bluuebunny/crossref_metadata_2025 huggingface dataset:
Benign paroxysmal torticollis of infancy: An underdiagnosed condition
Authors: Hadjipanayis Adamos , Efstathiou Elisavet , Neubauer David
Published: February 2015

Benign paroxysmal torticollis is probably an under‐diagnosed condition of infancy. It is a self‐limiting disorder characterised by periods of unusual, sustained posture of the head and neck, during which the head tilts to one side. Episodes are often accompanied by marked autonomic features, irritability, ataxia, apathy and drowsiness. They last several hours to a few days and are often recurring every few weeks. They subside within the pre‐school years; however, during later childhood, there is a tendency to develop migraine. Three cases of benign paroxysmal torticollis are presented and are compared with cases in the literature. A telephone survey has been conducted to determine what is the general awareness of paediatricians of this condition in Cyprus. Eighty‐two paediatricians were randomly selected out of 235 paediatricians. All of them agreed to participate. Our cases revealed that benign paroxysmal torticollis may coexist with other problems during infancy. The telephone survey showed that only two out of eighty‐two (2.4%) of the paediatricians are aware of the condition, and none of them was confident regarding the management. Our telephone survey clearly shows that Cypriot paediatricians are not familiar with benign paroxysmal torticollis in infancy which is a benign, self‐limiting disorder. It is essential to recognise the condition and to reassure parents of its benign course and not to be misdiagnosed for other disorders, such as epileptic seizures. We have shown again that benign paroxysmal torticollis in infancy may coexist with motor delay and hearing problems.
Ectoparasites of medical and veterinary importance: drug resistance and the need for alternative control methods
Authors: McNair Carol M
Published: February 2015

Objectives

Despite multiple attempts at eradication, many ectoparasites of humans and domestic livestock remain a persistent problem in the modern world. For many years, a range of pesticide drugs including organophosphates, organochlorides and synthetic pyrethroids provided effective control of these parasites; but intensive use of these drugs has led to the evolution of resistance in many target species. This paper aims to review the effectiveness of current control methods and discuss potential alternatives for the long term sustainable control of ectoparasites.

Key Findings

Important medical ectoparasites such as scabies mites, head lice and bed bugs present a significant public health problem, and so adequate control methods are essential. Ectoparasites of domestic livestock and farmed fish (for example sheep scab mites, poultry mites and sea lice) are also of concern given the increasing strain on the world's food supply. These parasites have become resistant to several classes of pesticide, making control very difficult. Recently, an increasing amount of research has focussed on alternative control methods such as insect growth regulators, biological control using essential oils or fungi, as well as vaccine development against some ectoparasites of medical and veterinary importance.

Drug resistance is prevalent in all of the ectoparasites discussed in this review. A wide variety of alternative control methods have been identified, however further research is necessary in order for these to be used to successfully control ectoparasitic diseases in the future.
Investigation of the interactions of enteric and hydrophilic polymers to enhance dissolution of griseofulvin following hot melt extrusion processing
Authors: Bennett Ryan C , Keen Justin M , Bi Yunxia (Vivian) , Porter Stuart , Dürig Thomas , McGinity James W
Published: February 2015

Objectives

This study focuses on the application of hot melt extrusion (HME) to produce solid dispersions containing griseofulvin (GF) and investigates the in-vitro dissolution performance of HME powders and resulting tablet compositions containing HME-processed dispersions.

Methods

Binary, ternary and quaternary dispersions containing GF, enteric polymer (Eudragit L100-55 or AQOAT-LF) and/or vinyl pyrrolidone-based polymer (Plasdone K-12 povidone or S-630 copovidone) were processed by HME. Two plasticizers, triethyl citrate (TEC) and acetyl tributyl citrate (ATBC), were incorporated to aid in melt processing and to modify release of GF in neutral media following a pH-change in dissolution. Products were characterized for GF recovery, degrees of compositional amorphous character, intermolecular interactions and non-sink dissolution performance.

Key findings

Binary dispersions exhibited lower maximum observed concentration values and magnitudes of supersaturated GF in neutral media dissolution in comparison with the ternary dispersions. The quaternary HME products, 1 : 2 : 1 : 0.6 GF : L100-55 : S-630 : ATBC and GF : AQOAT-LF : K-12 : ATBC, were determined as the most optimal concentration-enhancing compositions due to increased hydrogen bonding of enteric functional groups with carbonyl/acetate groups of vinyl pyrrolidone-based polymers, reduced compositional crystallinity and presence of incorporated hydrophobic plasticizer.

Conclusions

HME products containing combinations of concentration-enhancing polymers can supersaturate and sustain GF dissolution to greater magnitudes in neutral media following the pH-transition and be compressed into immediate-release tablets exhibiting similar dissolution profiles.
A gastro-resistant ovalbumin bi-layered mini-tablet-in-tablet system for the delivery of L
actobacillus acidophilus probiotic to simulated human intestinal and colon conditions
Authors: Govender Mershen , Choonara Yahya Essop , van Vuuren Sandy , Kumar Pradeep , du Toit Lisa Claire , Pillay Viness
Published: February 2015

Objectives

The viability of probiotic bacteria during formulation processes and delivery is vital to ensure health benefits. This study focuses on the use of gastro-resistant denatured ovalbumin for the targeted delivery of probiotic Lactobacillus acidophilus to simulated human intestinal and colon conditions through a bi-layered mini-tablet-in-tablet system (BMTTS).

