bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear Dependence in the Discovery of Differentially Expressed Genes
Authors: Deller J. R. , Radha Hayder , McCormick J. Justin , Wang Huiyan
Published: April 2012

Microarray data are used to determine which genes are active in response to a changing cell environment. Genes are “discovered” when they are significantly differentially expressed in the microarray data collected under the differing conditions. In one prevalent approach, all genes are assumed to satisfy a null hypothesis,ℍ0, of no difference in expression. Afalse discovery(type 1 error) occurs whenℍ0is incorrectly rejected. The quality of a detection algorithm is assessed by estimating itsnumber of false discoveries,F. Work involving the second-moment modeling of thez-value histogram (representing gene expression differentials) has shown significantly deleterious effects of intergene expression correlation on the estimate ofF. This paper suggests that nonlinear dependencies could likewise be important. With an applied emphasis, this paper extends the “moment framework” by including third-moment skewness corrections in an estimator ofF. This estimator combines observed correlation (corrected for sampling fluctuations) with the information from easily identifiable null cases. Nonlinear-dependence modeling reduces the estimation error relative to that of linear estimation. Third-moment calculations involve empirical densities of3×3covariance matrices estimated using very few samples. The principle of entropy maximization is employed to connect estimated moments toFinference. Model results are tested with BRCA and HIV data sets and with carefully constructed simulations.
A Study of Community Band Participants: Implications for Music Education
Authors: Mantie Roger
Published: April 2012

As viewed through the theoretical frameworks of Lave and Wenger’s situated learning, leisure theory, and quality-of-life theory, the purpose of this study was to examine the characteristics, attitudes and perceptions of adult community band musicians (N = 275) in nine randomly selected ensembles in order to glean insights into how music education might facilitate (a) more meaningful connections between school and community, and (b) greater lifespan engagement with participatory music making. The "typical" survey respondent was over 45, physically healthy, white, nonsmoker, nondrinker, churchgoer, well-educated, upper-middle class, married with children, active in the community, studied piano and sung in a choir at some point, learned their instrument in school, enjoyed classical music, and chose to play in the band for both musical and social reasons. Significant differences between those who learned to play their instrument in school and those who did not were minimal. Implications for music educators concerned about the "carryover" of school music to music making later in life are discussed.
The Effect of Lip Synching on Musicians’ Ability to Detect Errors in a Choral Score
Authors: Napoles Jessica
Published: April 2012

The purpose of this study was to investigate whether lip synching (moving one’s mouth but not making audible noise) would affect musicians’ ability to detect errors in a choral score. University music education majors (N = 60) listened to eight excerpts of choral music that included purposefully inserted errors and were asked to (a) lip sync the text while listening to four of the excerpts, and (b) just to listen to the other four excerpts. They listed any errors they perceived in the score. Results indicated that lip synching had no effect on musicians’ ability to detect errors (p > .05). Participants correctly identified significantly more errors in the soprano line than in the bass line (p < .001). There was a significant three-way interaction between order, lip-sync condition, and voicing, indicating that participants performed better on the second task, irrespective of lip-sync condition, but only with soprano errors.
Partnering With the NIH: Now Part of the â€œValue Propositionâ€ for Start-ups
Authors: Ferguson Steve
Published: April 2012

For many years the United States has led the world in government support for non-military research and development (R&D), especially support for work that directly relates to health and human development. Â A focal point for such federal investments to date in biomedical research has been the National Institutes of Health (NIH) along with other government laboratories and university-based research programs.Â Â  Base funding provided by the NIH alone reached Â $31.2 billion (excluding economic stimulus funds) in fiscal year 2011 with approximately 10% of this funding spent on internal NIH R&D projects (intramural research) utilizing the work of aboutÂ  6,000 scientists.Â  The balance was used to support the work of 325,000 non-government scientists (extramural research) at 3,000 various colleges, universities and research organizations such as Johns Hopkins University and others throughout the world. Each year this biomedical research leads to a large variety of novel basic and clinical research discoveries â€“ all of which generally require commercial partners in order to develop them into products for hospital, physician or patient use.Â  Thus federal laboratories and universities need and actively seek corporate partners or licensees to commercialize their federally-funded research into products in order to help fulfill their fundamental missions in healthcare, medical education and training.
Strategic Engagement of the Science-Business Media
Authors: Gunn Moira A.
Published: April 2012

As surely as the bio-enterprise can benefit from positive media coverage, it cannot thrive in the face of unanswered negative and/or inaccurate media attention. On all counts, the bio-enterprise must be able to strategically engage with the media at every stage in its life cycle. This article describes the global science-business media landscape, including traditional media and emergent social media and information in the online space. Current research is used to document the interdependence of media, how sources of information feed media coverage, the challenges of science communication in the broader context of business, and the effect of media engagement by the CEO. A strategic model is presented which relates the bio-enterprise to global media, providing a larger framework within which to develop media action plans at critical junctures in the life of the bio-enterprise. Further documented is the difference between journalistic and non-journalistic media, and how journalistic ethics and standards guidelines work with ethical persuasion practices to the benefit of the bio-enterprise.
The Art of the Cap Table
Authors: Stevens Ashley John
Published: April 2012

