bluuebunny/crossref_metadata_2025 huggingface dataset:
PROPAGAÇÃO DA VIDEIRA ‘NIAGARA ROSADA’ (Vitis labrusca) ENXERTADA SOBRE O PORTA-ENXERTO ‘VR-043-43’ (V. vinifera X V. rotundifolia)
Authors: BOTELHO Renato Vasconcelos , SOUZA Joacir , SCHREIDER Everton , PIRES Erasmo José Paioli , TERRA Maurilo Monteiro
Published: January 2015

Visando desenvolver uma tecnologia para antecipação da produção de mudas da videira cv. Niagara Rosada enxertada sobre o porta-enxerto ’VR-043-43’, desenvolveu-se um experimento em condições de viveiro. Foram utilizados os seguintes tratamentos: T1 – Estacas herbáceas plantadas em janeiro de 2006 e enxertadas em setembro de 2006, (enxertia de inverno); T2 – Estacas lenhosas plantadas e enxertadas simultaneamente em setembro de 2006 (enxertia de inverno); T3 – Estacas herbáceas plantadas em janeiro de 2006 e enxertadas em dezembro de 2006 (enxertia verde); T4 – Estacas herbáceas plantadas e enxertadas simultaneamente em março de 2007 (enxertia verde). Para as enxertias foram usados os métodos de inglês complicado e fenda cheia. Após 90 dias da enxertia, foram avaliadas as seguintes variáveis: porcentagem de sobrevivência, comprimento médio da brotação do enxerto e diâmetro da base da brotação. Para as variáveis porcentagem de sobrevivência e diâmetro da base da brotação os melhores resultados foram obtidos para estacas herbáceas enraizadas em janeiro e enxertia de inverno em setembro, no entanto, este tratamento atingiu apenas 43% de sobrevivência. Em relação aos métodos de enxertia, a fenda cheia se destacou para as variáveis comprimento e diâmetro da brotação. Para a variável porcentagem de sobrevivência não houve diferenças significativas entre os dois métodos de enxertia.
PRODUÇÃO DE FORRAGEM E PERFILHAMENTO EM PASTOS DE CAPIM TANZÂNIA-1 ADUBADOS COM DOSES DE NITROGÊNIO
Authors: HOESCHL André Ricardo , CANTO Marcos Weber do , BONA FILHO Amadeu , MORAES Aníbal
Published: January 2015

O experimento de pastejo foi conduzido na Fazenda Nossa Senhora Aparecida, situada no município de Astorga, região Noroeste do Paraná, Brasil. O experimento visou avaliar quatro doses de nitrogênio (N) aplicadas ao solo de pastagens de capim Tanzânia-1 (Panicum maximum Jacq.). As doses avaliadas de N foram 100, 200, 300 e 400 kg ha-1 e o delineamento experimental utilizado foi o inteiramente casualizado com duas repetições. O período experimental foi de 10/11/2001 a 15/04/2002. Os animais usados foram machos inteiros da raça Nelore e o método de pastejo empregado foi o de lotação contínua e taxa de lotação variável. A altura do pasto foi mantida o mais próximo possível de 60 cm em todas as unidades experimentais. A taxa de acúmulo de massa seca (MS) apresentou resposta linear positiva (P<0,0112) com o aumento da quantidade de N aplicada. As taxas de acúmulo foram de 76, 113, 138 e 152 kg de MS ha-1 dia-1, respectivamente para as doses de N de 100, 200, 300 e 400 kg ha-1. A produção de forragem aumentou linearmente (P<0,03) com o aumento da quantidade de N aplicada. A análise estatística revelou aumento linear (P<0,05) da massa individual por perfilho com o aumento da dose de N. A densidade populacional de perfilhos vegetativos apresentou comportamento quadrático (P<0,003) com a elevação das doses de adubo nitrogenado.
ESCALA DIAGRAMÁTICA PARA AVALIAR SEVERIDADE DE MILDIO NA SOJA
Authors: KOWATA Ligia Sayko , MAY-DE-MIO Louise Larissa , DALLA-PRIA Maristella , SANTOS Hellen Aparecida Arantes do
Published: January 2015

O míldio, causado por Peronospora manshurica, é uma doença secundária na cultura da soja, entretanto, em regiões mais frias e úmidas, tem ocorrido com maior freqüência. Neste trabalho foi desenvolvida e validada uma escala diagramática para quantificar a severidade de míldio na soja. Foram coletadas 200 folhas em Castro (PR), destas foram selecionadas 100 folhas exsicatadas em melhor estado de conservação contendo os diferentes níveis de severidade e em seguida numeradas para determinar as áreas das lesões e das folhas e calcular a severidade real por folha. A escala considerou os limites de severidade mínima e máxima observados no campo e os níveis intermediários seguiram incrementos logarítmicos, obtendo oito níveis: 0,08; 0,30; 1,10; 3,39; 12,85; 34,92; 66,13 e 87,65%. Para a validação sete avaliadores, sendo três com e quatro sem experiência estimaram a área lesionada, antes e após o uso da escala. Por meio de regressão linear os valores de severidade reais e estimados foram confrontados e os resultados de acurácia e precisão foram satisfatórios. Os valores do coeficiente de determinação após o uso da escala apresentaram aumento atingindo níveis de 0,97. Em relação ao gráfico de dispersão do erro constatou-se que em 100% dos casos houve melhora, diminuindo o número de notas acima de 10% de erro de 16 para 8,2. Ao utilizar o programa Assistat, o teste F apontou diferença estatística no R2 quando utilizada a escala, a qual mostrou-se adequada e poderá ser utilizada para avaliar a severidade em experimentos.
The data and safety monitoring board in sponsored pediatric clinical trials: practical applications
Authors: M. Lad Pramod , Dahl Rebecca
Published: January 2015

