bluuebunny/crossref_metadata_2025 huggingface dataset:
Phadiatop Infant® detects IgE‐mediated diseases among pre‐school children: a prospective study
Authors: Nilsson Caroline , Lilja Gunnar , Nordlund Monica , Berthold Malin , Borres Magnus P.
Published: September 2011

To cite this article: Nilsson C, Lilja L, Nordlund M, Berthold M, Borres MP. Phadiatop Infant® detects IgE‐mediated diseases among pre‐school children: a prospective study. Pediatr Allergy Immunol 2011; Doi: 10.1111/j.1399‐3038.2011.01203.x

Background:  IgE‐sensitization to food and inhalant allergens may precede and accompany the appearance of clinical symptoms of allergic diseases. The aim was to study the diagnostic capacity of Phadiatop® Infant (Phinf) for detecting IgE‐sensitization at 5 yr of age and further to evaluate the predictive capacity of Phinf longitudinally with regard to sensitization and allergic symptoms in pre‐school children.

Methods:  Two hundred and one children with complete data on sIgE testing for 10 individual allergens, Phinf analyses, and clinical evaluations at 2 and 5 yr of age were evaluated.

Results:  The diagnostic performance of Phinf, applied at the age of 5 and compared to specific IgE testing, gave a sensitivity of 84% and a specificity of 98%. The positive and negative predictive values were 97% and 92%, respectively. A positive Phinf test at 2 yr increased the odds 35.6‐fold (95% CI 11.8–107) for IgE‐sensitization and 14.7‐fold (95% CI 4.4–49.7) for any allergic symptom at 5 yr of age. The association (OR) between Phinf and current symptoms was, at 2 and 5 yr of age, 3.6 (95% CI 1.6–7.9) and 18.4 (95% CI 7.4–45.8), respectively.

Conclusions:  Phinf seems to be a reliable tool for predicting future sensitization as well as allergic symptoms in young children.
Vegetative reproduction capacities of floodplain willows – cutting response to competition and biomass loss
Authors: Radtke A. , Mosner E. , Leyer I.
Published: September 2011

While several studies on regeneration in Salicaceae have focused on seedling recruitment, little is known about factors controlling their vegetative reproduction. In two greenhouse experiments, we studied the response of floodplain willows (Salix fragilis, S. viminalis, S. triandra) to competition with Poa trivialis, and to shoot and root removal when planted as vegetative cuttings. In the first experiment, growth performance variables were analysed in relation to full competition, shoot competition, root competition and control, taking into account two different water levels. After 9 weeks, shoots were removed and the resprouting capacity of the bare cuttings was recorded. In the second experiment, the cutting performance of the three floodplain and an additional two fen willow species (S. cinerea, S. aurita) was compared when grown in three different soil compositions and with two different water levels. After 9 weeks, shoot and root biomass was removed and the bare cuttings were replanted to test their ability to resprout. Cutting performance and secondary resprouting were negatively affected by full and shoot competition while root competition had no or weak effects. The floodplain species performed better than the fen species in all soil types and water levels. Secondary resprouting capacity was also higher in the floodplain species, which showed an additional strong positive response to the previous waterlogging treatment. The results contribute to understanding of the vegetative regeneration ecology of floodplain willows, and suggest that the use of vegetative plantings in restoration plantings could be an effective strategy for recovering floodplain forests.
Detection of Chlamydophila pneumoniae in cats with conjunctivitis
Authors: Sibitz Christina , Rudnay Elisabeth C. , Wabnegger Leila , Spergser Joachim , Apfalter Petra , Nell Barbara
Published: September 2011

Objective  To determine the presence of chlamydial species including recently described chlamydial agents as well as the human pathogen Chlamydophila pneumoniae in feline conjunctivitis.

Animal studied  Twenty five cats without and 49 cats with conjunctivitis were tested for chlamydia using a Chlamydiaceae real time (RT) PCR (targeting the 23S rRNA gene sequence), a Chlamydiales PCR (targeting the 16S rRNA gene sequence), and cell culture. The PCR products of all positive samples were sequenced and subsequently analyzed using a basic local alignment search tool search.

Results  Chlamydiaceae RT PCR and subsequent sequence analyses identified C. pneumoniae in five cats in the conjunctivitis group. The presence of Chlamydophila felis was shown in two cats with conjunctivitis. Chlamydiae related to uncultured members of Chlamydiales were detected in three conjunctivitis cases and in one cat without clinical symptoms.