Methods

The BMTTS consists of two gastro-resistant ovalbumin mini-tablets containing L. acidophilus suspended in lactose and eudragit S100 for targeted intestinal and colonic delivery respectively. Luminescence has been utilized to ensure probiotic viability during formulation processes in addition to determining all probiotic release profiles. The mechanism of probiotic release from the ovalbumin matrix was ascertained using mathematical modelling and molecular docking studies. Magnetic resonance imaging and differential scanning calorimetry are also included as part of the in-vitro characterization of the ovalbumin system.

Key findings

The BMTTS was effective in the delivery of L. acidophilus to simulated human intestinal and colon conditions. Formulation processes were furthermore determined to maintain probiotic viability. Statistical analysis of the release data noted a significant effect of pH denaturation on the release properties of ovalbumin. Magnetic resonance imaging results have indicated a decrease in ovalbumin matrix size upon exposure to simulated intestinal fluid. Molecular docking studies carried out depicted the interaction and binding positions inherent to the ovalbumin–pancreatic trypsin interaction complex indicating the possible enzymatic degradation of ovalbumin leading to the release of the probiotic from the protein matrix.

Conclusions

The BMTTS has been determined to be effective in the protection and delivery of probiotic L. acidophilus to simulated human intestinal and colonic conditions. Molecular docking analysis has noted that pancreatin exerts a significant effect on probiotic release from the gastro-resistant ovalbumin matrix.
Stimulating effects of a diet negative in dietary cation–anion difference on calcium absorption from the rumen in sheep
Authors: Wilkens M.R. , Praechter C. , Breves G. , Schröder B.
Published: February 2015

The concept of feeding anionic salts in late gestation is widely used to prevent milk fever in dairy cows. While the effects of these diets on renal Ca excretion and tissue responsiveness towards parathyroid hormone have clearly been demonstrated, data on a potential impact on gastrointestinal Ca absorption are conflicting. Therefore, the aim of this study was to investigate the influence of feeding a diet negative in dietary cation–anion difference (DCAD) on ruminal mineral concentrations, fermentation products, electrophysiological properties of rumen epithelia and Ca flux rates. For this purpose, sheep were kept for 3 weeks on diets that were either positive or negative in DCAD. The induction of a compensated hyperchloremic metabolic acidosis could be demonstrated by increased plasma Cl and enhanced concentrations of ionised Ca, while plasma concentrations of and base excess were decreased with the low DCAD diet. Neither transmural potential differences nor fermentation products were affected, but ruminal concentrations of Cl and Mg as well as the relation of ionised to total Ca were increased. Ussing chamber experiments revealed alterations of electrophysiological parameters and an increase in the electroneutral component of Ca flux rates from the mucosal to the serosal side of rumen epithelium. As plasma calcitriol concentrations were not affected, it can be concluded that the administration of anionic salts results in a vitamin D‐independent stimulation of ruminal Ca transport.
Small‐band Fixed‐bAsymptotics for Weighted Covariance Estimation in Fractional Cointegration
Authors: Hualde Javier , Iacone Fabrizio
Published: February 2015

In a standard cointegrating framework, Phillips (1991) introduced the weighted covariance (WC) estimator of cointegrating parameters. Later, Marinucci (2000) applied this estimator to fractional circumstances and, like Phillips (1991), analysed the so‐called small‐basymptotic approximation to its sampling distribution. Recently, an alternative limiting theory (fixed‐basymptotics) has been successfully employed to approximate sampling distributions. With the purpose of comparing both approaches, we derive here the fixed‐blimit of WC estimators in a fractional setting, filling also some gaps in the traditional (small‐b) theory. We also provide some Monte Carlo evidence that suggests that the fixed‐blimit is more accurate.
A Smooth Block Bootstrap for Statistical Functionals and Time Series
Authors: Gregory Karl B. , Lahiri Soumendra N. , Nordman Daniel J.
Published: February 2015

Unlike with independent data, smoothed bootstraps have received little consideration for time series, although data smoothing within resampling can improve bootstrap approximations, especially when target distributions depend on smooth population quantities (e.g., marginal densities). For approximating a broad class statistics formulated through statistical functionals (e.g., LL‐estimators, and sample quantiles), we propose a smooth bootstrap by modifying a state‐of‐the‐art (extended) tapered block bootstrap (TBB). Our treatment shows that the smooth TBB applies to time series inference cases not formally established with other TBB versions. Simulations also indicate that smoothing enhances the block bootstrap.
On the Transmission of Memory in Garch‐in‐Mean Models
Authors: Conrad Christian , Karanasos Menelaos
Published: February 2015

In this article, we show that in times series models with in‐mean and level effects, persistence will be transmitted from the conditional variance to the conditional mean and vice versa. Hence, by studying the conditional mean/variance independently, one will obtain a biased estimate of the true degree of persistence. For the specific example of an AR(1)‐APARCH(1,1)‐in‐mean‐level process, we derive the autocorrelation function, the impulse response function and the optimal predictor. Under reasonable assumptions, the AR(1)‐APARCH(1,1)‐in‐mean‐level process will be observationally equivalent to an autoregressive moving average (ARMA)(2,1) process with the largest autoregressive root being close to one. We illustrate the empirical relevance of our results with applications to S&P 500 return and US inflation data.
Double Bootstrap Confidence Intervals in the Two‐Stage DEA Approach
Authors: Chronopoulos Dimitris K. , Girardone Claudia , Nankervis John C.
Published: February 2015

