bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary conservation of an atypical glucocorticoid‐responsive element in the human tyrosine hydroxylase gene
Authors: Sheela Rani C. S. , Soto‐Pina Alexandra , Iacovitti Lorraine , Strong Randy
Published: May 2013

The human tyrosine hydroxylase (hTH) gene has a 42 bp evolutionarily conserved region designated (CR) II at −7.24 kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7 bp activator protein‐1 (AP‐1)‐like motif in the rat TH gene. We cloned this hTH‐CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH‐CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7 bp 5′‐TGACTAA at −7243 bp completely abolished the Dex‐stimulated Luc activity of hTH‐CRII construct. The AP‐1 agonist, tetradeconoyl‐12,13‐phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP‐1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid‐responsive element in a 7 bp AP‐1‐like motif in the promoter region at −7.24 kb of the human TH gene.
Human choroid plexus papilloma cells efficiently transport glucose and vitamin C
Authors: Ulloa Viviana , García‐Robles María , Martínez Fernando , Salazar Katterine , Reinicke Karin , Pérez Fernando , Godoy David F. , Godoy Alejandro S. , Nualart Francisco
Published: May 2013

In vitro and in vivo studies suggest that the basolateral membrane of choroid plexus cells, which is in contact with blood vessels, is involved in the uptake of the reduced form of vitamin C, ascorbic acid (AA), through the sodium‐vitamin C cotransporter, (SVCT2). Moreover, very low levels of vitamin C were observed in the brains of SVCT2‐null mice. The oxidized form of vitamin C, dehydroascorbic acid (DHA), is incorporated through the facilitative glucose transporters (GLUTs). In this study, the contribution of SVCT2 and GLUT1 to vitamin C uptake in human choroid plexus papilloma (HCPP) cells in culture was examined. Both the functional activity and the kinetic parameters of GLUT1 and SVCT2 in cells isolated from HCPP were observed. Finally, DHA uptake by GLUT1 in choroid plexus cells was assessed in the presence of phorbol‐12‐myristate‐13‐acetate (PMA)‐activated human neutrophils. A marked increase in vitamin C uptake by choroid plexus cells was observed that was associated with superoxide generation and vitamin C oxidation (bystander effect). Thus, vitamin C can be incorporated by epithelial choroid plexus papilloma cells using the basolateral polarization of SVCT2 and GLUT1. This mechanism may be amplified with neutrophil infiltration (inflammation) of choroid plexus tumors.

image

In choroid plexus papilloma cells, the vitamin C transporters SVCT2 and GLUT1 are polarized to the basolateral epithelial membrane, where SVCT2 is essential for AA flux from the blood vessels into the brain. However, neutrophils, attracted by inflammation or the tumor microenvironment, can oxidize extracellular AA to DHA, thereby enabling its uptake through GLUT1. For the first time, we show the in vivo and in vitro basolateral co‐distribution of functional SVCT2 and GLUT1 in epithelial cells. We postulate that patients with choroid plexus papillomas may continue to transport vitamin C from the blood to CSF. However, increased transport of oxidized vitamin C could generate pro‐oxidative conditions that may help control tumor growth.
Voiding Dysfunction in Spinocerebellar Ataxia Type 31
Authors: SUGIYAMA Megumi , SAKAKIBARA Ryuji , TATENO Fuyuki , YANO Masashi , TAKAHASHI Osamu , KISHI Masahiko , TSUYUSAKI Yohei , YAMAMOTO Tatsuya , UCHIYAMA Tomoyuki , YAMANISHI Tomonori , YAMAGUCHI Chiharu , NOMURA Fumio
Published: May 2013

Objective

To describe a case of SCA31 who presented with possible neurogenic voiding dysfunction.

Methods

A case report.

Results

A 73‐year‐old man with a 5‐year history of cerebellar ataxia developed partial urinary retention. His father and a sister had cerebellar ataxia. Brain magnetic resonance imaging revealed cerebellar atrophy, and gene analysis revealed TGGAA repeat prolongation, and he was diagnosed with spinocerebellar ataxia 31. Urodynamics revealed normal bladder filling but a slightly weak detrusor and a post‐void residual urine volume of 130 mL, whereas his prostate volume was normal (26 mL). External sphincter electromyography revealed neurogenic change in the motor unit potentials. In order to lessen the post‐void residual, hewas started on 15mg/day pilocarpine with benefit. The weak detrusor and sphincter electromyography abnormality indicated involvement of the sacral spinal cord in this disorder.

Conclusion

Neurogenic urinary retention in SCA31 can be listed in the clinical differential diagnosis of cerebellar ataxia. However, possible outflow obstruction in men should always be explored.
Impaired Vascular KATP Function Attenuates Exercise Capacity in Obese Zucker Rats
Authors: Lu Silu , Xiang Lusha , Clemmer John S. , Gowdey Andrew R. , Mittwede Peter N. , Hester Robert L.
Published: May 2013

Objective

Obese subjects exhibit decreased exercise capacity (VO2max). We have shown that vascular KATP channel mediates arteriolar dilation to muscle contraction. We hypothesize that exercise capacity is decreased in obesity due to impaired vascular KATP function.

