bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study
Authors: Tseng Chia-Lin , Oxlade Olivia , Menzies Dick , Aspler Anne , Schwartzman Kevin
Published: January 2011

Background

The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country - Zambia - relative to the existing strategy of directly observed treatment, short course (DOTS) and current level of bacille Calmette-Guérin (BCG) vaccination coverage.

Methods

We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005) in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398%) of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy.

Results

Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TB-related deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated). This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated). With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial development cost.

Conclusions

Investment in an improved TB vaccine is predicted to result in considerable cost savings, as well as a reduction in TB morbidity and TB-related mortality, when added to existing control strategies. For a vaccine with waning efficacy, a prime-boost strategy is more cost-effective in the long term.
Galectin-1 is expressed in early-type neural progenitor cells and down-regulates neurogenesis in the adult hippocampus
Authors: Imaizumi Yoichi , Sakaguchi Masanori , Morishita Tsuyoshi , Ito Mamoru , Poirier Françoise , Sawamoto Kazunobu , Okano Hideyuki
Published: January 2011

Background

In the adult mammalian brain, neural stem cells (NSCs) proliferate in the dentate gyrus (DG) of the hippocampus and generate new neurons throughout life. A multimodal protein, Galectin-1, is expressed in neural progenitor cells (NPCs) and implicated in the proliferation of the NPCs in the DG. However, little is known about its detailed expression profile in the NPCs and functions in adult neurogenesis in the DG.

Results

Our immunohistochemical and morphological analysis showed that Galectin-1 was expressed in the type 1 and 2a cells, which are putative NSCs, in the subgranular zone (SGZ) of the adult mouse DG. To study Galectin-1's function in adult hippocampal neurogenesis, we madegalectin-1knock-out mice on the C57BL6 background and characterized the effects on neurogenesis. In the SGZ of thegalectin-1knock-out mice, increased numbers of type 1 cells, DCX-positive immature progenitors, and NeuN-positive newborn neurons were observed. Using triple-labeling immunohistochemistry and morphological analyses, we found that the proliferation of the type-1 cells was increased in the SGZ of thegalectin-1knock-out mice, and we propose that this proliferation is the mechanism for the net increase in the adult neurogenesis in these knock-out mice DG.

Conclusions

Galectin-1 is expressed in the neural stem cells and down-regulates neurogenesis in the adult hippocampus.
The Simple Triage Scoring System (STSS) successfully predicts mortality and critical care resource utilization in H1N1 pandemic flu: a retrospective analysis
Authors: Adeniji Kayode A , Cusack Rebecca
Published: January 2011

Introduction

Triage protocols are only initiated when it is apparent that resource deficits will occur across a broad geographical area despite efforts to expand or acquire additional capacity. Prior to the pandemic the UK Department of Health (DOH) recommended the use of a staged triage plan incorporating Sepsis-related Organ Failure Assessment (SOFA) developed by the Ontario Ministry of Health to assist in the triage of critical care admissions and discharges during an influenza outbreak in the UK. There are data to suggest that had it been used in the recent H1N1 pandemic it may have led to inappropriate limitation of therapy if surge capacity had been overwhelmed.

Methods

We retrospectively reviewed the performance of the Simple Triage Scoring System (STSS) as an indicator of the utilization of hospital resources in adult patients with confirmed H1N1 admitted to a university teaching hospital. Our aim was to compare it against the staged initial SOFA score process with regards to mortality, need for intensive care admission and requirement for mechanical ventilation and assess its validity.

Results

Over an 8 month period, 62 patients with confirmed H1N1 were admitted. Forty (65%) had documented comorbidities and 27 (44%) had pneumonic changes on their admission CXR. Nineteen (31%) were admitted to the intensive care unit where 5 (26%) required mechanical ventilation (MV). There were 3 deaths. The STSS group categorization demonstrated a better discriminating accuracy in predicting critical care resource usage with a receiver operating characteristic area under the curve (95% confidence interval) for ICU admission of 0.88 (0.78-0.98) and need for MV of 0.91 (0.83-0.99). This compared to the staged SOFA score of 0.77 (0.65-0.89) and 0.87 (0.72-1.00) respectively. Low mortality rates limited analysis on survival predictions.

Conclusions

The STSS accurately risk stratified patients in this cohort according to their risk of death and predicted the likelihood of admission to critical care and the requirement for MV. Its single point in time, accuracy and easily collected component variables commend it as an alternative reproducible system to facilitate the triage and treatment of patients in any future influenza pandemic.
Bone Mineral Density and Testicular Failure: Evidence for a Role of Vitamin D 25-Hydroxylase in Human Testis
Authors: Foresta Carlo , Strapazzon Giacomo , De Toni Luca , Perilli Lisa , Di Mambro Antonella , Muciaccia Barbara , Sartori Leonardo , Selice Riccardo
Published: January 2011

Working Hypothesis:

Mutations in the CYP2R1 gene, highly expressed in the testis and encoding vitamin D 25-hydroxylase, result in a vitamin D deficiency and a defective calcium homeostasis leading to rickets.

