bluuebunny/crossref_metadata_2025 huggingface dataset:
Under-recognition and reporting of dengue in Cambodia: a capture–recapture analysis of the National Dengue Surveillance System
Authors: VONG S. , GOYET S. , LY S. , NGAN C. , HUY R. , DUONG V. , WICHMANN O. , LETSON G. W. , MARGOLIS H. S. , BUCHY P.
Published: June 2011

Robust disease burden estimates are important for decision-making concerning introduction of new vaccines. Dengue is a major public health problem in the tropics but robust disease burden estimates are lacking. We conducted a two-sample, capture–recapture study in the largest province in Cambodia to determine disease under-recognition to the National Dengue Surveillance System (NDSS). During 2006–2008, community-based active surveillance for acute febrile illness was conducted in 0- to 19-year-olds in rural and urban areas combined with testing for dengue virus infection. Of 14 354 individuals under active surveillance (22 498 person-seasons), the annual incidence ranged from 13·4 to 57·8/1000 person-seasons. During the same period, NDSS incidence rates ranged from 1·1/1000 to 5·7/1000, which was 3·9- to 29·0-fold lower than found in the capture–recapture study. In hospitalized cases, the rate of under-recognition was 1·1- to 2·4-fold. This study shows the substantial degree of under-recognition/reporting of dengue and that reported hospitalized cases are not a good surrogate for estimating dengue disease burden.
Sharing of quorum-sensing signals and role of interspecies communities in a bacterial plant disease
Authors: Hosni Taha , Moretti Chiaraluce , Devescovi Giulia , Suarez-Moreno Zulma Rocio , Fatmi M' Barek , Guarnaccia Corrado , Pongor Sandor , Onofri Andrea , Buonaurio Roberto , Venturi Vittorio
Published: June 2011

Pathogenic bacteria interact not only with the host organism but most probably also with the resident microbial flora. In the knot disease of the olive tree (Olea europaea), the causative agent is the bacterium Pseudomonas savastanoi pv. savastanoi (Psv). Two bacterial species, namely Pantoea agglomerans and Erwinia toletana, which are not pathogenic and are olive plant epiphytes and endophytes, have been found very often to be associated with the olive knot. We identified the chemical signals that are produced by strains of the three species isolated from olive knot and found that they belong to the N-acyl-homoserine lactone family of QS signals. The luxI/R family genes responsible for the production and response to these signals in all three bacterial species have been identified and characterized. Genomic knockout mutagenesis and in planta experiments showed that virulence of Psv critically depends on QS; however, the lack of signal production can be complemented by wild-type E. toletana or P. agglomerans. It is also apparent that the disease caused by Psv is aggravated by the presence of the two other bacterial species. In this paper we discuss the potential role of QS in establishing a stable consortia leading to a poly-bacterial disease.
Illumina-based analysis of microbial community diversity
Authors: Degnan Patrick H , Ochman Howard
Published: June 2011

Microbes commonly exist in milieus of varying complexity and diversity. Although cultivation-based techniques have been unable to accurately capture the true diversity within microbial communities, these deficiencies have been overcome by applying molecular approaches that target the universally conserved 16S ribosomal RNA gene. The recent application of 454 pyrosequencing to simultaneously sequence thousands of 16S rDNA sequences (pyrotags) has revolutionized the characterization of complex microbial communities. To date, studies based on 454 pyrotags have dominated the field, but sequencing platforms that generate many more sequence reads at much lower costs have been developed. Here, we use the Illumina sequencing platform to design a strategy for 16S amplicon analysis (iTags), and assess its generality, practicality and potential complications. We fabricated and sequenced paired-end libraries of amplified hyper-variable 16S rDNA fragments from sets of samples that varied in their contents, ranging from a single bacterium to highly complex communities. We adopted an approach that allowed us to evaluate several potential sources of errors, including sequencing artifacts, amplification biases, non-corresponding paired-end reads and mistakes in taxonomic classification. By considering each source of error, we delineate ways to make biologically relevant and robust conclusions from the millions of sequencing reads that can be readily generated by this technology.
DddW, a third DMSP lyase in a model Roseobacter marine bacterium, Ruegeria pomeroyi DSS-3
Authors: Todd Jonathan D , Kirkwood Mark , Newton-Payne Simone , Johnston Andrew W B
Published: June 2011

Ruegeria pomeroyi DSS-3 is a model Roseobacter marine bacterium, particularly regarding its catabolism of dimethylsulfoniopropionate (DMSP), an abundant anti-stress molecule made by marine phytoplankton. We found a novel gene, dddW, which encodes a DMSP lyase that cleaves DMSP into acrylate plus the environmentally important volatile dimethyl sulfide (DMS). Mutations in dddW reduced, but did not abolish DMS production. Transcription of dddW was greatly enhanced by pre-growth of cells with DMSP, via a LysR-type regulator. Close DddW homologs occur in only one other Roseobacter species, and there are no close homologs and only a few related sequences in metagenomes of marine bacteria. In addition to DddW, R. pomeroyi DSS-3 had been shown to have two other, different, DMSP lyases, DddP and DddQ, plus an enzyme that demethylates DMSP, emphasizing the importance of this substrate for this model bacterium.
Remodelling of the endoplasmic reticulum during store‐operated calcium entry
Authors: Shen Wei‐Wei , Frieden Maud , Demaurex Nicolas
Published: June 2011

