDEWEB)

Klapper, Maja [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Boehme, Mike [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Nitz, Inke [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Doering, Frank [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany)

2007-04-27

The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4{alpha} (HNF-4{alpha}), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4{alpha} binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4{alpha} by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4{alpha}, that are both candidate genes for diabetes type 2, may be a powerful approach.

Bacillus Calmette-Guérin Vaccination Using a Microneedle Patch

Science.gov (United States)

Hiraishi, Yasuhiro; Nandakumar, Subhadra; Choi, Seong-O; Lee, Jeong Woo; Kim, Yeu-Chun; Posey, James E.; Sable, Suraj B.; Prausnitz, Mark R.

2011-01-01

Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guerin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising immunogenicity. Here, we report the design and engineering of a BCG-coated microneedle vaccine patch for a simple and improved intradermal delivery of the vaccine. The microneedle vaccine patch induced a robust cell-mediated immune response in both the lungs and spleen of guinea pigs. The response was comparable to the traditional hypodermic needle based intradermal BCG vaccination and was characterized by a strong antigen specific lymphocyte proliferation and IFN-γ levels with high frequencies of CD4+IFN-γ+, CD4+TNF-α+ and CD4+IFN-γ+TNF-α+ T cells. The BCG-coated microneedle vaccine patch was highly immunogenic in guinea pigs and supports further exploration of this new technology as a simpler, safer, and compliant vaccination that could facilitate increased coverage, especially in developing countries that lack adequate healthcare infrastructure. PMID:21277407

Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

DEFF Research Database (Denmark)

Petersen, Søren Lykke; Russell, Charlotte Astrid; Bendtzen, Klaus

2002-01-01

S bioassay detects 5 pg/ml of human recombinant IL-4 with no detection of IL-2 in concentrations below 500 pg/ml. We have found 72 h of culture optimal for detection of IL-2 and IL-4 produced by human mononuclear cells (MNC) in response to stimulation with phytohaemaglutinin and for detection of IL......-2 in human leukocyte antigen (HLA)-mismatched mixed leukocyte culture (MLC). An interindividual variation in cytokine accumulation was demonstrated for IL-4 but not for IL-2. With the use of 5x10(4) responder cells/well no IL-4 could be detected in HLA-mismatched MLC between days 1 and 16. The lack...

Effect of novel mucoadhesive buccal patches of carvedilol on isoprenaline-induced tachycardia

Directory of Open Access Journals (Sweden)

Navneet Verma

2014-01-01

Full Text Available The main aim of the study was designed to develop bioadhesive buccal patches of carvedilol (CR and evaluate for isoprenaline-induced tachycardia. Buccal patches of carvedilol were prepared by using chitosan (CH, sodium salt of carboxy methyl cellulose (NaCMC, and polyvinyl alcohol (PVA as mucoadhesive polymers. The solvent evaporation method was used for the preparation of buccal patches. The patches were evaluated for their physical characteristics like patch thickness, weight variation, content uniformity, folding endurance, surface pH, residence time, in vitro drug release, and in vivo pharmacodynamic study. The swelling index of the patches was found to be proportional to the polymer concentration, whereas surface pH of all the formulated bioadhesive patches was found to lie between neutral ranges. In-vitro release study shows that 94.75% drug was release in 8 hours from the patch, which containing 2% w/v chitosan. The folding endurance result shows good elasticity in all the patches.Application of buccal patches on buccal mucosa of rabbit shows a significant result in % inhibition of isoprenaline-induced tachycardia. Prepared buccal patches of chitosan, NaCMC, and PVA containing Carvedilol meet the ideal requirement for the delivery of cardiovascular drugs and inhibit the isoprenaline tachycardia.

Biocide patch tests

DEFF Research Database (Denmark)

Andersen, Klaus Ejner; Veien, Niels

1985-01-01

Routine patch testing with a series of 6 industrial biocides containing methylene-bis-thiocyanate (Cytox 3522), benzisothiazolin-3-one (BIT), chlorocresol (Preventol CMK), 2-n-octyl-4-isothiazolin-3-one (Kathon 893), polyhydroxymethylene monobenzylether (Preventol D2) or 1,3,5-tris (hydroxy......-ethyl) hexahydrotriazine (Grotan BK) was carried out in 6 Danish out-patient clinics to evaluate guinea pig allergy test results with the same compounds. A total of 1652 consecutive patients with dermatitis were tested. The usefulness of this patch test battery was limited. There were a few positive reactions to Cytox...... of male patients and atopics, but significant differences in the frequencies of occupational cases, hand eczemas, and leg ulcers/stasis dermatitis, indicating possible variations in referral patterns, use of patch tests, and/or environmental factors....

Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human.

Science.gov (United States)

Takahashi, Yoh-hei; Westfield, Gerwin H; Oleskie, Austin N; Trievel, Raymond C; Shilatifard, Ali; Skiniotis, Georgios

2011-12-20

Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like complexes from yeast to human, respectively. Here we have reconstituted fully functional yeast Set1/COMPASS and human MLL/COMPASS-like complex in vitro and have identified the minimum subunit composition required for histone H3K4 methylation. These subunits include the methyltransferase C-terminal SET domain of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, and Cps25/Dpy30, which are all common components of the COMPASS family from yeast to human. Three-dimensional (3D) cryo-EM reconstructions of the core yeast complex, combined with immunolabeling and two-dimensional (2D) EM analysis of the individual subcomplexes reveal a Y-shaped architecture with Cps50 and Cps30 localizing on the top two adjacent lobes and Cps60-Cps25 forming the base at the bottom. EM analysis of the human complex reveals a striking similarity to its yeast counterpart, suggesting a common subunit organization. The SET domain of Set1 is located at the juncture of Cps50, Cps30, and the Cps60-Cps25 module, lining the walls of a central channel that may act as the platform for catalysis and regulative processing of various degrees of H3K4 methylation. This structural arrangement suggested that COMPASS family members function as exo-methylases, which we have confirmed by in vitro and in vivo studies.

Development of novel double-decker microneedle patches for transcutaneous vaccine delivery.

Science.gov (United States)

Ono, Akihiko; Azukizawa, Hiroaki; Ito, Sayami; Nakamura, Yuki; Asada, Hideo; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Hirobe, Sachiko; Okada, Naoki

2017-10-30

Microneedle (MN) patches have great potential as transcutaneous vaccine delivery devices because MNs can effectively deliver vaccine antigen into the skin through the micropores formed in the stratum corneum by low-invasive and painless skin puncturing. This study aims to develop novel double-decker MN patches which have not only high safety and efficacy but also broad applicability to various vaccine antigens. We developed two types of MN patches (PGA-MN and Nylon-MN) that are made from polyglycolic acid and Nylon-6. In pre-clinical studies, both MN patches could demonstrably deliver antigens into resected human dermal tissue, prolong antigen deposition and increase antigen-specific IgG levels after vaccination compared with conventional injections. We demonstrated both MN patches could be safely applied to human skin because no broken MNs or significant skin irritation were observed after applications in the clinical research. PGA-MN was suggested to be superior to Nylon-MN regarding human skin puncturability based on measurements of transepidermal water loss and needle failure force. A high content of tetravalent influenza hemagglutinin antigens loaded on PGA-MN could stably maintain HA titers at 35°C for 1year. Overall, double-decker MN patches can reliably and safely puncture human skin and are promising as effective transcutaneous vaccine delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

Patch photopatch test at Manipal

Directory of Open Access Journals (Sweden)

Panja Arindrajit

1994-01-01

Full Text Available Patch and photopatch testing was performed on 55 patients with history of photosensitivity using Scandanavian photo patch test antigens obtained from Chemotechnique Diagnostics AB Sweden. The commonest reactions were seen to perfume mix 4 (21.0%, PABA 3 (15.78%, promethazine hydrochloride 3 (15.78%, chlorpromazine hydrochloride 3 (15.78%, balsam of peru 2 (10.52%, usnic acid, hexachlorophane, musk ambrette and 6 methyl coumarin showed 1 positive reaction each (5.26% suggesting either phototoxicity or photo sensitization. Patch and photo patch test positive reaction suggesting allergic sensitisation was seen to balsam of peru 3 (23.0% perfume mix 3 (23.0% promethazine hydrochloride 2 (15.3% and PABA, 6 methyl coumarin, tribromosalicylanilide, atranorin and wood mix showed positive reaction in one case each (7.69%. We conclude that photoxic or photo allergic reaction is a problem in India and patch photo patch test should be performed in all cases of idiopathic light eruptions to rule out photo sensitisation and in cases where photo sensitivity of exogenous origin is suspected.

Development and characterization of mucoadhesive buccal patches of salbutamol sulphate.

Science.gov (United States)

Patel, Rajesh Singh; Poddar, S S

2009-01-01

Mucoadhesive patch releasing the drug in the oral cavity at predetermined rate may present distinct advantages over traditional dosage forms such as tablets, gels and solutions. The present study was concerned with the preparation and evaluation of mucoadhesive buccal patches for the controlled systemic delivery of Salbutamol sulphate to avoid first pass hepatic metabolism. The developed patches were evaluated for the physicochemical, mechanical and drug release characteristics. The patches showed desired mechanical and physicochemical properties to withstand environment of oral cavity. The in-vitro release study showed that patches could deliver drug to the oral mucosa for a period of 7 h. the patches exhibited adequate stability when tested under accelerated conditions.

Formulation of Polyherbal Patches Based on Polyvinyl Alcohol and Hydroxypropylmethyl Cellulose: Characterization and In Vitro Evaluation.

Science.gov (United States)

Suksaeree, Jirapornchai; Nawathong, Noramon; Anakkawee, Rinrada; Pichayakorn, Wiwat

2017-10-01

The purpose of this research was to prepare and characterize polyherbal patches made from polyvinyl alcohol (PVA) and hydroxypropylmethyl cellulose (HPMC) with glycerine as a plasticizer. Polyherbal extracts were Luk-Pra-Kob recipes extracted with 95% ethanol. They were prepared by mixing the polymer solutions and glycerine in a beaker; subsequently, the polyherbal extracts were homogeneously mixed. Then, they were transferred into a Petri dish and dried in a hot-air oven at 70 ± 2°C for 5 h. The dry polyherbal patches were evaluated for physicochemical properties by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and a scanning electron microscope. They were studied for in vitro release and skin permeation of the marker active compound (E)-4-(3',4'-dimethoxyphenyl)but-3-en-l-ol (compound D) using a modified Franz-type diffusion cell. The polyherbal patches made from PVA as a matrix layer were homogeneous, smooth, and compact relative to HPMC-containing polyherbal patches. The selected polyherbal patches made from PVA produced a release profile with an initial burst effect in which compound D release was 74.21 ± 6.13% within 8 h, but compound D could permeate the pig skin only 37.28 ± 5.52% and was highly accumulated in newborn pig skin at 35.90 ± 6.72%. The in vitro release and skin permeation kinetics of compound D were fitted to the Higuchi model. The polyherbal patches made from PVA could be suitably used for herbal medicine application.

Copper complex N(4)-ortho-toluyl-2-acetylpyridine thiosemicarbazone - ({sup 64}Cu)(H2Ac4oT)Cl - internal dosimetry: animal model and human extrapolation

Energy Technology Data Exchange (ETDEWEB)

Rodrigues, Josianne L.; Silva, Paulo R.O.; Santos, Raquel G.; Ferreira, Andrea V., E-mail: jlr@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2011-07-01

Thiosemicarbazones have attracted great pharmacological interest because of their biological properties, such as cytotoxic activity against multiple strains of human tumors. Due to the excellent properties of {sup 64}Cu, the copper complex N(4)-ortho-toluyl-2-acetylpyridine thiosemicarbazone (({sup 64}Cu)(H2Ac4oT)Cl) was developed for tumor detection by positron emission tomography. The radiopharmaceuticals were produced in the nuclear reactor TRIGA-IPR-R1 from CDTN. At the present work, ({sup 64}Cu)(H2Ac4oT)Cl biokinetic data (evaluated in mice bearing Ehrlich tumor) were treated by MIRD formalism to perform Internal Dosimetry studies. Doses in several organs of mice were determinate, as well as in implanted tumor, for ({sup 64}Cu)(H2Ac4oT)Cl. Doses results obtained for animal model were extrapolated to humans assuming a similar concentration ratio among various tissues between mouse and human. In the extrapolation, it was used human organ masses from Cristy/Eckerman phantom. Both penetrating and non-penetrating radiation from {sup 64}Cu in the tissue were considered in dose calculations. (author)

Patch-occupancy models indicate human activity as major determinant of forest elephant Loxodonta cyclotis seasonal distribution in an industrial corridor in Gabon

Science.gov (United States)

Buij, R.; McShea, W.J.; Campbell, P.; Lee, M.E.; Dallmeier, F.; Guimondou, S.; Mackaga, L.; Guisseougou, N.; Mboumba, S.; Hines, J.E.; Nichols, J.D.; Alonso, A.

2007-01-01

The importance of human activity and ecological features in influencing African forest elephant ranging behaviour was investigated in the Rabi-Ndogo corridor of the Gamba Complex of Protected Areas in southwest Gabon. Locations in a wide geographical area with a range of environmental variables were selected for patch-occupancy surveys using elephant dung to assess seasonal presence and absence of elephants. Patch-occupancy procedures allowed for covariate modelling evaluating hypotheses for both occupancy in relation to human activity and ecological features, and detection probability in relation to vegetation density. The best fitting models for old and fresh dung data sets indicate that (1) detection probability for elephant dung is negatively related to the relative density of the vegetation, and (2) human activity, such as presence and infrastructure, are more closely associated with elephant distribution patterns than are ecological features, such as the presence of wetlands and preferred fresh fruit. Our findings emphasize the sensitivity of elephants to human disturbance, in this case infrastructure development associated with gas and oil production. Patch-occupancy methodology offers a viable alternative to current transect protocols for monitoring programs with multiple covariates.

Role of collector alternating charged patches on transport of Cryptosporidium parvum oocyst in a patchwise charged heterogeneous micromodel

Energy Technology Data Exchange (ETDEWEB)

Liu, Yuanyuan; Zhang, Changyong; Hu, Dehong; Kuhlenschmidt, Mark S.; Kuhlenschmidt, Theresa B.; Mylon, Steven E.; Kong, Rong; Bhargava, Rohit; Nguyen, Thanh H.

2013-02-04

The role of collector surface charge heterogeneity on transport of Cryptosporidium parvum oocyst and carboxylate microsphere in 2-dimensional micromodels was studied. The cylindrical silica collectors within the micromodels were coated with 0, 10, 20, 50 and 100% Fe2O3 patches. The experimental values of average single collector removal efficiencies (η) of the Fe2O3 patches and on the entire collectors were determined. In the presence of significant (>3500 kT) Derjaguin–Landau–Verwey–Overbeek (DLVO) energy barrier between the microspheres and the silica collectors at pH 5.8 and 8.1, the values of η determined for Fe2O3 patches were significantly less (p < 0.05, t-test) than that obtained for collectors coated entirely with Fe2O3. However, η on Fe2O3 patches for microspheres at pH 4.4 and for oocysts at pH 5.8 and 8.1, where the DLVO energy barrier was relatively small (ca. 200-360 kT), were significantly greater (p < 0.05, t-test) than that on the collectors coated entirely with Fe2O3. The dependence of η determined for Fe2O3 patches on the DLVO energy barrier indicated the importance of periodic favorable and unfavorable electrostatic interactions between colloids and collectors with alternating Fe2O3 and silica patches. Differences between experimentally determined η and that predicted by a patchwise geochemical heterogeneous model was observed, but can be explained by the model’s lack of consideration for the spatial distribution of charge heterogeneity on the collector surface and colloid migration on patchwise heterogeneous collectors.

Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

Science.gov (United States)

Arora, Priyanka; Mukherjee, Biswajit

2002-09-01

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

Postoperative fentanyl patch versus subacromial bupivacaine infusion in arthroscopic shoulder surgery.

Science.gov (United States)

Merivirta, Riika; Äärimaa, Ville; Aantaa, Riku; Koivisto, Mari; Leino, Kari; Liukas, Antti; Kuusniemi, Kristiina

2013-07-01

The purpose of our study was to compare the effectiveness of subacromial bupivacaine infusion and a transdermal fentanyl patch in the treatment of postoperative pain after arthroscopic shoulder surgery. Sixty patients with rotator cuff disease scheduled for elective arthroscopic shoulder surgery were enrolled in the study. For the treatment of postoperative pain, 30 patients constituted group F and received a 12.0-μg/h fentanyl patch for 72 hours and saline solution infusion in a subacromial manner at the rate of 4 mL/h. The remaining 30 patients constituted group B and received a placebo patch and an infusion of 2.5-mg/mL bupivacaine in a subacromial manner for 72 hours. The primary outcome measure was the postoperative numerical rating scale pain score. The consumption of opioids, ibuprofen, and acetaminophen was also recorded. The Constant scores and general recovery were followed up until the 90th postoperative day. There was no statistically significant difference in the numerical rating scale scores (P = .60) between the groups. No differences in the use of rescue analgesic were observed except that the patients receiving bupivacaine used more ibuprofen (median, 1,200 mg v 600 mg) during the day of surgery (P = .042). No difference was found in general recovery between the groups. A fentanyl patch delivering 12-μg/h fentanyl offers an easy and safe treatment option as a part of multimodal analgesia with few adverse effects in the treatment of postoperative pain in a carefully selected patient group after arthroscopic shoulder surgery. Level I, randomized controlled trial. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis.

Science.gov (United States)

Han, Song Hee; Hur, Min Seok; Kim, Min Jung; Kim, Bo Mi; Kim, Kyoung Woon; Kim, Hae Rim; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

2017-10-01

Previous studies have shown the expression of histamine H 4 receptor (H4R) on CD4 + T cells, especially human CD4 + T h 2-polarized T cells. This study aimed to investigate the role of H4R on these effector T cells in psoriasis. We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4 + T cells. Then, we identified H4R expression in dermal CD4 + T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4 + T cells with several inflammatory cytokines. The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to T h 17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4 + T cells were polarized into T h 17 cells, we observed a tendency toward suppressed IL-17 secretion. Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4 + T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

Science.gov (United States)

Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

2008-02-04

The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

Patch-augmented rotator cuff repair: influence of the patch fixation technique on primary biomechanical stability.

Science.gov (United States)

Jung, Christian; Spreiter, Gregor; Audigé, Laurent; Ferguson, Stephen J; Flury, Matthias

2016-05-01

There is an ongoing debate about the potential of patch augmentation to improve biomechanical stability and healing associated with rotator cuff repair. The biomechanical properties of three different patch-augmented rotator cuff repair techniques were assessed in vitro and compared with a standard repair. Dermal collagen patch augmentation may increase the primary stability and strength of the repaired tendon in vitro, depending on the technique used for patch application. Forty cadaveric sheep shoulders with dissected infraspinatus tendons were randomized into four groups (n = 10/group) for tendon repair using a knotless double-row suture anchor technique. A xenologous dermal extracellular matrix patch was used for augmentation in the three test groups using an "integrated", "cover", or "hybrid" technique. Tendons were preconditioned, cyclically loaded from 10 to 30 N at 1 Hz, and then loaded monotonically to failure. Biomechanical properties and the mode of failure were evaluated. Patch augmentation significantly increased the maximum load at failure by 61 % in the "cover" technique test group (225.8 N) and 51 % in the "hybrid" technique test group (211.4 N) compared with the non-augmented control group (140.2 N) (P ≤ 0.015). For the test group with "integrated" patch augmentation, the load at failure was 28 % lower (101.6 N) compared with the control group (P = 0.043). There was no significant difference in initial and linear stiffness among the four experimental groups. The most common mode of failure was tendon pullout. No anchor dislocation, patch disruption or knot breakage was observed. Additional patch augmentation with a collagen patch influences the biomechanical properties of a rotator cuff repair in a cadaveric sheep model. Primary repair stability can be significantly improved depending on the augmentation technique.

Cooperation of Ad-hING4 and 125I seed in tumor-suppression on human pancreatic cancer xenograft in nude mice

International Nuclear Information System (INIS)

Zhai Hongyan; Fa Yihua; Su Chenghai; Yang Jicheng; Sheng Weihua; Xie Yufeng

2009-01-01

This work is to investigate the combined tumor-suppression effect of Adenovirus-mediated human ING4 (Ad-hING4) and 125 I seed on human pancreatic cancer xenograft and the possible mechanisms. Ad-hING4 recombinant adenovirus vector was transected into QBI-293A cells and high titre adenovirus was obtained. Subcutaneous tumor models were established with 25 nude mice with human pancreatic cancer cell line PANC-1. They were randomly divided into 5 groups: PBS control group, Ad carrier group, 125 I seed brachytherapy group, Ad-hING4 gene treatment group, combined 125 I seed and Ad-hING4 group. The tumor volumes were measured every 5 days after treatment, and were sacrificed on the 20th day. The tumors were measured and weighed to determine the ratio of tumor-suppression and Jin-Shi q value. Morphological changes of tumor cells,the tissue injury and apoptotic index AI were examined on pathological sections. MVD, Survivin and Caspase3 were tested in immunohistochemistry. The results show that the tumor-suppressive ratio of the 125 I seed group, Ad-hING4 group, combined treatment group were,respectively, 34.19%(P 0.05). It can be concluded that 125 I seed and Ad-hING4 inhibit the growth of PANC-1 pancreatic cancer on nude mice significantly. These indicate a synergy of the combined treatments in tumor-suppression and Ad-hING4 is a promising novel radiosensitizer. The mechanisms of tumor-suppressive may be multi-pathways such as down-regulation the expression of Survivin and up-regulation the expression of Caspase3 to induce apoptosis and inhibit angiogenesis. (authors)

Patch size has no effect on insect visitation rate per unit area in garden-scale flower patches

Science.gov (United States)

Garbuzov, Mihail; Madsen, Andy; Ratnieks, Francis L. W.

2015-01-01

Previous studies investigating the effect of flower patch size on insect flower visitation rate have compared relatively large patches (10-1000s m2) and have generally found a negative relationship per unit area or per flower. Here, we investigate the effects of patch size on insect visitation in patches of smaller area (range c. 0.1-3.1 m2), which are of particular relevance to ornamental flower beds in parks and gardens. We studied two common garden plant species in full bloom with 6 patch sizes each: borage (Borago officinalis) and lavender (Lavandula × intermedia 'Grosso'). We quantified flower visitation by insects by making repeated counts of the insects foraging at each patch. On borage, all insects were honey bees (Apis mellifera, n = 5506 counts). On lavender, insects (n = 737 counts) were bumble bees (Bombus spp., 76.9%), flies (Diptera, 22.4%), and butterflies (Lepidoptera, 0.7%). On both plant species we found positive linear effects of patch size on insect numbers. However, there was no effect of patch size on the number of insects per unit area or per flower and, on lavender, for all insects combined or only bumble bees. The results show that it is possible to make unbiased comparisons of the attractiveness of plant species or varieties to flower-visiting insects using patches of different size within the small scale range studied and make possible projects aimed at comparing ornamental plant varieties using existing garden flower patches of variable area.

Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration.

Science.gov (United States)

Gredes, Tomasz; Gedrange, Tomasz; Hinüber, Claudia; Gelinsky, Michael; Kunert-Keil, Christiane

2015-05-01

Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB) induced ectopic bone formation after implantation into the back muscle of rats. The objective of our in vivo study was to evaluate the osteogenic potential of pure PHB patches in surgically created cranial defects. For this, PHB patches were analyzed after implantation in surgically created defects on the cranium of adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue specimens containing PHB patches were processed and analyzed histologically as well as molecular-biologically. After 4 weeks, the PHB patches were completely embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration proceeding from bearing bone was found in 50% of all treated animals, whereas all PHB treated cavities showed both bone formation and embedding of the patches in bone 12 weeks after surgery. Furthermore, all slices showed pronounced development of blood vessels. Histomorphometric analysis presented a regenerated bone mean value between 46.4 ± 16.1% and 54.2 ± 19.3% after 4-12 weeks of healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold increased expression in PHB treated defects compared to controls. Real-time RT-PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in cranium defects after treatment with PHB patches compared to untreated bony defects of the same cranium. Within the limits of the presented animal investigation, it could conclude that the tested PHB patches featured a good biocompatibility and an osteoconductive character. Copyright © 2014 Elsevier GmbH. All rights reserved.

Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets.

Science.gov (United States)

Herfst, Sander; Mok, Chris K P; van den Brand, Judith M A; van der Vliet, Stefan; Rosu, Miruna E; Spronken, Monique I; Yang, Zifeng; de Meulder, Dennis; Lexmond, Pascal; Bestebroer, Theo M; Peiris, J S Malik; Fouchier, Ron A M; Richard, Mathilde

2018-01-01

Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to continued

Image quality assessment based on inter-patch and intra-patch similarity.

Directory of Open Access Journals (Sweden)

Fei Zhou

Full Text Available In this paper, we propose a full-reference (FR image quality assessment (IQA scheme, which evaluates image fidelity from two aspects: the inter-patch similarity and the intra-patch similarity. The scheme is performed in a patch-wise fashion so that a quality map can be obtained. On one hand, we investigate the disparity between one image patch and its adjacent ones. This disparity is visually described by an inter-patch feature, where the hybrid effect of luminance masking and contrast masking is taken into account. The inter-patch similarity is further measured by modifying the normalized correlation coefficient (NCC. On the other hand, we also attach importance to the impact of image contents within one patch on the IQA problem. For the intra-patch feature, we consider image curvature as an important complement of image gradient. According to local image contents, the intra-patch similarity is measured by adaptively comparing image curvature and gradient. Besides, a nonlinear integration of the inter-patch and intra-patch similarity is presented to obtain an overall score of image quality. The experiments conducted on six publicly available image databases show that our scheme achieves better performance in comparison with several state-of-the-art schemes.

Study of LCP based flexible patch antenna array

KAUST Repository

Ghaffar, Farhan A.

2012-07-01

Wrapping of a two element LCP based patch antenna array is studied in this work. For the first time, the designed array is bent in both E and H planes to observe the effect on the radiation and impedance performance of the antenna. The 38 GHz simulation results reveal better performance for H plane bending as compared to E plane bending. A 100 um thick substrate is used for the design which is best suited for flexible antenna applications. Gain variations of 1.1 dB and 1.4 dB are observed for the two orientations while a significantly increased impedance bandwidth of 3 % is obtained with H plane wrapping. The design is highly suitable for broadband micro-cellular backhaul applications. © 2012 IEEE.

Alternative splicing targeting the hTAF4-TAFH domain of TAF4 represses proliferation and accelerates chondrogenic differentiation of human mesenchymal stem cells.

Directory of Open Access Journals (Sweden)

Jekaterina Kazantseva

Full Text Available Transcription factor IID (TFIID activity can be regulated by cellular signals to specifically alter transcription of particular subsets of genes. Alternative splicing of TFIID subunits is often the result of external stimulation of upstream signaling pathways. We studied tissue distribution and cellular expression of different splice variants of TFIID subunit TAF4 mRNA and biochemical properties of its isoforms in human mesenchymal stem cells (hMSCs to reveal the role of different isoforms of TAF4 in the regulation of proliferation and differentiation. Expression of TAF4 transcripts with exons VI or VII deleted, which results in a structurally modified hTAF4-TAFH domain, increases during early differentiation of hMSCs into osteoblasts, adipocytes and chondrocytes. Functional analysis data reveals that TAF4 isoforms with the deleted hTAF4-TAFH domain repress proliferation of hMSCs and preferentially promote chondrogenic differentiation at the expense of other developmental pathways. This study also provides initial data showing possible cross-talks between TAF4 and TP53 activity and switching between canonical and non-canonical WNT signaling in the processes of proliferation and differentiation of hMSCs. We propose that TAF4 isoforms generated by the alternative splicing participate in the conversion of the cellular transcriptional programs from the maintenance of stem cell state to differentiation, particularly differentiation along the chondrogenic pathway.

Biomaterials for drug delivery patches.

Science.gov (United States)

Santos, Lúcia F; Correia, Ilídio J; Silva, A Sofia; Mano, João F

2018-06-15

The limited efficiency of conventional drugs has been instigated the development of new and more effective drug delivery systems (DDS). Transdermal DDS, are associated with numerous advantages such its painless application and less frequent replacement and greater flexibility of dosing, features that triggered the research and development of such devices. Such systems have been produced using either biopolymer; or synthetic polymers. Although the first ones are safer, biocompatible and present a controlled degradation by human enzymes or water, the second ones are the most currently available in the market due to their greater mechanical resistance and flexibility, and non-degradation over time. This review highlights the most recent advances (mainly in the last five years) of patches aimed for transdermal drug delivery, focusing on the different materials (natural, synthetic and blends) and latest designs for the development of such devices, emphasizing also their combination with drug carriers that enable enhanced drug solubility and a more controlled release of the drug over the time. The benefits and limitations of different patches formulations are considered with reference to their appliance to transdermal drug delivery. Furthermore, a record of the currently available patches on the market is given, featuring their most relevant characteristics. Finally, a list of most recent/ongoing clinical trials regarding the use of patches for skin disorders is detailed and critical insights on the current state of patches for transdermal drug delivery are also provided. Copyright © 2018. Published by Elsevier B.V.

Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008 - 2011).

Science.gov (United States)

Ferreira, Vitor F; da Rocha, David R; da Silva, Fernando C; Ferreira, Patrícia G; Boechat, Núbia A; Magalhães, Jorge L

2013-03-01

The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these

Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology

Science.gov (United States)

Ikram, Md.; Gilhotra, Neeraj; Gilhotra, Ritu Mehra

2015-01-01

Background: This study was undertaken with an aim to systematically design a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology (RSM) by employing 32 full factorial design. Materials and Methods: Mucoadhesive buccal patches were prepared using different grades of hydroxypropyl methylcellulose (HPMC) (K4M and K100M) and polyvinylpyrrolidone-K30 by solvent casting method. The amount of the release retardant polymers – HPMC K4M (X1) and HPMC K100M (X2) was taken as an independent variable. The dependent variables were the burst release in 30 min (Y1), cumulative percentage release of drug after 8 h (Y2) and swelling index (Y3) of the patches. In vitro release and swelling studies were carried out and the data were fitted to kinetic equations. Results: The physicochemical, bioadhesive, and swelling properties of patches were found to vary significantly depending on the viscosity of the polymers and their combination. Patches showed an initial burst release preceding a more gradual sustained release phase following a nonfickian diffusion process. Discussion: The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared, facilitated with the RSM. PMID:26682205

A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of Ik1 Ion Channels in Real-Time

Directory of Open Access Journals (Sweden)

Birgit Goversen

2018-01-01

Full Text Available An important aspect of the Comprehensive In Vitro Proarrhythmia Assay (CiPA proposal is the use of human stem cell-derived cardiomyocytes and the confirmation of their predictive power in drug safety assays. The benefits of this cell source are clear; drugs can be tested in vitro on human cardiomyocytes, with patient-specific genotypes if needed, and differentiation efficiencies are generally excellent, resulting in a virtually limitless supply of cardiomyocytes. There are, however, several challenges that will have to be surmounted before successful establishment of hSC-CMs as an all-round predictive model for drug safety assays. An important factor is the relative electrophysiological immaturity of hSC-CMs, which limits arrhythmic responses to unsafe drugs that are pro-arrhythmic in humans. Potentially, immaturity may be improved functionally by creation of hybrid models, in which the dynamic clamp technique joins simulations of lacking cardiac ion channels (e.g., IK1 with hSC-CMs in real-time during patch clamp experiments. This approach has been used successfully in manual patch clamp experiments, but throughput is low. In this study, we combined dynamic clamp with automated patch clamp of iPSC-CMs in current clamp mode, and demonstrate that IK1 conductance can be added to iPSC-CMs on an automated patch clamp platform, resulting in an improved electrophysiological maturity.

Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.

Science.gov (United States)

Hauschild, Axel; Popp, Georg; Stockfleth, Eggert; Meyer, Karl-Gustav; Imberger, Dirk; Mohr, Peter; Itschert, Götz; Kaufmann, Roland; Neuber, Karsten; Frambach, Yvonne; Gollnick, Harald; Brunnert, Marcus; Stocker, Marcus; Ortland, Christoph; Karrer, Sigrid

2009-02-01

Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK). To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK. Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events. A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range. The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.

Patch time allocation and oviposition behavior in response to patch quality and the presence of a generalist predator in Meteorus pulchricornis (Hymenoptera: Braconidae).

Science.gov (United States)

Sheng, Sheng; Ling, Meng; Fu-An, Wu; Baoping, Li

2015-01-01

Foraging parasitoids often must estimate local risk of predation just as they must estimate local patch value. Here, we investigate the effects a generalist predator Chlaenius bioculatus (Coleoptera: Carabidae), has on the oviposition behavior and the patch residence decisions of a solitary parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae) in response to the varying host quality of Spodoptera litura (Lepidoptera: Noctuidae) larvae (L2 and L4). M. pulchricornis attacked more L4 than on L2 hosts, with the difference in attack rate varying depending on predation treatments, greater in the presence (either actively feeding or not) of the predator than in the absence of it. The parasitoid attacked fewer L2 and L4 hosts when the predator was actively feeding than when it was not feeding or not present in the patch. M. pulchricornis decreased the patch leaving tendency with increasing rejections of hosts, but increased the tendency in response to the presence of the predator as compared with the absence of it, and furthermore, increased the patch leaving tendency when the predator was actively feeding as compared with when it was not. Our study suggests that M. pulchricornis can exploit high quality patches while minimizing predation risk, by attacking more hosts in high quality patches while reducing total patch time in response to risk of predation. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Visual and confocal microscopic interpretation of patch tests to benzethonium chloride and benzalkonium chloride.

Science.gov (United States)

Benjamin, Bohaty; Chris, Fricker; Salvador, González; Melissa, Gill; Susan, Nedorost

2012-08-01

Quaternary ammonium compounds (Quats), such as benzalkonium chloride (BAC) and benzethonium chloride (BEC), are widely used as antibacterial active ingredients and preservatives in personal care products, disinfectants, and ophthalmic preparations. BAC is known to be a marginal irritant when patch tested at 0.15% aq. Data on BEC are limited. To differentiate irritant from allergic patch test reactions to quaternary ammonium compounds. Eight subjects who were considered likely to react based on history of rash after exposure to disinfectants or a history of prior positive patch test to BAC were recruited, as well as two patients undergoing routine patch testing. BAC (0.15% aq), BAC (0.15% pet), BEC (0.05% aq), BEC (0.15% pet), BEC (0.15% aq), BEC (0.5% aq), sodium lauryl sulfate (2.0%), and deionized water were applied under Finn chambers for 48 h. Four days and 7 days after application, the sites were examined visually and then by in vivo reflectance confocal microscopy (RCM) which was interpreted by blinded experts. Two patients with definite allergic reactions according to visual patch test reads and RCM were clinically relevant. Cross-reaction between BEC and BAC was demonstrated in one patient. RCM imaging correlated well with clinical scoring and interpretation of patch test reactions in terms of irritancy vs. allergy for BEC and BAC. Relevant allergic reactions to quats occur in humans. Possible cross-reaction was noted to occur between BAC and BEC. RCM appears to be a useful tool in distinguishing between irritancy and sensitization during patch testing to BAC and BEC. Further study of prevalence and best test concentration and vehicle is needed. © 2011 John Wiley & Sons A/S.

Synthesis of conjugated chitosan and its effect on drug permeation from transdermal patches.

