bluuebunny/crossref_metadata_2025 huggingface dataset:
Rituximab protects podocytes and exerts anti‐proteinuric effects in rat adriamycin‐induced nephropathy independent of B‐lymphocytes
Authors: Takahashi Yuichi , Ikezumi Yohei , Saitoh Akihiko
Published: February 2016

Aim

This study was aimed at examining the effects of treatment with rituximab, a chimeric monoclonal antibody against the protein CD20, in a B‐lymphocyte independent adriamycin‐induced rat model of nephrotic syndrome. Rituximab is an emerging rescue therapy used in patients with complicated nephrotic syndrome and, therefore, we sought to elucidate the apparent B‐lymphocyte independent mechanism underlying its anti‐proteinuric effect.

Methods

Adriamycin‐induced nephropathy was established in Wistar rats by intravenously injecting 10 mg/kg of adriamycin, which were then treated with rituximab or purified human IgG weekly and euthanized on day 28. Proteinuria, glomerular expression of sphingomyelin phosphodiesterase acid‐like 3b protein, and podocyte‐related proteins were examined using immunofluorescence staining and a reverse transcription‐polymerase chain reaction.

Results

Rituximab treatment of rats with adriamycin‐induced nephropathy significantly reduced urinary protein excretion 14 to 28 days after induction of disease, compared with those treated with purified normal human IgG. Furthermore, rituximab treatment also prevented the reduction of glomerular nephrin and podocin expression on day 28. Double‐immunofluorescence staining revealed that after in vivo administration, rituximab was bound to the glomeruli, which also expressed synaptopodin or sphingomyelin phosphodiesterase, acid‐like 3b. Moreover, sphingomyelin phosphodiesterase, acid‐like 3b expression was significantly decreased on day 28 of adriamycin‐induced nephropathy, which was also prevented by rituximab.

Conclusions

This study demonstrated that rituximab directly affected glomerular podocytes and ameliorated proteinuria in adriamycin‐induced nephropathy in rats. Furthermore, protection of podocyte function by rituximab may be mediated by direct modulation of a sphingomyelin phosphodiesterase, acid‐like 3b‐dependent mechanism.
Problematising the problem: a critical interpretive review of the literature pertaining to older people with cognitive impairment who fall while hospitalised
Authors: Rushton Carole
Published: February 2016

This article presents a reflexive account by way of a critical interpretive review of the literature pertaining to falls of older people with cognitive impairment who have been hospitalised in an acute care setting. A key aim of this review was to use thematic analysis and problematisation to challenge assumptions underpinning the current falls literature and to bring into consideration alternate foci of research and new approaches to falls research. An innovative approach is used to generate descriptive and interpretive summaries of the literature which are presented graphically to reveal the prevailing themes and assumptions within. It is argued that currently, falls research in the context of cognitive impairment is constrained by scientism. Meta‐paradigmatic approaches, which have the potential to provide a better understanding of why falls may or may not occur among this particular subgroup of older people, are proposed as an alternative.
Systemic neutralization of TGF‐β attenuates osteoarthritis
Authors: Xie Liang , Tintani Francis , Wang Xiao , Li Fengfeng , Zhen Gehua , Qiu Tao , Wan Mei , Crane Janet , Chen Qianming , Cao Xu
Published: February 2016

Osteoarthritis (OA) is a major source of pain and disability worldwide with no effective medical therapy due to poor understanding of its pathogenesis. Transforming growth factor β (TGF‐β) has been reported to play a role in subchondral bone pathology and articular cartilage degeneration during the progression of OA. In this study, we demonstrated that systemic use of a TGF‐β–neutralizing antibody (1D11) attenuates OA progression by targeting subchondral bone pathological features in rodent OA models. Systemic administration of 1D11 preserves the subchondral bone microarchitecture, preventing articular cartilage degeneration by inhibition of excessive TGF‐β activity, in both subchondral bone and the circulation. Moreover, the aberrant increases in the numbers of blood vessels, nestin+ mesenchymal stromal/stem cells, and osterix+ osteoblast progenitors were normalized by 1D11 systemic injection. Thus, systemic neutralization of excessive TGF‐β ligands effectively prevented OA progression in animal models, with promising clinical implications for OA treatment.
Co‐expression of the protease furin in Nicotiana benthamiana leads to efficient processing of latent transforming growth factor‐β1 into a biologically active protein
Authors: Wilbers Ruud H. P. , Westerhof Lotte B. , van Raaij Debbie R. , van Adrichem Marloes , Prakasa Andreas D. , Lozano‐Torres Jose L. , Bakker Jaap , Smant Geert , Schots Arjen
Published: February 2016