SOCE (store‐operated calcium entry) is a ubiquitous cellular mechanism linking the calcium depletion of the ER (endoplasmic reticulum) to the activation of PM (plasma membrane) Ca2+‐permeable channels. The activation of SOCE channels favours the entry of extracellular Ca2+ into the cytosol, thereby promoting the refilling of the depleted ER Ca2+ stores as well as the generation of long‐lasting calcium signals. The molecules that govern SOCE activation comprise ER Ca2+ sensors [STIM1 (stromal interaction molecule 1) and STIM2], PM Ca2+‐permeable channels {Orai and TRPC [TRP (transient receptor potential) canonical]} and regulatory Ca2+‐sensitive cytosolic proteins {CRACR2 [CRAC (Ca2+ release‐activated Ca2+ current) regulator 2]}. Upon Ca2+ depletion of the ER, STIM molecules move towards the PM to bind and activate Orai or TRPC channels, initiating calcium entry and store refilling. This molecular rearrangement is accompanied by the formation of specialized compartments derived from the ER, the pre‐cER (cortical ER) and cER. The pre‐cER appears on the electron microscope as thin ER tubules enriched in STIM1 that extend along microtubules and that are devoid of contacts with the PM. The cER is located in immediate proximity to the PM and comprises thinner sections enriched in STIM1 and devoid of chaperones that might be dedicated to calcium signalling. Here, we review the molecular interactions and the morphological changes in ER structure that occur during the SOCE process.
Re-evaluation of the impact of ternary additions of Ni and Cu on the A1 to L1 transformation in FePt films
Authors: Wang B. , Barmak K.
Published: June 2011

The impact of ternary additions of Ni (1.6–21.5 at. %) and Cu (1.3–17.3 at. %) on the A1 (face centered cubic, fcc) to L10 phase transformation in FePt films has been re-evaluated based on compositions obtained using energy dispersive x-ray spectrometry (EDS). The data presented here serve as corrections to results reported in six previous studies [D. C. Berry and K. Barmak, J. Appl. Phys. 102, 024912 (2007); 101, 014905 (2007); 99, 08G901 (2006); D. C. Berry, J. Kim, K. Barmak, K. Wierman, E. B. Svedberg, and J. K. Howard, Scr. Mater. 53, 423 (2005); K. Barmak, J. Kim, D. C. Berry, W. N. Hanani, K. Wierman, E. B. Svedberg, and J. K. Howard, J. Appl. Phys. 97, 024902 (2005); K. Barmak, J. Kim, D. C. Berry, K. W. Wierman, E. B. Svedberg, and J. K. Howard, ibid. 95, 7486 (2004)]. The new EDS compositions do not change the following conclusions of these previous studies: (i) when ternary FeNiPt and FeCuPt alloys are compared with binary FePt alloys with the same Pt content, it is seen that additions of Ni slow the transformation kinetics, whereas additions of Cu have no measurable impact on the kinetics, (ii) the Curie temperature of the L10 phase is lowered by additions of Ni or Cu, (iii) the Curie temperature of the A1 phase is increased by additions of Ni, but lowered by additions of Cu, and (iv) the transformation enthalpy is lowered by large additions of Ni, but is unaffected by additions of Cu. The ordering behavior of FeCuPt alloys as evidenced by the kinetic ordering temperature is compared with other reports in the literature based on magnetic measurements.
Thomas-forbidden particle capture
Authors: Carter John H. , Lieber Michael
Published: June 2011

At high energies, in particle-capture processes between ions and atoms, classical kinematic requirements show that generally double-collision Thomas processes dominate. However, for certain mass-ratios these processes are kinematically forbidden. This paper explores the possibility of capture for such processes by triple or higher order collision processes.
Observation of an asymmetrical effect when introducing Zr in Mg/Co multilayers
Authors: Le Guen K. , Hu M.-H. , André J.-M. , Zhou S. K. , Li H. Ch. , Zhu J. T. , Wang Z. S. , Meny C. , Galtayries A. , Jonnard P.
Published: June 2011

We have developed Mg/Co, Mg/Zr/Co, Mg/Co/Zr, and Mg/Zr/Co/Zr periodic multilayers and measured at 25.1 nm a reflectivity (R) highly sensitive to the material order within the period. To understand why Mg/Co/Zr is a more efficient mirror (R=50%) than Mg/Zr/Co and Mg/Zr/Co/Zr (∼40%), we have probed the interface quality through time-of-flight secondary ion mass spectrometry and nuclear magnetic resonance measurements. The Zr-on-Co interface is found quite sharp while a strong intermixing process is evidenced between the upper Co and lower Zr layers, responsible for the decrease in optical contrast and subsequent R loss.
Activity patterns of bats at house roosts near Adelaide
Authors: Sanderson K. J. , Jaeger D. A. , Bonner J. F. , Jansen L.
Published: June 2011