Science.gov (United States)

Satheeshababu, B K; Shivakumar, K L

2013-03-01

The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug.

A Compact Size 4–19.1 GHz Heart Shape UWB Antenna with Triangular Patches

Directory of Open Access Journals (Sweden)

Gokmen Isik

2013-01-01

Full Text Available An ultrawideband antenna is designed, simulated, and realized. To overcome the narrow bandwidth characteristics of basic patch antennas, the structure of the radiation pattern is optimized by the aid of elliptical and rectangular patches. Also triangular patches are applied to the antenna edge in order to enhance the VSWR and gain properties. A typical VSWR of 1.5 (less than 2 in the whole frequency range and a typical gain of 2 dBi (mainly above 1 dBi in the whole frequency range are observed. The simulations present that the designed antenna has a bandwidth ratio of ~5 : 1 within the frequency range of 4–19.1 GHz with compact dimensions of 25 × 26 mm2. It is fabricated on a 0.5 mm thick, RO3035 substrate. The input impedance, gain, and radiation characteristics of the antenna are also presented. With these properties, it is verified that, with its novel shape, the proposed antenna can be used for various UWB applications.

Recent and relict topography of Boo Bee patch reef, Belize

Science.gov (United States)

Halley, R.B.; Shinn, E.A.; Hudson, J.H.; Lidz, B.; Taylor, D.L.

1977-01-01

Five core borings were taken on and around Boo Bee Patch Reef to better understand the origin of such shelf lagoon reefs. The cores reveal 4 stages of development: (1) subaerial exposure of a Pleistocene "high" having about 8 meters of relief, possibly a Pleistocene patch reef; (2) deposition of peat and impermeable terrigenous clay 3 meters thick around the high; (3) initiation of carbonate sediment production by corals and algae on the remaining 5 meters of hard Pleistocene topography and carbonate mud on the surrounding terrigenous clay; and (4) accelerated organic accumulation on the patch reef. Estimates of patch reef sedimentation rates (1.6 m/1000 years) are 3 to 4 times greater than off-reef sedimentation rates (0.4-0.5 m/1000 years). During periods of Pleistocene sedimentation on the Belize shelf, lagoon patch reefs may have grown above one another, stacking up to form reef accumulation of considerable thickness.

Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel*

Science.gov (United States)

Chen, Jeffery; Guo, Jun; Yang, Tonghua; Li, Wentao; Lamothe, Shawn M.; Kang, Yudi; Szendrey, John A.; Zhang, Shetuan

2015-01-01

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K+ conditions. In the present study, we addressed whether hERG internalization occurs under normal K+ conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K+-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell-surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K+ exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K+ medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane-bound hERG channels. PMID:26152716

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex.

Science.gov (United States)

Naumann, Robert K; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L; Brecht, Michael

2016-03-01

To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin-positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin-negative and calbindin-positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin-positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin-positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10-fold over a 20,000-fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation

Directory of Open Access Journals (Sweden)

Porter Christopher J

2007-09-01

Full Text Available Abstract Background SNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs. These microarrays report hybridization of DNA fragments and therefore can be used for the purpose of detecting genomic fragments. Results Here, we demonstrate that a SNP microarray can be effectively used in this way to perform chromatin immunoprecipitation (ChIP on chip as an alternative to tiling microarrays. We illustrate this novel application by mapping whole genome histone H4 hyperacetylation in human myoblasts and myotubes. We detect clusters of hyperacetylated histone H4, often spanning across up to 300 kilobases of genomic sequence. Using complementary genome-wide analyses of gene expression by DNA microarray we demonstrate that these clusters of hyperacetylated histone H4 tend to be associated with expressed genes. Conclusion The use of a SNP array for a ChIP-on-chip application (ChIP on SNP-chip will be of great value to laboratories whose interest is the determination of general rules regarding the relationship of specific chromatin modifications to transcriptional status throughout the genome and to examine the asymmetric modification of chromatin at heterozygous loci.

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch.

Science.gov (United States)

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M L; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G

2015-01-01

Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment

Characteristics of recombinantly expressed rat and human histamine H3 receptors.

Science.gov (United States)

Wulff, Birgitte S; Hastrup, Sven; Rimvall, Karin

2002-10-18

Human and rat histamine H(3) receptors were recombinantly expressed and characterized using receptor binding and a functional cAMP assay. Seven of nine agonists had similar affinities and potencies at the rat and human histamine H(3) receptor. S-alpha-methylhistamine had a significantly higher affinity and potency at the human than rat receptor, and for 4-[(1R*,2R*)-2-(5,5-dimethyl-1-hexynyl)cyclopropyl]-1H-imidazole (Perceptin) the preference was the reverse. Only two of six antagonists had similar affinities and potencies at the human and the rat histamine H(3) receptor. Ciproxifan, thioperamide and (1R*,2R*)-trans-2-imidazol-4 ylcyclopropyl) (cyclohexylmethoxy) carboxamide (GT2394) had significantly higher affinities and potencies at the rat than at the human histamine H(3) receptor, while for N-(4-chlorobenzyl)-N-(7-pyrrolodin-1-ylheptyl)guanidine (JB98064) the preference was the reverse. All antagonists also showed potent inverse agonism properties. Iodoproxyfan, Perceptin, proxyfan and GR175737, compounds previously described as histamine H(3) receptor antagonists, acted as full or partial agonists at both the rat and the human histamine H(3) receptor. Copyright 2002 Elsevier Science B.V.

Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.

Science.gov (United States)

Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A

2013-06-01

The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.

Diagnostic Yield of Extended Cardiac Patch Monitoring in Patients with Stroke or TIA.

Science.gov (United States)

Tung, Christie E; Su, Derek; Turakhia, Mintu P; Lansberg, Maarten G

2014-01-01

It is important to evaluate patients with transient ischemic attack (TIA) or stroke for atrial fibrillation (AF) because the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. This study describes the diagnostic yield of a patch-based, single-use, and water-resistant 14-day continuous cardiac rhythm monitor (ZIO Patch) in patients with stroke or TIA. We obtained data from the manufacturer and servicer of the ZIO Patch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented. One thousand one hundred seventy-one monitoring reports were analyzed. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2-14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0-99.5%). AF was present in 5.0% of all reports. The mean duration before the first episode of paroxysmal AF (PAF) was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 h. The mean PAF burden was 12.7% of the total monitoring duration. Excellent quality of the recordings and very good patient compliance coupled with a substantial proportion of AF detection beyond the first 48 h of monitoring suggest that the cardiac patch is superior to conventional 48-h Holter monitors for AF detection in patients with stroke or TIA.

Coevolution of patch-type dependent emigration and patch-type dependent immigration.

Science.gov (United States)

Weigang, Helene C

2017-08-07

The three phases of dispersal - emigration, transfer and immigration - are affecting each other and the former and latter decisions may depend on patch types. Despite the inevitable fact of the complexity of the dispersal process, patch-type dependencies of dispersal decisions modelled as emigration and immigration are usually missing in theoretical dispersal models. Here, I investigate the coevolution of patch-type dependent emigration and patch-type dependent immigration in an extended Hamilton-May model. The dispersing population inhabits a landscape structured into many patches of two types and disperses during a continuous-time season. The trait under consideration is a four dimensional vector consisting of two values for emigration probability from the patches and two values for immigration probability into the patches of each type. Using the adaptive dynamics approach I show that four qualitatively different dispersal strategies may evolve in different parameter regions, including a counterintuitive strategy, where patches of one type are fully dispersed from (emigration probability is one) but individuals nevertheless always immigrate into them during the dispersal season (immigration probability is one). I present examples of evolutionary branching in a wide parameter range, when the patches with high local death rate during the dispersal season guarantee a high expected disperser output. I find that two dispersal strategies can coexist after evolutionary branching: a strategy with full immigration only into the patches with high expected disperser output coexists with a strategy that immigrates into any patch. Stochastic simulations agree with the numerical predictions. Since evolutionary branching is also found when immigration evolves alone, the present study is adding coevolutionary constraints on the emigration traits and hence finds that the coevolution of a higher dimensional trait sometimes hinders evolutionary diversification. Copyright © 2017

Lidocaine patches reduce pain in trauma patients with rib fractures.

Science.gov (United States)

Zink, Karen A; Mayberry, John C; Peck, Ellen G; Schreiber, Martin A

2011-04-01

Rib fracture pain is notoriously difficult to manage. The lidocaine patch is effective in other pain scenarios with an excellent safety profile. This study assesses the efficacy of lidocaine patches for treating rib fracture pain. A prospectively gathered cohort of patients with rib fracture was retrospectively analyzed for use of lidocaine patches. Patients treated with lidocaine patches were matched to control subjects treated without patches. Subjective pain reports and narcotic use before and after patch placement, or equivalent time points for control subjects, were gathered from the chart. All patients underwent long-term follow-up, including a McGill Pain Questionnaire (MPQ). Twenty-nine patients with lidocaine patches (LP) and 29 matched control subjects (C) were analyzed. During the 24 hours before patch placement, pain scores and narcotic use were similar (LP 5.3, C 4.6, P = 0.19 and LP 51, C 32 mg morphine, P = 0.17). In the 24 hours after patch placement, LP patients had a greater decrease in pain scores (LP 1.2, C 0.0, P = 0.01) with no change in narcotic use (LP -8.4, C 0.5-mg change in morphine, P = 0.25). At 60 days, LP patients had a lower MPQ pain score (LP 7.7, C 12.2, P rib fracture pain. Lidocaine patches resulted in a sustained reduction in pain, outlasting the duration of therapy.

The hedgehog receptor patched is involved in cholesterol transport.

Directory of Open Access Journals (Sweden)

Michel Bidet

Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

Sleep Sleeping Patch

Institute of Scientific and Technical Information of China (English)

2008-01-01

The Sleep Sleeping Patch is a new kind of external patch based on modern sleep medicine research achievements, which uses the internationally advanced transdermal therapeutic system (TTS). The Sleep Sleeping Patch transmits natural sleep inducers such as peppermint and liquorice extracts and melatonin through the skin to induce sleep. Clinical research proves that the Sleep Sleeping Patch can effectively improve insomnia and the quality of sleep. Highly effective: With the modern TTS therapy,

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex

Science.gov (United States)

Naumann, Robert K.; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L.

2016-01-01

ABSTRACT To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin‐positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin‐negative and calbindin‐positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin‐positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin‐positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10‐fold over a 20,000‐fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. J. Comp. Neurol. 524:783–806, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26223342

pH distribution in human tumors

International Nuclear Information System (INIS)

Thistlethwaite, A.J.; Leeper, D.B.; Moylan, D.J.; Nerlinger, R.E.

1984-01-01

pH distribution in human tumors is being determined to evaluate this parameter as a prognostic indicator of hyperthermia response. pH is measured by a modified glass pH electrode (21g, model MI 408, Microelectrodes, Inc., Londonderry, NH) inserted through an 18g open-ended Angiocath. Eight tumors have been evaluated to date; and of those, 3 were also assayed after the first heat treatment coincident with determination of blood flow. Tumors were between 2-5 cm, of various histologies, and of primary, recurrent, or metastatic origin. 2-4 measurements were made per tumor. Pretreatment readings were between 6.4 and 7.2 pH units. As tumor blood flow increased after 1 hr heating (41.5 - 43 0 ) pH rose 0.1 - 0.3 units. Normal rat muscle yields pH readings of 7.35 - 7.45. Although there was considerable heterogeneity of pH within tumors, accuracy and drift were not a problem. 5-15 min were required for pH stabilization after catheter insertion and <5 min after electrode insertion. A saline wheal was used for anesthesia to preclude modification of pH by anesthetics. Patient tolerance has not been a problems. This study suggests that human tumor tissue has a preponderance of areas more acidic than normal tissue. This may serve to sensitize tumor cells to hyperthermia and provide a prognostic indicator of tumor response

Histological distinction between early allergic and irritant patch test reactions

DEFF Research Database (Denmark)

Vestergaard, L; Clemmensen, Ole; Sørensen, Flemming Brandt

1999-01-01

no recognizable changes except a slight follicular spongiosis in 1 patient. The 2 pathologists agreed independently on the correct classification in 6 out of 7 cases (p=0.0156). We tested an optimized model, selecting non-irritant allergens and a well-known irritant. Further investigations are needed to elucidate......Comparative light microscopic studies have revealed subtle differences between allergic and irritant reactions in the skin. In the search for specific differences, we focussed on the early inflammatory response. This pilot study was conducted to test the hypothesis that follicular spongiosis can...... differentiate between early allergic and irritant patch test reactions. 8 patients with known contact allergy to either colophony or quarternium-15 participated in the study. In each patient, allergic and irritant patch tests reactions were elicited, and 4-mm punch biopsies were taken after 6 8 h from...

Adult 4-H Volunteer Empowerment in 4-H Youth Development Settings

Science.gov (United States)

Olsen, Pamela

2009-01-01

The primary purpose of this study was to determine which factors related to adult 4-H volunteer empowerment in 4-H youth development settings. This study examined the relationship of adult 4-H volunteers' perceived leadership styles of Oregon 4-H Youth Development Educators (YDE) to the adult 4-H volunteer sense of empowerment. In addition,…

[(3)H]8-Ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]-purin-5-one ([(3)H]PSB-11), a novel high-affinity antagonist radioligand for human A(3) adenosine receptors.

Science.gov (United States)

Müller, Christa E; Diekmann, Martina; Thorand, Mark; Ozola, Vita

2002-02-11

This study describes the preparation and binding properties of [(3)H]PSB-11, a novel, potent, and selective antagonist radioligand for human A(3) adenosine receptors (ARs). [(3)H]PSB-11 binding to membranes of Chinese hamster ovary (CHO) cells expressing the human A(3) AR was saturable and reversible. Saturation experiments showed that [(3)H]PSB-11 labeled a single class of binding sites with high affinity (K(D)=4.9 nM) and limited capacity (B(max)=3500 fmol/mg of protein). PSB-11 is highly selective versus the other adenosine receptor subtypes. The new radioligand shows an extraordinarily low degree of non-specific binding rendering it a very useful tool for studying the (patho)physiological roles of A(3 )ARs.

Human CD4 restores normal T cell development and function in mice deficient in murine CD4

OpenAIRE

1994-01-01

The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positiv...

Nickel patch test reactivity and the menstrual cycle

DEFF Research Database (Denmark)

Rohold, A E; Halkier-Sørensen, L; Thestrup-Pedersen, K

1994-01-01

Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation to the menstr......Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation...... were tested first on day 7-10 and the other half first on day 20-24. There was no difference in the degree of patch test reactivity, when the results from day 7-10 and day 20-24 were compared (p > 0.4). However, when we compared the patch test results from the first and second test procedure, we found...... of positive patch tests led to an increased skin reactivity towards the same allergen, when the patients were retested weeks later....

The effect of transdermal nicotine patches on sleep and dreams.

Science.gov (United States)

Page, F; Coleman, G; Conduit, R

2006-07-30

This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

Histamine H4 receptor in oral lichen planus.

Science.gov (United States)

Salem, A; Al-Samadi, A; Stegajev, V; Stark, H; Häyrinen-Immonen, R; Ainola, M; Hietanen, J; Konttinen, Y T

2015-04-01

Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts. Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circularly Polarized Slotted Microstrip Patch Antenna with Finite Ground Plane

Directory of Open Access Journals (Sweden)

Sanyog Rawat

2012-12-01

Full Text Available In this paper a new geometry of circularly polarized patch antenna is proposed with improved bandwidth. The radiation performance of proposed patch antenna is investigated using IE3D simulation software and its performance is compared with that of conventional rectangular patch antenna. The simulated return loss, axial ratio and impedance with frequency for the proposed antenna are reported in this paper. It is shown that by selecting suitable ground-plane dimensions, air gap and location of the slots, the impedance bandwidth can be enhanced upto 10.15% as compared to conventional rectangular patch (4.24% with an axial ratio bandwidth of 4.05%.

Synthesis of N-(5-(Substitutedphenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine from 4-Amino-4H-1,2,4-triazole

Directory of Open Access Journals (Sweden)

Ashvin D. Panchal

2011-01-01

Full Text Available N-(4H-1,2,4-Triazol-4-ylacetamide (2 were prepared by reaction of 4-amino-4H-1,2,4-triazole (1 with acetyl chloride in dry benzene. It has been reacted with various aromatic aldehyde to afford 3-(substitutedphenyl-N-(4H-1,2,4-triazol-4-ylacrylamide (3a-e. The synthesis of N-(5-substitutedphenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine (4a-e is achieved by the cyclisation of 3a-e with hydrazine hydrate in ethanol. The structures of synthesized compounds were characterized by 1H NMR and IR spectroscopic studies. The purity of the compounds was checked by thin layer chromatography.

Capsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury: Two Case Reports.

Science.gov (United States)

Trbovich, Michelle; Yang, Huiqing

2015-08-01

Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. A retrospective review was conducted on the effects of the patch in two patients with spinal cord injury and neuropathic pain refractory to standard treatments. Two weeks after application, both patients reported complete pain relief. Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury.

Uptake of 3H-choline and synthesis of 3H-acetylcholine by human penile corpus cavernosum

International Nuclear Information System (INIS)

Blanco, R.; Saenz de Tejada, I.; Azadzoi, K.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A.

1986-01-01

The neuroeffectors which relax penile smooth muscle and lead to erection are unknown; physiological studies of human corpus cavernosum, in vitro, have suggested a significant role of cholinergic neurotransmission. To further characterize the importance of cholinergic nerves, biopsies of human corpus cavernosum were obtained at the time of penile prosthesis implantation. Tissues were incubated in 3 H-choline (10 -5 M, 80 Ci/mmol) in oxygenated physiological salt solution at 37 0 C, pH 7.4 for 1 hour. Radiolabelled compounds were extracted with perchloric acid (0.4 M) and acetylcholine and choline were separated by HPLC; 14 C-acetylcholine was used as internal standard. 3 H-choline was accumulated by the tissues (20 +/- 1.9 fmol/mg), and 3 H-acetylcholine was synthesized (4.0 +/- 1.1 fmol/mg). In control experiments, heating of the tissue blocked synthesis of 3 H-acetylcholine. Inhibition of high affinity choline transport by hemicholinium-3 (10 -5 M) diminished tissue accumulation of 3 H-choline and significantly reduced the synthesis of 3 H-acetylcholine (0.5 +/ 0.2 fmol/mg, p < 0.05). These results provide direct evidence of neuronal accumulation of choline and enzymatic conversion to acetylcholine in human corpus cavernosum. Taken together with the physiological studies, it can be concluded that cholinergic neurotransmission in human corpus cavernosum plays a role in penile erection

SO4= uptake and catalase role in preconditioning after H2O2-induced oxidative stress in human erythrocytes.

Science.gov (United States)

Morabito, Rossana; Remigante, Alessia; Di Pietro, Maria Letizia; Giannetto, Antonino; La Spada, Giuseppina; Marino, Angela

2017-02-01

Preconditioning (PC) is an adaptive response to a mild and transient oxidative stress, shown for the first time in myocardial cells and not described in erythrocytes so far. The possible adaptation of human erythrocytes to hydrogen peroxide (H 2 O 2 )-induced oxidative stress has been here verified by monitoring one of band 3 protein functions, i.e., Cl - /HCO 3 - exchange, through rate constant for SO 4 = uptake measurement. With this aim, erythrocytes were exposed to a mild and transient oxidative stress (30 min to either 10 or 100 μM H 2 O 2 ), followed by a stronger oxidant condition (300- or, alternatively, 600-μM H 2 O 2 treatment). SO 4 = uptake was measured by a turbidimetric method, and the possible role of catalase (CAT, significantly contributing to the anti-oxidant system in erythrocytes) in PC response has been verified by measuring the rate of H 2 O 2 degradation. The preventive exposure of erythrocytes to 10 μM H 2 O 2 , and then to 300 μM H 2 O 2 , significantly ameliorated the rate constant for SO 4 = uptake with respect to 300 μM H 2 O 2 alone, showing thus an adaptive response to oxidative stress. Our results show that (i) SO 4 = uptake measurement is a suitable model to monitor the effects of a mild and transient oxidative stress in human erythrocytes, (ii) band 3 protein anion exchange capability is retained after 10 μM H 2 O 2 treatment, (iii) PC response induced by the 10 μM H 2 O 2 pretreatment is clearly detected, and (iv) PC response, elicited by low-concentrated H 2 O 2 , is mediated by CAT enzyme and does not involve band 3 protein tyrosine phosphorylation pathways. Erythrocyte adaptation to a short-term oxidative stress may serve as a basis for future studies about the impact of more prolonged oxidative events, often associated to aging, drug consumption, chronic alcoholism, hyperglycemia, or neurodegenerative diseases.

Preexisting CD4+ T-cell immunity in human population to avian influenza H7N9 virus: whole proteome-wide immunoinformatics analyses.

Directory of Open Access Journals (Sweden)

Venkata R Duvvuri

Full Text Available In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies. Hence, the assessment of preexisting CD4+ T-cell immunity to conserved epitopes shared between H7N9 and human influenza A viruses (IAV is critical. A comparative whole proteome-wide immunoinformatics analysis was performed to predict the CD4+ T-cell epitopes that are commonly conserved within the proteome of H7N9 in reference to IAV subtypes (H1N1, H2N2, and H3N2. The CD4+ T-cell epitopes that are commonly conserved (∼ 556 were further screened against the Immune Epitope Database (IEDB to validate their immunogenic potential. This analysis revealed that 45.5% (253 of 556 epitopes are experimentally proven to induce CD4+ T-cell memory responses. In addition, we also found that 23.3% of CD4+ T-cell epitopes have ≥ 90% of sequence homology with experimentally defined CD8+ T-cell epitopes. We also conducted the population coverage analysis across different ethnicities using commonly conserved CD4+ T-cell epitopes and corresponding HLA-DRB1 alleles. Interestingly, the indigenous populations from Canada, United States, Mexico and Australia exhibited low coverage (28.65% to 45.62% when compared with other ethnicities (57.77% to 94.84%. In summary, the present analysis demonstrate an evidence on the likely presence of preexisting T-cell immunity in human population and also shed light to understand the potential risk of H7N9 virus among indigenous populations, given their high susceptibility during previous pandemic influenza events. This information is crucial for public health policy, in targeting priority groups for immunization programs.

A rivastigmine patch for the treatment of Alzheimer's disease and Parkinson's disease dementia.

Science.gov (United States)

Cummings, Jeffrey; Winblad, Bengt

2007-11-01

Rivastigmine patch is the first transdermal treatment to be approved for Alzheimer's disease (AD) and Parkinson's disease dementia in the USA and for AD in Europe. It provides smooth, continuous drug delivery, and has the potential to maintain rivastigmine concentrations within an optimal therapeutic window while avoiding the peaks and troughs associated with oral drug delivery. The target dose, rivastigmine 9.5 mg/24 h patch (a 10 cm(2) patch), is given once daily and requires a simple one-step dose titration to the therapeutic dose. In a 24-week study in 1195 AD patients, the rivastigmine 9.5 mg/24 h patch provided similar efficacy to the highest dose range of capsules, with approximately three-times fewer reports of nausea and vomiting. Patients in the 9.5 mg/24 h patch and 12 mg/day capsule groups evidenced significant improvements versus placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale-Cognitive subscale; and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change; in addition to the following secondary outcome measures: Alzheimer's Disease Cooperative Study-Activities of Daily Living scale; Mini-Mental State Examination; and Trail Making Test Part A for assessment of attention, visual tracking and motor processing speed. Treatment differences on the Neuropsychiatric Inventory and Ten Point Clock-drawing Test did not reach statistical significance in this study. The patch may be the optimal way to treat dementia patients with rivastigmine.

The art and science of mission patches and their origins in society

Science.gov (United States)

Brumfitt, A.; Thompson, L. A.; Raitt, D.

2008-06-01

Space exploration utilizes some of the latest and highest technology available to human kind; synonymous with space exploration is the mission patch. This specialized art form popularizes the exploration of space with millions of mission patches sold around the world. Space tourism and education centres like the Kennedy Space Centre rely heavily on each space shuttle launch to support their merchandising of mission patches, from the traditional sew on badge to T shirts. Do mission patches tell a story? Are they Art? What is the origin and role of this art form in society? The art form of space mission patches combines the 21st century relevance with heraldic origins predating the ninth century. The space mission patch is designed by the astronauts themselves if it is a manned mission. As an education tool teachers and educators use the space mission patch to engage their students in the excitement of space exploration, the mission patch design is utilized as an education tool in literature, science and art. The space mission patch is a particularly powerful message medium. This paper looks at the origins of the space mission patch, its relevance to art and its impact on society.

The extracellular loop 2 (ECL2 of the human histamine H4 receptor substantially contributes to ligand binding and constitutive activity.

Directory of Open Access Journals (Sweden)

David Wifling

Full Text Available In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R shows extraordinarily high constitutive activity. In the extracellular loop (ECL, replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R.

Directly patching high-level exchange-correlation potential based on fully determined optimized effective potentials

Science.gov (United States)

Huang, Chen; Chi, Yu-Chieh

2017-12-01

The key element in Kohn-Sham (KS) density functional theory is the exchange-correlation (XC) potential. We recently proposed the exchange-correlation potential patching (XCPP) method with the aim of directly constructing high-level XC potential in a large system by patching the locally computed, high-level XC potentials throughout the system. In this work, we investigate the patching of the exact exchange (EXX) and the random phase approximation (RPA) correlation potentials. A major challenge of XCPP is that a cluster's XC potential, obtained by solving the optimized effective potential equation, is only determined up to an unknown constant. Without fully determining the clusters' XC potentials, the patched system's XC potential is "uneven" in the real space and may cause non-physical results. Here, we developed a simple method to determine this unknown constant. The performance of XCPP-RPA is investigated on three one-dimensional systems: H20, H10Li8, and the stretching of the H19-H bond. We investigated two definitions of EXX: (i) the definition based on the adiabatic connection and fluctuation dissipation theorem (ACFDT) and (ii) the Hartree-Fock (HF) definition. With ACFDT-type EXX, effective error cancellations were observed between the patched EXX and the patched RPA correlation potentials. Such error cancellations were absent for the HF-type EXX, which was attributed to the fact that for systems with fractional occupation numbers, the integral of the HF-type EXX hole is not -1. The KS spectra and band gaps from XCPP agree reasonably well with the benchmarks as we make the clusters large.

Patch dynamics of a foraging assemblage of bees.

Science.gov (United States)

Wright, David Hamilton

1985-03-01

The composition and dynamics of foraging assemblages of bees were examined from the standpoint of species-level arrival and departure processes in patches of flowers. Experiments with bees visiting 4 different species of flowers in subalpine meadows in Colorado gave the following results: 1) In enriched patches the rates of departure of bees were reduced, resulting in increases in both the number of bees per species and the average number of species present. 2) The reduction in bee departure rates from enriched patches was due to mechanical factors-increased flower handling time, and to behavioral factors-an increase in the number of flowers visited per inflorescence and in the number of inflorescences visited per patch. Bees foraging in enriched patches could collect nectar 30-45% faster than those foraging in control patches. 3) The quantitative changes in foraging assemblages due to enrichment, in terms of means and variances of species population sizes, fraction of time a species was present in a patch, and in mean and variance of the number of species present, were in reasonable agreement with predictions drawn from queuing theory and studies in island biogeography. 4) Experiments performed with 2 species of flowers with different corolla tube lengths demonstrated that manipulation of resources of differing availability had unequal effects on particular subsets of the larger foraging community. The arrival-departure process of bees on flowers and the immigration-extinction process of species on islands are contrasted, and the value of the stochastic, species-level approach to community composition is briefly discussed.

Esophageal motility and 24-h pH profiles of patients with heterotopic gastric mucosa in the cervical esophagus.

Science.gov (United States)

Korkut, Esin; Bektaş, Mehmet; Alkan, Murat; Ustün, Yusuf; Meco, Cem; Ozden, Ali; Soykan, Irfan

2010-02-01

Heterotopic gastric mucosa occurs as a flat island of red mucosa in the proximal third of the esophagus where it gives rise to the cervical inlet patch. The aims of this study were to investigate the esophageal motility pattern and 24-h pH profiles of patients with cervical inlet patch. Thirty patients (16 women, mean age: 44.9 years, range: 23-72) diagnosed as having heterotopic gastric mucosa in the cervical esophagus with upper gastrointestinal symptoms had undergone esophageal motility testing and 24-h pH monitorisation with a double-channel pH probe. Manometric investigation was abnormal in 7 patients (non-specific esophageal motor disorder in 4 patients, esophageal hypomotility in 1 patient, and hypotensive LES in 2 patients). Pathological acid reflux (pHesophagus (percentage of total time of pHmotor dysfunction and "acid independent episodes" from the patches. These abnormalities may be responsible for some of the symptoms of HGM patients. Copyright 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Fault-patch stress-transfer efficiency in presence of sub-patch geometric complexity

KAUST Repository

Zielke, Olaf

2015-04-01

It is well known that faults are not planar surfaces. Instead they exhibit self-similar or self-affine properties that span a wide range of spatial (sub-micrometer to tens-of-kilometer). This geometric fault roughness has a distinct impact on amount and distribution of stresses/strains induced in the medium and on other portions of the fault. However, when numerically simulated (for example in multi-cycle EQ rupture simulations or Coulomb failure stress calculations) this roughness is largely ignored: individual fault patches --the incremental elements that build the fault surface in the respective computer models-- are planar and fault roughness at this and lower spatial scales is not considered. As a result, the fault-patch stress-transfer efficiency may be systematically too large in those numerical simulations with respect to the "actual" efficiency level. Here, we investigate the effect of sub-patch geometric complexity on fault-patch stress-transfer efficiency. For that, we sub-divide a fault patch (e.g., 1x1km) into a large number of sub-patches (e.g., 20x20m) and determine amount of induced stresses at selected positions around that patch for different levels and realizations of fault roughness. For each fault roughness level, we compute mean and standard deviation of the induced stresses, enabling us to compute the coefficient of variation. We normalize those values with stresses from the corresponding single (planar) fault patch, providing scaling factors and their variability for stress transfer efficiency. Given a certain fault roughness that is assumed for a fault, this work provides the means to implement the sub-patch fault roughness into investigations based on fault-patch interaction schemes.

Electrophysiological Analysis of human Pluripotent Stem Cell-derived Cardiomyocytes (hPSC-CMs) Using Multi-electrode Arrays (MEAs).

Science.gov (United States)

Sala, Luca; Ward-van Oostwaard, Dorien; Tertoolen, Leon G J; Mummery, Christine L; Bellin, Milena

2017-05-12

Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine. This would be facilitated by deriving hPSC-CMs from patients or susceptible individuals as hiPSCs. For all applications, however, precise measurement and analysis of hPSC-CM electrical properties are essential for identifying changes due to cardiac ion channel mutations and/or drugs that target ion channels and can cause sudden cardiac death. Compared with manual patch-clamp, multi-electrode array (MEA) devices offer the advantage of allowing medium- to high-throughput recordings. This protocol describes how to dissociate 2D cell cultures of hPSC-CMs to small aggregates and single cells and plate them on MEAs to record their spontaneous electrical activity as field potential. Methods for analyzing the recorded data to extract specific parameters, such as the QT and the RR intervals, are also described here. Changes in these parameters would be expected in hPSC-CMs carrying mutations responsible for cardiac arrhythmias and following addition of specific drugs, allowing detection of those that carry a cardiotoxic risk.

Impacts of feedlot floor condition, deposition frequency, and inhibitors on N2O and CH4 emissions from feedlot dung and urine patches.

Science.gov (United States)

Liao, Wenhua; Liu, Chunjing; Gao, Zhiling

2018-04-09

Patches of dung and urine are major contributors to the feedlot gas emissions. This study investigated the impacts of dung deposition frequency (partly reflecting animal stocking density of a feedlot), dairy feedlot floor conditions (old floor indicated with the presence of consolidated manure pad [CMP] vs. new floor with the absence of consolidated manure pad [CMPn]), and application of dicyandiamide (DCD) and hydroquinone (HQ) on nitrous oxide (N 2 O) and methane (CH 4 ) emissions from patches in the laboratory, and the integrative impacts were expressed in terms of global warming potential (CO 2 -equivalent). Dung deposition frequency, feedlot floor condition, and application of inhibitors showed inverse impacts on N 2 O and CH 4 emissions from patches. Greenhouse gas (GHG) emissions from the dung, urine, and dung+urine patches on the CMP feedlot surface were approximately 7.48, 87.35, and 7.10 times those on the CMPn feedlot surface (P emissions from CMP and CMPn feedlot surfaces under high deposition frequency condition were approximately 10 and 1.7 times those under low-frequency condition. Moreover, application of HQ slightly reduced the GHG emission from urine patches, by 14.9% (P > 0.05), while applying DCD or DCD+HQ significantly reduced the GHG, by 60.3% and 65.0%, respectively (P emission factors for feedlots. In the future, field measurements to quantitatively evaluate the relative contribution of nitrification and denitrification to the N 2 O emissions of feedlot surfaces are highly required for effective N 2 O control. This study shows that feedlot CH 4 and N 2 O emissions inversely respond to the dicyandiamide (DCD) application. Applying DCD significantly reduces GHG emissions of feedlot urine patches. Feedlot floor condition and stocking density strongly impact feedlot GHG emissions. Including feedlot floor condition and stocking density in the feedlot EF determining process is necessary.

Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

Directory of Open Access Journals (Sweden)

Kaytlyn A Gerbin

Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice.

Science.gov (United States)

Lee, I-Chi; Lin, Wei-Ming; Shu, Jwu-Ching; Tsai, Shau-Wei; Chen, Chih-Hao; Tsai, Meng-Tsan

2017-01-01

Dissolving microneedles (MNs) display high efficiency in delivering poorly permeable drugs and vaccines. Here, two-layer dissolving polymeric MN patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were fabricated with a two-step casting and centrifuging process to localize the insulin in the needle and achieve efficient transdermal delivery of insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine 6G and fluorescein isothiocyanate-labeled insulin (insulin-FITC) can gradually diffuse from the puncture sites to deeper tissue. Ex vivo drug-release profiles showed that 50% of the insulin was released and penetrated across the skin after 1 h, and the cumulative permeation reached 80% after 5 h. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MN patches on diabetic mice for glucose regulation. The total area above the glucose level versus time curve as an index of hypoglycemic effect was 128.4 ± 28.3 (% h) at 0.25 IU/kg. The relative pharmacologic availability and relative bioavailability (RBA) of insulin from MN patches were 95.6 and 85.7%, respectively. This study verified that the use of gelatin/CMC MN patches for insulin delivery achieved a satisfactory RBA compared to traditional hypodermic injection and presented a promising device to deliver poorly permeable protein drugs for diabetic therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 84-93, 2017. © 2016 Wiley Periodicals, Inc.

