bluuebunny/crossref_metadata_2025 huggingface dataset:
RFID-Based Vehicle Positioning and Its Applications in Connected Vehicles
Authors: Wang Jianqiang , Ni Daiheng , Li Keqiang
Published: March 2014

This paper proposed an RFID-based vehicle positioning approach to facilitate connected vehicles applications. When a vehicle passes over an RFID tag, the vehicle position is given by the accurate position stored in the tag. At locations without RFID coverage, the vehicle position is estimated from the most recent tag location using a kinematics integration algorithm till updates from the next tag. The accuracy of RFID positioning is verified empirically in two independent ways with one using radar and the other a photoelectric switch. The former is designed to verify whether the dynamic position obtained from RFID tags matches the position measured by radar that is regarded as accurate. The latter aims to verify whether the position estimated from the kinematics integration matches the position obtained from RFID tags. Both means supports the accuracy of RFID-based positioning. As a supplement to GPS which suffers from issues such as inaccuracy and loss of signal, RFID positioning is promising in facilitating connected vehicles applications. Two conceptual applications are provided here with one in vehicle operational control and the other in Level IV intersection control.
PypeTree: A Tool for Reconstructing Tree Perennial Tissues from Point Clouds
Authors: Delagrange Sylvain , Jauvin Christian , Rochon Pascal
Published: March 2014

The reconstruction of trees from point clouds that were acquired with terrestrial LiDAR scanning (TLS) may become a significant breakthrough in the study and modelling of tree development. Here, we develop an efficient method and a tool based on extensive modifications to the skeletal extraction method that was first introduced by Verroust and Lazarus in 2000. PypeTree, a user-friendly and open-source visual modelling environment, incorporates a number of improvements into the original skeletal extraction technique, making it better adapted to tackle the challenge of tree perennial tissue reconstruction. Within PypeTree, we also introduce the idea of using semi-supervised adjustment tools to address methodological challenges that are associated with imperfect point cloud datasets and which further improve reconstruction accuracy. The performance of these automatic and semi-supervised approaches was tested with the help of synthetic models and subsequently validated on real trees. Accuracy of automatic reconstruction greatly varied in terms of axis detection because small (length < 3.5 cm) branches were difficult to detect. However, as small branches account for little in terms of total skeleton length, mean reconstruction error for cumulated skeleton length only reached 5.1% and 1.8% with automatic or semi-supervised reconstruction, respectively. In some cases, using the supervised tools, a perfect reconstruction of the perennial tissue could be achieved.
A Fuzzy Controller for Lower Limb Exoskeletons during Sit-to-Stand and Stand-to-Sit Movement Using Wearable Sensors
Authors: Taslim Reza Sharif , Ahmad Norhafizan , Choudhury Imtiaz , Ghazilla Raja
Published: March 2014

Human motion is a daily and rhythmic activity. The exoskeleton concept is a very positive scientific approach for human rehabilitation in case of lower limb impairment. Although the exoskeleton shows potential, it is not yet applied extensively in clinical rehabilitation. In this research, a fuzzy based control algorithm is proposed for lower limb exoskeletons during sit-to-stand and stand-to-sit movements. Surface electromyograms (EMGs) are acquired from the vastus lateralis muscle using a wearable EMG sensor. The resultant acceleration angle along the z-axis is determined from a kinematics sensor. Twenty volunteers were chosen to perform the experiments. The whole experiment was accomplished in two phases. In the first phase, acceleration angles and EMG data were acquired from the volunteers during both sit-to-stand and stand-to-sit motions. During sit-to-stand movements, the average acceleration angle at activation was 11°–48° and the EMG varied from −0.19 mV to +0.19 mV. On the other hand, during stand-to-sit movements, the average acceleration angle was found to be 57.5°–108° at the activation point and the EMG varied from −0.32 mV to +0.32 mV. In the second phase, a fuzzy controller was designed from the experimental data. The controller was tested and validated with both offline and real time data using LabVIEW.
The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease
Authors: Sallée Marion , Dou Laetitia , Cerini Claire , Poitevin Stéphane , Brunet Philippe , Burtey Stéphane
Published: March 2014

Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular diseases and suffer from accelerated atherosclerosis. CKD patients are permanently exposed to uremic toxins, making them good candidates as pathogenic agents. We focus here on uremic toxins from tryptophan metabolism because of their potential involvement in cardiovascular toxicity: indolic uremic toxins (indoxyl sulfate, indole-3 acetic acid, and indoxyl-β-d-glucuronide) and uremic toxins from the kynurenine pathway (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid). Uremic toxins derived from tryptophan are endogenous ligands of the transcription factor aryl hydrocarbon receptor (AhR). AhR, also known as the dioxin receptor, interacts with various regulatory and signaling proteins, including protein kinases and phosphatases, and Nuclear Factor-Kappa-B. AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and some polychlorinated biphenyls is associated with an increase in cardiovascular disease in humans and in mice. In addition, this AhR activation mediates cardiotoxicity, vascular inflammation, and a procoagulant and prooxidant phenotype of vascular cells. Uremic toxins derived from tryptophan have prooxidant, proinflammatory, procoagulant, and pro-apoptotic effects on cells involved in the cardiovascular system, and some of them are related with cardiovascular complications in CKD. We discuss here how the cardiovascular effects of these uremic toxins could be mediated by AhR activation, in a “dioxin-like” effect.
Development of Lectin-Linked Immunomagnetic Separation for the Detection of Hepatitis A Virus
Authors: Ko Sang-Mu , Kwon Joseph , Vaidya Bipin , Choi Jong , Lee Hee-Min , Oh Myung-Joo , Bae Hyeun-Jong , Cho Se-Young , Oh Kyung-Seo , Kim Duwoon
Published: March 2014

