bluuebunny/crossref_metadata_2025 huggingface dataset:
Frágeis e Invisíveis: saúde e condições de vida de pessoas idosas privadas de liberdade
Authors: Minayo Maria Cecília de Souza , Constantino Patricia
Published: May 2024

São incontestes as relevantes contribuições que a presente obra traz, sobretudo para o campo da saúde coletiva, tanto do ponto de vista metodológico quanto do ponto de vista teórico-analítico, tornando-se leitura indispensável a quem utiliza as políticas públicas como objeto de estudo. É prodigioso como a autora nos revela seus estranhamentos e busca ampliar as conexões e os agentes numa ampla e ativa teia de significados e produção de sentidos. Seu texto é um convite à reflexão sobre as aparências, as normas instituídas, as possibilidades de subversão dos consensos, a produção de outras realidades e o acolhimento das diferenças. Também é um convite à elaboração de outros horizontes possíveis.
Heuristic algorithm for lot sizing and scheduling on identical parallel machines
Authors: Książek Roger
Published: May 2024

In this paper a newly developed heuristic algorithm for lotsizing and scheduling on identical parallel machines is presented. A basic concept and an aim of lotsizing and scheduling are described and clarified. Furthermore, models for considered problems for fixed and variable demand  as well as for one and many identical parallel machines are presented. A concept and a formal description of newly developed heuristic algorithm is described. The paper includes in details the obtained results and solutions of conducted experiments and the description of used data sets.
Assessment of the impact of 3D printed water-lubricated cutless bearings material on vibration parameters.
Authors: Blaut Jędrzej
Published: May 2024

The tested bearings were subjected to equal loads and rotational speeds, using water as the lubricant. Analysis showed that they achieved the best vibration damping at lower speeds, between 600 and 1100 rpm. Comparative studies of bearings made of different materials, such as available on the market bearings  made of rubber, bearings printed with a 3D printer from PETG, PLA, ABS or Tribo filament materials, revealed differences in their vibration damping ability and operational stability. Conclusions from the study suggest that higher vibration acceleration may increase the radius of the trajectory, which may affect the function and performance of the bearings. The importance of the operational stability of water-lubricated plain bearings cannot be assessed solely on the basis of the RMS of vibration acceleration or trajectory radius. Both of these parameters are crucial from the user's point of view, especially in the context of various applications such as electric boats.
Parallel processing of quickly and slowly mobilized reserve vesicles in hippocampal synapses
Authors: Rodriguez Gotor Juan Jose , Mahfooz Kashif , Perez-Otano Isabel , Wesseling John F
Published: May 2024

Vesicles within presynaptic terminals are thought to be segregated into a variety of readily releasable and reserve pools. The nature of the pools and trafficking between them is not well understood, but pools that are slow to mobilize when synapses are active are often assumed to feed pools that are mobilized more quickly, in a series. However, electrophysiological studies of synaptic transmission have suggested instead a parallel organization where vesicles within slowly and quickly mobilized reserve pools would separately feed independent reluctant- and fast-releasing subdivisions of the readily releasable pool. Here, we use FM-dyes to confirm the existence of multiple reserve pools at hippocampal synapses and a parallel organization that prevents intermixing between the pools, even when stimulation is intense enough to drive exocytosis at the maximum rate. The experiments additionally demonstrate extensive heterogeneity among synapses in the relative sizes of the slowly and quickly mobilized reserve pools, which suggests equivalent heterogeneity in the numbers of reluctant and fast-releasing readily releasable vesicles that may be relevant for understanding information processing and storage.
Coupling and uncoupling of midline morphogenesis and cell flow in amniote gastrulation
Authors: Asai Rieko , Prakash Vivek N , Sinha Shubham , Prakash Manu , Mikawa Takashi
Published: May 2024

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.
Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model
Authors: Xue Yunlu , Zhou Yimin , Cepko Constance L
Published: May 2024

Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are >100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP’s structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.
Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats
Authors: Cardani Silvia , Janes Tara A , Betzner William , Pagliardini Silvia
Published: May 2024

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity. Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naive rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced expression of both Task2 and Gpr4, two CO2/pH sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.
The RNA-binding activity of the TRIM-NHL protein NHL-2 is essential for miRNA-mediated gene regulation
Authors: Saadat Nasim , Colson Rhys N. , Grimme Acadia L. , Seroussi Uri , Anderson Joshua W. , Claycomb Julie M. , Wilce Matthew C. J. , McJunkin Katherine , Wilce Jacqueline A. , Boag Peter R.
Published: May 2024