Conclusion  This study detects for the first time, the known human pathogen C. pneumoniae in feline conjunctivitis cases using Chlamydiaceae RT PCR and sequence analyses.
AN EXTENDED HIERARCHICAL LINGUISTIC MODEL FOR DECISION‐MAKING PROBLEMS
Authors: Espinilla Macarena , Liu Jun , Martínez Luis
Published: September 2011

In multi‐expert decision making (MEDM) problems the experts provide their preferences about the alternatives according to their knowledge. Because they can have different knowledge, educational backgrounds, or experiences, it seems logical that they might use different evaluation scales to express their opinions. In the present article, we focus on decision problems defined in uncertain contexts where such uncertainty is modeled by means of linguistic information, therefore the decision makers would use different linguistic scales to express their evaluations on the alternatives, i.e., multigranular linguistic scales. Several computational approaches have been presented to manage multigranular linguistic scales in decision problems. Although they provide good results in some cases, still present limitations. A new approach, so‐called extended linguistic hierarchies, is presented here for managing multigranular linguistic scales to overcome those limitations, an MEDM case study is given to illustrate the proposed method.
Subjective Perceptions Associated with the Ascending and Descending Slopes of Breath Alcohol Exposure Vary with Recent Drinking History
Authors: Wetherill Leah , Morzorati Sandra L. , Foroud Tatiana , Windisch Kyle , Darlington Todd , Zimmerman Ulrich S. , Plawecki Martin H. , O’Connor Sean J.
Published: September 2011

Background:  The differentiator model predicts that individuals with a positive family history of alcoholism (FHA) or heavy alcohol consumers will feel more sensitive to the effects of alcohol on the ascending phase of the blood alcohol content while feeling less sedated on the descending phase. This study tested whether subjective perceptions are sensitive to the slope of breath alcohol concentration (BrAC) and whether that sensitivity is associated with an FHA and/or recent drinking history (RDH).

Methods:  Family‐history‐positive (FHP, n = 27) and family‐history‐negative (FHN, n = 27) young adult nondependent drinkers were infused intravenously with alcohol in 2 sessions separated by 1 week. After 20 minutes, one session had an ascending BrAC (+3.0 mg%/min), while the other session had a descending BrAC (−1 mg%/min). The BrAC for both sessions at this point was approximately 60 mg%, referred to as the crossover point. Subjective perceptions of intoxication, high, stimulated, and sedation were sampled frequently and then interpolated to the crossover point. Within‐subject differences between ascending and descending responses were examined for associations with FHA and/or RDH.

Results:  Recent moderate drinkers reported increased perceptions of feeling intoxicated (p < 0.023) and high (p < 0.023) on the ascending slope compared with the descending slope. In contrast, recent light drinkers felt more intoxicated and high on the descending slope.

Conclusions:  Subjective perceptions in young adult social drinkers depend on the slope of the BrAC when examined in association with RDH. These results support the differentiator model hypothesis concerning the ascending slope and suggest that moderate alcohol consumers could be at risk for increased alcohol consumption because they feel more intoxicated and high on the ascending slope. Subjects did not feel less sedated on the descending slope, contrary to the differentiator model but replicating several previous studies.
Effect of experimentally induced climate change on the seed bank of a Mediterranean shrubland
Authors: del Cacho Montse , Saura‐Mas Sandra , Estiarte Marc , Peñuelas Josep , Lloret Francisco
Published: September 2011

Questions

We studied the soil seed bank under field‐simulated climate change conditions and addressed the following questions: Is the effect of climate change on seed banks more evident in areas without vegetation? Are short‐lived species more sensitive to this directional climate change than long‐lived species?

Location

A Mediterranean shrubland in the Garraf Natural Park, NE Spain.

Methods

Directional climate change was induced through manipulating temperature and rainfall over almost 9 yr. Soil seed banks were assessed using the seedling emergence method.

Results

Under drought and warming treatments, the total number of germinating seeds decreased by 47% and 43%, respectively, in non‐vegetated areas. In contrast, no effect was found for areas with vegetation cover. Reduced seed bank density was particularly pronounced for short‐lived species (therophytes plus hemicryptophytes), which dropped by 60% and 69%, respectively, in the drought and warming treatments in open areas, while no significant changes were observed under vegetation. In non‐vegetated areas, the reduction in seed bank density was similar in all species. In contrast, a shift in the relative abundance of seed bank species was apparent under shrub canopies.

Conclusions

As experimental climatic manipulations of Mediterranean shrublands demonstrate a trend towards an increase in open areas under drought conditions, a decrease in the seed bank of short‐lived species in these areas may potentially result in a positive feedback that would accentuate the loss of vegetation cover under predicted future climate conditions.
Optimization of the Enzymatic Hydrolysis of Blue Shark Skin
Authors: Rodríguez‐Díaz Julio C. , Kurozawa Louise E. , Netto Flavia M. , Hubinger Miriam D.
Published: September 2011

