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Publications (28)199.71 Total impact
Article: A novel plant-produced Pfs25 fusion subunit vaccine induces long-lasting transmission blocking antibody responses.[Show abstract] [Hide abstract]
ABSTRACT: Malaria transmission blocking vaccines (TBV) directed against proteins expressed on sexual stages of Plasmodium falciparum in the mosquito midgut are considered an effective means to reduce malaria transmission. Antibodies induced by TBV block sporogonic development in the mosquito, and thus transmission to the next human host. The Pfs25 protein, expressed on the surface of gametes, zygotes and ookinetes, is one of the primary targets for TBV development. Using a plant virus-based transient expression system, we have successfully produced Pfs25 fused to a modified lichenase (LicKM) carrier in Nicotiana benthamiana, purified and characterized the protein (Pfs25-FhCMB), and evaluated this vaccine candidate in animal models for the induction of transmission blocking antibodies (TBA). Soluble Pfs25-FhCMB was expressed in plants at a high level, and induced TBA that persisted for up to 6 months post immunization in mice and rabbits. These data demonstrate the potential of the new malaria vaccine candidate and also support feasibility of expressing Plasmodium antigens in a plant-based system.Human Vaccines and Therapeutics 08/2014; 11(1). · 3.64 Impact Factor
Article: Cytotoxic Markers Associate with Protection against Malaria in Human Volunteers Immunized with Plasmodium falciparum Sporozoites.The Journal of infectious diseases. 05/2014;
Article: A scalable assessment of Plasmodium falciparum transmission in the standard membrane feeding assay using transgenic parasites expressing GFP-luciferase.[Show abstract] [Hide abstract]
ABSTRACT: The development of drugs and vaccines to reduce malaria transmission is an important part of eradication plans. The transmission reducing activity (TRA) of these agents is currently determined in the standard membrane feeding assay (SMFA) based on subjective microscopical read-outs and with limitations in up-scaling and throughput. Utilising a Plasmodium falciparum strain expressing the firefly luciferase protein, we present a luminescence based approach to SMFA evaluation that eliminates the requirement for mosquito dissections in favour of a simple approach where whole mosquitoes are homogenised and examined directly for luciferase activity. Analysis of 6860 Anopheles stephensi mosquitoes across 68 experimental feeds shows that the luminescence assay was as sensitive as microscopy for infection detection. The mean luminescence intensity of individual and pooled mosquitoes accurately quantifies mean oocyst intensity and generates comparable TRA estimates. The luminescence assay presented here could increase SMFA throughput so that 10-30 experimental feeds could be evaluated in a single 96-well plate. This new method of assessing Plasmodium infection and transmission intensity could expedite the screening of novel drug compounds, vaccine candidates and sera from malaria exposed individuals for TRA. Luminescence-based estimates of oocyst intensity in individual mosquitoes should be interpreted with caution.The Journal of Infectious Diseases 05/2014; · 5.85 Impact Factor
Article: A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages.[Show abstract] [Hide abstract]
ABSTRACT: Effective control and eventual eradication of malaria drives the imperative need for clinical development of a malaria vaccine. Asexual parasite forms are responsible for clinical disease and death while apathogenic gametocytes are responsible for transmission from man to mosquito. Vaccines that combine antigens from both stages may provide direct protection and indirect benefit by reducing the force of infection. We constructed a chimeric antigen composed of a fragment of the Plasmodium falciparum (Pf) glutamate-rich protein fused in frame to a correctly folded fragment of Pfs48/45. The chimera was produced in Lactococcus lactis and induced robust antibody responses in rodents to the individual components. Specific antibodies showed strong transmission blocking activity against multiple Pf-strains in the standard membrane feeding assay and functional activity against asexual stages in the antibody dependent cellular inhibition assay. The combined data provide a strong rationale for entering the next phase of clinical grade production and testing.Vaccine 03/2014; · 3.77 Impact Factor
Article: Sporozoite Immunization of Human Volunteers under Mefloquine Prophylaxis Is Safe, Immunogenic and Protective: A Double-Blind Randomized Controlled Clinical Trial.[Show abstract] [Hide abstract]
ABSTRACT: Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which is the only other licensed anti-malarial chemoprophylactic drug that does not affect pre-erythrocytic stages, exposure to which is considered essential for induction of protection by CPS immunization. In a double blind randomized controlled clinical trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS immunizations by bites from eight P. falciparum infected mosquitoes each, at monthly intervals. Four control volunteers received mefloquine prophylaxis and bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers, respectively. Furthermore, specific antibody levels and cellular immune memory responses were comparable between both groups. We therefore conclude that mefloquine and chloroquine are equally effective in CPS-induced immune responses and protection.PLoS ONE 01/2014; 9(11):e112910. · 3.53 Impact Factor