The conserved TRIM-NHL protein, NHL-2, plays a key role in small RNA pathways in Caenorhabditis elegans . NHL-2 has been shown to interact with U-rich RNA through its NHL domain, but the importance to its biological function is unknown. We defined the crystal structure of the NHL domain to 1.4 Å resolution and identified residues that affect affinity for U-rich RNA. Functional analysis of an NHL-2 RNA-binding loss-of-function mutant demonstrated defects in the heterochronic pathway, suggesting that RNA binding is essential for its role in this miRNA pathway. Processing bodies were enlarged in the NHL-2 RNA-binding mutant, suggesting a defect in mRNA decay. We also identified the eIF4E binding protein IFET-1 as a strong synthetic interactor with NHL-2 and the DEAD box RNA helicase CGH-1 (DDX6), linking NHL-2 function to translation repression. We demonstrated that in the absence of NHL-2, there was an enrichment of miRNA transcripts associated with the miRNA pathway Argonaute proteins ALG-2 and ALG-2. We demonstrate that NHL-2 RNA-binding activity is essential for let-7 family miRNA-mediated translational repression. We conclude that the NHL-2, CGH-1, and IFET-1 regulatory axes work with the core miRISC components to form an effector complex that is required for some, but not all, miRNAs.
Light-driven synchronization of optogenetic clocks
Authors: Cannarsa Maria Cristina , Liguori Filippo , Pellicciotta Nicola , Frangipane Giacomo , Di Leonardo Roberto
Published: May 2024

Synthetic genetic oscillators can serve as internal clocks within engineered cells to program periodic expression. However, cell-to-cell variability introduces a dispersion in the characteristics of these clocks that drives the population to complete desynchronization. Here, we introduce the optorepressilator, an optically controllable genetic clock that combines the repressilator, a three-node synthetic network in E. coli, with an optogenetic module enabling to reset, delay, or advance its phase using optical inputs. We demonstrate that a population of optorepressilators can be synchronized by transient green light exposure or entrained to oscillate indefinitely by a train of short pulses, through a mechanism reminiscent of natural circadian clocks. Furthermore, we investigate the system’s response to detuned external stimuli observing multiple regimes of global synchronization. Integrating experiments and mathematical modeling, we show that the entrainment mechanism is robust and can be understood quantitatively from single cell to population level.
Germination Indices and Seedling Growth Parameters in Maize under Salinity Stress with Varying Concentrations of Giberellic Acid (GA)
Authors: Matter Hanim Mohi EldenAhmed , Ahmed Badr ELdin Abdelgadir Mohamad , Idris Abdelmalik Omar Ahmed
Published: May 2024

Salinity stress is one of the factors limiting seed emergence and seedling development in sunflower at New halfa scheme in East of Sudan. A study of two factors pots experiment was conducted during winter season of 2019 to evaluate germination indices and seedling growth characters of maize seeds under salinity stress with varying concentrations of synthetic growth regulator namely (GA3). The experiment was laid out according RCBD with three replications. Treatments consisted of five levels of salinity (0, 0.5, 1.0, 1.5 and 2% ) designated as Na0, Na0.5, Na1.0 ,Na1.5 and Na2.0, and  four levels of GA3 were (0, 50,75 and 100 p.pm) designated as G0, G50, G75 and G100, respectively,. The studied parameters include germination indices; daily germination (MDG), daily germination speed (DGS), final germination percentage (FGP), mean emergence time (MET), mean Energy of germination (EE), emergence index (EI), coefficient of uniformity of emergence (CUE) and vigour index (SVI). Also, seedling fresh and dry weight, shoot length and root length were measured, and the shoot/root ratio was calculated. The negative effects of salinity stress significantly decreased germination indices and seedlings growth characters in a dose dependent manner. The results showed that, application of GA3 at medium levels concentration (specify those doses) increased all studied parameters. In conclusion, application of high Ga3 levels enhanced all germination indices and seedlings growth characters while high salinity levels reduced these traits of maize seeds. Such result has made the base for further study that should be conducted in different seasons with different growth regulators involving different parameters of other crops.
Assessing Diet & Trophic Position of Fish in Chenderoh Reservoir, Malaysia: SCA & SIA Approach
Authors: Sultana Muneera , Aziz Amirul Aizal Abdul , Fadzil Nurul Fazlinda Mohd , Rosli Farah Mastura , Koon Yap Soon , Fadhlullah Widad , Hashim Zarul Hazrin Bin
Published: May 2024