Methods

The VO2max was measured in LZR and OZR by treadmill running before and following treatment with the KATP blocker glibenclamide i.p. One week later, the spinotrapezius muscle was prepared for in vivo microscopy. Arcade arteriolar diameters were measured following muscle contraction or application of the KATP opener cromakalim before and after glibenclamide application. In additional animals, LZR and OZR were treated with apocynin for five weeks. VO2max and arteriolar dilation experiments were repeated.

Results

The OZR exhibited decreased VO2max, functional and cromakalim‐induced vasodilation as compared with LZR. Glibenclamide had no effect on VO2max and functional vasodilation in OZR, but significantly inhibited responses in LZR. Vascular superoxide levels and NADPH oxidase activity were increased in OZR, but reduced in apocynin‐treated OZR. Apocynin increased the VO2max, functional and cromakalim‐induced vasodilation in OZR with no effect in LZR.

Conclusions

Exercise capacity is dependent on vascular KATP channel function. The reduced exercise capacity in OZR appears to be due in part to superoxide‐mediated impairment in vascular KATP function.
Echinocandins in invasive candidiasis
Authors: Simon John , Sun Hsin‐Yun , Leong Hoe Nam , Barez Marie Yvette C. , Huang Po‐Yen , Talwar Deepak , Wang Jen‐Hsien , Mansor Melor , Wahjuprajitno Bambang , Patel Atul , Wittayachanyapong Siriporn , Sany B. Shoib Mohd , Lin Sheng‐Fong , Dimopoulos George
Published: May 2013

We summarise a recent meeting, sponsored by Pfizer Inc., where experts in Asia shared their clinical experience in managingIC. The echinocandins have demonstrated good activity against non‐albicansinfections and also azole‐resistant strains, both preclinically and in recent clinical trials. As well as proving efficacious, echinocandins have a favourable safety profile and are well tolerated, including among inpatient subpopulations, such as transplant recipients and those with renal or hepatic dysfunction. In addition the echinocandins generally have minimal drug–drug interactions, unlike the oral azoles, which have multiple effects on cytochrome P450‐mediated drug metabolism. Echinocandins are characterised by a good safety profile, few drug–drug interactions and good susceptibilities. With the increase in potentially azole‐resistant non‐albicansinfections, echinocandins may become the first‐line treatment of choice for many patients.
Immunological control of cell cycle aberrations for the avoidance of oncogenesis: the case of tetraploidy
Authors: Senovilla Laura , Galluzzi Lorenzo , Castedo Maria , Kroemer Guido
Published: May 2013

Tetraploid cells—cells that contain twice the normal amount of DNA—are more prone to neoplastic transformation than their normal, diploid counterparts since they are genomically unstable and frequently undergo asymmetric, multipolar cell divisions. Similar to many other genomic aberrations, tetraploidization is normally avoided by multiple, nonredundant cell‐intrinsic mechanisms that are tied to cell cycle checkpoints. Unexpectedly, tetraploidization is also under the control of a cell‐extrinsic mechanism determined by the immune system. Indeed, oncogene‐ or carcinogen‐induced cancers developing in immunodeficient mice contain cells with a higher DNA content than similar tumors growing in immunocompetent hosts. Moreover, cancer cell lines that have been rendered tetraploid in vitro grow normally in immunodeficient mice, yet almost fail to generate tumors in immunocompetent animals. One of the mechanisms whereby the immune system recognizes tetraploid cells originates from tetraploidy causing an endoplasmic reticulum (ER) stress response that culminates in the exposure of the ER protein calreticulin on the cell surface. Hence, tetraploidy exemplifies a potentially oncogenic alteration that is repressed by a combination of cell‐autonomous mechanisms and immunosurveillance. Oncogenesis and tumor progression require the simultaneous failure of both such control systems.
Cancer‐induced immunosuppressive cascades and their reversal by molecular‐targeted therapy
Authors: Kawakami Yutaka , Yaguchi Tomonori , Sumimoto Hidetoshi , Kudo‐Saito Chie , Tsukamoto Nobuo , Iwata‐Kajihara Tomoko , Nakamura Shoko , Nishio Hiroshi , Satomi Ryosuke , Kobayashi Asuka , Tanaka Mayuri , Park Jeong Hoon , Kamijuku Hajime , Tsujikawa Takahiro , Kawamura Naoshi
Published: May 2013

Immunological status in tumor tissues varies among patients. Infiltration of memory‐type CD8+ T cells into tumors correlates with prognosis of patients with various cancers. However, the mechanism of the differential CD8+ T cell infiltration has not been well investigated. In general, tumor‐associated microenvironments, including tumor and sentinel lymph nodes, are under immunosuppressive conditions such that the immune system is not able to eliminate cancer cells without immune‐activating interventions. Constitutive activation of various signaling pathways in human cancer cells triggers multiple immunosuppressive cascades that involve various cytokines, chemokines, and immunosuppressive cells. Signaling pathway inhibitors could inhibit these immunosuppressive cascades by acting on either cancer or immune cells, or both. In addition, common signaling mechanisms are often utilized for multiple hallmarks of cancer (e.g., cell proliferation/survival, invasion/metastasis, and immunosuppression). Therefore, targeting these common signaling pathways may be an attractive strategy for cancer therapy including immunotherapy.
Preventing cancer by targeting abnormally expressed self‐antigens: MUC1 vaccines for prevention of epithelial adenocarcinomas
Authors: Beatty Pamela L. , Finn Olivera J.
Published: May 2013