The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus to cells. In this study, we initially investigated the effects of pH (4.0–10.0) and metal ions (Fe2+, Co2+, Cu2+, Mg2+, K+, and Ca2+) on the binding of HAV to oyster digestive cells. The lowest relative binding (RB) of HAV to the cells was found at pH 4.0 and in FeSO4 solution (64.6% and 68.1%, respectively). To develop an alternative to antibody-dependent immunomagnetic separation prior to detection of HAV using RT-PCR, the binding of HAV to five lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Ulex europaeus agglutinin (UEA-1) and soybean agglutinin (SBA), was evaluated using ELISAs. SBA showed significantly higher RB to HAV than the other lectins tested. In addition, HAV could be concentrated within 30 min using SBA-linked magnetic bead separation (SMS) prior to the RT-PCR assay. Our findings demonstrate the feasibility of using SMS combined with RT-PCR to detect HAV at dilutions ranging from 10−1–10−4 of a HAV stock (titer: 104 TCID50/mL).
Improved Stem Cell-Derived Motoneuron Survival, Migration, Sprouting, and Innervation with Enhanced Expression of Polysialic Acid
Authors: Maarouf Abderrahman El , Yaw Damali Moyo-Lee , Rutishauser Urs
Published: March 2014

Motoneurons (MNs) derived from mouse embryonic stem cells (ESCs) begin to express low levels of polysialic acid (PSA) at the time when they acquire an ability to migrate and extend neurites. PSA is known to promote cell migration and process outgrowth/guidance in the developing nervous system. To test if experimentally enhanced expression of PSA would augment these cellular events, the PSA-synthesizing polysialyltransferase was introduced into ESCs. In culture, the resulting higher PSA expression specifically increased neurite outgrowth and cell migration from differentiated embryoid bodies. In addition, the MN population obtained after sorting for HB9::GFP expression showed enhanced survival as well as extensive neurite outgrowth. Following transplantation of ESC-derived MNs into an adult sciatic nerve devoid of endogenous axons, the PSA augmentation increased the numbers of axons growing toward the denervated muscles. Migration of some transplanted cells inside the nerve toward muscle was also enhanced. Moreover, higher PSA expression selectively affected target innervation. It produced greater numbers of neuromuscular junctions in a predominantly fast twitch muscle and had no effect in a slow twitch muscle. These findings suggest that engineering of PSA expression in ESC could serve as an enhancement for MN cell therapy.
Differential Clearance of Rat and Human Bone Marrow-Derived Mesenchymal Stem Cells from the Brain after Intra-arterial Infusion in Rats
Authors: Khabbal Joonas , Kerkelä Erja , Mitkari Bhimashankar , Raki Mari , Nystedt Johanna , Mikkonen Ville , Bergström Kim , Laitinen Saara , Korhonen Matti , Jolkkonen Jukka
Published: March 2014

Intra-arterial (IA) delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) has shown potential as a minimally invasive therapeutic approach for stroke. The aim of the present study was to determine the whole-body biodistribution and clearance of technetium-99m (99mTc)-labeled rat and human BM-MSCs after IA delivery in a rat model of transient middle cerebral artery occlusion (MCAO) using single-photon emission computed tomography (SPECT). Our hypothesis was that xenotransplantation has a major impact on the behavior of cells. Male RccHan: Wistar rats were subjected to sham operation or MCAO. Twenty-four hours after surgery, BM-MSCs (2×106 cells/animal) labeled with 99mTc were infused into the external carotid artery. Whole-body SPECT images were acquired 20 min, 3 h, and 6 h postinjection, after which rats were sacrificed, and organs were collected and weighed for measurement of radioactivity. The results showed that the majority of the cells were located in the brain and especially in the ipsilateral hemisphere immediately after cell infusion both in sham-operated and MCAO rats. This was followed by fast disappearance, particularly in the case of human cells. At the same time, the radioactivity signal increased in the spleen, kidney, and liver, the organs responsible for destroying cells. Further studies are needed to demonstrate whether differential cell behavior has any functional impact.
BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery after Transplantation in Hypoxic–Ischemic Stroke
Authors: Rosenblum Sahar , Smith Tenille N. , Wang Nancy , Chua Joshua Y. , Westbroek Erick , Wang Kendrick , Guzman Raphael
Published: March 2014