Activity patterns of bats in rural areas near Adelaide (South Australia) were monitored systematically at one roost (holding Mormopterus planiceps) and episodically at two others (holding Chalinolobus morio and Nyctophilus geoffroyi) from March 1999 to March 2001. Bats were active from about late August to mid May, and left roosts each night about half an hour after sunset. Exit times were 15 min (mean) for M. planiceps (66 nights), 27-40 min for C. morio (4 nights) and 13-20 min for N. geoffroyi (3 nights), with significant correlation between numbers of M. planiceps exiting and sunset temperatures. M. planiceps were active near the roost before midnight, with very little activity after midnight. C. morio were active near the roost over the whole of some evenings. Most N. geoffroyi activity near the roost was recorded as bats returned just before sunrise and as they left after sunset, with low activity near the roost overnight. Temperatures were logged hourly in two roosts, and exceeded 40�C on some days. Visual observations showed that C. morio were sometimes located in different positions in the roost, and that they vacated the house roost over winter.
. Management issues of urban common brushtail possums Trichosurus vulpecula: a loved or hated neighbour.
Authors: Eymann J. , Herbert C. A. , Cooper D. W.
Published: June 2011

The common brushtail possum (Trichosurus vulpecula) has readily adapted to the expanding urban settings of its native Australian environment. This has lead to conflict with humans due to T.�vulpecula?s seemingly bold behaviour in suburbia. Current management strategies encourage people to live harmoniously with possums. However, despite the cooperation of many residents, some object to this policy and illegally remove T.�vulpecula from their properties. Wildlife managers are seeking alternative management options that aim to reduce conflict with people. These include fertility control methods which may be used to adjust possum numbers in a publicly acceptable way. Nest boxes are frequently recommended as alternative den sites for T.�vulpecula which reside in man-made structures. The disease status of possums may alter the rationale for their management in urban areas, due to the potential consequences for humans, domestic animals and possum conservation. Understanding the biology and behaviour of T.�vulpecula can greatly enhance the ability to select and successfully utilise adequate methods and solve outstanding issues. As such, this paper aims to review the scientific knowledge on possum populations as well as urban possum management policies and potential management tools.
Climate related sea-level variations over the past two millennia
Authors: Kemp Andrew C. , Horton Benjamin P. , Donnelly Jeffrey P. , Mann Michael E. , Vermeer Martin , Rahmstorf Stefan
Published: June 2011

We present new sea-level reconstructions for the past 2100 y based on salt-marsh sedimentary sequences from the US Atlantic coast. The data from North Carolina reveal four phases of persistent sea-level change after correction for glacial isostatic adjustment. Sea level was stable from at least BC 100 until AD 950. Sea level then increased for 400 y at a rate of 0.6 mm/y, followed by a further period of stable, or slightly falling, sea level that persisted until the late 19th century. Since then, sea level has risen at an average rate of 2.1 mm/y, representing the steepest century-scale increase of the past two millennia. This rate was initiated between AD 1865 and 1892. Using an extended semiempirical modeling approach, we show that these sea-level changes are consistent with global temperature for at least the past millennium.
CD9 tetraspanin generates fusion competent sites on the egg membrane for mammalian fertilization
Authors: Jégou Antoine , Ziyyat Ahmed , Barraud-Lange Virginie , Perez Eric , Wolf Jean Philippe , Pincet Frédéric , Gourier Christine
Published: June 2011

CD9 tetraspanin is the only egg membrane protein known to be essential for fertilization. To investigate its role, we have measured, on a unique acrosome reacted sperm brought in contact with an egg, the adhesion probability and strength with a sensitivity of a single molecule attachment. Probing the binding events at different locations of wild-type egg we described different modes of interaction. Here, we show that more gamete adhesion events occur on Cd9 null eggs but that the strongest interaction mode disappears. We propose that sperm–egg fusion is a direct consequence of CD9 controlled sperm–egg adhesion properties. CD9 generates adhesion sites responsible for the strongest of the observed gamete interaction. These strong adhesion sites impose, during the whole interaction lifetime, a tight proximity of the gamete membranes, which is a requirement for fusion to take place. The CD9-induced adhesion sites would be the actual location where fusion occurs.
A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin
Authors: Reiling Jan H. , Clish Clary B. , Carette Jan E. , Varadarajan Malini , Brummelkamp Thijn R. , Sabatini David M.
Published: June 2011