Article: Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity.[Show abstract] [Hide abstract]
ABSTRACT: Volunteers immunized under chloroquine chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) develop complete, long-lasting protection against homologous sporozoite challenge. Chloroquine affects neither sporozoites nor liver-stages, but kills only asexual forms in erythrocytes once released from the liver into the circulation. Consequently, CPS immunization exposes the host to antigens from both preerythrocytic and blood stages, and induced immunity might target either of these stages. We therefore explored the life cycle stage specificity of CPS-induced protection. Twenty-five malaria-naïve volunteers were enrolled in a clinical trial, 15 of whom received CPS immunization. Five immunized subjects and five controls received a sporozoite challenge by mosquito bites, whereas nine immunized and five control subjects received an i.v. challenge with P. falciparum-infected erythrocytes. The latter approach completely bypasses preerythrocytic stages, enabling a direct comparison of protection against either life cycle stage. CPS-immunized subjects (13 of 14) developed anticircumsporozoite antibodies, whereas only one volunteer generated minimal titers against typical blood-stage antigens. IgG from CPS-immunized volunteers did not inhibit asexual blood-stage growth in vitro. All CPS-immunized subjects (5 of 5) were protected against sporozoite challenge. In contrast, nine of nine CPS-immunized subjects developed parasitemia after blood-stage challenge, with identical prepatent periods and blood-stage multiplication rates compared with controls. Intravenously challenged CPS-immunized subjects showed earlier fever and increased plasma concentrations of inflammatory markers D-dimer, IFN-γ, and monokine induced by IFN-γ than i.v. challenged controls. The complete lack of protection against blood-stage challenge indicates that CPS-induced protection is mediated by immunity against preerythrocytic stages. However, evidence is presented for immune recognition of P. falciparum-infected erythrocytes, suggesting memory responses unable to generate functional immunity.Proceedings of the National Academy of Sciences 04/2013; · 9.81 Impact Factor
Article: A Plant-Produced Pfs25 VLP Malaria Vaccine Candidate Induces Persistent Transmission Blocking Antibodies against Plasmodium falciparum in Immunized Mice.[Show abstract] [Hide abstract]
ABSTRACT: Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.PLoS ONE 01/2013; 8(11):e79538. · 3.53 Impact Factor
Article: The relevance and applicability of oocyst prevalence as a read-out for mosquito feeding assays.[Show abstract] [Hide abstract]
ABSTRACT: Mosquito feeding assays are important in evaluations of malaria transmission-reducing interventions. The proportion of mosquitoes with midgut oocysts is commonly used as an outcome measure, but in natural low intensity infections the effect of oocyst non-rupture on mosquito infectivity is unclear. By identifying ruptured as well as intact oocysts, we show that in low intensity P. falciparum infections i) 66.7-96.7% of infected mosquitoes experienced oocyst rupture between 11-21 days post-infection, ii) oocyst rupture led invariably to sporozoite release, iii) oocyst rupture led to salivary gland infections in 97.8% of mosquitoes, and iv) 1250 (IQR 313-2400) salivary gland sporozoites were found per ruptured oocyst. These data show that infectivity can be predicted with reasonable certainty from oocyst prevalence in low intensity infections. High throughput methods for detecting infection in whole mosquitoes showed that 18s PCR but not circumsporozoite ELISA gave a reliable approximation of mosquito infection rates on day 7 post-infection.Scientific Reports 01/2013; 3:3418. · 5.08 Impact Factor
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ABSTRACT: There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum - one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year. Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host-seeking female An. gambiae s.s. mosquitoes. In behavioural experiments we showed that P. falciparum-infected An. gambiae mosquitoes were significantly more attracted to human odors than uninfected mosquitoes. Both P. falciparum-infected and uninfected mosquitoes landed significantly more on a substrate emanating human skin odor compared to a clean substrate. However, significantly more infected mosquitoes landed and probed on a substrate emanating human skin odor than uninfected mosquitoes. This is the first demonstration of a change of An. gambiae behaviour in response to olfactory stimuli caused by infection with P. falciparum. The results of our study provide vital information that could be used to provide better predictions of how malaria is transmitted from human being to human being by An. gambiae s.s. females. Additionally, it highlights the urgent need to investigate this interaction further to determine the olfactory mechanisms that underlie the differential behavioural responses. In doing so, new attractive compounds could be identified which could be used to develop improved mosquito traps for surveillance or trapping programmes that may even specifically target P. falciparum-infected An. gambiae s.s. females.PLoS ONE 01/2013; 8(5):e63602. · 3.53 Impact Factor