Intra-arterial neural stem cell (NSC) therapy has the potential to improve long-term outcomes after stroke. Here we evaluate if pretreatment of NSCs with brain-derived neurotrophic factor (BDNF) prior to transplantation improves cell engraftment and functional recovery following hypoxic–ischemic (HI) stroke. Human embryonic-derived NSCs with or without BDNF pretreatment (1 h, 100 ng/ml) were transplanted 3 days after HI stroke. Functional recovery was assessed using the horizontal ladder test. Cell engraftment was evaluated using bioluminescence imaging (BLI) and histological counts of SC121+ cells. Fluoro-Jade C (FJC) and NeuN stains were used to evaluate neuroprotection. The effect of BDNF on NSCs was analyzed using a migration assay, immunocytochemistry, Luminex proteomic assay, and RT-qPCR.BLI analysis demonstrated significantly higher photon flux in the BDNF-treated NSC group compared to untreated NSC ( p = 0.049) and control groups ( p = 0.0021) at 1 week after transplantation. Immunohistochemistry confirmed increased transplanted cell survival in the cortex ( p = 0.0126) and hippocampus ( p = 0.0098) of animals injected with BDNF-treated NSCs compared to untreated NSCs. Behavioral testing revealed that the BDNF-treated NSC group demonstrated increased sensorimotor recovery compared to the untreated NSC and control groups ( p < 0.001) over the 1-month period ( p < 0.001) following transplantation. A significant improvement in performance was found in the BDNF-treated NSC group compared to the control group at 14, 21, and 28 ( p < 0.05) days after transplantation. The cortex and hippocampus of the BDNF-treated NSC group had significantly more SC121+ NSCs ( p = 0.0125, p = 0.0098), fewer FJC+ neurons ( p = 0.0370, p = 0.0285), and a higher percentage of NeuN+ expression ( p= 0.0354) in the cortex compared to the untreated NSC group. BDNF treatment of NSCs resulted in significantly greater migration to SDF-1, secretion of M-CSF, VEGF, and expression of CXCR4, VCAM-1, Thrombospondins 1 and 2, and BDNF. BDNF pretreatment of NSCs results in higher initial NSC engraftment and survival, increased neuroprotection, and greater functional recovery when compared to untreated NSCs.
DIAGNOSING THE EFFECTS OF LEADER-MEMBER EXCHANGE QUALITY ON PERFORMANCE IN THE CONTEXT OF ORGANIZATIONAL CULTURE: A CASE FROM TURKISH FAMILY-OWNED BUSINESSES
Authors: Unnu Nazli Ayse Ayyildiz , Kesken Julide
Published: March 2014

The main purpose of this study was to diagnose the effects of leader-member exchange (LMX) quality on performance in the context of organizational and Turkish culture. The study was conducted in two family-owned businesses (FOBs), as they are very important structures in which in-group and out-group formations can be seen. Firm A (33 employees representing 41 dyads) and Firm B (61 employees representing 60 dyads) were especially chosen as they enabled us to apply the coding system leading to effective evaluation of surveys as the unit of analysis is “dyads”. In this framework, this study offers an important contribution to the international management literature as positive effects of LMX quality on firm performance, subordinate performance, intention to leave and job satisfaction were found within the context of organizational and Turkish culture. As the proportion of FOBs is almost 95% in Turkey, they represent Turkish economy and business culture well, leading to more generalizable results. Thus, firms can lead to increase in both subordinate and firm performance by creating an organizational culture in which high quality leader-member relationships are emphasized, finally leading to positive organizational outcomes.
Evaluation of physiological responses of cardiac and blood parameters after incremental exercise on field and laboratory tests in eventing horses
Authors: Azevedo J.F. , Miranda A.C.T. , Ramos M.T. , Oliveira C.A.A. , Padilha F.G.F. , Silva V.P. , Baldani C.D. , Almeida F.Q.
Published: March 2014

This study was carried out to model data of plasma lactate and glucose concentrations, heart rate and haematocrit in eventing horses after incremental speed tests on the field and on a high speed treadmill. The experimental design was a duplicate Latin square, with two tests, on the field and on a treadmill. Eight eventing Brazilian Sport Horses were used, five males and three females, with mean age of 7.4 years old, and average body weight of 479 kg. The protocol for the incremental speed test on the treadmill consisted of 10 minutes of warm up walking and trotting; followed by gallops at initial speed of 5.0 m/s, with increments of 1.0 m/s every minute up to 10.0 m/s. The treadmill inclination was 4% during the gallops. At the end of the test, horses were trotted at 4.0 m/s during 4 minutes, walked at 1.7 m/s during 6 minutes and rested thereafter on the treadmill. The protocol used on the field test consisted of 10 minutes of warm up walking and trotting; followed by 4 steps of one minute at 5.0, 7.0, 8.0 and 10.0 m/s, with 3 minutes intervals of walking recovery between each step. After the test the horses recovered at rest and were monitored during 60 minutes. An exponential regression described the reduction of plasma lactate concentration and heart rate better than a linear regression. The reduction of the haematocrit was better described by a linear regression. It was not possible to adjust plasma glucose concentration during recovery from exercise test on a regression equation because there was no difference (P>0.05) among its mean values.
Determining dehydration and its compartmentation in horses at rest and with exercise: a concise review and focus on multi-frequency bioelectrical impedance analysis
Authors: Lindinger M.I.
Published: March 2014

Multi-frequency bioelectrical impedance analysis (MFBIA) has been, and likely will increasingly be, used to rapidly and non-invasively assess the time course of volume losses and recovery in horses. Dehydration in performance horses is frequently the cause of health and performance problems, and presently used techniques for objectively quantifying optimum hydration are time consuming and challenging to perform accurately. Dehydration can take a number of different forms, with a balanced loss of water and electrolytes from both extra- and intracellular fluid compartments, or a primarily extracellular or intracellular dehydration. This review summarises the current state of knowledge regarding the quantification of dehydration, losses of water and electrolytes from extra- and intracellular fluid compartments. The effects of dehydration on exercise performance, muscle function, cardiovascular function, thermoregulation and feeding are briefly summarised. The review provides a quantitative description of the magnitude and time course of compartmental fluid losses and recovery in horses in response to feeding and due to exercise at different intensities and durations representing the endurance horse to the track race horse. Effective rehydration requires knowledge of the losses from the main body fluid compartments, which is now possible using MFBIA technology. The present review outlines the key approaches that have been used to assess dehydration in horses, including the new technique of MFBIA.
Descriptive epidemiology of race-day jockey falls and injuries in New Zealand
Authors: Bolwell C. , Rogers C. , Gee E.
Published: March 2014