A DOUBLE E SHAPED MICROSTRIP PATCH ANTENNA FOR MULTIBAND APPLICATIONS

Directory of Open Access Journals (Sweden)

Pristin K Mathew

2014-06-01

Full Text Available This paper presents a dual band Compact double E shaped Microstrip Patch antenna with enhanced gain for Worldwide Interoperability for Microwave Access (WI-MAX, Universal Mobile Telecommunication Systems (UMTS and Satellite applications. The modified E shaped patch antenna is designed using CADFEKO and the results of return loss, Voltage Standing Wave Ratio (VSWR, gain of the proposed antenna are compared with a conventional E shaped patch antenna. The results show that the double E shaped wideband patch antenna has an impedance bandwidth of 10.7 % with a return loss of -13.6dB, -12.4 dB, -12.1dB and -14.2dB at resonant frequencies of 1.96 GHz, 3.62 GHz, 5.76 GHz and 6.82 GHz, whereas a conventional E shaped patch antenna operates at 2.5 GHz, 3.4 GHz and 5.5 GHz with a return loss of -16 dB each and impedance bandwidth of 10.6 %. Both the antennas uses Coaxial Probe feeding technique and Flame Retardant 4 (FR-4 as the substrate material with a thickness of 2.87 mm. A parametric study has been done so as to understand the effect of each parameter to obtain a better performance and optimised results.

Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog.

Science.gov (United States)

Tukachinsky, Hanna; Petrov, Kostadin; Watanabe, Miyako; Salic, Adrian

2016-10-04

The Hedgehog cell-cell signaling pathway is crucial for animal development, and its misregulation is implicated in numerous birth defects and cancers. In unstimulated cells, pathway activity is inhibited by the tumor suppressor membrane protein, Patched. Hedgehog signaling is triggered by the secreted Hedgehog ligand, which binds and inhibits Patched, thus setting in motion the downstream events in signal transduction. Despite its critical importance, the mechanism by which Hedgehog antagonizes Patched has remained unknown. Here, we show that vertebrate Patched1 inhibition is caused by direct, palmitate-dependent interaction with the Sonic Hedgehog ligand. We find that a short palmitoylated N-terminal fragment of Sonic Hedgehog binds Patched1 and, strikingly, is sufficient to inhibit it and to activate signaling. The rest of Sonic Hedgehog confers high-affinity Patched1 binding and internalization through a distinct binding site, but, surprisingly, it is not absolutely required for signaling. The palmitate-dependent interaction with Patched1 is specifically impaired in a Sonic Hedgehog mutant causing human holoprosencephaly, the most frequent congenital brain malformation, explaining its drastically reduced potency. The palmitate-dependent interaction is also abolished in constitutively inhibited Patched1 point mutants causing the Gorlin cancer syndrome, suggesting that they might adopt a conformation distinct from the wild type. Our data demonstrate that Sonic Hedgehog signals via the palmitate-dependent arm of a two-pronged contact with Patched1. Furthermore, our results suggest that, during Hedgehog signaling, ligand binding inhibits Patched by trapping it in an inactive conformation, a mechanism that explains the dramatically reduced activity of oncogenic Patched1 mutants.

Experimental patch testing with chromium-coated materials.

Science.gov (United States)

Bregnbak, David; Thyssen, Jacob P; Jellesen, Morten S; Zachariae, Claus; Johansen, Jeanne D

2017-06-01

Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. To examine patch test reactivity to chromium-coated discs. We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients. Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent

DEFF Research Database (Denmark)

Kress, Hans G; Boss, Hildegard; Delvin, Thomas

2010-01-01

AIM: The pharmacokinetic profiles of the two commercially available transdermal fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h), used to manage severe chronic pain, were compared regarding their systemic exposure, rate of absorption, and safety. METHODS: Transdermal m...

Fast Homoepitaxial Growth of 4H-SiC Films on 4° off-Axis Substrates in a SiH4-C2H4-H2 System

International Nuclear Information System (INIS)

Liu Bin; Sun Guo-Sheng; Liu Xing-Fang; Zhang Feng; Dong Lin; Zheng Liu; Yan Guo-Guo; Liu Sheng-Bei; Zhao Wan-Shun; Wang Lei; Zeng Yi-Ping; Wang Zhan-Guo; Li Xi-Guang; Yang Fei

2013-01-01

Homoepitaxial growth of 4H-SiC epilayers is conducted in a SiH 4 -C 2 H 4 -H 2 system by low pressure hot-wall vertical chemical vapor deposition (CVD). Thick epilayers of 45 μm are achieved at a high growth rate up to 26 μm/h under an optimized growth condition, and are characterized by using a Normaski optical microscope, a scanning electronic microscope (SEM), an atomic force microscope (AFM) and an x-ray diffractometer (XRD), indicating good crystalline quality with mirror-like smooth surfaces and an rms roughness of 0.9 nm in a 5 μm × 5μm area. The dependence of the 4H-SiC growth rate on growth conditions on 4° off-axis 4H-SiC substrates and its mechanism are investigated. It is found that the H 2 flow rate could influence the surface roughness, while good surface morphologies without Si droplets and epitaxial defects such as triangular defects could be obtained by increasing temperature

Numerical evaluation of human exposure to WiMax patch antenna in tablet or laptop.

Science.gov (United States)

Siervo, Beatrice; Morelli, Maria Sole; Landini, Luigi; Hartwig, Valentina

2018-04-30

The use of wireless communication devices, such as tablets or laptops, is increasing among children. Only a few studies assess specific energy absorption rate (SAR) due to exposure from wireless-enabled tablets and laptops, in particular with Worldwide Interoperability for Microwave Access (WiMax) technology. This paper reports the estimation of the interaction between an E-shaped patch antenna (3.5 GHz) and human models, by means of finite-difference time-domain (FDTD) method. Specifically, four different human models (young adult male, young adult female, pre-teenager female, male child) in different exposure conditions (antenna at different distances from the human model, in different positions, and orientations) were considered and whole-body, 10 and 1 g local SAR and magnetic field value (Bmax) were evaluated. From our results, in some worst-case scenarios involving male and female children's exposure, the maximum radiofrequency energy absorption (hot spots) is located in more sensitive organs such as eye, genitals, and breast. Bioelectromagnetics. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Closed-Loop Real-Time Imaging Enables Fully Automated Cell-Targeted Patch-Clamp Neural Recording In Vivo.

Science.gov (United States)

Suk, Ho-Jun; van Welie, Ingrid; Kodandaramaiah, Suhasa B; Allen, Brian; Forest, Craig R; Boyden, Edward S

2017-08-30

Targeted patch-clamp recording is a powerful method for characterizing visually identified cells in intact neural circuits, but it requires skill to perform. We previously developed an algorithm that automates "blind" patching in vivo, but full automation of visually guided, targeted in vivo patching has not been demonstrated, with currently available approaches requiring human intervention to compensate for cell movement as a patch pipette approaches a targeted neuron. Here we present a closed-loop real-time imaging strategy that automatically compensates for cell movement by tracking cell position and adjusting pipette motion while approaching a target. We demonstrate our system's ability to adaptively patch, under continuous two-photon imaging and real-time analysis, fluorophore-expressing neurons of multiple types in the living mouse cortex, without human intervention, with yields comparable to skilled human experimenters. Our "imagepatching" robot is easy to implement and will help enable scalable characterization of identified cell types in intact neural circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Dose Accuracy of Durable and Patch Insulin Infusion Pumps

Science.gov (United States)

Jahn, Luis G.; Capurro, Jorge J.; Levy, Brian L.

2013-01-01

Background: As all major insulin pump manufacturers comply with the international infusion pump standard EN 60601-2-24:1998, there may be a general assumption that all pumps are equal in insulin-delivery accuracy. This research investigates single-dose and averaged-dose accuracy of incremental basal deliveries for one patch model and three durable models of insulin pumps. Method: For each pump model, discrete single doses delivered during 0.5 U/h basal rate infusion over a 20 h period were measured using a time-stamped microgravimetric system. Dose accuracy was analyzed by comparing single doses and time-averaged doses to specific accuracy thresholds (±5% to ±30%). Results: The percentage of single doses delivered outside accuracy thresholds of ±5%, ±10%, and ±20% were as follows: Animas OneTouch® Ping® (43.2%, 14.3%, and 1.8%, respectively), Roche Accu-Chek® Combo (50.6%, 24.4%, and 5.5%), Medtronic Paradigm® RevelTM/VeoTM (54.2%, 26.7%, and 6.6%), and Insulet OmniPod® (79.1%, 60.5%, and 34.9%). For 30 min, 1 h, and 2 h averaging windows, the percentage of doses delivered outside a ±15% accuracy were as follows: OneTouch Ping (1.0%, 0.4%, and 0%, respectively), Accu-Chek Combo (4.2%, 3.5%, and 3.1%), Paradigm Revel/Veo (3.9%, 3.1%, and 2.2%), and OmniPod (33.9%, 19.9%, and 10.3%). Conclusions: This technical evaluation demonstrates significant differences in single-dose and averaged-dose accuracy among the insulin pumps tested. Differences in dose accuracy were most evident between the patch pump model and the group of durable pump models. Of the pumps studied, the Animas OneTouch Ping demonstrated the best single-dose and averaged-dose accuracy. Further research on the clinical relevance of these findings is warranted. PMID:23911184

An Adhesive Patch-Based Skin Biopsy Device for Molecular Diagnostics and Skin Microbiome Studies.

Science.gov (United States)

Yao, Zuxu; Moy, Ronald; Allen, Talisha; Jansen, Burkhard

2017-10-01

A number of diagnoses in clinical dermatology are currently histopathologically confirmed and this image recognition-based confirmation generally requires surgical biopsies. The increasing ability of molecular pathology to corroborate or correct a clinical diagnosis based on objective gene expression, mutation analysis, or molecular microbiome data is on the horizon and would be further supported by a tool or procedure to collect samples non-invasively. This study characterizes such a tool in form of a 'bladeless' adhesive patch-based skin biopsy device. The performance of this device was evaluated through a variety of complementary technologies including assessment of sample biomass, electron microscopy demonstrating the harvesting of layers of epidermal tissue, and isolation of RNA and DNA from epidermal skin samples. Samples were obtained by application of adhesive patches to the anatomical area of interest. Biomass assessment demonstrated collection of approximately 0.3mg of skin tissue per adhesive patch and electron microscopy confirmed the nature of the harvested epidermal skin tissue. The obtained tissue samples are stored in a stable fashion on adhesive patches over a wide range of temperatures (-80oC to +60oC) and for extended periods of time (7 days or more). Total human RNA, human genomic DNA and microbiome DNA yields were 23.35 + 15.75ng, 27.72 + 20.71ng and 576.2 + 376.8pg, respectively, in skin samples obtained from combining 4 full patches collected non-invasively from the forehead of healthy volunteers. The adhesive patch skin sampling procedure is well tolerated and provides robust means to obtain skin tissue, RNA, DNA, and microbiome samples without involving surgical biopsies. The non-invasively obtained skin samples can be shipped cost effectively at ambient temperature by mail or standard courier service, and are suitable for a variety of molecular analyses of the skin microbiome as well as of keratinocytes, T cells, dendritic cells

Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.

Science.gov (United States)

Bista, Sudeep R; Haywood, Alison; Hardy, Janet; Norris, Ross; Hennig, Stefanie

2016-06-01

This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. © 2015, The American College of Clinical Pharmacology.

Development of a Spirulina Extract/Alginate-Imbedded PCL Nanofibrous Cosmetic Patch.

Science.gov (United States)

Byeon, Seon Yeong; Cho, Myung Kwon; Shim, Kyou Hee; Kim, Hye Jin; Song, Hyeon Gi; Shin, Hwa Sung

2017-09-28

Cosmetic patches have recently been developed as skin products for personal care owing to rapid advances in the technology of delivery of active ingredients, moisture, and adhesiveness to skin. Alginate and Spirulina are typical marine resources used in cosmetic products. This research involved the development of a Spirulina extract-impregnated alginate nanofiber cosmetic patch supported by a polycaprolactone (PCL) nanofiber cover ( Spi /Alg-PCL NF patch). In addition to the ability of alginate to affect moisture and adhesiveness to skin, the impregnation of Spirulina extract strengthened those abilities as well as its own bioactive effectiveness. All fabrication processing steps were undertaken in aqueous solution. The three components (alginate, Spirulina extract, and PCL) had no detected cytotoxicity in human keratinocyte cell-based examination. In addition, wetting the pre-dried patch on the skin resulted in the Spirulina extract being released within 30 min. The results indicate the excellence of the Spi /Alg-PCL NF patch as a skin-care cosmetic device.

Electrical characteristics of schottky barriers on 4H-SiC: The effects of barrier height nonuniformity

Science.gov (United States)

Skromme, B. J.; Luckowski, E.; Moore, K.; Bhatnagar, M.; Weitzel, C. E.; Gehoski, T.; Ganser, D.

2000-03-01

Electrical properties, including current-voltage (I-V) and capacitance-voltage (C-V) characteristics, have been measured on a large number of Ti, Ni, and Pt-based Schottky barrier diodes on 4H-SiC epilayers. Various nonideal behaviors are frequently observed, including ideality factors greater than one, anomalously low I-V barrier heights, and excess leakage currents at low forward bias and in reverse bias. The nonidealities are highly nonuniform across individual wafers and from wafer to wafer. We find a pronounced linear correlation between I-V barrier height and ideality factor for each metal, while C-V barrier heights remain constant. Electron beam induced current (EBIC) imaging strongly suggests that the nonidealities result from localized low barrier height patches. These patches are related to discrete crystal defects, which become visible as recombination centers in the EBIC images. Alternative explanations involving generation-recombination current, uniform interfacial layers, and effects related to the periphery are ruled out.

Planar patch clamp: advances in electrophysiology.

Science.gov (United States)

Brüggemann, Andrea; Farre, Cecilia; Haarmann, Claudia; Haythornthwaite, Ali; Kreir, Mohamed; Stoelzle, Sonja; George, Michael; Fertig, Niels

2008-01-01

Ion channels have gained increased interest as therapeutic targets over recent years, since a growing number of human and animal diseases have been attributed to defects in ion channel function. Potassium channels are the largest and most diverse family of ion channels. Pharmaceutical agents such as Glibenclamide, an inhibitor of K(ATP) channel activity which promotes insulin release, have been successfully sold on the market for many years. So far, only a small group of the known ion channels have been addressed as potential drug targets. The functional testing of drugs on these ion channels has always been the bottleneck in the development of these types of pharmaceutical compounds.New generations of automated patch clamp screening platforms allow a higher throughput for drug testing and widen this bottleneck. Due to their planar chip design not only is a higher throughput achieved, but new applications have also become possible. One of the advantages of planar patch clamp is the possibility of perfusing the intracellular side of the membrane during a patch clamp experiment in the whole-cell configuration. Furthermore, the extracellular membrane remains accessible for compound application during the experiment.Internal perfusion can be used not only for patch clamp experiments with cell membranes, but also for those with artificial lipid bilayers. In this chapter we describe how internal perfusion can be applied to potassium channels expressed in Jurkat cells, and to Gramicidin channels reconstituted in a lipid bilayer.

Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

Directory of Open Access Journals (Sweden)

Mohd Nauman Saleem

2016-01-01

Full Text Available The Transdermal Drug Delivery System (TDDS is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra, Zanjabeel (Zingiber officinale, Podina (Mentha arvensis, and Sirka (Vinegar were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics.

Imaging of adenovirus-mediated expression of human sodium iodide symporter (hNIS) by 99mTcO4 scan in mice

International Nuclear Information System (INIS)

Lee, Won Woo; Moon, D. H.; Park, S. Y.; Jin, J.; Kim, S. J.; Lee, H.

2002-01-01

We have evaluated the feasibility of human sodium iodide symporter (hNIS) as a reporter gene by 99m TcO 4 scan in vivo. Recombinant adenovirus encoding hNIS (Rad-hNIS) gene was introduced to FRO cell. hNIS expression was assessed by western blot and 99m TcO 4 uptake in vitro. 99m TcO 4 scan were obtained in BALB/c mice 48 hrs post injection of Tris buffer, Rad-hNIS (1x10 9 or 2x10 8 pfu), or Rad-LacZ (1x10 9 pfu) via the tail vein (n=5-7 for each group). Biodistribution study and RT-PCR were performed. A series of 99m TcO 4 scans were obtained in 2 mice until 21 days post Rad-hNIS injection. FRO readily expressed hNIS protein and incorporated significantly higher level of 99m TcO 4 in vitro. With 99m TcO 4 scan, prominent hepatic uptake was observed only in the mice with 1x10 9 pfu of Rad-hNIS. Liver/lung ratio was increased in this group from 15 (5.7±2.5) till 60 min(6.7±3.6) (p 99m TcO 4 uptake (22.7±11.2 %ID/g) and hNIS mRNA expression were exclusively noticed in livers of this group. The persistent hepatic uptake was observed for up one week. NaClO 4 inhibited the hepatic uptake of 99m TcO 4 . hNIS holds a promising potential as an effective reporter gene for noninvasive/repeated imaging in combination with 99m TcO 4

Birth Control Patch

Science.gov (United States)

... Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Birth Control Patch KidsHealth / For Teens / Birth Control Patch What's ...

Efficient immortalization of primary human cells by p16INK4a-specific short hairpin RNA or Bmi-1, combined with introduction of hTERT.

Science.gov (United States)

Haga, Kei; Ohno, Shin-ichi; Yugawa, Takashi; Narisawa-Saito, Mako; Fujita, Masatoshi; Sakamoto, Michiie; Galloway, Denise A; Kiyono, Tohru

2007-02-01

Activation of telomerase is sufficient for immortalization of some types of human cells but additional factors may also be essential. It has been proposed that stress imposed by inadequate culture conditions induces senescence due to accumulation of p16(INK4a). Here, we present evidence that many human cell types undergo senescence by activation of the p16(INK4a)/Rb pathway, and that introduction of Bmi-1 can inhibit p16(INK4a) expression and extend the life span of human epithelial cells derived from skin, mammary gland and lung. Introduction of p16(INK4a)-specific short hairpin RNA, as well as Bmi-1, suppressed p16(INK4a) expression in human mammary epithelial cells without promoter methylation, and extended their life span. Subsequent introduction of hTERT, the telomerase catalytic subunit, into cells with low p16(INK4a) levels resulted in efficient immortalization of three cell types without crisis or growth arrest. The majority of the human mammary epithelial cells thus immortalized showed almost normal ploidy as judged by G-banding and spectral karyotyping analysis. Our data suggest that inhibition of p16(INK4a) and introduction of hTERT can immortalize many human cell types with little chromosomal instability.

Human V4 and ventral occipital retinotopic maps

Science.gov (United States)

Winawer, Jonathan; Witthoft, Nathan

2016-01-01

The ventral surface of the human occipital lobe contains multiple retinotopic maps. The most posterior of these maps is considered a potential homolog of macaque V4, and referred to as human V4 (‘hV4’). The location of the hV4 map, its retinotopic organization, its role in visual encoding, and the cortical areas it borders have been the subject of considerable investigation and debate over the last 25 years. We review the history of this map and adjacent maps in ventral occipital cortex, and consider the different hypotheses for how these ventral occipital maps are organized. Advances in neuroimaging, computational modeling, and characterization of the nearby anatomical landmarks and functional brain areas have improved our understanding of where human V4 is and what kind of visual representations it contains. PMID:26241699

Correlation of open cell-attached and excised patch clamp techniques.

Science.gov (United States)

Filipovic, D; Hayslett, J P

1995-11-01

The excised patch clamp configuration provides a unique technique for some types of single channel analyses, but maintenance of stable, long-lasting preparations may be confounded by rundown and/or rapid loss of seal. Studies were performed on the amiloride-sensitive Na+ channel, located on the apical surface of A6 cells, to determine whether the nystatin-induced open cell-attached patch could serve as an alternative configuration. Compared to excised inside-out patches, stable preparations were achieved more readily with the open cell-attached patch (9% vs. 56% of attempts). In both preparations, the current voltage (I-V) relation was linear, current amplitudes were equal at opposite equivalent clamped voltages, and Erev was zero in symmetrical Na+ solutions, indicating similar Na+ activities on the cytosolic and external surfaces of the patch. Moreover, there was no evidence that nystatin altered channel activity in the patch because slope conductance (3-4pS) and Erev (75 mV), when the bath was perfused with a high K:low Na solution (ENa = 80 mV), were nearly equal in both patch configurations. Our results therefore indicate that the nystatin-induced open cell-attached patch can serve as an alternative approach to the excised inside-out patch when experiments require modulation of univalent ions in the cytosol.

The average effective dose of 4-amino-5-(furan-2-yl-4H-1 ,2,4-triazole-3-thiol in experimental hepatitis

Directory of Open Access Journals (Sweden)

I. M. Belay

2014-04-01

Full Text Available The work presents the research of the average effective dose of 4-amino-5-(furan-2-yl-4H-1,2,4-triazole-3-thiol in experimental hepatitis. Recalculations conducted for the human with the sensitivity coefficient, average effective dose for human is 13,87 mg/kg.

Anterior temporal face patches: A meta-analysis and empirical study

Directory of Open Access Journals (Sweden)

Rebecca J. Von Der Heide

2013-02-01

Full Text Available Studies of nonhuman primates have reported face sensitive patches in the ventral anterior temporal lobes (ATL. In humans, ATL resection or damage causes an associative prosopagnosia in which face perception is intact but face memory is compromised. Some fMRI studies have extended these findings using famous and familiar faces. However, it is unclear whether these regions in the human ATL are in locations comparable to those reported in non-human primates, typically using unfamiliar faces. We present the results of two studies of person memory: a meta-analysis of existing fMRI studies and an empirical fMRI study using optimized imaging parameters. Both studies showed left-lateralized ATL activations to familiar individuals while novel faces activated the right ATL. Activations to famous faces were quite ventral, similar to what has been reported in monkeys. These findings suggest that face memory-sensitive patches in the human ATL are in the ventral/polar ATL.

Granisetron Transdermal Patch

Science.gov (United States)

Granisetron transdermal patches are used to prevent nausea and vomiting caused by chemotherapy. Granisetron is in a class of medications called 5HT3 ... Granisetron transdermal comes as a patch to apply to the skin. It is usually applied 24 to ...

Non-standard patch test

Directory of Open Access Journals (Sweden)

Astri Adelia

2018-06-01

Full Text Available In managing contact dermatitis, identification of the causative agent is essential to prevent recurrent complaints. Patch test is the gold standard to identify the causative agent. Nowadays, there are many patch test standard materials available in the market, but do not include all the materials that potentially cause contact dermatitis. Patch test using patient’s own products or later we refer to as non-standard materials, is very helpful in identifying the causative agents of contact dermatitis. Guidance is needed in producing non-standard patch test materials in order to avoid test results discrepancy.

Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.

Science.gov (United States)

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Kamezawa, Miho; Yamada, Ichimaro; Sasaki, Sigeru; Uebaba, Kazuo; Matsumoto, Hideo; Hoshino, Yuichi

2016-01-01

The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch. Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

Synthesis of symmetrical 2,2',4,4'-tetrasubstituted [4,4'-bithiazole]-5,5'(4H,4'H)-diones and their reactions with some nucleophiles

DEFF Research Database (Denmark)

Andersen, Kenneth K.; Bray, Diana D.; Kjær, Anders

1997-01-01

steric factors. X-Ray crystallography established the structure of the dehydrodimer (4R*,4R'*)-2,2'-diethoxy-4,4'-dibenzyl-[4,4'-bithiazole]-5,5'(4H,4 'H)-dione. One stereoisomer of 2,2'-diphenyl-4,4'-dimethyl-[4,4'-bithiazole]-5,5'(4H,4'H)-dione and a mixture of the stereoisomers 2,2'-diphenyl-4......-carboxylic acid and piperidylamide, was established by X-ray crystallography. Treatment of stereoisomeric mixtures of 2,2'-diethoxy-4,4'-bithiazolones with HCl in benzene gave the corresponding racemic and meso bis-(N-carboxythioanhydride)s. A stereoisomeric mixture of the bis...

Mechanisms of sampling interstitial fluid from skin using a microneedle patch.

Science.gov (United States)

Samant, Pradnya P; Prausnitz, Mark R

2018-05-01

Although interstitial fluid (ISF) contains biomarkers of physiological significance and medical interest, sampling of ISF for clinical applications has made limited impact due to a lack of simple, clinically useful techniques that collect more than nanoliter volumes of ISF. This study describes experimental and theoretical analysis of ISF transport from skin using microneedle (MN) patches and demonstrates collection of >1 µL of ISF within 20 min in pig cadaver skin and living human subjects using an optimized system. MN patches containing arrays of submillimeter solid, porous, or hollow needles were used to penetrate superficial skin layers and access ISF through micropores (µpores) formed upon insertion. Experimental studies in pig skin found that ISF collection depended on transport mechanism according to the rank order diffusion sampling is transport through the dermis. Based on these studies and other considerations like safety and convenience for future clinical use, we designed an MN patch prototype to sample ISF using suction as the driving force. Using this approach, we collected ISF from human volunteers and identified the presence of biomarkers in the collected ISF. In this way, sampling ISF from skin using an MN patch could enable collection of ISF for use in research and medicine.

Study of LCP based flexible patch antenna array

KAUST Repository

Ghaffar, Farhan A.; Shamim, Atif; Roy, Langis

2012-01-01

Wrapping of a two element LCP based patch antenna array is studied in this work. For the first time, the designed array is bent in both E and H planes to observe the effect on the radiation and impedance performance of the antenna. The 38 GHz

Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol.

Science.gov (United States)

Fili, S; Valmas, A; Norrman, M; Schluckebier, G; Beckers, D; Degen, T; Wright, J; Fitch, A; Gozzo, F; Giannopoulou, A E; Karavassili, F; Margiolaki, I

2015-09-01

This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50-8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.

Nicotine patches improve mood and response speed in a lexical decision task.

Science.gov (United States)

Gentry, M V; Hammersley, J J; Hale, C R; Nuwer, P K; Meliska, C J

2000-01-01

The effects of smoking a cigarette or wearing a transdermal nicotine patch on mood and lexical decision-making were tested in eight smokers. Each participant was tested after 4 hours of smoking abstinence, under 4 conditions: placebo (very low nicotine) cigarette, nicotine cigarette, placebo patch, and nicotine patch. Relative to placebo, wearing the nicotine patch reduced Profile of Mood States (POMS) Total Mood Disturbance and Fatigue/Inertia scores, while increasing the speed of some types of lexical decisions. Smoking a nicotine cigarette did not affect reaction times, but unexpectedly decreased the accuracy of Word/ Nonword lexical decisions. Thus, transdermal nicotine may improve mood and facilitate longterm memory search and/or attentional processes in nicotine-deprived smokers.

Study of ZrO2-H2SO4-(NH4)2SO4(NH4Cl)-H2O systems

International Nuclear Information System (INIS)

Motov, D.L.; Sozinova, Yu.P.; Rys'kina, M.P.

1988-01-01

Regions of formation, composition and solubility of ammonium sulfatozirconates (ASZ) in ZrO 2 -H 2 SO 4 -(NH 4 ) 2 SO 4 (NH 4 Cl)-H 2 O systems at 25 and 75 deg C are studied by the isothermal method. Five ASZ: (NH 4 ) 2 Zr(OH) 2 (SO 4 ) 2 , NH 4 ZrOH(SO 4 ) 2 xH 2 O, NH 4 ZrO 0.5 (OH) 2 SO 4 x1.5H 2 O, (NH 4 ) 2 Zr(SO 4 ) 3 x2H 2 O, (NH 4 ) 4 Zr(SO 4 ) 4 x4H 2 O are detected, their properties are investigated. Main sulfates are new compounds never described ealier

Patch Test Negative Generalized Dermatitis.

Science.gov (United States)

Spiker, Alison; Mowad, Christen

2016-01-01

Allergic contact dermatitis is a common condition in dermatology. Patch testing is the criterion standard for diagnosis. However, dermatitis is not always caused by an allergen, and patch testing does not identify a culprit in every patient. Generalized dermatitis, defined as eczematous dermatitis affecting greater than 3 body sites, is often encountered in dermatology practice, especially patch test referral centers. Management for patients with generalized dermatitis who are patch test negative is challenging. The purpose of this article is to outline an approach to this challenging scenario and summarize the paucity of existing literature on patch test negative generalized dermatitis.

A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks

DEFF Research Database (Denmark)

Huang, Hongda; Strømme, Caroline B; Saredi, Giulia

2015-01-01

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase......, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required...... for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling...

A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks.

Science.gov (United States)

Huang, Hongda; Strømme, Caroline B; Saredi, Giulia; Hödl, Martina; Strandsby, Anne; González-Aguilera, Cristina; Chen, Shoudeng; Groth, Anja; Patel, Dinshaw J

2015-08-01

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling histones genome wide during DNA replication.

Study on the preparation of 166Ho-patch for a skin cancer treatment

International Nuclear Information System (INIS)

Kim, Y. M.; Kim, K. H.; Han, K. H.; Park, E. W.; Shin, B. C.; Park, K. B.; Lee, J. D.

1998-01-01

Radioactive patch containing holmium-166 has been developed for skin cancer treatment, and then applied to animal model and patients with malignant skin cancer. 165Ho-Patch prepared by dissolving polyurethane and 165 Ho(NO 3 ) 3 ·5H 2 O in mixing solvent of DMF and THF and casting on aluminium dish was irradiated in ''HANARO'' reactor ( Φth = 1.25 X 1013 n/cm 2 '·sec, power = 15 MW), which results in preparing 166 Ho-Patch emitting β energy of Max. 1.86 MeV (51 %), 1.78 MeV (48 %), mean 0.67 MeV and low γ energy. The 166 Ho-Patch specially designed was applied to the superficial skin cancers. Their efficacy and safety have been investigated for several months. Radioactive patch was ready to prepare by post-irradiation without special danger by radioactive material. Skin tumor could be successfully treated with 166 Ho-Patch in animal model and patients. In animal model and patients, the world's first noninvasive 166Ho-Patch readily prepared by post-irradiation proved to be safe and effective in treatment for skin cancer

3-Ethyl-4-[(E-(4-fluorobenzylideneamino]-1H-1,2,4-triazole-5(4H-thione

Directory of Open Access Journals (Sweden)

Alphonsus D'souza

2012-05-01

Full Text Available In the title compound, C11H11FN4S, the dihedral angle between the 1,2,4-triazole ring and the benzene ring is 25.04 (12° and an intramoleuclar C—H...S interaction leads to an S(6 ring. In the crystal, inversion dimers linked by pairs of N—H...S hydrogen bonds generate R22(8 loops.

Discover 4-H Clubs: The Essential Resource for 4-H

Science.gov (United States)

MacArthur, Stacey; Nelson, Cindy; Brower, Naomi; Memmott, Margie; Peterson, Gaelynn

2016-01-01

Obstacles facing new 4-H volunteers include time constraints and difficulty finding project-specific information, resources, and opportunities available for club members. As a solution to these obstacles and an aid for assisting volunteers in becoming confident in delivering information to youth, content experts produced Discover 4-H Clubs, a…

Rational Design and Enhanced Biocompatibility of a Dry Adhesive Medical Skin Patch

KAUST Repository

Kwak, Moon Kyu

2011-07-28

A new type of medical skin patch is developed that contains high-density, mushroom-like micropillars. Such dry-adhesive micropillars are highly biocompatible, have minimized side effects, and provide reasonable normal adhesion strength. To arrive at optimal conditions for the dry adhesive skin patch, the proper design of various structural and material parameters of micropillars is investigated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficacy of a bleomycin microneedle patch for the treatment of warts.

Science.gov (United States)

Ryu, Ha Ryeong; Jeong, Hye-Rin; Seon-Woo, Hye-Seung; Kim, Jung Soo; Lee, Seul Ki; Kim, Hee Joo; Baek, Jin Ok; Park, Jung-Hwan; Roh, Joo Young

2018-02-01

Warts are a common skin disease caused by infection of the human papilloma virus. Most treatments involving physical destruction of the infected cells, such as cryotherapy and electrocautery, are limited by intense pain, failure, or recurrences. Our aim was to compare the therapeutic effects of a newly developed bleomycin microneedle patch with cryotherapy in the treatment of warts. Forty-two patients with more than two wart lesions were included in the study. The two treatment modalities were randomly applied to different warts on each patient. Treatment efficacy was assessed using the Physician's Global Assessment (PGA) and the Patient's Global Assessment (PaGA). Mean PGA and PaGA scores were not significantly different between cryotherapy and bleomycin microneedle patch treatment. It was also determined that the mean size of all the warts treated with either modality shrank about equally at weeks 8 and 16 after initial treatment. Thus, treatment efficacy of the bleomycin microneedle patch was comparable to that of conventional cryotherapy. According to a visual analogue scale of pain, bleomycin microneedle patch treatment was significantly less painful than cryotherapy (p microneedle patch was more tolerable for patients who were reluctant to receive the painful treatment. Thus, the bleomycin microneedle patch can be an effective, convenient, and innovative treatment modality for warts.

Patch testing of 490 patients in Hong Kong.

Science.gov (United States)

Lee, T Y; Lam, T H

1996-07-01

Patch testing, using European standard allergens and suspected causative substances brought in by patients, was carried out in 490 patients with eczema in Hong Kong and 437 completed the test. Before patch testing, 244, 141 and 105 patients were diagnosed as having contact dermatitis, endogenous eczema and unclassified eczema, respectively. After patch testing, the diagnosis of the causal agent was changed in 54 contact dermatitis patients, and 18% of endogenous eczema patients and 34% of unclassified eczema patients were re-diagnosed as contact dermatitis. In the patients with a final diagnosis of contact dermatitis, 19.5% were positive to fragrance mix, followed by nickel sulfate (16.4%) and cobalt chloride (11.3%). The commonest causative agents for contact dermatitis were soap or detergent (22.0%) and traditional Chinese medicine (17.3%); the latter was a more common cause of contact dermatitis than Western medicine (9.0%) or metals (13.4%). The prevalence of allergic reaction to fragrance in Hong Kong was higher than among Chinese in Beijing, Shanghai, Taipei or Singapore (78% ethnic Chinese). Dermatologists should have a high index of suspicion about traditional medications and should patch test with the suspected substance when patients give a history of use.

Meningococcal factor H-binding protein vaccines with decreased binding to human complement factor H have enhanced immunogenicity in human factor H transgenic mice.

Science.gov (United States)

Rossi, Raffaella; Granoff, Dan M; Beernink, Peter T

2013-11-04

Factor H-binding protein (fHbp) is a component of a meningococcal vaccine recently licensed in Europe for prevention of serogroup B disease, and a second vaccine in clinical development. The protein specifically binds human factor H (fH), which down-regulates complement activation and enhances resistance to bactericidal activity. There are conflicting data from studies in human fH transgenic mice on whether binding of human fH to fHbp vaccines decreases immunogenicity, and whether mutant fHbp vaccines with decreased fH binding have enhanced immunogenicity. fHbp can be classified into two sub-families based on sequence divergence and immunologic cross-reactivity. Previous studies of mutant fHbp vaccines with low fH binding were from sub-family B, which account for approximately 60% of serogroup B case isolates. In the present study, we evaluated the immunogenicity of two mutant sub-family A fHbp vaccines containing single substitutions, T221A or D211A, which resulted in 15- or 30-fold lower affinity for human fH, respectively, than the corresponding control wild-type fHbp vaccine. In transgenic mice with high serum concentrations of human fH, both mutant vaccines elicited significantly higher IgG titers and higher serum bactericidal antibody responses than the control fHbp vaccine that bound human fH. Thus, mutations introduced into a sub-family A fHbp antigen to decrease fH binding can increase protective antibody responses in human fH transgenic mice. Collectively the data suggest that mutant fHbp antigens with decreased fH binding will result in superior vaccines in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Smart ECG Monitoring Patch with Built-in R-Peak Detection for Long-Term HRV Analysis.