Transforming growth factor beta (TGF‐β) is a signalling molecule that plays a key role in developmental and immunological processes in mammals. Three TGF‐β isoforms exist in humans, and each isoform has unique therapeutic potential. Plants offer a platform for the production of recombinant proteins, which is cheap and easy to scale up and has a low risk of contamination with human pathogens. TGF‐β3 has been produced in plants before using a chloroplast expression system. However, this strategy requires chemical refolding to obtain a biologically active protein. In this study, we investigated the possibility to transiently express active human TGF‐β1 in Nicotiana benthamiana plants. We successfully expressed mature TGF‐β1 in the absence of the latency‐associated peptide (LAP) using different strategies, but the obtained proteins were inactive. Upon expression of LAP‐TGF‐β1, we were able to show that processing of the latent complex by a furin‐like protease does not occur in planta. The use of a chitinase signal peptide enhanced the expression and secretion of LAP‐TGF‐β1, and co‐expression of human furin enabled the proteolytic processing of latent TGF‐β1. Engineering the plant post‐translational machinery by co‐expressing human furin also enhanced the accumulation of biologically active TGF‐β1. This engineering step is quite remarkable, as furin requires multiple processing steps and correct localization within the secretory pathway to become active. Our data demonstrate that plants can be a suitable platform for the production of complex proteins that rely on specific proteolytic processing.
Biogenesis of water splitting by photosystem II during de‐etiolation of barley (Hordeum vulgare L.)
Authors: Shevela Dmitriy , Arnold Janine , Reisinger Veronika , Berends Hans‐Martin , Kmiec Karol , Koroidov Sergey , Bue Ann Kristin , Messinger Johannes , Eichacker Lutz A.
Published: February 2016

Etioplasts lack thylakoid membranes and photosystem complexes. Light triggers differentiation of etioplasts into mature chloroplasts, and photosystem complexes assemble in parallel with thylakoid membrane development. Plastids isolated at various time points of de‐etiolation are ideal to study the kinetic biogenesis of photosystem complexes during chloroplast development. Here, we investigated the chronology of photosystem II (PSII) biogenesis by monitoring assembly status of chlorophyll‐binding protein complexes and development of water splitting via O2 production in plastids (etiochloroplasts) isolated during de‐etiolation of barley (Hordeum vulgare L.). Assembly of PSII monomers, dimers and complexes binding outer light‐harvesting antenna [PSII‐light‐harvesting complex II (LHCII) supercomplexes] was identified after 1, 2 and 4 h of de‐etiolation, respectively. Water splitting was detected in parallel with assembly of PSII monomers, and its development correlated with an increase of bound Mn in the samples. After 4 h of de‐etiolation, etiochloroplasts revealed the same water‐splitting efficiency as mature chloroplasts. We conclude that the capability of PSII to split water during de‐etiolation precedes assembly of the PSII‐LHCII supercomplexes. Taken together, data show a rapid establishment of water‐splitting activity during etioplast‐to‐chloroplast transition and emphasize that assembly of the functional water‐splitting site of PSII is not the rate‐limiting step in the formation of photoactive thylakoid membranes.
Long‐term effects of pneumococcal colonization during early childhood wheezing
Authors: Backman Katri , Piippo‐Savolainen Eija , Ollikainen Hertta , Pelli Minna , Koskela Heikki , Korppi Matti
Published: February 2016

Background

Bacterial colonization during wheezing in early childhood has been associated with short‐term relapses of wheezing, but no study has addressed the effects of Streptococcus pneumoniae colonization on long‐term outcome of wheezing. The aim of the present study was therefore to evaluate whether pneumococcal (PNC) colonization during the first wheezing episode in early childhood is a determinant of asthma, atopy or lung function in the long term.

Methods

In 1981–82 83 infants were hospitalized for first wheezing episode at <24 months of age. PNC colonization was defined as positive nasopharyngeal aspirate for S. pneumoniae either in culture or antigen detection on hospital admission. Atopy and repeated wheezing or asthma were diagnosed on all follow‐up visits from infancy until the age of 28–31 years. Spirometry was conducted at the ages of 8–10, 18–20 and 28–31 years.

Results

PNC colonization was found in 25/83 infants (30%) during hospitalization for wheezing in infancy. PNC colonization was not associated with later atopy, repeated wheezing, asthma or lung function at any time during the 30 year follow up.

Conclusion

PNC colonization during the first wheezing episode in early childhood is not a determinant of subsequent wheezing or later asthma, atopy or lung function in childhood, adolescence or adulthood.
Identification of genes involved in rice seed priming in the early imbibition stage
Authors: Cheng J. , Wang L. , Zeng P. , He Y. , Zhou R. , Zhang H. , Wang Z.
Published: February 2016

Phase II of seed imbibition is a critical process during seed priming. To identify genes involved in rice seed priming, the altered proteins between the dry and imbibed (24 h) seeds were compared using a two‐dimensional gel electrophoresis system in this study. Ten significantly changed proteins (fold change ≥ twofold; P < 0.01) were successfully identified, which could be categorised as carbohydrate and protein biosynthesis and metabolism‐related, signalling‐related, storage and stress‐related proteins. A meta‐analysis indicated that the highest expression of the identified genes was at the milk and dough stages and in the endosperm tissue. Quantitative real‐time PCR analysis showed that there was significant variation in gene expression (except FAD‐dependent oxidoreductase) in embryos during seed priming (0–48 h). The expression of genes associated with stress appeared at the early imbibition stage, while those associated with carbohydrate metabolism, protein synthesis and signalling increased at the late imbibition stage. Three identified proteins (glucose‐1‐phosphate adenylyltransferase large subunit, aminotransferase and prolamin precursor) had similar transcript and protein expression patterns in embryos. Based on phenotype and gene expression, the optimal stop time for seed priming is 24 h, when these three genes have relatively low expression, followed by significant induction during imbibition in embryos. These three genes are ideal candidate biomarkers for rice seed priming.
Photosynthetic limitation of several representative subalpine species in the Catalan Pyrenees in summer
Authors: Fernàndez‐Martínez J. , Fleck I.
Published: February 2016