The objective of the study was to determine the incidence of race-day jockey falls and describe the reporting of injuries occurring during Thoroughbred racing in New Zealand. Details on jockey falls and injuries were extracted from official stipendiary stewards' reports and denominator data on all race starts were obtained for all races that occurred between 1 August 2008 and 28 February 2013. A fall included any event of the jockey being dislodged from the horse, once the jockey had mounted to start the race proceedings. Incidence rates for jockey falls stratified by type of race were calculated for race-level variables of interest: year, season, race number, race distance and track condition. During the study period there were 816 jockey falls, of which 92 occurred before the race and resulted in the horse being scratched (withdrawn) from the race. The incidence of jockey falls was 2.2 per 1000 rides (95% confidence interval (CI)=1.9-2.5) for flat races and 84.7 per 1000 rides (95% CI=76.6-93.5) for jump races. Just under half of the jockey falls in flat races occurred pre-race (195/418; 46.6%), 42% (179/418) of falls occurred during the race and 10.5% (44/418) of falls occurred post-race. In total, 19.1% (80/418) and 17.3% (69/398) of jockey falls resulted in injury to the jockey in flat and jump races, respectively. Nearly 90% (69/80) of jockeys injured in flat races were stood down from their next race and most injured jockeys required a medical certificate before racing again. The incidence of jockey falls was higher in jump races than flat races, but was comparable to those reported internationally. Incidence rates for falls in flat races were lower than those reported in Europe and Australia.
Communication and Interculturality
Authors: Villegas Juan Carlos Suárez
Published: March 2014

Citizenship as status implies the acknowledgment of individual rights as well as social ones. This very acceptance requires the consideration of all citizens as equal despite any personal difference and it represents an aim that is mostly dependent on the mass-media social function. The formal acknowledgment of the citizenship would be scarcely important if identity stereotypes and prejudice-based discrimination occurred during citizen's vital happenings. Today, citizenship must include the communicative dimension as part of the social integration project. Societies are every day more intercultural, and media play an essential role in representing the other. As part of a Grundtvig project on intercultural education, the author conducted an experience with journalistic ethics students of the Communication School at the University of Seville. From this experience, the author reflects on multiculturalism as a necessary tool in the training of future journalists.
Persuasive Games as Social Action Agents
Authors: Ruggiero Dana
Published: March 2014

Persuasive games are an interdisciplinary area covering a range of fields. This article examines persuasive games through current trends in research as potential agents of social action. The implications of persuasive games for learning are analyzed through education and communication theories, suggesting that persuasive techniques are of primary importance and that procedures and ethos connect learners to experiences. The article first provides a historical overview of persuasive games, highlighting key background and influences. It then defines persuasive games through learning and communication theories, and discusses the implications of persuasive games as social action agents in research, policy, and practice.
Acceptability of Video Games Technology for Medical Emergency Training
Authors: Knight James F.
Published: March 2014

Using the technology acceptance model (TAM), this study aimed to investigate the acceptability of video game technologies (serious games) for medical emergency procedure and decision making training. Using the Triage Trainer, a prototype serious game for the triage sieve process, differences between gamers and non-gamers, males and females, and the effects of ratings of computer self efficacy (i.e. computer skill and gaming skill) and attitudes towards computers (i.e. enthusiasm and anxiety) on the acceptance model were also investigated. The results show significant correlations for computer self-efficacy and attitude variables with the perceived ease of use (PEOU), perceived usefulness (PU) and attitudes towards use (ATU) of the game. Multiple regression showed that 52% of the variance in ATU was explained by the PU and PEOU. However, none of the secondary variables (self efficacy or emotions) had a significant effect on the ATU, PU and PEOU over and above each other.
Developing an Ultrasonography Simulator Training Tool
Authors: Sokolowski John A. , Banks Catherine M. , Garcia Hector M. , Richards William T.
Published: March 2014

This paper presents the development of an Ultrasonography Simulator Training Tool. Ultrasonography is a user-dependent technology; operators must possess both physical and cognitive ultrasonography capability to include mechanical manipulation of the probe, image capture, and interpretation of pathology. There are three major challenges in developing a simulator training tool that provides both the physical (hardware) and cognitive (software-visualization) learning experience: 1) graphical user interface design, 2) hardware utilization and interface, and 3) the integration of software for simulating volume of ultrasound beams and visualization of images (imagery data). This tool is being being developed with educator input from conceptual design to final product validation. The initial output of this effort is a prototype real-time, dynamic ultrasound simulator training tool specific for cardiac interrogation. The tool has been crafted to accommodate a dedicated teaching component that is extendable with additional anatomical imagery and teaching materials to include instructor observation capability.
A Queueing-Game Model for Making Decisions About Order Penetration Point in Supply Chain in Competitive Environment
Authors: Teimoury Ebrahim , Fathi Mahdi
Published: March 2014