The Data and Safety Monitoring Board (DSMB) monitors the progress of clinical trials for safety and implements stopping rules as needed. Although NIH and FDA guidelines recommend the use of a DSMB for phase I, II, and III pediatric clinical trials, the manner in which the DSMB is constituted has received little attention. In this study we reviewed the Institutional Review Board (IRB) applications submitted between 2008 and 2012 at our institution (Children’s Hospital Los Angeles) for phase I, II and III studies which were multi-site, sponsored and performed under a sponsor’s Investigation New Drug Application (IND) for the type of data and safety monitoring that was being used. Our results indicate that approximately two-third of the studies used an independent DSMB, 10% utilized a sponsor’s DSMB and the remaining studies (25%) did not utilize a DSMB and relied instead on safety monitoring by the Principal Investigator (PI) and the medical monitor/director. This pattern was observed across all study phases and for blinded as well as unblinded studies. Our result suggests that a Data and Safety Monitoring Plan (DSMP), although required by the IRB, is rarely submitted by the sponsor at the time of application. Instead the DSMP is submitted to the IRB by the PI on IRB supplied templates. IRB review of these completed templates were critical to ensuring DSMB related compliance. Additionally, a significant percent of sponsored clinical trials used the PI or an individual designated as medical director/monitor, rather than constituting a DSMB.
Native architecture of the Chlamydomonas chloroplast revealed by in situ cryo-electron tomography
Authors: Engel Benjamin D , Schaffer Miroslava , Kuhn Cuellar Luis , Villa Elizabeth , Plitzko Jürgen M , Baumeister Wolfgang
Published: January 2015

Chloroplast function is orchestrated by the organelle's intricate architecture. By combining cryo-focused ion beam milling of vitreous Chlamydomonas cells with cryo-electron tomography, we acquired three-dimensional structures of the chloroplast in its native state within the cell. Chloroplast envelope inner membrane invaginations were frequently found in close association with thylakoid tips, and the tips of multiple thylakoid stacks converged at dynamic sites on the chloroplast envelope, implicating lipid transport in thylakoid biogenesis. Subtomogram averaging and nearest neighbor analysis revealed that RuBisCO complexes were hexagonally packed within the pyrenoid, with ∼15 nm between their centers. Thylakoid stacks and the pyrenoid were connected by cylindrical pyrenoid tubules, physically bridging the sites of light-dependent photosynthesis and light-independent carbon fixation. Multiple parallel minitubules were bundled within each pyrenoid tubule, possibly serving as conduits for the targeted one-dimensional diffusion of small molecules such as ATP and sugars between the chloroplast stroma and the pyrenoid matrix.
Teaching for the future
Authors: Raman Indira M
Published: January 2015

Reading and discussing classic papers can be an effective way of teaching graduate students how to learn the skills they will need for a career in research, as Indira M Raman explains.
Multiporosity flow in fractured low‐permeability rocks
Authors: Kuhlman Kristopher L. , Malama Bwalya , Heath Jason E.
Published: January 2015

A multiporosity extension of classical double and triple‐porosity fractured rock flow models for slightly compressible fluids is presented. The multiporosity model is an adaptation of the multirate solute transport model of Haggerty and Gorelick (1995) to viscous flow in fractured rock reservoirs. It is a generalization of both pseudo steady state and transient interporosity flow double‐porosity models. The model includes a fracture continuum and an overlapping distribution of multiple rock matrix continua, whose fracture‐matrix exchange coefficients are specified through a discrete probability mass function. Semianalytical cylindrically symmetric solutions to the multiporosity mathematical model are developed using the Laplace transform to illustrate its behavior. The multiporosity model presented here is conceptually simple, yet flexible enough to simulate common conceptualizations of double and triple‐porosity flow. This combination of generality and simplicity makes the multiporosity model a good choice for flow modelling in low‐permeability fractured rocks.
A Tumor Targeted Chimeric Peptide for Synergistic Endosomal Escape and Therapy by Dual‐Stage Light Manipulation
Authors: Han Kai , Lei Qi , Jia Hui‐Zhen , Wang Shi‐Bo , Yin Wei‐Na , Chen Wei‐Hai , Cheng Si‐Xue , Zhang Xian‐Zheng
Published: January 2015

In this study, a pH sensitive chimeric peptide is developed to codeliver a photosensitizer, protoporphyrin IX (PpIX), and plasmid DNA simultaneously. In the presence of matrix metalloproteinase‐2 (MMP‐2), the chimeric peptide undergoes the process of hydrolysis of PLGVR peptide sequence, exfoliation of PEG, and increase of positive charges. As a result, the chimeric peptide can be preferentially uptaken by MMP‐2 rich tumor cells. To realize synergistic effect of drug and gene delivery, a dual‐stage light irradiation strategy is developed, i.e., the short time light irradiation can efficiently enhance the endosomal escape of the chimeric peptide/PpIX/DNA complexes by the formation the reactive oxygen species (ROS), resulting in synergistic endosomal escape and improved DNA expression. In addition, due to the screened phototoxicity of PpIX, short time light irradiation does not lead to detectable changes in the cell viability. After the gene transfection, the screened phototoxicity of PpIX is subsequently stimulated by long time irradiation to achieve high synergistic efficacy of photodynamic and gene therapies. Both in vitro and in vivo studies confirm the chimeric peptide‐based nanocarrier with a good synergistic effect is a promising nanoplatform for tumor treatments.
The Impact of Aspect Ratio on the Biodistribution and Tumor Homing of Rigid Soft‐Matter Nanorods
Authors: Shukla Sourabh , Eber Fabian J. , Nagarajan Adithy S. , DiFranco Nicholas A. , Schmidt Nora , Wen Amy M. , Eiben Sabine , Twyman Richard M. , Wege Christina , Steinmetz Nicole F.
Published: January 2015