Abstract:  Enzymatic hydrolysis of Blue shark skin using Protamex™ was evaluated seeking optimal process conditions. The influence of temperature (45 to 65 °C), pH (6.8 to 8), and enzyme/substrate ratio (E/S; 1% to 5%) on the responses of degree of hydrolysis and protein recovery were determined and process optimization was performed looking for maximum value of the responses. Optimum conditions were established (T = 51 °C, E/S = 4%, and pH = 7.1) and model validation was accomplished by triplicate. Under these conditions protein hydrolysates were prepared and characterized by their amino acid composition, peptide size distribution, and antioxidant capacity by ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays. A degree of hydrolysis of 19.3% and protein recovery of 90.3% were obtained at optimal conditions. Chemical score indicated that the hydrolysate supplies minimal essential amino acid requirements for adults. Molecular weight of peptides on the hydrolysate was below 6.5 kDa. Enzymatic hydrolysis process was efficient for recovery of low molecular weight peptides with important nutritional content and antioxidant activity (FRAP = 12 μmol eq. in FeSO4.7H2O/g of protein, TEAC = 225.3 μmol eq. in trolox/g of protein).
Comparison of Process Capability Index and SPC Control Limits Calculations When Using Different Inspection Tools
Authors: Gadalla Mohamed A. , Popielarczyk Miroslaw
Published: September 2011

A common practice in the manufacturing environment is to use different measuring tools for inspecting engineering products. These measuring tools range from hand held tools (manual) such as venire caliper, to manufactured inspection gages, and general purpose coordinate metrology based inspection tools such as: Coordinate Measuring Machine (CMM). Selecting the correct measuring tool is critical to measure the variation resulting from a manufacturing process. Three experiments have been conducted to evaluate the effect of this decision on the process capability index (Cpk), and the Statistical Process Control (SPC) control limits. It was found that the data collected from the CMM tends to be clustered around the process mean, while it is more spread for the other inspection tools. This situation leads to higher process capability index when the data is collected from a CMM compared with the other measuring tools. It also leads to variation in the calculations of the SPC control limits. This may cause in-consistency, confusion, and may result in unnecessary false alarms. A standard deviation monitoring graph has been suggested to monitor the capability of the measuring system to ensure the integrity of the interpretation of the output of the SPC system.
Effects of Aspect Ratio and Side Constraints on Elastic Buckling of Multi Wall Structures and Tubes
Authors: Chattopadhyay Arka P. , Frink Elizabeth , Lease Kevin , Xin X. J.
Published: September 2011

Buckling of plates and tubes plays an important role in structural safety and energy absorption. Although buckling of plates and tubes has been studied theoretically and experimentally in the past, the effects of aspect ratio and side constraint on buckling of multi-wall structures and tubes has not been investigated systematically. In this work, finite element simulations have been carried out to investigate the buckling behavior of multi-wall structures and tubes. A series of one- to three-panel walls and square tubes with various aspect ratios were simulated. The critical aspect ratios causing buckling mode transition were obtained and compared with theoretical predictions available in the literature. Effects of wall angle and side constraint on buckling behavior were investigated. The relevance of research findings to honeycomb-like structures was discussed.
A New Method for Determination of the Pre-Form Shapes and Their Corresponding Pressures in Tube-Hydroforming Process of SUS 304 in a Square Die
Authors: Tabatabaei S. A. , Panahi M. Shariat , Tabatabaei S. M. , Mashhadi M. Mosavi
Published: September 2011

The pre-form design in hydroforming process plays a key role in improving product quality, such as defect-free property and proper final product. This approach, however, leads not only to the increase of significant tool cost but also to the extended down-time of the production equipment. It is thus necessary to reduce time and man power through an effective method of pre-form design. In this paper, the equi-potential lines designed in the electric field are introduced to find an appropriate pre-form shape. The equi-potential lines generated between two conductors of different voltages show similar trends for minimum work paths between the undeformed shape and the deformed shape. Based on this similarity, the equi-potential lines obtained by arrangement of the initial and final shapes are utilized for the design of the pre-form, and then the finite element simulations are done for finding the forming pressure of each pre-form shape. Finally, the pre-form and its corresponding forming pressure with other parameters are used for training an artificial neural network. This trained neural network can be used for estimating the proper pre-form shape and forming pressure for a SUS304 tube inside an square die or other configurations of die (Geometrical shape) and tube (Diameter and thickness).
Fabrication of Supports for Solid Oxide Fuel Cells by Powder Injection Molding
Authors: Panahi Ali Keshavarz , Miyanaji Hadi , Taheri Moein , Janbakhsh Milad
Published: September 2011

In this paper the processing steps for producing SOFC (Solid Oxide Fuel Cell) supports by means of PIM (Powder Injection Molding) technique were investigated. Injection molding parameters in this study were divided into pressure-related (injection pressure and packing pressure), temperature-related (nozzle temperature and mold temperature), and time-related (injection rate and holding time) parameters. Keeping the other parameters (pressure-related, temperature-related and time-related parameters) constant at an optimized value, the effects of each of the molding parameters above were investigated. The results show that the short shot, warpage, weld line and void are the most common defects in molded parts. According to the results the short shot could be seen in low values of injection pressure, injection rate, nozzle and mold temperature. Also, warpage could be seen in high values of mold temperature, injection and packing pressure. Poor weld line was another defect that could be seen in low values of injection pressure, injection rate, nozzle and mold temperature. Also the void was one of the most common defects that could be seen in high values of injection rate and nozzle temperatures. Finally, using optimized molding parameters, the molded parts underwent debinding and sintering processes. Based on the results of thermal shock tests and the porosity measurements of the sintered parts, these molded parts possessed relatively desirable characteristics.
Indirect Approach to Ultrasonic Superposition in Micro-EDM
Authors: Schubert Andreas , Wolf Nicolas , Zeidler Henning , Schneider Jo¨rg
Published: September 2011