Prophylactic vaccines based on tumor‐associated antigens (TAAs) have elicited concerns due to their potential toxicity. Because TAAs are considered self‐antigens, the prediction is that such vaccines will induce autoimmunity. While this has been observed in melanoma, where an antitumor immune response leads to vitiligo, autoimmunity has almost never been seen following vaccination with numerous other TAAs. We hypothesized that antigen choice determines outcome and have been working to identify TAAs whose expression differs between normal and tumor tissue, and thus could elicit antitumor immunity without autoimmunity. Studies on the epithelial TAA MUC1 have revealed that, compared to MUC1 on normal cells, tumors, premalignant lesions, and noncancerous pathologies affecting epithelial cells express abnormal MUC1, which is not a self‐antigen but rather an abnormal disease‐associated antigen (DAA). This distinction, which can be made for many known TAAs, has broad implications for the design and acceptance of preventative cancer vaccines.
Dendritic cell immunotherapy
Authors: Sabado Rachel Lubong , Bhardwaj Nina
Published: May 2013

The U.S. Food and Drug Administration's approval of the first cell‐based immunotherapy has rejuvenated interest in the field. Early clinical trials have established the ability of dendritic cell (DC) immunotherapy to exploit a patient's own immune system to induce antitumor immune responses. However, suboptimal conditions for generating potent immunostimulatory DCs, in addition to the suppression mediated by the tumor microenvironment, have contributed to limited clinical success in vivo. Therefore, combining DC vaccines with new approaches that enhance immunogenicity and overcome the regulatory mechanisms underlying peripheral tolerance may be key to achieving effective, durable, antitumor immune responses that translate to better clinical outcomes.
Mass mortality of an asteriid starfish (Forcipulatida, Asteroidea, Echinodermata) from the late Maastrichtian (Late Cretaceous) of Morocco
Authors: GALE ANDY , VILLIER LOÏC
Published: May 2013

Abstract:  A mass occurrence, numbering tens of thousands of individuals in a single lens, belonging to a single species of asteroid, is described from the late Maastrichtian (Late Cetaceous) of Morocco. The lens of partially silicified asteroidal limestone is made up largely of fully articulated specimens of similar size and probably represents the mass mortality of a single recruitment. By comparison with mass strandings of the present‐day species Asterias rubens (Linnaeus), it can be inferred that a feeding swarm of individuals was swept into a submarine channel by either a storm or an exceptionally strong tidal current, and permanently buried. The genus and species are herein described as Cretasterias reticulatus gen. et sp. nov. The exceptional preservation of the material enables the identification of wreath organs (clusters of crossed pedicellariae set in a dermal pad around spines) for the first time in the fossil record. Comparison between extant Asteriidae, putative fossil asteriids and C. reticulatus provides ambiguous evidence of its affinities; it appears to display a combination of plesiomorphic and derived characters. It is shown that all Mesozoic forcipulatid asteroids described so far share a very simple arm construction (single row of adradial ossicles) unknown in adult extant Forcipulatida.
A new Patagonian species ofCricosaurus(Crocodyliformes, Thalattosuchia): first evidence ofCricosaurusin Middle–Upper Tithonian lithographic limestone from Gondwana
Authors: HERRERA YANINA , GASPARINI ZULMA , FERNÁNDEZ MARTA S.
Published: May 2013

Abstract: Upper Jurassic (Tithonian) deposits in north‐western Patagonia, Argentina, have yielded rich and taxonomically diverse assemblages of marine reptiles. These assemblages are also remarkable by their quality of preservation and are represented by ichthyosaurs, plesiosaurs, turtles and crocodyliforms. Despite the abundant crocodyliform record, only two metriorhynchid taxa have been identified:Cricosaurus araucanensisandDakosaurus andiniensis. Here we described a new species ofCricosaurus, which represents the second species ofCricosaurusin the Tithonian of the Neuquén Basin, and the first metriorhynchid found in lithographic limestone from Gondwana. Furthermore, this specimen has the most complete postcranial remains of any metriorhynchid from South America. The new species is characterized by a short distance between the premaxilla and the nasal, a relatively narrow interorbital width, 23–25 mandibular teeth, bicarinated teeth with fine apicobasally aligned ridges, interalveolar spaces between the first seven teeth approximately 1.5 times longer than the anteroposterior diameter of the respective alveoli. To test the assignment of the new species toCricosaurus, we carried out two phylogenetic analyses. In both analyses,Cricosaurus lithographicussp. nov. is nested with other species referred to this genus. This new species has peculiar enamel ornamentation, characterized by numerous, fine apicobasally aligned ridges, when compared to other species of the genus.
In situ stems: preservation states and growth habits of the Pennsylvanian (Carboniferous) calamitaleans based upon new studies of Calamites Sternberg, 1820 in the Duckmantian at Brymbo, North Wales, UK
Authors: Thomas Barry A.
Published: May 2013