Information on the photosynthetic process and its limitations is essential in order to predict both the capacity of species to adapt to conditions associated with climate change and the likely changes in plant communities. Considering that high‐mountain species are especially sensitive, three species representative of subalpine forests of the Central Catalan Pyrenees: mountain pine (Pinus uncinata Mill.), birch (Betula pendula Roth) and rhododendron (Rhododendron ferrugineum L.) were studied under conditions associated with climate change, such as low precipitation, elevated atmospheric [CO2] and high solar irradiation incident at Earth's surface, in order to detect any photosynthetic limitations. Short‐term high [CO2] increased photosynthesis rates (A) and water use efficiency (WUE), especially in birch and mountain pine, whereas stomatal conductance (gs) was not altered in either species. Birch showed photosynthesis limitation through stomatal closure related to low rainfall, which induced photoinhibition and early foliar senescence. Rhododendron was especially affected by high irradiance, showing early photosynthetic saturation in low light, highest chlorophyll content, lowest gas exchange rates and least photoprotection. Mountain pine had the highest A, photosynthetic capacity (Amax) and light‐saturated rates of net CO2 assimilation (Asat), which were maintained under reduced precipitation. Furthermore, maximum quantum yield (Fv/Fm), thermal energy dissipation, PRI and SIPI radiometric index, and ascorbate content indicated improved photoprotection with respect to the other two species. However, maximum velocity of carboxylation of RuBisco (Vcmax) indicated that N availability would be the main photosynthetic limitation in this species.
The carbonic anhydrase domain of plant mitochondrial complex I
Authors: Fromm Steffanie , Senkler Jennifer , Zabaleta Eduardo , Peterhänsel Christoph , Braun Hans‐Peter
Published: February 2016

The mitochondrial NADH dehydrogenase complex (complex I) consists of several functional domains which independently arose during evolution. In higher plants, it contains an additional domain which includes proteins resembling gamma‐type carbonic anhydrases. The Arabidopsis genome codes for five complex I‐integrated gamma‐type carbonic anhydrases (γCA1, γCA2, γCA3, γCAL1, γCAL2), but only three copies of this group of proteins form an individual extra domain. Biochemical analyses revealed that the domain is composed of one copy of either γCAL1 or γCAL2 plus two copies of the γCA1/γCA2 proteins. Thus, the carbonic anhydrase domain can have six distinct subunit configurations. Single and double mutants with respect to the γCA/γCAL proteins were employed to genetically dissect the function of the domain. New insights into complex I biology in plants will be reviewed and discussed.
Immunolocalization of the Anti‐Müllerian Hormone (AMH) in Caprine Follicles and the Effects of AMH on In Vitro Culture of Caprine Pre‐antral Follicles Enclosed in Ovarian Tissue
Authors: Rocha RMP , Lima LF , Carvalho AA , Chaves RN , Bernuci MP , Rosa‐e‐Silva ACJS , Rodrigues APR , Campello CC , Figueiredo JR
Published: February 2016

Contents

The aims of this study were to evaluate the localization, by immunohistochemistry, of the anti‐Müllerian hormone (AMH) in goat ovaries and to investigate its effects on the in vitro survival and development of caprine pre‐antral follicles enclosed in fragments of ovarian tissue. Pre‐antral follicles were cultured in vitro for 1 or 7 days in α‐MEM+ in the absence or presence of kit ligand (KL; 50 ng/ml, positive control) or AMH (50 or 150 ng/ml). The results showed that AMH was localized in oocytes and granulosa cells from the primordial follicle to antral follicle stages. Addition of AMH maintained the percentage of developing follicles, similar to that in the uncultured control; however, the percentage of developing follicles was significantly lower than that in the cultured control and KL. Nonetheless, addition of AMH to the culture medium did not affect survival rates and follicular growth. In conclusion, this study demonstrated that the expression of AMH varies according to the compartment and stage of follicular development. Furthermore, AMH inhibits the activation of caprine primordial follicles.
Stromatoporoid growth forms and Devonian reef fabrics in the Upper Devonian Alexandra Reef System, Canada – Insight on the challenges of applying Devonian reef facies models
Authors: MacNeil Alex J. , Jones Brian
Published: February 2016