Micro Electro Discharge Machining is a well known process for machining microstructures with highest precision in hard and brittle or tough materials. The deeper the structures and therefore higher the aspect ratio, the more difficult it is to remove the ablated particles from the discharge zone and keep the process in stable condition. Flushing can be aided by vibration of either tool or workpiece. Thus, applying ultrasonic vibration to micro EDM has proven to enhance the process significantly. The vibration is most efficiently induced via the tool or workpiece directly to the discharge zone. However, to achieve an ultrasonic vibration of the tool or workpiece, a complex vibration system that operates in resonant mode is needed. Any crucial change of the vibrating parts results in a demanding and therefore expensive adjustment of the vibrating system. With this setup, the application of ultrasonic vibration is only profitable for large scale serial production. In this work a different approach of ultrasonic superposition to the EDM is proposed. A highly focused ultrasonic vibration is induced into the dielectric in a way to directly influence the discharge zone. This indirect ultrasonic superposition can be easily applied since it is independent of the tool or workpiece geometry. Experiments are carried out to examine the effects of the indirect ultrasonic superposition on the EDM process. First results show the possibility of enhancing micro-EDM by this approach.
Development of HA-PLGA Scaffold Encapsulating Intact BMP-2 Using Solid Freeform Fabrication Technology
Authors: Shim Jin-Hyung , Kim Jong Young , Kang Kyung Shin , Park Jung Kyu , Hahn Sei Kwang , Cho Dong-Woo
Published: September 2011

Tissue engineering is an interdisciplinary field that focuses on restoring and repairing tissues or organs. Cells, scaffolds, and biomolecules are recognized as three main components of tissue engineering. Solid freeform fabrication (SFF) technology is required to fabricate three-dimensional (3D) porous scaffolds to provide a 3D environment for cellular activity. SFF technology is especially advantageous for achieving a fully interconnected, porous scaffold. Bone morphogenic protein-2 (BMP-2), an important biomolecule, is widely used in bone tissue engineering to enhance bone regeneration activity. However, methods for the direct incorporation of intact BMP-2 within 3D scaffolds are rare. In this work, 3D porous scaffolds with poly(lactic-co-glycolic acid) chemically grafted hyaluronic acid (HA-PLGA), in which intact BMP-2 was directly encapsulated, were successfully fabricated using SFF technology. BMP-2 was previously protected by poly(ethylene glycol) (PEG), and the BMP-2/PEG complex was incorporated in HA-PLGA using an organic solvent. The HAPLGA/PEG/BMP-2 mixture was dissolved in chloroform and deposited via a multi-head deposition system (MHDS), one type of SFF technology, to fabricate a scaffold for tissue engineering. An additional air blower system and suction were installed in the MHDS for the solvent-based fabrication method. An in vitro evaluation of BMP-2 release was conducted, and prolonged release of intact BMP-2, for up to 28 days, was confirmed. After confirmation of advanced proliferation of pre osteoblasts, a superior differentiation effect of the HA-PLGA/PEG/BMP-2 scaffold was validated by measuring high expression levels of bone-specific markers, such as alkaline phosphatase (ALP) and osteocalcin (OC). We show that our solvent-based fabrication is a non-toxic method for restoring cellular activity. Moreover, the HAPLGA/PEG/BMP-2 scaffold was effective for bone regeneration.
Improvement of Geometric Accuracy in Incremental Forming by Using a Squeezing Toolpath Strategy With Two Forming Tools
Authors: Malhotra Rajiv , Cao Jian , Ren Feng , Kiridena Vijitha , Xia Z. Cedric
Published: September 2011

Single Point Incremental Forming (SPIF) is plagued by an unavoidable and unintended bending in the region of the sheet between the current tool position and the fixture, which leads to significant geometric inaccuracies. Double Sided Incremental Forming (DSIF) uses two tools, one on each side of the sheet to form the sheet into the desired shape. This work explores the capabilities of DSIF in terms of improving the geometric accuracy as compared to SPIF by using a novel toolpath strategy in which the sheet is locally squeezed between the two tools. Experiments and simulations are performed to show that this strategy can improve the geometric accuracy of the component significantly. An examination of the forming forces indicates that after a certain amount of deformation using this strategy a loss of contact occurs between the bottom tool and the sheet. The effects of this on the geometric accuracy are discussed as well.
Process Mechanics in Deep Rolling of Magnesium-Calcium (MgCa) Biomaterial
Authors: Salahshoor M. , Guo Y. B.
Published: September 2011