Calamitalean stems that are preserved in growth position in Carboniferous sedimentary deposits have been described many times in the literature as either pith casts or stem casts. Many of these in situ stems show branching, which gives some information on their patterns of growth. Their manner of preservation is discussed in the light of a new stand of well‐preserved in situ stem and branch pith casts of Calamites discovered in mid to upper Duckmantian sandstone at Brymbo in the Wrexham Coalfield of North Wales. Analysis of a brown mineralized layer surrounding the casts and below the black compression remains of the stem tissues has shown the presence of goethite, muscovite, quartz and kaolin. Deposition of these minerals around the inside of the central stem cavity would have provided rigidity and sufficient support, while the pith cavity filled with sediments. The outer tissues would then have been compressed to form a thin coal layer around the mineralized infill of the pith cavity. Cross sections of stems were found clustered together in relatively small areas, and kernel density map and nearest neighbour analysis suggest that each small patch of these pith casts represents an individual plant spread by rhizomatous growth. Stems found in ironstone nodules are external casts of leafy stems preserved by the deposition of siderite on their surfaces. A length of rhizome found at Brymbo was similarly preserved as a cast in ironstone.
Introgression of productivity and other desirable traits from ricebean (Vigna umbellata) into black gram (Vigna mungo)
Authors: Singh Inderjit , Sandhu Jeet S. , Gupta Shashi K. , Singh Sarvjeet
Published: May 2013

Crosses were performed to introgress genes for productivity and other desirable traits from ricebean (Vigna umbellata) into black gram (Vigna mungo). Crossability was very poor in black gram × ricebean crosses, and only two to nine true hybrid plants were obtained. Plant fertility was very poor in initial generations, but was improved gradually from F2 onwards. Twenty‐four uniform progenies, bulked in F7, were evaluated for yield potential. The percentage increase/decrease in yield ranged from −35.48 to 50.31 over the check cultivar (‘Mash338’, female parent). All the progenies were found resistant to Mungbean yellow mosaic virus, Cercospora leaf spot and Bacterial leaf spot diseases. Overall, it was found that desirable traits such as high pod number, seed weight, productivity and resistance to diseases have been introgressed successfully into black gram from ricebean. A derivative line, KUG114, recorded yield superiority of 39.45% over the check cultivar ‘Mash338’ on the average of 14 multilocation research trials. It was released under the name ‘Mash114’ for cultivation in the Punjab state.
Overexpression of microRNA319 impacts leaf morphogenesis and leads to enhanced cold tolerance in rice (Oryza sativa L.)
Authors: YANG CHUNHUA , LI DAYONG , MAO DONGHAI , LIU XUE , JI CHENGJUN , LI XIAOBING , ZHAO XIANFENG , CHENG ZHUKUAN , CHEN CAIYAN , ZHU LIHUANG
Published: May 2013

MicroRNA319 (miR319) family is one of the conserved microRNA (miRNA) families among diverse plant species. It has been reported that miR319 regulates plant development in dicotyledons, but little is known at present about its functions in monocotyledons. In rice (Oryza sativa L.), the MIR319 gene family comprises two members, Osa‐MIR319a and Osa‐MIR319b. Here, we report an expression pattern analysis and a functional characterization of the two Osa‐MIR319 genes in rice. We found that overexpressing Osa‐MIR319a and Osa‐MIR319b in rice both resulted in wider leaf blades. Leaves of osa‐miR319 overexpression transgenic plants showed an increased number of longitudinal small veins, which probably accounted for the increased leaf blade width. In addition, we observed that overexpressing osa‐miR319 led to enhanced cold tolerance (4 °C) after chilling acclimation (12 °C) in transgenic rice seedlings. Notably, under both 4 and 12 °C low temperatures, Osa‐MIR319a and Osa‐MIR319b were down‐regulated while the expression of miR319‐targeted genes was induced. Furthermore, genetically down‐regulating the expression of either of the two miR319‐targeted genes, OsPCF5 and OsPCF8, in RNA interference (RNAi) plants also resulted in enhanced cold tolerance after chilling acclimation. Our findings in this study demonstrate that miR319 plays important roles in leaf morphogenesis and cold tolerance in rice.
Validity and reliability testing of the Swedish version of Melbourne Decision Making Questionnaire
Authors: Isaksson Ulf , Hajdarević Senada , Jutterström Lena , Hörnsten Åsa
Published: May 2013

Background

The Melbourne Decision‐Making Questionnaire (MDMQ) is an attempt to capture and measure coping strategies that people use. The instrument had not previously been translated into Swedish. The aim of this study was to evaluate validity and reliability of the Swedish version of the MDMQ.

Method

A Swedish translation was performed and back‐translated. A group of five pilot readers evaluated content validity. The translated questionnaire was tested among 735 patients, healthcare workers, healthcare students and teachers. A parallel analysis (PA), exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed.

Result

An initial EFA with a four‐factor solution showed a low concordance with the original 22‐item four‐factor model with a very low Cronbach's alpha in one of the dimensions. However, a second EFA with a three‐factor solution showed a good model fit for the Swedish translation of the Melbourne Decision‐Making Questionnaire (MDMQ‐S) with a satisfactory Cronbach's alpha. A CFA showed a goodness of fit after deleting six items.