This study is dedicated to Order Penetration Point (OPP) strategic decision making which is the boundary between Make-To-Order (MTO) and Make-To-Stock (MTS) policies. This paper considers two competing supply chains in which a manufacturer produces semi-finished items on a MTS basis for a retailer that will customize the items on a MTO basis. The two-echelon supply chain offers multi-product to a market comprised of homogenous customers who have different preferences and willingness to pay. The retailer wishes to determine the optimal OPP, the optimal semi-finished goods buffer size, and the price of the products. Moreover, the authors consider both integrated scenario (shared capacity model) and competition scenario (Stackelberg queueing-game model) in this paper. A matrix geometric method is utilized to evaluate various performance measures for this system and then, optimal solutions are obtained by enumeration techniques. The suggested queueing approach is based on a new perspective between the operation and marketing functions which captures the interactions between several factors including inventory level, price, OPP, and delivery lead time. Finally, parameter sensitivity analyses are carried out and the effect of demand on the profit function, the effect of prices ratio on completion rates ratio and buffer sizes ratio and the variations of profit function for different prices, completion percents, and buffer sizes are examined in both scenarios.
Multi-Level Programming Approach to a Closed-loop Supply Chain Network Design
Authors: Ghayebloo Sima , Tarok Mohammad Jafar , Abedzadeh Mostafa , Diallo Claver
Published: March 2014

In this paper, the authors address the problem of network design for a closed-loop supply chain. The problem is formulated as a mixed zero-one bi-level optimization model, with the manufacturer as the leader who minimizes his costs at the upper level, and a forwarding agent dealt with as the follower. The leader decides on the locations of the facilities, and the forwarding agent builds the forward and reverse transportation plans so as to minimize the total transportation cost. A genetic algorithm solution method is used to obtain the Stackelberg solution. Furthermore, the algorithm uses penalty functions to handle the constraints. The solution algorithm is implemented in Matlab, utilizing LINGO 11.0 (2008) to solve each lower level problem instance. Finally, the accuracy of the model is tested on a set of numerical experiments.
An Improved Measurement Model for Internal Integration
Authors: Radhakrishnan Abirami , Thiruvadi Sheela , David Dessa
Published: March 2014

One of the critical success factors in supply chain management is Internal Integration within the firms. In this study the authors have examined this construct in greater depth and have developed an improved measurement model grounded in systems and contingency theories. The authors have validated the model by conducting a large scale empirical study and by collecting data from 154 buyer-supplier dyads. The authors have established the construct validity by using refined Confirmatory Factor Analysis Multi-Trait Multi-Method Approach. The authors have used multiple perspectives from fields such as operations management, information systems management, and inter-organizational relationship management to present a richer construct.
IκBε Is a Key Regulator of B Cell Expansion by Providing Negative Feedback on cRel and RelA in a Stimulus-Specific Manner
Authors: Alves Bryce N. , Tsui Rachel , Almaden Jonathan , Shokhirev Maxim N. , Davis-Turak Jeremy , Fujimoto Jessica , Birnbaum Harry , Ponomarenko Julia , Hoffmann Alexander
Published: March 2014

The transcription factor NF-κB is a regulator of inflammatory and adaptive immune responses, yet only IκBα was shown to limit NF-κB activation and inflammatory responses. We investigated another negative feedback regulator, IκBε, in the regulation of B cell proliferation and survival. Loss of IκBε resulted in increased B cell proliferation and survival in response to both antigenic and innate stimulation. NF-κB activity was elevated during late-phase activation, but the dimer composition was stimulus specific. In response to IgM, cRel dimers were elevated in IκBε-deficient cells, yet in response to LPS, RelA dimers also were elevated. The corresponding dimer-specific sequences were found in the promoters of hyperactivated genes. Using a mathematical model of the NF-κB–signaling system in B cells, we demonstrated that kinetic considerations of IκB kinase–signaling input and IκBε’s interactions with RelA- and cRel-specific dimers could account for this stimulus specificity. cRel is known to be the key regulator of B cell expansion. We found that the RelA-specific phenotype in LPS-stimulated cells was physiologically relevant: unbiased transcriptome profiling revealed that the inflammatory cytokine IL-6 was hyperactivated in IκBε−/− B cells. When IL-6R was blocked, LPS-responsive IκBε−/− B cell proliferation was reduced to near wild-type levels. Our results provide novel evidence for a critical role for immune-response functions of IκBε in B cells; it regulates proliferative capacity via at least two mechanisms involving cRel- and RelA-containing NF-κB dimers. This study illustrates the importance of kinetic considerations in understanding the functional specificity of negative-feedback regulators.
Enhanced Antibody Responses to an HIV-1 Membrane-Proximal External Region Antigen in Mice Reconstituted with Cultured Lymphocytes
Authors: Holl T. Matt , Yang Guang , Kuraoka Masayuki , Verkoczy Laurent , Alam S. Munir , Moody M. Anthony , Haynes Barton F. , Kelsoe Garnett
Published: March 2014