Magnesium-Calcium (MgCa) alloys have received considerable attention recently in medical device manufacturing industry specially in making biodegradable bone implants. Deep rolling (DR) is as a promising manufacturing technique to adjust surface characteristics of implants with the ultimate goal of being able to adjust corrosion rates of MgCa implants. Contact mechanics between rolling ball and the workpiece is essential to understand the DR process. Contact mechanics is further complicated by the normal force reduction due to hydraulic pressure loss at the tip of DR tool, and the penetration depth reduction due to elastic recovery. The measured normal force, in this study, shows maximum 23% reduction compared to theoretical value. The normal force drop is not uniform and increases with increasing applied pressure. A 2D axisymmetric, semi-infinite FEM model is developed and validated to predict the amount of elastic recovery after deep rolling. The dynamic mechanical behavior of the material is simulated using the internal state variable (ISV) plasticity model and implemented in FEM code using a user material subroutine. The simulated dent geometry agrees with the measured ones in terms of profile and depth. Simulation results suggest 8% elastic recovery on average.
Surface Integrity and Fatigue Strength of Hard Milled Surfaces
Authors: Li W. , Guo Y. B. , Barkey M. E. , Guo C. , Liu Z. Q.
Published: September 2011

Tool flank wear during hard milling adversely affects surface integrity and, therefore, fatigue strength of machined components. Surface integrity and machining accuracy deteriorate when tool wear progresses. In this paper, surface integrity and its impact on endurance limit of AISI H13 tool steel (50 ± 1 HRC) by milling using PVD coated tools are studied. The evolutions of surface integrity including surface roughness, microhardness and microstructure were characterized at three levels of tool flank wear (VB = 0, 0.1mm, 0.2mm). At each level of tool flank wear, the effects of cutting speed, feed, and radial depth-of-cut on surface integrity were investigated respectively. Fatigue endurance limits of the machined surfaces at different reliability levels were calculated and correlated with the experimentally determined fatigue life. The good surface finish and significant strain-hardening on the machined surfaces enhance endurance limit, which enables machined components have a fatigue life over 106 cycles.
Constant Current Density Compression Behavior of 304 Stainless Steel and Ti-6Al-4V During Electrically-Assisted Forming
Authors: Jones Joshua J. , Mears Laine
Published: September 2011

A metal forming technique which has more recently come of interest as an alternative to processes that use elevated temperatures at some stage during manufacturing is Electrically-Assisted Forming (EAF). EAF is a processing technique which applies electrical current through the workpiece concurrently while the material is being formed. At present, this method has only been studied on an experimental level in laboratory settings, and the heuristic results show increased fracture strain, reduced flow stress, and reduced springback; the enhanced process capability is beyond the range that would be expected from pure resistive heating alone. Thus far, when applying the electrical current through the workpiece during deformation, the current magnitude flowing through the workpiece has remained constant. Hence, for a compression loading, the current flux or density decreases as a result of an increasing specimen area. This work examines the effect of a non-constant current density (NCCD) and a constant current density (CCD) on the deformation behavior of 304 Stainless Steel and Ti-6Al-4V during uniaxial compression testing. Additionally, the application of a CCD is used to modify existing empirically-based EAF flow stress models for these materials. From this testing, it is shown that a CCD during forming can significantly reduce the flow stress of the material as compared to the NCCD tests. The reductions in the flow stress were increased at higher strains by approximately 30% and 15% for the 304 Stainless Steel and Ti-6Al-4V, respectively. More importantly, these flow stress curves are better representative of how the material responds to an applied electrical current as the specimen shape change is removed from the results. Also, the NCCD tests were approximated using an existing empirically-based EAF flow stress model and the CCD tests concluded that a new flow stress predictor model be introduced.
Phosphoproteomic Analysis of
Salmonella
-Infected Cells Identifies Key Kinase Regulators and SopB-Dependent Host Phosphorylation Events
Authors: Rogers Lindsay D. , Brown Nat F. , Fang Yuan , Pelech Steven , Foster Leonard J.
Published: September 2011

The foodborne pathogen
Salmonella
triggers distinct phosphorylation events in host cells to promote infection.
Fluoroquinolone Efflux in Streptococcus suis Is Mediated by SatAB and Not by SmrA
Authors: Escudero Jose Antonio , San Millan Alvaro , Gutierrez Belen , Hidalgo Laura , La Ragione Roberto M. , AbuOun Manal , Galimand Marc , Ferrándiz María José , Domínguez Lucas , de la Campa Adela G. , Gonzalez-Zorn Bruno
Published: September 2011