This article provides an overview of the impact of raising capital on the equity ownership structure of a biotechnology company. The equity ownership structure as captured in a table of capitalization determines how the fruits of success will be divided between founders, management and investors at an exit event such as an acquisition or initial public offering. The evolution of the Cap Table is captured and described through multiple financing events and scenarios and illustrates how value is allocated to the various parties involved in the transactions as the company grows and develops.
Achieving optimal financial and strategic transaction outcomes for small to mid-sized privately funded start-ups
Authors: Chen Benjamin P , Nicholas Christa
Published: April 2012

Non-dilutive funding and equity capital are two key reasons why life sciences companies pursue strategic partnerships. In fact alliances are also strong contributors to successful â€œexitsâ€, whether Mergers and Acquisitions (M&A) (~ 40% of partnerships ultimately resulted in acquisition by the partner) or stand-alone market entry (80% of approved biopharmaceutical products from 2000-2010 had a commercial partner on board)1. In the current environment, strategic alliances and funding can come from many sources, including the traditional â€œlarge pharmaâ€ universe â€“ but the question remains: How best for a small management team to gain access to and maximize success with these sources? The focus of this article is to describe how entrepreneurs can leverage external expertise, intermediaries to achieve their near term and longer-term objectives.
Opção pela técnica híbrida de Tagger para obturação de canais radiculares em clínica de pós-graduação em endodontia
Authors: Tavares Warley Luciano Fonseca , Lopes Renata Carvalho Portes , Borges Daliana Cristina Pereira Caixeta , Henriques Luiz Carlos Feitosa , Sobrinho Antônio Paulino Ribeiro
Published: April 2012

Objetivo: Avaliar a técnica de eleição para obturação de canais radiculares em clínica de pós-graduação em endodontia. Materiais e Métodos: Foram analisados prontuários de pacientes atendidos por estudantes docurso de especialização em endodontia do Instituto de Estudos da Saúde (IES) em Belo Horizonte, Brasil, entre agosto de 2009 a novembro de 2010. Resultados: Nesse período foram obturados 404 dentes. Desse total, em32 dentes (7,92%) foi utilizada a técnica da condensação lateral, em 4 (0,99%) a técnica de ondas contínuas, enquanto 368 dentes (91,08%) tiveram os canais radiculares obturados pela técnica híbrida de Tagger. Foiobservado um percentual significativo dos estudantes pelo uso da técnica híbrida de Tagger em associação à instrumentação rotatória (p<0,05). Conclusão: Os estudantes do curso de especialização em endodontiado IES tiveram uma predileção para o uso da técnica híbrida de Tagger na obturação do sistema de canais radiculares no período avaliado.Descritores: Obturação do canal radicular.
Coffee
Authors: Wasserman Gerald S. , Bradbury Allan , Cruz Theodore , Penson Simon
Published: April 2012

Coffee was originally consumed as a food in ancient Abyssinia and was presumably cultivated by Arabians in ∼ 575 AD. In 1725 the first coffee plant was planted in the Western Hemisphere, in Martinique and its cultivation expanded rapidly. Most coffees from different areas possess characteristic flavors. Commercial roasters obtain preferred flavors by blending or mixing the varieties before or after roasting. For example. Colombian coffees are considered mild and aromatic; Brazilian coffees are considered heavy body and slightly aromatic. Green coffee processing is discussed. Organic coffee cultivation has become a niche market since sustainable farming and fair trade are of current interest. Instant coffee is the dried water extract of ground, roasted coffee. Methods of decaffeinating of coffee are discussed. Biotechnology techniques are implemented through tissue culture and genetic modification to improve crops and flavor. Coffee consumption of 3‐5 cups per day show no negative effects. Chicory is a coffee substitute.
Self‐Assembling Nanotubes Consisting of Rigid Cyclic γ‐Peptides
Authors: Li Liangchun , Zhan Hongmei , Duan Pengfei , Liao Jian , Quan Junming , Hu Yu , Chen Zhongzhu , Zhu Jin , Liu Minghua , Wu Yun‐Dong , Deng Jingen
Published: April 2012

Self‐assembling cyclic peptide nanotubes (SPNs) have been extensively studied due to their potential applications in biology and material sciences. Cyclic γ‐peptides, which have a larger conformational space, have received less attention than the cyclic α‐ and β‐peptides. The self‐assembly of cyclic homo‐γ‐tetrapeptide based on cis‐3‐aminocyclohexanecarboxylic acid (γ‐Ach) residues, which can be easily synthesized by a one‐pot process is investigated. Fourier transform infrared (FTIR) and NMR analysis along with density functional theory (DFT) calculations indicate that the cyclic homo‐γ‐tetrapeptide, with a non‐planar conformation, can self‐assemble into nanotubes through hydrogen‐bond‐mediated parallel stacking. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) experiments reveal the formation of bundles of nanotubes in CH2Cl2/hexane, but individual nanotubes and bundles of only two nanotubes are obtained in water. The integration of TEG (triethylene glycol) monomethyl ether chains and cyclopeptide backbones may allow the control of width of single nanotubes.
Iridium‐Catalyzed Asymmetric Allylic Etherification and Ring‐Closing Metathesis Reaction for Enantioselective Synthesis of Chromene and 2,5‐Dihydrobenzo[b]oxepine Derivatives
Authors: He Hu , Ye Ke‐Yin , Wu Qing‐Feng , Dai Li‐Xin , You Shu‐Li
Published: April 2012