Objective:

Our aim was to investigate CYP2R1 expression in pathological testis samples and relate this to vitamin D metabolism in testiculopathic patients.

Design, Patients, Setting:

Testis samples for in vitro study and 98 young men were transversally evaluated at Padova's Center for Male Gamete Cryopreservation.

Methods:

CYP2R1 mRNA expression and protein production were evaluated by quantitative RT-PCR, Western blot analysis, and immunofluorescence. Hormonal and bone-marker levels, and bone densitometry by dual-energy x-ray absorptiometry, were determined in patients with Sertoli-cell-only syndrome and severe hypospermatogenesis.

Results:

We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome (P < 0.05) and a colocalization with INSL-3, a Leydig cell marker, at immunofluorescence. In all testiculopathic patients 25-hydroxyvitamin D levels were significantly lower and PTH levels higher compared to controls (P < 0.05). Furthermore, testiculopathic patients showed osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy x-ray absorptiometry in the femoral neck and lumbar spine (for all parameters, P < 0.05).

Conclusions:

Our data show an association between testiculopathy and alteration of the bone status, despite unvaried androgen and estrogen levels and no other evident cause of vitamin D reduction. Further studies in larger cohorts are needed to confirm our results.
Effects of Insulin Sensitivity, Body Composition, and Fitness on Lipoprotein Particle Sizes and Concentrations Determined by Nuclear Magnetic Resonance
Authors: Irving Brian A. , Nair K. Sreekumaran , Srinivasan Manivannan
Published: January 2011

Context:

Insulin resistance has been reported to be associated with development of atherogenic dyslipidemia. However, the confounding effects that obesity and low levels of cardiorespiratory fitness have on the relationship between insulin resistance and the development of atherogenic dyslipidemia remain to be adequately addressed.

Objective:

This study sought to examine the independent and combined effects of insulin sensitivity, body composition, and cardiorespiratory fitness on lipoprotein particle sizes and concentrations.

Methods:

Eight-four healthy, nondiabetic men (n = 43) and women (n = 41) were studied. The participants had a wide range of ages (18–30 and 65–80 yr), body composition (7.2–52.8% fat), and cardiorespiratory fitness (VO2 peak, 13.5–66.2 ml/kg·min). Body composition, cardiorespiratory fitness, insulin sensitivity, and lipoprotein particle profiles were assessed using dual-energy x-ray absorptiometry, cardiopulmonary exercise testing, a hyperinsulinemic-euglycemic clamp, and nuclear magnetic resonance spectroscopy, respectively.

Results:

Low levels of insulin sensitivity and cardiorespiratory fitness and higher levels of adiposity were associated with the accumulation of small, dense, low-density lipoprotein particles; small high-density lipoprotein particles; triglycerides; and very low-density lipoprotein particles. Multivariate forward-stepwise regression revealed that higher levels of adiposity, in particular truncal fat, were the strongest predictor of the lipoprotein particle size and concentration data, followed by insulin sensitivity.

Conclusions:

As expected, the accumulation of atherogenic lipoprotein particles (e.g. small, dense, low-density lipoprotein particles and small, high-density lipoprotein particles) was associated with low levels of insulin sensitivity, cardiorespiratory fitness, and higher levels of adiposity. However, multivariate forward-stepwise regression revealed that triglycerides, followed by truncal fat mass, were the strongest predictors of the lipoprotein particle size and concentration data.
Capicua DNA-binding sites are general response elements for RTK signaling inDrosophila
Authors: Ajuria Leiore , Nieva Claudia , Winkler Clint , Kuo Dennis , Samper Núria , Andreu María José , Helman Aharon , González-Crespo Sergio , Paroush Ze'ev , Courey Albert J. , Jiménez Gerardo
Published: January 2011

RTK/Ras/MAPK signaling pathways play key functions in metazoan development, but how they control expression of downstream genes is not well understood. In Drosophila, it is generally assumed that most transcriptional responses to RTK signal activation depend on binding of Ets-family proteins to specific cis-acting sites in target enhancers. Here, we show that several Drosophila RTK pathways control expression of downstream genes through common octameric elements that are binding sites for the HMG-box factor Capicua, a transcriptional repressor that is downregulated by RTK signaling in different contexts. We show that Torso RTK-dependent regulation of terminal gap gene expression in the early embryo critically depends on Capicua octameric sites, and that binding of Capicua to these sites is essential for recruitment of the Groucho co-repressor to the huckebein enhancer in vivo. We then show that subsequent activation of the EGFR RTK pathway in the neuroectodermal region of the embryo controls dorsal-ventral gene expression by downregulating the Capicua protein, and that this control also depends on Capicua octameric motifs. Thus, a similar mechanism of RTK regulation operates during subdivision of the anterior-posterior and dorsal-ventral embryonic axes. We also find that identical DNA octamers mediate Capicua-dependent regulation of another EGFR target in the developing wing. Remarkably, a simple combination of activator-binding sites and Capicua motifs is sufficient to establish complex patterns of gene expression in response to both Torso and EGFR activation in different tissues. We conclude that Capicua octamers are general response elements for RTK signaling in Drosophila.
The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes
Authors: Holt Janet E. , Tran Suzanne M.-T. , Stewart Jessica L. , Minahan Kyra , García-Higuera Irene , Moreno Sergio , Jones Keith T.
Published: January 2011