Streptococcus suis
is an emerging zoonotic pathogen. With the lack of an effective vaccine, antibiotics remain the main tool to fight infections caused by this pathogen. We have previously observed a reserpine-sensitive fluoroquinolone (FQ) efflux phenotype in this species. Here, SatAB and SmrA, two pumps belonging to the ATP binding cassette (ABC) and the major facilitator superfamily (MFS), respectively, have been analyzed in the fluoroquinolone-resistant clinical isolate BB1013. Genes encoding these pumps were overexpressed either constitutively or in the presence of ciprofloxacin in this strain. These genes could not be cloned in plasmids in
Escherichia coli
despite strong expression repression. Finally, site-directed insertion of
smrA
and
satAB
in the
amy
locus of the
Bacillus subtilis
chromosome using ligated PCR amplicons allowed for the functional expression and study of both pumps. Results showed that SatAB is a narrow-spectrum fluoroquinolone exporter (norfloxacin and ciprofloxacin), susceptible to reserpine, whereas SmrA was not involved in fluoroquinolone resistance. Chromosomal integration in
Bacillus
is a novel method for studying efflux pumps from Gram-positive bacteria, which enabled us to demonstrate the possible role of SatAB, and not SmrA, in fluoroquinolone efflux in
S. suis
.
Blue Dye and Red Light, a Dynamic Combination for Prophylaxis and Treatment of Cutaneous Candida albicans Infections in Mice
Authors: Dai Tianhong , Bil de Arce Vida J. , Tegos George P. , Hamblin Michael R.
Published: September 2011

The objective of this study was to investigate photodynamic therapy (PDT), using blue dye and red light, for prophylaxis and treatment of cutaneous
Candida albicans
infections in mice. A mouse model of skin abrasion infected with
C. albicans
was developed by inoculating wounds measuring 1.2 cm by 1.2 cm with 10
6
or 10
7
CFU. The use of a luciferase-expressing strain of
C. albicans
allowed real-time monitoring of the extent of infection in mice noninvasively through bioluminescence imaging. The phenothiazinium salts toluidine blue O (TBO), methylene blue (MB), and new methylene blue (NMB) were compared as photosensitizers (PS) for the photodynamic inactivation of
C. albicans
in vitro
. PDT
in vivo
was initiated either at 30 min or at 24 h after fungal inoculation to investigate the efficacies of PDT for both prophylaxis and treatment of infections. Light at 635 ± 15 nm or 660 ± 15 nm was delivered with a light dose of 78 J/cm
2
(for PDT at 30 min postinfection) or 120 J/cm
2
(for PDT at 24 h postinfection) in multiple exposures with bioluminescence imaging taking place after each exposure of light.
In vitro
studies showed that NMB was superior to TBO and MB as the PS in the photodynamic inactivation of
C. albicans
. The efficacy of PDT was related to the ratio of PS concentration to fungal cell density. PDT
in vivo
initiated either at 30 min or at 24 h postinfection significantly reduced
C. albicans
burden in the infected mouse skin abrasion wounds. These data suggest that PDT is a viable approach for prophylaxis and treatment of cutaneous
C. albicans
infections.
Contribution of Serotype and Genetic Background to Virulence of Serotype 3 and Serogroup 11 Pneumococcal Isolates
Authors: McAllister Lauren J. , Ogunniyi Abiodun D. , Stroeher Uwe H. , Leach Amanda J. , Paton James C.
Published: September 2011

The capsular serotype has long been associated with the virulence of
Streptococcus pneumoniae
. Here we present an in-depth study of phenotypic and genetic differences between serotype 3 and serogroup 11
S. pneumoniae
clinical isolates from both the general and indigenous populations of Australia. Both serotypes/groups included clonally unrelated strains with differences in well-known polymorphic virulence genes, such as
nanA
and
pspA
, as demonstrated by multilocus sequence typing and Western blot analysis. Nonetheless, the serotype 3 strains were consistently and significantly more virulent in mice than the serogroup 11 strains. Despite extensive genomic analysis, noncapsular genes common to one serotype/group but not the other were not identified. Nevertheless, following the conversion of a serotype 11A isolate to serotype 3 and subsequent analysis in an intranasal infection model, it was evident that both capsular and noncapsular factors determine the virulence phenotype in mice. However, it appears that these noncapsular factors vary from strain to strain.
Exploiting network effects in the provisioning of large scale systems
Authors: Nair Jayakrishnan , Wierman Adam , Zwart Bert
Published: September 2011

Online services today are characterized by a highly congestion sensitive user base, that also experiences strong positive network effects. A majority of these services are supported by advertising and are offered for free to the end user. We study the problem of optimal capacity provisioning for a profit maximizing firm operating such an online service in the asymptotic regime of a large market size. We show that network effects heavily influence the optimal capacity provisioning strategy, as well as the profit of the firm. In particular, strong positive network effects allow the firm to operate the service with fewer servers, which translates to increased profit.
Nanofibrous Resonant Membrane for Acoustic Applications
Authors: Kalinová K.
Published: September 2011