Iridium‐catalyzed asymmetric etherifications of allylic carbonates with 2‐vinylphenols and 2‐allylphenols were realized. With a catalyst generated from 2 mol% of [Ir(cod)Cl]2 (cod=cycloocta‐1,5‐diene) and 4 mol% of the phosphoramidite ligand L2, the etherification products were obtained in excellent ees and then subjected to the ring‐closing metathesis reaction providing an efficient synthesis of enantioenriched 2H‐chromene and 2,5‐dihydrobenzo[b]oxepine derivatives.
Enzyme replacement therapy improves joint motion and outcome of the 12‐min walk test in a mucopolysaccharidosis type VI patient previously treated with bone marrow transplantation
Authors: Sohn Young Bae , Park Sung Won , Kim Se‐Hwa , Cho Sung‐Yoon , Ji Sun‐Tae , Kwon Eun Kyung , Han Sun Ju , Oh Se Jung , Park Yong Jae , Ko Ah‐Ra , Paik Kyung‐Hoon , Lee Jeehun , Lee Dong Hwan , Jin Dong‐Kyu
Published: April 2012

Mucopolysaccharidosis type VI (MPS VI; Maroteaux–Lamy syndrome, OMIM #253200) is a rare disorder involving multiple organs and manifested particularly by severe skeletal abnormalities. Bone marrow transplantation (BMT) improves cardiopulmonary function and facial features, but has limited success in ameliorating skeletal abnormalities and short stature. Here, we report the outcome of enzyme replacement therapy (ERT) with recombinant human arylsulfatase‐B (ASB, Naglazyme®, BioMarin, Novato, CA) in an MPS VI patient who received BMT 10 years prior to ERT induction. Administration of weekly Naglazyme® for 18 months was effective in improving range of motion in several joints [shoulders (improvement of flexion (Right/Left): 40°/55°; improvement of extension 30°/40°; improvement of abduction 10°/10°), elbows (improvement of flexion 25°/25°; improvement of extension 10°/15°), hips (improvement of flexion 25°/10°), and knees (improvement of flexion 45°/40°; improvement of extension 50°/60°)]. Improvement in the outcome of the 12‐min walk test (70% increase) and 3‐min stair‐climbing test (29% increase) was also noted after ERT. Because ERT improved clinical features in an MPS VI patient who had undergone prior BMT, the role of ERT post successful BMT in MPS VI needs further investigation. © 2012 Wiley Periodicals, Inc.
Clinical and molecular characterization of a second case of 7p22.1 microduplication
Authors: Preiksaitiene Egle , Kasnauskiene Jurate , Ciuladaite Zivile , Tumiene Birute , Patsalis Philippos C. , Kučinskas Vaidutis
Published: April 2012

The use of high‐resolution microarray technology for investigation of patients with intellectual disability and/or congenital anomalies provided the unique possibility to identify new microdeletion/microduplication syndromes and discover the dosage sensitive genes, which are implicated in the manifestation of various genetic conditions. Microduplication of the 7p22.1 region, 1.7 Mb in size, has very recently been reported, representing the smallest interstitional 7p duplication, associated with specific facial features and speech delay. We report on a patient with an even smaller 7p22.1 de novo microduplication, 1 Mb in size, detected in a 14.5‐year‐old patient with mild intellectual disability and similar facial dysmorphism, including macrocephaly, ocular hypertelorism, low‐set ears, and other features. There are 15 RefSeq genes included in this duplication. ACTB gene is a strong candidate gene for the alteration of craniofacial development. Further cases with similar duplications will contribute to the delineation of a potential new microduplication syndrome of 7p22.1. © 2012 Wiley Periodicals, Inc.
Generation n + 1: Projected numbers of babies born to women with PKU compared to babies with PKU in the United States in 2009
Authors: Resta Robert
Published: April 2012

Newborn PKU screening has been available since the mid‐1960s, and the first group of screened babies is now a complete reproductive cohort (age 15–44). Untreated maternal PKU (MPKU) often results in significant developmental and physical disabilities in exposed fetuses, and could potentially offset some or all of the benefits produced by newborn PKU screening and dietary treatment. Based on the age distribution of the United States population in 2009, and using different estimates of PKU frequency (1/10,000; 1/15,000; 1/20,000), the projected number of babies born to women with PKU was compared to the projected number of babies born with PKU. In 2009, there were about 62,000,000 women age 15–44, with a fertility rate of 66.7 births/1,000 women. Of these women, depending on the incidence of PKU, 3,097–6,195 were estimated to have PKU, and they would have delivered 207–413 babies. In that same year, the number of births was 4,118,055, which would have resulted in 206–412 babies with PKU. Thus, in the United States, at all estimates of PKU frequency, the number of babies exposed to MPKU is equal to the number of babies born with PKU. This ratio varies with the fertility rate but is not dependent on the incidence of PKU. The benefits of newborn PKU screening and treatment could be significantly curtailed if adequate resources, education, and funding are not available to follow and monitor women with MPKU and their babies. © 2012 Wiley Periodicals, Inc.
Nosology and epidemiology in autism: Classification counts
Authors: Fisch Gene S.
Published: April 2012