Conclusion

After testing the MDMQ‐S, we found support for validity and reliability of the instrument. We found the 16‐item version of MDMQ‐S to be satisfactory concerning the subscales vigilance, procrastination and buck‐passing. However, we found no support that the hypervigilance dimension could be measured by the MDMQ‐S.
Inference in Targeted Group‐Sequential Covariate‐Adjusted Randomized Clinical Trials
Authors: Chambaz Antoine , van der Laan Mark J.
Published: May 2013

This article is devoted to the construction and asymptotic study of adaptive, group‐sequential, covariate‐adjusted randomized clinical trials analysed through the prism of the semiparametric methodology of targeted maximum likelihood estimation. We show how to build, as the data accrue group‐sequentially, a sampling design that targets a user‐supplied optimal covariate‐adjusted design. We also show how to carry out sound statistical inference based on such an adaptive sampling scheme (therefore extending some results known in the independent and identically distributed setting only so far), and how group‐sequential testing applies on top of it. The procedure is robust (i.e. consistent even if the working model is mis‐specified). A simulation study confirms the theoretical results and validates the conjecture that the procedure may also be efficient.
No effect of antifungal compounds on functional properties of human antifungal T‐helper type 1 cells
Authors: Tramsen L. , Schmidt S. , Koehl U. , Huenecke S. , Latgé J.‐P. , Roeger F. , Schubert R. , Klingebiel T. , Lehrnbecher T.
Published: May 2013

Despite the availability of new antifungal compounds, invasive fungal disease is associated with a high mortality in hematopoietic stem cell transplant (HSCT) recipients. A growing body of evidence suggests that T lymphocytes from the T‐helper type 1 (TH1) play an important role in the antifungal host defense, and preliminary data indicate a potential benefit of infusing donor‐derived antifungal TH1 cells to HSCT patients suffering from invasive fungal disease. Unfortunately, it is unclear to date whether the function of these cells is affected by concomitantly administered antifungal agents. We therefore analyzed the effects of various concentrations of commonly used antifungal compounds such as amphotericin B, caspofungin, fluconazole, voriconazole, and posaconazole on the functional properties of cultivated human antifungal TH1 cells. None of the antifungal compounds tested significantly influenced the secretion of interferon‐γ and tumor necrosis factor‐α, and only posaconazole at high concentrations slightly decreased proliferation of antifungal TH1 cells. Our data indicate that the antifungal agents tested do not significantly affect the functional properties of antifungal TH1 cells and can therefore be concomitantly administered.
Have we improved use of medicines in developing and transitional countries and do we know how to? Two decades of evidence
Authors: Holloway K. A. , Ivanovska V. , Wagner A. K. , Vialle‐Valentin C. , Ross‐Degnan D.
Published: May 2013

Objective

To assess progress in improving use of medicines in developing and transitional countries by reviewing empirical evidence, 1990–2009, concerning patterns of primary care medicine use and intervention effects.

Methods

We extracted data on medicines use, study setting, methodology and interventions from published and unpublished studies on primary care medicine use. We calculated the medians of six medicines use indicators by study year, country income level, geographic region, facility ownership and prescriber type. To estimate intervention impacts, we calculated greatest positive (GES) and median effect sizes (MES) from studies meeting accepted design criteria.

Results

Our review comprises 900 studies conducted in 104 countries, reporting data on 1033 study groups from public (62%), and private (mostly for profit) facilities (26%), and households. The proportion of treatment according to standard treatment guidelines was 40% in public and <30% in private‐for‐profit sector facilities. Most indicators showed suboptimal use and little progress over time: Average number of medicines prescribed per patient increased from 2.1 to 2.8 and the percentage of patients receiving antibiotics from 45% to 54%. Of 405 (39%) studies reporting on interventions, 110 (27%) used adequate study design and were further analysed. Multicomponent interventions had larger effects than single component ones. Median GES was 40% for provider and consumer education with supervision, 17% for provider education alone and 8% for distribution of printed education materials alone. Median MES showed more modest improvements.

Conclusions

Inappropriate medicine use remains a serious global problem.
Thermospermine levels are controlled by an auxin‐dependent feedback loop mechanism in Populus xylem
Authors: Milhinhos Ana , Prestele Jakob , Bollhöner Benjamin , Matos Andreia , Vera‐Sirera Francisco , Rambla José L. , Ljung Karin , Carbonell Juan , Blázquez Miguel A. , Tuominen Hannele , Miguel Célia M.
Published: May 2013

Polyamines are small polycationic amines that are widespread in living organisms. Thermospermine, synthesized by thermospermine synthase ACAULIS5 (ACL5), was recently shown to be an endogenous plant polyamine. Thermospermine is critical for proper vascular development and xylem cell specification, but it is not known how thermospermine homeostasis is controlled in the xylem. We present data in the Populus model system supporting the existence of a negative feedback control of thermospermine levels in stem xylem tissues, the main site of thermospermine biosynthesis. While over‐expression of the ACL5 homologue in Populus, POPACAULIS5, resulted in strong up‐regulation of ACL5 expression and thermospermine accumulation in leaves, the corresponding levels in the secondary xylem tissues of the stem were similar or lower than those in the wild‐type. POPACAULIS5 over‐expression had a negative effect on accumulation of indole‐3‐acetic acid, while exogenous auxin had a positive effect on POPACAULIS5 expression, thus promoting thermospermine accumulation. Further, over‐expression of POPACAULIS5 negatively affected expression of the class III homeodomain leucine zipper (HD‐Zip III) transcription factor gene PttHB8, a homologue of AtHB8, while up‐regulation of PttHB8 positively affected POPACAULIS5 expression. These results indicate that excessive accumulation of thermospermine is prevented by a negative feedback control of POPACAULIS5 transcript levels through suppression of indole‐3‐acetic acid levels, and that PttHB8 is involved in the control of POPACAULIS5 expression. We propose that this negative feedback loop functions to maintain steady‐state levels of thermospermine, which is required for proper xylem development, and that it is dependent on the presence of high concentrations of endogenous indole‐3‐acetic acid, such as those present in the secondary xylem tissues.
The effect of 1% tropicamide‐induced mydriasis and cycloplegia on spherical refraction of the adult horse
Authors: McMullen Richard J. , Davidson Michael G. , Gilger Brian C.
Published: May 2013

Objectives

To determine the effects of tropicamide 1% on the refractive state of the adult equine globe and identify the most appropriate time period (in relation to mydriasis) to perform streak retinoscopy.