The present study assessed and compared the diet and trophic positions (TP) of two carnivorous fish H. macrolepidota and C. ocellaris from Chenderoh Reservoir, Malaysia. The focal goal of the study was to understand the effects of invasive non-indigenous species (NIS), C. ocellaris, on the native indigenous (IS) fish species, H. macrolepidota. Data were acquired from September 2014 to February 2015 within the study area. The assessment was grounded in stomach content analysis (SCA) and stable isotope analysis (SIA), which collectively clarified the feeding habits and trophic positions (TP) of these selected fish. In total, 184 fish samples (comprising 64 individuals of H. macrolepidota and 120 individuals of C. ocellaris) underwent stomach content analysis (SCA). Additionally, 24 individuals (12 of H. macrolepidota and 12 of C. ocellaris), sampled from December 2014 to February 2015, were selected for stable isotope analysis (SIA). The mean RGL values for H. macrolepidota and C ocellaris were 0.98 ± 0.18 and 1.10 ± 0.15 (Mean ± SD), respectively, aligning with known ranges for carnivorous fish. These values also clarified that both species occupy higher TP in the food web as tertiary or quaternary consumers. SCA findings also revealed that fish and crustaceans were the predominant food categories for H. macrolepidota, while C. ocellaris predominantly fed on fish. The mean stomach fullness index (MSF) and the gastrosomatic index (GSI) corroborated the differences in the foraging performance of the fishes, with C. ocellaris having a higher MSF (2.03) compared to H. macrolepidota (0.65). These implied that C. ocellaris had plentiful of food and encountered fewer diet-related challenges in the ecosystem. From SIA, δ13C values indicated that the primary carbon sources for both species are C3 plants, particularly aquatic vegetation. Further, δ15N values further ensured that both H. macrolepidota and C. ocellaris are carnivorous in nature and occupy higher TP in the ecosystem.
The Association between Dietary Intake and Lifestyle Patterns of People with Type 2 Diabetes Mellitus in Manipur, India
Authors: Chanu Mongjam Priyangka , Singh Namita
Published: May 2024

The aim of the study was to examine the association between dietary intake and lifestyle pattern of diabetes patients in Manipur. Tribal and non tribal respondents between 45-64 years of age were randomly selected from the Regional Institute of Medical Sciences (RIMS) Hospital Manipur. Total number of 200 study subjects, 100 tribal and 100 non tribal subjects constituted the study. The information was collected on socio-demographic profile, clinical, anthropometric measurements and dietary intakes of the patients by using interview schedule and 24-hour dietary recall methods. The data were analyzed and tabulated using statistical tools such as frequency, percentage, mean, standard deviation and Pearson’s correlation test. The key results indicate that alcohol consumption, elevated triglycerides levels, low energy, oils and sugar intake were notably linked with the prevalence of diabetes. Additionally, low calcium intake, particularly among non tribal individuals, demonstrated a significant correlation with elevated Fasting Blood Glucose (FBG) levels, suggesting a potential risk factor for Type 2 diabetes. Moreover, low calcium intake among the non-tribal community was associated with increased Post Prandial (PP) test results, indicating a rise in post-meal glucose levels. Notably, tribal energy intake and non-tribal protein consumption were significantly associated with HbA1c levels, reflecting their impact on glycemic control.
Effect of Drought Stress on Morpho Phenological and Yield Parameters in Sorghum Genotypes
Authors: R Navyashree , U V Mummigatti , P Nethra , B Basavaraj , N G Hanamaratti
Published: May 2024

Drought stress is a major challenge for sorghum production, particularly during the reproductive stage. This study investigated the effects of drought stress on sorghum genotypes, focusing on their morpho-phenological characteristics and yield parameters. A field experiment was conducted over two rabi seasons (2021-22 and 2022-23) at the University of Agricultural Science, Dharwad, India. Twenty sorghum genotypes were evaluated under both irrigated and rainfed conditions using a split-plot design with two replications. Water stress reduced sorghum plant height, with a mean height of 190.41 cm under irrigated conditions and 176.50 cm under rainfed conditions at 90 days after sowing. Water stress advanced the physiological maturity by 10 days compared to irrigated condition. Yield parameters revealed significant differences, the mean grain yield was 70.23 g/plant for irrigated conditions and 54.54 g/plant for rainfed conditions. Water stress also had an impact on harvest index, with irrigated conditions having a mean harvest index of 30.91% and rainfed conditions having a mean harvest index of 28.13%. Genotypes by overall performance Phule Anuradha, BJV 44, and M-35-1 tolerated water stress, by minimizing yield reduction by drought.
Identification of Quaternary Shape Memory Alloys with Near‐Zero Thermal Hysteresis and Unprecedented Functional Stability
Authors: Zarnetta Robert , Takahashi Ryota , Young Marcus L. , Savan Alan , Furuya Yasubumi , Thienhaus Sigurd , Maaß Burkhard , Rahim Mustafa , Frenzel Jan , Brunken Hayo , Chu Yong S. , Srivastava Vijay , James Richard D. , Takeuchi Ichiro , Eggeler Gunther , Ludwig Alfred
Published: May 2010