Science.gov (United States)

Lee, W K; Yoon, H; Park, K S

2016-07-01

Since heart rate variability (HRV) analysis is widely used to evaluate the physiological status of the human body, devices specifically designed for such applications are needed. To this end, we developed a smart electrocardiography (ECG) patch. The smart patch measures ECG using three electrodes integrated into the patch, filters the measured signals to minimize noise, performs analog-to-digital conversion, and detects R-peaks. The measured raw ECG data and the interval between the detected R-peaks can be recorded to enable long-term HRV analysis. Experiments were performed to evaluate the performance of the built-in R-wave detection, robustness of the device under motion, and applicability to the evaluation of mental stress. The R-peak detection results obtained with the device exhibited a sensitivity of 99.29%, a positive predictive value of 100.00%, and an error of 0.71%. The device also exhibited less motional noise than conventional ECG recording, being stable up to a walking speed of 5 km/h. When applied to mental stress analysis, the device evaluated the variation in HRV parameters in the same way as a normal ECG, with very little difference. This device can help users better understand their state of health and provide physicians with more reliable data for objective diagnosis.

Bandwidth enhancement of a microstrip patch antenna for ultra-wideband applications

Science.gov (United States)

Anum, Khanda; Singh, Milind Saurabh; Mishra, Rajan; Tripathi, G. S.

2018-04-01

The microstrip antennas are used where size, weight, cost, and performance are constraints. Microstrip antennas (MSA) are being used in many government and commercial applications among which it is mostly used in wireless communication. The proposed antenna is designed for Ultra-wideband (UWB), it is designed on FR4 substrate material with ɛr = 4.3 and 0.0025 loss tangent. The shape and size of patch in microstrip patch antenna plays an important role in its performance. In the proposed antenna design the respective changes have been introduced which includes slotting the feedline,adding a curved slot in patch and change in patch shape itself to improve the bandwidth of the conventional antenna. The simulated results of proposed antenna shows impedance bandwidth (defined by 10 dB return loss) of 2-11.1GHz, VSWRcommunication at 7.25-8.395 GHz.

Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

Science.gov (United States)

Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Characterization of hERG1a and hERG1b potassium channels-a possible role for hERG1b in the I (Kr) current

DEFF Research Database (Denmark)

Larsen, Anders Peter; Olesen, Søren-Peter; Grunnet, Morten

2008-01-01

I (Kr) is the fast component of the delayed rectifier potassium currents responsible for the repolarization of the cardiac muscle. The molecular correlate underlying the I (Kr) current has been identified as the hERG1 channel. Recently, two splice variants of the hERG1 alpha-subunit, hERG1a and hERG......1b, have been shown to be co-expressed in human cardiomyocytes. In this paper, we present the electrophysiological characterization of hERG1a, hERG1b, and co-expressed hERG1a/b channels in a mammalian expression system using the whole-cell patch clamp technique. We also quantified the messenger RNA...... (mRNA) levels of hERG1a and hERG1b in human cardiac tissue, and based on the expressed ratios, we evaluated the resulting currents in Xenopus laevis oocytes. Compared to hERG1a channels, activation was faster for both hERG1b and hERG1a/b channels. The deactivation kinetics was greatly accelerated...

Cloning and characterization of a novel human zinc finger gene, hKid3, from a C2H2-ZNF enriched human embryonic cDNA library

International Nuclear Information System (INIS)

Gao Li; Sun Chong; Qiu Hongling; Liu Hui; Shao Huanjie; Wang Jun; Li Wenxin

2004-01-01

To investigate the zinc finger genes involved in human embryonic development, we constructed a C 2 H 2 -ZNF enriched human embryonic cDNA library, from which a novel human gene named hKid3 was identified. The hKid3 cDNA encodes a 554 amino acid protein with an amino-terminal KRAB domain and 11 carboxyl-terminal C 2 H 2 zinc finger motifs. Northern blot analysis indicates that two hKid3 transcripts of 6 and 8.5 kb express in human fetal brain and kidney. The 6 kb transcript can also be detected in human adult brain, heart, and skeletal muscle while the 8.5 kb transcript appears to be embryo-specific. GFP-fused hKid3 protein is localized to nuclei and the ZF domain is necessary and sufficient for nuclear localization. To explore the DNA-binding specificity of hKid3, an oligonucleotide library was selected by GST fusion protein of hKid3 ZF domain, and the consensus core sequence 5'-CCAC-3' was evaluated by competitive electrophoretic mobility shift assay. Moreover, The KRAB domain of hKid3 exhibits transcription repressor activity when tested in GAL4 fusion protein assay. These results indicate that hKid3 may function as a transcription repressor with regulated expression pattern during human development of brain and kidney

Analysis of the distribution of DNA repair patches in the DNA-nuclear matrix complex from human cells

International Nuclear Information System (INIS)

Mullenders, L.H.F.

1983-01-01

The distribution of ultraviolet-induced repair patches along DNA loops attached to the nuclear matrix, was investigated by digestion with DNA-degrading enzymes and neutral sucrose gradient centrifugation. When DNA was gradually removed by DNAase 1, pulse label incorporated by ultraviolet-irradiated cells during 10 min in the presence of hydroxyurea or hydroxyurea/arabinosylcytosine showed similar degradation kinetics as prelabelled DNA. No preferential association of pulse label with the nuclear matrix was observed, neither within 30 min nor 13 h after iiradiation. When the pulse label was incorporated by replicative synthesis under the same conditions, a preferential association of newly-synthesized DNA with the nuclear matrix was observed. Single-strand specific digestion with nuclease S 1 of nuclear lysates from ultraviolet-irradiated cells, pulse labelled in the presence of hydroxyurea/arabinosylcytosine, caused a release of about 70% of the prelabelled DNA and 90% of the pulse-labelled DNA from the rapidly sedimenting material in sucrose gradients. The results suggest no specific involvement of the nuclear matrix in repair synthesis, a random distribution of repair patches along the DNA loops, and simultaneously multiple incision events per DNA loop. (Auth.)

Analysis of the distribution of DNA repair patches in the DNA-nuclear matrix complex from human cells

Energy Technology Data Exchange (ETDEWEB)

Mullenders, L.H.F. (Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese); Zeeland, A.A. van; Natarajan, A.T. (Cohen (J.A.) Inst. voor Radiopathologie en Stralenbescherming, Leiden (Netherlands))

1983-09-09

The distribution of ultraviolet-induced repair patches along DNA loops attached to the nuclear matrix, was investigated by digestion with DNA-degrading enzymes and neutral sucrose gradient centrifugation. When DNA was gradually removed by DNAase 1, pulse label incorporated by ultraviolet-irradiated cells during 10 min in the presence of hydroxyurea or hydroxyurea/arabinosylcytosine showed similar degradation kinetics as prelabelled DNA. No preferential association of pulse label with the nuclear matrix was observed, neither within 30 min nor 13 h after irradiation. When the pulse label was incorporated by replicative synthesis under the same conditions, a preferential association of newly-synthesized DNA with the nuclear matrix was observed. Single-strand specific digestion with nuclease S/sub 1/ of nuclear lysates from ultraviolet-irradiated cells, pulse labelled in the presence of hydroxyurea/arabinosylcytosine, caused a release of about 70% of the prelabelled DNA and 90% of the pulse-labelled DNA from the rapidly sedimenting material in sucrose gradients. The results suggest no specific involvement of the nuclear matrix in repair synthesis, a random distribution of repair patches along the DNA loops, and simultaneously multiple incision events per DNA loop.

Both population size and patch quality affect local extinctions and colonizations

OpenAIRE

Franzén, Markus; Nilsson, Sven G.

2009-01-01

Currently, the habitat of many species is fragmented, resulting in small local populations with individuals occasionally dispersing between the remaining habitat patches. In a solitary bee metapopulation, extinction probability was related to both local bee population sizes and pollen resources measured as host plant population size. Patch size, on the other hand, had no additional predictive power. The turnover rate of local bee populations in 63 habitat patches over 4 years was high, with 7...

Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.

Science.gov (United States)

Rajabi, Mina; Roxhed, Niclas; Shafagh, Reza Zandi; Haraldson, Tommy; Fischer, Andreas Christin; Wijngaart, Wouter van der; Stemme, Göran; Niklaus, Frank

2016-01-01

This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.

[3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor

International Nuclear Information System (INIS)

Branchek, T.; Adham, N.; Macchi, M.; Kao, H.T.; Hartig, P.R.

1990-01-01

The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to [3H]ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding the serotonin 5-HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both [3H]DOB and [3H]ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5'-(beta, gamma-imido) triphosphate [Gpp(NH)p] to this system caused a rightward shift and steepening of agonist competition curves for [3H] ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity [3H]DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that [3H]DOB and [3H]ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein

Evaluation of the medical devices benchmark materials in the controlled human patch testing and in the RhE in vitro skin irritation protocol.

NARCIS (Netherlands)

Kandárová, Helena; Bendova, Hana; Letasiova, Silvia; Coleman, Kelly P; De Jong, Wim H; Jírova, Dagmar

2018-01-01

Several irritants were used in the in vitro irritation medical device round robin. The objective of this study was to verify their irritation potential using the human patch test (HPT), an in vitro assay, and in vivo data. The irritants were lactic acid (LA), heptanoic acid (HA), sodium dodecyl

Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.

Science.gov (United States)

Fraga, Mario F; Ballestar, Esteban; Villar-Garea, Ana; Boix-Chornet, Manuel; Espada, Jesus; Schotta, Gunnar; Bonaldi, Tiziana; Haydon, Claire; Ropero, Santiago; Petrie, Kevin; Iyer, N Gopalakrishna; Pérez-Rosado, Alberto; Calvo, Enrique; Lopez, Juan A; Cano, Amparo; Calasanz, Maria J; Colomer, Dolors; Piris, Miguel Angel; Ahn, Natalie; Imhof, Axel; Caldas, Carlos; Jenuwein, Thomas; Esteller, Manel

2005-04-01

CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.

Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.

Directory of Open Access Journals (Sweden)

Mai T Q Le

2008-10-01

Full Text Available Prior to 2007, highly pathogenic avian influenza (HPAI H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.

The sensitization potential of sunscreen after ablative fractional skin resurfacing using modified human repeated insult patch test.

Science.gov (United States)

Boonchai, Waranya; Sathaworawong, Angkana; Wongpraparut, Chanisada; Wanitphakdeedecha, Rungsima

2015-10-01

Ablative fractional skin resurfacing has become popular and proven to be useful in treating scars, photoaging and wrinkles. Although post-inflammatory hyperpigmentation (PIH) is the most common complication especially in dark-skinned patients like Asian. Several modalities have been used to overcome the PIH. To determine the sensitization potential of sunscreen applied immediately after ablative fractional skin resurfacing. Sixty volunteers were recruited. Of these 30 subjects were from previous ablative fractional skin resurfacing study who applied broad-spectrum sunscreen containing anti-inflammatory agent starting on the first day after resurfacing and another 30 non-resurfacing subjects had applied the same sunscreen on the intact skin. All subjects were patch/photopatch tested for sensitization study by using modified human repeated insult patch test (HRIPT). There were significantly higher sensitization rate of UV-filter, octocrylene and the sunscreen in resurfacing group than in non-resurfacing group. Early application of sunscreen after ablative fractional skin resurfacing has increased the incidence of sensitization potential of sunscreen. The sunscreen is recommended to start using from D3 after fractional ablative skin resurfacing to ensure the complete recovery of skin barrier and minimize the risk of sensitization.

Case Series: Keratolimbal Allograft as a Patch Graft for Glaucoma Drainage Devices.

Science.gov (United States)

Ahmed, Sarah F; Schmutz, Mason; Mosaed, Sameh

2017-09-01

Tube exposure remains one of the most common complications after glaucoma drainage device (GDD) implantation, despite various types of patch grafts available today. We present a 4 patient case series following the effectivity of the keratolimbal allograft (KLAL) as a patch graft for cases of tube exposure. Given its inherent population of stem cells, our hypothesis was that this highly replicative, biological tissue would provide an adequate means of glaucoma tube coverage. The subset of patients chosen for the KLAL patch graft all had a history of abnormally scarred conjunctiva or thin sclera. The aim of utilizing the KLAL patch with its associated donor conjunctival and scleral ring was also to provide additional reinforcement and adequate tube coverage in the setting of compromised native tissue. Four patients comprised of 2 males and 2 females with a minimum postoperative period of 12 months. All GDDs were initially implanted with a limbal-based incision using either Ahmed glaucoma valve or Baerveldt drainage implant. Three of the 4 patients received the KLAL patch graft after tube exposure with scleral patch graft and 1 patient received KLAL as the primary graft during initial tube placement. Two of the 4 eyes experienced tube re-exposure postoperatively at 2 and 3 months, respectively. Both of these cases had a history of prior tube exposure after scleral patch graft and both were tubes placed in the pars plana. Interestingly, the patients with failed grafts were younger with a history of more ocular surgeries as compared with the patients with graft viable eyes. Through our case series, we found that the KLAL utilized as a patch graft over GDD tubes has the potential for favorable outcomes in certain subtypes of eyes. Although further large scale investigation will be necessary to better define the risk factors associated with graft failure, proving the graft's viability is a crucial first step.

Initial 2-year results of CardioCel® patch implantation in children.

Science.gov (United States)

Pavy, Carine; Michielon, Guido; Robertus, Jan Lukas; Lacour-Gayet, François; Ghez, Olivier

2018-03-01

We present the initial 2-year results of CardioCel® patch (Admedus Regen Pty Ltd, Perth, WA, Australia) implantation in paediatric patients with congenital heart diseases. This was a single-centre retrospective study with prospectively collected data of all patients aged 18 years and under operated for congenital heart disease. The patch was introduced in 2014, with clinical practice committee approval and a special consent in case of an Ozaki procedure. Standard follow-up was performed with systematic clinical exams and echocardiograms. In case of reoperation or graft failure, the patch was removed and sent for a histological examination. Between March 2014 and April 2016, 101 patients had surgical repair using a CardioCel patch. The mean age was 22 (±36.3) months, and the mean weight was 9.7 (±10.3) kg. No infections and no intraoperative implantation difficulties were associated with the patch. The median follow-up period was 212 (range 4-726) days. The overall 30-day postoperative mortality was 3.8% (n = 4), none of which were related to graft failure. Five children were reoperated because of graft failure, 4 of whom had the patch implanted for aortic and were aged less than 10 days. The indications for patch implantation in the aortic position were aortopulmonary window, truncus arteriosus, coarctation and aortic arch hypoplasia repair. The median time between the first and the second operation for graft failure was 245 (range 5-480) days. Our experience shows that the patch is well tolerated in the septal, valvar and pulmonary artery positions. However, we experienced graft failures in infants in the aortic position. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

1H and 2H NMR relaxation study on the phase transitions of (NH4)3H(SO4)2 and (ND4)3D(SO4)2 single crystals

International Nuclear Information System (INIS)

Lim, Ae Ran; Jeong, Se-Young

2006-01-01

T 1 , T 1ρ and T 2 for the 1 H and 2 H nuclei in (NH 4 ) 3 H(SO 4 ) 2 and (ND 4 ) 3 D(SO 4 ) 2 single crystals grown using the slow evaporation method were measured for phases I, II, III, IV and V. The 1 H T 1 , T 1ρ , and T 2 values were found to exhibit different trends in phases II and III: T 1 , T 1ρ and T 2 for 1 H do not change significantly near the phase transition at 265 K, whereas near 413 K they change discontinuously. We conclude that the NH 4 + and H(SO 4 ) 2 - ions do not play an important role in the III-II phase transition, but do play important roles in the II-I phase transition. The liquid-like nature of the 1 H T 1ρ and T 2 above 413 K is indicative of the destruction and reconstruction of hydrogen bonds. Moreover, the phase transitions of the (NH 4 ) 3 H(SO 4 ) 2 crystal are accompanied by changes in the molecular motion of the (NH 4 ) + ions. The variations with temperature of the 2 H T 1 and T 2 of (ND 4 ) 3 D(SO 4 ) 2 crystals are not similar to those observed for the 1 H T 1 and T 2 . Our comparison of the results for (NH 4 ) 3 H(SO 4 ) 2 and (ND 4 ) 3 D(SO 4 ) 2 crystals indicates the following: the 1 H T 1ρ and T 2 of the (NH 4 ) + and H(SO 4 ) 2 - ions above T C1 are characteristic of fast, liquid-like motion, which is not the case for (ND 4 ) 3 D(SO 4 ) 2 ; and the 2 H T 1 of D(SO 4 ) 2 - in (ND 4 ) 3 D(SO 4 ) 2 is longer than the 2 H T 1 of (ND 4 ) + in contrast to the results for (NH 4 ) 3 H(SO 4 ) 2 crystals

Depletion and repopulation of lymphocytes in Peyer's patches of mice after total lymphoid irradiation

International Nuclear Information System (INIS)

Ermak, T.H.; Steger, H.J.; Owen, R.L.; Strober, S.

1988-01-01

The depletion and repopulation of lymphocytes in specific cellular domains of mouse Peyer's patches were examined following total lymphoid irradiation (TLI). BALB/c mice 5-months-old were given 17 fractionated doses of irradiation to a total of 3400 to 4250 rads over a 4-week period, and Peyer's patches were examined by immunohistochemistry at 1 to 4 days and 1 to 4 weeks after TLI. Cryostat sections were labeled with monoclonal antibodies directed against B220 (B cells), Thy-1.2 (all T cells), L3T4 (helper T cells), and Ly-2 (cytotoxic/suppressor T cells). In depleted mice, Peyer's patches were greatly reduced in size in comparison to controls, although the structural framework of follicles, domes, and interfollicular areas was still present. B cells in follicles were reduced to a small core of B220+ cells interspersed with nonlymphocytic cells. T cells were virtually eliminated from the patch except for a small population of Thy-1.2+ cells that were neither L3T4+ nor Ly-2+ in follicle domes. During early stages of repopulation at 1 to 2 weeks after TLI, follicles increased in size and were populated by helper T cells but Peyer's patches lacked discrete interfollicular T cell regions. At 3 to 4 weeks after TLI, T cell regions were found in interfollicular areas. The results indicate that morphologically distinct cellular domains are maintained in Peyer's patches after TLI which are sequentially repopulated by immigrating lymphocytes

Expression of hPNAS-4 Radiosensitizes Lewis Lung Cancer

International Nuclear Information System (INIS)

Zeng Hui; Yuan Zhu; Zhu Hong; Li Lei; Shi Huashan; Wang Zi; Fan Yu; Deng Qian; Zeng Jianshuang; He Yinbo; Xiao Jianghong; Li Zhiping

2012-01-01

Purpose: This study aimed to transfer the hPNAS-4 gene, a novel apoptosis-related human gene, into Lewis lung cancer (LL2) and observe its radiosensitive effect on radiation therapy in vitro and in vivo. Methods and Materials: The hPNAS-4 gene was transfected into LL2 cells, and its expression was detected via western blot. Colony formation assay and flow cytometry were used to detect the growth and apoptosis of cells treated with irradiation/PNAS-4 in vitro. The hPNAS-4 gene was transferred into LL2-bearing mice through tail vein injection of the liposome/gene complex. The tumor volumes were recorded after radiation therapy. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect the tumor cell growth and apoptosis in vivo. Results: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue, and its overexpressions were confirmed via western blot analysis. Compared with the control, empty plasmid, hPNAS-4, radiation, and empty plasmid plus radiation groups, the hPNAS-4 plus radiation group more significantly inhibited growth and enhanced apoptosis of LL2 cells in vitro and in vivo (P<.05). Conclusions: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue and was expressed in both LL2 cell and tumor tissue. The hPNAS-4 gene therapy significantly enhanced growth inhibition and apoptosis of LL2 tumor cells by radiation therapy in vitro and in vivo. Therefore, it may be a potential radiosensitive treatment of radiation therapy for lung cancer.

Cross-species Analyses Unravel the Complexity of H3K27me3 and H4K20me3 in the Context of Neural Stem Progenitor Cells.

Science.gov (United States)

Rhodes, Christopher T; Sandstrom, Richard S; Huang, Shu-Wei Angela; Wang, Yufeng; Schotta, Gunnar; Berger, Mitchel S; Lin, Chin-Hsing Annie

2016-06-01

Neural stem progenitor cells (NSPCs) in the human subventricular zone (SVZ) potentially contribute to life-long neurogenesis, yet subtypes of glioblastoma multiforme (GBM) contain NSPC signatures that highlight the importance of cell fate regulation. Among numerous regulatory mechanisms, the post-translational methylations onto histone tails are crucial regulator of cell fate. The work presented here focuses on the role of two repressive chromatin marks tri-methylations on histone H3 lysine 27 (H3K27me3) and histone H4 lysine 20 (H4K20me3) in the adult NSPC within the SVZ. To best model healthy human NSPCs as they exist in vivo for epigenetic profiling of H3K27me3 and H4K20me3, we utilized NSPCs isolated from the adult SVZ of baboon brain ( Papio anubis ) with brain structure and genomic level similar to human. The putative role of H3K27me3 in normal NSPCs predominantly falls into the regulation of gene expression, cell cycle, and differentiation, whereas H4K20me3 is involved in DNA replication/repair, metabolism, and cell cycle. Using conditional knock-out mouse models to diminish Ezh2 and Suv4-20h responsible for H3K27me3 and H4K20me3, respectively, we found that both repressive marks have irrefutable function for cell cycle regulation in the NSPC population. While both EZH2/H3K27me3 and Suv4-20h/H4K20me3 have implication in cancers, our comparative genomics approach between healthy NSPCs and human GBM specimens revealed that substantial sets of genes enriched with H3K27me3 and H4K20me3 in the NSPCs are altered in the human GBM. In sum, our integrated analyses across species highlight important roles of H3K27me3 and H4K20me3 in normal and disease conditions in the context of NSPC.

Cross-species analyses unravel the complexity of H3K27me3 and H4K20me3 in the context of neural stem progenitor cells

Directory of Open Access Journals (Sweden)

Christopher T. Rhodes

2016-06-01

Full Text Available Neural stem progenitor cells (NSPCs in the human subventricular zone (SVZ potentially contribute to lifelong neurogenesis, yet subtypes of glioblastoma multiforme (GBM contain NSPC signatures that highlight the importance of cell fate regulation. Among numerous regulatory mechanisms, the posttranslational methylations onto histone tails are crucial regulator of cell fate. The work presented here focuses on the role of 2 repressive chromatin marks trimethylations on histone H3 lysine 27 (H3K27me3 and histone H4 lysine 20 (H4K20me3 in the adult NSPC within the SVZ. To best model healthy human NSPCs as they exist in vivo for epigenetic profiling of H3K27me3 and H4K20me3, we used NSPCs isolated from the adult SVZ of baboon brain (Papio anubis with brain structure and genomic level similar to human. The putative role of H3K27me3 in normal NSPCs predominantly falls into the regulation of gene expression, cell cycle, and differentiation, whereas H4K20me3 is involved in DNA replication/repair, metabolism, and cell cycle. Using conditional knockout mouse models to diminish Ezh2 and Suv4-20h responsible for H3K27me3 and H4K20me3, respectively, we found that both repressive marks have irrefutable function for cell cycle regulation in the NSPC population. Although both EZH2/H3K27me3 and Suv4-20h/H4K20me3 have implication in cancers, our comparative genomics approach between healthy NSPCs and human GBM specimens revealed that substantial sets of genes enriched with H3K27me3 and H4K20me3 in the NSPCs are altered in the human GBM. In sum, our integrated analyses across species highlight important roles of H3K27me3 and H4K20me3 in normal and disease conditions in the context of NSPC.

Ethyl 2-amino-4-(4-bromophenyl-6-methoxy-4H-benzo[h]chromene-3-carboxylate

Directory of Open Access Journals (Sweden)

Seik Weng Ng

2013-03-01

Full Text Available In the title compound, C23H20BrNO4, the pyran ring has a flattened boat conformation with the O and methine C atoms lying to one side of the plane [0.160 (5 and 0.256 (6 Å, respectively] defined by the remaining atoms. Nevertheless, the 4H-benzo[h]chromene ring system approximates a plane (r.m.s. deviation = 0.116 Å with the bromobenzene ring almost perpendicular [dihedral angle = 83.27 (16°] and the ester group coplanar [C—C—C—O = 3.4 (5°]; the methoxy substituent is also coplanar [C—O—C—C = 174.5 (3°]. In addition to an intramolecular N—H...O(ester carbonyl hydrogen bond, the ester carbonyl O atom also forms an intermolecular N—H...O hydrogen bond with the second amine H atom, generating a zigzag supramolecular chain along the c axis in the crystal packing. The chains are linked into layers in the bc plane by N—H...Br hydrogen bonds, and these layers are consolidated into a three-dimensional architecture by C—H...π interactions.

Combinatorial modification of human histone H4 quantitated by two-dimensional liquid chromatography coupled with top down mass spectrometry.

Science.gov (United States)

Pesavento, James J; Bullock, Courtney R; LeDuc, Richard D; Mizzen, Craig A; Kelleher, Neil L

2008-05-30

Quantitative proteomics has focused heavily on correlating protein abundances, ratios, and dynamics by developing methods that are protein expression-centric (e.g. isotope coded affinity tag, isobaric tag for relative and absolute quantification, etc.). These methods effectively detect changes in protein abundance but fail to provide a comprehensive perspective of the diversity of proteins such as histones, which are regulated by post-translational modifications. Here, we report the characterization of modified forms of HeLa cell histone H4 with a dynamic range >10(4) using a strictly Top Down mass spectrometric approach coupled with two dimensions of liquid chromatography. This enhanced dynamic range enabled the precise characterization and quantitation of 42 forms uniquely modified by combinations of methylation and acetylation, including those with trimethylated Lys-20, monomethylated Arg-3, and the novel dimethylated Arg-3 (each <1% of all H4 forms). Quantitative analyses revealed distinct trends in acetylation site occupancy depending on Lys-20 methylation state. Because both modifications are dynamically regulated through the cell cycle, we simultaneously investigated acetylation and methylation kinetics through three cell cycle phases and used these data to statistically assess the robustness of our quantitative analysis. This work represents the most comprehensive analysis of histone H4 forms present in human cells reported to date.

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain.

Science.gov (United States)

Dave, Mabel N; Silva, Juan E; Eliçabe, Ricardo J; Jeréz, María B; Filippa, Verónica P; Gorlino, Carolina V; Autenrieth, Stella; Autenrieth, Ingo B; Di Genaro, María S

2016-11-01

Yersinia enterocolitica evades the immune response by injecting Yersinia outer proteins (Yops) into the cytosol of host cells. YopH is a tyrosine phosphatase critical for Yersinia virulence. However, the mucosal immune mechanisms subverted by YopH during in vivo orogastric infection with Y. enterocolitica remain elusive. The results of this study revealed neutrophil recruitment to Peyer's patches (PP) after infection with a YopH-deficient mutant strain (Y. enterocolitica ΔyopH). While the Y. enterocolitica wild-type (WT) strain in PP induced the major neutrophil chemoattractant CXCL1 mRNA and protein levels, infection with the Y. enterocolitica ΔyopH mutant strain exhibited a higher expression of the CXCL1 receptor, CXCR2, in blood neutrophils, leading to efficient neutrophil recruitment to the PP. In contrast, migration of neutrophils into PP was impaired upon infection with Y. enterocolitica WT strain. In vitro infection of blood neutrophils revealed the involvement of YopH in CXCR2 expression. Depletion of neutrophils during Y. enterocolitica ΔyopH infection raised the bacterial load in PP. Moreover, the clearance of WT Y. enterocolitica was improved when an equal mixture of Y. enterocolitica WT and Y. enterocolitica ΔyopH strains was used in infecting the mice. This study indicates that Y. enterocolitica prevents early neutrophil recruitment in the intestine and that the effector protein YopH plays an important role in the immune evasion mechanism. The findings highlight the potential use of the Y. enterocolitica YopH-deficient strain as an oral vaccine carrier. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial.

Science.gov (United States)

Rouphael, Nadine G; Paine, Michele; Mosley, Regina; Henry, Sebastien; McAllister, Devin V; Kalluri, Haripriya; Pewin, Winston; Frew, Paula M; Yu, Tianwei; Thornburg, Natalie J; Kabbani, Sarah; Lai, Lilin; Vassilieva, Elena V; Skountzou, Ioanna; Compans, Richard W; Mulligan, Mark J; Prausnitz, Mark R

2017-08-12

Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat

Large-scale binding ligand prediction by improved patch-based method Patch-Surfer2.0.

Science.gov (United States)

Zhu, Xiaolei; Xiong, Yi; Kihara, Daisuke

2015-03-01

Ligand binding is a key aspect of the function of many proteins. Thus, binding ligand prediction provides important insight in understanding the biological function of proteins. Binding ligand prediction is also useful for drug design and examining potential drug side effects. We present a computational method named Patch-Surfer2.0, which predicts binding ligands for a protein pocket. By representing and comparing pockets at the level of small local surface patches that characterize physicochemical properties of the local regions, the method can identify binding pockets of the same ligand even if they do not share globally similar shapes. Properties of local patches are represented by an efficient mathematical representation, 3D Zernike Descriptor. Patch-Surfer2.0 has significant technical improvements over our previous prototype, which includes a new feature that captures approximate patch position with a geodesic distance histogram. Moreover, we constructed a large comprehensive database of ligand binding pockets that will be searched against by a query. The benchmark shows better performance of Patch-Surfer2.0 over existing methods. http://kiharalab.org/patchsurfer2.0/ CONTACT: dkihara@purdue.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Patch tests with fragrance mix II and its components.

Science.gov (United States)

Pónyai, Györgyi; Németh, Ilona; Altmayer, Anita; Nagy, Gabriella; Irinyi, Beatrix; Battyáni, Zita; Temesvári, Erzsébet

2012-01-01

Fragrance mix II (FM II) was initiated to detect contact hypersenstitivity (CH) to fragrances that could not have been identified previously. The aim of this multicenter study was to map the frequency of CH to FM II and its components in Hungary. Six centers participated in the survey from 2009 to 2010. A total off 565 patients (434 women and 131 men) with former skin symptoms provoked by scented products were patch tested. The tests were performed with Brial GmbH D-Greven allergens. In the environmental patch test series, FM II, FM I, Myroxylon pereirae, colophonium, wood-tar mix, propolis, and sesquiterpene lactone mix were tested as fragrance allergens. The FM II components (citral, farnesol, coumarin, citronellol, α-hexyl-cinnamaldehyde, and hydroxy-isohexyl-3-cyclohexene-carboxaldehyde [Lyral]) were also tested. Contact hypersenstitivity to any fragrances was detected in 28.8%, to FM II in 17.2% of the patients. Contact hypersenstitivity to hydroxy-isohexyl-3-cyclohexene-carboxaldehyde was observed in 7.3%, to coumarin in 5.1%, to α-hexyl-cinnamaldehyde in 3.5%, to citral in 3.4%, to farnesol in 2.5%, and to citronellol in 1.2%. Of the FM II-positive cases, 48.4% showed isolated CH reaction. The frequency of CH to FM II is 17.2% in the tested, selected Hungarian population. The CH to FM II and its components could not have been revealed without the present test materials.

The development of striatal patch/matrix organization after prenatal methylazoxymethanol: a combined immunocytochemical and bromo-deoxy-uridine birthdating study.

Science.gov (United States)

Snyder-Keller, A M

1995-10-01

The antimitotic drug methylazoxymethanol was used to destroy striatal patch neurons during their three-day-period of neurogenesis in the rat. Single or multiple injections of methylazoxymethanol were given during embryonic days 13-15, the period when patch neurons are known to undergo their final cell division. Methylazoxymethanol treatments produced a dramatic reduction in striatal volume. Immunocytochemical analysis revealed the continued presence of patches of neurons that were substance P-immunoreactive and devoid of calbindin and enkephalin immunoreactivity. Both the number of patches and relative volume occupied by patches was reduced in methylazoxymethanol-treated striata. Patch neurons could also be labelled by an intrastriatal injection of FluoroGold during the first postnatal week. The early ingrowth of nigrostriatal dopamine afferents was less noticeably patchy in the methylazoxymethanol-treated animals, in part owing to an overall increase in density. Large reductions in the number of neurons immunoreactive for choline acetyltransferase were observed, whereas NADPH diaphorase-stained neurons were not reduced unless methylazoxymethanol was given on embryonic day 15. Injections of bromo-deoxy-uridine, either during or after the 24 h that each methylazoxymethanol injection was considered to be effective, revealed that (i) some patch neurons continued to be generated in the 24-h period following methylazoxymethanol administration, and (ii) many patch neurons were generated after the effects of methylazoxymethanol had worn off. These findings demonstrate that it was impossible to completely eliminate the patches using methylazoxymethanol injections during the period of patch neurogenesis. However, methylazoxymethanol treatment during this time did produce a dramatic loss of cells and a relatively greater reduction in patch volume. Despite this disruption, the appropriate compartmentalization of neuroactive substances appeared to be maintained.

A clinical study of transdermal contraceptive patch in Thai adolescence women.

Science.gov (United States)

Piyasirisilp, Rachatapon; Taneepanichskul, Surasak

2008-02-01

To study cycle control, compliance and safety of a transdermal contraceptive patch in adolescent Thai women. Fifty-eight healthy women were assigned to receive 3 cycles of contraceptive patch (ethinyl estradiol 20 microg and norelgestromin 150 microg/day). All participants aged 16-20 years were invited to participate from the family planning clinic at King Chulalongkorn Memorial Hospital. Data were collected on adverse effects, perceived advantages and disadvantages, body weight, blood pressure, patch detachments and compliance. Data were analyzed using mean, percentage and student's t-test. The participants' average age was 19.4 years, height 158.8 cm, weight 51.8 kg, BMI 20.8 Kg/m2. The most location of patch application was the abdomen and the most adverse event was breast tenderness (31.0%) followed by application site reaction, nausea vomiting and headache respectively. The breast symptom was mild in severity. The participants reported decrease in dysmenorrhea and shorter duration of bleeding. There were no significant changes in body weight and blood pressure. The improvement of their facial acne was reported. There were no pregnancies during use and the adhesion of the contraceptive patch is excellent. Partial patch detachment was reported in only 6.9%. No completed patch detachment was found. The present study found an overall positive impression of a new transdermal contraceptive patch. The good compliance and few side effects were demonstrated. The adhesive patch contraceptive was excellent.

Experimental infection of clade 1.1.2 (H5N1), clade 2.3.2.1c (H5N1) and clade 2.3.4.4 (H5N6) highly pathogenic avian influenza viruses in dogs.

Science.gov (United States)

Lyoo, K S; Na, W; Phan, L V; Yoon, S W; Yeom, M; Song, D; Jeong, D G

2017-12-01

Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs may act as an intermediate host, increasing the potential for zoonotic transmission of influenza viruses. Virus transmission and pathologic changes in HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were investigated. Mild respiratory signs and antibody response were shown in dogs intranasally infected with the viruses. Lung histopathology showed lesions that were associated with moderate interstitial pneumonia in the infected dogs. In this study, HPAI H5N6 virus replication in dogs was demonstrated for the first time. Dogs have been suspected as a "mixing vessel" for reassortments between avian and human influenza viruses to occur. The replication of these three subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve as intermediate hosts for avian-human influenza virus reassortment if they are also co-infected with human influenza viruses. © 2017 Blackwell Verlag GmbH.