FZR1, an activator of the anaphase-promoting complex/cyclosome (APC/C), is recognized for its roles in the mitotic cell cycle. To examine its meiotic function in females we generated an oocyte-specific knockout of the Fzr1 gene (Fzr1Δ/Δ). The total number of fully grown oocytes enclosed in cumulus complexes was 35-40% lower in oocytes from Fzr1Δ/Δ mice and there was a commensurate rise in denuded, meiotically advanced and/or fragmented oocytes. The ability of Fzr1Δ/Δ oocytes to remain prophase I/germinal vesicle (GV) arrested in vitro was also compromised, despite the addition of the phosphodiesterase milrinone. Meiotic competency of smaller diameter oocytes was also accelerated by Fzr1 loss. Cyclin B1 levels were elevated ~5-fold in Fzr1Δ/Δ oocytes, whereas securin and CDC25B, two other APC/CFZR1 substrates, were unchanged. Cyclin B1 overexpression can mimic the effects of Fzr1 loss on GV arrest and here we show that cyclin B1 knockdown in Fzr1Δ/Δ oocytes affects the timing of meiotic resumption. Therefore, the effects of Fzr1 loss are mediated, at least in part, by raised cyclin B1. Thus, APC/CFZR1 activity is required to repress cyclin B1 levels in oocytes during prophase I arrest in the ovary, thereby maintaining meiotic quiescence until hormonal cues trigger resumption.
Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate fetal lung development
Authors: Xu Bing , Chen Cheng , Chen Hui , Zheng Song-Guo , Bringas Pablo , Xu Min , Zhou Xianghong , Chen Di , Umans Lieve , Zwijsen An , Shi Wei
Published: January 2011

Bone morphogenetic protein 4 (Bmp4) is essential for lung development. To define the intracellular signaling mechanisms by which Bmp4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells. Abrogation of lung epithelial-specific Smad1, but not Smad5, resulted in retardation of lung branching morphogenesis and reduced sacculation, accompanied by altered distal lung epithelial cell proliferation and differentiation and, consequently, severe neonatal respiratory failure. By combining cDNA microarray with ChIP-chip analyses, Wnt inhibitory factor 1 (Wif1) was identified as a novel target gene of Smad1 in the developing mouse lung epithelial cells. Loss of Smad1 transcriptional activation of Wif1 was associated with reduced Wif1 expression and increased Wnt/β-catenin signaling activity in lung epithelia, resulting in specific fetal lung abnormalities. This suggests a novel regulatory loop of Bmp4-Smad1-Wif1-Wnt/β-catenin in coordinating BMP and Wnt pathways to control fetal lung development.
Digestive efficiency of Knysna and purple-crested turacos fed varying concentrations of equicaloric and equimolar artificial fruit
Authors: Wilson Amy-Leigh , Downs Colleen T.
Published: January 2011

Avian frugivores have been somewhat poorly studied with regards to the effects that different fruit sugar types and concentrations have on their digestive efficiencies. Therefore, two relatively large South African frugivores, the Knysna turaco (Tauraco corythaix) and the purple-crested turaco (Gallirex porphyreolophus), were fed artificial fruit that contained equicaloric and equimolar concentrations of different sugars, to determine their daily food and energy intake, digestive efficiencies and digestive transit times. The artificial fruit contained 6.6, 12.4 or 22%, or 0.42, 0.83 or 1.66 mol l–1 sucrose or glucose. Food intake of both turaco species increased with decreasing sugar concentration and molarity, irrespective of sugar type, suggesting compensatory mechanisms for energy requirements. Apparent assimilation efficiencies of both turaco species ranged from 61.4-90.0% and 60.2-92.4% for equicaloric and equimolar artificial fruit diets, respectively. Digestive transit times for both turaco species were slowed with an increase in sugar concentration and molarity, irrespective of sugar type. Consequently these two frugivores appear to be tolerant of sugar type and would be expected to select fruits based on energy yields. Future studies of the composition of indigenous forest fruit sugars may give insight into food preferences of the turaco species and their role as potential seed dispersers of fruiting tree species.
Deconstructing honeybee vitellogenin: novel 40 kDa fragment assigned to its N terminus
Authors: Havukainen Heli , Halskau Øyvind , Skjaerven Lars , Smedal Bente , Amdam Gro V.
Published: January 2011