Tunicamycin (TM) inhibits eukaryotic asparagine-linked glycosylation, protein palmitoylation, ganglioside production, proteoglycan synthesis, 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity, and cell wall biosynthesis in bacteria. Treatment of cells with TM elicits endoplasmic reticulum stress and activates the unfolded protein response. Although widely used in laboratory settings for many years, it is unknown how TM enters cells. Here, we identify in an unbiased genetic screen a transporter of the major facilitator superfamily, major facilitator domain containing 2A (MFSD2A), as a critical mediator of TM toxicity. Cells without MFSD2A are TM-resistant, whereas MFSD2A-overexpressing cells are hypersensitive. Hypersensitivity is associated with increased cellular TM uptake concomitant with an enhanced endoplasmic reticulum stress response. Furthermore, MFSD2A mutant analysis reveals an important function of the C terminus for correct intracellular localization and protein stability, and it identifies transmembrane helical amino acid residues essential for mediating TM sensitivity. Overall, our data uncover a critical role for MFSD2A by acting as a putative TM transporter at the plasma membrane.
MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis
Authors: Kurowska-Stolarska Mariola , Alivernini Stefano , Ballantine Lucy E. , Asquith Darren L. , Millar Neal L. , Gilchrist Derek S. , Reilly James , Ierna Michelle , Fraser Alasdair R. , Stolarski Bartosz , McSharry Charles , Hueber Axel J. , Baxter Derek , Hunter John , Gay Steffen , Liew Foo Y. , McInnes Iain B.
Published: June 2011

MicroRNA (miRNA) species (miR) regulate mRNA translation and are implicated as mediators of disease pathology via coordinated regulation of molecular effector pathways. Unraveling miR disease-related activities will facilitate future therapeutic interventions. miR-155 recently has been identified with critical immune regulatory functions. Although detected in articular tissues, the functional role of miR-155 in inflammatory arthritis has not been defined. We report here that miR-155 is up-regulated in synovial membrane and synovial fluid (SF) macrophages from patients with rheumatoid arthritis (RA). The increased expression of miR-155 in SF CD14+cells was associated with lower expression of the miR-155 target, Src homology 2-containing inositol phosphatase-1 (SHIP-1), an inhibitor of inflammation. Similarly, SHIP-1 expression was decreased in CD68+cells in the synovial lining layer in RA patients as compared with osteoarthritis patients. Overexpression of miR-155 in PB CD14+cells led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines. Conversely, inhibition of miR-155 in RA synovial CD14+cells reduced TNF-α production. Finally, miR-155–deficient mice are resistant to collagen-induced arthritis, with profound suppression of antigen-specific Th17 cell and autoantibody responses and markedly reduced articular inflammation. Our data therefore identify a role of miR-155 in clinical and experimental arthritis and suggest that miR-155 may be an intriguing therapeutic target.
Structural and biochemical characterization of two binding sites for nucleation-promoting factor WASp-VCA on Arp2/3 complex
Authors: Ti Shih-Chieh , Jurgenson Christopher T. , Nolen Bradley J. , Pollard Thomas D.
Published: June 2011

Actin-related protein (Arp) 2/3 complex mediates the formation of actin filament branches during endocytosis and at the leading edge of motile cells. The pathway of branch formation is ambiguous owing to uncertainty regarding the stoichiometry and location of VCA binding sites on Arp2/3 complex. Isothermal titration calorimetry showed that the CA motif from the C terminus of fission yeast WASP (Wsp1p) bound to fission yeast and bovine Arp2/3 complex with a stoichiometry of 2 to 1 and very different affinities for the two sites (
K
d
s of 0.13 and 1.6 μM for fission yeast Arp2/3 complex). Equilibrium binding, kinetic, and cross-linking experiments showed that (
i
) CA at high-affinity site 1 inhibited Arp2/3 complex binding to actin filaments, (
ii
) low-affinity site 2 had a higher affinity for CA when Arp2/3 complex was bound to actin filaments, and (
iii
) Arp2/3 complex had a much higher affinity for free CA than VCA cross-linked to an actin monomer. Crystal structures showed the C terminus of CA bound to the low-affinity site 2 on Arp3 of bovine Arp2/3 complex. The C helix is likely to bind to the barbed end groove of Arp3 in a position for VCA to deliver the first actin subunit to the daughter filament.
Arp2/3 complex is bound and activated by two WASP proteins
Authors: Padrick Shae B. , Doolittle Lynda K. , Brautigam Chad A. , King David S. , Rosen Michael K.
Published: June 2011

Actin related protein 2/actin related protein 3 (Arp2/3) complex nucleates new actin filaments in eukaryotic cells in response to signals from proteins in the Wiskott–Aldrich syndrome protein (WASP) family. The conserved VCA domain of WASP proteins activates Arp2/3 complex by inducing conformational changes and delivering the first actin monomer of the daughter filament. Previous models of activation have invoked a single VCA acting at a single site on Arp2/3 complex. Here we show that activation most likely involves engagement of two distinct sites on Arp2/3 complex by two VCA molecules, each delivering an actin monomer. One site is on Arp3 and the second is on ARPC1 and Arp2. The VCAs at these sites have distinct roles in activation. Our findings reconcile apparently conflicting literature on VCA activation of Arp2/3 complex and lead to a new model for this process.
Extent and limits of cooperation in animals
Authors: Cheney Dorothy L.
Published: June 2011