The size and shape of nanocarriers can affect their fate in vivo, but little is known about the effect of nanocarrier aspect ratio on biodistribution in the setting of cancer imaging and drug delivery. The production of nanoscale anisotropic materials is a technical challenge. A unique biotemplating approach based on of rod‐shaped nucleoprotein nanoparticles with predetermined aspect ratios (AR 3.5, 7, and 16.5) is used. These rigid, soft‐matter nanoassemblies are derived from tobacco mosaic virus (TMV) components. The role of nanoparticle aspect ratio is investigated, while keeping the surface chemistries constant, using either PEGylated stealth nanoparticles or receptor‐targeted RGD‐displaying formulations. Aspect ratio has a profound impact on the behavior of the nanoparticles in vivo and in vitro. PEGylated nanorods with the lowest aspect ratio (AR 3.5) achieve the most efficient passive tumor‐homing behavior because they can diffuse most easily, whereas RGD‐labeled particles with a medium aspect ratio (AR 7) are more efficient at tumor targeting because this requires a balance between infusibility and ligand–receptor interactions. The in vivo behavior of nanoparticles can therefore be tailored to control biodistribution, longevity, and tumor penetration by modulating a single parameter: the aspect ratio of the nanocarrier.
Obstructive sleep apnea in young infants with Down Syndrome evaluated in a Down Syndrome specialty clinic
Authors: Goffinski Alida , Stanley Maria A. , Shepherd Nicole , Duvall Nichole , Jenkinson Sandra B. , Davis Charlene , Bull Marilyn J. , Roper Randall J.
Published: January 2015

Children with Down syndrome (DS) experience congenital and functional medical issues that predispose them to obstructive sleep apnea (OSA). Research utilizing stringent age criteria among samples of infants with DS and OSA is limited. This study examines clinical correlates of OSA among infants with DS. A retrospective chart review was conducted of infants ≤6 months of age referred to a DS clinic at a tertiary children's hospital over five‐years (n = 177). Chi‐square tests and binary logistic regression models were utilized to analyze the data. Fifty‐nine infants underwent polysomnography, based on clinical concerns. Of these, 95% (56/59) had studies consistent with OSA. Among infants with OSA, 71% were identified as having severe OSA (40/56). The minimum overall prevalence of OSA among the larger group of infants was 31% (56/177). Significant relationships were found between OSA and dysphagia, congenital heart disease (CHD), prematurity, gastroesophageal reflux disease (GERD), and other functional and anatomic gastrointestinal (GI) conditions. Results indicate that odds of OSA in this group are higher among infants with GI conditions in comparison to those without. Co‐occurring dysphagia and CHD predicted the occurrence of OSA in 36% of cases with an overall predictive accuracy rate of 71%. Obstructive sleep apnea is relatively common in young infants with DS and often severe. Medical factors including GI conditions, dysphagia and CHD may help to identify infants who are at greater risk and may warrant evaluation. Further studies are needed to assess the impact of OSA in infants with DS. © 2015 Wiley Periodicals, Inc.
A Synthetic Adenylation‐Domain‐Based tRNA‐Aminoacylation Catalyst
Authors: Giessen Tobias W. , Altegoer Florian , Nebel Annika J. , Steinbach Roman M. , Bange Gert , Marahiel Mohamed A.
Published: January 2015

The incorporation of non‐proteinogenic amino acids represents a major challenge for the creation of functionalized proteins. The ribosomal pathway is limited to the 20–22 proteinogenic amino acids while nonribosomal peptide synthetases (NRPSs) are able to select from hundreds of different monomers. Introduced herein is a fusion‐protein‐based design for synthetic tRNA‐aminoacylation catalysts based on combining NRPS adenylation domains and a small eukaryotic tRNA‐binding domain (Arc1p‐C). Using rational design, guided by structural insights and molecular modeling, the adenylation domain PheA was fused with Arc1p‐C using flexible linkers and achieved tRNA‐aminoacylation with both proteinogenic and non‐proteinogenic amino acids. The resulting aminoacyl‐tRNAs were functionally validated and the catalysts showed broad substrate specificity towards the acceptor tRNA. Our strategy shows how functional tRNA‐aminoacylation catalysts can be created for bridging the ribosomal and nonribosomal worlds. This opens up new avenues for the aminoacylation of tRNAs with functional non‐proteinogenic amino acids.
Designing Elastic Organic Crystals: Highly Flexible Polyhalogenated N‐Benzylideneanilines
Authors: Ghosh Soumyajit , Mishra Manish Kumar , Kadambi Sourabh B. , Ramamurty Upadrasta , Desiraju Gautam R.
Published: January 2015