Vitellogenin, an egg-yolk protein precursor common to oviparous animals, is found abundantly in honeybee workers – a caste of helpers that do not usually lay eggs. Instead, honeybee vitellogenin (180 kDa) participates in processes other than reproduction: it influences hormone signaling, food-related behavior, immunity, stress resistance and longevity. The molecular basis of these functions is largely unknown. Here, we establish and compare the molecular properties of vitellogenin from honeybee hemolymph (blood) and abdominal fat body, two compartments that are linked to vitellogenin functions. Our results reveal a novel 40 kDa vitellogenin fragment in abdominal fat body tissue, the main site for vitellogenin synthesis and storage. Using MALDI-TOF combined with MS/MS mass-spectroscopy, we assign the 40 kDa fragment to the N terminus of vitellogenin, whereas a previously observed 150 kDa fragment corresponded to the remainder of the protein. We show that both protein units are N glycosylated and phosphorylated. Focusing on the novel 40 kDa fragment, we present a homology model based on the structure of lamprey lipovitellin that includes a conserved β-barrel-like shape, with a lipophilic cavity in the interior and two insect-specific loops that have not been described before. Our data indicate that the honeybee fat body vitellogenin experiences cleavage unlike hemolymph vitellogenin, a pattern that can suggest a tissue-specific role. Our experiments advance the molecular understanding of vitellogenin, of which the multiple physiological and behavioral effects in honeybees are well established.
Modeling of Operational Safeguard for Power Productions in the Nuclear Power Plants (NPPs)
Authors: Woo Tae-Ho , Lee Un-Chul
Published: January 2011

Power operations for secure performance are investigated using non-linear algorithm. The object of the simulation is to find the safe operation with safeguard for the life-extension of the operations. The network effect of the game theory is used for the quantification which is incorporated with the Monte-Carlo method. The characteristics of the nuclear power plants (NPPs) are analyzed by the designed occurrence value as the refueling factor (RF) and the safeguard measures factor (SMF) which are used for the basic element. The random sampling for the event frequency is used by the characteristics of network effect method like the zero-sum quantification, because it is impossible to expect the time of terror incident exactly. Three kinds of considerations are basic elements as the nuclear fuel, system, and safeguard properties which are organized as an aspect of safeguard considerations. The maximum value of secure operation is the 13.0 in 14th month and the minimum value is 1.0 in several months during 10 years. Hence, the stability of the secure power operation increases 13 times higher than the lowest value in this study. The conclusions give that the secure operation is changeable in the designed NPPs.
Preparation and Characterization of Textural and Energetic Parameters of Common and Functionalized SBA-15 Mesoporous Silicas
Authors: Vargas Diana P. , Legnoverde María S. , Giraldo Liliana , Basaldella Elena , Moreno-Piraján Juan C.
Published: January 2011

A set of SBA-15 ordered mesoporous silicas presenting different surface acidities was obtained by organo-functionalization. Amino and sulphonic groups were attached onto the silica surface in order to determine the influence of organo-functionalization with acidic and basic moieties on the adsorption properties of silica. Cephalexin, an antibiotic molecule characterized by its zwitterionic nature, was selected as the adsorbate. The obtained matrices were characterized by scanning electron microscopy, energy dispersive X-ray analysis and nitrogen adsorption isotherms at 77 K. Enthalpies of immersion into water, benzene and cephalexin solutions were measured by immersion calorimetry, and the cephalexin adsorption capacities of the different matrices were also determined. The structure of SBA-15 was conserved in the functionalized samples despite a noticeable reduction in the BET surface area, pore volume and pore size. It was found that the inclusion of amino groups promoted interaction between the adsorbent and adsorbate, thereby favouring the retention of cephalexin.
Woods Charred at Low Temperatures and Their Modification for the Adsorption of Cr(VI) Ions from Aqueous Solution
Authors: Li Zhenze , Katsumi Takeshi , Inui Toru , Imaizumi Shigeyoshi
Published: January 2011

Despite being prepared at higher temperatures and involving greater energy consumption, activated carbons always show a smaller capacity and affinity towards the adsorption of Cr(VI) ions. After a brief review regarding Cr(VI) ion contamination and treatment, the preparation of a novel biosorbent from pyrolyzed wood char for Cr(VI) ion adsorption is described. Pyrolysis was conducted at temperatures within the range 200–350 °C, thereby helping to protect beneficial functional groups, saving energy and hence reducing costs.