Improving the functional stability of shape memory alloys (SMAs), which undergo a reversible martensitic transformation, is critical for their applications and remains a central research theme driving advances in shape memory technology. By using a thin‐film composition‐spread technique and high‐throughput characterization methods, the lattice parameters of quaternary Ti–Ni–Cu–Pd SMAs and the thermal hysteresis are tailored. Novel alloys with near‐zero thermal hysteresis, as predicted by the geometric non‐linear theory of martensite, are identified. The thin‐film results are successfully transferred to bulk materials and near‐zero thermal hysteresis is observed for the phase transformation in bulk alloys using the temperature‐dependent alternating current potential drop method. A universal behavior of hysteresis versus the middle eigenvalue of the transformation stretch matrix is observed for different alloy systems. Furthermore, significantly improved functional stability, investigated by thermal cycling using differential scanning calorimetry, is found for the quaternary bulk alloy Ti50.2Ni34.4Cu12.3Pd3.1.
Use of Reversal Nanoimprinting of Nanoparticles to Prepare Flexible Waveguide Sensors Exhibiting Enhanced Scattering of the Surface Plasmon Resonance
Authors: Wan Dehui , Chen Hsuen‐Li , Lai Yu‐Ting , Yu Chen‐Chieh , Lin King‐Fu
Published: May 2010

A flexible surface plasmon resonance (SPR)‐based scattering waveguide sensor is prepared by directly imprinting hollow gold nanoparticles (NPs) and solid gold NPs onto flexible polycarbonate (PC) plates—without any surface modification—using a modified reversal nanoimprint lithography technology. Controlling the imprinting conditions, including temperature and pressure, allows for the fine adjustment of the depths of the embedded metal NPs and their SPR properties. This patterning approach exhibits a resolution down to the submicrometer level. A 3D finite‐difference time domain simulation is used to examine the optical behavior of light propagating parallel to the air/substrate interface within the near‐field regime. Consistent with the simulations, almost an order of magnitude enhancement in the scattering signal after transferring the metal NPs from the glass mold to the PC substrate is obtained experimentally. The enhanced signal is attributed to the particles' strong scattering of the guiding‐mode waves (within the waveguide) and the evanescent wave (above the waveguide) simultaneously. Finally, the imprinting conditions are optimized to obtain a strongly scattering bio/chemical waveguide sensor.
Polymer Photovoltaics with Alternating Copolymer/Fullerene Blends and Novel Device Architectures
Authors: Inganäs Olle , Zhang Fengling , Tvingstedt Kristofer , Andersson Lars Mattias , Hellström Stefan , Andersson Mats R.
Published: May 2010

The synthesis of novel conjugated polymers, designed for the purpose of photovoltaic energy conversion, and their properties in polymer/fullerene materials and photovoltaic devices are reviewed. Two families of main‐chain polymer donors, based on fluorene or phenylene and donor–acceptor–donor comonomers in alternating copolymers, are used to absorb the high‐energy parts of the solar spectrum and to give high photovoltages in combinations with fullerene acceptors in devices. These materials are used in alternative photovoltaic device geometries with enhanced light incoupling to collect larger photocurrents or to enable tandem devices and enhance photovoltage.
Newborn and carrier screening for spinal muscular atrophy
Authors: Prior Thomas W. , Snyder Pamela J. , Rink Britton D. , Pearl Dennis K. , Pyatt Robert E. , Mihal David C. , Conlan Todd , Schmalz Betsy , Montgomery Laura , Ziegler Katie , Noonan Carolee , Hashimoto Sayaka , Garner Shannon
Published: May 2010

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. The homozygous absence of SMN1 exon 7 has been observed in the majority of patients and is being utilized as a reliable and sensitive SMA diagnostic test. Treatment and prevention of SMA are complementary responses to the challenges presented by SMA. Even though a specific therapy for SMA is not currently available, a newborn screening test may allow the child to be enrolled in a clinical trial before irreversible neuronal loss occurs and enable patients to obtain more proactive treatments. Until an effective treatment is found to cure or arrest the progression of the disease, prevention of new cases through accurate diagnosis and carrier and prenatal diagnosis is of the utmost importance. The goal of population‐based SMA carrier screening is to identify couples at risk for having a child with SMA, thus allowing carriers to make informed reproductive choices. During this study we performed two pilot projects addressing the clinical applicability of testing in the newborn period and carrier screening in the general population. We have demonstrated that an effective technology does exist for newborn screening of SMA. We also provide an estimate of the carrier frequency among individuals who accepted carrier screening, and report on patient's knowledge and attitudes toward SMA testing. © 2010 Wiley‐Liss, Inc.
Preliminary evidence of accumulation of stress during translocation in mantled howlers
Authors: Aguilar‐Cucurachi M.A. Socorro , Dias Pedro A.D. , Rangel‐Negrín Ariadna , Chavira Roberto , Boeck Lourdes , Canales‐Espinosa Domingo
Published: May 2010