The intermolecular interactions and structural features in crystals of seven halogenated N‐benzylideneanilines (Schiff bases), all of which exhibit remarkable flexibility, were examined to identify the common packing features that are the raison d’être for the observed elasticity. The following two features, in part related, were identified as essential to obtain elastic organic crystals: 1) A multitude of weak and dispersive interactions, including halogen bonds, which may act as structural buffers for deformation through easy rupture and reformation during bending; and 2) corrugated packing patterns that would get interlocked and, in the process, prevent long‐range sliding of molecular planes.
Predicting the Switchable Screw Sense in Fluorene‐Based Polymers
Authors: Pietropaolo Adriana , Wang Yue , Nakano Tamaki
Published: January 2015

A chirality‐switching free‐energy landscape was reconstructed on a 43‐mer of poly(9,9‐dioctylfluoren‐2,7‐diyl) (PDOF). The simulations were conducted on amorphous silica surface as well as in the vacuum phase for a single chain or for a group of sixteen chains. The achiral‐to‐chiral transition occurs only on amorphous silica (activation free‐energy 35 kcal mol−1), where the enantiomeric (homochiral) basins are detected. This was supported by the experiments where effective chirality induction to PDOF using circularly polarized light (CPL) was attained only for a film deposited on a quartz glass and not for a solution or a suspension. These results indicate that interactions of PDOF with amorphous silica play a crucial role in chirality switching. Importance of chain assembling was also indicated. Theoretical ECD spectra of the enantiomeric basins containing a 51 helix reproduce the experimental spectra.
“Heterogeneity within Order” in Metal–Organic Frameworks
Authors: Furukawa Hiroyasu , Müller Ulrich , Yaghi Omar M.
Published: January 2015

Metal–organic frameworks (MOFs) are constructed by linking inorganic units with organic linkers to make extended networks. Though more than 20 000 MOF structures have been reported most of these are ordered and largely composed of a limited number of different kinds building units, and very few have multiple different building units (heterogeneous). Although heterogeneity and multiplicity is a fundamental characteristic of biological systems, very few synthetic materials incorporate heterogeneity without losing crystalline order. Thus, the question arises: how do we introduce heterogeneity into MOFs without losing their ordered structure? This Review outlines strategies for varying the building units within both the backbone of the MOF and its pores to produce the heterogeneity that is sought after. The impact this heterogeneity imparts on the properties of a MOF is highlighted. We also provide an update on the MOF industry as part of this themed issue for the 150th anniversary of BASF.
Controlling the Subtle Energy Balance in Protic Ionic Liquids: Dispersion Forces Compete with Hydrogen Bonds
Authors: Fumino Koichi , Fossog Verlaine , Stange Peter , Paschek Dietmar , Hempelmann Rolf , Ludwig Ralf
Published: January 2015

The properties of ionic liquids are determined by the energy‐balance between Coulomb‐interaction, hydrogen‐bonding, and dispersion forces. Out of a set of protic ionic liquids (PILs), including trialkylammonium cations and methylsulfonate and triflate anions we could detect the transfer from hydrogen‐bonding to dispersion‐dominated interaction between cation and anion in the PIL [(C6H13)3NH][CF3SO3]. The characteristic vibrational features for both ion‐pair species can be detected and assigned in the far‐infrared spectra. Our approach gives direct access to the relative strength of hydrogen‐bonding and dispersion forces in a Coulomb‐dominated system. Dispersion‐corrected density functional theory (DFT) calculations support the experimental findings. The dispersion forces could be quantified to contribute about 2.3 kJ mol−1 per additional methylene group in the alkyl chains of the ammonium cation.
Mechanical and barrier properties of soy protein isolate films plasticized with a mixture of glycerol and dendritic polyglycerol
Authors: Božič Mojca , Majerič Martina , Denac Matjaž , Kokol Vanja
Published: January 2015

Soy protein isolate (SPI) films plasticized with different contents of short and linear glycerol (G) and hyperbranched dendritic polyglycerol (DPG) in the presence of water were prepared for the first time with kneading and compression molding; these were analyzed in relation to their visual, morphological, microstructural, mechanical, and water‐ and oxygen‐barrier properties. It was shown that the film prepared with a mixture of 15G15DPG (where the numbers represent the weight percentage of the respective compound) had a higher tensile strength (∼14.4%), lower elongation at break (∼85.7%), and improved water‐barrier (∼54.6%) and oxygen‐barrier (∼84.1%) properties compared to the SPI film plasticized only with 30G. The attenuated total reflectance–Fourier transform infrared spectra of the plasticized SPI films indicated that such properties were related to the approximately 11.3% higher conversion of SPI from the α‐helical conformation to the intramolecular β‐sheet structures for the 15G15DPG films. This resulted in finer films with lower surface roughnesses and surface areas. On the other hand, further increases in G and DPG revealed an opposite effect and worsened the properties; this was much more pronounced by the increased DPG amount because of SPI unfolding and aggregation and resulted in microporous films. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41837.
Social inclusivity through public transportation: a strategic approach to improve quality of life in developing countries
Authors: Gunaruwan T. Lalithasiri , Jayasekera D. Harshanee W.
Published: January 2015

Welfare services such as healthcare and education are commonly recognised as determinants of physical quality of life indices during the early phases of development in the third world. In order to benefit from these services, it is important that the general public have the mobility means to access welfare provision centres. However, very low vehicle ownership under the conditions of low per‐capita incomes and large shares of population living in deep rural areas prevent the masses from accessing such services, thereby retarding the process of social development, which is reflected in the very poor physical quality of life indices in low‐income countries.