Existing facies models for Devonian reef systems can be divided into high‐energy and low‐energy types. A number of assumptions have been made in the development of these models and, in some cases, criteria that distinguish important aspects of the models are poorly defined. The Upper Devonian Alexandra Reef System contains a variety of reef fabrics from different depositional environments and is ideal for studying the range of environments in which stromatoporoids thrived and the facies from these different environments. A wide variety of stromatoporoid growth forms including laminar, tabular, anastamosing laminar and tabular, domal, bulbous, dendroid, expanding conical, concave‐up whorled‐laminar, concave‐up massive tabular and platy‐multicolumnar are present in the Alexandra Reef System. The whorled‐laminar and massive tabular concave‐up growth forms are virtually undocumented from other Devonian reefs but were common in the reef front of the Alexandra, where they thrived in a low‐energy environment around and below fair‐weather wave base. In contrast, high‐energy parts of the reef margin were dominated by bioclastic rubble deposits with narrow ribbon‐like discontinuous bodies of laminar stromatoporoid framestone. In the lagoon, laminar stromatoporoids formed steep‐sided sediment‐dominated bioherms in response to sea‐level rise and flooding. Relying mostly on the different reef facies in the Alexandra system, a new classification scheme for Devonian reef fabrics has been developed. Devonian reef fabrics can be classified as being: (i) sediment‐laden metazoan dominated; (ii) metazoan–microbial dominated (boundstone); (iii) metazoan dominated (framestone); or (iv) metazoan–marine cement dominated. Distinction of these fabrics carries important sedimentary and palaeoecological implications for reconstructing the depositional environment. With examples from the Alexandra Formation, it is demonstrated that reef facies accumulated in a range of depositional environments and that the simple observation of massive stromatoporoids with or without microbial deposits does not automatically imply a high‐energy reef margin, as otherwise portrayed in a number of the existing facies models for these systems.
Effects of Nordic walking training on functional parameters in Parkinson's disease: a randomized controlled clinical trial
Authors: Monteiro E.P. , Franzoni L.T. , Cubillos D.M. , de Oliveira Fagundes A. , Carvalho A.R. , Oliveira H.B. , Pantoja P.D. , Schuch F.B. , Rieder C.R. , Martinez F.G. , Peyré‐Tartaruga L.A.
Published: February 2016

We compare the effects of Nordic walking training (NW) and Free walk (FW) on functional parameters (motor symptoms, balance) and functional mobility (Timed Up and Go at Self‐selected Speed – TUGSS, and at forced speed, TUGFS; Self‐selected Walking Speed, SSW; locomotor rehabilitation index, LRI) of Parkinson's disease (PD) patients. The study included 33 patients with clinical diagnosis of idiopathic PD, and staging between 1 and 4 in the Hoehn and Yahr scale (H&Y) randomized into two groups: NW (N = 16) and FW (N = 17) for 6 weeks. Baseline characteristics were compared trough a one‐way ANOVA. Outcomes were analyzed using the Generalized Estimation Equations (GEE) with a Bonferroni post‐hoc. Data were analyzed using SPSS v.20.0. Improvements in UPDRS III (P < 0.001), balance scores (P < 0.035), TUGSS distance (P < 0.001), TUGFS distance (P < 0.001), SSW (P < 0.001), and LRI (P < 0.001) were found for both groups. However, the NW group showed significant differences (P < 0.001) when compared to the FW group for the functional mobility. We conclude the NW improves functional parameters and walking mobility demonstrating that NW is as effective as the FW, including benefits for FW on the functional mobility of people with PD.
Teaching the assessment of normality using large easily‐generated real data sets
Authors: Kulp Christopher W. , Sprechini Gene D.
Published: February 2016

A classroom activity is presented, which can be used in teaching students statistics with an easily generated, large, real world data set. The activity consists of analyzing a video recording of an object. The colour data of the recorded object can then be used as a data set to explore variation in the data using graphs including histograms, quantile–quantile plots and scatterplots, and to indicate possible formal analyses.
SPAWNN: A Toolkit for SPatial Analysis With Self‐Organizing Neural Networks
Authors: Hagenauer Julian , Helbich Marco
Published: February 2016

This article introduces the SPAWNN toolkit, an innovative toolkit for spatial analysis with self‐organizing neural networks, which is published as free and open‐source software (http://www.spawnn.org). It extends existing toolkits in three important ways. First, the SPAWNN toolkit distinguishes between self‐organizing neural networks and spatial context models with which the networks can be combined to incorporate spatial dependence and provides implementations for both. This distinction maintains modularity and enables a multitude of useful combinations for analyzing spatial data with self‐organizing neural networks. Second, SPAWNN interactively links different self‐organizing networks and data visualizations in an intuitive manner to facilitate explorative data analysis. Third, it implements cutting‐edge clustering algorithms for identifying clusters in the trained networks. Toolkits such as SPAWNN are particularly needed when researchers and practitioners are confronted with large amounts of complex and high‐dimensional data. The computational performance of the implemented algorithms is empirically demonstrated using high‐dimensional synthetic data sets, while the practical functionality highlighting the distinctive features of the toolkit is illustrated with a case study using socioeconomic data of the city of Philadelphia, Pennsylvania.
The modified corneocyte surface area measurement as an index of epidermal barrier properties: inverse correlation with transepidermal water loss
Authors: Momota Yutaka , Shimada Kenichiro , Noguchi Azusa , Saito Akio , Nozawa Satoshi , Niina Ayaka , Tani Kenji , Azakami Daigo , Ishioka Katsumi , Sako Toshinori
Published: February 2016

Background

Corneocyte surface area (CSA) is as established parameter for skin barrier function in humans. Measurement of canine CSA has been previously reported but has not been validated.