Because the absorption of lower-frequency sound is problematic with fibrous material made up of coarser fibers, highly efficient sound absorption materials must be developed. The focus of this paper is on the development of a new material with high acoustic absorption characteristics. For low-frequency absorption, structures based upon the resonance principle of nanofibrous layers are employed in which the resonance of some elements allows acoustic energy to be converted into thermal energy. A nanofibrous membrane was produced by an electrostatic spinning process from an aqueous solution of polyvinyl alcohol and the acoustic characteristics of the material measured. The resonant frequency prediction for the nanofibrous membrane is based on research into its production parameters. The distance between electrodes during the electrostatic spinning process determines the average diameter of the nanofibers, and the outlet velocity of the material determines its area density. The average diameter of nanofibers was measured using the Lucia software package directly from an electron microscope image. The resonant frequency of nanofibrous membranes was determined from the sound absorption coefficient and transmission loss measurement.
On Benzofuroindole Analogues as Smooth Muscle Relaxants
Authors: dela Peña Ike , Cheong Jae Hoon
Published: September 2011

At least two laboratories have independently reported the synthesis of benzofuroindole compounds having potential therapeutic implications in many disease states including those that involve smooth muscle hyperactivity. Through a series of in vitro screenings, they demonstrated the efficacy (and selectivity) of these compounds to potentiate large conductance calcium‐ (Ca2+‐) activated K+ (BKCa) channels, by far, the most characterized of all Ca2+‐dependent K+ channels. Interestingly, promising benzofuroindole derivatives such as compound 7 (10H‐benzo[4,5]furo[3,2‐b]indole) and compound 22 (4‐chloro‐7‐trifluoromethyl‐10H‐benzo[4,5]furo[3,2‐b]indole‐1‐carboxylic acid) both exhibited high bladder (versus aorta) selectivity, making them attractive alternative treatments for bladder overactivity. In recent reports, compound 22 (LDD175 or TBIC) also showed inhibition of ileum and uterine contractions, indicating multiple target tissues, which is not surprising as BKCa channels are ubiquitously expressed in the animal and human tissues. In this paper, the authors discuss the value of benzofuroindole compounds and the challenges that need to be overcome if they were considered as smooth muscle relaxants.
Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats
Authors: Korivi Mallikarjuna , Hou Chien-Wen , Huang Chih-Yang , Lee Shin-Da , Hsu Ming-Fen , Yu Szu-Hsien , Chen Chung-Yu , Liu Yung-Yang , Kuo Chia-Hua
Published: September 2011

Despite regular exercise benefits, acute exhaustive exercise elicits oxidative damage in liver. The present study determined the hepatoprotective properties of ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats. Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1 mg/kg bodyweight). After 10-week treatment, ten rats from each group performed exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric acid reactive substance (TBARS) (67%) and protein carbonyls (56%), were significantly (P<0.01) elevated after exhaustive exercise but alleviated in ginsenoside-Rg1 pretreated rats. Furthermore, exhaustive exercise drastically decreased glutathione (GSH) content (∼79%) with concurrent decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. However, these changes were attenuated in Rg1 group. Additionally, increased xanthine oxidase (XO) activity and nitric oxide (NO) levels after exercise were also inhibited by Rg1 pretreatment. For the first time, our findings provide strong evidence that ginsenoside-Rg1 can protect the liver against exhaustive exercise-induced oxidative damage.
Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview
Authors: Chai Hwa Chia , Phipps Maude Elvira , Chua Kek Heng
Published: September 2011

SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes includeMHCgenes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring inMHCgenes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6.
Telomere Shortening Alters the Kinetics of the DNA Damage Response after Ionizing Radiation in Human Cells
Authors: Drissi Rachid , Wu Jing , Hu Yafang , Bockhold Carol , Dome Jeffrey S.
Published: September 2011