Since its initial description by Kanner in 1943, the criteria by which a diagnosis of autism or autism‐like disorders was made—and their alleged etiologies portrayed—have undergone manifold changes, from a psychiatric disorder engendered by “refridgerator” parents to a neurodevelopmental disability produced in the main by genetic abnormalities. In addition, the behavioral characterization of autism has also entered the public consciousness and professional domains increasingly in the past 30 years, the effects of which we are continually coming to terms. A diagnosis of autism that once seemed quite unusual is now considered almost epidemic. Increasing numbers of individuals diagnosed with autism and related pervasive developmental disabilities will, in turn, affect the calculated prevalence of the disorder. In this essay, I attempt to account for the increasing prevalence of autism and autism‐related disorders by examining its changing criteria, the individuals and instruments used to make the diagnosis, the reliability and validity of same, and the sample sizes and other aspects of the methodology needed to make an accurate estimate of its prevalence. © 2012 Wiley Periodicals, Inc.
Superior self‐cleaning features on wool fabric using TiO2/Ag nanocomposite optimized by response surface methodology
Authors: Montazer Majid , Behzadnia Amir , Moghadam Mohammad Bameni
Published: April 2012

Wool fabrics with superior self‐cleaning properties produced using titanium dioxide/silver nanocomposite. The TiO2/Ag nanocomposite first synthesized under ultraviolet (UV) irradiation and sonication and then applied on wool fabrics along with citric acid (CA) as a crosslinking agent to stabilize the nanoparticles on the wool surface. The optimum conditions of different properties of the treated wool fabrics obtained using response surface methodology as a statistical method. The role of three independent variables including titanium dioxide/silver nanocomposite (TiO2/Ag), CA, and sodium hypophosphite evaluated to optimize the processing conditions. Fabrics color variation determined after irradiation with three diverse UV sources including sunlight, UV‐A, and UV‐C rays. Increasing the concentration of TiO2/Ag nanocomposite increased the color removal and decreased the water absorption time. Further, increasing the concentration of CA led to increase adsorption of TiO2/Ag nanocomposite on the fabric surface improved self‐cleaning features of treated wool fabrics. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Spot laser melt electrospinning of a fiber bundle composed of poly(lactide)/poly(ethylene‐co‐vinyl alcohol) pie wedge fibers
Authors: Shimada Naoki , Ogata Nobuo , Nakane Koji , Ogihara Takashi
Published: April 2012

The melt‐electrospinning system with a spot‐like carbon dioxide laser melting device was used to form fibers directly from solid‐like polymer rods. Fiber bundles were made from pie wedge fibers comprised of poly(lactide) (PLA) and poly(ethylene‐co‐vinyl alcohol) (EVOH) by gathering the fibers and twisting them together, and then melt electrospinning was performed for the bundles using the spinning system. Nanofibers with an average fiber diameter of ca. 400 nm were successfully obtained from the bundle by the optimization of manufacturing parameters such as laser output power, voltage, and collector distance. To investigate the morphological structure of the electrospun fibers, each structural component was extracted from the fibers with its solvent. It was found that three types of fibers with different morphology were produced during the melt‐electrospinning process: fibers consisting of only a PLA component, fibers consisting of only an EVOH component, and fibers consisting of a PLA/EVOH mixture. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Melt rheological and compatibility properties of recycled poly(ethylene terephthalate)/ poly(acrylonitrile‐butadiene‐styrene) blends
Authors: Wang Hai , Qian Qingrong , Jiang Xia , Liu Xinping , Xiao Liren , Huang Baoquan , Chen Qinghua
Published: April 2012

In this study, a series of maleic anhydride (MA)‐grafted poly(acrylonitrile‐butadiene‐styrene) (ABS‐g‐MAH) were prepared via a melt banbury process on a RM‐200B torque rheometer and used as a compatibilizer for recycled poly(ethylene terephthalate)/poly(acrylonitrile‐butadiene‐styrene) (R‐PET/ABS) blends. The melt rheological and compatibility properties of R‐PET/ABS blends were investigated. It had been found that 5 wt % of MA was an optimum concentration for the preparation of ABS‐g‐MAH. About 1 wt % of ABS‐g‐MAH prepared at the MA optimum conditions shows good compatibility for the basic blend of R‐PET/ABS 85/15 w/w. Rheological and SEM characterizations confirmed that the phase reversal of blends occurred at R‐PET/ABS ratio of 75/25 w/w. DMA results indicated that R‐PET was partially miscible with ABS, and ABS‐g‐MAH was an efficient compatibilizer for R‐PET/ABS blends. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Comparative analysis of probe‐based ramp metering with detector‐based and pretimed ramp metering
Authors: Kattan Lina , Saidi Saeid
Published: April 2012