We have shown that the protective HIV-1 Ab, 2F5, avidly reacts with a conserved mammalian self-Ag, kynureninase, and that the development of B cells specific for the 2F5 epitope is constrained by immunological tolerance. These observations suggest that the capacity to mount Ab responses to the 2F5 epitope is mitigated by tolerance, but such capacity may be latent in the pretolerance and/or anergic B cell pools. In this study, we use B cell tetramer reagents to track the frequencies of B cells that recognize the HIV-1 2F5 epitope (SP62): in C57BL/6 mice, SP62-binding transitional B cells are readily identified in bone marrow but are lost during subsequent development. Unsurprisingly then, immunization with SP62 immunogen does not elicit significant humoral responses in normal C57BL/6 mice. Reconstitution of Rag1null mice with normal congenic B cells that have matured in vitro restores the capacity to mount significant serum Ab and germinal center responses to this HIV-1 epitope. These B cell cultures are permissive for the development of autoreactive B cells and support the development of SP62-specific B cell compartments normally lost in 2F5 Ab knockin mice. The recovery of humoral responses to the 2F5/SP62 epitope of HIV-1 by reconstitution with B cells containing forbidden, autoreactive clones provides direct evidence that normal C57BL/6 mice latently possess the capacity to generate humoral responses to a conserved, neutralizing HIV-1 epitope.
Xenograft Tolerance and Immune Function of Human T Cells Developing in Pig Thymus Xenografts
Authors: Kalscheuer Hannes , Onoe Takashi , Dahmani Alexander , Li Hao-Wei , Hölzl Markus , Yamada Kazuhiko , Sykes Megan
Published: March 2014

Transplantation of xenogeneic thymus tissue allows xenograft tolerance induction in the highly disparate pig-to-mouse model. Fetal swine thymus (SW THY) can support the generation of a diverse human T cell repertoire that is tolerant of the pig in vitro. We demonstrate that SW THY generates all human T cell subsets, including regulatory T cells (Tregs), in similar numbers as fetal human thymus (HU THY) grafts in immunodeficient mice receiving the same human CD34+ cells. Peripheral T cells are specifically tolerant to the mouse and to the human and porcine donors, with robust responses to nondonor human and pig Ags. Specific tolerance is observed to pig skin grafts sharing the THY donor MHC. SW THY–generated peripheral Tregs show similar function, but include lower percentages of naive-type Tregs compared with HU THY–generated Tregs. Tregs contribute to donor-pig specific tolerance. Peripheral human T cells generated in SW THY exhibit reduced proportions of CD8+ T cells and reduced lymphopenia-driven proliferation and memory-type conversion, accelerated decay of memory-type cells, and reduced responses to protein Ags. Thus, SW thymus transplantation is a powerful xenotolerance approach for human T cells. However, immune function may be further enhanced by strategies to permit positive selection by autologous HLA molecules.
Relapsing–Remitting Central Nervous System Autoimmunity Mediated by GFAP-Specific CD8 T Cells
Authors: Sasaki Katsuhiro , Bean Angela , Shah Shivanee , Schutten Elizabeth , Huseby Priya G. , Peters Bjorn , Shen Zu T. , Vanguri Vijay , Liggitt Denny , Huseby Eric S.
Published: March 2014

Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons, and axons. Historically, MS has been thought to be a CD4 T cell–mediated autoimmune disease of CNS white matter. However, recent studies identified CD8 T cell infiltrates and gray matter lesions in MS patients. These findings suggest that CD8 T cells and CNS Ags other than myelin proteins may be involved during the MS disease process. In this article, we show that CD8 T cells reactive to glial fibrillary acidic protein (GFAP), a protein expressed in astrocytes, can avoid tolerance mechanisms and, depending upon the T cell–triggering event, drive unique aspects of inflammatory CNS autoimmunity. In GFAP-specific CD8 TCR-transgenic (BG1) mice, tissue resident memory-like CD8 T cells spontaneously infiltrate the gray matter and white matter of the CNS, resulting in a relapsing–remitting CNS autoimmunity. The frequency, severity, and remissions from spontaneous disease are controlled by the presence of polyclonal B cells. In contrast, a viral trigger induces GFAP-specific CD8 T effector cells to exclusively target the meninges and vascular/perivascular space of the gray and white matter of the brain, causing a rapid, acute CNS disease. These findings demonstrate that the type of CD8 T cell–triggering event can determine the presentation of distinct CNS autoimmune disease pathologies.
Transcription Factor IRF4 Regulates Germinal Center Cell Formation through a B Cell–Intrinsic Mechanism
Authors: Willis Simon N. , Good-Jacobson Kim L. , Curtis Joan , Light Amanda , Tellier Julie , Shi Wei , Smyth Gordon K. , Tarlinton David M. , Belz Gabrielle T. , Corcoran Lynn M. , Kallies Axel , Nutt Stephen L.
Published: March 2014

In response to antigenic stimulation, mature B cells interact with follicular helper T cells in specialized structures called germinal centers (GCs), which leads to the development of memory B cells and Ab-secreting plasma cells. The transcription factor IFN regulatory factor 4 (IRF4) is essential for the formation of follicular helper T cells and thus GCs, although whether IRF4 plays a distinct role in GC B cells remains contentious. RNAseq analysis on ex vivo-derived mouse B cell populations showed that Irf4 was lowly expressed in naive B cells, highly expressed in plasma cells, but absent from GC B cells. In this study, we used conditional deletion of Irf4 in mature B cells as well as wild-type and Irf4-deficient mixed bone marrow chimeric mice to investigate how and where IRF4 plays its essential role in GC formation. Strikingly, GC formation was severely impaired in mice in which Irf4 was conditionally deleted in mature B cells, after immunization with protein Ags or infection with Leishmania major. This effect was evident as early as day 5 following immunization, before the development of GCs, indicating that Irf4 was required for the development of early GC B cells. This defect was B cell intrinsic because Irf4-deficient B cells in chimeric mice failed to participate in the GC in response to L. major or influenza virus infection. Taken together, these data demonstrate a B cell–intrinsic requirement for IRF4 for not only the development of Ab secreting plasma cells but also for GC formation.
Cutting Edge: Control of Mycobacterium tuberculosis Infection by a Subset of Lung Parenchyma–Homing CD4 T Cells
Authors: Sakai Shunsuke , Kauffman Keith D. , Schenkel Jason M. , McBerry Cortez C. , Mayer-Barber Katrin D. , Masopust David , Barber Daniel L.
Published: March 2014