Individuals in many animal species are strongly motivated to form close social bonds and to attend to the social interactions of others. Some animals may also recognize other individuals’ intentions and simple mental states. Such curiosity appears to be adaptive, because it enables observers to learn about others’ status and relationships and to anticipate future events without direct participation. However, many questions remain unresolved. In particular, it remains unclear whether animals keep track of favors given and received when interacting with others, and whether they rely on memory of past cooperative acts when anticipating future ones. Primates appear to possess many of the cognitive abilities required for human-like contingent cooperation. However, most investigations of captive primates have indicated that cooperation is seldom contingency-based, and that interactions are not influenced by inequity aversion or sensitivity to cheaters. In contrast, several experiments with nonprimates have found that animals can take into account recent interactions when supporting others, suggesting that the apparent rarity of contingent cooperation in primates may not stem from cognitive constraints. Instead, individuals may tolerate short-term inequities in favors given and received because most cooperation occurs among long-term reciprocating partners.
The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy
Authors: Read Andrew F. , Day Troy , Huijben Silvie
Published: June 2011

The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet “radical pathogen cure” maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.
Cooperation and competition in a cliff-dwelling people
Authors: Strassmann Beverly I.
Published: June 2011

In animals that breed cooperatively, adult individuals will sometimes delay reproduction to act as helpers at the nest who raise young that are not their genetic offspring. It has been proposed that humans are also a cooperatively breeding species because older daughters, grandmothers, and other kin and nonkin may provide significant childcare. Through a prospective cohort study of children's (n= 1,700) growth and survival in the Dogon of Mali, I show that cooperative breeding theory is a poor fit to the family dynamics of this population. Rather than helping each other, siblings competed for resources, producing a tradeoff between the number of maternal siblings and growth and survival. It did not take a village to raise a child; children fared the same in nuclear as in extended families. Of critical importance was the degree of polygyny, which created conflicts associated with asymmetries in genetic relatedness. The risk of death was higher and the rate of growth was slower in polygynous than monogamous families. The hazard of death for Dogon children was twofold higher if the resident paternal grandmother was alive rather than dead. This finding may reflect the frailty of elderly grandmothers who become net consumers rather than net producers in this resource-poor society. Mothers were of overwhelming importance for child survival and could not be substituted by any category of kin or nonkin. The idea of cooperative breeding taken from animal studies is a poor fit to the complexity and diversity of kin interactions in humans.
Detection and avoidance of a carnivore odor by prey
Authors: Ferrero David M. , Lemon Jamie K. , Fluegge Daniela , Pashkovski Stan L. , Korzan Wayne J. , Datta Sandeep Robert , Spehr Marc , Fendt Markus , Liberles Stephen D.
Published: June 2011

Predator–prey relationships provide a classic paradigm for the study of innate animal behavior. Odors from carnivores elicit stereotyped fear and avoidance responses in rodents, although sensory mechanisms involved are largely unknown. Here, we identified a chemical produced by predators that activates a mouse olfactory receptor and produces an innate behavioral response. We purified this predator cue from bobcat urine and identified it to be a biogenic amine, 2-phenylethylamine. Quantitative HPLC analysis across 38 mammalian species indicates enriched 2-phenylethylamine production by numerous carnivores, with some producing >3,000-fold more than herbivores examined. Calcium imaging of neuronal responses in mouse olfactory tissue slices identified dispersed carnivore odor-selective sensory neurons that also responded to 2-phenylethylamine. Two prey species, rat and mouse, avoid a 2-phenylethylamine odor source, and loss-of-function studies involving enzymatic depletion of 2-phenylethylamine from a carnivore odor indicate it to be required for full avoidance behavior. Thus, rodent olfactory sensory neurons and chemosensory receptors have the capacity for recognizing interspecies odors. One such cue, carnivore-derived 2-phenylethylamine, is a key component of a predator odor blend that triggers hard-wired aversion circuits in the rodent brain. These data show how a single, volatile chemical detected in the environment can drive an elaborate danger-associated behavioral response in mammals.
Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform
Authors: Hu Che-Ming J. , Zhang Li , Aryal Santosh , Cheung Connie , Fang Ronnie H. , Zhang Liangfang
Published: June 2011

Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Here we report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural erythrocyte membranes, including both membrane lipids and associated membrane proteins for long-circulating cargo delivery. The structure, size and surface zeta potential, and protein contents of the erythrocyte membrane-coated nanoparticles were verified using transmission electron microscopy, dynamic light scattering, and gel electrophoresis, respectively. Mice injections with fluorophore-loaded nanoparticles revealed superior circulation half-life by the erythrocyte-mimicking nanoparticles as compared to control particles coated with the state-of-the-art synthetic stealth materials. Biodistribution study revealed significant particle retention in the blood 72 h following the particle injection. The translocation of natural cellular membranes, their associated proteins, and the corresponding functionalities to the surface of synthetic particles represents a unique approach in nanoparticle functionalization.
Role of IL-1 receptor-associated kinase-M (IRAK-M) in priming of immune and inflammatory responses by nitrogen bisphosphonates
Authors: Norton John T. , Hayashi Tomoko , Crain Brian , Corr Maripat , Carson Dennis A.
Published: June 2011