Contextual factors usually assume an important role in determining firms' productive efficiencies. Nevertheless, identifying them in a regression framework might be complicated. The problem arises from the efficiencies being correlated with each other when estimated by Data Envelopment Analysis, rendering standard inference methods invalid. Simar and Wilson (2007) suggest the use of bootstrap algorithms that allow for valid statistical inference in this context. This article extends their work by proposing a double bootstrap algorithm for obtaining confidence intervals with improved coverage probabilities. Moreover, acknowledging the computational burden associated with iterated bootstrap procedures, we provide an algorithm based on deterministic stopping rules, which is less computationally demanding. Monte Carlo evidence shows considerable improvement in the coverage probabilities after iterating the bootstrap procedure. The results also suggest that percentile confidence intervals perform better than their basic counterpart.
Dispersal potential mediates effects of local and landscape factors on plant species richness in maeulsoop forests of Korea
Authors: Koh Insu , Reineking Björn , Park Chan‐Ryul , Lee Dowon
Published: February 2015

Questions

At what spatial scales do plant species with different dispersal potentials respond to landscape characteristics? Do seed rain data support these scale‐dependent responses? Does the relative importance of local factors and surrounding landscape characteristics vary according to species dispersal potential?

Location

Agricultural landscape, Jinan County, Korea.

Methods

Forest plant species from 15 traditional Korean village forests, maeulsoops, were recorded and categorized into short‐distance dispersal (SDD) and long‐distance dispersal (LDD) species based on dispersal mode. Seed rain samples were collected every 2 wk for 4 mo and identified at the genus level. Local factors (anthropogenic influence and maeulsoop area) were assessed through field surveys and satellite imagery. Landscape characteristics surrounding maeulsoops (forest cover diversity, composition and fragmentation) were assessed at multiple spatial scales using Shannon‐Wiener index and PCA. The best regression model at each scale was identified by model selection based on AICc, and the effect of each explanatory variable on species richness was quantified with hierarchical partitioning.

Results

A total of 107 forest plant species (39 SDD and 68 LDD) were recorded, and a total of 25 bird‐dispersed genera were identified in seed rain samples. Species richness in plant records and genus richness in seed samples were strongly affected by anthropogenic influence and maeulsoop area, respectively. SDD species richness was significantly and positively influenced by total forest cover at small scales of around 150 m. In contrast, LDD species richness was significantly influenced by deciduous forest cover at large scales (1500–3500 m). At these larger scales, the relative importance of landscape characteristics for species richness was higher for LDD than for SDD. These results for LDD species were most notably supported by genus richness in seed rain data.

Conclusions

The most important findings of the study highlight that (1) plant species responses to forest cover are scale‐dependent; and (2) dispersal potential mediates the effects of local and landscape factors on plant species richness. The results suggest that conservation strategies for native forest species in maeulsoops should not only focus on habitat‐specific characteristics but also consider species‐specific interactions with surrounding landscapes.
Embedded Damage Localization Subsystem Based on Elastic Wave Propagation
Authors: Wandowski Tomasz , Malinowski Pawel , Ostachowicz Wieslaw , Rawski Mariusz , Tomaszewicz Pawel , Luba Tadeusz , Borowik Grzegorz
Published: February 2015

This article presents an embedded signal processing subsystem constituting a part of a whole structural health monitoring system (SHM). Typical SHM system is responsible for elastic wave generation and sensing, signal acquisition, and signal processing. Signal processing subsystem was designed with the aim of localizing damage utilizing elastic wave propagation in the interrogated structure. The embedded signal processing subsystem is realized in a field programmable gate array chip, which also implements a damage localization algorithm designed for creating damage maps that can indicate elastic wave reflection sites within the investigated structure. Elastic waves are generated and received using a prototype electronic system developed specially for this purpose. Piezoelectric transducers are arranged in networks with different geometrical configurations (strip, cross, and square). Elastic waves are excited by a five‐cycle tone burst signal with carrier frequency of 220 kHz. The investigated structure is a simple isotropic panel made out of aluminum alloy. First, dispersion curves are computed on the basis of registered elastic wave signals. These are subsequently used in the damage localization process. The damage localization process utilizes the base antisymmetric A0 mode. This article presents results of experimental verification of the developed damage localization algorithm as well as results of damage localization by the embedded subsystem.
Divisome‐dependent subcellular localization of cell–cell joining protein SepJ in the filamentous cyanobacterium Anabaena
Authors: Ramos‐León Félix , Mariscal Vicente , Frías José E. , Flores Enrique , Herrero Antonia
Published: February 2015