Th1 cells are critical for containment of Mycobacterium tuberculosis infection, but little else is known about the properties of protective CD4 T cell responses. In this study, we show that the pulmonary Th1 response against M. tuberculosis is composed of two populations that are either CXCR3hi and localize to lung parenchyma or are CX3CR1hiKLRG1hi and are retained within lung blood vasculature. M. tuberculosis–specific parenchymal CD4 T cells migrate rapidly back into the lung parenchyma upon adoptive transfer, whereas the intravascular effectors produce the highest levels of IFN-γ in vivo. Importantly, parenchymal T cells displayed greater control of infection compared with the intravascular counterparts upon transfer into susceptible T cell–deficient hosts. Thus, we identified a subset of naturally generated M. tuberculosis–specific CD4 T cells with enhanced protective capacity and showed that control of M. tuberculosis correlates with the ability of CD4 T cells to efficiently enter the lung parenchyma rather than produce high levels of IFN-γ.
Evolution of a quality testing program for improving malting barley in Canada
Authors: Edney M. J. , MacLeod A. L. , LaBerge D. E.
Published: March 2014

Edney, M. J., MacLeod, A. L. and LaBerge, D. E. 2014. Evolution of a quality testing program for improving malting barley in Canada. Can. J. Plant Sci. 94: 535–544. The quality of Canadian malting barley has continually improved since malt barley was exported in the late 1800s. Improvements were linked to a dynamic evaluation system that evolved with a better understanding of malting biochemistry and as suitable methods were developed. Methods became more accurate and more specific in their ability to define quality. They progressed from sensory evaluation, to surmising malt quality from barley protein levels, to the first micro-maltings followed by automated laboratory-scale maltings. Malt quality analysis started simply with malt extract and diastatic power followed by wort protein. As the necessity for cell wall breakdown became better understood, analyses like wort viscosity, fine/coarse grind extract differences and wort β-glucan were adopted. A continuum of cultivars were released in Canada, based on this evaluation system, starting with the six-rowed releases OAC 21, then Montcalm and Bonanza, followed by the two-rowed releases Betzes, Klages, Harrington and AC Metcalfe. Release of future cultivars will depend on an evolving evaluation system that could include; barley homogeneity, specific starch-degrading enzymes, individual amino acids and specific traits such as low lipoxygenase and low phytic acid barley. The result will be development and release of cultivars with better defined quality that can fill specialized niches in the malting and brewing industries of the future.
On the integrality of the Witten–Reshetikhin–Turaev 3-manifold invariants
Authors: Beliakova Anna , Chen Qi , Le Thang
Published: March 2014

We prove that the

\mathrm{SU}(2)

Witten–Reshetikhin–Turaev invariant of any 3-manifold with any colored link inside at any root of unity is an algebraic integer. As a byproduct, we get a new proof of the integrality of the

\mathrm{SO}(3)

Witten–Reshetikhin–Turaev invariant for any 3-manifold with any colored link inside at any root of unity of odd order.
Longitudinal Evaluation of Enteric Protozoa in Haitian Children by Stool Exam and Multiplex Serologic Assay
Authors: Moss Delynn M. , Priest Jeffrey W. , Hamlin Kathy , Derado Gordana , Herbein Joel , Petri William A. , Lammie Patrick J.
Published: March 2014

Haitian children were monitored longitudinally in a filariasis study. Included were stool samples examined for Giardia intestinalis and Entamoeba histolytica cysts, and serum specimens analyzed for immunoglobulin G (IgG) responses to eight recombinant antigens from G. intestinalis (variant-specific surface protein [VSP1–VSP5]), E. histolytica (lectin adhesion molecule [LecA]), and Cryptosporidium parvum (17- and 27-kDa) using a multiplex bead assay. The IgG responses to VSP antigens peaked at 2 years of age and then diminished and were significantly lower (P < 0.002) in children > 4.5 years than in children < 4.5 years. The IgG responses to Cryptosporidium tended to increase with age. The IgG responses to LecA and VSP antigens and the prevalence of stools positive for cysts were significantly higher (P < 0.037 and P < 0.035, respectively) in the rainy season than in the dry season. The multiplex bead assay provides a powerful tool for analyzing serologic responses to multiple pathogens.
Molecular Detection of Hepatitis E Virus in Rivers in the Philippines
Authors: Li Tian-Cheng , Yang Tingting , Shiota Tomoyuki , Yoshizaki Sayaka , Yoshida Hiromu , Saito Mariko , Imagawa Toshifumi , Malbas Fidelino F. , Lupisan Socorro P. , Oshitani Hitoshi , Wakita Takaji , Ishii Koji
Published: March 2014