In this paper, a probe‐based adaptive ramp metering approach has been developed and compared with a detector‐based and pretimed ramp metering approaches using PARAMICS microsimulation model made by Quadstone Limited. Both examined probe‐based and detector‐based ramp metering approaches adopt the same problem formulation; however, they differ by the data source that provides estimates of their input parameters. The probe‐based approach takes as main input space mean speed extracted from vehicle probes moving constantly on the entire freeway. The detector‐based approach takes the density readings directly from point detectors placed upstream and downstream of each on‐ramp. The developed approach formulates the ramp metering rates to simultaneously reduce freeway travel time and decrease delays on ramps. A dynamic weighting scheme is adopted in this formulation to give different weighting schemes to the various freeway sections and the on‐ramps. These weights are able to adjust dynamically based on prevailing and forecasted traffic conditions to give priority in each step to the sections of the freeways or/and on‐ramps experiencing critical traffic conditions. The comparative analysis of the three ramp metering approaches was conducted on an 8‐km freeway section on Highway 2 in Calgary, Alberta, Canada. The results of the analysis indicate that the probe‐based algorithm consistently outperformed the two other approaches in terms of all performance measures. The probe‐based approach is shown to exceed the performance of the detector‐based approach with a market share of vehicle probes as low as 3%. The results of the analysis are promising and show the effectiveness of developing ramp metering control algorithms taking the main input parameters from vehicle probes on the freeway. Copyright © 2012 John Wiley & Sons, Ltd.
Development and validation of a highly sensitive LC‐MS/MS‐ESI method for the determination of bicalutamide in mouse plasma: application to a pharmacokinetic study
Authors: Sharma Kuldeep , Pawar Gopal V. , Giri Sanjeev , Rajagopal Sriram , Mullangi Ramesh
Published: April 2012

A highly sensitive, rapid assay method has been developed and validated for the estimation of bicalutamide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative‐ion mode. The assay procedure involves extraction of bicalutamide and tolbutamide (internal standard, IS) from mouse plasma with a simple protein precipitation method. Chromatographic separation was achieved using an isocratic mobile phase (0.2% formic acid:acetonitrile, 35:65, v/v) at a flow rate of 0.5 mL/min on an Atlantis dC18 column (maintained at 40 ± 1°C) with a total run time of 3.0 min. The MS/MS ion transitions monitored were m/z 428.9 → 254.7 for bicalutamide and m/z 269.0 → 169.6 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 1.04 ng/mL and the linearity range extended from 1.04 to 1877 ng/mL. The intra‐ and inter‐day precisions were in the ranges of 0.49–4.68 and 2.62–4.15, respectively. Copyright © 2012 John Wiley & Sons, Ltd.
Quantitative HPLC of pigments of irregularly coloured eggshells: application to aliquots of powdered shell from quail
Authors: Gorchein A.
Published: April 2012

Twelve quail eggshells from farmed Coturnix coturnix japonica were separately ground to fine powder and two aliquots of each (average weights 13.86 mg and 51.90 mg) were extracted with formic acid. Biliverdin (38–284 pmol/mg) and protoporphyrin (841–1666 pmol/mg) were measured by HPLC. There was good agreement between the values for the corresponding samples and with those for two entire eggshells from the same source. The preparation of a homogenate as a powder from heterogeneously pigmented eggshells has the advantage that not all of the sample needs to be initially extracted for analysis and residual material can be stored in a stable form and used for repeat measurements and for longitudinal studies. Copyright © 2012 John Wiley & Sons, Ltd.
Cytotoxicity of a Novel Oil/Water Microemulsion System Loaded with Mitomycin‐C in In Vitro Lung Cancer Models
Authors: Kotmakchiev Mustafa , Kantarcı Gülten , Çetintaş Vildan B. , Ertan Gökhan
Published: April 2012

Strategy, Management and Health Policy

Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I‐III Regulatory, Quality, Manufacturing
Postmarketing Phase IV

The aim of the study was to develop a novel oil/water microemulsion system to increase the cytotoxic effect of mitomycin C (MMC) on human lung cancer cell lines through comparison to the conventional MMC solution. The microemulsion formulation was composed of soybean oil, lecithin, Tween 80, ethanol, and water. Characterization of the microemulsions was carried out by means of particle size, viscosity, conductivity, storage stability, in vitro drug release, and in vitro hemolysis. Putative anticancer activity was determined using Calu1 and A549 carcinoma cell lines with an XTT [2,3‐bis‐(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide] cell proliferation assay. Drug release from the MMC‐loaded microemulsion was sustained for more than 5 h while release from MMC solution was completed within 2 h. Based on the results of cytotoxicity study, a higher anticancer effect was observed with mitomycin C‐loaded microemulsion (MMC‐M), with IC
50 values being approximately twofold to fourfold higher than that seen with the MMC solution on Calu1 and A549 carcinoma cell lines, respectively. In conclusion, MMC microemulsion has several advantages including slower drug release, a more pronounced anticancer effect at lower MMC doses, potentially leading to lower systemic toxicity potential if leakage occurs from the tumor site.
The ecological–evolutionary interplay: density‐dependent sexual selection in a migratory songbird
Authors: Ryder Thomas B. , Fleischer Robert C. , Shriver W. Greg , Marra Peter P.
Published: April 2012