Heterocyst‐forming cyanobacteria are multicellular organisms that grow as filaments that can be hundreds of cells long. Septal junction complexes, of which SepJ is a possible component, appear to join the cells in the filament. SepJ is a cytoplasmic membrane protein that contains a long predicted periplasmic section and localizes not only to the cell poles in the intercellular septa but also to a position similar to a Z ring when cell division starts suggesting a relation with the divisome. Here, we created a mutant of Anabaena sp. strain PCC 7120 in which the essential divisome gene ftsZ is expressed from a synthetic NtcA‐dependent promoter, whose activity depends on the nitrogen source. In the presence of ammonium, low levels of FtsZ were produced, and the subcellular localization of SepJ, which was investigated by immunofluorescence, was impaired. Possible interactions of SepJ with itself and with divisome proteins FtsZ, FtsQ and FtsW were investigated using the bacterial two‐hybrid system. We found SepJ self‐interaction and a specific interaction with FtsQ, confirmed by co‐purification and involving parts of the SepJ and FtsQ periplasmic sections. Therefore, SepJ can form multimers, and in Anabaena, the divisome has a role beyond cell division, localizing a septal protein essential for multicellularity.
The Brassica napus receptor‐like protein RLM2 is encoded by a second allele of the LepR3/Rlm2 blackleg resistance locus
Authors: Larkan Nicholas J. , Ma Lisong , Borhan Mohammad Hossein
Published: February 2015

Leucine‐rich repeat receptor‐like proteins (LRR‐RLPs) are highly adaptable parts of the signalling apparatus for extracellular detection of plant pathogens. Resistance to blackleg disease of Brassica spp. caused by Leptosphaeria maculans is largely governed by host race‐specific R‐genes, including the LRR‐RLP gene LepR3. The blackleg resistance gene Rlm2 was previously mapped to the same genetic interval as LepR3. In this study, the LepR3 locus of the Rlm2 Brassica napus line ‘Glacier DH24287’ was cloned, and B. napus transformants were analysed for recovery of the Rlm2 phenotype. Multiple B. napus, B. rapa and B. juncea lines were assessed for sequence variation at the locus. Rlm2 was found to be an allelic variant of the LepR3 LRR‐RLP locus, conveying race‐specific resistance to L. maculans isolates harbouring AvrLm2. Several defence‐related LRR‐RLPs have previously been shown to associate with the RLK SOBIR1 to facilitate defence signalling. Bimolecular fluorescence complementation (BiFC) and co‐immunoprecipitation of RLM2‐SOBIR1 studies revealed that RLM2 interacts with SOBIR1 of Arabidopsis thaliana when co‐expressed in Nicotiana benthamiana. The interaction of RLM2 with AtSOBIR1 is suggestive of a conserved defence signalling pathway between B. napus and its close relative A. thaliana.
Exploration of peptides bound to MHC class I molecules in melanoma
Authors: Pritchard Antonia L. , Hastie Marcus L. , Neller Michelle , Gorman Jeffrey J. , Schmidt Chris W. , Hayward Nicholas K.
Published: February 2015

Advancements in high‐resolution HPLC and mass spectrometry have reinvigorated the application of this technology to identify peptides eluted from immunopurified MHC class I molecules. Three melanoma cell lines were assessed using w6/32 isolation, peptide elution and HPLC purification; peptides were identified by mass spectrometry. A total of 13 829 peptides were identified; 83–87% of these were 8–11 mers. Only approximately 15% have been described before. Subcellular locations of the source proteins showed even sampling; mRNA expression and total protein length were predictive of the number of peptides detected from a single protein. HLA‐type binding prediction for 10 078 9/10 mer peptides assigned 88–95% to a patient‐specific HLA subtype, revealing a disparity in strength of predicted binding. HLA‐B*27‐specific isolation successfully identified some peptides not found using w6/32. Sixty peptides were selected for immune screening, based on source protein and predicted HLA binding; no new peptides recognized by antimelanoma T cells were discovered. Additionally, mass spectrometry was unable to identify several epitopes targeted ex vivo by one patient's T cells.
Skin colour, skin redness and melanin biometric measurements: comparison study between Antera® 3D, Mexameter® and Colorimeter®
Authors: Matias Ana Rita , Ferreira Marta , Costa Paulo , Neto Patrícia
Published: February 2015

Background

The actual skin colorimeters analyse reflect values from a limited number of broad spectral bands and consequently present limited reproducibility and specificity when measuring skin colour. Here, Antera 3D®, a new device which uses reflectance mapping of seven different light wavelengths spanning the entire visible spectrum, has been compared with Mexameter® MX‐18, an established narrow‐band reflectance spectrophotometer and with Colorimeter® CL‐400, an established tristimulus colorimetric instrument.

Methods

Thirty volunteers were exposed to a controlled ultra‐violet B light. Measurements with Antera 3D®, Mexameter® MX‐18 and Colorimeter® CL‐400 were done before treatment and after 2, 7 and 14 days.

Results

Antera 3D® showed to have a better sensitivity and specificity than Mexameter® MX‐18 regarding the melanin parameter. A similar sensitivity between Antera 3D® and Mexameter® MX‐18 was found for erythema determination and also for the Commission Internationale de l'Eclairage L*, a* and b* parameters between Antera 3D® and Colorimeter® CL‐400. Good correlations were observed for all the parameters analysed. Repeatability of Mexameter® MX‐18 and Colorimeter® CL‐400 values were lower than that of Antera 3D® for all the parameters analysed.