In vitro cytotoxicity and apoptotic inducing activity of the synthesized 4-aryl-4H-chromenes derivatives against human cancer cell lines

Directory of Open Access Journals (Sweden)

Mohagheghi MA

2009-09-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: 4-Aryl-4H-chromenes are novel anticancer agents which induce apoptosis in cancer cells. These compounds were found to induce apoptosis by targeting the tubulin/microtubule system in cell proliferation process. The aim of this study was to report cyototoxic and apoptosis inducing activities of a new series of synthesized 4-aryl-4H-chromenes compounds."n"n Methods: The in vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated against a paned of human cancer cell lines including MCF-7 (breast carcinoma, A549 (lung carcinoma, HEPG-2 (liver carcinoma, SW-480 (colon adenocarcinoma, U87-MG (glioblastoma, 1321N1 (astrocytoma, and DAOY (medulloblastoma. The percentage of growth inhibitory activity was evaluated using MTT colorimetric assay versus controls not treated with test derivatives. The data for etoposide, a well known anticancer drug, was included for comparison. For each compound, the 50% inhibitory concentration (IC50 were determined. Apoptosis inducing activity were assessed by DAPI staining."n"n Results: Preliminary screening showed that those chromenes analogs bearing phenyl-isoxazole-3-yl substitution or the derivatives containing methoxyphenyl in chromene ring exhibited

Collection of analytes from microneedle patches.

Science.gov (United States)

Romanyuk, Andrey V; Zvezdin, Vasiliy N; Samant, Pradnya; Grenader, Mark I; Zemlyanova, Marina; Prausnitz, Mark R

2014-11-04

Clinical medicine and public health would benefit from simplified acquisition of biological samples from patients that can be easily obtained at point of care, in the field, and by patients themselves. Microneedle patches are designed to serve this need by collecting dermal interstitial fluid containing biomarkers without the dangers, pain, or expertise needed to collect blood. This study presents novel methods to collect biomarker analytes from microneedle patches for analysis by integration into conventional analytical laboratory microtubes and microplates. Microneedle patches were made out of cross-linked hydrogel composed of poly(methyl vinyl ether-alt-maleic acid) and poly(ethylene glycol) prepared by micromolding. Microneedle patches were shown to swell with water up to 50-fold in volume, depending on degree of polymer cross-linking, and to collect interstitial fluid from the skin of rats. To collect analytes from microneedle patches, the patches were mounted within the cap of microcentrifuge tubes or formed the top of V-bottom multiwell microplates, and fluid was collected in the bottom of the tubes under gentle centrifugation. In another method, microneedle patches were attached to form the bottom of multiwell microplates, thereby enabling in situ analysis. The simplicity of biological sample acquisition using microneedle patches coupled with the simplicity of analyte collection from microneedles patches integrated into conventional analytical equipment could broaden the reach of future screening, diagnosis, and monitoring of biomarkers in healthcare and environmental/workplace settings.

Imaging of adenovirus-mediated expression of human sodium iodide symporter (hNIS) by {sup 99m}TcO{sub 4} scan in mice

Energy Technology Data Exchange (ETDEWEB)

Lee, Won Woo; Moon, D. H.; Park, S. Y.; Jin, J.; Kim, S. J.; Lee, H. [Ulsan University College of Medicine, Seoul (Korea, Republic of)

2002-07-01

We have evaluated the feasibility of human sodium iodide symporter (hNIS) as a reporter gene by {sup 99m}TcO{sub 4} scan in vivo. Recombinant adenovirus encoding hNIS (Rad-hNIS) gene was introduced to FRO cell. hNIS expression was assessed by western blot and {sup 99m}TcO{sub 4} uptake in vitro. {sup 99m}TcO{sub 4} scan were obtained in BALB/c mice 48 hrs post injection of Tris buffer, Rad-hNIS (1x10{sup 9} or 2x10{sup 8} pfu), or Rad-LacZ (1x10{sup 9} pfu) via the tail vein (n=5-7 for each group). Biodistribution study and RT-PCR were performed. A series of {sup 99m}TcO{sub 4} scans were obtained in 2 mice until 21 days post Rad-hNIS injection. FRO readily expressed hNIS protein and incorporated significantly higher level of {sup 99m}TcO{sub 4} in vitro. With {sup 99m}TcO{sub 4} scan, prominent hepatic uptake was observed only in the mice with 1x10{sup 9} pfu of Rad-hNIS. Liver/lung ratio was increased in this group from 15 (5.7{+-}2.5) till 60 min(6.7{+-}3.6) (p<0.01). Significantly increased {sup 99m}TcO{sub 4} uptake (22.7{+-}11.2 %ID/g) and hNIS mRNA expression were exclusively noticed in livers of this group. The persistent hepatic uptake was observed for up one week. NaClO{sub 4} inhibited the hepatic uptake of {sup 99m}TcO{sub 4}. hNIS holds a promising potential as an effective reporter gene for noninvasive/repeated imaging in combination with {sup 99m}TcO{sub 4}.

Histone H4 Lysine 20 methylation

DEFF Research Database (Denmark)

Jørgensen, Stine; Schotta, Gunnar; Sørensen, Claus Storgaard

2013-01-01

of histones have emerged as key regulators of genomic integrity. Intense research during the past few years has revealed histone H4 lysine 20 methylation (H4K20me) as critically important for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin...... compaction. The distinct H4K20 methylation states are mediated by SET8/PR-Set7 that catalyses monomethylation of H4K20, whereas SUV4-20H1 and SUV4-20H2 enzymes mediate further H4K20 methylation to H4K20me2 and H4K20me3. Disruption of these H4K20-specific histone methyltransferases leads to genomic...

The system Ba(H2PO4)2-Sr(H2PO4)2-H3PO4(30%)-H2O at 25, 40 and 60 deg C

International Nuclear Information System (INIS)

Taranenko, N.P.; Serebrennikova, G.M.; Stepin, B.D.; Oboznenko, Yu.V.

1982-01-01

The system Ba(H 2 PO 4 ) 2 -Sr(H 2 PO 4 ) 2 -H 3 PO 4 (30%)-H 2 O (25 deg C) belongs to eutonic type systems. Solubility isotherms of salt components at 40 and 60 deg C are calculated. Polytherms (25-60 deg C) of solubility of monosubstituted barium and strontium phosphates in 30-60% H 3 PO 4 are obtained. The value of cocrystallization coefficient of Sr 2 + and Ba(H 2 PO 4 ) 2 Dsub(Sr)=0.042+-0.005 remains stable in the temperature range of 25-60 deg C and concentrations 30-60% phosphoric acid at initial content [Sr 2 + ]=1x10 - 2 mass%

Silencing of B7-H4 suppresses the tumorigenicity of the MGC-803 human gastric cancer cell line and promotes cell apoptosis via the mitochondrial signaling pathway.

Science.gov (United States)

Zhou, Donghui; Zhou, Yong; Li, Chao; Yang, Lina

2018-04-01

B7-H4 is a transmembrane protein which is a member of the B7 superfamily. It is overexpressed in various types of cancer, including gastric cancer. However, the effects of B7-H4 on the tumorigenicity of gastric cancer and the underlying mechanisms have not yet been fully explored. Thus, the aim of this study was to examine the effects of B7-H4 on the tumorigenicity of gastric cancer cells and to elucidate the underlying mechanisms. For this purpose, B7-H4 expression in gastric cancer tissues was detected by immunohistochemical staining. The effects of B7-H4 on the biological behavior of the MGC-803 human gastric cancer cell line were examined by Cell Counting kit-8 (CCK-8) assay, cell cycle analysis, wound healing assay, Annexin V/propidium iodide staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Moreover, the expression levels of apoptotic markers, such as cleaved caspase‑3, cleaved caspase‑9, Bcl-2 and Bax were examined by western blot analysis. Immunohistochemical staining revealed that a high expression of B7-H4 was found in about 41.8% of tissues obtained from patients with gastric cancer. Comparative analysis revealed that B7-H4 expression significantly correlated with lymph node metastasis and the TNM stage. The results of CCK-8 assay, cell cycle analysis, wound healing assay, Annexin V/propidium iodide staining assay and TUNEL assay all demonstrated that the silencing of B7-H4 by small interfering RNA decreased cell proliferation, suppressed cell motility, and induced cell cycle arrest and the apoptosis of MGC-803 human gastric cancer cells. Furthermore, the results of western blot analysis indicated that the downregulation of B7-H4 induced the apoptosis of the MGC-803 cells via the mitochondrial signaling pathway through the activation of caspase‑3 and caspase‑9, and by altering the Bax/Bcl-2 ratio in a manner that favored apoptosis. Based on the findings on human gastric cancer cell line MGC-803, the

Patch testing and allergen-specific serum IgE and IgG antibodies in the diagnosis of canine adverse food reactions.

Science.gov (United States)

Bethlehem, Simone; Bexley, Jennifer; Mueller, Ralf S

2012-02-15

Adverse food reaction (AFR) is a common differential diagnosis for pruritic dogs. The only way to diagnose AFR is an elimination diet of 6-8 weeks with a protein and a carbohydrate source not previously fed. In humans, patch testing has been shown to be a useful tool to diagnose food allergies. In veterinary medicine, serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for such diets. The aim of this study was to determine sensitivity, specificity, negative and positive predictability of patch testing with and serum antibody testing for a variety of common food stuffs. Twenty-five allergic dogs underwent an elimination diet and individual rechallenge with selected food stuffs, food patch testing and serum testing for food-antigen specific IgE and IgG. Eleven clinically normal control dogs only were subjected to patch and serum testing. The sensitivity and specificity of the patch test were 96.7 and 89.0% respectively, negative and positive predictability were 99.3 and 63.0%. For IgE and IgG the sensitivity was 6.7 and 26.7%, specificity were 91.4 and 88.3%, the negative predictive values 80.7 and 83.7% and the positive predictive values were 15.4 and 34.8%. Based on these results, a positive reaction of a dog on these tests is not very helpful, but a negative result indicates that this antigen is tolerated well. We conclude that patch testing (and to a lesser degree serum testing) can be helpful in choosing ingredients for an elimination diet in a dog with suspected AFR. Copyright © 2012. Published by Elsevier B.V.

Design and synthesis of novel platelet fibrinogen receptor antagonists with 2H-1,4-benzoxazine-3(4H)-one scaffold. A systematic study.

Science.gov (United States)

Anderluh, Marko; Cesar, Jozko; Stefanic, Petra; Kikelj, Danijel; Janes, Damjan; Murn, Jernej; Nadrah, Kristina; Tominc, Mojca; Addicks, Elisabeth; Giannis, Athanassios; Stegnar, Mojca; Dolenc, Marija Sollner

2005-01-01

New platelet glycoprotein IIb/IIIa (GP IIb/IIIa, integrin alpha(IIb)beta3) antagonists were prepared on a 2H-1,4-benzoxazine-3(4H)-one scaffold. Their anti-aggregatory activities in human platelet rich plasma and their affinity towards alpha(IIb)beta3 and alpha(V)beta3 integrins were assessed. Various substitution positions and side chain variations were studied. In contrast to the generally accepted model, compounds containing ethyl esters as aspartate mimetics were in general more active than the corresponding free acids. We suggest an explanation for the observed behaviour of these new compounds.

The COMPASS Family of Histone H3K4 Methylases: Mechanisms of Regulation in Development and Disease Pathogenesis

Science.gov (United States)

Shilatifard, Ali

2014-01-01

The Saccharomyces cerevisiae Set1/COMPASS was the first histone H3 lysine 4 (H3K4) methylase identified over ten years ago. Since then, it has been demonstrated that Set1/COMPASS and its enzymatic product, H3K4 methylation, is highly conserved across the evolutionary tree. Although there is only one COMPASS in yeast, human cells bear at least six COMPASS family members each capable of methylating H3K4 with non-redundant functions. In yeast, the monoubiquitination of histone H2B by Rad6/Bre1 is required for proper H3K4 and H3K79 trimethylations. This histone crosstalk and its machinery are also highly conserved from yeast to human. In this review, the process of histone H2B monoubiquitination-dependent and independent histone H3K4 methylation as a mark of active transcription, enhancer signatures, and developmentally poised genes will be discussed. The misregulation of histone H2B monoubiquitination and H3K4 methylation results in the pathogenesis of human diseases including cancer. Recent findings in this regard will also be examined. PMID:22663077

Generalized peritonitis requiring re-operation after leakage of omental patch repair of perforated peptic ulcer.

Science.gov (United States)

Maghsoudi, Hemmat; Ghaffari, Alireza

2011-01-01

Peptic ulcer perforations are a common emergency, but available literature is silent on the exact definition, incidence, management, and complications of peritonitis due to omental patch leakage. Retrospective data were collected on 422 patients who underwent omental patch repair of perforated peptic ulcer between March 20, 1999 and March 20, 2006. The definitive diagnosis of perforated peptic ulcer and omental patch leakage was obtained at surgery. Seventeen (4%) patients experienced generalized peritonitis due to omental patch leakage. Mean age was 60.6 years. Mortality rate was 29.4%, and the mean hospital stay was 23.6 days. Delay in surgical approach, shock on admission, and age were all significantly associated with increased mortality. Peritonitis due to omental patch leakage can result in significant morbidity and mortality. The most common causes of omental patch leakage and operative procedures were unknown and reinsertion of omentum, respectively. Factors such as shock on admission or delayed surgery, have significantly contributed to fatal outcomes and need careful attention.

Reinforcement of a plate weakened by multiple holes with several patches for different types of plate-patch attachment

KAUST Repository

Zemlyanova, A.

2014-01-24

The most general situation of the reinforcement of a plate with multiple holes by several patches is considered. There is no restriction on the number and the location of the patches. Two types of patch attachment are considered: only along the boundary of the patch or both along the boundary of the patch and the boundaries of the holes which this patch covers. The unattached boundaries of the holes may be loaded with given in-plane stresses. The mechanical problem is reduced to a system of singular integral equations which can be further reduced to a system of Fredholm equations. A new numerical procedure for the solution of the system of singular integral equations is proposed in this paper. It is demonstrated on numerical examples that this procedure has advantages in the case of multiple patches and holes and allows achievement of better numerical convergence with less computational effort.

DEA deformed stretchable patch antenna

International Nuclear Information System (INIS)

Jiang, X-J; Jalali Mazlouman, S; Menon, C; Mahanfar, A; Vaughan, R G

2012-01-01

A stretchable patch antenna (SPA) whose frequency is tuned by a planar dielectric elastomer actuator (DEA) is presented in this paper. This mechanically reconfigurable antenna system has a configuration resembling a pre-stretched silicone belt. Part of the belt is embedded with a layer of conductive liquid metal to form the patch antenna. Part of the belt is sandwiched between conductive electrodes to form the DEA. Electrical activation of the DEA results in a contraction of the patch antenna, and as a result, in a variation of its resonance frequency. Design and fabrication steps of this system are presented. Measurement results for deformation, resonance frequency variation and efficiency of the patch antenna are also presented. (paper)

Patching. Restitching business portfolios in dynamic markets.

Science.gov (United States)

Eisenhardt, K M; Brown, S L

1999-01-01

In turbulent markets, businesses and opportunities are constantly falling out of alignment. New technologies and emerging markets create fresh opportunities. Converging markets produce more. And of course, some markets fade. In this landscape of continuous flux, it's more important to build corporate-level strategic processes that enable dynamic repositioning than it is to build any particular defensible position. That's why smart corporate strategists use patching, a process of mapping and remapping business units to create a shifting mix of highly focused, tightly aligned businesses that can respond to changing market opportunities. Patching is not just another name for reorganizing; patchers have a distinctive mindset. Traditional managers see structure as stable; patching managers believe structure is inherently temporary. Traditional managers set corporate strategy first, but patching managers keep the organization focused on the right set of business opportunities and let strategy emerge from individual businesses. Although the focus of patching is flexibility, the process itself follows a pattern. Patching changes are usually small in scale and made frequently. Patching should be done quickly; the emphasis is on getting the patch about right and fixing problems later. Patches should have a test drive before they're formalized but then be tightly scripted after they've been announced. And patching won't work without the right infrastructure: modular business units, fine-grained and complete unit-level metrics, and companywide compensation parity. The authors illustrate how patching works and point out some common stumbling blocks.

Spatial patterns of ponderosa pine regeneration in high-severity burn patches

Science.gov (United States)

Suzanne M. Owen; Carolyn H. Sieg; Andrew J. Sanchez. Meador; Peter Z. Fule; Jose M. Iniguez; L. Scott. Baggett; Paula J. Fornwalt; Michael A. Battaglia

2017-01-01

Contemporary wildfires in southwestern US ponderosa pine forests can leave uncharacteristically large patches of tree mortality, raising concerns about the lack of seed-producing trees, which can prevent or significantly delay ponderosa pine regeneration. We established 4-ha plots in high-severity burn patches in two Arizona wildfires, the 2000 Pumpkin and 2002 Rodeo-...

Super wideband characteristics of monopolar patch antenna

Directory of Open Access Journals (Sweden)

Xi Chen

2013-12-01

Full Text Available A simple method of acquiring super wideband characteristics for monopolar patch antenna is proposed. Through adopting a modified cone as feeding and radiating structure, the monopolar patch antenna can reach the impedance bandwidth of more than 1:23.4 for voltage standing wave ratio (VSWR ≤ 2. In the whole operating band, the antenna has the like-monopole omnidirectional radiation patterns and the peak gains of 3.8–8.7 dB. Meanwhile, the height of the antenna is just 0.074λ(c, and the diameter of the radiated body is 0.205λ(c, which is smaller than other ultra-wideband omnidirectional antenna.

Influence of habitat quality, population size, patch size, and connectivity on patch-occupancy dynamics of the middle spotted woodpecker.

Science.gov (United States)

Robles, Hugo; Ciudad, Carlos

2012-04-01

Despite extensive research on the effects of habitat fragmentation, the ecological mechanisms underlying colonization and extinction processes are poorly known, but knowledge of these mechanisms is essential to understanding the distribution and persistence of populations in fragmented habitats. We examined these mechanisms through multiseason occupancy models that elucidated patch-occupancy dynamics of Middle Spotted Woodpeckers (Dendrocopos medius) in northwestern Spain. The number of occupied patches was relatively stable from 2000 to 2010 (15-24% of 101 patches occupied every year) because extinction was balanced by recolonization. Larger and higher quality patches (i.e., higher density of oaks >37 cm dbh [diameter at breast height]) were more likely to be occupied. Habitat quality (i.e., density of large oaks) explained more variation in patch colonization and extinction than did patch size and connectivity, which were both weakly associated with probabilities of turnover. Patches of higher quality were more likely to be colonized than patches of lower quality. Populations in high-quality patches were less likely to become extinct. In addition, extinction in a patch was strongly associated with local population size but not with patch size, which means the latter may not be a good surrogate of population size in assessments of extinction probability. Our results suggest that habitat quality may be a primary driver of patch-occupancy dynamics and may increase the accuracy of models of population survival. We encourage comparisons of competing models that assess occupancy, colonization, and extinction probabilities in a single analytical framework (e.g., dynamic occupancy models) so as to shed light on the association of habitat quality and patch geometry with colonization and extinction processes in different settings and species. ©2012 Society for Conservation Biology.

PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.

Science.gov (United States)

Somogyi, Orsolya; Zelko, Romana

2016-11-01

Transdermal therapy with medical patches is a simple possibility in home medication. As the correct use of patches has a decisive impact from the point of its modulator effect.A questionnaire survey was developed to explore level of patients' knowledge of the correct use of transdermal patches. A survey was administered in thirteen Hungarian community pharmacies from October of 2012 to May of 2015. Most of the participants, men and women over 18 years of age (n = 233), used major analgesic patches (fentanyl); the remainder were given nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis testing it was assumed that men were more likely to use a razor for skin depilation before patch application than women as their denser pelage hinders patch adhesion. The hypothesis testing showed no significant gender difference in razor use (X² = 0.201; p = 0.654). Pharmacists should direct patients to avoid using soap for skin cleansing before patch application because only 22 percent of the participants always avoided its use. Since only 9 tests were flawless from 233 completed questionnaires. Many patients do not understand how to correctly apply a transdermal dosage patch. Pharmacists should teach their correct application based on results.

2-(4-Fluorophenyl-2H-chromen-4(3H-one

Directory of Open Access Journals (Sweden)

Michał Wera

2012-02-01

Full Text Available In the crystal structure of the title compound, C15H11FO2, molecules form inversion dimers through pairs of weak C—H...O hydrogen bonds. Dimers oriented in parallel, linked by C—H...π contacts, are arranged in columns along the b axis. The fluorophenyl ring and the benzene ring of the 2H-chromen-4(3H-one unit are inclined to one another by 70.41 (16°. They are respectively parallel in a given column or almost perpendicular [oriented at an angle of 87.8 (1°] in neighbouring (inversely oriented columns, forming a herringbone pattern.

Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.

Science.gov (United States)

Choi, Hee Youn; Kim, Yo Han; Hong, Donghyun; Kim, Seong Su; Bae, Kyun-Seop; Lim, Hyeong-Seok

2015-08-01

We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model. This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea. The population PK analysis was performed using NONMEM software, version 7.3. From the final PK model, we simulated repeat patch application results assuming various transdermal absorption rates. Based on the clinical trial data, novel donepezil patches with doses of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), and 175 mg/50 cm(2) were placed on each subject. A linear one-compartment, first-order elimination with sequential zero- and first-order absorption model best described the donepezil plasma concentrations after patch application. Simulated results on the basis of the PK model showed that repeat application of the patches of 87.5 mg/25 cm(2) and 175 mg/50 cm(2) every 72 h would cover the therapeutic range of donepezil and reach steady-state faster with fewer fluctuations in concentration compared to typical oral administrations. A linear one-compartment with sequential zero- and first-order absorption model was effective for describing the PKs of donepezil after application of patch. Based on this analysis, 87.5 mg/25 cm(2) or 175 mg/50 cm(2) patch application every 72 h is expected to achieve the desired plasma concentration of donepezil.

Clinical effect of 1g/L anthocyanin eye-patch for mild and moderate dry eye

Directory of Open Access Journals (Sweden)

Ke-Hua Wang

2018-05-01

Full Text Available AIM:To evaluate the clinic efficacy of 1g/L anthocyanin eye-patch for mild and moderate dry eye. METHODS: In this prospective and multicenter study, a total of 320 cases(640 eyeswith mild and moderate dry eye were enrolled from 8 Aier Eye Hospitals in Changsha, Chongqing, Wuhan and so on from October 2016 to April 2017. The patients were assigned to eye patch group(160 casesand artificial tears group(160 casesbased on random number table. The patients in eye-patch group used 1g/L of anthocyanin eye-patch for more than 6h during night sleep, while the patients in artificial tears group used polyvinyl alcohol eye drops for 4 times per day. The evaluation of symptoms and signs were conducted on 1d before the treatment and 14d after the treatment. The evaluation of symptoms adopted the Ocular Surface Disease Index(OSDI, while the observation of signs included tear secretion test(Schirmer Ⅰ test, SⅠt, first noninvasive tear breakup time(NITBUTfas well as average noninvasive tear breakup time(NITBUTavmeasured by Oculus ocular surface analyser. RESULTS: OSDI score, NITBUTf and NITBUTav in the two groups after treatment were significantly improved compared with that before treatment, and the difference had a statistical significance(PP>0.05. There was no significant difference in OSDI score, NITBUTf, NITBUTav and SⅠt between the two groups after treatment(P>0.05.CONCLUSION: The 1g/L anthocyanin eye-patch has similar efficacy with artificial tears for mild and moderate dry eye, which can effectively improve the symptoms and tear film stability.

Lactobacilli Dominance and Vaginal pH: Why is the Human Vaginal Microbiome Unique?

Directory of Open Access Journals (Sweden)

Elizabeth A. Miller

2016-12-01

Full Text Available The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus, which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies (N=21 mammals for pH and 14 mammals for lactobacilli abundance. We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4 to 7.8. Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli abundance and multiple metrics of STD or birth injury risk (P-values ranged from 0.13 to 0.99. Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non-human

Microstrip patch antenna for simultaneous strain and temperature sensing

Science.gov (United States)

Mbanya Tchafa, F.; Huang, H.

2018-06-01

A patch antenna, consisting of a radiation patch, a dielectric substrate, and a ground plane, resonates at distinct fundamental frequencies that depend on the substrate dielectric constant and the dimensions of the radiation patch. Since these parameters change with the applied strain and temperature, this study investigates simultaneous strain and temperature sensing using a single antenna that has two fundamental resonant frequencies. The theoretical relationship between the antenna resonant frequency shifts, the temperature, and the applied strain was first established to guide the selection of the dielectric substrate, based on which an antenna sensor with a rectangular radiation patch was designed and fabricated. A tensile test specimen instrumented with the antenna sensor was subjected to thermo-mechanical tests. Experiment results validated the theoretical predictions that the normalized antenna resonant frequency shifts are linearly proportional to the applied strain and temperature changes. An inverse method was developed to determine the strain and temperature changes from the normalized antenna resonant frequency shifts, yielding measurement uncertainty of 0.4 °C and 17.22 μ \\varepsilon for temperature and strain measurement, respectively.

Photo-patch and patch tests in patients with dermatitis over the photo-exposed areas: A study of 101 cases from a tertiary care centre in India.

Science.gov (United States)

Sharma, Vinod Kumar; Bhari, Neetu; Wadhwani, Ashok Roopchand; Bhatia, Riti

2018-02-01

Many patients with dermatitis over photo-exposed body areas are positive to many contact allergens and have a pre-existing allergic contact dermatitis. This study included patients who presented to a tertiary centre in India with dermatitis on photo-exposed body areas suspected of chronic actinic dermatitis. Their detailed histories were recorded and cutaneous and systemic examinations were performed. Patch testing was done in all the patients and photo-patch testing was carried out in 86 patients. Altogether 101 patients were included (69 males, 32 females). The most common presentation was lichenified hyperpigmented plaques on the photo-exposed sites. Photosensitivity was recorded in 64 (63%) patients and summer exacerbation in 52 (52%). Exposure to the Parthenium hysterophorus weed was recorded in 70 (69%) patients, 27 (26.7%) had a history of hair dye application and 20 (20%) had a history of atopy. Photo-patch test was positive in 11 (12.8%) patients and patch testing was positive in 71 (70%). Parthenium hysterophorus was the most common allergen implicated and was positive in three (4%) photo-patch and 52 (52%) patch tests. Other positive photo-patch test allergens were perfume mix, balsam of Peru, thiuram mix, Compositae mix and promethazine hydrochloride. Other common patch test allergens were parthenolide, colophony, fragrance mix and p-phenylenediamine (PPD) base. In the Indian population parthenium and perfume mix are the most common photoallergens in patients with dermatitis over photo-exposed areas, while parthenium, colophony, fragrance mix and PPD are the common positive allergens. © 2016 The Australasian College of Dermatologists.

Ophthalmic antihistamines and H1-H4 receptors.

Science.gov (United States)

Wade, Laurie; Bielory, Leonard; Rudner, Shara

2012-10-01

Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1-H4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. We retrieved the binding affinities for nineteen antihistamines. For H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280, 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 ,000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 ,400 nM), to H3. Data on binding affinities to the H4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = >10, 000 nM) for H4 receptors. This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.

Detectability and acceptability of continuous pulse signals for the MemoPatch® device, an electronic skin patch intended to deliver tactile medication reminder signals

Directory of Open Access Journals (Sweden)

Abraham I

2015-02-01

Full Text Available Ivo Abraham,1–3 Jan De Geest,2 Wim De Geest,2 Elke De Troy,4 Karen MacDonald3 1Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ, USA; 2TheraSolve, Diepenbeek, Belgium; 3Matrix45, Tucson, AZ, USA; 4Jessa Ziekenhuis, Hasselt, Belgium Background: Unintended forgetfulness is the most common cause of medication nonadherence. MemoPatch® is an electronic skin patch intended to deliver discreet tactile medication reminder stimuli. This study aimed 1 to evaluate, within an experimental setup, the detectability and acceptability of fifteen continuous bipolar pulse signals; 2 to identify variables, if any, associated with differential perception of the candidate reminder signals; and 3 to collect safety data as reported by subjects or observed by staff. Methods: This was a laboratory experiment involving 147 healthy adult volunteers (55.1% female, 98.0% Caucasian, with age 41.8±16.0 years, body mass index [BMI] 24.7±4.4, upper body adiposity 28.5%±8.3% body fat, and skin impedance 367.6±140.8Ω and using an experimental version of the MemoPatch®. Following four training signals administered in fixed order, subjects were exposed to a set of fifteen randomly sequenced signals varying in rise and fall time, width, and current, to be rated in terms of detectability ("too weak", "appropriate", or "too strong" and acceptability. Results: Ratings of "appropriate" were virtually independent of such variables as sex, BMI, upper body adiposity, and skin impedance at the patch location. Five signals were rated as "appropriate" by ≥67% of subjects and acceptable by ≥95% of subjects, virtually independently of the indicators of interest, and were retained as candidate signals for use in next stages of development and commercialization. Nine adverse events, none serious, were observed in six subjects. Conclusion: This study yielded five effective and safe candidate signals for potential use in the MemoPatch

Ammonia volatilization from artificial dung and urine patches measured by the equilibrium concentration technique (JTI method)

Science.gov (United States)

Saarijärvi, K.; Mattila, P. K.; Virkajärvi, P.

The aim of this study was to investigate the dynamics of ammonia (NH 3) volatilization from intensively managed pastures on a soil type typical of the dairy production area in Finland and to clarify the effect of rainfall on NH 3 volatilization. The study included two experiments. In Experiment 1 the total amount of NH 3-N emitted was calculated based on the annual surface coverage of dung (4%) and urine (17%). The application rate of total N in the simulated dung and urine patches was approximately 47 g N m -2 and 113 g N m -2, respectively. In Experiment 1 the general level of NH 3 emissions from the urine patches was high and the peak volatilization rate was 0.54 g NH 3-N m -2 h -1. As expected, emissions from the dung pats were clearly lower with a maximum rate of 0.10 g NH 3-N m -2 h -1. The total emission calculated for the whole pasture area (stocking rate four cows ha -1 y -1, urine coverage 17% and dung coverage 4%) was 16.1 kg NH 3-N ha -1. Approximately 96% of the total emission originated from urine. In Experiment 2 we measured the emissions from urine only and the treatments on the urine patches were: (1) no irrigation, (2) 5+5 mm and (3) 20 mm irrigation. The peak emission rates were 0.13, 0.09 and 0.04 g NH 3-N m -2 h -1 and the total emissions were 6.9, 3.0 and 1.7 kg NH 3-N ha -1, for treatments (1), (2) and (3), respectively. In both measurements over 80% of the total emission occurred during the first 48 h and there was a clear diurnal rhythm. Increasing rainfall markedly decreased NH 3 emission. Volatilization was highest with dry and warm soil. The JTI method appeared to be suitable for measuring NH 3 volatilization in this kind of experiment. According to our results, the importance of pastures as a source of NH 3 emission in Finland is minor.

Sub-Patch Roughness in Earthquake Rupture Investigations

KAUST Repository

Zielke, Olaf; Mai, Paul Martin

2016-01-01

Fault geometric complexities exhibit fractal characteristics over a wide range of spatial scales (<µm to >km) and strongly affect the rupture process at corresponding scales. Numerical rupture simulations provide a framework to quantitatively investigate the relationship between a fault's roughness and its seismic characteristics. Fault discretization however introduces an artificial lower limit to roughness. Individual fault patches are planar and sub-patch roughness –roughness at spatial scales below fault-patch size– is not incorporated. Does negligence of sub-patch roughness measurably affect the outcome of earthquake rupture simulations? We approach this question with a numerical parameter space investigation and demonstrate that sub-patch roughness significantly modifies the slip-strain relationship –a fundamental aspect of dislocation theory. Faults with sub-patch roughness induce less strain than their planar-fault equivalents at distances beyond the length of a slipping fault. We further provide regression functions that characterize the stochastic effect sub-patch roughness.

Sub-Patch Roughness in Earthquake Rupture Investigations

KAUST Repository

Zielke, Olaf

2016-02-13

Fault geometric complexities exhibit fractal characteristics over a wide range of spatial scales (<µm to >km) and strongly affect the rupture process at corresponding scales. Numerical rupture simulations provide a framework to quantitatively investigate the relationship between a fault\\'s roughness and its seismic characteristics. Fault discretization however introduces an artificial lower limit to roughness. Individual fault patches are planar and sub-patch roughness –roughness at spatial scales below fault-patch size– is not incorporated. Does negligence of sub-patch roughness measurably affect the outcome of earthquake rupture simulations? We approach this question with a numerical parameter space investigation and demonstrate that sub-patch roughness significantly modifies the slip-strain relationship –a fundamental aspect of dislocation theory. Faults with sub-patch roughness induce less strain than their planar-fault equivalents at distances beyond the length of a slipping fault. We further provide regression functions that characterize the stochastic effect sub-patch roughness.

Synthesis of (R)-5-(Di[2,3-3H2]propylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one-([3H]U-86170) and (R)-5-([2,3-3H2]propylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij) quinolin-2(1H)-one ([3H]U-91356)

International Nuclear Information System (INIS)

Moon, M.W.; Hsi, R.S.P.

1992-01-01

(R)-5-(diallylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (12b) was prepared in 9% overall yield from 3-aminoquinoline. Reaction of 12b in ethyl acetate with tritium gas in presence of a 5% platinum on carbon catalyst afforded a mixture of (R)-5-(di[2,3- 3 H 2 ]propylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2(1H)-one ([ 3 H]U-86170, 69 Ci/mmol) and (R)-5-([2,3- 3 H 2 ]-propylamino)5,6-dihydro-4H-imidazo-[4,5,1-ij]quinolin-2(1H)-one ( [ 3 H]U-91356, 34 Ci/mmol) which was separated by preparative reverse-phase chromatography. U-86170 and U-91356 are potent dopamine D2 agonists. The labelled compounds are useful for drug disposition studies. [ 3 H]U-86170 is also useful as a dopamine D2 agonist radioligand for receptor binding studies. (author)

Compressed sensing for high-resolution nonlipid suppressed 1 H FID MRSI of the human brain at 9.4T.

Science.gov (United States)

Nassirpour, Sahar; Chang, Paul; Avdievitch, Nikolai; Henning, Anke

2018-04-29

The aim of this study was to apply compressed sensing to accelerate the acquisition of high resolution metabolite maps of the human brain using a nonlipid suppressed ultra-short TR and TE 1 H FID MRSI sequence at 9.4T. X-t sparse compressed sensing reconstruction was optimized for nonlipid suppressed 1 H FID MRSI data. Coil-by-coil x-t sparse reconstruction was compared with SENSE x-t sparse and low rank reconstruction. The effect of matrix size and spatial resolution on the achievable acceleration factor was studied. Finally, in vivo metabolite maps with different acceleration factors of 2, 4, 5, and 10 were acquired and compared. Coil-by-coil x-t sparse compressed sensing reconstruction was not able to reliably recover the nonlipid suppressed data, rather a combination of parallel and sparse reconstruction was necessary (SENSE x-t sparse). For acceleration factors of up to 5, both the low-rank and the compressed sensing methods were able to reconstruct the data comparably well (root mean squared errors [RMSEs] ≤ 10.5% for Cre). However, the reconstruction time of the low rank algorithm was drastically longer than compressed sensing. Using the optimized compressed sensing reconstruction, acceleration factors of 4 or 5 could be reached for the MRSI data with a matrix size of 64 × 64. For lower spatial resolutions, an acceleration factor of up to R∼4 was successfully achieved. By tailoring the reconstruction scheme to the nonlipid suppressed data through parameter optimization and performance evaluation, we present high resolution (97 µL voxel size) accelerated in vivo metabolite maps of the human brain acquired at 9.4T within scan times of 3 to 3.75 min. © 2018 International Society for Magnetic Resonance in Medicine.