Hypothesis/Objectives

The aim of this study was to evaluate the validity of CSA as a barrier function parameter in dogs.

Animals

Six clinically normal beagle dogs.

Methods

CSA was measured and compared with transepidermal water loss (TEWL) using sequential tape stripping of the stratum corneum as a model of acute barrier disruption. Then, CSA and TEWL were measured at four anatomical sites (groin, lower back, nasal bridge and pinna). The correlation between the two indices was also evaluated.

Results

From the results of sequential tape stripping, CSA values gradually decreased with increasing number of tape strippings. The CSA values were inversely correlated with the TEWL ones. The two indices at different sites were variable and were strongly correlated.

Conclusions and clinical importance

Canine CSA was demonstrated to be a useful parameter for the canine skin barrier function. The results from the anatomical sites imply that the cephalic sites (nasal bridge and pinna) were lower than others in skin barrier function.
Real-dihedral harmonic Maass forms and CM-values of Hilbert modular functions
Authors: Li Yingkun
Published: February 2016

In this paper, we study real-dihedral harmonic Maass forms and their Fourier coefficients. The main result expresses the values of Hilbert modular forms at twisted CM 0-cycles in terms of these Fourier coefficients. This is a twisted version of the main theorem in Bruinier and Yang [CM-values of Hilbert modular functions, Invent. Math.163(2006), 229–288] and provides evidence that the individual Fourier coefficients are logarithms of algebraic numbers in the appropriate real-quadratic field. From this result and numerical calculations, we formulate an algebraicity conjecture, which is an analogue of Stark’s conjecture in the setting of harmonic Maass forms. Also, we give a conjectural description of the primes appearing in CM-values of Hilbert modular functions.
Perpetuation of torsade de pointes in heterogeneous hearts: competing foci or re‐entry?
Authors: Vandersickel Nele , de Boer Teun P. , Vos Marc A. , Panfilov Alexander V.
Published: February 2016

Key points

The underlying mechanism of torsade de pointes (TdP) remains of debate: perpetuation may be due to (1) focal activity or (2) re‐entrant activity.

The onset of TdP correlates with action potential heterogeneities in different regions of the heart.

We studied the mechanism of perpetuation of TdP in silico using a 2D model of human cardiac tissue and an anatomically accurate model of the ventricles of the human heart.

We found that the mechanism of perpetuation TdP depends on the degree of heterogeneity. If the degree of heterogeneity is large, focal activity alone can sustain a TdP, otherwise re‐entrant activity emerges.

This result can help to understand the relationship between the mechanisms of TdP and tissue properties and may help in developing new drugs against it.

Torsade de pointes (TdP) can be the consequence of cardiac remodelling, drug effects or a combination of both. The mechanism underlying TdP is unclear, and may involve triggered focal activity or re‐entry. Recent work by our group has indicated that both cases may exist, i.e. TdPs induced in the chronic atrioventricular block (CAVB) dog model may have a focal origin or are due to re‐entry. Also it was found that heterogeneities might play an important role. In the current study we have used computational modelling to further investigate the mechanisms involved in TdP initiation and perpetuation, especially in the CAVB dog model, by the addition of heterogeneities with reduced repolarization reserve in comparison with the surrounding tissue. For this, the TNNP computer model was used for computations. We demonstrated in 2D and 3D simulations that ECGs with the typical TdP morphology can be caused by both multiple competing foci and re‐entry circuits as a result of introduction of heterogeneities, depending on whether the heterogeneities have a large or a smaller reduced repolarization reserve in comparison with the surrounding tissue. Large heterogeneities can produce ectopic TdP, while smaller heterogeneities will produce re‐entry‐type TdP.
A Mixed Interval Arithmetic/Affine Arithmetic Approach for Robust Design Optimization With Interval Uncertainty
Authors: Wang Shaobo , Qing Xiangyun
Published: February 2016

Uncertainty is ubiquitous throughout engineering design processes. Robust optimization (RO) aims to find optimal solutions that are relatively insensitive to input uncertainty. In this paper, a new approach is presented for single-objective RO problems with an objective function and constraints that are continuous and differentiable. Both the design variables and parameters with interval uncertainties are represented as affine forms. A mixed interval arithmetic (IA)/affine arithmetic (AA) model is subsequently utilized in order to obtain affine approximations for the objective and feasibility robustness constraint functions. Consequently, the RO problem is converted to a deterministic problem, by bounding all constraints. Finally, nonlinear optimization solvers are applied to obtain a robust optimal solution for the deterministic optimization problem. Some numerical and engineering examples are presented in order to demonstrate the advantages and disadvantages of the proposed approach. The main advantage of the proposed approach lies in the simplicity of the conversion from a nonlinear RO problem with interval uncertainty to a deterministic single-looped optimization problem. Although this approach cannot be applied to problems with black-box models, it requires a minimal use of IA/AA computation and applies some widely used advanced solvers to single-looped optimization problems, making it more suitable for applications in engineering fields.
Modeling Large Spatial Deflections of Slender Bisymmetric Beams in Compliant Mechanisms Using Chained Spatial-Beam Constraint Model
Authors: Chen Guimin , Bai Ruiyu
Published: February 2016