Conclusion

Antera 3D®, such as Mexameter® MX‐18 and Colorimeter® CL‐400, are robust, sensitive and precise equipment for the skin colour analysis.
Efficacy of education followed by computerized provider order entry with clinician decision support to reduce red blood cell utilization
Authors: Zuckerberg Gabriel S. , Scott Andrew V. , Wasey Jack O. , Wick Elizabeth C. , Pawlik Timothy M. , Ness Paul M. , Patel Nishant D. , Resar Linda M.S. , Frank Steven M.
Published: February 2015

BACKGROUND

Two necessary components of a patient blood management program are education regarding evidence‐based transfusion guidelines and computerized provider order entry (CPOE) with clinician decision support (CDS). This study examines changes in red blood cell (RBC) utilization associated with each of these two interventions.

STUDY DESIGN AND METHODS

We reviewed 5 years of blood utilization data (2009‐2013) for 70,118 surgical patients from 10 different specialty services at a tertiary care academic medical center. Three distinct periods were compared: 1) before blood management, 2) education alone, and 3) education plus CPOE. Changes in RBC unit utilization were assessed over the three periods stratified by surgical service. Cost savings were estimated based on RBC acquisition costs.

RESULTS

For all surgical services combined, RBC utilization decreased by 16.4% with education alone (p = 0.001) and then changed very little (2.5% increase) after subsequent addition of CPOE (p = 0.64). When we compared the period of education plus CPOE to the pre–blood management period, the overall decrease was 14.3% (p = 0.008; 2102 fewer RBC units/year, or a cost avoidance of $462,440/year). Services with the highest massive transfusion rates (≥10 RBC units) exhibited the least reduction in RBC utilization.

CONCLUSIONS

Adding CPOE with CDS after a successful education effort to promote evidence‐based transfusion practice did not further reduce RBC utilization. These findings suggest that education is an important and effective component of a patient blood management program and that CPOE algorithms may serve to maintain compliance with evidence‐based transfusion guidelines.
Does offering human immunodeficiency virus testing at the time of blood donation reduce transfusion transmission risk and increase disclosure counseling? Results of a randomized controlled trial, São Paulo, Brazil
Authors: Goncalez Thelma T. , Blatyta Paula F. , Santos Fernanda M. , Montebello Sandra , Esposti Sandra P.D. , Hangai Fatima N. , Salles Nanci A. , Mendrone Alfredo , Truong Hong‐Ha M. , Sabino Ester C. , McFarland Willi
Published: February 2015

BACKGROUND

In a randomized controlled trial (RCT) in a blood bank in São Paulo, we tested the hypotheses that offering client‐centered human immunodeficiency virus (HIV) counseling and testing to blood donors would: 1) reduce the risk of HIV contamination in the blood supply by diverting higher‐risk, test‐seeking donors away from donation and 2) increase return for results and referrals to care.

STUDY DESIGN AND METHODS

We randomly selected weeks between August 2012 and May 2013 when donors were offered HIV counseling and testing (n = 6298), leaving usual procedure weeks as control (n = 5569).

RESULTS

Few candidate donors chose HIV testing (n = 81, 1.3%). There was no significant difference in herpes simplex virus Type 2 (HSV‐2) prevalence (a marker of sexual risk) among donors during intervention weeks compared to control (10.4% vs. 11.1%, p = 0.245). No donor choosing testing was HIV infected, and there was no difference in HSV‐2 prevalence between testers and donors (9.9% vs. 10.4%, p = 0.887). Returning for positive results did not differ between testers and donors (three of three vs. 58 of 80, p = 0.386). A higher proportion of donors acknowledged that HIV testing was a strong motivation to donate during intervention weeks compared to control (2.6% vs. 2.0%, p = 0.032).

CONCLUSION

The evidence of our RCT is that offering HIV counseling and testing at the time of donation would not change the risk of contamination in the blood supply, nor improve results disclosure and referral to care.
Exploring the heterogeneity of the hematopoietic stem and progenitor cell pool in cord blood: simultaneous staining for side population, aldehyde dehydrogenase activity, and CD34 expression
Authors: Frändberg Sofia , Boreström Cecilia , Li Susann , Fogelstrand Linda , Palmqvist Lars
Published: February 2015

BACKGROUND

The stem cell content in cord blood (CB) units is routinely assessed regarding nucleated cells, CD34+ cell count, and number of colony‐forming units (CFUs). Efforts are made toward finding better ways of defining stemness of CB units. Side population (SP) phenotype and activity of aldehyde dehydrogenase (ALDH) are functional markers of stemness that can be assayed using flow cytometry.

STUDY DESIGN AND METHODS

We have developed a protocol for simultaneous determination of CD34+, SP, and ALDH+ populations in relation to immature white blood cells (CD45dim) in CB. Viable nucleated cells were consecutively stained for SP and ALDH activity and with antibodies against the CD45, CD34, and CD117 antigens.

RESULTS

The SP and ALDH+ populations could reliably be measured simultaneously. The median sizes of the SP and the ALDH+ populations were 0.85 and 3.3% of CD45dim cells, respectively. There was no overlap between the SP and ALDH+ populations. Cells that were ALDH+ expressed CD34 and CD117, but SP cells were negative for these markers. The ALDH+ cell content correlated with CD34+ cell content (p < 0.001) and with CFU–granulocyte‐macrophage (GM; p = 0.03) but not with total CFUs. SP did not correlate with CD34+, CFU‐GM, or total CFU.