Little is understood about how environmental heterogeneity influences the spatial dynamics of sexual selection. Within human‐dominated systems, habitat modification creates environmental heterogeneity that could influence the adaptive value of individual phenotypes. Here, we used the gray catbird to examine if the ecological conditions experienced in the suburban matrix (SM) and embedded suburban parks (SP) influence reproductive strategies and the strength of sexual selection. Our results show that these habitats varied in a key ecological factor, breeding density. Moreover, this ecological factor was closely tied to reproductive strategies such that local breeding density predicted the probability that a nest would contain extra‐pair offspring. Partitioning reproductive variance showed that while within‐pair success was more important in both habitats, extra‐pair success increased the opportunity for sexual selection by 39% at higher breeding densities. Body size was a strong predictor of relative reproductive success and was under directional selection in both habitats. Importantly, our results show that the strength of sexual selection did not differ among habitats at the landscape scale but rather that fine‐scale variation in an ecological factor, breeding density, influenced sexual selection on male phenotypes. Here, we document density‐dependent sexual selection in a migratory bird and hypothesize that coarse‐scale environmental heterogeneity, in this case generated by anthropogenic habitat modification, changed the fine‐scale ecological conditions that drove the spatial dynamics of sexual selection.
Methyl 1,2‐Orthoesters as Useful Glycosyl Donors in Glycosylation Reactions: A Comparison with n‐Pent‐4‐enyl 1,2‐Orthoesters
Authors: Uriel Clara , Ventura Juan , Gómez Ana M. , López J. Cristóbal , Fraser‐Reid Bert
Published: April 2012

Mannopyranose‐derived methyl 1,2‐orthoacetates (R = Me) and ‐benzoates (R = Ph) can function as glycosyl donors – upon BF3·Et2O activation in CH2Cl2 – in glycosylation reactions with monosaccharide acceptors to afford disaccharides in good yields. In the process, glycosylation is preferred to acid‐catalyzed rearrangement leading to methyl mannopyranosides. Methyl 1,2‐orthoesters can be also used in regioselective glycosylation protocols with monosaccharide diols, in which they display good regioselectivity.
The cause of unproportionately large higher mode contributions in the inelastic seismic responses of high‐rise core‐wall buildings
Authors: Munir A. , Warnitchai P.
Published: April 2012

In the conventional seismic design of high‐rise reinforced concrete core‐wall buildings, the design demands such as design shear and bending moment in the core wall are typically determined by the response spectrum analysis procedure, and a plastic hinge is allowed to form at the wall base to limit the seismic demands. In this study, it is demonstrated by using a 40‐story core‐wall building that this conventional approach could lead to an unsafe design where the true demands—the maximum inelastic seismic demands induced by the maximum considered earthquake—could be several times greater than the design demands and be unproportionately dominated by higher vibration modes. To identify the cause of this problem, the true demands are decomposed into individual modal contributions by using the uncoupled modal response history analysis procedure. The results show that the true demands contributed by the first mode are reasonably close to the first‐mode design demands, while those contributed by other higher modes are much higher than the corresponding modal design demands. The flexural yielding in the plastic hinge at the wall base can effectively suppress the seismic demands of the first mode. For other higher modes, however, a similar yielding mechanism is either not fully mobilized or not mobilized at all, resulting in unexpectedly large contributions from higher modes. This finding suggests several possible approaches to improve the seismic design and to suppress the seismic demands of high‐rise core‐wall buildings. Copyright © 2012 John Wiley & Sons, Ltd.
Subspace system identification of support excited structures—part II: gray‐box interpretations and damage detection
Authors: Kim Junhee , Lynch Jerome P.
Published: April 2012

A theoretical framework is presented for the estimation of the physical parameters of a structure (i.e., mass, stiffness, and damping) from measured experimental data (i.e., input–output or output‐only data). The framework considers two state‐space models: a physics‐based model derived from first principles (i.e., white‐box model) and a data‐driven mathematical model derived by subspace system identification (i.e., black‐box model). Observability canonical form conversion is introduced as a powerful means to convert the data‐driven mathematical model into a physically interpretable model that is termed a gray‐box model. Through an explicit linking of the white‐box and gray‐box model forms, the physical parameters of the structural system can be extracted from the gray‐box model in the form of a finite element discretization. Prior to experimental verification, the framework is numerically verified for a multi‐DOF shear building structure. Without a priori knowledge of the structure, mass, stiffness, and damping properties are accurately estimated. Then, experimental verification of the framework is conducted using a six‐story steel frame structure under support excitation. With a priori knowledge of the lumped mass matrix, the spatial distribution of structural stiffness and damping is estimated. With an accurate estimation of the physical parameters of the structure, the gray‐box model is shown to be capable of providing the basis for damage detection. With the use of the experimental structure, the gray‐box model is used to reliably estimate changes in structural stiffness attributed to intentional damage introduced. Copyright © 2012 John Wiley & Sons, Ltd.
ICV‐transplanted human glial precursor cells are short‐lived yet exert immunomodulatory effects in mice with EAE
Authors: Kim Heechul , Walczak Piotr , Muja Naser , Campanelli James T. , Bulte Jeff W.M.
Published: April 2012