Nitrogen bisphosphonates (NBPs) are commonly prescribed for osteoporosis but have also been found to induce inflammatory reactions and to delay the progression of breast cancer. The inflammatory and anticancer effects of the NBPs might be associated with an ability to modulate innate immune signaling. In mice, intraperitoneal NBP administration causes a rapid influx of neutrophils and monocytes that is dependent on the myeloid differentiation primary response gene 88 (MyD88) mediator of Toll-like receptor (TLR) and IL-1 signaling. Bone marrow chimeras demonstrate that this inflammatory response is partially dependent on TLR4 expression by hematopoietic cells and the IL-1 receptor on radioresistant cells. In vitro, NBPs directly stimulate neither murine bone marrow-derived mononuclear cells nor human peripheral blood mononuclear cells, but rather prime them to produce increased amounts of cytokines when exposed to IL-1 or TLR ligands. This potentiation is mediated by a reduction in IL-1 receptor-associated kinase-M, a negative regulator of MyD88-dependent signaling. In vivo, this property renders the NBPs as effective adjuvants that enhance both cellular and antibody responses to antigens.
The application of Vollenweider's eutrophication models for assessing ecosystem health: Hamilton Harbour (Lake Ontario) example
Authors: Munawar M. , Fitzpatrick M.
Published: June 2011

This note is motivated by the classical Vollenweider eutrophication models which were instrumental in the phosphorus abatement provisions of the Great Lakes Water Quality Agreement. The models were revisited as a tool for assessing the ecosystem health of Areas of Concern in terms of Beneficial Use Impairments and potential recovery. The models indicated that Hamilton Harbour is a hyper-eutrophic environment in spite of continued phosphorus abatement management efforts. The utility and potential of these models have been demonstrated and recommended for application not only in Areas of Concern, but also other stressed environments.
Limnological responses to changes in the thermal mixing regime in Lake Biwa associated with global warming
Authors: Sakamoto Mitsuru
Published: June 2011

In Lake Biwa, restoration of water quality was achieved through the control of phosphorus discharges from the drainage basin. Recently, additional concerns have arisen regarding accelerating hypolimnetic deoxygenation and changes in the flora and seasonal periodicity of phytoplankton. Based on the analysis of the monitoring survey data, the effects of the changes in lake water mixing due to global warming on phytoplankton dynamics were examined using the seasonal [NO3] changes in surface water as a marker of the vertical mixing of water column. Autumnal increases in the surface water [NO3] started one month earlier after 1990. It was concluded that earlier onset of the fall overturn after 1990 was due to warming of the hypolimnion by warm winters after 1990. Because of diverse impacts of climate change and anthropogenic activities on lakes, and less predictability of their cumulative effects, increased knowledge of these effects is an urgent requirement for the progress of limnological science under global warming.
Conserving Time in the Classroom: The Clicker Technique
Authors: Anderson Lindsay S. , Healy Alice F. , Kole James A. , Bourne Lyle E.
Published: June 2011

Any technique that conserves classroom instructional time without sacrificing the amount learned is of great educational value. This research compared a laboratory analogue of the clicker technique to analogues of other classroom pedagogical methods that all involve repeated testing during teaching. The clicker analogue mimics the classroom practice of dropping material that is understood by the majority of the class, as revealed by testing with clicker questions, from further lecture. A fact learning and retrieval paradigm was used, in which college students learned facts about unfamiliar countries. Compressing instruction time based on group-level performance produced as much learning as no compression and as compression based on individual-level performance. Results suggest that the clicker technique is an efficient and cost-effective method of conserving instructional time without loss of amount learned.
Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species
Authors: Qian Li , Wythe Joshua D. , Liu Jiandong , Cartry Jerome , Vogler Georg , Mohapatra Bhagyalaxmi , Otway Robyn T. , Huang Yu , King Isabelle N. , Maillet Marjorie , Zheng Yi , Crawley Timothy , Taghli-Lamallem Ouarda , Semsarian Christopher , Dunwoodie Sally , Winlaw David , Harvey Richard P. , Fatkin Diane , Towbin Jeffrey A. , Molkentin Jeffery D. , Srivastava Deepak , Ocorr Karen , Bruneau Benoit G. , Bodmer Rolf
Published: June 2011

Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart–specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K+ channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42–Tinman interaction. To determine whether a Cdc42–Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1.
Cdc55 coordinates spindle assembly and chromosome disjunction during meiosis
Authors: Bizzari Farid , Marston Adele L.
Published: June 2011

During meiosis, two consecutive nuclear divisions follow a single round of deoxyribonucleic acid replication. In meiosis I, homologues are segregated, whereas in meiosis II, sister chromatids are segregated. This requires that the sequential assembly and dissolution of specialized chromosomal factors are coordinated with two rounds of spindle assembly and disassembly. How these events are coupled is unknown. In this paper, we show, in budding yeast, that the protein phosphatase 2A regulatory subunit Cdc55 couples the loss of linkages between chromosomes with nuclear division by restraining two other phosphatases, Cdc14 and PP2ARts1. Cdc55 maintains Cdc14 sequestration in the nucleolus during early meiosis, and this is essential for the assembly of the meiosis I spindle but not for chromosomes to separate. Cdc55 also limits the formation of PP2A holocomplexes containing the alternative regulatory subunit Rts1, which is crucial for the timely dissolution of sister chromatid cohesion. Therefore, Cdc55 orders passage through the meiotic divisions by ensuring a balance of phosphatases.
Plasma response to externally applied resonant magnetic perturbations
Authors: Yu Q. , Günter S.
Published: June 2011