CONCLUSIONS

We show that simultaneous detection of the CD34, SP, and ALDH+ cells is clearly feasible using only small amounts of CB. In CB, ALDH+, and CD34+ cells are overlapping populations distinctly separated from the SP population. The difference in relation to the capacity for colony growth between ALDH+ and SP underlines that they define different cell populations.
Impact of genetic variation in the SMIM1 gene on Vel expression levels
Authors: Haer‐Wigman Lonneke , Stegmann Tamara C. , Solati Shabnam , Ait Soussan Aïcha , Beckers Erik , van der Harst Pim , van Hulst‐Sundermeijer Marga , Ligthart Peter , van Rhenen Dick , Schepers Hein , de Haas Masja , van der Schoot C. Ellen
Published: February 2015

BACKGROUND

Serologic determination of the Vel– phenotype is challenging due to variable Vel expression levels. In this study we investigated the genetic basis for weak Vel expression levels and developed a high‐throughput genotyping assay to detect Vel– donors.

STUDY DESIGN AND METHODS

In 548 random Caucasian and 107 Vel+w donors genetic variation in the SMIM1 gene was studied and correlated to Vel expression levels. A total of 3366 Caucasian, 621 black, and 333 Chinese donors were screened with a high‐throughput genotyping assay targeting the SMIM1*64_80del allele.

RESULTS

The Vel+w phenotype is in most cases caused by the presence of one SMIM1 allele carrying the major allele of the rs1175550 SNP in combination with a SMIM1*64_80del allele or in few cases caused by the presence of the SMIM1*152T>A or SMIM1*152T>G allele. In approximately 6% of Vel+w donors genetic factors in SMIM1 could not explain the weak expression. We excluded the possibility that lack of expression of another blood group system was correlated with weak Vel expression levels. Furthermore, using a high‐throughput Vel genotyping assay we detected two Caucasian Vel– donors.

CONCLUSION

Weak Vel expression levels are caused by multiple genetic factors in SMIM1 and probably also by other genetic or environmental factors. Due to the variation in Vel expression levels, serologic determination of the Vel– phenotype is difficult and a genotyping assay targeting the c.64_80del deletion in SMIM1 should be used to screen donors for the Vel– phenotype.
On the Properties of a Traveling Ruck in a Flexible Strip
Authors: O'Keefe A. N. , Gooch S. D.
Published: February 2015

This paper concerns the analysis of a traveling ruck. A ruck is the resulting postbuckled shape created when the ends of a slender, flexible, flat-lying strip of non-negligible self-weight are displaced toward one another. We consider the case of a semi-infinite strip with a fixed end displacement such that the shape of the ruck remains constant. The first mode of vibration of such a ruck is a translational rolling motion parallel to the length of the strip. In this paper, we calculate the potential energy of the static ruck and determine the relationship between the translational velocity and the kinetic energy of the traveling ruck. The results are formulated as nondimensional terms so that the methodology, developed in this paper, can be applied more generally. Results of physical testing show good comparison to predictions. The results from the study are applied to establish the feasibility of creating a large-scale kinetic sculpture, Sun, Land, and Sea. Sun, Land, and Sea is a kinetic sculpture proposed by internationally renowned artist Len Lye. The sculpture would feature a 3 m tall ruck that travels a distance of 45 m along a stainless steel strip.
Characterization of the Discrepancies Between Four-Dimensional Phase-Contrast Magnetic Resonance Imaging and In-Silico Simulations of Cerebrospinal Fluid Dynamics
Authors: Heidari Pahlavian Soroush , Bunck Alexander C. , Loth Francis , Shane Tubbs R. , Yiallourou Theresia , Robert Kroeger Jan , Heindel Walter , Martin Bryn A.
Published: February 2015

The purpose of the present study was to compare subject-specific magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) simulations with time-resolved three-directional (3D) velocity-encoded phase-contrast MRI (4D PCMRI) measurements of the cerebrospinal fluid (CSF) velocity field in the cervical spinal subarachnoid space (SSS). Three-dimensional models of the cervical SSS were constructed based on MRI image segmentation and anatomical measurements for a healthy subject and patient with Chiari I malformation. CFD was used to simulate the CSF motion and compared to the 4D PCMRI measurements. Four-dimensional PCMRI measurements had much greater CSF velocities compared to CFD simulations (1.4 to 5.6× greater). Four-dimensional PCMRI and CFD both showed anterior and anterolateral dominance of CSF velocities, although this flow feature was more pronounced in 4D PCMRI measurements compared to CFD. CSF flow jets were present near the nerve rootlets and denticulate ligaments (NRDL) in the CFD simulation. Flow jets were visible in the 4D PCMRI measurements, although they were not clearly attributable to nerve rootlets. Inclusion of spinal cord NRDL in the cervical SSS does not fully explain the differences between velocities obtained from 4D PCMRI measurements and CFD simulations.
An Approach to Identify Six Sigma Robust Solutions of Multi/Many-Objective Engineering Design Optimization Problems
Authors: Ray Tapabrata , Asafuddoula Md , Singh Hemant Kumar , Alam Khairul
Published: February 2015