Rapid establishment of a regular distribution of adult tropical Drosophila parasitoids in a multi-patch environment by patch defence behaviour.

Science.gov (United States)

de Jong, Peter W; Hemerik, Lia; Gort, Gerrit; van Alphen, Jacques J M

2011-01-01

Females of the larval parasitoid of Drosophila, Asobara citri, from sub-Saharan Africa, defend patches with hosts by fighting and chasing conspecific females upon encounter. Females of the closely related, palearctic species Asobara tabida do not defend patches and often search simultaneously in the same patch. The effect of patch defence by A. citri females on their distribution in a multi-patch environment was investigated, and their distributions were compared with those of A. tabida. For both species 20 females were released from two release-points in replicate experiments. Females of A. citri quickly reached a regular distribution across 16 patches, with a small variance/mean ratio per patch. Conversely, A. tabida females initially showed a clumped distribution, and after gradual dispersion, a more Poisson-like distribution across patches resulted (variance/mean ratio was closer to 1 and higher than for A. citri). The dispersion of A. tabida was most probably an effect of exploitation: these parasitoids increasingly made shorter visits to already exploited patches. We briefly discuss hypotheses on the adaptive significance of patch defence behaviour or its absence in the light of differences in the natural history of both parasitoid species, notably the spatial distribution of their hosts.

Improved image registration by sparse patch-based deformation estimation.

Science.gov (United States)

Kim, Minjeong; Wu, Guorong; Wang, Qian; Lee, Seong-Whan; Shen, Dinggang

2015-01-15

Despite intensive efforts for decades, deformable image registration is still a challenging problem due to the potential large anatomical differences across individual images, which limits the registration performance. Fortunately, this issue could be alleviated if a good initial deformation can be provided for the two images under registration, which are often termed as the moving subject and the fixed template, respectively. In this work, we present a novel patch-based initial deformation prediction framework for improving the performance of existing registration algorithms. Our main idea is to estimate the initial deformation between subject and template in a patch-wise fashion by using the sparse representation technique. We argue that two image patches should follow the same deformation toward the template image if their patch-wise appearance patterns are similar. To this end, our framework consists of two stages, i.e., the training stage and the application stage. In the training stage, we register all training images to the pre-selected template, such that the deformation of each training image with respect to the template is known. In the application stage, we apply the following four steps to efficiently calculate the initial deformation field for the new test subject: (1) We pick a small number of key points in the distinctive regions of the test subject; (2) for each key point, we extract a local patch and form a coupled appearance-deformation dictionary from training images where each dictionary atom consists of the image intensity patch as well as their respective local deformations; (3) a small set of training image patches in the coupled dictionary are selected to represent the image patch of each subject key point by sparse representation. Then, we can predict the initial deformation for each subject key point by propagating the pre-estimated deformations on the selected training patches with the same sparse representation coefficients; and (4) we

The Histamine H4 Receptor: From Orphan to the Clinic

Directory of Open Access Journals (Sweden)

Robin L. Thurmond

2015-03-01

Full Text Available The histamine H4 receptor (H4R was first noted as a sequence in genomic databases that had features of a G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this receptor and determine if it represented a drug target. Taking advantage of the vast literature on histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma and pruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronic pruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists to the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into

*New* CRITICAL Windows Security patch

CERN Multimedia

2003-01-01

On 10 September 2003, Microsoft issued a new CRITICAL security patch, MS03-039. It must be URGENTLY applied on ALL WINDOWS systems, which are not centrally managed for security patches. This includes Experiment computers, Home computers and Windows Portable and Desktop systems not running NICE. Details of the security hole and patch for MS03-039 (which also includes MS03-026) are at: http://cern.ch/it-div/news/hotfix-MS03-039.asp http://www.microsoft.com/technet/security/bulletin/MS03-039.asp

*New*: CRITICAL Windows Security patch

CERN Multimedia

2003-01-01

On 10 September 2003, Microsoft issued a new CRITICAL security patch, MS03-039. It must be URGENTLY applied on ALL WINDOWS systems, which are not centrally managed for security patches. This includes Experiment computers, Home computers and Windows Portable and Desktop systems not running NICE. Details of the security hole and patch for MS03-039 (which also includes MS03-026) are at: http://cern.ch/it-div/news/hotfix-MS03-039.asp http://www.microsoft.com/technet/security/bulletin/MS03-039.asp

Localization and Tracking of Submerged Phytoplankton Bloom Patches by an Autonomous Underwater Vehicle

Science.gov (United States)

Godin, M. A.; Ryan, J. P.; Zhang, Y.; Bellingham, J. G.

2012-12-01

Observing plankton in their drifting frame of reference permits effective studies of marine ecology from the perspective of microscopic life itself. By minimizing variation caused simply by advection, observations in a plankton-tracking frame of reference focus measurement capabilities on the processes that influence the life history of populations. Further, the patchy nature of plankton populations motivates use of sensor data in real-time to resolve patch boundaries and adapt observing resources accordingly. We have developed capabilities for population-centric plankton observation and sampling by autonomous underwater vehicles (AUVs). Our focus has been on phytoplankton populations, both because of their ecological significance - as the core of the oceanic food web and yet potentially harmful under certain bloom conditions, as well as the accessibility of their signal to simple optical sensing. During the first field deployment of these capabilities in 2010, we tracked a phytoplankton patch containing toxigenic diatoms and found that their toxicity correlated with exposure to resuspended sediments. However, this first deployment was labor intensive as the AUV drove in a pre-programmed pattern centered around a patch-marking drifter; it required a boat deployment of the patch-marking drifter and required full-time operators to periodically estimate of the position of the patch with respect to the drifter and adjust the AUV path accordingly. In subsequent field experiments during 2011 and 2012, the Tethys-class long-range AUVs ran fully autonomous patch tracking algorithms which detected phytoplankton patches and continually updated estimates of each patch center by driving adaptive patterns through the patch. Iterations of the algorithm were generated to overcome the challenges of tracking advecting and evolving patches while minimizing human involvement in vehicle control. Such fully autonomous monitoring will be necessary to perform long-term in

4-Phenethylthio-2-phenylpyrazolo[1,5-a][1,3,5]triazin-7(6H-one

Directory of Open Access Journals (Sweden)

Sergey A. Smolnikov

2017-12-01

Full Text Available Exploring the pharmacologically important pyrazolo[1,5-a][1,3,5]triazin-7(6H-one scaffold for the construction of new bioactive compounds, we developed a synthesis of 4-phenethylthio-2-phenylpyrazolo[1,5-a][1,3,5]triazin-7(6H-one (4 via S-alkylation of 2-phenyl-4-thioxopyrazolo[1,5-a][1,3,5]triazine-7(6H-one (3, prepared by the double ring closure of pyrazole and triazine rings upon the treatment of 1-cyanoacetyl-4-benzoylthiosemicarbazide (2 with alkali. The antiproliferative activity of 4 against human lung cancer (A549 and human breast cancer (MDA-MB231 cell lines was investigated. Compound 4 was found to be more active against lung cancer cells than breast cancer cells.

Modulation of the human equilibrative nucleoside transporter1 (hENT1) activity by IL-4 and PMA in B cells from chronic lymphocytic leukemia.

Science.gov (United States)

Fernández Calotti, Paula; Galmarini, Carlos María; Cañones, Cristian; Gamberale, Romina; Saénz, Daniel; Avalos, Julio Sánchez; Chianelli, Mónica; Rosenstein, Ruth; Giordano, Mirta

2008-02-15

Nucleoside transporters (NTs) are essential for the uptake of therapeutic nucleoside analogs, broadly used in cancer treatment. The mechanisms responsible for NT regulation are largely unknown. IL-4 is a pro-survival signal for chronic lymphocytic leukemia (CLL) cells and has been shown to confer resistance to nucleoside analogs. The aim of this study was to investigate whether IL-4 is able to modulate the expression and function of the human equilibrative NT1 (hENT1) in primary cultures of CLL cells and, consequently, to affect cytotoxicity induced by therapeutic nucleosides analogs. We found that treatment with IL-4 (20 ng/ml for 24 h) increased mRNA hENT1 expression in CLL cells without affecting that of normal B cells. Given that the enhanced mRNA levels of hENT1 in CLL cells did not result in increased transport activity, we examined the possibility that hENT1 induced by IL-4 may require post-translational modifications to become active. We found that the acute stimulation of PKC in IL-4-treated CLL cells by short-term incubation with PMA significantly increased hENT1 transport activity and favoured fludarabine-induced apoptosis. By contrast, and in line with previous reports, IL-4 plus PMA protected CLL cells from a variety of cytotoxic agents. Our findings indicate that the combined treatment with IL-4 and PMA enhances hENT1 activity and specifically sensitizes CLL cells to undergo apoptosis induced by fludarabine.

The human repeated insult patch test in the 21st century: a commentary.

Science.gov (United States)

Basketter, David A

2009-01-01

The human repeated insult patch test (HRIPT) is over half a century old, but is still used in several countries as a confirmatory test in the safety evaluation of skin sensitizers. This is despite the criticism it receives from an ethical perspective and regarding the scientific validity of such testing. In this commentary, the HRIPT is reviewed, with emphasis on ethical aspects and where the test can, and cannot, contribute in a scientifically meaningful manner to safety evaluation. It is concluded that where there is a specific rationale for testing, for example, to substantiate a no-effect level for a sensitizing chemical or to ensure that matrix effects are not making an unexpected contribution to sensitizing potency, then rigorous independent review may confirm that an HRIPT is ethical and scientifically justifiable. The possibility that sensitization may be induced in volunteers dictates that HRIPTs should be conducted rarely and in cases where the benefits overwhelmingly outweigh the risk. However, for the very large majority of HRIPTs conducted concerning the risk of skin sensitization, there is neither scientific justification nor any other merit.

Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model

DEFF Research Database (Denmark)

Billeskov, Rolf; Christensen, Jan Pravsgaard; Aagaard, Claus

2013-01-01

a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more......-γ single producing CD4 T cell subsets correlated with protection in the mouse TB model. Moreover, our data demonstrated that the H28 vaccine antigen was able to induce strong protection in both a mouse and a non-human primate TB model....

Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature

Science.gov (United States)

Vassilieva, Elena V.; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T.; Esser, E. Stein; Pewin, Winston P.; Pulit-Penaloza, Joanna A.; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna

2015-01-01

Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study we evaluated the immunogenicity of H1N1, H3N2 and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25°C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by SRID assay and immune responses to vaccination in BALB/c mice. After a single immunization all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least three months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability. PMID:25895053

Reinforcement of a plate weakened by multiple holes with several patches for different types of plate-patch attachment

KAUST Repository

Zemlyanova, A.

2014-01-01

the boundary of the patch or both along the boundary of the patch and the boundaries of the holes which this patch covers. The unattached boundaries of the holes may be loaded with given in-plane stresses. The mechanical problem is reduced to a system

Disruptive coloration in woodland camouflage: evaluation of camouflage effectiveness due to minor disruptive patches

Science.gov (United States)

Selj, Gorm K.; Heinrich, Daniela H.

2016-10-01

We present results from an observer based photosimulation study of generic camouflage patterns, intended for military uniforms, where three near-identical patterns have been compared. All the patterns were prepared with similar effective color, but were different in how the individual pattern patches were distributed throughout the target. We did this in order to test if high contrast (black) patches along the outline of the target would enhance the survivability when exposed to human observers. In the recent years it has been shown that disruptive coloration in the form of high contrast patches are capable of disturbing an observer by creating false edges of the target and consequently enhance target survivability. This effect has been shown in different forms in the Animal Kingdom, but not to the same extent in camouflaged military targets. The three patterns in this study were i) with no disruptive preference, ii) with a disruptive patch along the outline of the head and iii) with a disruptive patch on the outline of one of the shoulders. We used a high number of human observers to assess the three targets in 16 natural (woodland) backgrounds by showing images of one of the targets at the time on a high definition pc screen. We found that the two patterns that were thought to have a minor disruptive preference to the remaining pattern were more difficult to detect in some (though not all) of the 16 scenes and were also better in overall performance when all the scenes were accounted for.

Long-term stability of influenza vaccine in a dissolving microneedle patch.

Science.gov (United States)

Mistilis, Matthew J; Joyce, Jessica C; Esser, E Stein; Skountzou, Ioanna; Compans, Richard W; Bommarius, Andreas S; Prausnitz, Mark R

2017-04-01

This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25 °C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than 1 year at 25 °C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60 °C for 4 months, multiple freeze-thaw cycles, or electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.

Drug Delivery and Transport into the Central Circulation: An Example of Zero-Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.

Science.gov (United States)

Cawello, Willi; Braun, Marina; Andreas, Jens-Otto

2018-01-13

Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.

Effects of nickel treatment on H3K4 trimethylation and gene expression.

Directory of Open Access Journals (Sweden)

Kam-Meng Tchou-Wong

Full Text Available Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl(2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3, a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq. The effect of NiCl(2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl(2. This study may provide insights into the epigenetic mechanism(s underlying the carcinogenicity of nickel compounds.

Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

Science.gov (United States)

Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

2014-10-01

To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

Synthesis and crystal structure of 4-fluorobenzylammonium dihydrogen phosphate, [FC6H4CH2NH3]H2PO4

Directory of Open Access Journals (Sweden)

Ali Rayes

2016-12-01

Full Text Available The asymmetric unit of the title salt, [p-FC6H4CH2NH3]+·H2PO4−, contains one 4-fluorobenzylammonium cation and one dihydrogen phosphate anion. In the crystal, the H2PO4− anions are linked by O—H...O hydrogen bonds to build corrugated layers extending parallel to the ab plane. The FC6H4CH2NH3+ cations lie between these anionic layers to maximize the electrostatic interactions and are linked to the H2PO4− anions through N—H...O hydrogen bonds, forming a three-dimensional supramolecular network. Two hydrogen atoms belonging to the dihydrogen phosphate anion are statistically occupied due to disorder along the OH...HO direction.

Syntheses of 4-aminobutanoic acid-2,2-/sup 2/H/sub 2/ and -4,4-/sup 2/H/sub 2/ and progabide-2,2-/sup 2/H/sub 2/ and -4,4-/sup 2/H/sub 2/

Energy Technology Data Exchange (ETDEWEB)

Davis, B.

1987-10-01

4-Aminobutanoic acid-2,2-/sup 2/H/sub 2/ and -4,4-/sup 2/H/sub 2/ were synthesized in high yield with high deuterium incorporation, and then converted into the corresponding deuterium-labelled anti-convulsant drug, progabide, by means of a transimination reaction.

Functional expression of human adenine nucleotide translocase 4 in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Takashi Hamazaki

2011-04-01

Full Text Available The adenine nucleotide translocase (ANT mediates the exchange of ADP and ATP across the inner mitochondrial membrane. The human genome encodes multiple ANT isoforms that are expressed in a tissue-specific manner. Recently a novel germ cell-specific member of the ANT family, ANT4 (SLC25A31 was identified. Although it is known that targeted depletion of ANT4 in mice resulted in male infertility, the functional biochemical differences between ANT4 and other somatic ANT isoforms remain undetermined. To gain insight into ANT4, we expressed human ANT4 (hANT4 in yeast mitochondria. Unlike the somatic ANT proteins, expression of hANT4 failed to complement an AAC-deficient yeast strain for growth on media requiring mitochondrial respiration. Moreover, overexpression of hANT4 from a multi-copy plasmid interfered with optimal yeast growth. However, mutation of specific amino acids of hANT4 improved yeast mitochondrial expression and supported growth of the AAC-deficient yeast on non-fermentable carbon sources. The mutations affected amino acids predicted to interact with phospholipids, suggesting the importance of lipid interactions for function of this protein. Each mutant hANT4 and the somatic hANTs exhibited similar ADP/ATP exchange kinetics. These data define common and distinct biochemical characteristics of ANT4 in comparison to ANT1, 2 and 3 providing a basis for study of its unique adaptation to germ cells.

Differential expression gene profiling in human lymphocyte after 6 h irradiated

International Nuclear Information System (INIS)

Li Jianguo; Qin Xiujun; Zhang Wei; Xu Chaoqi; Li Weibin; Dang Xuhong; Zuo Yahui

2011-01-01

Objective: To provide the evidence of health damage for the staff irradiated from the gene level. Methods: The study analyzed the differential transcriptional profile of normal human lymphocyte and human lymphocyte irradiated with 0.1 Gy, 0.2 Gy, 0.5 Gy, 1.0 Gy by whole genome chip after 6 h irradiated. Results: The results showed that there were 1177 differentially expressed genes with 0.1 Gy after 6 h irradiation, and there were 1922 differentially expressed genes with 0.2 Gy after 6 h irradiation, and there were 492 differentially expressed genes with 0.5 Gy after 6 h irradiation, 2615 differentially expressed genes with 1.0 Gy after 6 h irradiation, 114 differentially expressed genes in 4 dose points after 6 h irradiation. RT-PCR results indicated that the relative quantity's result of EGR1, HLA-DMB and TAIAP1 was consistent with gene chip data. Conclusion: The study found many significant different genes in human lymphocyte with different doses after 6 h irradiation, which will provide a basis for the further radiation-different-genes and the mechanism of radiation damage. (authors)

Effects of a transdermal lidocaine patch on indicators of postoperative pain in dogs undergoing midline ovariohysterectomy.

Science.gov (United States)

Merema, Danielle K; Schoenrock, Emily K; Le Boedec, Kevin; McMichael, Maureen A

2017-05-15

OBJECTIVE To determine the effects of a transdermal lidocaine patch (TLP) on indicators of postoperative pain in healthy dogs following ovariohysterectomy. DESIGN Randomized, blinded controlled trial. ANIMALS 40 healthy shelter-owned female dogs admitted to a student surgery program for ovariohysterectomy. PROCEDURES Dogs were randomly assigned to receive after ovariohysterectomy a 5-cm-wide strip of TLP applied topically on both sides of the incision, for the full length of the incision and a wound dressing (n = 19) or a placebo patch (nonmedicated wound dressing; 21). All dogs underwent midline ovariohysterectomy. Immediately afterward, dogs received 2 IM morphine injections, carprofen (SC, q 12 h for 2 days), and the assigned patch (left in place for 18 hours). Postoperative comfort was evaluated by use of the short form of the Glasgow Composite Measures Pain Scale and serum cortisol concentrations measured prior to premedication and 1, 2, 4, 6, 8, 10, and 18 hours after surgery. RESULTS No significant difference in pain scores or serum cortisol concentrations was identified between dogs that received the TLP and dogs that received a placebo patch after ovariohysterectomy. CONCLUSIONS AND CLINICAL RELEVANCE The TLP provided no additional analgesic benefit to dogs treated concurrently with recommended doses of morphine and carprofen following ovariohysterectomy. Additional studies are needed to investigate whether similar results might be achieved in dogs treated concurrently with other analgesics. (J Am Vet Med Assoc 2017;250:1140-1147).

CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA.

Science.gov (United States)

Riccardo, Federica; Iussich, Selina; Maniscalco, Lorella; Lorda Mayayo, Saray; La Rosa, Giuseppe; Arigoni, Maddalena; De Maria, Raffaella; Gattino, Francesca; Lanzardo, Stefania; Lardone, Elena; Martano, Marina; Morello, Emanuela; Prestigio, Simone; Fiore, Alessandra; Quaglino, Elena; Zabarino, Sara; Ferrone, Soldano; Buracco, Paolo; Cavallo, Federica

2014-07-15

Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model. Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated. hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response. Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting. ©2014 American Association for Cancer Research.

[H3N(CH2)4NH3]2[Al4(C2O4)(H2PO4)2(PO4)4].4[H2O]: A new layered aluminum phosphate-oxalate

International Nuclear Information System (INIS)

Peng Li; Li Jiyang; Yu Jihong; Li Guanghua; Fang Qianrong; Xu Ruren

2005-01-01

A new layered inorganic-organic hybrid aluminum phosphate-oxalate [H 3 N(CH 2 ) 4 NH 3 ] 2 [Al 4 (C 2 O 4 )(H 2 PO 4 ) 2 (PO 4 ) 4 ].4[H 2 O](AlPO-CJ25) has been synthesized hydrothermally, by using 1,4-diaminobutane (DAB) as structure-directing agent. The structure has been solved by single-crystal X-ray diffraction analysis and further characterized by IR, 31 P MAS NMR, TG-DTA as well as compositional analyses. Crystal data: the triclinic space group P-1, a=8.0484(7) A, b=8.8608(8) A, c=13.2224(11) A, α=80.830(6) deg. , β=74.965(5) deg. , γ=78.782(6) deg. , Z=2, R 1[ I >2 σ ( I )] =0.0511 and wR 2(alldata) =0.1423. The alternation of AlO 4 tetrahedra and PO 4 tetrahedra gives rise to the four-membered corner-sharing chains, which are interconnected through AlO 6 octahedra to form the layered structure with 4,6-net sheet. Interestingly, oxalate ions are bis-bidentately bonded by participating in the coordination of AlO 6 , and bridging the adjacent AlO 6 octahedra. The layers are held with each other through strong H-bondings between the terminal oxygens. The organic ammonium cations and water molecules are located in the large cavities between the interlayer regions. -- Graphical abstract: The alternation of AlO 4 tetrahedra and PO 4 tetrahedra gives rise to the four-membered corner-sharing chains, which are interconnected through AlO 6 octahedra to form the layered structure with 4,6-net sheet. Oxalate ions are bis-bidentately boned by participating in the coordination of AlO 6 , and bridging the adjacent AlO 6 octahedra

Bold Ideas for the 4th H in 4-H: Teen Identified Concerns and Actions

Directory of Open Access Journals (Sweden)

Virginia Brown

2015-03-01

Full Text Available This article summarizes a literature review; teen-identified health concerns and issues; and teen bold ideas for actions. Findings from the National 4-H Council and Molina Healthcare Teens Take on Health initiative are provided and implications for 4-H programming tied to the new Cooperative Extension National Framework for Health and Wellness are addressed. The article is intended as background for Extension educators, volunteers and administrators as they review the 4-H Healthy Living Mission Mandate, learn what mattered to teens and consider how to incorporate the findings into state and local 4-H youth development programming.

A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of the Rivastigmine Patch in Japanese Patients with Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Yu Nakamura

2011-06-01

Full Text Available Background: As of 2010, the rivastigmine patch was licensed for the treatment of Alzheimer’s disease (AD in 64 countries. Methods: This 24-week, multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy, safety and tolerability of the 5-cm2 (9-mg loading dose; 4.6 mg/24 h delivery rate and 10-cm2 (18-mg loading dose; 9.5 mg/24 h delivery rate rivastigmine patch in Japanese patients with AD. Results: In the primary analysis population (intent-to-treat last observation carried forward at week 24, delayed deterioration was seen with the 10-cm2 patch versus placebo on the Japanese version of the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-J cog; p = 0.005 and the Japanese version of the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC plus-J; p = 0.067. Participants receiving the rivastigmine patch showed numerically less decline versus placebo at week 24 on the CIBIC plus-J, although this did not reach statistical significance. Statistical significance for the CIBIC plus-J was met following adjustment for body weight and baseline Mini-Mental State Examination score as dynamic allocation factors (p = 0.042 and on the Disability Assessment for Dementia (DAD; p = 0.024 and Mental Function Impairment (MENFIS; p = 0.016 subscales. Serious adverse events were rare and were consistent with the known safety profile of the rivastigmine patch. Conclusion: The rivastigmine patch has a favorable efficacy and tolerability profile in Japanese patients with AD.

U Patch Antenna for RFID and Wireless Applications

International Nuclear Information System (INIS)

Abi Saad, R.; Melhem, Z.; Nader, C.; Zaatar, Y.; Zaouk, D.

2011-01-01

in this paper, we propose a new multi-band patch antenna structure for embedded RFID (Radio Frequency Identification) readers and wireless communications. The proposed antenna is a dual band microstrip patch antenna using U-slot geometry. The operating frequencies of the proposed antenna are chosen as 2.4 and 0.9 (GHz), obtained by optimizing the physical dimensions of the U-slot. Several parameters have been investigated using Ansoft Designer software. The antenna is fed through a quarter wavelength transformer for impedance matching. An additional layer of alumina is added above the surface of the conductors to increase the performance of the antenna. (author)

Dual band multi frequency rectangular patch microstrip antenna with flyswatter shaped slot for wireless systems

International Nuclear Information System (INIS)

Bhardwaj, Dheeraj; Saraswat, Shriti; Gulati, Gitansh; Shekhar, Snehanshu; Joshi, Kanika; Sharma, Komal

2016-01-01

In this paper a dual band planar antenna has been proposed for IEEE 802.16 Wi-MAX /IEEE 802.11 WLAN/4.9 GHz public safety applications. The antenna comprises a frequency bandwidth of 560MHz (3.37GHz-3.93GHz) for WLAN and WiMAX and 372MHz (4.82GHz-5.192GHz) for 4.9 GHz public safety applications and Radio astronomy services (4.8-4.94 GHz). The proposed antenna constitutes of a single microstrip patch reactively loaded with three identical steps positioned in a zig-zag manner towards the radiating edges of the patch. The coaxially fed patch antenna characteristics (radiation pattern, antenna gain, antenna directivity, current distribution, S_1_1) have been investigated. The antenna design is primarily focused on achieving a dual band operation.

Dual band multi frequency rectangular patch microstrip antenna with flyswatter shaped slot for wireless systems

Energy Technology Data Exchange (ETDEWEB)

Bhardwaj, Dheeraj, E-mail: dbhardwaj.bit@gmail.com [Department of Physics, BIT-Mesra-Jaipur Campus, Jaipur 302017 (India); Saraswat, Shriti, E-mail: saraswat.srishti@gmail.com; Gulati, Gitansh, E-mail: gitanshgulati@gmail.com; Shekhar, Snehanshu, E-mail: snehanshushekhar.bit@gmail.com; Joshi, Kanika, E-mail: kanika.karesh@gmail.com [Department of Electronics & Communication, BIT-Mesra-Jaipur Campus, Jaipur 302017 (India); Sharma, Komal, E-mail: kbhardwaj18@gmail.com [Department of Physics, Swami Keshvanand Institute of Technology, Jaipur 302017 (India)

2016-03-09

In this paper a dual band planar antenna has been proposed for IEEE 802.16 Wi-MAX /IEEE 802.11 WLAN/4.9 GHz public safety applications. The antenna comprises a frequency bandwidth of 560MHz (3.37GHz-3.93GHz) for WLAN and WiMAX and 372MHz (4.82GHz-5.192GHz) for 4.9 GHz public safety applications and Radio astronomy services (4.8-4.94 GHz). The proposed antenna constitutes of a single microstrip patch reactively loaded with three identical steps positioned in a zig-zag manner towards the radiating edges of the patch. The coaxially fed patch antenna characteristics (radiation pattern, antenna gain, antenna directivity, current distribution, S{sub 11}) have been investigated. The antenna design is primarily focused on achieving a dual band operation.

Dual band multi frequency rectangular patch microstrip antenna with flyswatter shaped slot for wireless systems

Science.gov (United States)

Bhardwaj, Dheeraj; Saraswat, Shriti; Gulati, Gitansh; Shekhar, Snehanshu; Joshi, Kanika; Sharma, Komal

2016-03-01

In this paper a dual band planar antenna has been proposed for IEEE 802.16 Wi-MAX /IEEE 802.11 WLAN/4.9 GHz public safety applications. The antenna comprises a frequency bandwidth of 560MHz (3.37GHz-3.93GHz) for WLAN and WiMAX and 372MHz (4.82GHz-5.192GHz) for 4.9 GHz public safety applications and Radio astronomy services (4.8-4.94 GHz). The proposed antenna constitutes of a single microstrip patch reactively loaded with three identical steps positioned in a zig-zag manner towards the radiating edges of the patch. The coaxially fed patch antenna characteristics (radiation pattern, antenna gain, antenna directivity, current distribution, S11) have been investigated. The antenna design is primarily focused on achieving a dual band operation.

p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

Directory of Open Access Journals (Sweden)

Lena Willkomm

Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

Science.gov (United States)

Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

2017-01-01

Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

Allergic contact dermatitis from ophthalmic products: can pre-treatment with sodium lauryl sulfate increase patch test sensitivity?

Science.gov (United States)

Corazza, Monica; Virgili, Annarosa

2005-05-01

In patients suspected of allergic contact dermatitis because of topical ophthalmic medicaments, patch tests performed with patients' own products are often negative. The irritant anionic surfactant sodium lauryl sulfate (SLS) may alter the stratum corneum and increase antigen penetration. Pre-treatment of the skin with SLS 0.5% for 24 h was performed in the sites of patch tests with patients' own products in 15 selected patients. In patients previously negative to their own products tested with conventional patch tests, SLS pre-treatment showed 6 new relevant positive reactions and induced a stronger positive reaction in 1 patient. SLS pre-treatment could be proposed as an alternative promising method, which may increase sensitivity of patch tests with patients' own products.

The influence of Metolose structure on the free volume and the consequent metoprolol tartrate release of patches.

Science.gov (United States)

Papp, József; Marton, Sylvia; Süvegh, Károly; Zelkó, Romána

2009-01-01

Matrix-type patches containing Metoprolol tartrate were prepared from two types of Metolose and acrylate polymers. Metolose SM 4000 and Metolose 90SH 100.000SR were applied in different proportions in the patches where the total polymer content was kept constant in each sample. The purpose of the study was to investigate the effect of Metolose structure on the free volume of the patches and the consequent drug release profile. The drug release profiles were characterized by zero-order and first-order models. The results indicate that Metolose, containing hydroxypropyl ether groups and methyl ether groups, enables the formation of H-bonds, thus increasing the free volume holes and the consequent extent and rate of drug release of patches.

Forest Patch Size, Land Use, and Mesic Forest Herbs in the French Broad River Basin, North Carolina

Science.gov (United States)

Scott M. Pearson; Alan B. Smith; Monica G. Turner

1998-01-01

The effect of forest fragmentation on cove-forest herbs was studied in the Southern Blue Ridge Province. Patches of mesic forests were sampled with 4 ha study plots. The coverage and density of herb species were greater in large patches (>200 ha) than in small patches (

Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

Science.gov (United States)

Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

2017-01-01

Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of Buccal Patches for Delivery of Darifenacin from Beta-Cyclodextrin Complexes

Directory of Open Access Journals (Sweden)

Swati C. Jagdale

2014-01-01

Full Text Available Drug-cyclodextrin complexes improve aqueous solubility and dissolution rate of poorly water-soluble drugs. Solubilisation followed by buccal delivery of poorly water-soluble drugs can be advantageous for increasing drug absorption. Darifenacin is an antispasmodic used against urinary incontinence and specifically blocks M3 muscarinic acetylcholine receptors in smooth muscle. M3 receptors are mainly located in exocrine glands, smooth muscle and vascular endothelium. The oral absorption of darifenacin is poor owing to its low solubility. It also has poor bioavailability (15-19% due to a high rate of first-pass metabolism. Complexation with beta-cyclodextrin was carried out to enhance solubility. The best results were obtained by co-grinding in a 1:1 molar ratio of drug: β-cyclodextrin. The solid inclusion complexes were characterized by DSC, X-ray diffractometry and FTIR. Inclusion complexes showed higher dissolution rates than the pure drug. Controlledrelease mucoadhesive patches were prepared with two hydroxypropyl methylcellulose (HPMC polymers, K100M CR and K15. The patches were assessed for surface pH, folding endurance, swelling, mucoadhesive properties, in-vitro residence time, vapor transmission test and in-vitro (cellophane, egg membrane and exvivo (goat buccal mucosa release. Formulations Ha2 (2% HPMC K100M CR and Pa4 (4% HPMC K15 showed good mucoadhesive strength, in-vitro and exvivo residence times, with controlled release for 10 hours.

Electrospun silk fibroin fibers for storage and controlled release of human platelet lysate.

Science.gov (United States)

Pignatelli, Cataldo; Perotto, Giovanni; Nardini, Marta; Cancedda, Ranieri; Mastrogiacomo, Maddalena; Athanassiou, Athanassia

2018-04-17

Human platelet lysate (hPL) is a pool of growth factors and cytokines able to induce regeneration of different tissues. Despite its good potentiality as therapeutic tool for regenerative medicine applications, hPL has been only moderately exploited in this field. A more widespread adoption has been limited because of its rapid degradation at room temperature that decreases its functionality. Another limiting factor for its extensive use is the difficulty of handling the hPL gels. In this work, silk fibroin-based patches were developed to address several points: improving the handling of hPL, enabling their delivery in a controlled manner and facilitating their storage by creating a device ready to use with expanded shelf life. Patches of fibroin loaded with hPL were synthesized by electrospinning to take advantage of the fibrous morphology. The release kinetics of the material was characterized and tuned through the control of fibroin crystallinity. Cell viability assays, performed with primary human dermal fibroblasts, demonstrated that fibroin is able to preserve the hPL biological activity and prolong its shelf-life. The strategy of storing and preserving small active molecules within a naturally-derived, protein-based fibrous scaffold was successfully implemented, leading to the design of a biocompatible device, which can potentially simplify the storage and the application of the hPL on a human patient, undergoing medical procedures such as surgery and wound care. Human platelets lysate (hPL) is a mixture of growth factors and cytokines able to induce the regeneration of damaged tissues. This study aims at enclosing hPL in a silk fibroin electrospun matrix to expand its utilization. Silk fibroin showed the ability to preserve the hPL activity at temperature up to 60 °C and the manipulation of fibroin's crystallinity provided a tool to modulate the hPL release kinetic. This entails the possibility to fabricate the hPL silk fibroin patches in advance and

Windows Security patch required

CERN Multimedia

3004-01-01

This concerns Windows PCs (XP, 2000, NT) which are NOT centrally managed at CERN for security patches, e.g. home PCs, experiment PCs, portables,... A security hole which can give full privileges on Windows systems needs to be URGENTLY patched. Details of the security hole and hotfix are at: http://cern.ch/it-div/news/hotfix-MS03-026.asp http://www.microsoft.com/technet/security/bulletin/MS03-026.asp

1-Methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H-one

Directory of Open Access Journals (Sweden)

Mohamed El Hafi

2018-03-01

Full Text Available The title molecule, C6H6N4O, is essentially planar [dihedral angle between the rings = 0.46 (9°]. The crystal structure consists of sheets of molecules lying parallel to (\\overline{1}11 formed by a combination of N—H...O, C—H...O and C—H...H hydrogen bonds. The sheets are connected through π–π stacking interactions.

Randomized, double-blind, placebo-controlled trial using lidocaine patch 5% in traumatic rib fractures.