Public transportation could offer a viable and affordable solution to this apparent ambivalence. It could permit mobility for poor masses in spite of low per‐capita vehicle ownership enabled by the national income levels. The present research demonstrates this strategic niche through an econometric examination of the evolution of the physical quality of life indices such as maternal mortality, infant mortality and literacy as against the healthcare, education and affordable mobility proxies in post‐independent Sri Lanka. The country, which was then referred to as Ceylon, is often cited as a rare example of achieving social inclusion and reduced marginalisation and thereby a high social welfare standing, in spite of relatively poor per‐capita income levels. Copyright © 2015 John Wiley & Sons, Ltd.
A nanogold resonance Rayleigh scattering method for determination of trace As based on the hydride nanoreaction
Authors: Jiang Caina , Chen Chunqiang , Lu Zujun , Liu Qingye , Tang Meiling , Liang Aihui , Jiang Zhiliang
Published: January 2015

In H2SO4 solution, As(III) was reduced to arsine (AsH3) by NaBH4, and was absorbed in HAuCl4 solution to form nanogold particles (NGs) that exhibited a resonance Rayleigh scattering (RRS) effect at 370 nm. Under the selected conditions, when the As(III) concentration increased the RRS peak also increased due to the formation of more NGs. There was a linear correlation between RRS intensity and As(III) concentration in the range 6–1000 ng/mL, with a detection limit of 3 ng/mL. This new hydride generation–nanogold reaction RRS (HG–NG RRS) method was applied to determine trace amounts of As in milk samples, with satisfactory results. Copyright © 2015 John Wiley & Sons, Ltd.
Tissue distribution and excretion study of neopanaxadiol in rats by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry
Authors: Geng Cong , Yin Jian‐yuan , Yu Xiu‐hua , Liu Jing‐yan , Yang Yu‐xia , Sun De‐ya , Meng Qin , Wei Zhong‐lin , Liu Ji‐hua
Published: January 2015

Neopanaxadiol (NPD), a major ginsenoside in Panax ginseng C. A. Meyer (Araliaceae), was reported to have neuroprotective effect. In this study, a method of ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UPLC/QTOF‐MS) was developed and validated for quantitative analysis of NPD in tissues, urine and feces, using liquid–liquid extraction (LLE) to isolate NPD from different biological samples, and chromatographic separation was performed on an Agilent Zorbax Stable Bond C18 (2.1 × 50 mm, 1.8 µm) column with 0.1% formic acid in water and acetonitrile. All standard calibration curves were linear (all r2 > 0.995) within the test range. After oral administration, NPD was extensively distributed to most of the tissues without long‐term accumulation. The higher levels were observed in stomach and intestine, followed by kidney and liver. Approximately 64.56 ± 20.32% of administered dose in feces and 0.0233 ± 0.0356% in urine were found within 96 h, which indicated that the major elimination route was fecal excretion. This analytical method was applied to the study of NPD distribution and excretion in rats after oral intake for the first time. The results we found here are helpful for us to understand the pharmacological effects of NPD, as well as its toxicity. Copyright © 2014 John Wiley & Sons, Ltd.
A simple and sensitive LC‐MS/MS method for the determination of sotalol in rat plasma
Authors: Feng Zhiping , Yu Siyuan , Liu Wei , Yang Li , Liu Yang , Zhai Suodi , Wang Fang , Zhang Xianhua
Published: January 2015

A sensitive, rapid and robust HPLC method with tandem mass spectrometry (HPLC/MS/MS) detection has been developed and validated for the quantification of sotalol in rat plasma. Plasma samples were precipitated with acetonitrile before analysis. The chromatographic separation was performed on an Atlantis hydrophilic interaction liquid chromatography Silica column (50 × 2.1 mm, 3 µm) with a gradient mobile phase of 10 mm NH4COOH (containing 0.2% of formic acid) as buffer A and acetonitrile as mobile phase B. Sotalol (m/z 273.2 → 255.1) and atenolol (the internal standard, IS, m/z 267.2 → 190.1) were monitored under positive ionization mode with 5500 QTRAP. Retention time of sotalol and the IS were 2.69 and 3.43 min, respectively. The linear range was 5–500 nm based on the analysis of 0.1 mL of plasma. The intrabatch precision ranged from 1.2 to 6.1%, and the inter‐batch precision was from 3.3 to 6.5%. The coefficient of variation of IS‐normalized matrix factor was 7.6%. Experiments for stability were performed and the analyte was sufficiently stable. A run time of 6 min for each injection made it possible to analyze a high throughput of plasma samples. The assay was successfully applied to the determination of sotalol in rat plasma after a micro‐dose oral administration. Copyright © 2014 John Wiley & Sons, Ltd.
Insights into pH‐induced metabolic switch by flux balance analysis
Authors: Ivarsson Marija , Noh Heeju , Morbidelli Massimo , Soos Miroslav
Published: January 2015