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ABSTRACT: We established a new field clone of Plasmodium falciparum (Pf) for use in controlled human malaria infections (CHMI) and vaccine studies to complement the current small portfolio of Pf strains, primarily based on NF54. The Cambodian clone NF135.C10 consistently produced gametocytes and generated substantial numbers of sporozoites in Anopheles mosquitoes and diverged from NF54 parasites by genetic markers. In a CHMI trial, three of five volunteers challenged by mosquitoes infected with NF135.C10 and four of five challenged with NF54 developed parasitaemia as detected by microscopy. The two strains induced similar clinical signs and symptoms as well as cellular immunological responses.The Journal of Infectious Diseases 11/2012; · 5.85 Impact Factor
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ABSTRACT: Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.Clinical and vaccine Immunology: CVI 06/2011; 18(8):1351-7. · 2.60 Impact Factor
Article: Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study.[Show abstract] [Hide abstract]
ABSTRACT: We have shown that immunity to infection with Plasmodium falciparum can be induced experimentally in malaria-naive volunteers through immunisation by bites of infected mosquitoes while simultaneously preventing disease with chloroquine prophylaxis. This immunity was associated with parasite-specific production of interferon γ and interleukin 2 by pluripotent effector memory cells in vitro. We aim to explore the persistence of protection and immune responses in the same volunteers. In an open-label study at the Radboud University Nijmegen Medical Centre (Nijmegen, Netherlands), from November to December, 2009, we rechallenged previously immune volunteers (28 months after immunisation) with the bites of five mosquitoes infected with P falciparum. Newly recruited malaria-naive volunteers served as infection controls. Our primary outcome was the detection of blood-stage parasitaemia by microscopy. We assessed the kinetics of parasitaemia with real-time quantitative PCR (rtPCR) and recorded clinical signs and symptoms. In-vitro production of interferon γ and interleukin 2 by effector memory T cells was studied after stimulation with sporozoites and red blood cells infected with P falciparum. Differences in cellular immune responses between the study groups were assessed with the Mann-Whitney test. This study is registered with ClinicalTrials.gov, number NCT00757887. Four of six immune volunteers were microscopically negative after rechallenge. rtPCR-based detection of blood-stage parasites in these individuals was negative throughout follow-up. Patent parasitaemia was delayed in the remaining two immunised volunteers. In-vitro assays showed the long-term persistence of parasite-specific pluripotent effector memory T-cell responses in protected volunteers. The four protected volunteers reported several mild to moderate adverse events, of which the most commonly reported symptom was headache (one to three episodes per volunteer). The two patients with delayed patency had adverse events similar to those in the control group. Artificially induced immunity lasts longer than generally recorded after natural exposure; providing a new avenue of research into the mechanisms of malaria immunity. Dioraphte Foundation.The Lancet 05/2011; 377(9779):1770-6. · 39.21 Impact Factor
Article: Antibodies to plant-produced Plasmodium falciparum sexual stage protein Pfs25 exhibit transmission blocking activity.[Show abstract] [Hide abstract]
ABSTRACT: Malaria is a serious and sometimes fatal mosquito-borne disease caused by a protozoan parasite. Each year, it is estimated that over one million people are killed by malaria, yet the disease is preventable and treatable. Developing vaccines against the parasite is a critical component in the fight against malaria and these vaccines can target different stages of the pathogen's life cycle. We are targeting sexual stage proteins of P. falciparum which are found on the surface of the parasite reproductive cells present in the mosquito gut. Antibodies against these proteins block the progression of the parasite's life cycle in the mosquito, and thus block transmission to the next human host. Transmission blocking vaccines are essential to the malaria eradication program to ease the disease burden at the population level. We have successfully produced multiple versions of the Pfs25 antigen in a plant virus-based transient expression system and have evaluated these vaccine candidates in an animal model. The targets are expressed in plants at a high level, are soluble and most importantly, generate strong transmission blocking activity as determined by a standard membrane feeding assay. These data demonstrate the feasibility of expressing Plasmodium antigens in a plant-based system for the economic production of a transmission blocking vaccine against malaria.Human vaccines 01/2011; 7 Suppl:191-8. · 3.14 Impact Factor