The influence of pH, concentration, adsorbent dosage, ionic strength and equilibration time on Cr(VI) ion adsorption by this biosorbent was investigated. It was shown that the char obtained at 200 °C possessed the highest Cr(VI) ion retention capacity (31.96 mg/g) but required the longest equilibration time (> 47 d). Coating the char with nano-scale iron oxide greatly improved its adsorption affinity towards Cr(VI) ions, with a higher adsorption affinity (Henry's law Kd = 2.988 ℓ/mg) and an enhanced Cr(VI) ion adsorption capacity (53.45 mg/g) being accomplished within a much shorter equilibration time (24 h). Spectroscopic studies confirmed that complexation of Cr(VI) ions occurred via surface hydroxy groups. The methods proposed for preparing and modifying wood char are likely to be applicable in industrial wastewater treatment.
Modelling the Excitation Force of a Standard Tapping Machine on Lightweight Floor Structures
Authors: Rabold Andreas , Buchschmid Martin , Düster Alexander , Müller Gerhard , Rank Ernst
Published: January 2011

Up to now the research and development in the field of building acoustics is based mainly on measurements. In consequence the development and optimization of a new building component is a very tedious and expensive task. A considerable reduction of these costs could be achieved, if the optimization relying on measurements would be replaced – at least to some extent – by a computational prediction model. For these models it is necessary to represent not only the component and the adjacent rooms but also the excitation in a suitable way. This paper gives an overview of models for the excitation generated by a standard tapping machine taking into account the interaction between the impacting steel cylinders of the tapping machine and the vibrating surface of the floor.
An Inverse Force Measurement Method to Determine the Injected Structure-Borne Sound Power from an Installation into a Building Element
Authors: Schevenels Pieter , van der Linden Peter J. G. , Vermeir Gerrit
Published: January 2011

In structure-borne sound problems in buildings, knowledge of the contact forces between vibrating equipment and a receiving element is often required. When multiplying these forces with the simultaneously measured velocities at the contact points of the equipment, the structure-borne sound power can be determined, which is the quantity governing the sound energy transfer from a source space to a receiving space. Measuring contact forces directly is however not straightforward. Therefore, a structural-acoustical method is used to determine the contact forces inversely. This technique is already used in the automotive industry, but applications in buildings are rather rare. The installation used is a vibrating platform, which induces tonal, low-frequency vibrations into the building. Therefore, the used sound source has to perform well for low frequencies. The resulting forces are used for structure-borne sound power calculation and verified by comparing the sound pressure, caused by this injected power, with measured sound pressure.
Sound Absorption Characteristics of a Precast Panel System Made from Environmentally Sustainable Concrete
Authors: Rajagopalan Priyadarsini , Krezel Adam
Published: January 2011

This paper investigates the sound absorption characteristics of a precast panel system made from an environmentally sustainable concrete which can be used as an acoustical material. A current research project undertaken at the School of Architecture and Building, Deakin University, aims at utilising alternative materials and innovative approach to concrete precasting in the production of architecturally pleasing concrete panels. The normal incidence sound absorption coefficients of the assemblies were measured using an impedance tube. In general, the peak frequencies reduced with increasing thickness of concrete. The preliminary results indicate that the sound absorption of a three-layer variation of the panel meet design specifications related to acoustic performance. The major benefits of this investigated approach to concrete and concrete precasting are the ease of tunability to specific peak frequency, improved aesthetics and utilisation of industrial waste.
Bifurcation Analysis of Thermoacoustic Instability in a Horizontal Rijke Tube
Authors: Subramanian Priya , Mariappan Sathesh , Sujith R. I. , Wahi Pankaj
Published: January 2011

A bifurcation analysis of the dynamical behavior of a horizontal Rijke tube model is performed in this paper. The method of numerical continuation is used to obtain the bifurcation plots, including the amplitude of the unstable limit cycles. Bifurcation plots for the variation of nondimensional heater power, damping coefficient and the heater location are obtained for different values of time lag in the system. Subcritical bifurcation was observed for variation of parameters and regions of global stability, global instability and bistability are characterized. Linear and nonlinear stability boundaries are obtained for the simultaneous variation of two parameters of the system. The validity of the small time lag assumption in the calculation of linear stability boundary has been shown to fail at typical values of time lag of system. Accurate calculation of the linear stability boundary in systems with explicit time delay models, must therefore, not assume a small time lag assumption. Interesting dynamical behavior such as co-existing multiple attractors, quasiperiodic behavior and period doubling route to chaos have been observed in the analysis of the model. Comparison of the linear stability boundaries and bifurcation behavior from this reduced order model are shown to display trends similar to experimental data.
A Bendable Load Stiffened Wing for Small UAVs
Authors: Jagdale Vijay , Ifju Peter , Stanford Bret , Albertani Roberto
Published: January 2011