Based on recent finding that applied resonant magnetic perturbation (RMP) can either increase or decrease the local electron density gradient around the resonant surface (Yu and Günter 2009 Nucl. Fusion
49 062001), the plasma response to the RMP of a single helicity is studied numerically by further taking into account the electron energy transport. It is found that the changes in the local electron density and temperature by RMPs are coupled. If the local parallel heat diffusivity and/or the island width are sufficiently large, the local electron temperature profile flattens, which enhances the change in the local electron density gradient. Depending on the plasma parameters, either the plasma rotation frequency or the electron diamagnetic frequency (electron pressure gradient) can be significantly changed by RMPs, and these two changes affect each other. With a reduced set of equations that does not include the electron energy transport equation, the particle transport in stochastic magnetic fields is found to be similar to that across a single magnetic island.
Real-time control of the safety factor profile diagnosed by magneto-hydrodynamic activity on the Tore Supra tokamak
Authors: Imbeaux F. , Lennholm M. , Ekedahl A. , Pastor P. , Aniel T. , Brémond S. , Decker J. , Devynck P. , Dumont R. , Giruzzi G. , Maget P. , Mazon D. , Merle A. , Molina D. , Moreau P. , Saint-Laurent F. , Ségui J.L. , Zarzoso D.
Published: June 2011

Real-time control is essential for many aspects of tokamak operation. A key parameter to control is the current profile, since both confinement properties and magneto-hydrodynamic (MHD) activity depend on it in quite a sensitive way. The long pulse capability of the Tore Supra tokamak has allowed a unique type of experiment, where successive stationary states of the safety factor profile, defined by their MHD activity, are established and controlled in real time. Multiple target stationary states could be requested and reached during the main heating phase of a single plasma discharge. Experiments have been carried out featuring (i) control of the presence/absence of sawteeth with varying plasma parameters, (ii) obtaining and sustaining a ‘hot core’ plasma regime without MHD activity and (iii) recovery from a voluntarily triggered deleterious MHD regime. During these experiments, the influence of fast ions on MHD stability could be observed and characterized, as well as indications of an enhanced ‘hot core’ confinement in electron heat transport during quiescent MHD states.
A diffusive model for halo width growth during vertical displacement events
Authors: Eidietis N.W. , Humphreys D.A.
Published: June 2011

The electromagnetic loads produced by halo currents during vertical displacement events (VDEs) impose stringent requirements on the strength of ITER in-vessel components. A predictive understanding of halo current evolution is essential for ensuring the robust design of these components. A significant factor determining that evolution is the plasma resistance, which is a function of three quantities: the resistivities of the core and halo regions, and the halo region width. A diffusive model of halo width growth during VDEs has been developed, which provides one part of a physics basis for predictive halo current simulations. The diffusive model was motivated by DIII-D observations that VDEs with cold post-thermal quench plasma and a current decay time much faster than the vertical motion (type I VDE) possess much wider halo region widths than warmer plasma VDEs, where the current decay is much slower than the vertical motion (type II). A 2D finite element code is used to model the diffusion of toroidal halo current during selected type I and type II DIII-D VDEs. The model assumes a core plasma region within the last closed flux surface (LCFS) diffusing current into a halo plasma filling the vessel outside the LCFS. LCFS motion and plasma temperature are prescribed from experimental observations. The halo width evolution produced by this model compares favourably with experimental measurements of type I and type II toroidal halo current width evolution.
Performance of multi-aperture grid extraction systems for an ITER-relevant RF-driven negative hydrogen ion source
Authors: Franzen P. , Gutser R. , Fantz U. , Kraus W. , Falter H. , Fröschle M. , Heinemann B. , McNeely P. , Nocentini R. , Riedl R. , Stäbler A. , Wünderlich D.
Published: June 2011

The ITER neutral beam system requires a negative hydrogen ion beam of 48 A with an energy of 0.87 MeV, and a negative deuterium beam of 40 A with an energy of 1 MeV. The beam is extracted from a large ion source of dimension 1.9 × 0.9 m2 by an acceleration system consisting of seven grids with 1280 apertures each. Currently, apertures with a diameter of 14 mm in the first grid are foreseen.

In 2007, the IPP RF source was chosen as the ITER reference source due to its reduced maintenance compared with arc-driven sources and the successful development at the BATMAN test facility of being equipped with the small IPP prototype RF source (
of the area of the ITER NBI source). These results, however, were obtained with an extraction system with 8 mm diameter apertures.