Studies of telomerase-deficient mice and human cell lines have showed that telomere shortening enhances sensitivity to ionizing radiation (IR). The molecular basis for this observation remains unclear. To better understand the connection between telomere shortening and radiation sensitivity, we evaluated components of the DNA damage response pathway in normal human fibroblasts with short and long telomeres. Late-passage cells with short telomeres showed enhanced sensitivity to IR compared with early-passage cells with longer telomeres. Compared with early-passage cells, late-passage cells had a higher baseline level of phosphorylated H2AX protein (γH2AX) before IR but diminished peak levels of H2AX phosphorylation after treatment with IR. Both the appearance and disappearance of γH2AX foci were delayed in late-passage cells, indicative of delayed DNA repair. In contrast to the situation with H2AX, ATM and p53 phosphorylation kinetics were similar in early- and late-passage cells, but phosphorylation of the chromatin-bound ATM targets SMC1 and NBS1 was delayed in late-passage cells. Because impaired phosphorylation associated with short telomeres was restricted to chromatin-bound ATM targets, chromatin structure was assessed. DNA from cells with short telomeres was more resistant to digestion with micrococcal nuclease, indicative of compacted chromatin. Moreover, cells with short telomeres showed histone acetylation and methylation profiles consistent with heterochromatin. Together our data suggest a model in which short telomeres induce chromatin structure changes that limit access of activated ATM to its downstream targets on the chromatin, thereby providing a potential explanation for the increased radiation sensitivity seen with telomere shortening. Cancer Prev Res; 4(12); 1973–81. ©2011 AACR.
Effects of Manidipine and Delapril in Hypertensive Patients With Type 2 Diabetes Mellitus
Authors: Ruggenenti Piero , Lauria Giuseppe , Iliev Ilian Petrov , Fassi Anna , Ilieva Aneliya Parvanova , Rota Stefano , Chiurchiu Carlos , Barlovic Drazenka Pongrac , Sghirlanzoni Angelo , Lombardi Raffaella , Penza Paola , Cavaletti Guido , Piatti Maria Luisa , Frigeni Barbara , Filipponi Marco , Rubis Nadia , Noris Greta , Motterlini Nicola , Ene-Iordache Bogdan , Gaspari Flavio , Perna Annalisa , Zaletel Jelka , Bossi Antonio , Dodesini Alessandro Roberto , Trevisan Roberto , Remuzzi Giuseppe ,   for the DEMAND Study Investigators
Published: September 2011

To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range [IQR]) was 0.32 mL/min per 1.73 m
2
(IQR: 0.16–0.50 mL/min per 1.73 m
2
) on combined therapy, 0.36 mL/min per 1.73 m
2
(IQR: 0.18–0.53 mL/min per 1.73 m
2
) on delapril, and 0.30 mL/min per 1.73 m
2
(IQR: 0.12–0.50 mL/min per 1.73 m
2
) on placebo (
P
=0.87 and
P
=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04–0.78;
P
=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07–0.99;
P
=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24–0.87;
P
=0.017) and 0.52 (0.27–0.99;
P
=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (
P
=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.
Development of Statistical Typhoon Intensity Prediction: Application to Satellite-Observed Surface Evaporation and Rain Rate (STIPER)
Authors: Gao Si , Chiu Long S.
Published: September 2011

A statistical–dynamical model has been used for operational guidance for tropical cyclone (TC) intensity prediction. In this study, several multiple linear regression models and neural network (NN) models are developed for the intensity prediction of western North Pacific TCs at 24-, 48-, and 72-h intervals. The multiple linear regression models include a model of climatology and persistence (CLIPER), a model based on the Statistical Typhoon Intensity Prediction System (STIPS), which serves as the base regression model (BASE), and a model of STIPS with additional satellite estimates of surface evaporation (SLHF) and inner-core rain rate (IRR, STIPER model). A revised equation for the TC maximum potential intensity is derived using Tropical Rainfall Measuring Mission Microwave Imager optimally interpolated sea surface temperature data, which have higher temporal and spatial resolutions. Analyses of the resulting models show the marginal improvement of STIPER over BASE. However, IRR and SLHF are found to be significant predictors in the predictor pool. Neural network models using the same predictors as STIPER show reductions of the mean absolute errors of 7%, 11%, and 16% relative to STIPER for 24-, 48-, and 72-h forecasts, respectively. The largest improvement is found for the intensity forecasts of the rapidly intensifying and rapidly decaying TCs.
Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment
Authors: Chu Su , McDonald Tinisha , Lin Allen , Chakraborty Sujata , Huang Qin , Snyder David S. , Bhatia Ravi
Published: September 2011

Imatinib mesylate treatment markedly reduces the burden of leukemia cells in chronic myelogenous leukemia (CML) patients. However, patients remain at risk for relapse on discontinuing treatment. We have previously shown that residual BCR-ABL+ progenitors can be detected in CML patients within the first 2 years of imatinib treatment. However, reduced rates of relapse and continued decline of BCR-ABL levels with prolonged treatment, together with the ability of selected patients to maintain remission after discontinuing treatment, led us to investigate whether prolonged imatinib exposure resulted in reduction or elimination of BCR-ABL+ stem cells. We evaluated BCR-ABL expression in CD34+CD38+ (38+) committed progenitors and CD34+CD38− (38−) stem/primitive progenitor cells in samples from CML patients on imatinib treatment for at least 4 years with cytogenetic and molecular response. High levels of BCR-ABL expression were maintained over time in the 38− stem cell fraction. The absolute frequency of BCR-ABL+ cells as determined by limiting dilution analysis was consistently higher in 38− compared with 38+ cells. Transplantation into NOD/SCID-IL2Rγ-chain knockout mice demonstrated that BCR-ABL+ cells had long-term in vivo repopulating capacity. These results directly demonstrate that BCR-ABL+ stem cells persist in CML patients despite prolonged treatment with imatinib, and support ongoing efforts to target this population.