A bendable load stiffened wing, developed at the University of Florida, has the ability to load stiffen in the positive flight load direction while remaining compliant in the opposite direction, enabling UAV storage inside smaller packing volumes. The wing employs an under-cambered airfoil with a swept planform providing dissimilar stiffness in the flight load and the folding direction. A comparative experimental study is performed using two wing geometries; straight camber and swept camber. The load stiffening ability is tested by performing three point bend tests while monitoring the wing root airfoil shape change using a visual image correlation technique. For the wing utilizing a swept camber design, increase in the root airfoil camber with increased loading resulted in a load stiffening structure. Swept camber wing showed a higher load carrying capacity (7 g's load factor) over a straight camber wing design (2 g's load factor), still maintaining the compliant nature in the folding direction. Long term storage induced creep deformations are small in both of the wing geometries. By increasing the wing stiffness, sweepback helps in reducing spanwise residual creep strain. Wind tunnel tests at Re = 7×104 of both the straight camber and the swept camber wing show similar L/D ratios. The sweepback helps in improving the static stability of the wing. Thus the bendable load stiffened wing has a clear advantage of offering stiffness improvement and reducing storage induced creep residual strains while maintaining the aerodynamic efficiency and improving the static stability of the wing.
Plasma N-Glycan Profiling by Mass Spectrometry for Congenital Disorders of Glycosylation Type II
Authors: Guillard Maïlys , Morava Eva , van Delft Floris L , Hague Rosie , Körner Christian , Adamowicz Maciej , Wevers Ron A , Lefeber Dirk J
Published: January 2011

BACKGROUND

Determination of the genetic defect in patients with a congenital disorder of glycosylation (CDG) is challenging because of the wide clinical presentation, the large number of gene products involved, and the occurrence of secondary causes of underglycosylation. Transferrin isoelectric focusing has been the method of choice for CDG screening; however, improved methods are required for the molecular diagnosis of patients with CDG type II.

METHODS

Plasma samples with a typical transferrin isofocusing profile were analyzed. N-glycans were released from these samples by PNGase F [peptide-N4-(acetyl-β-glucosaminyl)-asparagine amidase] digestion, permethylated and purified, and measured on a MALDI linear ion trap mass spectrometer. A set of 38 glycans was used for quantitative comparison and to establish reference intervals for such glycan features as the number of antennae, the level of truncation, and fucosylation. Plasma N-glycans from control individuals, patients with known CDG type II defects, and patients with a secondary cause of underglycosylation were analyzed.

RESULTS

CDGs due to mannosyl (α-1,6-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT2), β-1,4-galactosyltransferase 1 (B4GALT1), and SLC35C1 (a GDP-fucose transporter) defects could be diagnosed directly from the N-glycan profile. CDGs due to defects in proteins involved in Golgi trafficking, such as subunit 7 of the conserved oligomeric Golgi complex (COG7) and subunit V0 a2 of the lysosomal H+-transporting ATPase (ATP6V0A2) caused a loss of triantennary N-glycans and an increase of truncated structures. Secondary causes with liver involvement were characterized by increased fucosylation, whereas the presence of plasma sialidase produced isolated undersialylation.

CONCLUSIONS

MALDI ion trap analysis of plasma N-glycans documents features that discriminate between primary and secondary causes of underglycosylation and should be applied as the first step in the diagnostic track of all patients with an unsolved CDG type II.
Enhancement of Heat Transfer Characteristics of Transformer Oil by Addition of Aluminium Nanoparticles
Authors: Rajesh E. , Prabhu K. Narayan
Published: January 2011

A two step approach involving the synthesis of Al nanoparticles by mechanical milling followed by dispersion of the nanoparticles in the base fluid is adopted in the present work to prepare transformer oil based nanofluids. Stainless steel (AISI 304) probes of diameter 15 mm and height 70 mm were used to determine the cooling rate intensities of nanofluids. Heat transfer coefficients were determined using Kobasko’s method. A dynamic contact angle analyzer was used to determine the contact angle of the droplet on the substrate. The addition of Al nanoparticles to the base fluid decreases the wettability and improves its heat transfer capability. The vapour phase stage existed for a longer period of time for transformer oil than for Al-transformer oil based nanofluids. The dispersion of nanoparticles in the base fluid is believed to disrupt the vapour blanket stage in the early stage of the cooling process. The peak heat transfer coefficient increases with an increase in the Al nanoparticle content in the oil. The addition of 0.5 vol % nanoparticles enhances the peak heat transfer coefficient by about 70 %.
Tracking Vocal Pitch through Noise: Neural Correlates in Nonprimary Auditory Cortex
Authors: Riecke Lars , Walter Anke , Sorger Bettina , Formisano Elia
Published: January 2011

In natural environments, a sound can be heard as stable despite the presence of other occasionally louder sounds. For example, when a portion in a voice is replaced by masking noise, the interrupted voice may still appear illusorily continuous. Previous research found that continuity illusions of simple interrupted sounds, such as tones, are accompanied by weaker activity in the primary auditory cortex (PAC) during the interruption than veridical discontinuity percepts of these sounds. Here, we studied whether continuity illusions of more natural and more complex sounds also emerge from this mechanism. We used psychophysics and functional magnetic resonance imaging in humans to measure simultaneously continuity ratings and blood oxygenation level-dependent activity to vowels that were partially replaced by masking noise. Consistent with previous results on tone continuity illusions, we found listeners' reports of more salient vowel continuity illusions associated with weaker activity in auditory cortex (compared with reports of veridical discontinuity percepts of physically identical stimuli). In contrast to the reduced activity to tone continuity illusions in PAC, this reduction was localized in the right anterolateral Heschl's gyrus, a region that corresponds more to the non-PAC. Our findings suggest that the ability to hear differently complex sounds as stable during other louder sounds may be attributable to a common suppressive mechanism that operates at different levels of sound representation in auditory cortex.
Flexible, Task-Dependent Use of Sensory Feedback to Control Hand Movements
Authors: Knill David C. , Bondada Amulya , Chhabra Manu
Published: January 2011