Modeling large spatial deflections of flexible beams has been one of the most challenging problems in the research community of compliant mechanisms. This work presents a method called chained spatial-beam constraint model (CSBCM) for modeling large spatial deflections of flexible bisymmetric beams in compliant mechanisms. CSBCM is based on the spatial-beam constraint model (SBCM), which was developed for the purpose of accurately predicting the nonlinear constraint characteristics of bisymmetric spatial beams in their intermediate deflection range. CSBCM deals with large spatial deflections by dividing a spatial beam into several elements, modeling each element with SBCM, and then assembling the deflected elements using the transformation defined by Tait–Bryan angles to form the whole deflection. It is demonstrated that CSBCM is capable of solving various large spatial deflection problems either the tip loads are known or the tip deflections are known. The examples show that CSBCM can accurately predict large spatial deflections of flexible beams, as compared to the available nonlinear finite element analysis (FEA) results obtained by ansys. The results also demonstrated the unique capabilities of CSBCM to solve large spatial deflection problems that are outside the range of ansys.
Toward Incorporating the Infant Weight Into Incubator's Automatic Temperature Control
Authors: Al-Naami Bassam , Al-Hinnawi Abdel-Razzak , Al-Kiswani Ahmad , Dahabreh Ala'a , Al-Assaf Faris , Kullab Mohd
Published: February 2016

A premature infant needs a stable thermal environment. This paper studies if the infant weight can be employed in the standard heat regulation system in incubators. This was done in two stages. First, a weight sensor was designed by means of using strain gauge in order to provide weight measurement. Later, a heat regulation circuit was designed and implemented by means of using a microcontroller. The humidity, environmental and skin temperature, and infant's weight are measured and used as inputs. The experiments showed that infant's weight can be successfully added to the control circuit in the incubator instrument. The results showed that infant's weight can productively contribute in temperature control with good confidence. The average standard error was equal to 0.48 °C. The results reveal that the infant's weight can contribute to increase quality assurance of incubators.
Analysis of Turbulent Natural and Mixed Convection Flows Using the v2–f Model
Authors: Kumar Singh Nikhil , Premachandran B.
Published: February 2016

The main objective of this work is to investigate the performance of the v2–f model for the predictions of turbulent natural and mixed convection flows. For this purpose, a finite volume-based flow solver is developed for a collocated grid arrangement, and the v2–f model is implemented for turbulence modeling. For natural convection flows, a tall cavity with the aspect ratio of 28.68 is selected as a test case. Mixed convection in a square cavity, ascending flow in a vertical pipe with constant wall flux, and fully developed mixed convection in a vertical channel are considered as test cases for buoyancy-driven mixed convection flows. To evaluate the performance of the v2–f model, results obtained from the present study have been compared with the existing data of experimental studies or direct numerical simulations (DNS). Results obtained from two-equation models, viz., the RNG k-ε, realizable k-ε, and SST k-ω models are also presented for comparison. Overall, the v2–f model predicts flow and heat transfer characteristics of natural and mixed convection flows satisfactorily.
Hydraulic Performance Comparison Between the Newly Designed Common Feeding and Standard Common Rail Injection Systems for Diesel Engines
Authors: Ferrari A. , Paolicelli F. , Pizzo P.
Published: February 2016

A new-generation common feeding (CF) fuel injection system without rail has been compared with the standard common rail (CR) apparatus for diesel engine passenger cars. The high-pressure pump in the CF apparatus is connected directly to the injectors, and a volume of about 2.5 cm3 is integrated at the pump delivery. Experimental tests on solenoid injectors have been carried out for the CF and CR apparatus at a hydraulic test rig. The dependence of the injected volumes and total injector leakages on the energizing time (ET) of the two systems has been investigated for different rail pressure levels. Furthermore, the measured injected flow-rates of the CF and CR systems have been compared for single and pilot–main injection events. In general, the injection performance of the two systems is very similar, even though the differences occur in the high-pressure transients. The dynamics of the pressure waves changes because the high-pressure hydraulic layouts of the two systems are different, and the propagation and reflection of the rarefaction waves, triggered by the injection events, occur in different ways. A previously developed one-dimensional (1D) code for the CF high-pressure layout has been further validated by means of a comparison with the experimental data. The effects of either a calibrated orifice installed at the pump delivery or an injector-integrated Minirail on the CF performance have been investigated by means of the model. Numerical parametrical tests have also been conducted on the pump-to-injector pipe length. The additional orifices that can be installed in the high-pressure circuit of the CF are effective, provided their diameter is smaller than the diameter of any other orifice inserted in the injector. Furthermore, the presence of a Minirail within the injector has an impact on the injected flow-rates of small injections, such as pilot, pre, after, and post, and also induces a reduction in the energy stored in the pressure waves. Another relevant active damping strategy of the pressure waves for the CF involves shortening the pump-to-injector pipe as much as possible. Finally, the fluid dynamical transients within the solenoid injector have been discussed for the CF and CR systems. The numerical time distributions of the main variables within the injector are shown to be independent of the presence of the rail in the layout.
Development of Low-Drift Nickel-Based Thermocouples for High-Temperature Applications
Authors: Scervini Michele
Published: February 2016