Translocation—an extensively used conservation tool—is a potentially stressful event, as animals are exposed to multiple stressors and cannot predict or control the changes in their environment. Therefore, it may be expected that during a translocation program stress accumulates and social behavior changes. Here, we present data from a translocation of four adult mantled howlers (Alouatta palliata), which was conducted in southern Veracruz (Mexico). We found that stress (measured in fecal corticosterone) increased during translocation, but that the rate of both affiliative and agonistic interactions remained unchanged. Females showed higher levels of corticosterone than males throughout translocation, although no sex differences were observed in social interactions. Our findings provide a preliminary evidence for accumulation of physiological stress during translocation in primates, and may have implications for decisions concerning releasing practices. Am. J. Primatol. 72:805–810, 2010.© 2010 Wiley‐Liss, Inc.
WoS query partitioner: A tool to retrieve very large numbers of items from the Web of Science using different source‐based partitioning approaches
Authors: Alonso Sergio , Cabrerizo Francisco Javier , Herrera‐Viedma Enrique , Herrera Francisco
Published: May 2010

Thomson Reuters' Web of Science (WoS) is undoubtedly a great tool for scientiometrics purposes. It allows one to retrieve and compute different measures such as the total number of papers that satisfy a particular condition; however, it also is well known that this tool imposes several different restrictions that make obtaining certain results difficult. One of those constraints is that the tool does not offer the total count of documents in a dataset if it is larger than 100,000 items. In this article, we propose and analyze different approaches that involve partitioning the search space (using the Source field) to retrieve item counts for very large datasets from the WoS. The proposed techniques improve previous approaches: They do not need any extra information about the retrieved dataset (thus allowing completely automatic procedures to retrieve the results), they are designed to avoid many of the restrictions imposed by the WoS, and they can be easily applied to almost any query. Finally, a description of WoS Query Partitioner, a freely available and online interactive tool that implements those techniques, is presented.
Online assessment of biofilm development, sloughing and forced detachment in tube reactor by means of magnetic resonance microscopy
Authors: Wagner Michael , Manz Bertram , Volke Frank , Neu Thomas R. , Horn Harald
Published: May 2010

Magnetic resonance microscopy (MRM) was successfully applied for non‐invasive online monitoring of biofilm development, sloughing, and forced detachment. Biofilm cultivation was performed in a tube reactor directly placed in the MRM scanner. Based on the differences in relaxation time of free and bound protons, the distributed water signal was allocated to the bulk and the biofilm phase. The velocity of the flowing water in the tube reactor was measured in all three directions (x,y, andz) at spatial resolutions of 78 µm. From the velocity data, maps of flow gradients (shear rates) were derived. The experiments showed that a more compact biofilm structure is sloughed off in total with nearly no biomass left on the substratum. Continued biofilm cultivation resulted in filamentous biofilm structures, which did not show any sloughing. Experiments at higher Reynolds numbers were performed in order to force biofilm detachment. Continuous measuring of proton velocity and biomass was used to characterize the different stages of biofilm development. The measurements revealed that biofilms are able to resist extremely high local shear stress being raised up to factor of 20 compared to the mean local shear stress acting on the complete biofilm surface. The maximum local shear stress of single biofilm structures exposed to flow was found to be on average seven times higher compared to the mean local shear stress of the entire biofilm surface. MRM was able to visualize and quantify the development of biofilms and interaction of biofilms with the surrounding fluid at the meso‐scale. It is suggested that detachment and sloughing depends on both internal and external structural parameters. Biotechnol. Bioeng. 2010;107: 172–181. © 2010 Wiley Periodicals, Inc.
Intracellular metabolite determination in the presence of extracellular abundance: Application to the penicillin biosynthesis pathway in Penicillium chrysogenum
Authors: Douma Rutger D. , de Jonge Lodewijk P. , Jonker Caspar T.H. , Seifar Reza M. , Heijnen Joseph J. , van Gulik Walter M.
Published: May 2010

Important steps in metabolic pathways are formed by the transport of substrates and products over the cell membrane. The study of in vivo transport kinetics requires accurate quantification of intra‐ and extracellular levels of the transported compounds. Especially in case of extracellular abundance, the proper determination of intracellular metabolite levels poses challenges. Efficient removal of extracellular substrates and products is therefore important not to overestimate the intracellular amounts. In this study we evaluated two different rapid sampling methods, one combined with cold filtration and the other with centrifugation, for their applicability to determine intracellular amounts of metabolites which are present in high concentrations in the extracellular medium. The filtration‐based method combines fast sampling and immediate quenching of cellular metabolism in cold methanol, with rapid and effective removal of all compounds present outside the cells by means of direct filtration and subsequent filtration‐based washing. In the centrifugation‐based method, removal of the extracellular metabolites from the cells was achieved by means of multiple centrifugation and resuspension steps with the cold quenching solution. The cold filtration method was found to be highly superior to the centrifugation method to determine intracellular amounts of metabolites related to penicillin‐G biosynthesis and allowed the quantification of compounds of which the extracellular amounts were 3–4 orders of magnitude higher than the intracellular amounts. Using this method for the first time allowed to measure the intracellular levels of the side chain precursor phenylacetic acid (PAA) and the product penicillin‐G of the penicillin biosynthesis pathway, compounds of which the transport mechanism in Penicillium chrysogenum is still far from being sufficiently understood. Biotechnol. Bioeng. 2010;107: 105–115. © 2010 Wiley Periodicals, Inc.
Radius of gyration of plasmid DNA isoforms from static light scattering
Authors: Latulippe David R. , Zydney Andrew L.
Published: May 2010