We tested whether changing accuracy demands for simple pointing movements leads humans to adjust the feedback control laws that map sensory signals from the moving hand to motor commands. Subjects made repeated pointing movements in a virtual environment to touch a button whose shape varied randomly from trial to trial—between squares, rectangles oriented perpendicular to the movement path, and rectangles oriented parallel to the movement path. Subjects performed the task on a horizontal table but saw the target configuration and a virtual rendering of their pointing finger through a mirror mounted between a monitor and the table. On one-third of trials, the position of the virtual finger was perturbed by ±1 cm either in the movement direction or perpendicular to the movement direction when the finger passed behind an occluder. Subjects corrected quickly for the perturbations despite not consciously noticing them; however, they corrected almost twice as much for perturbations aligned with the narrow dimension of a target than for perturbations aligned with the long dimension. These changes in apparent feedback gain appeared in the kinematic trajectories soon after the time of the perturbations, indicating that they reflect differences in the feedback control law used throughout the duration of movements. The results indicate that the brain adjusts its feedback control law for individual movements “on demand” to fit task demands. Simulations of optimal control laws for a two-joint arm show that accuracy demands alone, coupled with signal-dependent noise, lead to qualitatively the same behavior.
Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior
Authors: Schoffelmeer Anton N. M. , Drukarch Benjamin , De Vries Taco J. , Hogenboom François , Schetters Dustin , Pattij Tommy
Published: January 2011

Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [3H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [3H]norepinephrine in nucleus accumbens slices, but not on that of [3H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocaine-sensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.
Protein Quantification at the Single Vesicle Level Reveals That a Subset of Synaptic Vesicle Proteins Are Trafficked with High Precision
Authors: Mutch Sarah A. , Kensel-Hammes Patricia , Gadd Jennifer C. , Fujimoto Bryant S. , Allen Richard W. , Schiro Perry G. , Lorenz Robert M. , Kuyper Christopher L. , Kuo Jason S. , Bajjalieh Sandra M. , Chiu Daniel T.
Published: January 2011

Protein sorting represents a potential point of regulation in neurotransmission because it dictates the protein composition of synaptic vesicles, the organelle that mediates transmitter release. Although the average number of most vesicle proteins has been estimated using bulk biochemical approaches (Takamori et al., 2006), no information exists on the intervesicle variability of protein number, and thus on the precision with which proteins are sorted to vesicles. To address this, we adapted a single molecule quantification approach (Mutch et al., 2007) and used it to quantify both the average number and variance of seven integral membrane proteins in brain synaptic vesicles. We report that four vesicle proteins, SV2, the proton ATPase, Vglut1, and synaptotagmin 1, showed little intervesicle variation in number, indicating they are sorted to vesicles with high precision. In contrast, the apparent number of VAMP2/synaptobrevin 2, synaptophysin, and synaptogyrin demonstrated significant intervesicle variability. These findings place constraints on models of protein function at the synapse and raise the possibility that changes in vesicle protein expression affect vesicle composition and functioning.
Multiple Targets of μ-Opioid Receptor-Mediated Presynaptic Inhibition at Primary Afferent Aδ- and C-Fibers
Authors: Heinke Bernhard , Gingl Ewald , Sandkühler Jürgen
Published: January 2011

Agonists at μ-opioid receptors (MORs) represent the gold standard for the treatment of severe pain. A key element of opioid analgesia is the depression of nociceptive information at the first synaptic relay in spinal pain pathways. The underlying mechanisms are, however, largely unknown. In spinal cord slices with dorsal roots attached prepared from young rats, we determined the inhibitory effect of the selective MOR agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) on monosynaptic Aδ- and C-fiber-evoked EPSCs in lamina I neurons. DAMGO depressed presynaptically Aδ- and C-fiber-mediated responses, indicating that MORs are expressed on central terminals of both fiber types. We next addressed the mechanisms of presynaptic inhibition. The effect of DAMGO at both Aδ- and C-fiber terminals was mainly mediated by an inhibition of N-type voltage-dependent Ca2+channels (VDCCs), and to a lesser extent of P/Q-type VDCCs. Inhibition by DAMGO was not reduced by K+channel blockers. The rate of miniature EPSCs was reduced by DAMGO in a dose-dependent manner. The opioid also reduced Ca2+-dependent, ionomycin-induced EPSCs downstream of VDCCs. DAMGO had no effect on the kinetics of vesicle exocytosis in C-fiber terminals, but decreased the rate of unloading of Aδ-fiber boutons moderately, as revealed by two-photon imaging of styryl dye destaining. Together, these results suggest that binding of opioids to MORs reduces nociceptive signal transmission at central Aδ- and C-fiber synapses mainly by inhibition of presynaptic N-type VDCCs. P/Q-type VDCCs and the transmitter release machinery are targets of opioid action as well.
Discrete Neuroanatomical Networks Are Associated with Specific Cognitive Abilities in Old Age
Authors: Wen Wei , Zhu Wanlin , He Yong , Kochan Nicole A. , Reppermund Simone , Slavin Melissa J. , Brodaty Henry , Crawford John , Xia Aihua , Sachdev Perminder
Published: January 2011