Human glial precursor cells (hGPs) have potential for remyelinating lesions and are an attractive cell source for cell therapy of multiple sclerosis (MS). To investigate whether transplanted hGPs can affect the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we evaluated the therapeutic effects of transplanted hGPs together with the in vivo fate of these cells using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). At 14 days post‐EAE induction, mice (n = 19) were intracerebroventricularly (ICV) injected with 5 × 105 hGPs that were magnetically labeled with superparamagnetic iron oxide (SPIO) particles as MR contrast agent and transduced with firefly luciferase for BLI of cell survival. Control mice (n = 18) received phosphate buffered saline (PBS) vehicle only. The severity of EAE clinical disability in the hGP‐transplanted group was significantly suppressed (P < 0.05) with concomitant inhibition of ConA and MOG‐specific T cell proliferation in the spleen. Astrogliosis was reduced and a lower activity of macrophages and/or microglia was observed in the spinal cord (P < 0.05). On MRI, SPIO signal was detected within the lateral ventricle from 1 day post‐transplantation and remained there for up to 34 days. BLI indicated that most cells did not survive beyond 5–10 days, consistent with the lack of detectable migration into the brain parenchyma and the histological presence of an abundance of apoptotic cells. Transplanted hGPs could not be detected in the spleen. We conclude that ICV transplantation of short‐lived hGPs can have a remote therapeutic effect through immunomodulation from within the ventricle, without cells directly participating in remyelination. © 2012 Wiley Periodicals, Inc.
Molecular and cellular mechanisms involved in the trypanosoma cruzi/host cell interplay
Authors: Romano Patricia Silvia , Cueto Juan Agustín , Casassa Ana Florencia , Vanrell María Cristina , Gottlieb Roberta A. , Colombo María Isabel
Published: April 2012

The protozoan parasite Trypanosoma cruzi has a complex biological cycle that involves vertebrate and invertebrate hosts. In mammals, the infective trypomastigote form of this parasite can invade several cell types by exploiting phagocytic‐like or nonphagocytic mechanisms depending on the class of cell involved. Morphological studies showed that when trypomastigotes contact macrophages, they induce the formation of plasma membrane protrusions that differ from the canonical phagocytosis that occurs in the case of noninfective epimastigotes. In contrast, when trypomastigotes infect epithelial or muscle cells, the cell surface is minimally modified, suggesting the induction of a different class of process. Lysosomal‐dependent or ‐independent T. cruzi invasion of host cells are two different models that describe the molecular and cellular events activated during parasite entry into nonphagocytic cells. In this context, we have previously shown that induction of autophagy in host cells before infection favors T. cruzi invasion. Furthermore, we demonstrate that autophagosomes and the autophagosomal protein LC3 are recruited to the T. cruzi entry sites and that the newly formed T. cruzi parasitophorous vacuole has characteristics of an autophagolysosome. This review summarizes the current knowledge of the molecular and cellular mechanisms of T. cruzi invasion in nonphagocytic cells. Based on our findings, we propose a new model in which T. cruzi takes advantage of the upregulation of autophagy during starvation to increase its successful colonization of host cells. 2012 IUBMB IUBMB Life, 2012
Development of a biodegradable bone cement for craniofacial applications
Authors: Henslee Allan M. , Gwak Dong‐Ho , Mikos Antonios G. , Kasper F. Kurtis
Published: April 2012

This study investigated the formulation of a two‐component biodegradable bone cement comprising the unsaturated linear polyester macromer poly(propylene fumarate) (PPF) and crosslinked PPF microparticles for use in craniofacial bone repair applications. A full factorial design was employed to evaluate the effects of formulation parameters such as particle weight percentage, particle size, and accelerator concentration on the setting and mechanical properties of crosslinked composites. It was found that the addition of crosslinked microparticles to PPF macromer significantly reduced the temperature rise upon crosslinking from 100.3°C ± 21.6°C to 102.7°C ± 49.3°C for formulations without microparticles to 28.0°C ± 2.0°C to 65.3°C ± 17.5°C for formulations with microparticles. The main effects of increasing the particle weight percentage from 25 to 50% were to significantly increase the compressive modulus by 37.7 ± 16.3 MPa, increase the compressive strength by 2.2 ± 0.5 MPa, decrease the maximum temperature by 9.5°C ± 3.7°C, and increase the setting time by 0.7 ± 0.3 min. Additionally, the main effects of increasing the particle size range from 0–150 μm to 150–300 μm were to significantly increase the compressive modulus by 31.2 ± 16.3 MPa and the compressive strength by 1.3 ± 0.5 MPa. However, the particle size range did not have a significant effect on the maximum temperature and setting time. Overall, the composites tested in this study were found to have properties suitable for further consideration in craniofacial bone repair applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2252–2259, 2012.
Innovative magnetic scaffolds for orthopedic tissue engineering
Authors: Panseri S. , Russo A. , Giavaresi G. , Sartori M. , Veronesi F. , Fini M. , Salter D. M. , Ortolani A. , Strazzari A. , Visani A. , Dionigi C. , Bock N. , Sandri M. , Tampieri A. , Marcacci M.
Published: April 2012

The use of magnetism in tissue engineering is a very promising approach, in fact magnetic scaffolds are able not only to support tissue regeneration, but they can be activated and work like a magnet attracting functionalized magnetic nanoparticles (MNPs) injected close to the scaffold enhancing tissue regeneration. This study aimed to assess thein vivobiocompatibility and osteointegrative properties of novel magnetic scaffolds. Two hydroxyapatite/collagen (70/30 wt %) magnetic scaffolds were magnetized with two different techniques: direct nucleation of biomimetic phase and superparamagnetic nanoparticles (MNPs) on self‐assembling collagen fibers (MAG‐A) and scaffold impregnation in ferro‐fluid solution (MAG‐B). Magnetic scaffolds were implanted in rabbit distal femoral epiphysis and tibial mid‐diaphysis. Histopathological screening showed no inflammatory reaction due to MNPs. Significantly higher bone healing rate (ΔBHR) results were observed in MAG‐A in comparison to MAG‐B. Significant differences were also found between experimental times with an increase in ΔBHR from 2 to 4 weeks for both scaffolds in trabecular bone, while only for MAG‐B (23%,p< 0.05) in cortical bone. The proposed magnetic scaffolds seem to be promising for magnetic guiding in orthopedic tissue engineering applications and they will be suitable to treat also several pathologies in regenerative medicine area. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2278–2286, 2012.
Anatomical and scanning electron microscopic investigations of the tongue and laryngeal entrance in the long‐legged buzzard (Buteo rufinus, cretzschmar, 1829)
Authors: Erdoǧan Serkan , Pèrez William , Alan Aydin
Published: April 2012