This paper reports on the comparison of the source performance at BATMAN of an ITER-relevant extraction system equipped with chamfered apertures with a 14 mm diameter and 8 mm diameter aperture extraction system. The most important result is that there is almost no difference in the achieved current density—being consistent with ion trajectory calculations—and the amount of co-extracted electrons. Furthermore, some aspects of the beam optics of both extraction systems are discussed.
Response of a resistive and rotating tokamak to external magnetic perturbations below the Alfvén frequency
Authors: Chu M.S. , Lao L.L. , Schaffer M.J. , Evans T.E. , Strait E.J. , Liu Y.Q. , Lanctot M.J. , Reimerdes H. , Liu Y. , Casper T.A. , Gribov Yuri
Published: June 2011

Motivated by the recent experimental observation that plasma stability can be improved by external magnetic perturbations, the general problem of plasma response to external magnetic perturbations is investigated. Different (vacuum, ideal and resistive) plasma response models are considered and compared. Plasma response, in experiments where stabilization was achieved, is obtained through computation using the MARS-F code, with a plasma model that includes both plasma resistivity and rotation. The resultant magnetic field line stochasticity is much reduced from that obtained formerly using the vacuum plasma model. This reduced stochasticity is more consistent with the favourable experimental observation of enhanced stability. Examples are given for the response of an ITER plasma to perturbations generated by the correction coils; and the response of a plasma to external coils (antenna) up to the Alfvén frequency.
Significant effect of plasma compressibility on nonlinear mode coupling of Alfvén eigenmodes
Authors: Hirota M. , Aiba N.
Published: June 2011

Nonlinear mode coupling of the (shear) Alfvén eigenmodes (AEs) is studied both analytically and numerically to understand the effect of the magnetohydrodynamic nonlinearity on the saturation mechanism. The energy transfer via the mode coupling can restrict the amplitude to a level that is estimated by the frequency mismatch and the coupling coefficient among the coupled modes. For the cases of cylindrical and toroidal geometries, new numerical codes are developed to calculate the coupling coefficient directly according to the Lagrangian theory of weakly nonlinear perturbations. It is shown that the shear AEs can couple with each other through the small compressional components of their eigenfunctions. By assuming low-β plasma, an analytic estimation of the coupling coefficient
is derived in the cylindrical case. A coupling of reversed shear AEs in toroidal geometry indicates a more effective energy transfer at a lower amplitude level owing to the enhanced compressional perturbations in the poloidal sidebands.
Internal and external electron transport barriers in the RFX-mod reversed field pinch
Authors: Puiatti M.E. , Valisa M. , Agostini M. , Auriemma F. , Bonomo F. , Carraro L. , Fassina A. , Gobbin M. , Lorenzini R. , Momo B. , Scaggion A. , Zaniol B. , Alfier A. , Apolloni L. , Baruzzo M. , Bolzonella T. , Bonfiglio D. , Canton A. , Cappello S. , Cavazzana R. , Bello S. Dal , De Masi G. , Escande D.F. , Franz P. , Gazza E. , Guo S. , Innocente P. , Marchiori G. , Marrelli L. , Martin P. , Martines E. , Martini S. , Menmuir S. , Novello L. , Paccagnella R. , Piovesan P. , Piron L. , Predebon I. , Ruzzon A. , Sattin F. , Scarin P. , Soppelsa A. , Spizzo G. , Spagnolo S. , Spolaore M. , Terranova D. , Veranda M. , Vianello N. , Zanca P. , Zanotto L. , Zuin M.
Published: June 2011

An interesting result of magnetic chaos reduction in RFX-mod high current discharges is the development of strong electron transport barriers. An internal heat and particle transport barrier is formed when a bifurcation process changes the magnetic configuration into a helical equilibrium and chaos reduction follows, together with the formation of a null in theqshear. Strong temperature gradients develop, corresponding to a decreased thermal and particle transport. Turbulence analysis shows that the large electron temperature gradients are limited by the onset of micro-tearing modes, in addition to residual magnetic chaos. A new type of electron transport barrier with strong temperature gradients develops more externally (r/a= 0.8) accompanied by a 30% improvement of the global confinement time. The mechanism responsible for the formation of such a barrier is still unknown but it is likely associated with a local reduction of magnetic chaos. These external barriers develop primarily in situations of well-conditioned walls so that they might be regarded as attempts towards an L–H transition. Both types of barriers occur in high-current low-collisionality regimes. Analogies with tokamak and stellarators are discussed.
Place‐Based Income Inequality Clusters in the Rural North Central Region, 1979–2009
Authors: Peters David J.
Published: June 2011

This analysis identifies and describes clusters of persistently low and high income inequality for N = 7,353 non‐metropolitan block‐groups in the western part of the North Central Region. Analysis finds more low inequality than high inequality places in the region, but there are also large numbers of rising inequality places. Lower inequality places are found to have poorer demographic and economic outcomes than higher inequality places, contrary to what is found in the literature. Lower inequality places are also found to be more specialized in traditional agricultural and industrial sectors, while higher inequality places are more specialized in higher skilled services industries.