Recent progress on the new nickel-based thermocouples for high-temperature applications developed at the Department of Materials Science and Metallurgy in the University of Cambridge is described in this paper. Isothermal drift at temperatures above 1000 °C as a function of the thermocouple diameter has been studied for both conventional nickel-based thermocouples and the new nickel-based thermocouple. The new nickel-based thermocouple experiences a much reduced drift compared to conventional sensors. Tests in thermal cyclic conditions have been undertaken on conventional and new nickel-based thermocouples, showing a clear improvement for the new sensors at temperatures both higher and lower than 1000 °C. The improvements achievable with the new nickel-based thermocouple in both isothermal and thermal cycling conditions suggest that the new sensor can be used at high temperatures, where current conventional sensors are not reliable, as well as at temperatures lower than 1000 °C with improved performance compared to the conventional sensors.
Instrumentation Development and Validation for an Experimental Two-Phase Blowdown Facility
Authors: Hamouda Ouajih , Weaver David S. , Riznic Jovica
Published: February 2016

An experimental facility was designed and built to study the loading on steam generator tubes during a blowdown. The facility used refrigerant R-134a and measurements were taken for static and dynamic pressures as well as tube loading and temperatures. Commissioning experiments indicated that the off-the-shelf dynamic pressure transducers and load cells could not take the mechanical and thermal shock loading caused by the blowdown and produced spurious results of no value. This paper presents the instrumentation problems found, explains why they occurred, describes the remedial procedures employed, and outlines the instrumentation validation methodologies developed. The success of the instrumentation development is demonstrated in a series of experiments designed to assess the rapid transient measurement system.
Research on Metamodel-Based Global Design Optimization and Data Mining Methods
Authors: Song Liming , Guo Zhendong , Li Jun , Feng Zhenping
Published: February 2016

The turbomachinery cascades design is a typical high dimensional computationally expensive and black box problem, thus a metamodel-based design optimization and data mining method is proposed and programed in this work, which is intended to gain knowledge of design space except for optimal solutions. The method combines a Kriging-based global algorithm with data mining techniques of self-organizing map (SOM), analysis of variance (ANOVA), and parallel axis. NACA Rotor 37, a typical axial transonic rotor blade, is selected for the research. Through SOM analysis, the overall changing trend of performance indicators like isentropic efficiency, total pressure ratio, and so on for the rotor blade is nearly consistent; therefore, a single-objective design for maximizing isentropic efficiency of the rotor blade with constraints prescribed on total pressure ratio and mass flow rate is carried out. The computational fluid dynamics (CFD) evaluations needed for the Kriging-based optimization process amount to only 1/5 of that required when employing a modified differential evolution (DE) algorithm as the optimizer. The isentropic efficiency of related optimal solution is 1.74% higher than the reference design. Then, the interactions among design variables and critical performance indicators as well as common features of better solutions are analyzed via ANOVA and parallel axis. Particularly, an ANOVA-based optimization is tried, which can validate the detected significant variables and gain knowledge of subspace with minimum cost. By integrating data mining results with practical knowledge of aerodynamics, it is confirmed that the shock wave has the most significant influence on the aerodynamic performance of transonic rotor blades. The sweep in tip section is found to be responsible for slight tradeoff relation between isentropic efficiency and total pressure ratio. The combinations of forward lean, thinner section profile near the blade leading edge, and compound sweep are favorable to get better aerodynamic performance, which is validated by the configuration of optimal solution obtained by MBGO algorithm.
Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy
Authors: Andreozzi Jacqueline M. , Zhang Rongxiao , Gladstone David J. , Williams Benjamin B. , Glaser Adam K. , Pogue Brian W. , Jarvis Lesley A.
Published: February 2016

Purpose:

A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual‐field total skin electron beam therapy (TSET).

Methods:

Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge‐coupled device camera time‐gated to the Linac was used for Cherenkov emission imaging at sixty‐two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six‐dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment.

Results:

As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R2 = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent‐depth dose at midline (R2 = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated.