This research aimed to examine the morphological features of the tongue and laryngeal entrance of long‐legged buzzard by macroscopic and scanning electron microscopic methods. Two adult buzzards were used as material. The tongue was fairly elongated and terminated in oval shovel‐like apex. Scale‐like projections were localized on the apex and body of tongue. Both lateral sides of lingual body were contained considerably long thread‐like projections. Many orifices of lingual posterior salivary glands were discerned among scale‐like projections in median sulcus of the lingual body. Papillary crest of sharp conical papilla were observed on the between the body and root of the tongue. No conical papillae or other projections were existent on the root of the tongue, but numerous orifices of posterior salivary gland ducts were detected. In addition, orifices of anterior salivary gland ducts were present on the dorsal and lateral surfaces of the lingual body. Numerous conical papillae were observed on the caudal region of glottis and no conical papillae or any similar projection which were bordered the glottic fissure was noted. Anatomy of these organs in the long‐legged buzzard and white tailed eagle which are the member of the same family, Accipitridae, revealed very high similarity. Microsc. Res. Tech. 75:1245–1252, 2012. © 2012 Wiley Periodicals, Inc.
Detection of human bocavirus 1 and 2 from children with acute gastroenteritis in Japan
Authors: Khamrin Pattara , Thongprachum Aksara , Shimizu Hiroyuki , Okitsu Shoko , Mizuguchi Masashi , Hayakawa Satoshi , Maneekarn Niwat , Ushijima Hiroshi
Published: April 2012

This study reports the detection and the genetic characterization of HBoV, a new member in the Parvoviridae family. Among 177 fecal specimens collected from children with diarrhea younger than 5 years in Japan, 11 (6.2%) were positive for HBoV. Co‐infection with other enteric viruses (norovirus and adenovirus) was found in nine (81.8%) pediatric patients, while monoinfection by HBoV alone was detected in two (18.2%) cases. Nucleotide sequence analysis of 11 Japanese HBoV strains revealed that seven HBoV sequences were most closely related to other HBoV 1 reference strains, while the other four strains were similar to HBoV 2A. These results indicated that HBoV was one of the viral agents found in stool specimens collected from children with acute gastroenteritis and HBoV 1 and 2A circulated in Japan between 2009 and 2010 epidemic season. J. Med. Virol. 84:901–905, 2012. © 2012 Wiley Periodicals, Inc.
Prospective evaluation of a new automated nucleic acid extraction system using routine clinical respiratory specimens
Authors: Mengelle C. , Mansuy J.‐M. , Sandres‐Sauné K. , Barthe C. , Boineau J. , Izopet J.
Published: April 2012

The aim of the study was to evaluate the MagNA Pure 96™ nucleic acid extraction system using clinical respiratory specimens for identifying viruses by qualitative real‐time PCR assays. Three extraction methods were tested, that is, the MagNA Pure LC™, the COBAS Ampliprep™, and the MagNA Pure 96™ with 10‐fold dilutions of an influenza A(H1N1)pdm09 sample. Two hundred thirty‐nine respiratory specimens, 35 throat swabs, 164 nasopharyngeal specimens, and 40 broncho‐alveolar fluids, were extracted with the MagNA Pure 96™ and the COBAS Ampliprep™ instruments. Forty COBAS Ampliprep™ positive samples were also tested. Real‐time PCRs were used to identify influenza A and influenza A(H1N1)pdm09, rhinovirus, enterovirus, adenovirus, varicella zoster virus, cytomegalovirus, and herpes simplex virus. Similar results were obtained on RNA extracted from dilutions of influenza A(H1N1)pdm09 with the three systems: the MagNA Pure LC™, the COBAS Ampliprep™, and the MagNA Pure 96™. Data from clinical respiratory specimens extracted with the MagNA Pure 96™ and COBAS Ampliprep™ instruments were in 98.5% in agreement (P < 0.0001) for influenza A and influenza A(H1N1)pdm09. Data for rhinovirus were in 97.3% agreement (P < 0.0001) and in 96.8% agreement for enterovirus. They were in 100% agreement for adenovirus. Data for cytomegalovirus and HSV1‐2 were in 95.2% agreement (P < 0.0001). The MagNA Pure 96™ instrument is easy‐to‐use, reliable, and has a high throughput for extracting total nucleic acid from respiratory specimens. These extracts are suitable for molecular diagnosis with any type of real‐time PCR assay. J. Med. Virol. 84:906–911, 2012. © 2012 Wiley Periodicals, Inc.