Lactate accumulation in mammalian cell culture is known to impede cellular growth and productivity. The control of lactate formation and consumption in a hybridoma cell line was achieved by pH alteration during the early exponential growth phase. In particular, lactate consumption was induced even at high glucose concentrations at pH 6.8, whereas highly increased production of lactate was obtained at pH 7.8. Consequently, constraint‐based metabolic flux analysis was used to examine pH‐induced metabolic states in the same growth state. We demonstrated that lactate influx at pH 6.8 led cells to maintain high fluxes in the TCA cycle and malate‐aspartate shuttle resulting in a high ATP production rate. In contrast, under increased pH conditions, less ATP was generated and different ATP sources were utilized. Gene expression analysis led to the conclusion that lactate formation at high pH was enabled by gluconeogenic pathways in addition to facilitated glucose uptake. The obtained results provide new insights into the influence of pH on cellular metabolism, and are of importance when considering pH heterogeneities typically present in large scale industrial bioreactors. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:347–357, 2015
Expression of a collagen‐binding domain fusion protein: Effect of amino acid supplementation, inducer type, and culture conditions
Authors: Fruchtl McKinzie , Sakon Joshua , Beitle Robert
Published: January 2015

Collagen binding domain fusion proteins are of significant importance because of their potential as therapeutic biomaterials. In this paper, we investigate the production of such therapeutic proteins via fermentation of Escherichia coli on both an undefined medium and a defined medium. Defined media with amino acid supplementation provided higher amounts of therapeutic protein than undefined media with no supplementation. Additionally, utilizing lactose instead of isopropyl‐β‐d‐thio‐galactoside (IPTG) for induction and extending batch time yielded higher amounts of the model therapeutic. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:503–509, 2015
Aberrant DNA hypermethylation reduces the expression of the desmosome‐related molecule periplakin in esophageal squamous cell carcinoma
Authors: Otsubo Takeshi , Hagiwara Teruki , Tamura‐Nakano Miwa , Sezaki Takuhito , Miyake Oki , Hinohara Chihaya , Shimizu Toshio , Yamada Kazuhiko , Dohi Taeko , Kawamura Yuki I.
Published: January 2015

Periplakin (PPL), a member of the plakin family of proteins that localizes to desmosomes and intermediate filaments, is downregulated in human esophageal squamous cell carcinoma (ESCC). Little is known, however, about the molecular mechanism underlying the regulation of PPL expression and the contribution of PPL loss to the malignant property of the cancer is unclear. We demonstrated that PPL mRNA expression was significantly reduced in ESCC tissues compared with that in normal tissues. Therefore, we hypothesized that CpG hypermethylation is the cause of the downregulation of PPL. Bisulfite‐pyrosequencing of 17 cases demonstrated that the frequency of PPL methylation was higher in ESCC tissues than in normal tissues. When human ESCC cell lines were treated with 5‐aza‐2′‐deoxycytidine (5‐aza‐dC), a DNA‐methyltransferase inhibitor, PPL transcription was induced. Human KYSE270 ESCC cells do not stratify under ordinary culture conditions and rarely produce desmosomes; however, the forced expression of PPL promoted cell stratification. PPL induction also promoted adhesion to extracellular matrix but delayed cell migration. The abundance of desmosome‐like structures was greatly increased in PPL transfectant as determined by transmission electron microscopy. Very low expression of another desmosome protein EVPL in ESCC, even in PPL transfectant, also supported the significant role of PPL in desmosome formation and cell stratification. Our results first indicate that the downregulation of PPL mediated by DNA hypermethylation, which may play an important role in the loss of ESCC stratification and likely in metastatic phenotype.
An audit and feedback system for effective quality improvement in head and neck surgery: Can we become better surgeons?
Authors: Lewis Carol M. , Monroe Marcus M. , Roberts Dianna B. , Hessel Amy C. , Lai Stephen Y. , Weber Randal S.
Published: January 2015

BACKGROUND

An evaluation system was established for measuring physician performance. This study was designed to determine whether an initial evaluation with surgeon feedback improved subsequent performance.

METHODS

After an evaluation of an initial cohort of procedures (2004‐2008), surgeons were given risk‐adjusted individual feedback. Procedures in a postfeedback cohort (2009‐2010) were then assessed. Both groups were further stratified into high‐acuity procedure (HAP) and low‐acuity procedure (LAP) groups. Negative performance measures included the length of the perioperative stay (2 days or longer for LAPs and 11 days or longer for HAPs); perioperative blood transfusions; a return to the operating room within 7 days; and readmission, surgical site infections, and mortality within 30 days.

RESULTS

There were 2618 procedures in the initial cohort and 1389 procedures in the postfeedback cohort. Factors affecting performance included the surgeon, the procedure's acuity, and patient comorbidities. There were no significant differences in the proportions of LAPs and HAPs or in the prevalence of patient comorbidities between the 2 assessment periods. The mean length of stay significantly decreased for LAPs from 2.1 to 1.5 days (P = .005) and for HAPs from 10.5 to 7 days (P = .003). The incidence of 1 or more negative performance indicators decreased significantly for LAPs from 39.1% to 28.6% (P < .001) and trended downward for HAPs from 60.9% to 53.5% (P = .081).

CONCLUSIONS

Periodic assessments of performance and outcomes are essential for continual quality improvement. Significant decreases in the length of stay and negative performance indicators were seen after feedback. Therefore, an audit and feedback system may be an effective means of improving quality of care and reducing practice variability within a surgical department. Cancer 2015;121:1581–1587. © 2015 American Cancer Society.
Atypical urothelial tissue fragments in noninstrumented voided urine specimens are associated with low but significantly higher rates of urothelial neoplasia than benign‐appearing urothelial tissue fragments
Authors: Onur Irem , Rosenthal Dorothy L. , VandenBussche Christopher J.
Published: January 2015

BACKGROUND

The interpretation of urothelial tissue fragments (UTF) in voided urine (VU) specimens is controversial. If UTF contain cytomorphologically atypical cells, the diagnosis often becomes more challenging. The authors previously analyzed the outcome of patients with benign‐appearing UTF in 274 noninstrumented VU specimens. In this retrospective study, noninstrumented VU specimens containing UTF with atypical cytomorphological features (AUTF) were evaluated and compared with the previous results.