Despite the extensive interest in applications of plasmid DNA, there have been few direct measurements of the root mean square radius of gyration, RG, of different plasmid isoforms over a broad range of plasmid size. Static light scattering data were obtained using supercoiled, open‐circular, and linear isoforms of 5.76, 9.80, and 16.8 kbp plasmids. The results from this study extend the range of RG values available in the literature to plasmid sizes typically used for gene therapy and DNA vaccines. The experimental data were compared with available theoretical expressions based on the worm‐like chain model, with the best‐fit value of the apparent persistence length for both the linear and open‐circular isoforms being statistically identical at 46 nm. A new expression was developed for the radius of gyration of the supercoiled plasmid based on a model for linear DNA using an effective contour length that is equal to a fraction of the total contour length. These results should facilitate the development of micro/nano‐fluidic devices for DNA manipulation and size‐based separation processes for plasmid DNA purification. Biotechnol. Bioeng. 2010;107: 134–142. © 2010 Wiley Periodicals, Inc.
Rapid whole monoclonal antibody analysis by mass spectrometry: An Ultra scale‐down study of the effect of harvesting by centrifugation on the post‐translational modification profile
Authors: Reid C.Q. , Tait A. , Baldascini H. , Mohindra A. , Racher A. , Bilsborough S. , Smales C.M. , Hoare M.
Published: May 2010

With the trend towards the generation and production of increasing numbers of complex biopharmaceutical (protein based) products, there is an increased need and requirement to characterize both the product and production process in terms of robustness and reproducibility. This is of particular importance for products from mammalian cell culture which have large molecular structures and more often than not complex post‐translational modifications (PTMs) that can impact the efficacy, stability and ultimately the safety of the final product. It is therefore vital to understand how the operating conditions of a bioprocess affect the distribution and make up of these PTMs to ensure a consistent quality and activity in the final product. Here we have characterized a typical bioprocess and determined (a) how the time of harvest from a mammalian cell culture and, (b) through the use of an ultra scale‐down mimic how the nature of the primary recovery stages, affect the distribution and make up of the PTMs observed on a recombinant IgG4monoclonal antibody. In particular we describe the use of rapid whole antibody analysis by mass spectrometry to analyze simultaneously the changes that occur to the cleavage of heavy chain C‐terminal lysine residues and the glycosylation pattern, as well as the presence of HL dimers. The time of harvest was found to have a large impact upon the range of glycosylation patterns observed, but not upon C‐terminal lysine cleavage. The culture age had a profound impact on the ratio of different glycan moieties found on antibody molecules. The proportion of short glycans increased (e.g., (G0F)220–35%), with an associated decrease in the proportion of long glycans with culture age (e.g., (G2F)27–4%, and G1F/G2F from 15.2% to 7.8%). Ultra scale‐down mimics showed that subsequent processing of these cultures did not change the post‐translational modifications investigated, but did increase the proportion of half antibodies present in the process stream. The combination of ultra scale‐down methodology and whole antibody analysis by mass spectrometry has demonstrated that the effects of processing on the detailed molecular structure of a monoclonal antibody can be rapidly determined early in the development process. In this study we have demonstrated this analysis to be applicable to critical process design decisions (e.g., time of harvest) in terms of achieving a desired molecular structure, but this approach could also be applied as a selection criterion as to the suitability of a platform process for the preparation of a new drug candidate. Also the methodology provides means for bioprocess engineers to predict at the discovery phase how a bioprocess will impact upon the quality of the final product. Biotechnol. Bioeng. 2010;107: 85–95. © 2010 Wiley Periodicals, Inc.
Determination of aristolochic acid in urine using hollow fiber liquid‐phase microextraction combined with high‐performance liquid chromatography
Authors: Yang Yang , Chen Juan , Shi Yan‐Ping
Published: May 2010

A simple and efficient hollow fiber liquid‐phase microextraction (HF‐LPME) technique in conjunction with high‐performance liquid chromatography is presented for extraction and quantitative determination of aristolochic acid I in human urine samples. Several parameters influencing the efficiency of HF‐LPME were investigated and optimized, including extraction solvent, stirring rate, extraction time, pH of donor phase and acceptor phase. Excellent sample clean‐up was observed and good linearity with coefficient of 0.9999 was obtained in the range of 15.4–960 µg/L. This method provided a 230‐fold enrichment factor and good repeatability with relative standard deviations (RSD) lower than 6.0%. The limit of detection value for the analyte in urine sample was 0.01 µg/L at a signal‐to‐noise ratio of 3. The extraction recovery from urine samples was 61.8% with an RSD of 9.71%. Copyright © 2010 John Wiley & Sons, Ltd.
Increased expression of glucose transporter 3 in gerbil brains following magnesium sulfate treatment and focal cerebral ischemic injury
Authors: Huang Chih‐Yang , Liou Yi‐Fan , Chung Shu‐Ying , Pai Pei‐Ying , Kan Chung‐Ben , Kuo Chia‐Hua , Tsai Chang‐Hai , Tsai Fuu‐Jen , Chen Jia‐Long , Lin Jing‐Ying
Published: May 2010