Animals studied

Eight university‐owned mares of various ages and breeds.

Procedures

Topical tropicamide 1% was applied to one randomly selected eye from each of the horses to induce mydriasis and cycloplegia. The contralateral eyes served as controls. Streak retinoscopy and pupillometry were performed prior to, and every 5 min after tropicamide 1% installation for 90 min.

Results

All values are expressed as mean ± SD. Both horizontal (2.8 ± 0.74 mm) and vertical (7.3 ± 1.29 mm) mean pupil diameters increased significantly (P < 0.04) in the treatment eyes compared with the control eyes (horizontal [0.48 ± 0.85 mm] and vertical [1.06 ± 1.31 mm] pupil diameter). No significant differences in the refractive states of the treatment (horizontal: +0.25 ± 0.43 D and vertical: +0.41 ± 0.37 D) or control (horizontal: +0.34 ± 0.39 D and vertical: +0.41 ± 0.37 D) eyes were identified at any time point. Three of the eight treatment eyes demonstrated blurry or reversing streak reflexes during streak retinoscopy evaluation following the application of topical tropicamide 1%.

Conclusions

While these reflexes did not significantly influence streak retinoscopy results, their presence may subjectively influence a novice retinoscopist's ability to obtain accurate results. Therefore, optimal streak retinoscopy results may be obtained prior to, or 40‐ to 45‐min following the application of topical tropicamide 1%, once near‐maximal dilation has been achieved.
Probabilistic two-dimensional water-column and seabed inversion with self-adapting parameterizations
Authors: Dettmer Jan , Dosso Stan E.
Published: May 2013

This paper develops a probabilistic two-dimensional (2D) inversion for geoacoustic seabed and water-column parameters in a strongly range-dependent environment. Range-dependent environments in shelf and shelf-break regions are of increasing importance to the acoustical-oceanography community, and recent advances in nonlinear inverse theory and sampling methods are applied here for efficient probabilistic range-dependent inversion. The 2D seabed and water column are parameterized using highly efficient, self-adapting irregular grids which intrinsically match the local resolving power of the data and provide parsimonious solutions requiring few parameters to capture complex environments. The self-adapting parameterization is achieved by implementing the irregular grid as a trans-dimensional hierarchical Bayesian model with an unknown number of nodes which is sampled with the Metropolis-Hastings-Green algorithm. To improve sampling, population Monte Carlo is applied with a large number of interacting parallel Markov chains with adaptive proposal distributions. The inversion is applied to simulated data for a vertical-line array and several source locations to several kilometers range. Complex acoustic-pressure fields are computed using a parabolic equation model and results are considered in terms of 2D ensemble parameter estimates and credibility intervals.
Dynamical analysis of the nonlinear response of ultrasound contrast agent microbubbles
Authors: Carroll James M. , Calvisi Michael L. , Lauderbaugh Leal K.
Published: May 2013

The nonlinear response of spherical ultrasound contrast agent microbubbles is investigated to understand the effects of common shells on the dynamics. A compressible form of the Rayleigh–Plesset equation is combined with a thin-shell model developed by Lars Hoff to simulate the radial response of contrast agents subject to ultrasound. The responses of Albunex, Sonazoid, and polymer shells are analyzed through the application of techniques from dynamical systems theory such as Poincaré sections, phase portraits, and bifurcation diagrams to illustrate the qualitative dynamics and transition to chaos that occurs under certain changes in system parameters. Corresponding calculations of Lyapunov exponents provide quantitative data on the system dynamics. The results indicate that Albunex and polymer shells sufficiently stabilize the response to prevent transition to the chaotic regime throughout typical clinical ranges of ultrasound pressure and frequency. By contrast, Sonazoid shells delay the onset of chaos relative to an unshelled bubble but do not prevent it. A contour plot identifying regions of periodic and chaotic behavior over clinical ranges of ultrasound pressure and frequency is provided for Sonazoid. This work characterizes the nonlinear response of various ultrasound contrast agents, and shows that shell properties have a profound influence on the dynamics.
Variation in the production rate of biosonar signals in freshwater porpoises
Authors: Kimura Satoko , Akamatsu Tomonari , Wang Ding , Li Songhai , Wang Kexiong , Yoda Ken
Published: May 2013