METHODS

The Johns Hopkins Hospital electronic pathology database was searched for VU cases containing UTF over a 5‐year period.

RESULTS

A total of 170 noninstrumented VU specimens containing AUTF were identified. Twenty‐four specimens had subsequent or coincidental surgical pathology specimens with the following overall rates of neoplasia: high‐grade urothelial carcinoma: 8.8% (15 specimens), low‐grade urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with urolithiasis on follow‐up. Twenty‐five cases had follow‐up cytology specimens, all of which were negative for malignancy. Of 72 cases without histopathologic, radiologic, or cytopathologic follow‐up, 62 (86.1%) had a mean clinical follow‐up of 22.5 months and 10 cases did not have clinical follow‐up.

CONCLUSIONS

The presence of AUTF in noninstrumented VU is associated with low rates of urothelial neoplasia but a statistically higher risk of urothelial neoplasia than the presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high‐grade urothelial carcinoma is significantly higher in noninstrumented VU specimens containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition, urolithiasis is associated with AUTF in a substantial percentage of noninstrumented VU specimens. Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society. Cancer (Cancer Cytopathol) 2015;123:186–192. © 2014 American Cancer Society.
Physisorption and Chemisorption on Silver Clusters
Authors: Schmidt Martin , Masson Albert , Cheng Hai‐Ping , Bréchignac Catherine
Published: January 2015

Adsorption and coadsorption studies on free silver clusters show that nitrogen physisorbs like rare gases, whereas oxygen chemisorbs with similarities and differences to bulk silver surfaces. Silver nanoparticles activate, or even dissociate adsorbed oxygen molecules. The global electron configurations of the adsorbent and adsorbate dominate the stability at small clusters. This is more important than geometry and site effects. Due to electronic shell effects and electron pairing, the activation of oxygen strongly varies with size. At more than 40 free electrons in the complex, such quantum effects start to blur. The size dependence becomes smoother and general trends govern the reactivity, which is driven by the interaction between the charge state of the nanoparticle and the charge transfer of the reaction.
A FinFET SRAM cell design with BTI robustness at high supply voltages and high yield at low supply voltages
Authors: Ebrahimi Behzad , Asadpour Reza , Afzali‐Kusha Ali , Pedram Massoud
Published: January 2015

In this paper, a SRAM cell structure which uses pMOS access transistors and predischarged bitlines is presented. By using the strained pMOS transistor technology, the degradation of the read static noise margin (SNM) at high supply voltages due to the aging, especially in the presence of symmetric stress, is suppressed. In contrast to conventional cell, the write margin of the proposed cell does not degrade considerably at low supply voltages. To assess the efficacy, the proposed cell is compared with conventional cell for two cases of unstrained and strained pMOS. A comparative study is performed using mixed mode device/circuit simulations for a gate length of 22 nm. The results show that the read SNM degradation due to the symmetric aging at the supply voltage of 1 V is about 6% after three years for the proposed strained structure, while degradations are 14%, 12%, and 11% for the unstrained proposed structure, unstrained, and strained conventional structures, respectively. In addition, the proposed cell has both read and write cell sigma yields higher than six for supply voltages ranging from 1 V down to 0.5 V while the other structures have read or write yields less than six at the minimum supply voltage. Through some work function tuning, the cell sigma yields of the other structures reach above six for both read and write while being still lower than those of the proposed structure. Copyright © 2015 John Wiley & Sons, Ltd.
Genotoxicity of mesoporous silica nanoparticles in human embryonic kidney 293 cells
Authors: Zhang Quanan , Xu Hanfeng , Zheng Shengqin , Su Mu , Wang Jiandong
Published: January 2015

Mesoporous silica nanoparticles (MSNs) have been widely evaluated for their potential use as carriers for cancer diagnosis and therapy. Understanding the toxicity of MSNs is crucial to their biomedical applications. Although several groups have reported the cytotoxicity of MSNs, the genotoxicity (inducing genetic aberrations) of MSNs in normal human cells has not been extensively investigated. Gene amplification and mutation may initiate and promote carcinogenesis, and changes in mRNA expression can affect normal human physical functions. In this study, human embryonic kidney 293 (HEK293) cells were treated overnight with MSNs at a concentration of 120 µg/mL. The cells were assayed with fluorescent in situ hybridization to check for chromosome changes and gene amplification. Mutations in the epidermal growth factor receptor 1 (EGFR1) and KRAS genes were checked with DNA sequencing. The effects of MSNs on mRNA expression were investigated with an Agilent human mRNA microarray. No chromosomal alterations or gene mutations in EGFR or KRAS were observed in the control HEK293 cells or HEK293 cells exposed to MSNs. The microarray analysis showed that MSNs significantly altered gene expression. The expression of 579 genes was upregulated and that of 1263 genes was downregulated in HEK293 cells treated with MSNs compared with the control HEK293 cells. Our findings suggest that exposure to MSNs is genotoxic to normal human cells, leading to changes in the expression of some genes. This genotoxicity may cause cellular dysfunction and certain benign diseases. We have not shown that MSN exposure induces serious genotoxicity involving carcinogenesis. Copyright © 2015 John Wiley & Sons, Ltd.
Basic Study on Receiving Light Signal by LED for Bidirectional Visible Light Communications
Authors: Suzuki Kousuke , Asahi Kensaku , Watanabe Akira
Published: January 2015