Glucose is the primary energy substrate for neurons. Glucose transporter 3 (Glut3) localizes at the neuronal cellular membrane, which transports glucose from the extracelluar space into neurons. Ischemia results in an increased energy demand that is associated with profound changes in brain energy metabolism. Magnesium sulfate (MgSO4) ameliorates ischemia‐induced neuronal death in the rat and gerbil model. We investigated the effects of MgSO4 administration on the expression of Glut3 in cortex and hippocampus of gerbils during ischemia. The focal cerebral ischemia was produced by unilateral occlusion of the right common carotid artery and right middle cerebral artery. Following ischemia, Glut3 expression increased significantly versus non‐ischemic (contra‐lateral) cortex and hippocampus. MgSO4 treatment significantly increased the level of Glut3 expression in the non‐ischemic and ischemic cortex and hippocampus. We found that the MgSO4‐induced increase in Glut3 expression was not reversed by administration of U0126, a MEK kinase inhibitor. These results suggest that other factors may function to modulate the MgSO4‐induced Glut3 response. In all, our data showed that MgSO4 increases the expression of Glut3 in the cortex and hippocampus of gerbil brains both in non‐ischemia and ischemia status. However, the MEK signaling pathway might not be involved in MgSO4‐induced Glut3 expression following focal ischemia. Copyright © 2010 John Wiley & Sons, Ltd.
A fluorescent, paramagnetic and PEGylated gold/silica nanoparticle for MRI, CT and fluorescence imaging
Authors: van Schooneveld Matti M. , Cormode David P. , Koole Rolf , van Wijngaarden J. Timon , Calcagno Claudia , Skajaa Torjus , Hilhorst Jan , Hart Dannis C. 't , Fayad Zahi A. , Mulder Willem J. M. , Meijerink Andries
Published: May 2010

An important challenge in medical diagnostics is to design all‐in‐one contrast agents that can be detected with multiple techniques such as magnetic resonance imaging (MRI), X‐ray computed tomography (CT), positron emission tomography (PET), single photon emission tomography (SPECT) or fluorescence imaging (FI). Although many dual labeled agents have been proposed, mainly for combined MRI/FI, constructs for three imaging modalities are scarce. Here gold/silica nanoparticles with a poly(ethylene glycol), paramagnetic and fluorescent lipid coating were synthesized, characterized and applied as trimodal contrast agents to allow for nanoparticle‐enhanced imaging of macrophage cells in vitro via MRI, CT and FI, and mice livers in vivo via MRI and CT. This agent can be a useful tool in a multitude of applications, including cell tracking and target‐specific molecular imaging, and is a step in the direction of truly multi‐modal imaging. Copyright © 2010 John Wiley & Sons, Ltd.
An explicit form of all‐pole filter function with decreasing envelope of the summed sensitivity function
Authors: Pavlović Vlastimir D.
Published: May 2010

In this paper, the all‐pole lowpass filter function with the decreasing envelope of the summed sensitivity in the pass‐band is considered. The filter transfer function with maximal number of the ripples of the summed sensitivity in the pass‐band is obtained in the explicit form, by the application of the Chebyshev polynomials of the first kind. The slope of the decrease of the summed sensitivity envelope can be controlled by a free‐parameter α.

We derived a new approximation function in order to achieve small summed sensitivity in the filter pass‐band. Consequently, the sensitivity analysis was carried out and a comparison of the summed sensitivity and the group delay with respect to the classic all‐pole filters was given. The approach presented in this paper is based on that the minimization of the summed sensitivity is important for the reduction of the deviation of the magnitude response caused by temperature changes of the continuous‐time active filters implemented into the analog front end or as programmable chips. Copyright © 2010 John Wiley & Sons, Ltd.
Semi‐Analytical Model for Coupling Core and Edge Plasma
Authors: Sergeev V. , Kuteev B.
Published: May 2010

A semi‐analytical model that combines 1D transport model for plasma inside SOL and a 2D model for the SOL area have been developed for a quantitative conceptual analysis of the reactor parameters with lithium dust jet injection. The basic assumptions of the model and application results are discussed (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Verification of the 2D Tokamak Edge Modelling Codes for Conditions of Detached Divertor Plasma
Authors: Kotov V. , Reiter D. , Coster D. P. , Kukushkin A. S.
Published: May 2010