Article: Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival.[Show abstract] [Hide abstract]
ABSTRACT: Sulfadoxine-pyrimethamine (SP) is currently the drug of choice for intermittent preventive treatment of Plasmodium falciparum both in pregnancy and infancy. A prolonged parasite clearance time conferred by dhfr and dhps mutations is believed to be responsible for increased gametocyte prevalence in SP treated individuals. However, using a direct feeding assay in Mali, we showed that gametocytes present in peripheral venous blood post-SP treatment had reduced infectivity for Anopheles gambiae sensu stricto (ss) mosquitoes. We investigated the potential mechanisms involved in the dhfr and dhps quintuple mutant NF-135 and the single dhps 437 mutant NF-54. Concentrations of sulfadoxine (S) and pyrimethamine (P) equivalent to the serum levels of the respective drugs on day 3 (S=61 microg/ml, P=154.7 ng/ml) day 7 (S=33.8 microg/ml, P=66.6 ng/ml) and day 14 (S=14.2 microg/ml, P=15.7 ng/ml) post-SP treatment were used to study the effect on gametocytogenesis, gametocyte maturation and infectivity to Anopheles stephensi mosquitoes fed through an artificial membrane. The drugs readily induced gametocytogenesis in the mutant NF-135 strain but effectively killed the wild-type NF-54. However, both drugs impaired gametocyte maturation yielding odd-shaped non-exflagellating mature gametocytes. The concomitant ingestion of both S and P together with gametocytemic blood-meal significantly reduced the prevalence of oocyst positivity as well as oocyst density when compared to controls (P<0.001). In addition, day 3 concentrations of SP decreased mosquito survival by up to 65% (P<0.001). This study demonstrates that SP is deleterious in vitro for gametocyte infectivity as well as mosquito survival.International journal for parasitology 08/2010; 40(10):1221-8. · 3.39 Impact Factor
Article: The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania.[Show abstract] [Hide abstract]
ABSTRACT: Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses. Parasitaemic individuals (n = 116) were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16), developed circulating gametocytes by day 7 (n = 69) or between day 7 and 14 (n = 10) after treatment or did not develop gametocytes (n = 21). Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals). Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348) and 15.2% (53/348) of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-1(19) (48.1%; 137/285) and AMA-1 (52.4%; 129/246)(p<0.001). The prevalence of anti-Pfs230 (p = 0.026) and anti-Pfs48/45 antibodies (p = 0.017) increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01). In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.PLoS ONE 01/2010; 5(11):e14114. · 3.53 Impact Factor
Article: Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane.[Show abstract] [Hide abstract]
ABSTRACT: The spread of drug resistance has been a major obstacle to the control of malaria. The mechanisms underlying drug resistance in malaria seem to be complex and multigenic. The current literature on multiple drug resistance against anti-malarials has documented PfMDR1, an ATP-binding cassette (ABC) protein, as an important determinant of resistance. In the Plasmodium falciparum genome, there are several ABC transporters some of which could be putative drug transporting proteins. In order to understand the molecular mechanisms underlying drug resistance, characterization of these transporters is essential. The aim of this study was to characterize and localize putative ABC transporters. In the plasmoDB database, 16 members of the P. falciparum ABC family can be identified, 11 of which are putative transport proteins. A phylogenetic analysis of the aligned NBDs of the PfABC genes was performed. Antibodies against PfMRP1 (PfABCC1), PfMRP2 (PfABCC2), and PfMDR5 (PfABCB5) were generated, affinity purified and used in immunocytochemistry to localize the proteins in the asexual stages of the parasite. The ABC family members of P. falciparum were categorized into subfamilies. The ABC B subfamily was the largest and contained seven members. Other family members that could be involved in drug transport are PfABCC1, PfABCC2, PfABCG1, and PfABCI3. The expression and localization of three ABC transport proteins was determined. PfMRP1, PfMRP2, and PfMDR5 are localized to the plasma membrane in all asexual stages of the parasite. In conclusion, 11 of the 16 ABC proteins in the P. falciparum genome are putative transport proteins, some of which might be involved in drug resistance. Moreover, it was demonstrated that three of these proteins are expressed on the parasite's plasma membrane.Malaria Journal 09/2009; 8:205. · 3.49 Impact Factor