Conclusions:

Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.
Measurement of stiffness of standing trees and felled logs using acoustics: A review
Authors: Legg Mathew , Bradley Stuart
Published: February 2016

This paper provides a review on the use of acoustics to measure stiffness of standing trees, stems, and logs. An outline is given of the properties of wood and how these are related to stiffness and acoustic velocity throughout the tree. Factors are described that influence the speed of sound in wood, including the different types of acoustic waves which propagate in tree stems and lumber. Acoustic tools and techniques that have been used to measure the stiffness of wood are reviewed. The reasons for a systematic difference between direct and acoustic measurements of stiffness for standing trees, and methods for correction, are discussed. Other techniques, which have been used in addition to acoustics to try to improve stiffness measurements, are also briefly described. Also reviewed are studies which have used acoustic tools to investigate factors that influence the stiffness of trees. These factors include different silvicultural practices, geographic and environmental conditions, and genetics.
ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling
Authors: Wang Jun , Rouse Clay , Jasper Jeff S. , Pendergast Ann Marie
Published: February 2016

ABL kinase inhibitors could prevent breast cancer cells from breaking down bone to promote metastasis.
Bidirectional Transfer of Raltegravir in an
Ex Vivo
Human Cotyledon Perfusion Model
Authors: Vinot Cécile , Tréluyer Jean-Marc , Giraud Carole , Gavard Laurent , Peytavin Gilles , Mandelbrot Laurent
Published: February 2016

Placental transfer of the HIV integrase inhibitor raltegravir (RLT) was investigated in term human cotyledons in the maternal-to-fetal (
n
= 3) and fetal-to-maternal (
n
= 6) directions. In the maternal-to-fetal direction, the mean ± standard deviation (SD) fetal transfer rate (FTR) was 9.1% ± 1.4%, and the mean ± SD clearance index (IC), i.e., RLT FTR/antipyrine FTR, was 0.28 ± 0.05. In the fetal-to-maternal direction, the mean ± SD CI was 0.31 ± 0.09. Placental transfer of RLT was high in both directions.
OligoG CF-5/20 Disruption of Mucoid Pseudomonas aeruginosa Biofilm in a Murine Lung Infection Model
Authors: Hengzhuang Wang , Song Zhijun , Ciofu Oana , Onsøyen Edvar , Rye Philip D. , Høiby Niels
Published: February 2016

Biofilm growth is a universal survival strategy for bacteria, providing an effective and resilient approach for survival in an otherwise hostile environment. In the context of an infection, a biofilm provides resistance and tolerance to host immune defenses and antibiotics, allowing the biofilm population to survive and thrive under conditions that would destroy their planktonic counterparts. Therefore, the disruption of the biofilm is a key step in eradicating persistent bacterial infections, as seen in many types of chronic disease. In these studies, we used both
in vitro
minimum biofilm eradication concentration (MBEC) assays and an
in vivo
model of chronic biofilm infection to demonstrate the biofilm-disrupting effects of an alginate oligomer, OligoG CF-5/20. Biofilm infections were established in mice by tracheal instillation of a mucoid clinical isolate of
Pseudomonas aeruginosa
embedded in alginate polymer beads. The disruption of the biofilm by OligoG CF-5/20 was observed in a dose-dependent manner over 24 h, with up to a 2.5-log reduction in CFU in the infected mouse lungs. Furthermore,
in vitro
assays showed that 5% OligoG CF-5/20 significantly reduced the MBEC for colistin from 512 μg/ml to 4 μg/ml after 8 h. These findings support the potential for OligoG CF-5/20 as a biofilm disruption agent which may have clinical value in reducing the microbial burden in chronic biofilm infections.
A High-Affinity Native Human Antibody Disrupts Biofilm from Staphylococcus aureus Bacteria and Potentiates Antibiotic Efficacy in a Mouse Implant Infection Model
Authors: Estellés Angeles , Woischnig Anne-Kathrin , Liu Keyi , Stephenson Robert , Lomongsod Evelene , Nguyen Da , Zhang Jianzhong , Heidecker Manfred , Yang Yifan , Simon Reyna J. , Tenorio Edgar , Ellsworth Stote , Leighton Anton , Ryser Stefan , Gremmelmaier Nina Khanna , Kauvar Lawrence M.
Published: February 2016

Many serious bacterial infections are difficult to treat due to biofilm formation, which provides physical protection and induces a sessile phenotype refractory to antibiotic treatment compared to the planktonic state. A key structural component of biofilm is extracellular DNA, which is held in place by secreted bacterial proteins from the DNABII family: integration host factor (IHF) and histone-like (HU) proteins. A native human monoclonal antibody, TRL1068, has been discovered using single B-lymphocyte screening technology. It has low-picomolar affinity against DNABII homologs from important Gram-positive and Gram-negative bacterial pathogens. The disruption of established biofilm was observed
in vitro
at an antibody concentration of 1.2 μg/ml over 12 h. The effect of TRL1068
in vivo
was evaluated in a murine tissue cage infection model in which a biofilm is formed by infection with methicillin-resistant
Staphylococcus aureus
(MRSA; ATCC 43300). Treatment of the established biofilm by combination therapy of TRL1068 (15 mg/kg of body weight, intraperitoneal [i.p.] administration) with daptomycin (50 mg/kg, i.p.) significantly reduced adherent bacterial count compared to that after daptomycin treatment alone, accompanied by significant reduction in planktonic bacterial numbers. The quantification of TRL1068 in sample matrices showed substantial penetration of TRL1068 from serum into the cage interior. TRL1068 is a clinical candidate for combination treatment with standard-of-care antibiotics to overcome the drug-refractory state associated with biofilm formation, with potential utility for a broad spectrum of difficult-to-treat bacterial infections.