Science.gov (United States)

Ingalls, Nichole K; Horton, Zachary A; Bettendorf, Matthew; Frye, Ira; Rodriguez, Carlos

2010-02-01

The lidocaine patch 5% was developed to treat postherpetic neuralgia. Anecdotal experience at our institution suggests the lidocaine patch 5% decreases narcotic usage in patients with traumatic rib fractures. This trial was developed to define the patch's efficacy. Patients with rib fractures admitted to the trauma service at our Level I trauma center were enrolled and randomized in a 1 to 1 double-blind manner to receive a lidocaine patch 5% or placebo patch. Fifty-eight patients who met the inclusion criteria were enrolled from January 2007 to August 2008. Demographic and clinical information were recorded. The primary outcomes variable was total narcotic use, analyzed using the 1-tailed Mann-Whitney test. The secondary outcomes variables included non-narcotic pain medication, average pain score, pulmonary complications, and length of stay. Significance was defined based on a 1-sided test for the primary outcome and 2-sided tests for other comparisons, at p rib fractures, gender, trauma mechanism, preinjury lung disease, smoking history, percent of current smokers, and need for placement of chest tube between the lidocaine patch 5% and placebo groups. There was no difference between the lidocaine patch 5% and placebo groups, respectively, with regard to total IV narcotic usage: median, 0.23 units versus 0.26 units; total oral narcotics: median, 4 units versus 7 units; pain score: 5.6 +/- 0.4 versus 6.0 +/- 0.3 (mean +/- SEM); length of stay: 7.8 +/- 1.1 versus 6.2 +/- 0.7; or percentage of patients with pulmonary complications: 72.7% versus 72.0%. The lidocaine patch 5% does not significantly improve pain control in polytrauma patients with traumatic rib fractures.

A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis.

Science.gov (United States)

Chang, Hao; Zheng, Mengjia; Yu, Xiaojun; Than, Aung; Seeni, Razina Z; Kang, Rongjie; Tian, Jingqi; Khanh, Duong Phan; Liu, Linbo; Chen, Peng; Xu, Chenjie

2017-10-01

Skin interstitial fluid (ISF) is an emerging source of biomarkers for disease diagnosis and prognosis. Microneedle (MN) patch has been identified as an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administrated properties. However, long sampling time is still a serious problem which impedes timely metabolic analysis. In this study, a swellable MN patch that can rapidly extract ISF is developed. The MN patch is made of methacrylated hyaluronic acid (MeHA) and further crosslinked through UV irradiation. Owing to the supreme water affinity of MeHA, this MN patch can extract sufficient ISF in a short time without the assistance of extra devices, which remarkably facilitates timely metabolic analysis. Due to covalent crosslinked network, the MN patch maintains the structure integrity in the swelling hydrated state without leaving residues in skin after usage. More importantly, the extracted ISF metabolites can be efficiently recovered from MN patch by centrifugation for the subsequent offline analysis of metabolites such as glucose and cholesterol. Given the recent trend of easy-to-use point-of-care devices for personal healthcare monitoring, this study opens a new avenue for the development of MN-based microdevices for sampling ISF and minimally invasive metabolic detection. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Annealing study of the electron-irradiation-induced defects H4 and E11 in InP: Defect transformation (H4-E11)→H4'

International Nuclear Information System (INIS)

Bretagnon, T.; Bastide, G.; Rouzeyre, M.

1990-01-01

Capacitance spectroscopy has been used to study the two dominant deep levels, H 4 and E 11 , produced in InP by low-energy electron irradiation. The annealing rates of H 4 and E 11 in the p-type material are found to be identical, as is also the dependence on free-carrier recombination and on the chemical nature of the acceptor (Cd or Zn). Recombination-enhanced annealing converts these traps to a hole trap H 4 ' , which is not detectable by conventional deep-level transient spectroscopy. Its emission and capture properties are measured and analyzed. The similarity of the creation and annealing behavior of H 4 and E 11 shows that they share a common point defect. Our results lead to the tentative identification of the defect as a phosphorous vacancy-acceptor complex and we show how this may anneal to the H 4 ' center

Generic patch inference

DEFF Research Database (Denmark)

Andersen, Jesper; Lawall, Julia

2010-01-01

A key issue in maintaining Linux device drivers is the need to keep them up to date with respect to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spdiff, that identifies common changes...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

Systems Li2B4O7 (Na2B4O7, K2B4O7)-N2H3H4OH-H2O at 25 deg C

International Nuclear Information System (INIS)

Skvortsov, V.G.; Sadetdinov, Sh.V.; Akimov, V.M.; Mitrasov, Yu.N.; Petrova, O.V.; Klopov, Yu.N.

1994-01-01

Phase equilibriums in the Li 2 B 4 O 7 (Na 2 B 4 O 7 , K 2 B 4 O 7 )-N 2 H 3 H 4 OH-H 2 O systems were investigated by methods of isothermal solubility, refractometry and PH-metry at 25 deg C for the first time. Lithium and sodium tetraborates was established to form phases of changed composition mM 2 B 4 O 7 ·nN 2 H 3 C 2 H 4 OH·XH 2 O, where M=Li, Na with hydrazine ethanol. K 2 B 4 O 7 ·4H 2 O precipitates in solid phase in the case of potassium salt. Formation of isomorphous mixtures was supported by X-ray diffraction and IR spectroscopy methods

Features of change of permanent snow patches in the Mongun-Taiga Massif, 1966–2011

Directory of Open Access Journals (Sweden)

D. A. Ganyushkin

2013-01-01

Full Text Available The article is dedicated to perennial snow patches of Mongun-Taiga mountain massif (south-western Tuva, their morphology, present state and dynamics over the last 45 years. We created a scheme of snow patch classification with regard to genesis of relief and position on the slopes. Dynamics of snow patches is analyzed for periods between several time points – 1966 (on basis of aerial photos, 2000, 2007–2008 and 2011 (on basis of field measurements and observations. From 1966 to 2008 the number of snow patches decreased by 4 times, the total area – by 15 times, the altitudinal zone of snow patches moved 250–300 m up. In 2008–2011 the altitudinal zone of snow patches partly recovered, its lower limit moved 250 m down, periglacial snow patches recovered, a new type – snow patches of buried ice and debris-covered glaciers appeared. It could be the first face of the process of small glaciers recovery in the massif. Using the changes of the altitudinal position of snow patches in comparison with data of the closest meteorological station we estimated the amount of annual precipitation, critical for the existence of local snow patches.

Human fibrinogen and thrombin patch for extraluminal protection of intestinal anastomosis

Directory of Open Access Journals (Sweden)

Paulo Gustavo Kotze

2013-07-01

Full Text Available In spite of recent advances regarding equipment and surgical techniques in colorectal surgery, rates of anastomotic dehiscence (AD have remained stable throughout the years. The development of products to protect anastomosis aiming the reduction of AD rates has shown to be promising. Human fibrinogen and thrombin patch (HFTP Tachosil® have been used in experimental studies in animals and small case series in humans, with promising results. In this study, the authors describe the technique of HFTP use in details, aiming the protection of colorectal anastomosis, and retrospectively demonstrate the preliminary results in a pilot case series. HFTP was used in 4 patients submitted to conventional surgery. The procedures performed were: left colon resection, segmental colectomy (both for colorectal cancer, enteral anastomosis for fistula closure and right ileocolectomy. Anastomotic healing and absence of complications were observed in 3 patients, and the patient submitted to right ileocolectomy developed AD and died after reoperation. The use of HFTP is safe and can be indicated in selected cases. However, AD can occur even after the use of this strategy. Randomized controlled trials with larger samples of patients are needed in order to properly define the real benefits of this strategy in dehiscence prevention Resumo: Apesar dos avanços em equipamentos e técnica cirúrgica na cirurgia colorretal, os índices de deiscência de anastomose (DA tem permanecido estáveis nos últimos anos. O desenvolvimento de produtos que visam proteção das anastomoses para redução das taxas de DA tem se mostrado promissor. A membrana de fibrinogênio e trombina humanos (MFTH vem sendo utilizada em estudos experimentais e em pequenas séries de casos em humanos, com resultados promissores. Neste artigo os autores detalham a descrição técnica da utilização da MFTH na proteção de anastomoses colorretais, e demonstram os resultados preliminares em uma s

Functional expression of a proton-coupled organic cation (H+/OC antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood–brain barrier model

Directory of Open Access Journals (Sweden)

Shimomura Keita

2013-01-01

Full Text Available Abstract Background Knowledge of the molecular basis and transport function of the human blood–brain barrier (BBB is important for not only understanding human cerebral physiology, but also development of new central nervous system (CNS-acting drugs. However, few studies have been done using human brain capillary endothelial cells, because human brain materials are difficult to obtain. The purpose of this study is to clarify the functional expression of a proton-coupled organic cation (H+/OC antiporter in human brain capillary endothelial cell line hCMEC/D3, which has been recently developed as an in vitro human BBB model. Methods Diphenhydramine, [3H]pyrilamine and oxycodone were used as cationic drugs that proved to be H+/OC antiporter substrates. The in vitro uptake experiments by hCMEC/D3 cells were carried out under several conditions. Results Diphenhydramine and [3H]pyrilamine were both transported into hCMEC/D3 cells in a time- and concentration-dependent manner with Km values of 59 μM and 19 μM, respectively. Each inhibited uptake of the other in a competitive manner, suggesting that a common mechanism is involved in their transport. The diphenhydramine uptake was significantly inhibited by amantadine and quinidine, but not tetraethylammonium and 1-methyl-4-phenylpyridinium (substrates for well-known organic cation transporters. The uptake was inhibited by metabolic inhibitors, but was insensitive to extracellular sodium and membrane potential. Further, the uptake was increased by extracellular alkalization and intracellular acidification. These transport properties are completely consistent with those of previously characterized H+/OC antiporter in rat BBB. Conclusions The present results suggest that H+/OC antiporter is functionally expressed in hCMEC/D3 cells.

Smart thermal patch for adaptive thermotherapy

KAUST Repository

Hussain, Muhammad Mustafa

2015-11-12

A smart thermal patch for adaptive thermotherapy is provided. In an embodiment, the patch can be a stretchable, non-polymeric, conductive thin film flexible and non-invasive body integrated mobile thermal heater with wireless control capabilities that can be used to provide adaptive thermotherapy. The patch can be geometrically and spatially tunable on various pain locations. Adaptability allows the amount of heating to be tuned based on the temperature of the treated portion.

Spatial and temporal variation in sponge spicule patches at Station M, northeast Pacific.

Science.gov (United States)

Laguionie-Marchais, C; Kuhnz, L A; Huffard, C L; Ruhl, H A; Smith, K L

Changes in habitat-forming organisms can have complex consequences for associated species. Sessile epibenthic glass "plate" sponges (Porifera: Hexactinellida) are conspicuous inhabitants of soft-sediment abyssal areas and their siliceous spicules create persistent spicule patches on the seafloor. Sponge spicule patch density, spatial dispersion, and percent cover were examined over a seven-year period (2006-2013) using remotely operated vehicle videos from Station M in the abyssal northeast Pacific (50˚00N, 123˚00W, ~4,000 m depth). There was an apparent large increase in newly dead plate sponges in February 2007 compared with December 2006, with this trend continuing through June 2007 (mean 0.03 % cover increasing to 0.33 %). A second increase in mean percent cover of dead plate sponges occurred from May 2011 (0.24 %) through June 2012 (0.60 %). Among the 28 megafaunal taxa occurring in association with the patches, the distributions of three taxa [two sponge taxa (Porifera) and brittle stars (Ophiuroidea)] suggested selectivity for the sponge spicule patches. The community structure of visible megafauna within sponge spicule patches was different when compared with that outside the patches suggesting that the sponges, after death, provide preferred habitat patches for certain benthic megafauna. These findings indicate that sponge spicule patches contribute to habitat heterogeneity in space and time.

Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles.

Science.gov (United States)

Choi, Sun Young; Kwon, Hyun Jung; Ahn, Ga Ram; Ko, Eun Jung; Yoo, Kwang Ho; Kim, Beom Joon; Lee, Changjin; Kim, Daegun

2017-11-01

Hyaluronic acid (HA) has an immediate volumizing effect, due to its strong water-binding potential, and stimulates fibroblasts, causing collagen synthesis, with short- and long-term effects on wrinkle improvement. We investigated the efficacy and safety of HA microneedle patches for crow's feet wrinkles. Using a randomized spilt-face design, we compared microneedle patches with a topical application containing the same active ingredients. We enrolled 34 Korean female subjects with mild to moderate crow's feet wrinkles. The wrinkle on each side of the subject's face was randomly assigned to a HA microneedle patch or HA essence application twice a week for 8 weeks. Efficacy was evaluated at weeks 2, 4, and 8. Skin wrinkles were measured as average roughness using replica and PRIMOS. Skin elasticity was assessed using a cutometer. Two independent blinded dermatologists evaluated the changes after treatment using the global visual wrinkle assessment score. Subjects assessed wrinkles using the subject global assessment score. Skin wrinkles were significantly reduced and skin elasticity significantly increased in both groups, although improvement was greater in the patch group at week 8 after treatment. In the primary and cumulative skin irritation tests, the HA microneedle patch did not induce any skin irritation. The HA microneedle patch is more effective than the HA essence for wrinkle improvement and is a safe and convenient without skin irritation. © 2017 Wiley Periodicals, Inc.

DNA methylation in human fibroblasts following DNA damage and repair

International Nuclear Information System (INIS)

Kastan, M.B.

1984-01-01

Methylation of deoxycytidine (dCyd) incorporated by DNA excision repair synthesis in human diploid fibroblasts following damage with ultraviolet radiation (UV), N-methyl-N-nitrosourea, or N-acetoxy-2-acetylaminofluorene was studied utilizing [6- 3 H]dCyd to label repaired DNA specifically and high performance liquid chromatographic analysis to quantify the percentage of deoxycytidine converted to 5-methyldeoxycytidine (m 5 dCyd). In confluent, nondividing cells, methylation in repair patches induced by all three agents is slow and incomplete. Whereas after DNA replication a level of 3.4% m 5 dCyd is reached in less than 2 hours, following UV-stimulated repair synthesis in confluent cells it takes about 3 days to reach a level of approx.2.0% m 5 dCyd in the repair patch. This undermethylation of repair patches occurs throughout the genome. In cells from cultures in logarithmic-phase growth, m 5 dCyd formation in UV-induced repair patches occurs faster and to a greater extent, reaching a level of approx.2.7% in 10-20 hours. Pre-existing hypomethylated repair patches in confluent cells are methylated further when the cells are stimulated to divide; however, the repair patch may still not be fully methylated before cell division occurs. Thus DNA damage and repair may lead to heritable loss of methylation at some sites. The distribution within chromatin of m 5 dCyd in repair patches was also investigated. Over a wide range of extents of digestion by staphylococcal nuclease or deoxyribonuclease I, the level of hypomethylation in repaired DNA in nuclease sensitive and resistant regions of chromatin was constant relative to the genomic level of methylation in these regions. Similar conclusions were reached in experiments with isolated mononucleosomes

Sequential application of ligand and structure based modeling approaches to index chemicals for their hH4R antagonism.

Directory of Open Access Journals (Sweden)

Matteo Pappalardo

Full Text Available The human histamine H4 receptor (hH4R, a member of the G-protein coupled receptors (GPCR family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE and Iterative Stochastic Elimination (ISE approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼ 4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and

Sequential application of ligand and structure based modeling approaches to index chemicals for their hH4R antagonism.

Science.gov (United States)

Pappalardo, Matteo; Shachaf, Nir; Basile, Livia; Milardi, Danilo; Zeidan, Mouhammed; Raiyn, Jamal; Guccione, Salvatore; Rayan, Anwar

2014-01-01

The human histamine H4 receptor (hH4R), a member of the G-protein coupled receptors (GPCR) family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE) and Iterative Stochastic Elimination (ISE) approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼ 4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and increase the

*NEW* CRITICAL Windows Security patches

CERN Multimedia

2003-01-01

On 3 October and 10 September 2003, Microsoft issued new CRITICAL security patches MS03-040 and MS03-039. They must be URGENTLY applied on ALL WINDOWS systems, which are not centrally managed for security patches. This includes Experiment computers, Home computers and Windows Portable and Desktop systems not running NICE. Details of the security holes and patches are at: MS03-039: http://cern.ch/it-div/news/hotfix-MS03-039.asp http://www.microsoft.com/technet/security/bulletin/MS03-039.asp MS03-040: http://cern.ch/it-div/news/hotfix-MS03-040.asp http://www.microsoft.com/technet/security/bulletin/MS03-040.asp

Regioselectivity in the Thermal Rearrangement of Unsymmetrical 4-Methyl-4H-1,2,4-triazoles to 1-Methyl-1H-1,2,4-triazoles

Directory of Open Access Journals (Sweden)

Per H.J. Carlsen

2001-11-01

Full Text Available The rearrangement of 4-methyl-3,5-diaryl-4H-1,2,4-triazoles to the corresponding 1-methyl-3,5-diaryl-1H-1,2,4-triazoles showed regioselectivity comparable to that observed for the alkylation of 3,5-diaryl-1H-1,2,4-triazoles. This lends support to a proposed mechanism for the rearrangement that involves consecutive nucleophilic displacements steps.

Intelligent Patching of Conceptual Geometry for CFD Analysis

Science.gov (United States)

Li, Wu

2010-01-01

The iPatch computer code for intelligently patching surface grids was developed to convert conceptual geometry to computational fluid dynamics (CFD) geometry (see figure). It automatically uses bicubic B-splines to extrapolate (if necessary) each surface in a conceptual geometry so that all the independently defined geometric components (such as wing and fuselage) can be intersected to form a watertight CFD geometry. The software also computes the intersection curves of surface patches at any resolution (up to 10.4 accuracy) specified by the user, and it writes the B-spline surface patches, and the corresponding boundary points, for the watertight CFD geometry in the format that can be directly used by the grid generation tool VGRID. iPatch requires that input geometry be in PLOT3D format where each component surface is defined by a rectangular grid {(x(i,j), y(i,j), z(i,j)):1less than or equal to i less than or equal to m, 1 less than or equal to j less than or equal to n} that represents a smooth B-spline surface. All surfaces in the PLOT3D file conceptually represent a watertight geometry of components of an aircraft on the half-space y greater than or equal to 0. Overlapping surfaces are not allowed, but could be fixed by a utility code "fixp3d". The fixp3d utility code first finds the two grid lines on the two surface grids that are closest to each other in Hausdorff distance (a metric to measure the discrepancies of two sets); then uses one of the grid lines as the transition line, extending grid lines on one grid to the other grid to form a merged grid. Any two connecting surfaces shall have a "visually" common boundary curve, or can be described by an intersection relationship defined in a geometry specification file. The intersection of two surfaces can be at a conceptual level. However, the intersection is directional (along either i or j index direction), and each intersecting grid line (or its spine extrapolation) on the first surface should intersect

Patch layout generation by detecting feature networks

KAUST Repository

Cao, Yuanhao

2015-02-01

The patch layout of 3D surfaces reveals the high-level geometric and topological structures. In this paper, we study the patch layout computation by detecting and enclosing feature loops on surfaces. We present a hybrid framework which combines several key ingredients, including feature detection, feature filtering, feature curve extension, patch subdivision and boundary smoothing. Our framework is able to compute patch layouts through concave features as previous approaches, but also able to generate nice layouts through smoothing regions. We demonstrate the effectiveness of our framework by comparing with the state-of-the-art methods.

Comparison of estrus synchronization by controlled internal drug release device (CIDR) and adhesive transdermal progestin patch in postpartum beef cows.

Science.gov (United States)

Kajaysri, Jatuporn; Chumchoung, Chaiwat; Wutthiwitthayaphong, Supphathat; Suthikrai, Wanvipa; Sangkamanee, Praphai

2017-09-15

Estrous synchronization with progesterone based protocols has been essentially used in cattle industry. Although intravaginal devices have been commonly used, this technique may induce vaginitis. This study aimed at examining the efficiency of novel transdermal progestin patch on follicle development and comparing the progestin patch versus CIDR device on estrous synchronization, complication at treated site and pregnancy in beef cattle. In experiment 1, seven beef cows were treated with an adhesive transdermal progestin patch on the ventral surface of the proximal part of the tail for 7 days. The cows were daily examined the follicular development using ultrasonography starting on Day 0 till 3 days after hormone removal. Experiment 2, forty beef cows were divided into two equal groups (20 cows per group). The cows randomly allocated to received either vaginal insertion of CIDR (n = 20) or treated with an adhesive transdermal progestin patch (n = 20). The levels of plasma progesterone during the experiment and the numbers of standing estrous cows were recorded. Timed artificial inseminated (TAI) was performed at 60 h after CIDR or patch termination. Pregnancy rates were determined at 60 days after TAI. Experiment 1 revealed that the novel transdermal progestin patch could efficiently control follicular growth. All the seven treated cows had dominant follicle upon dermal patch removal indicating the effectiveness of the progestin patch. In experiment 2, the percentages of cows exhibited standing estrus were similar between transdermal patch (72.22%) and CIDR (70.00%). The levels of plasma progesterone during CIDR treatment were significantly higher (4.06 ± 1.65 ng/mL on Day 1 and 3.62 ± 1.60 ng/mL on Day 7) compared with transdermal patch (2.60 ± 1.43 ng/mL on Day 1 and 1.81 ± 1.57 ng/mL on Day 7). Three cows treated with CIDR (15%) developed vaginitis while none of cows had physically dermal reaction at adhesive site. Cows synchronized with

Allergic contact dermatitis in Danish children referred for patch testing - a nationwide multicentre study

DEFF Research Database (Denmark)

Simonsen, Anne Birgitte; Deleuran, Mette; Mortz, Charlotte Gotthard

2014-01-01

-17 years, 25.1% had one or more positive patch test reactions. The associated relevance was 66.4%. The most common sensitizers were metals, fragrances, and hair dyes. The frequency of positive patch test reactions and allergic contact dermatitis was significantly higher among girls. CONCLUSIONS: Allergic...

Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

Science.gov (United States)

Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

2013-01-01

The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

A new generation of anti-histamines : Histamine H4 receptor antagonists on their way to the clinic

NARCIS (Netherlands)

Engelhardt, Harald; Smits, Rogier A; Leurs, Rob; Haaksma, Eric E J; de Esch, Iwan J P

At the turn of the millennium, the DNA sequence encoding the histamine H4 receptor (H4R) was identified in data from human genome databases. Considering the clinical importance of H1R and H2R ligands, and the clinical trials that are ongoing for H3R ligands, the latest addition to the histamine

Characterisation of a human acid-sensing ion channel (hASIC1a) endogenously expressed in HEK293 cells.

Science.gov (United States)

Gunthorpe, M J; Smith, G D; Davis, J B; Randall, A D

2001-08-01

Acid-sensing ion channels (ASICs) are a new and expanding family of proton-gated cation (Na+/Ca2+) channels that are widely expressed in sensory neurons and the central nervous system. Their distribution suggests that they may play a critical role in the sensation of the pain that accompanies tissue acidosis and may also be important in detecting the subtle pH variations that occur during neuronal signalling. Here, using whole-cell patch-clamp electrophysiology and reverse transcriptase-polymerase chain reaction (RT-PCR), we show that HEK293 cells, a commonly used cell line for the expression and characterisation of many ion channels, functionally express an endogenous proton-gated conductance attributable to the activity of human ASIC1a. These data therefore represent the first functional characterisation of hASIC1 and have many important implications for the use of HEK293 cells as a host cell system for the study of ASICs, vanilloid receptor-1 and any other proton-gated channel. With this latter point in mind we have devised a simple desensitisation strategy to selectively remove the contribution of hASIC1a from proton-gated currents recorded from HEK293 cells expressing vanilloid receptor-1.

Bold Ideas for the 4th H in 4-H: Teen Identified Concerns and Actions

OpenAIRE

Virginia Brown; Bonnie Braun; JoAnne Leatherman

2015-01-01

This article summarizes a literature review; teen-identified health concerns and issues; and teen bold ideas for actions. Findings from the National 4-H Council and Molina Healthcare Teens Take on Health initiative are provided and implications for 4-H programming tied to the new Cooperative Extension National Framework for Health and Wellness are addressed. The article is intended as background for Extension educators, volunteers and administrators as they review the 4-H Healthy Living Missi...

Reversible Photoinduced Reductive Elimination of H2 from the Nitrogenase Dihydride State, the E(4)(4H) Janus Intermediate.

Science.gov (United States)

Lukoyanov, Dmitriy; Khadka, Nimesh; Yang, Zhi-Yong; Dean, Dennis R; Seefeldt, Lance C; Hoffman, Brian M

2016-02-03

We recently demonstrated that N2 reduction by nitrogenase involves the obligatory release of one H2 per N2 reduced. These studies focus on the E4(4H) "Janus intermediate", which has accumulated four reducing equivalents as two [Fe-H-Fe] bridging hydrides. E4(4H) is poised to bind and reduce N2 through reductive elimination (re) of the two hydrides as H2, coupled to the binding/reduction of N2. To obtain atomic-level details of the re activation process, we carried out in situ 450 nm photolysis of E4(4H) in an EPR cavity at temperatures below 20 K. ENDOR and EPR measurements show that photolysis generates a new FeMo-co state, denoted E4(2H)*, through the photoinduced re of the two bridging hydrides of E4(4H) as H2. During cryoannealing at temperatures above 175 K, E4(2H)* reverts to E4(4H) through the oxidative addition (oa) of the H2. The photolysis quantum yield is temperature invariant at liquid helium temperatures and shows a rather large kinetic isotope effect, KIE = 10. These observations imply that photoinduced release of H2 involves a barrier to the combination of the two nascent H atoms, in contrast to a barrierless process for monometallic inorganic complexes, and further suggest that H2 formation involves nuclear tunneling through that barrier. The oa recombination of E4(2H)* with the liberated H2 offers compelling evidence for the Janus intermediate as the point at which H2 is necessarily lost during N2 reduction; this mechanistically coupled loss must be gated by N2 addition that drives the re/oa equilibrium toward reductive elimination of H2 with N2 binding/reduction.

Potent radiolabeled human renin inhibitor, [3H]SR42128: enzymatic, kinetic, and binding studies to renin and other aspartic proteases

International Nuclear Information System (INIS)

Cumin, F.; Nisato, D.; Gagnol, J.P.; Corvol, P.

1987-01-01

The in vitro binding of [ 3 H]SR42128 (Iva-Phe-Nle-Sta-Ala-Sta-Arg), a potent inhibitor of human renin activity, to purified human renin and a number of other aspartic proteases was examined. SR42128 was found to be a competitive inhibitor of human renin, with a K/sub i/ of 0.35 nM at pH 5.7 and 2.0 nM at pH 7.4; it was thus more effective at pH 5.7 than at pH 7.4. Scatchard analysis of the interaction binding of [ 3 H]SR42128 to human renin indicated that binding was reversible and saturable at both pH 5.7 and pH 7.4. There was a single class of binding sites, and the K/sub D/ was 0.9 nM at pH 5.7 and 1 nM at pH 7.4. The association rate was 10 times more rapid at pH 5.7 than at pH 7.4, but there was no difference between the rates of dissociation of the enzyme-inhibitor complex at the two pHs. The effect of pH on the binding of [ 3 H]SR42128 to human renin, cathepsin D, pepsin, and gastricsin was also examined over the pH range 3-8. All the aspartic proteases had a high affinity for the inhibitor at low pH. However, at pH 7.4, [ 3 H]SR42128 was bound only to human renin and to none of the other aspartic proteases. Competitive binding studies with [ 3 H]SR42128 and a number of other inhibitors on human renin or cathepsin D were used to examine the relationships between structure and activity in these systems. The study as a whole indicates that pH plays a major role in the binding of [ 3 H]SR42128 to aspartic proteases and that the nature of the inhibitor residue reacting with the renin S 2 subsites is of critical importance for the specificity of the renin-inhibitor interaction

1,4-Dihydroxyquinoxaline-2,3(1H,4H-dione

Directory of Open Access Journals (Sweden)

Wolfgang Frey

2008-03-01

Full Text Available The asymmetric unit of the title compound, C8H6N2O4, contains one half-molecule; a twofold rotation axis bisects the molecule. The quinoxaline ring is planar, which can be attributed to electron delocalization. In the crystal structure, intermolecular O—H...O hydrogen bonds link the molecules into R22(10 motifs, leading to layers, which interact via phenyl–phenyl interactions (C...C distances in the range 3.238–3.521 Å.

Design and Analysis of Ultra-wideband Micro Strip Patch Antenna with Notch Band Characteristics

Directory of Open Access Journals (Sweden)

Kumar Omprakash

2016-01-01

Full Text Available A new design of ultra-wideband (UWB micro strip patch antenna with notch band characteristic for wireless local area network (WLAN application is presented in this paper. The proposed antenna consists of a rectangular patch with a partial ground plane that is fed by 50 Ω micro strip line. A notch band function is created by inserting overlapped one U-shape and one C-shape slot on the radiator patch, added additional patch to the ground plane side and slit in truncated ground plane. The proposed antenna potentially minimized frequency interference between WLAN and UWB system. This antenna with the size of 26 mm × 32 mm (W×L and the simulated results show that the antenna can operate over the frequency band between 3.1 and 10.45 GHz for voltage standing wave ratio (VSWR > 2 with band notch 5.06-5.825 GHz. Besides in the working band, the antenna shows good radiation pattern in the H-plane and the E-plane and has good time domain characteristic.

Subtype-specific, bi-component inhibition of SK channels by low internal pH

DEFF Research Database (Denmark)

Peitersen, Torben; Jespersen, Thomas; Jorgensen, Nanna K

2006-01-01

The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+-activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6...

Characteristic evolutions in numerical relativity using six angular patches

International Nuclear Information System (INIS)

Reisswig, Christian; Bishop, Nigel T; Lai, Chi Wai; Thornburg, Jonathan; Szilagyi, Bela

2007-01-01

The characteristic approach to numerical relativity is a useful tool in evolving gravitational systems. In the past this has been implemented using two patches of stereographic angular coordinates. In other applications, a six-patch angular coordinate system has proved effective. Here we investigate the use of a six-patch system in characteristic numerical relativity, by comparing an existing two-patch implementation (using second-order finite differencing throughout) with a new six-patch implementation (using either second- or fourth-order finite differencing for the angular derivatives). We compare these different codes by monitoring the Einstein constraint equations, numerically evaluated independently from the evolution. We find that, compared to the (second-order) two-patch code at equivalent resolutions, the errors of the second-order six-patch code are smaller by a factor of about 2, and the errors of the fourth-order six-patch code are smaller by a factor of nearly 50

Characteristic evolutions in numerical relativity using six angular patches

Energy Technology Data Exchange (ETDEWEB)

Reisswig, Christian [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany); Bishop, Nigel T [Department of Mathematical Sciences, University of South Africa, PO Box 392, Unisa 0003, South Africa (South Africa); Lai, Chi Wai [Department of Mathematical Sciences, University of South Africa, PO Box 392, Unisa 0003, South Africa (South Africa); Thornburg, Jonathan [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany); Szilagyi, Bela [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany)

2007-06-21

The characteristic approach to numerical relativity is a useful tool in evolving gravitational systems. In the past this has been implemented using two patches of stereographic angular coordinates. In other applications, a six-patch angular coordinate system has proved effective. Here we investigate the use of a six-patch system in characteristic numerical relativity, by comparing an existing two-patch implementation (using second-order finite differencing throughout) with a new six-patch implementation (using either second- or fourth-order finite differencing for the angular derivatives). We compare these different codes by monitoring the Einstein constraint equations, numerically evaluated independently from the evolution. We find that, compared to the (second-order) two-patch code at equivalent resolutions, the errors of the second-order six-patch code are smaller by a factor of about 2, and the errors of the fourth-order six-patch code are smaller by a factor of nearly 50.

Formulation and Optimization of Oral Mucoadhesive Patches of Myrtus Communis by Box Behnken Design.

Science.gov (United States)

Hashemi, Mahbubeh; Ramezani, Vahid; Seyedabadi, Mohammad; Ranjbar, Ali Mohamad; Jafari, Hossein; Honarvar, Mina; Fanaei, Hamed

2017-09-01

Purpose: Recurrent aphthous stomatitis (RAS) is the most common painful ulcerative disease of oral mucosa happening in ~20% of people. Aimed to develop Myrtus communis L. (Myrtle) containing oral patches, we applied box-behnken design to evaluate the effect of polymers such as Polyvinyl pyrrolidone (PVP), Gelatin, Methylcellulose (MC) and Pectin. Methods: The patches properties such as tensile strength, folding endurance, swelling index, thickness, mucoadhesive strength and the pattern of myrtle release were evaluated as dependent variables. Then, the model was adjusted according to the best fitted equation with box behnken design. Results: The results indicated that preparation of myrtle patch with hydrophilic polymers showed the disintegration time up to 24h and more. Using of polyvinyl pyrrolidone as a water soluble polymer and a pore-former polymer led to faster release of soluble materials from the patch to 29 (min -1 ). Also it decreases swelling index by increasing the patch disintegration. Gelatin and Pectin, with rigid matrix and water interaction properties, decreased the swelling ratio. Pectin increased the tensile strength, but gelatin produced an opposite effect. Thinner Myrtle patch (about 28µm) was obtained by formulation of methyl cellulose with equal ratio with polyvinyl pyrrolidone or gelatin. Conclusion: Altogether, the analysis showed that the optimal formulation was achieved with of 35.04 mg of Gelatin, 7.22 mg of Pectin, 7.20 mg of polyvinyl pyrrolidone, 50.52 mg of methyl cellulose and 20 mg of Myrtle extract.

Vascular effects of leukotriene D4 in human skin

DEFF Research Database (Denmark)

Bisgaard, H

1987-01-01

Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced...... as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes...

Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers.

Science.gov (United States)

Rasmussen, Scott; Horkan, Kathleen Halabuk; Kotler, Mitchell

2018-02-02

Smoking continues to be a major preventable cause of early mortality worldwide, and nicotine replacement therapy has been demonstrated to increase rates of abstinence among smokers attempting to quit. Nicotine transdermal systems (also known as nicotine patches) attach to the skin via an adhesive layer composed of a mixture of different-molecular-weight polyisobutylenes (PIBs) in a specific ratio. This randomized, single-dose, 2-treatment, crossover pharmacokinetic (PK) trial assessed the bioequivalence of nicotine patches including a replacement PIB adhesive (test) compared with the PIB adhesive historically used on marketed patches (reference). The test and reference patches were bioequivalent, as determined by the PK parameters of C max and AUC 0-t . In addition, the parameters T max and t 1/2 did not significantly differ between the 2 patches, supporting the bioequivalence finding from the primary analysis. The tolerability profiles of the patches containing the replacement and previously used PIB adhesives were similar; application-site adverse events did not significantly differ between test and reference patches. Overall, these data establish the bioequivalence of the nicotine patch with the replacement PIB adhesive formulation and the previously utilized PIB adhesive formulation. © 2018 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Molecular epidemiology and virulence of Escherichia coli O16:H5-ST131: comparison with H30 and H30-Rx subclones of O25b:H4-ST131.