The biosonar (click train) production rate of ten Yangtze finless porpoises and their behavior were examined using animal-borne data loggers. The sound production rate varied from 0 to 290 click trains per 10-min time interval. Large individual differences were observed, regardless of body size. Taken together, however, sound production did not differ significantly between daytime and nighttime. Over the 172.5 h of analyzed recordings, an average of 99.0% of the click trains were produced within intervals of less than 60 s, indicating that during a 1-min interval, the number of click trains produced by each porpoise was typically greater than one. Most of the porpoises exhibited differences in average swimming speed and depth between day and night. Swimming speed reductions and usage of short-range sonar, which relates to prey-capture attempts, were observed more often during nighttime. However, biosonar appears to be affected not only by porpoise foraging, but also by their sensory environment, i.e., the turbid Yangtze River system. These features will be useful for passive acoustic detection of the porpoises. Calculations of porpoise density or abundance should be conducted carefully because large individual differences in the sound production rate will lead to large estimation error.
An episodic memory-based solution for the acoustic-to-articulatory inversion problem
Authors: Demange Sébastien , Ouni Slim
Published: May 2013

This paper presents an acoustic-to-articulatory inversion method based on an episodic memory. An episodic memory is an interesting model for two reasons. First, it does not rely on any assumptions about the mapping function but rather it relies on real synchronized acoustic and articulatory data streams. Second, the memory inherently represents the real articulatory dynamics as observed. It is argued that the computational models of episodic memory, as they are usually designed, cannot provide a satisfying solution for the acoustic-to-articulatory inversion problem due to the insufficient quantity of training data. Therefore, an episodic memory is proposed, called generative episodic memory (G-Mem), which is able to produce articulatory trajectories that do not belong to the set of episodes the memory is based on. The generative episodic memory is evaluated using two electromagnetic articulography corpora: one for English and one for French. Comparisons with a codebook-based method and with a classical episodic memory (which is termed concatenative episodic memory) are presented in order to evaluate the proposed generative episodic memory in terms of both its modeling of articulatory dynamics and its generalization capabilities. The results show the effectiveness of the method where an overall root-mean-square error of 1.65 mm and a correlation of 0.71 are obtained for the G-Mem method. They are comparable to those of methods recently proposed.
Nonlinear effects contributing to hand-stopping tones in a horn
Authors: Ebihara Takayasu , Yoshikawa Shigeru
Published: May 2013

Hand stopping is a technique for playing the French horn while closing the bell relatively tightly using the right hand. The resulting timbre is called “penetrating” and “metallic.” The effect of hand stopping on the horn input impedance has been studied, but the tone quality has hardly ever been considered. In the present paper, the dominant physical cause of the stopped-tone quality is discussed in detail. Numerical calculations of the transmission function of the stopped-horn model and the measurements of both sound pressure and wall vibration in hand stopping are carried out. They strongly suggest that the metallicness of the stopped tone is characterized by the generation of higher harmonics extending over 10 kHz due to the rapidly corrugating waveform and that the associated wall vibration on the bell may be responsible for this higher harmonic generation. However, excitation experiments and immobilization experiments performed to elucidate the relationship between sound radiation and wall vibration deny their correlation. Instead, the measurement result of the mouthpiece pressure in hand stopping suggests that minute wave corrugations peculiar to the metallic stopped tones are probably formed by nonlinear sound propagation along the bore.
The response of phospholipid-encapsulated microbubbles to chirp-coded excitation: Implications for high-frequency nonlinear imaging
Authors: Shekhar Himanshu , Doyley Marvin M.
Published: May 2013

The current excitation strategy for harmonic and subharmonic imaging (HI and SHI) uses short sine-bursts. However, alternate pulsing strategies may be useful for enhancing nonlinear emissions from ultrasound contrast agents. The goal of this study was to corroborate the hypothesis that chirp-coded excitation can improve the performance of high-frequency HI and SHI. A secondary goal was to understand the mechanisms that govern the response of ultrasound contrast agents to chirp-coded and sine-burst excitation schemes. Numerical simulations and acoustic measurements were conducted to evaluate the response of a commercial contrast agent (Targestar-P®) to chirp-coded and sine-burst excitation (10 MHz frequency, peak pressures 290 kPa). The results of the acoustic measurements revealed an improvement in signal-to-noise ratio by 4 to 14 dB, and a two- to threefold reduction in the subharmonic threshold with chirp-coded excitation. Simulations conducted with the Marmottant model suggest that an increase in expansion-dominated radial excursion of microbubbles was the mechanism responsible for the stronger nonlinear response. Additionally, chirp-coded excitation detected the nonlinear response for a wider range of agent concentrations than sine-bursts. Therefore, chirp-coded excitation could be a viable approach for enhancing the performance of HI and SHI.
Impedance measurement of non-locally reactive samples and the influence of the assumption of local reaction
Authors: Brandão Eric , Mareze Paulo , Lenzi Arcanjo , da Silva Andrey R.
Published: May 2013

In this paper, the measurement of the absorption coefficient of non-locally reactive sample layers of thickness d1 backed by a rigid wall is investigated. The investigation is carried out with the aid of real and theoretical experiments, which assume a monopole sound source radiating sound above an infinite non-locally reactive layer. A literature search revealed that the number of papers devoted to this matter is rather limited in comparison to those which address the measurement of locally reactive samples. Furthermore, the majority of papers published describe the use of two or more microphones whereas this paper focuses on the measurement with the pressure-particle velocity sensor (PU technique). For these reasons, the assumption that the sample is locally reactive is initially explored, so that the associated measurement errors can be quantified. Measurements in the impedance tube and in a semi-anechoic room are presented to validate the theoretical experiment. For samples with a high non-local reaction behavior, for which the measurement errors tend to be high, two different algorithms are proposed in order to minimize the associated errors.
The influence of thyroarytenoid and cricothyroid muscle activation on vocal fold stiffness and eigenfrequencies
Authors: Yin Jun , Zhang Zhaoyan
Published: May 2013