Light emitting diodes (LEDs) are now used for lighting and illumination because of features such as low power consumption and long life. Lighting equipment has only LEDs, therefore it is necessary to install a photodetector to allow bidirectional communication. In this paper, we propose reception of a light signal by means of an LED for bidirectional visible light communications. We evaluate the characteristics of the LED used as a photodetector for bidirectional visible light communications through experiments. Further, we describe the newly developed experimental system that uses LEDs as a photodetector. Experiments show that an LED can be used not only as a light source but also as a photodetector for bidirectional visible light communications.
Meat subtypes and their association with colorectal cancer: Systematic review and meta‐analysis
Authors: Carr Prudence R. , Walter Viola , Brenner Hermann , Hoffmeister Michael
Published: January 2015

Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.
High‐risk HPV testing in the management of atypical glandular cells: A systematic review and meta‐analysis
Authors: Verdoodt Freija , Jiang Xuezhi , Williams Mark , Schnatz Peter F. , Arbyn Marc
Published: January 2015

Whereas the utility of high‐risk HPV (hrHPV) testing is widely accepted in triage of women with atypical squamous lesions, its role in managing atypical glandular cells (AGC) is not fully elucidated. A systematic review and meta‐analysis were performed to evaluate the accuracy of hrHPV testing in the management of women with AGC to detect underlying high‐grade intraepithelial neoplasia or worse, and adenocarcinoma in situ or worse (AIS+). Additionally, the diagnosis of extra‐cervical cancer was considered as an outcome in this review. A bibliographic database search (PubMed, EMBASE, CENTRAL) identified twelve eligible studies. The occurrence of cervical intraepithelial neoplasia grade two or worse including AIS+ (CIN2+/AIS+), was 19.8% among women with AGC, and 55.7% among women with AGC and concurrent squamous lesions (atypical squamous cells of undetermined significance or worse, ASC‐US+). The pooled sensitivity and specificity of hrHPV‐testing with Hybrid Capture 2 (HC2) to detect CIN2+/AIS+ in women with AGC was 90.0% (95% CI = 85.1–93.4%) and 75.1% (95% CI = 64.8–83.2%), respectively. Women who were hrHPV‐negative, demonstrated an increased risk for extra‐cervical malignancy (endometrium, fallopian tube, ovary). In women of 50y and older, a hrHPV‐negative result was linked with a 18.0% chance of extra‐cervical malignancy, while the chance of cervical pre‐cancer and cancer was 0.4 and 0.0%, respectively. In conclusion, given the high risk of underlying CIN2+/AIS+, women with AGC should be referred directly to colposcopy. However, hrHPV test results in combination with the age, appears to improve the diagnostic process by distinguishing the risk for cervical versus non‐cervical lesions.
Nicotine deprivation, temporal discounting and choice consistency in heavy smokers
Authors: Roewer Imme , Wiehler Antonius , Peters Jan
Published: January 2015

The subjective value of rewards declines the longer rewards are delayed into the future (“delay discounting”). Discounting behavior varies both as a function of an individual's trait and current state. The degree of discounting has repeatedly been associated with relapse following treatment of addiction. Therefore, the effects of acute drug deprivation on discounting processes are potentially of high clinical relevance. In two testing sessions (24 hr of nicotine deprivation vs. normal smoking) 37 heavy smoking participants made choices between immediate and delayed rewards as well as between shorter and longer delayed rewards. We found no evidence for an effect of nicotine deprivation on delay discounting of potentially real monetary rewards in both types of decision tasks. Although choice stochasticity was numerically increased after deprivation, this effect was not significant (p > .1). Participants responded significantly slower after nicotine deprivation. Our study supports previous findings that choice impulsivity as measured using discounting tasks is not affected by nicotine deprivation, at least not if real monetary rewards of lower amounts are at stake.
Occurrence of fenestral diaphragms and knots in renal glomerular endothelia of diabetic mutant MafA−/−MafK+ mice as revealed in embedment‐free transmission electron microscopy
Authors: Chaiciwamongkol Kowit , Toomsan Yanyong , Arnanteerakul Tansita , Kondo Hisatake , Hipkaeo Wiphawi
Published: January 2015

Using the advantages (high contrast and transparency and efficient 3D viewing) of embedment‐free section transmission electron microscopy (TEM), the occurrence of numerous fenestral diaphragms was clearly shown in 3D en‐face viewing of the renal glomerular capillary endothelium of severe overt diabetes mellitus mice, which were generally MafA‐deficient and simultaneously MafK‐overexpressed specifically in pancreatic β‐cells. This presents another example of nephritis‐induced diaphragmed fenestrae in the renal glomerular endothelium. In addition, knot‐/umbilicus‐like structures discrete from and larger than the central knots of regular diaphragms of fenestrated endothelium were clearly demonstrated to occur randomly in the renal glomerular endothelial fenestrae of mutant mice and wild ones. The knot‐structures were revealed to be protrusions of underlining basement lamina in conventional TEM by section‐tilting observation. Microsc. Res. Tech. 78:207–212, 2015. © 2015 Wiley Periodicals, Inc.