Science.gov (United States)

Dahbi, Ghizlane; Mora, Azucena; Mamani, Rosalia; López, Cecilia; Alonso, María Pilar; Marzoa, Juan; Blanco, Miguel; Herrera, Alexandra; Viso, Susana; García-Garrote, Fernando; Tchesnokova, Veronika; Billig, Mariya; de la Cruz, Fernando; de Toro, María; González-López, Juan José; Prats, Guillermo; Chaves, Fernando; Martínez-Martínez, Luis; López-Cerezo, Lorena; Denamur, Erick; Blanco, Jorge

2014-11-01

The present study was carried out to evaluate the prevalence of the clonal subgroup O16:H5-ST131 and the H30 and H30-Rx subclones among E. coli isolates causing extraintestinal infections and to know their virulence potential. The ST131 clonal group accounted for 490 (16%) of the 2995 isolates obtained from clinical samples in five Spanish hospitals during the study period (2005-2012). Among those 490 ST131 isolates, 456 belonged to serotype O25b:H4, 27 to O16:H5 and seven were O-non-typeable:H4 (ONT:H4). All 27 O16:H5 isolates showed fimH41, whereas fimH30 and fimH22 alleles were the most frequently detected among O25b:H4 isolates. The majority (381/490; 78%) of ST131 isolates belonged to H30 subclone, and 302 of 381 (79%) H30 isolates belonged to the H30-Rx subclone. Of the 27 O16:H5 isolates, 48% produced CTX-M-14; however, none produced CTX-M-15. In contrast, 46% of O25b:H4 isolates produced CTX-M-15 while only 2% produced CTX-M-14. More than a half of the O16:H5 isolates (56%) showed the ExPEC status which was significantly more prevalent within O25b:H4 isolates (81%) (P<0.01), especially among H30-Rx (97%) isolates. In the present study, a modified virotype scheme was applied within which approximately half (52%) of the O16:H5 isolates showed the C1 specific virotype. Despite their low virulence-gene score (mean of virulence genes 6.4 versus 8.5 in O25b:H4 isolates), six out of the 10 O16:H5 isolates assayed showed high virulence in the mouse model of sepsis (killed 90-100% of mice challenged). Furthermore, four O16:H5 isolates of virotypes A and C1, carrying K2 variant of group II capsule, showed lethality at 24h. Thus, certain O16:H5 fimH41 isolates show a similar in vivo virulence to that reported with the highly virulent O25b:H4 H30-Rx isolates (Mora et al., PLOS ONE 2014, e87025), supporting their potential virulence for humans. Copyright © 2014 Elsevier GmbH. All rights reserved.

Limonene hydroperoxide analogues show specific patch test reactions.

Science.gov (United States)

Christensson, Johanna Bråred; Hellsén, Staffan; Börje, Anna; Karlberg, Ann-Therese

2014-05-01

The fragrance terpene R-limonene is a very weak sensitizer, but forms allergenic oxidation products upon contact with air. The primary oxidation products of oxidized limonene, the hydroperoxides, have an important impact on the sensitizing potency of the oxidation mixture. One analogue, limonene-1-hydroperoxide, was experimentally shown to be a significantly more potent sensitizer than limonene-2-hydroperoxide in the local lymph node assay with non-pooled lymph nodes. To investigate the pattern of reactivity among consecutive dermatitis patients to two structurally closely related limonene hydroperoxides, limonene-1-hydroperoxide and limonene-2-hydroperoxide. Limonene-1-hydroperoxide, limonene-2-hydroperoxide, at 0.5% in petrolatum, and oxidized limonene 3.0% pet. were tested in 763 consecutive dermatitis patients. Of the tested materials, limonene-1-hydroperoxide gave most reactions, with 2.4% of the patients showing positive patch test reactions. Limonene-2-hydroperoxide and oxidized R-limonene gave 1.7% and 1.2% positive patch test reactions, respectively. Concomitant positive patch test reactions to other fragrance markers in the baseline series were frequently noted. The results are in accordance with the experimental studies, as limonene-1-hydroperoxide gave more positive patch test reactions in the tested patients than limonene-2-hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of concrete pavement patching techniques.

Science.gov (United States)

1989-01-01

This final report presents the results of a study undertaken to improve in concrete pavement patching techniques. Activities included an evaluation of the suitability of the impact hammer and maturity calculations for determining when a patch is read...

3-Benzyl-4-ethyl-1H-1,2,4-triazole-5(4H-thione

Directory of Open Access Journals (Sweden)

Zbigniew Karczmarzyk

2013-02-01

Full Text Available The title compound, C11H13N3S, exists in the 5-thioxo tautomeric form. The benzene ring exhibits disorder with a refined ratio of 0.77 (2:0.23 (2 for components A and B with a common bridgehead C atom. The 1,2,4-triazole ring is essentially planar, with a maximum deviation of 0.002 (3 Å for the benzyl-substituted C atom, and forms dihedral angles of 88.94 (18 and 86.56 (49° with the benzene rings of components A and B, respectively. The angle between the plane of the ethyl chain and the mean plane of 1,2,4-triazole ring is 88.55 (15° and this conformation is stabilized by an intramolecular C—H...S contact. In the crystal, pairs of N—H...S hydrogen bonds link molecules into inversion dimers. π–π interactions are observed between the triazole and benzene rings, with centroid–centroid separations of 3.547 (4 and 3.544 (12 Å for components A and B, and slippages of 0.49 (6 and 0.58 (15 Å, respectively.

Binocular iPad Game vs Patching for Treatment of Amblyopia in Children: A Randomized Clinical Trial.

Science.gov (United States)

Kelly, Krista R; Jost, Reed M; Dao, Lori; Beauchamp, Cynthia L; Leffler, Joel N; Birch, Eileen E

2016-12-01

Fellow eye patching has long been the standard treatment for amblyopia, but it does not always restore 20/20 vision or teach the eyes to work together. Amblyopia can be treated with binocular games that rebalance contrast between the eyes so that a child may overcome suppression. However, it is unclear whether binocular treatment is comparable to patching in treating amblyopia. To assess the effectiveness of a binocular iPad (Apple Inc) adventure game as amblyopia treatment and compare this binocular treatment with patching, the current standard of care. This investigation was a randomized clinical trial with a crossover design at a nonprofit eye research institute. Between February 20, 2015, and January 4, 2016, a total of 28 patients were enrolled in the study, with 14 randomized to binocular game treatment and 14 to patching treatment. Binocular game and patching as amblyopia treatments. The primary outcome was change in amblyopic eye best-corrected visual acuity (BCVA) at the 2-week visit. Secondary outcomes were change in stereoacuity and suppression at the 2-week visit and change in BCVA at the 4-week visit. Among 28 children, the mean (SD) age at baseline was 6.7 (1.4) years (age range, 4.6-9.5 years), and 7 (25%) were female. At baseline, the mean (SD) amblyopic eye BCVA was 0.48 (0.14) logMAR (approximately 20/63; range, 0.3-0.8 logMAR [20/40 to 20/125]), with 14 children randomized to the binocular game and 14 to patching for 2 weeks. At the 2-week visit, improvement in amblyopic eye BCVA was greater with the binocular game compared with patching, with a mean (SD) improvement of 0.15 (0.08) logMAR (mean [SD], 1.5 [0.8] lines) vs 0.07 (0.08) logMAR (mean [SD], 0.7 [0.8] line; P = .02) after 2 weeks of treatment. These improvements from baseline were significant for the binocular game (mean [SD] improvement, 1.5 [0.8] lines; P suppression improved from baseline at the 2-week visit for the binocular game (mean [SD], 4.82 [2.82] vs 3.24 [2.87]; P�

Minnesota 4-H Science of Agriculture Challenge: Infusing Agricultural Science and Engineering Concepts into 4-H Youth Development

Science.gov (United States)

Rice, Joshua E.; Rugg, Bradley; Davis, Sharon

2016-01-01

Youth involved in 4-H projects have been engaged in science-related endeavors for years. Since 2006, 4-H has invested considerable resources in the advancement of science learning. The new Minnesota 4-H Science of Agriculture Challenge program challenges 4-H youth to work together to identify agriculture-related issues in their communities and to…

Metamaterial Embedded Wearable Rectangular Microstrip Patch Antenna

Directory of Open Access Journals (Sweden)

J. G. Joshi

2012-01-01

Full Text Available This paper presents an indigenous low-cost metamaterial embedded wearable rectangular microstrip patch antenna using polyester substrate for IEEE 802.11a WLAN applications. The proposed antenna resonates at 5.10 GHz with a bandwidth and gain of 97 MHz and 4.92 dBi, respectively. The electrical size of this antenna is 0.254λ×0.5λ. The slots are cut in rectangular patch to reduce the bending effect. This leads to mismatch the impedance at WLAN frequency band; hence, a metamaterial square SRR is embedded inside the slot. A prototype antenna has been fabricated and tested, and the measured results are presented in this paper. The simulated and measured results of the proposed antenna are found to be in good agreement. The bending effect on the performance of this antenna is experimentally verified.

Expression of human beta-defensins-1-4 in thyroid cancer cells and new insight on biologic activity of hBD-2 in vitro.

Science.gov (United States)

Zhuravel, O V; Gerashchenko, O L; Khetsuriani, M R; Soldatkina, M A; Pogrebnoy, P V

2014-09-01

The study was aimed on analysis of human beta-defensin-1-4 (hBDs) mRNA expression in cultured thyroid cancer cells and evaluation of effects of recombinant hBD-2 (rec-hBD-2) on growth patterns, migration properties and expression of E-cadherin and vimentin in these cells. The study was performed on cultured follicular thyroid cancer WRO cells, papillary thyroid cancer TPC1 cells, and anaplastic thyroid cancer KTC-2 cells. For analysis of hBD-1-4 mRNA expression in thyroid cancer cells, semiquantitative RT-PCR was used. Effects of rec-hBD-2 on cell proliferation, viability, and migration were analyzed using direct cell counting, MTT test, and scratch assay respectively. Expression of vimentin and E-cadherin was evaluated by quantitative PCR (qPCR). By the data of RT-PCR, all three studied thyroid cancer cell lines express hBD-1 and -4 mRNA, but not hBD-2 mRNA, while hBD-3 expression was detected in WRO and KTC-2 cells. The treatment of TPC-1, WRO, and KTC-2 cells with 100-1000 nM rec-hBD-2 resulted in significant concentration-dependent suppression of cell proliferation, viability, and migratory property. By the data of qPCR, significant up-regulation of vimentin expression was registered in KTC-2 and WRO cells treated with 500 nM rec-hBD-2. Significant down-regulation of E-cadherin expression (p cells treated with the defensin. Also, it has been shown that TPC-1 cells treated with 500 nM rec-hBD-2 acquired more elongated morphology. The data demonstrate that hBD-2 in concentrations higher than 100 nM exerts significant concentration-dependent suppression of thyroid cancer cell growth and migration, and affects vimentin and E-cadherin expression dependent on histologic type of thyroid cancer cells.

Transparent Patch Antenna on a-Si Thin Film Glass Solar Module

OpenAIRE

Roo Ons, Maria; Shynu, S.; Ammann, Max; McCormack, Sarah; Norton, Brian

2011-01-01

An optically transparent microstrip patch mounted on the surface of a commercially available solar module is proposed. The patch comprises a thin sheet of clear polyester with a conductive coating. The amorphous silicon solar cells in the module are used as both photovoltaic generator and antenna ground plane. The proposed structure provides a peak gain of 3.96 dBi in the 3.4-3.8 GHz range without significantly compromising the light transmission in the module. A comparison between copper and...

Skin permeability and pharmacokinetics of diclofenac epolamine administered by dermal patch in Yorkshire-Landrace pigs

Directory of Open Access Journals (Sweden)

Tse S

2012-10-01

Full Text Available Susanna Tse,1 Kendall D Powell,2 Stephen MacLennan,3 Allan R Moorman,4 Craig Paterson,5 Rosonald R Bell11Pfizer Inc, Groton, CT, USA; 2Tandem Labs, Durham, NC, USA; 3BioCryst Pharmaceuticals Inc, Durham, NC, USA; 4Alta Vetta Pharmaceutical Consulting LLC, Durham, NC, USA; 5Salix Pharmaceuticals Inc, Raleigh, NC, USAPurpose: This study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire- Landrace pigs.Patients and methods: Twelve anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either the dermal patch (FLECTOR® patch, 10 × 14 cm; Alpharma Pharmaceuticals, a subsidiary of Pfizer Inc, New York, NY or 50 mg oral diclofenac (Voltaren®; Novartis, East Hanover, NJ. Tissue (skin area of 2 × 2 cm and underlying muscles approximately 2–3 cm in depth and blood (10 mL samples were collected at timed intervals up to 11.5 hours after initial patch application or oral administration. The concentrations of diclofenac in plasma, skin, and muscle samples were analyzed using validated ultra performance liquid chromatography tandem mass spectrometric methods.Results: Peak systemic exposure of diclofenac was very low by dermal application compared with oral administration (maximum concentration [Cmax] values of 3.5 vs 9640 ng/mL, respectively. Absorption of diclofenac into underlying muscles beneath the dermal patch was sustained, and followed apparently zero-order kinetics, with the skin serving as a depot with elevated concentrations of diclofenac. Concentrations of diclofenac in muscles beneath the patch application site were similar to corresponding tissues after oral administration (Cmax values of 879 and 1160 ng/mL, respectively. In contrast to the wide tissue distribution of diclofenac after oral administration, dermal patch application resulted in high concentrations of diclofenac only on the treated skin and immediate

Microneedle Patches as Drug and Vaccine Delivery Platform.

Science.gov (United States)

Li, Junwei; Zeng, Mingtao; Shan, Hu; Tong, Chunyi

2017-01-01

Transcutaneous delivery is the ideal method for delivering therapeutic reagents or vaccines into skin. With their promise of self-administration, cost-effective and high efficiency, microneedle patches have been studied intensively as therapeutic and vaccination delivery platform that replaces injection by syringe. This review aims to summarize the recent advancements of microneedle patches in application for drugs and vaccine delivery. We reviewed the most of recently published papers on microneedle patches, summarized their evolution, classification, state-of the-art capabilities and discussed promising application in drugs and vaccine delivery. With the rapid development of nanotechnology, microneedle patches have been improved by switching from undissolving to dissolving microneedles, and their safety has also improved dramatically. As a drug delivery tool, microneedle patches can deliver bioactive molecular of different physical size. Additionally, microneedle patches can be coated or encapsulate with DNA vaccine, subunit antigen, inactivated or live virus vaccine. Combining clinical results with the results of patient interview, microneedle patches are found to be feasible and are predicated to soon be acceptable for the medical service. In this review, we summarized the evolution, current and future application of microneedle patches as delivery vehicle for drugs and vaccines. Compared with traditional delivery tools, microneedle patches have many advantages, such as providing pain-free, non-invasive, convenient route for reagent administration and delivery, with no cold chain required for storage and transportation as well as decreasing sharp medical waste, needle-caused injury and transmission of blood-borne infectious disease in rural area. However, even though there are dramatic progress in preclinical investigation of microneedle patches, further testing will be required for clinical application. Further research should be implemented in multiple fields

Down regulation of ITGA4 and ITGA5 genes after formation of 3D spherules by human Wharton's jelly stem cells (hWJSCs).

Science.gov (United States)

Mostafavi-Pour, Zohreh; Ashrafi, Mohammad Reza; Talaei-Khozani, Tahereh

2018-06-01

Human Wharton's jelly mesenchymal stem cells (hWJSCs) are multipotent stem cells that could be aggregated into 3D spherules. ITGA4 and ITGA5 genes encode α4 and α5 subunits of integrins, respectively. In this study, we analyzed expression levels of ITGA4 and ITGA5 gene mRNAs in undifferentiated and 3D spherules forming hWJSCs in order to determine their expression pattern for possible future treatment of cancer cells in a co-culture fashion. For the purpose of obtaining hWJSCs, umbilical cords were collected from patients with caesarian section at full term delivery. The cells were then characterized according to cell surface markers using flow cytometry. Furthermore pluripotency of the obtained cells was verified. Subsequently the cells were aggregated in 3D spherules using hanging drop cultures. Expression levels of ITGA4 and ITGA5 gene mRNAs were determined by RT-PCR and Real time PCR, both in the initial undifferentiated cells and those aggregated in the spherules. The obtained hWJSCs demonstrated pluripotency, differentiating to adipogenic and osteogenic cells. They also expressed mesenchymal stem cell surface markers. Following the aggregation of these cells and formation of 3D spherules, mRNA expression levels of both genes were significantly reduced (P < 0.05) compared with the initial undifferentiated state. The results of this study demonstrated that aggregation of hWJSCs into spherules alters their expression of ITGA4 and ITGA5. The implications of such an alteration would require further research.

Stratum corneum profiles of inflammatory mediators in patch test reactions to common contact allergens and sodium lauryl sulfate.

Science.gov (United States)

Koppes, S A; Ljubojevic Hadzavdic, S; Jakasa, I; Franceschi, N; Jurakić Tončić, R; Marinović, B; Brans, R; Gibbs, S; Frings-Dresen, M H W; Rustemeyer, T; Kezic, S

2017-06-01

Recent studies have demonstrated allergen-specific differences in the gene expression of inflammatory mediators in patch tested skin. To determine levels of various inflammatory mediators in the stratum corneum (SC) after patch testing with common contact allergens and the skin irritant sodium lauryl sulfate (SLS). In total, 27 individuals who had previously patch tested positive to nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) or para-phenylenediamine were retested and then patch tested with SLS and petrolatum, with petrolatum serving as the patch test control. At 72 h, the test sites were clinically graded and the SC samples collected on adhesive tape. The levels of 18 of the 32 quantified mediators differed significantly from that of the control patches for at least one of the tested substances. SLS and MCI/MI induced the largest number of immunomediators. Interleukin (IL)-16 levels were significantly higher in patch test reactions in all allergens than they were in the controls, while no significant difference was detected for SLS. Furthermore, a strong negative correlation was found between strength of patch test reaction and IL-1α levels. Cytokine profiles in the SC of patch tested skin did not show a distinct allergen-specific pattern. However, MCI/MI induced a larger and wider immune response than the other allergens, perhaps due to its potency as an irritant. The levels of IL-16 were significantly increased in patch test reactions to allergens but not to SLS; thus, they may help clinicians to differentiate between allergic contact dermatitis and irritant contact dermatitis. © 2016 British Association of Dermatologists.

Real-time UV imaging of nicotin release from transdermal patch

DEFF Research Database (Denmark)

Østergaard, Jesper; Meng-Lund, Emil; Larsen, Susan Weng

2010-01-01

PURPOSE: This study was conducted to characterize UV imaging as a platform for performing in vitro release studies using Nicorette® nicotine patches as a model drug delivery system. METHODS: The rate of nicotine release from 2 mm diameter patch samples (Nicorette®) into 0.067 M phosphate buffer, p......H 7.40, was studied by UV imaging (Actipix SDI300 dissolution imaging system) at 254 nm. The release rates were compared to those obtained using the paddle-over-disk method. RESULTS: Calibration curves were successfully established which allowed temporally and spatially resolved quantification...... of nicotine. Release profiles obtained from UV imaging were in qualitative agreement with results from the paddle-over-disk release method. CONCLUSION: Visualization as well as quantification of nicotine concentration gradients was achieved by UV imaging in real time. UV imaging has the potential to become...

The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

International Nuclear Information System (INIS)

Mesarosova, Monika; Valovicova, Zuzana; Srancikova, Annamaria; Krajcovicova, Zdenka; Milcova, Alena; Sokolova, Romana; Schmuczerova, Jana; Topinka, Jan; Gabelova, Alena

2011-01-01

The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). A slight but significant level of gene mutations and DNA adducts detected in V79MZh3A4 cells treated with N-MeDBC, only at the highest concentration (30 μM), revealed that this sarcomagenic carcinogen was also metabolized by hCYP3A4. Surprisingly, DBC increased the frequency of 6-thioguanine resistant (6-TG r ) mutations only at the highest concentration (30 μM), while DiMeDBC failed to increase the frequency of these mutations. The resistance to 6-thioguanine is caused by the mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene. The molecular analysis of the coding region of Hprt gene showed a deletion of the entire exon 8 in DiMeDBC-induced 6-TG r mutants, while no changes in the nucleotide sequences were identified in 6-TG r mutants produced by DBC and N-MeDBC. Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism. - Highlights: → DBC activation via CYP3A4 resulted in micronuclei, DNA adduct formation and mutations in V79MZh3A4 cells. → The CYP3A4-mediated DiMeDBC activation caused micronuclei followed by apoptosis in V79MZh3A4 cells. → The genotoxic effects produced by N-MeDBC in V79MZh3A4 cells were negligible. → The hCYP3A4 may play an important role in DBC and DiMeDBC metabolism. → The CYP3A4 might only have a marginal function in N

Light transmission and preference of eye patches for occlusion treatment.

Directory of Open Access Journals (Sweden)

Hwan Heo

Full Text Available To investigate light transmission and preference for six eye patches for occlusion therapy.Six patches were examined, including; Ortopad Fun Pack, Ortopad Flesh, Kawamoto A-1, Kawamoto A-2, 3M Opticlude, and Everade Eye Guard. The size and the presence of a light blocking pad of patches were investigated. The amount of light transmitted through the patches was evaluated, using a digital light meter and a model eye, in three different environments; indoors with fluorescent light, outdoors on a sunny day, and strong light from illuminator. After patching the normal eye, the flash visual evoked potential (VEP was measured. Thirty patients with amblyopia or horizontal strabismus, who received occlusion therapy as initial treatment, were included. After using all six patches, patients completed a 7-item questionnaire regarding the patch preference for size, color and shape, adhesive power, pain with removal, skin irritation after removing patch, parent's preference and overall opinion.All patches had a light-blocking pad, except the 3M Nexcare. Ortopad had the strongest light blocking power in the three environments, and the 3M Nexcare had the weakest power. In flash VEP, Ortopad and Kawamoto patches showed flat, but 3M Nexcare and Everade Eye Guard showed normal response. There were significant preferential differences among the patches in all the items of the questionnaire (P<0.05. In comparison between the patches respectively, 3M Nexcare received the lowest satisfaction in pain when removing a patch and skin irritation after removing a patch. Kawamoto A-2 received the lowest score in the overall satisfaction.We found differences in the light-blocking power and in the preference of the various patches for the occlusion treatment. This is a pilot study regarding only characteristics and preferences of patches. Further clinical studies regarding the relationship between characteristics or preferences of patches and outcomes of occlusion treatment

4-(2,3-Dihydroxybenzylideneamino-3-methyl-1H-1,2,4-triazol-5(4H-one

Directory of Open Access Journals (Sweden)

Şamil Işık

2009-12-01

Full Text Available All the non-H atoms of the title compound, C10H10N4O3, are almost coplanar, the maximum deviation from planarity being 0.065 (3 Å. The dihedral angle between the aromatic rings is 1.66 (6°. The molecule adopts the enol–imine tautomeric form with an intramolecular hydrogen-bonding interaction between the Schiff base N atom and the hydroxy group. In the crystal, intermolecular N—H...O and O—H...O hydrogen bonds link the molecules into a three-dimensional network.

Development of radiolabelled compound using reactor produced RI - Development of Ho-166 skin patch for treatment of skin cancer

Energy Technology Data Exchange (ETDEWEB)

Park, Kyung Bae [Korea Atomic Energy Research Institute, Taejon (Korea); Ryu, Jei Man [Dong Wha Pharm. Ind. Co., Ltd., Seoul (Korea)

1999-04-01

A radioactive patch which can be treat the skin cancer by direct irradiation was prepared by blending Ho(NO{sub 3}){sub 3}, 5H{sub 2}O and polyurethane(PU) and then irradiating with neutron in the nuclear reactor. The blend formation of the film was fonfirmed by FT-IR. Degree of the distribution of holmium and solvent in remaining in the film was determined. Physical properties of the film by thermal analysis, mechanical measurement and surface analysis were characterized, respectively. To evaluate efficacy of the patch, it was applied to the tumor surface of the hairlessmous. Until 6 weeks of the patch treatment 7 mice with skin tumor were cured totally (7/13). And the other nuclear except for holmium was in patch was not detected. Furthermore, the patch was stable at room temperature, 40 deg C and 60 deg C. (author). 17 refs., 13 figs., 9 tabs.

Development of Novel Faster-Dissolving Microneedle Patches for Transcutaneous Vaccine Delivery.

Science.gov (United States)

Ono, Akihiko; Ito, Sayami; Sakagami, Shun; Asada, Hideo; Saito, Mio; Quan, Ying-Shu; Kamiyama, Fumio; Hirobe, Sachiko; Okada, Naoki

2017-08-03

Microneedle (MN) patches are promising for transcutaneous vaccination because they enable vaccine antigens to physically penetrate the stratum corneum via low-invasive skin puncturing, and to be effectively delivered to antigen-presenting cells in the skin. In second-generation MN patches, the dissolving MNs release the loaded vaccine antigen into the skin. To shorten skin application time for clinical practice, this study aims to develop novel faster-dissolving MNs. We designed two types of MNs made from a single thickening agent, carboxymethylcellulose (CMC) or hyaluronan (HN). Both CMC-MN and HN-MN completely dissolved in rat skin after a 5-min application. In pre-clinical studies, both MNs could demonstrably increase antigen-specific IgG levels after vaccination and prolong antigen deposition compared with conventional injections, and deliver antigens into resected human dermal tissue. In clinical research, we demonstrated that both MNs could reliably and safely puncture human skin without any significant skin irritation from transepidermal water loss measurements and ICDRG (International Contact Dermatitis Research Group) evaluation results.

Performance of patch repaired composite panels under fatigue loads

International Nuclear Information System (INIS)

Darwish, Feras H.; Hamoush, S.; Shivakumar, K.

2006-01-01

This paper evaluates the performance of bonded patch-scarf repairs of full scale laminated composite panels under cyclic load conditions. Nondestructive testing to characterize the quality of repairs and destructive testing to evaluate the performance of repaired panels were used in this study. Carbon/Epoxy prepreg material used was used to lay up six-ply (12 in. x 27 in. /305x686mm) (-60/60/0) s quasi-isotropic laminates. 7-ply scarf repair with a gradient of 0.5 inch (12.7mm) per layer was used to perform the repair of a damaged zone. The patch consisted of 7.5 inches (190mm) diameter adhesive film, 1 inch (25.4mm) diameter filler ply at 90fiber orientation, and six plies (2-7 inches (51-178mm) diameter) to match the lay-up of the parent material. The study was extended to include defective repairs. The defect was engineered by inserting a 1 inch (25.4 mm) circular Teflon flaw between the fifth and sixth layers of the patch. A total of 28 panels were prepared and divided into five categories: (1) three pristine panels (undamaged parental materials); (2) three damaged panels (1-inch-centered-hole); (3) two repaired panels with wrong fiber orientation; (4) nine good repaired panels, and (5) eleven defective repair panels (1 inch flaw). A nondestructive evaluation to check the conditions of the repairs was performed on most of the tested panels that include the pulse-echo C-scan and pseudo through transmission air coupled and water coupled C-scan. Based on the results of the experimental evaluation of this study, good repair restored 95% of the tensile strength while defective repair restored 90% of the tensile strength of the pristine panels. Under fatigue loading, panels repaired with a 1 inch delamination flaw within the patch layers showed a major reduction in fatigue life compared to the good repair panels under similar loading conditions. (author)

Biological cell controllable patch-clamp microchip

Science.gov (United States)

Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

2010-12-01

A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

The Cs2SO4-Ce2(SO4)3-H2SO4-H2O system at 150 and 200 deg C

International Nuclear Information System (INIS)

Bondar', S.A.; Belokoskov, V.I.; Trofimov, G.V.

1982-01-01

Solubility in the system Cs 2 SO 4 -Ce 2 (SO 4 ) 3 -H 2 SO 4 -H 2 O using the isothermal method at 150 and 200 deg C at molar ratios Cs 2 SO 4 :Ce 2 (SO 4 ) 3 =1:5 and conditions of sulfate crystallization Cs 2 SO 4 xCe 2 (SO 4 ) 3 , Ce 2 (SO 4 ) 3 x0.5H 2 SO 4 xnH 2 O (n=2-3) and Ce 2 (SO 4 ) 3 x3H 2 SO 4 are determined. Double sulfate Cs 2 SO 4 xCe 2 (SO 4 ) 3 is studied using the methods of crystallooptical, thermal, X-ray phase analyses and IR spectroscopy

Studies on the inactivation of human parvovirus 4.

Science.gov (United States)

Baylis, Sally A; Tuke, Philip W; Miyagawa, Eiji; Blümel, Johannes

2013-10-01

Human parvovirus 4 (PARV4) is a novel parvovirus, which like parvovirus B19 (B19V) can be a contaminant of plasma pools used to prepare plasma-derived medicinal products. Inactivation studies of B19V have shown that it is more sensitive to virus inactivation strategies than animal parvoviruses. However, inactivation of PARV4 has not yet been specifically addressed. Treatment of parvoviruses by heat or low-pH conditions causes externalization of the virus genome. Using nuclease treatment combined with real-time polymerase chain reaction, the extent of virus DNA externalization was used as an indirect measure of the inactivation of PARV4, B19V, and minute virus of mice (MVM) by pasteurization of albumin and by low-pH treatment. Infectivity studies were performed in parallel for B19V and MVM. PARV4 showed greater resistance to pasteurization and low-pH treatment than B19V, although PARV4 was not as resistant as MVM. There was a 2- to 3-log reduction of encapsidated PARV4 DNA after pasteurization and low-pH treatment. In contrast, B19V was effectively inactivated while MVM was stable under these conditions. Divalent cations were found to have a stabilizing effect on PARV4 capsids. In the absence of divalent cations, even at neutral pH, there was a reduction of PARV4 titer, an effect not observed for B19V or MVM. In the case of heat treatment and incubation at low pH, PARV4 shows intermediate resistance when compared to B19V and MVM. Divalent cations seem important for stabilizing PARV4 virus particles. © 2013 American Association of Blood Banks.

Yeast RNA viruses as indicators of exosome activity: human exosome hCsl4p participates in RNA degradation in Saccharomyces cerevisiae'.

Science.gov (United States)

Ramírez-Garrastacho, Manuel; Esteban, Rosa

2011-12-01

The exosome is an evolutionarily conserved 10-mer complex involved in RNA metabolism, located in both the nucleus and the cytoplasm. The cytoplasmic exosome plays an important role in mRNA turnover through its 3'→5' exonucleolytic activity. The superkiller (SKI) phenotype of yeast was originally identified as an increase of killer toxin production due to elevated levels of the L-A double-stranded RNA (dsRNA) Totivirus and its satellite toxin-encoding M dsRNA. Most SKI genes were later shown to be either components of the exosome or modulators of its activity. Variations in the amount of Totivirus are, thus, good indicators of yeast exosome activity, and can be used to analyse its components. Furthermore, if exosome proteins of higher eukaryotes were functional in S. cerevisiae, these viruses would provide a simple tool to analyse their function. In this work, we have found that hCSL4, the human orthologue of SKI4 in the yeast exosome, rescues the null phenotype of the deletion mutant. hCsl4p shares with Ski4p conserved S1 RNA-binding domains, but lacks the N-terminal third of Ski4p. Nevertheless, it interacts with the Dis3p exonuclease of yeast exosome, and partially complements the superkiller phenotype of ski4-1 mutation. The elimination of the N-terminal third of Ski4p does not affect its activity, indicating that it is dispensable for RNA degradation. We have also identified the point mutation G152E in hCSL4, equivalent to the ski4-1 mutation G253E, which impairs the activity of the protein, thus validating our approach of using yeast RNA virus to analyse the exosome of higher eukaryotes. Copyright © 2011 John Wiley & Sons, Ltd.

Formaldehyde concentration in diagnostic patch testing

DEFF Research Database (Denmark)

Trattner, A; Johansen, J D; Menné, T

1998-01-01

Exposure to formaldehyde is common from both consumer products and industry. The reliability of the patch test is essential for the diagnosis of formaldehyde allergy as it is difficult to suspect from the patient's history. The recommended formaldehyde patch test concentration has been reduced over...

The effect of pH and ADP on ammonia affinity for human glutamate dehydrogenases

DEFF Research Database (Denmark)

Zaganas, Ioannis; Pajecka, Kamilla; Nielsen, Camilla Wendel

2013-01-01

Glutamate dehydrogenase (GDH) uses ammonia to reversibly convert α-ketoglutarate to glutamate using NADP(H) and NAD(H) as cofactors. While GDH in most mammals is encoded by a single GLUD1 gene, humans and other primates have acquired a GLUD2 gene with distinct tissue expression profile. The two...... human isoenzymes (hGDH1 and hGDH2), though highly homologous, differ markedly in their regulatory properties. Here we obtained hGDH1 and hGDH2 in recombinant form and studied their Km for ammonia in the presence of 1.0 mM ADP. The analyses showed that lowering the pH of the buffer (from 8.0 to 7.......0) increased the Km for ammonia substantially (hGDH1: from 12.8 ± 1.4 mM to 57.5 ± 1.6 mM; hGDH2: from 14.7 ± 1.6 mM to 62.2 ± 1.7 mM), thus essentially precluding reductive amination. Moreover, lowering the ADP concentration to 0.1 mM not only increased the K0.5 [NH4 (+)] of hGDH2, but also introduced...

Potential antimicrobial agents from triazole-functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones.

Science.gov (United States)

Bollu, Rajitha; Banu, Saleha; Bantu, Rajashaker; Reddy, A Gopi; Nagarapu, Lingaiah; Sirisha, K; Kumar, C Ganesh; Gunda, Shravan Kumar; Shaik, Kamal

2017-12-01

A series of substituted triazole functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones were synthesized by employing click chemistry and further characterized based on 1 H NMR, 13 C NMR, IR and mass spectral studies. All the synthesized derivatives were screened for their in vitro antimicrobial activities. Further, molecular docking studies were accomplished to explore the binding interactions between 1,2,3-triazol-4-yl-2H-benzo[b][1,4]oxazin-3(4H)-one and the active site of Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCS). These docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9c, 9d and 9e were identified as promising antimicrobial leads. Copyright © 2017 Elsevier Ltd. All rights reserved.

Surgery for left ventricular aneurysm: early and late survival after simple linear repair and endoventricular patch plasty.

Science.gov (United States)

Lundblad, Runar; Abdelnoor, Michel; Svennevig, Jan Ludvig

2004-09-01

Simple linear resection and endoventricular patch plasty are alternative techniques to repair postinfarction left ventricular aneurysm. The aim of the study was to compare these 2 methods with regard to early mortality and long-term survival. We retrospectively reviewed 159 patients undergoing operations between 1989 and 2003. The epidemiologic design was of an exposed (simple linear repair, n = 74) versus nonexposed (endoventricular patch plasty, n = 85) cohort with 2 endpoints: early mortality and long-term survival. The crude effect of aneurysm repair technique versus endpoint was estimated by odds ratio, rate ratio, or relative risk and their 95% confidence intervals. Stratification analysis by using the Mantel-Haenszel method was done to quantify confounders and pinpoint effect modifiers. Adjustment for multiconfounders was performed by using logistic regression and Cox regression analysis. Survival curves were analyzed with the Breslow test and the log-rank test. Early mortality was 8.2% for all patients, 13.5% after linear repair and 3.5% after endoventricular patch plasty. When adjusted for multiconfounders, the risk of early mortality was significantly higher after simple linear repair than after endoventricular patch plasty (odds ratio, 4.4; 95% confidence interval, 1.1-17.8). Mean follow-up was 5.8 +/- 3.8 years (range, 0-14.0 years). Overall 5-year cumulative survival was 78%, 70.1% after linear repair and 91.4% after endoventricular patch plasty. The risk of total mortality was significantly higher after linear repair than after endoventricular patch plasty when controlled for multiconfounders (relative risk, 4.5; 95% confidence interval, 2.0-9.7). Linear repair dominated early in the series and patch plasty dominated later, giving a possible learning-curve bias in favor of patch plasty that could not be adjusted for in the regression analysis. Postinfarction left ventricular aneurysm can be repaired with satisfactory early and late results. Surgical