The influence of the thyroarytenoid (TA) and cricothyroid (CT) muscle activation on vocal fold stiffness and eigenfrequencies was investigated in a muscularly controlled continuum model of the vocal folds. Unlike the general understanding that vocal fold fundamental frequency was determined by vocal fold tension, this study showed that vocal fold eigenfrequencies were primarily determined by vocal fold stiffness. This study further showed that, with reference to the resting state of zero strain, vocal fold stiffness in both body and cover layers increased with either vocal fold elongation or shortening. As a result, whether vocal fold eigenfrequencies increased or decreased with CT/TA activation depended on how the CT/TA interaction influenced vocal fold deformation. For conditions of strong CT activation and thus an elongated vocal fold, increasing TA contraction reduced the degree of vocal fold elongation and thus reduced vocal fold eigenfrequencies. For conditions of no CT activation and thus a resting or slightly shortened vocal fold, increasing TA contraction increased the degree of vocal fold shortening and thus increased vocal fold eigenfrequencies. In the transition region of a slightly elongated vocal fold, increasing TA contraction first decreased and then increased vocal fold eigenfrequencies.
Studying the sea with sound
Authors: Dosso Stan E. , Dettmer Jan
Published: May 2013

Because electromagnetic radiation is strongly attenuated in seawater while sound propagates efficiently to long (even global) ranges, scientists and engineers have devised many ingenious methods to use acoustics in the ocean in place of light, radio, and microwaves. Myriad underwater acoustic applications include remote sensing, remote control, communications, navigation, and source detection/localization. This talk will present a semi-historical overview of the use of sound to study the sea (including the seabed), from philosophical musings of Aristotle, through the Renaissance, two world wars, and into the modern era of advanced measurement technologies and computer analysis. A final emphasis involves on-going research to estimate seabed geophysical properties and quantify their uncertainty and variability using a variety of ocean acoustic measurements and probabilistic inversion theory.
An objective measure for the sensitivity of the room impulse response
Authors: Prislan Rok , Brunskog Jonas , Jacobsen Finn , Jeong Cheol-Ho
Published: May 2013

This study is relevant for a number of important acoustic measurements in reverberation rooms such as measurement of sound transmission and measurement of sound power levels of noise sources. From a pair of impulse responses measured in a room differing only in the position of the sound source, it might be possible to quantify the sensitivity of the room due to changes in initial conditions. Such changes are linked to mixing. The proposed measure is the maximum of the absolute value of the cross-correlation between the time windowed sections of the two impulse responses. By integrating this quantity normalized by the energy of the impulse response of the room, a single number rating is obtained. The proposed measure is examined experimentally, and the results are discussed. The results indicate that the number of absorbers and diffusers in the room influences the proposed measures systematically.
Achieving Leadership in Energy and Environmental Design acoustical requirements in a commercial office project
Authors: Salter Ethan
Published: May 2013

This paper will discuss a recently completed a Leadership in Energy and Environmental Design Commercial Interiors (LEED-CI) office renovation project in San Francisco, California. The project had multiple aims: office space, test laboratory for new materials and technologies, and teaching tool for clients and students. The owner, an acoustical consulting firm, decided on LEED-CI certification because of the belief that acoustic comfort could be achieved while simultaneously meeting other LEED requirements (e.g., design, products and materials, construction methods, and operations). Recently, acoustical requirements have been adopted into various LEED rating systems because occupant acoustic comfort in many LEED-certified buildings has been poor. The organization responsible for LEED, the US Green Building Council, is taking steps to more comprehensively adopt acoustical standards throughout their portfolio. By using the LEED Innovation in Design (ID) Pilot Credit Library, projects can attempt to achieve a wider range of potential credits. One of those credits, Pilot Credit 24, addresses acoustic comfort, including sound isolation, speech privacy, background noise, and reverberation time. The project is one of the first to achieve Pilot Credit 24 requirements. This paper will discuss the project design objectives, Pilot Credit 24 requirements, and how the project achieved those requirements.
Design, optimization, and testing of door-grille silencers
Authors: Shankar Vivek V. , Hodgson Murray
Published: May 2013

It is a common practice to install doors that have openings in them to improve cross airflow through horizontal ventilation. However, excessive outdoor noise and poor noise privacy are known associated issues. Grilles are often installed in these door openings to address this issue. While they may reduce the noise level slightly, they have proven not to be very effective. Effective silencers would be too thick to be installed in doors. This work investigates the design and development of a novel door silencer that reduces the sound transmission to acceptable limits without compromising the airflow. A model of the silencer has been designed and tested—using the Acoustics module of the COMSOL Finite Element software—in a diffuse field environment, and validated with STC ratings. The airflow was modeled using the COMSOL CFD module. The dimensions of the ventilation opening and its position in the door have also been optimized. A real prototype of the model has then been built and its performance tested. Various design guidelines have then been proposed for the design of these doors.