In order to be practical, solutions of engineering design optimization problems must be robust, i.e., competent and reliable in the face of uncertainties. While such uncertainties can emerge from a number of sources (imprecise variable values, errors in performance estimates, varying environmental conditions, etc.), this study focuses on problems where uncertainties emanate from the design variables. While approaches to identify robust optimal solutions of single and multi-objective optimization problems have been proposed in the past, we introduce a practical approach that is capable of solving robust optimization problems involving many objectives building on authors’ previous work. Two formulations of robustness have been considered in this paper, (a) feasibility robustness (FR), i.e., robustness against design failure and (b) feasibility and performance robustness (FPR), i.e., robustness against design failure and variation in performance. In order to solve such formulations, a decomposition based evolutionary algorithm (DBEA) relying on a generational model is proposed in this study. The algorithm is capable of identifying a set of uniformly distributed nondominated solutions with different sigma levels (feasibility and performance) simultaneously in a single run. Computational benefits offered by using polynomial chaos (PC) in conjunction with Latin hypercube sampling (LHS) for estimating expected mean and variance of the objective/constraint functions has also been studied in this paper. Last, the idea of redesign for robustness has been explored, wherein selective component(s) of an existing design are altered to improve its robustness. The performance of the strategies have been illustrated using two practical design optimization problems, namely, vehicle crash-worthiness optimization problem (VCOP) and a general aviation aircraft (GAA) product family design problem.
A corpus of noise-induced word misperceptions for Spanish
Authors: Tóth Máté Attila , García Lecumberri María Luisa , Tang Yan , Cooke Martin
Published: February 2015

Word misperceptions are valuable in designing and evaluating detailed computational models of speech perception, especially when a number of listeners agree on the misperceived word. The current paper describes the elicitation of a corpus of Spanish word misperceptions induced by different types of noise. Stimuli were presented using an adaptive procedure designed to promote the rapid discovery of misperceptions. The final corpus contains 3235 misperceptions along with speech and masker waveforms, permitting further experimental and modeling studies into the origin of each misperception. The corpus is available online as an open resource.
Cardiac hypertrophy induced by active Raf depends on Yorkie-mediated transcription
Authors: Yu Lin , Daniels Joseph P. , Wu Huihui , Wolf Matthew J.
Published: February 2015

Proteins in the Hippo pathway regulate Raf-mediated cardiac hypertrophy in flies.
Turning down inflammation with dopamine
Authors: Gough Nancy R.
Published: February 2015

Dopamine signaling through the D1 receptor stimulates the ubiquitylation and autophagosomal degradation of the NLRP3 component of the inflammasome.
Is mTOR a good guy or bad guy in Huntington’s disease?
Authors: Ferrarelli Leslie K.
Published: February 2015

Striatal-specific activation of the kinase complex mTORC1 may improve pathological symptoms of Huntington’s disease.
ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation
Authors: Daly Seth M. , Elmore Bradley O. , Kavanaugh Jeffrey S. , Triplett Kathleen D. , Figueroa Mario , Raja Huzefa A. , El-Elimat Tamam , Crosby Heidi A. , Femling Jon K. , Cech Nadja B. , Horswill Alexander R. , Oberlies Nicholas H. , Hall Pamela R.
Published: February 2015

Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibility to host killing.
Staphylococcus aureus
is a major cause of invasive skin and soft tissue infections (SSTIs) in both the hospital and community settings, and it is also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by the accessory gene regulator (
agr
) controls virulence factor production essential for causing SSTIs. We recently identified ω-hydroxyemodin (OHM), a polyhydroxyanthraquinone isolated from solid-phase cultures of
Penicillium restrictum
, as a suppressor of QS and a compound sought for the further characterization of the mechanism of action. At concentrations that are nontoxic to eukaryotic cells and subinhibitory to bacterial growth, OHM prevented
agr
signaling by all four
S. aureus agr
alleles. OHM inhibited QS by direct binding to AgrA, the response regulator encoded by the
agr
operon, preventing the interaction of AgrA with the
agr
P2 promoter. Importantly, OHM was efficacious in a mouse model of
S. aureus
SSTI. Decreased dermonecrosis with OHM treatment was associated with enhanced bacterial clearance and reductions in inflammatory cytokine transcription and expression at the site of infection. Furthermore, OHM treatment enhanced the immune cell killing of
S. aureus
in vitro
in an
agr
-dependent manner. These data suggest that bacterial disarmament through the suppression of
S. aureus
QS may bolster the host innate immune response and limit inflammation.
Population Pharmacokinetic Modeling of Plasma and Intracellular Ribavirin Concentrations in Patients with Chronic Hepatitis C Virus Infection
Authors: Wu Liviawati S. , Rower Joseph E. , Burton James R. , Anderson Peter L. , Hammond Kyle P. , Baouchi-Mokrane Fafa , Everson Gregory T. , Urban Thomas J. , D'Argenio David Z. , Kiser Jennifer J.
Published: February 2015