There have been many attempts at explaining age-related cognitive decline on the basis of regional brain changes, with the usual but inconsistent findings being that smaller gray matter volumes in certain brain regions predict worse cognitive performance in specific domains. Additionally, compromised white matter integrity, as suggested by white matter hyperintensities or decreased regional white matter fractional anisotropy, has an adverse impact on cognitive functions. The human brain is, however, a network and it may be more appropriate to relate cognitive functions to properties of the network rather than specific brain regions. We report on graph theory-based analyses of diffusion tensor imaging tract-derived connectivity in a sample of 342 healthy individuals aged 72–92 years. The cognitive domains included processing speed, memory, language, visuospatial, and executive functions. We examined the association of these cognitive assessments with both the connectivity of the whole brain network and individual cortical regions. We found that the efficiency of the whole brain network of cortical fiber connections had an influence on processing speed and visuospatial and executive functions. Correlations between connectivity of specific regions and cognitive assessments were also observed, e.g., stronger connectivity in regions such as superior frontal gyrus and posterior cingulate cortex were associated with better executive function. Similar to the relationship between regional connectivity efficiency and age, greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions. For the first time, regional anatomical connectivity maps related to processing speed and visuospatial and executive functions in the elderly are identified.
Improved Motion Perception and Impaired Spatial Suppression following Disruption of Cortical Area MT/V5
Authors: Tadin Duje , Silvanto Juha , Pascual-Leone Alvaro , Battelli Lorella
Published: January 2011

As stimulus size increases, motion direction of high-contrast patterns becomes increasingly harder to perceive. This counterintuitive behavioral result, termed “spatial suppression,” is hypothesized to reflect center–surround antagonism—a receptive field property ubiquitous in sensory systems. Prior research proposed that spatial suppression of motion signals is a direct correlate of center–surround antagonism within cortical area MT. Here, we investigated whether human MT/V5 is indeed causally involved in spatial suppression of motion signals. The key assumption is that a disruption of neural mechanisms that play a critical role in spatial suppression could allow these normally suppressed motion signals to reach perceptual awareness. Thus, our hypothesis was that a disruption of MT/V5 should weaken spatial suppression and, consequently, improve motion perception of large, moving patterns. To disrupt MT/V5, we used offline 1 Hz transcranial magnetic stimulation (TMS)—a method that temporarily attenuates normal functioning of the targeted cortex. Early visual areas were also targeted as a control site. The results supported our hypotheses and showed that disruption of MT/V5 improved motion discrimination of large, moving stimuli, presumably by weakening surround suppression strength. This effect was specific to MT/V5 stimulation and contralaterally presented stimuli. Evidently, the critical neural constraints limiting motion perception of large, high-contrast stimuli involve MT/V5. Additionally, our findings mimic spatial suppression deficits that are observed in several patient populations and implicate impaired MT/V5 processes as likely neural correlates for the reported perceptual abnormalities in the elderly, patients with schizophrenia and those with a history of depression.
FMRP Regulates the Transition from Radial Glial Cells to Intermediate Progenitor Cells during Neocortical Development
Authors: Saffary Roya , Xie Zhigang
Published: January 2011

During vertebrate cortical neurogenesis, radial glial cells (RGCs) serve as neural stem cells that generate neurons directly or indirectly through intermediate progenitor cells (IPCs). The transition from RGCs to IPCs is a key step in determining overall neuronal production and may underlie evolutionary expansion of the cerebral cortex. Here we show that this transition is controlled by fragile X mental retardation protein (FMRP), an RNA-binding protein whose deficiency causes fragile X syndrome. Analysis of mouse embryos electroporated with FMRP small hairpin RNA and knock-out mouse embryos lacking FMRP reveals that specific loss of FMRP causes depletion of neocortical RGCs due to an RGC-to-IPC cell fate change. The RGC depletion is associated with altered F-actin organization and can be largely rescued by overexpressing profilin 1 (Pfn1), a core actin regulatory protein promoting F-actin formation. Our data suggest that FMRP suppresses the transition from RGCs to IPCs during neocortical development by an actin-dependent mechanism.