The paper discusses verification of the ITER edge modelling code SOLPS 4.3 (B2‐EIRENE). Results of the benchmark against SOLPS 5.0 are shown for standard JET test cases. Special two‐point formulas are employed in SOLPS 4.3 to analyze the results of numerical simulations. The applied relations are exact in frame of the equations solved by the B2 code. This enables simultaneous check of the parallel momentum and energy balances and boundary conditions. Transition to divertor detachment is analyzed quantitatively as it appears in the simulations in terms of the coupled momentum and energy balance (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Multi‐Fluid Modeling of Low‐Recycling Divertor Regimes
Authors: Smirnov R. D. , Pigarov A. Yu. , Krasheninnikov S. I. , Rognlien T. D. , Soukhanovskii V. A. , Rensink M. E. , Maingi R. , Skinner C. H. , Stotler D. P. , Bell R. E. , Kugel H. W.
Published: May 2010

The low‐recycling regimes of divertor operation in a single‐null NSTX magnetic configuration are studied using computer simulations with the edge plasma transport code UEDGE. The edge plasma transport properties pertinent to the low‐recycling regimes are demonstrated. These include the flux‐limited character of the parallel heat transport and the high plasma temperatures with the flattened profiles in the scrape‐off‐layer. It is shown that to maintain the balance of particle fluxes at the core interface the deuterium gas puffing rate should increase as the divertor recycling coefficient decreases. The radial profiles of the heat load to the outer divertor plate, the upstream radial plasma profiles, and the effects of the cross‐field plasma transport in the low‐recycling regimes are discussed. It is also shown that recycling of lithium impurities evaporating from the divertor plate at high surface temperatures can reverse the low‐recycling divertor operational regime to the high‐recycling one and may cause thermal instability of the divertor plate (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Numerical Analysis of Divertor Plasma for Demo‐CREST
Authors: Ishida M. , Maeki K. , Hiwatari R. , Bonnin X. , Zhu S. , Hatayama A. , Schneider R. , Coster D.
Published: May 2010

The numerical analysis of the demonstration fusion reactor Demo‐CREST has been carried out; this analysis focuses on impurity seeding. Several design activities for DEMO have been carried out; however, its detailed divertor plasma analysis remains to be carried out. Therefore, in this study, we discuss the possibility of neon puffing in Demo‐CREST to decrease the power load to the divertor plate by using the B2‐EIRENE code. It has been shown that the radiation power loss by neon increases with upstream plasma density and that the peak power load to the divertor plate comes close to the allowable level by using the preliminary divertor configuration (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Accumulation Process of High‐Z Impurity in Toroidal Rotating Tokamak Plasma
Authors: Hoshino K. , Takizuka T. , Nakano T.
Published: May 2010

The accumulation process of high‐Z impurity in toroidal rotating tokamak plasma is investigated. A new inward pinch of high‐Z impurity due to the ionization/recombination processes is derived using an analytic model. This inward pinch is driven by the large deviation of a drift orbit from a magnetic surface and the resultant variation of the charge state along the drift orbit. The pinch velocity increases with increasing toroidal rotation speed in both the co‐direction and the ctr‐direction. The inward pinch expected by the analytic model is really observed in the numerical simulation using the IMPGYRO code (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A method to prepare isotonic dextran–salt solutions
Authors: Fischer Thomas M.
Published: May 2010

To increase, in rheological studies of red cells, the viscosity of suspending media, high‐molecular‐weight polymers, e.g., dextrans, are added to electrolyte solutions. However, dextrans at typical concentrations (e.g., 15% w/w) contribute an appreciable portion to the osmotic pressure of the suspending medium. To keep the volume of red cells normal, the concentration of electrolyte has to be reduced. In our hands, osmometry of dextran–salt solutions (DSSs) was not reliable, probably due to the increased viscosity. Therefore, a method was devised in which the concentration of electrolyte required to achieve normal red cell volume was determined experimentally using the red cell itself as an osmometer. Packed unwashed red cells were added to DSSs with different concentrations of electrolyte. Swelling or shrinking of the red cells was monitored by a change in the refractive index of the suspending medium. Six different dextrans (MW 40 kDa to 2000 kDa) were tested. The concentration of electrolyte at which the red cell volume did not change upon suspension in these DSSs did not depend on the MW of the dextrans. For a dextran concentration of 15% (w/w), the addition of electrolytes had to be reduced by about 1/4 with respect to an isotonic pure electrolyte solution. © 2010 International Society for Advancement of Cytometry
Medical complications of bulimia nervosa and their treatments
Authors: Mehler Philip S.
Published: May 2010

Objective:

To present a cogent and practical review of the medical complications and their treatment in patients with bulimia nervosa.

Method:

Thorough review of the medical literature from 1990 to current in regards to the medical complications of bulimia nervosa and the therapeutic intervention that are effective to treat them.

Results:

Extensive and detailed review of the medical complications of bulimia nervosa. © 2010 by Wiley Periodicals, Inc.