Ribavirin, a guanosine analog, is a broad-spectrum antiviral agent. Ribavirin has been a fundamental component of the treatment of hepatitis C virus (HCV) infection for decades, but there is a very limited understanding of the clinical pharmacology of this drug. Furthermore, it is associated with a major dose-limiting toxicity, hemolytic anemia. Ribavirin undergoes intracellular phosphorylation by host enzymes to ribavirin monophosphate (RMP), ribavirin diphosphate (RDP), and ribavirin triphosphate (RTP). The intracellular forms have been associated with antiviral and toxic effects
in vitro
, but the kinetics of these phosphorylated moieties have not been fully elucidated
in vivo
. We developed a model to characterize the plasma pharmacokinetics of ribavirin and the difference between intracellular phosphorylation kinetics in red cells (nonnucleated) and in peripheral blood mononuclear cells (nucleated). A time-independent two-compartment model with first-order absorption described the plasma data well. The cellular phosphorylation kinetics was described by a one-compartment model for RMP, with the formation rate driven by plasma concentrations and the first-order degradation rate. RDP and RTP rapidly reached equilibrium with RMP. Concomitant telaprevir use, inosine triphosphatase genetics, creatinine clearance, weight, and sex were significant covariates. The terminal ribavirin half-life in plasma and phosphorylated anabolites in cells was approximately 224 h. We found no evidence of time-dependent kinetics. These data provide a foundation for uncovering concentration-effect associations for ribavirin and determining the optimal dose and duration of this drug for use in combination with newer direct-acting HCV agents. (This study has been registered at ClinicalTrials.gov under registration no. NCT01097395.)
Application of a Seven-Target Pyrosequencing Assay To Improve the Detection of Neuraminidase Inhibitor-Resistant Influenza A(H3N2) Viruses
Authors: Tamura Daisuke , Okomo-Adhiambo Margaret , Mishin Vasiliy P. , Guo Zhu , Xu Xiyan , Villanueva Julie , Fry Alicia M. , Stevens James , Gubareva Larisa V.
Published: February 2015

National U.S. influenza antiviral surveillance incorporates data generated by neuraminidase (NA) inhibition (NI) testing of isolates supplemented with NA sequence analysis and pyrosequencing analysis of clinical specimens. A lack of established correlates for clinically relevant resistance to NA inhibitors (NAIs) hinders interpretation of NI assay data. Nonetheless, A(H3N2) viruses are commonly monitored for moderately or highly reduced inhibition in the NI assay and/or for the presence of NA markers E119V, R292K, and N294S. In 2012 to 2013, three drug-resistant A(H3N2) viruses were detected by NI assay among isolates (
n
= 1,424); all showed highly reduced inhibition by oseltamivir and had E119V. In addition, one R292K variant was detected among clinical samples (
n
= 1,024) by a 3-target pyrosequencing assay. Overall, the frequency of NAI resistance was low (0.16% [4 of 2,448]). To screen for additional NA markers previously identified in viruses from NAI-treated patients, the pyrosequencing assay was modified to include Q136K, I222V, and deletions encompassing residues 245 to 248 (del245-248) and residues 247 to 250 (del247-250). The 7-target pyrosequencing assay detected NA variants carrying E119V, Q136, and del245-248 in an isolate from an oseltamivir-treated patient. Next, this assay was applied to clinical specimens collected from hospitalized patients and submitted for NI testing but failed cell culture propagation. Of the 27 clinical specimens tested, 4 (15%) contained NA changes: R292K (
n
= 2), E119V (
n
= 1), and del247-250 (
n
= 1). Recombinant NAs with del247-250 or del245-248 conferred highly reduced inhibition by oseltamivir, reduced inhibition by zanamivir, and normal inhibition by peramivir and laninamivir. Our results demonstrated the benefits of the 7-target pyrosequencing assay in conducting A(H3N2) antiviral surveillance and testing for clinical care.
A Fluorescent Microplate Assay Quantifies Bacterial Efflux and Demonstrates Two Distinct Compound Binding Sites in AcrB
Authors: Iyer Ramkumar , Ferrari Annette , Rijnbrand R. , Erwin Alice L.
Published: February 2015

A direct assay of efflux by
Escherichia coli
AcrAB-TolC and related multidrug pumps would have great value in discovery of new Gram-negative antibiotics. The current understanding of how efflux is affected by the chemical structure and physical properties of molecules is extremely limited, derived from antibacterial data for compounds that inhibit growth of wild-type
E. coli
. We adapted a previously described fluorescent efflux assay to a 96-well microplate format that measured the ability of test compounds to compete for efflux with Nile Red (an environment-sensitive fluor), independent of antibacterial activity. We show that Nile Red and the lipid-sensitive probe DiBAC
4
-(3) [bis-(1,3-dibutylbarbituric acid)-trimethine oxonol] can quantify efflux competition in
E. coli
. We extend the previous findings that the tetracyclines compete with Nile Red and show that DiBAC
4
-(3) competes with macrolides. The extent of the competition shows a modest correlation with the effect of the
acrB
deletion on MICs within the compound sets for both dyes. Crystallographic studies identified at least two substrate binding sites in AcrB, the proximal and distal pockets. High-molecular-mass substrates bound the proximal pocket, while low-mass substrates occupied the distal pocket. As DiBAC
4
-(3) competes with macrolides but not with Nile Red, we propose that DiBAC
4
-(3) binds the proximal pocket and Nile Red likely binds the distal site. In conclusion, competition with fluorescent probes can be used to study the efflux process for diverse chemical structures and may provide information as to the site of binding and, in some cases, enable rank-ordering a series of related compounds by efflux.