To understand the hepatitis E virus (HEV)-pollution status in the environment in the Philippines, a total of 12 water samples were collected from rivers in Manila City for detection of HEV RNA. Three of 12 samples were positive for HEV RNA indicating that HEV is circulating in the Philippines. Phylogenetic analysis classified all of the HEV sequences into genotype 3.
Performance of Point-of-Care Diagnostics for Glucose, Lactate, and Hemoglobin in the Management of Severe Malaria in a Resource-Constrained Hospital in Uganda
Authors: Hawkes Michael , Conroy Andrea L. , Opoka Robert O. , Namasopo Sophie , Liles W. Conrad , John Chandy C. , Kain Kevin C.
Published: March 2014

Severe malaria is frequently managed without access to laboratory testing. We report on the performance of point-of-care tests used to guide the management of a cohort of 179 children with severe malaria in a resource-limited Ugandan hospital. Correlation coefficients between paired measurements for glucose (i-STAT and One Touch Ultra), lactate (i-STAT and Lactate Scout), and hemoglobin (Hb; laboratory and i-STAT) were 0.86, 0.85, and 0.73, respectively. The OneTouch Ultra glucometer readings deviated systematically from the i-STAT values by +1.7 mmol/L. Lactate Scout values were systematically higher than i-STAT by +0.86 mmol/L. Lactate measurements from either device predicted subsequent mortality. Hb estimation by the i-STAT instrument was unbiased, with upper and lower limits of agreement of −34 and +34 g/L, and it was 91% sensitive and 89% specific for the diagnosis of severe anemia (Hb < 50 g/L). New commercially available bedside diagnostic tools, although imperfect, may expedite clinical decision-making in the management of critically ill children in resource-constrained settings.
Transport of aerosol to the Arctic: analysis of CALIOP and French aircraft data during the spring 2008 POLARCAT campaign
Authors: Ancellet G. , Pelon J. , Blanchard Y. , Quennehen B. , Bazureau A. , Law K. S. , Schwarzenboeck A.
Published: March 2014

Abstract. Lidar and in situ observations performed during POLARCAT campaign are reported here in terms of statistics to characterize aerosol properties over northern Europe using daily airborne measurements conducted between Svalbard Island and Scandinavia from 30 March to 11 April 2008. It is shown that during this period, a rather large number of aerosol layers was observed in the troposphere, with a backscatter ratio at 532 nm of 1.2 (1.5 below 2 km, 1.2 between 5 and 7 km and a minimum in-between). Their sources were identified using multispectral backscatter and depolarization airborne lidar measurements after careful calibration analysis. Transport analysis and comparisons between in situ and airborne lidar observations are also provided to assess the quality of this identification. Comparison with level 1 backscatter observations of the spaceborne CALIOP lidar were done to adjust CALIOP multispectral observations to airborne observations on a statistical basis. Re-calibration for CALIOP daytime 1064 nm signals led to an increase of their values by about 30% in agreement with previous analyses. No re-calibration is made at 532 nm, but scattering ratios appear to be biased low. Regional analyses in the European Arctic then performed as a test, emphasize the potential of the CALIOP spaceborne lidar to further monitor more in depth properties of the aerosol layers over Arctic using infrared and depolarization observations. The CALIOP April 2008 global distribution of the aerosol backscatter reveal two regions with large backscatter below 2 km: the Northern Atlantic between Greenland and Norway, and Northern Siberia. The aerosol color ratio increase between the sources regions and the observations at latitudes above 70° N is consistent with a growth of the aerosol size once transported to the Arctic. The distribution of the aerosol optical properties in the mid troposphere supports the known main transport pathways between mid-latitudes and the Arctic.
Sub-3 nm particle size and composition dependent response of a nano-CPC battery
Authors: Kangasluoma J. , Kuang C. , Wimmer D. , Rissanen M. P. , Lehtipalo K. , Ehn M. , Worsnop D. R. , Wang J. , Kulmala M. , Petäjä T.
Published: March 2014

Abstract. In this study we built a nano-CPC (condensation particle counter) battery, consisting of four ultrafine CPCs optimized for the detection of sub-3 nm particles. Two of the CPCs use diethylene glycol as a working fluid: a laminar type diethlylene glycol CPC and a mixing type Airmodus A09 particle size magnifier. The other two CPCs are a laminar type TSI 3025A and a TSI 3786 with butanol and water as the working fluids, respectively. The nano-CPC battery was calibrated with seven different test aerosols: tetraheptyl ammonium bromide, ammonium sulfate, sodium chloride, tungsten oxide, sucrose, candle flame products and limonene ozonolysis products. The results show that ammonium sulfate and sodium chloride have a higher activation efficiency with the water-based 3786 than with the butanol-based 3025A, whereas the other aerosols were activated better with butanol than with water as the working fluid. It is worthwhile to mention that sub-2 nm limonene ozonolysis products were detected very poorly with all of the CPCs, butanol being the best fluid to activate the oxidation products. To explore how the detection efficiency is affected if the aerosol is an internal mixture of two different chemical substances, we made the first attempt to control the mixing state of sub-3 nm laboratory generated aerosol. We show that we generated an internally mixed aerosol of ammonium sulfate nucleated onto tungsten oxide seed particles, and observed that the activation efficiency of the internally mixed clusters was a function of the internal mixture composition.