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ABSTRACT: An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites. We exposed 15 healthy volunteers--with 10 assigned to a vaccine group and 5 assigned to a control group--to bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with Plasmodium falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. We assessed humoral and cellular responses before vaccination and before the challenge to investigate correlates of protection. All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes. In contrast, patent parasitemia (i.e., parasites found in the blood on microscopical examination) developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. In this model, we identified the induction of parasite-specific pluripotent effector memory T cells producing interferon-gamma, tumor necrosis factor alpha, and interleukin-2 as a promising immunologic marker of protection. Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.)New England Journal of Medicine 08/2009; 361(5):468-77. · 54.42 Impact Factor
Article: Dynamic histone H3 epigenome marking during the intraerythrocytic cycle of Plasmodium falciparum.[Show abstract] [Hide abstract]
ABSTRACT: Epigenome profiling has led to the paradigm that promoters of active genes are decorated with H3K4me3 and H3K9ac marks. To explore the epigenome of Plasmodium falciparum asexual stages, we performed MS analysis of histone modifications and found a general preponderance of H3/H4 acetylation and H3K4me3. ChIP-on-chip profiling of H3, H3K4me3, H3K9me3, and H3K9ac from asynchronous parasites revealed an extensively euchromatic epigenome with heterochromatin restricted to variant surface antigen gene families (VSA) and a number of genes hitherto unlinked to VSA. Remarkably, the vast majority of the genome shows an unexpected pattern of enrichment of H3K4me3 and H3K9ac. Analysis of synchronized parasites revealed significant developmental stage specificity of the epigenome. In rings, H3K4me3 and H3K9ac are homogenous across the genes marking active and inactive genes equally, whereas in schizonts, they are enriched at the 5' end of active genes. This study reveals an unforeseen and unique plasticity in the use of the epigenetic marks and implies the presence of distinct epigenetic pathways in gene silencing/activation throughout the erythrocytic cycle.Proceedings of the National Academy of Sciences 07/2009; 106(24):9655-60. · 9.81 Impact Factor
Article: The Plasmodium falciparum protein Pfg27 is dispensable for gametocyte and gamete production, but contributes to cell integrity during gametocytogenesis.[Show abstract] [Hide abstract]
ABSTRACT: In the human malaria parasite Plasmodium falciparum, gametocyte maturation is a process remarkably longer than in other malaria species, accompanied by expression of 2-300 sexual stage-specific proteins. Disruption of several of their encoding genes so far showed that only the abundant protein Pfg27, produced at the onset of sexual differentiation, is essential for gametocyte production. In contrast with what has been previously described, here we show that P. falciparum pfg27 disruptant lines are able to undergo all stages of gametocyte maturation, and are able to mature into gametes. A fraction of Pfg27-defective gametocytes show, however, distinct abnormalities in intra- and extra-cellular membranous compartments, such as accumulation of parasitophorous vacuole-derived vesicles in the erythrocyte cytoplasm, large intracellular vacuoles and discontinuities in their trilaminar cell membrane. This work revises current knowledge on the role of Pfg27, indicating that the protein is not required for parasite entry into sexual differentiation, and suggesting that it is instead involved in maintaining cell integrity in the uniquely long gametocytogenesis of P. falciparum.Molecular Microbiology 07/2009; 73(2):180-93. · 5.03 Impact Factor
Article: Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice.[Show abstract] [Hide abstract]
ABSTRACT: Malaria kills >1 million people each year, in particular in sub-Saharan Africa. Although asexual forms are directly responsible for disease and death, sexual stages account for the transmission of Plasmodium parasites from human to the mosquito vector and therefore the spread of the parasite in the population. Development of a malaria vaccine is urgently needed to reduce morbidity and mortality. Vaccines against sexual stages of Plasmodium falciparum are meant to decrease the force of transmission and consequently reduce malaria burden. Pfs48/45 is specifically expressed in sexual stages and is a well established transmission-blocking (TB) vaccine candidate. However, production of correctly folded recombinant Pfs48/45 protein with display of its TB epitopes has been a major challenge. Here, we show the production of a properly folded Pfs48/45 C-terminal fragment by simultaneous coexpression with four periplasmic folding catalysts in Escherichia coli. This C-terminal fragment fused to maltose binding protein was produced at medium scale with >90% purity and a stability over at least a 9-month period. It induces uniform and high antibody titers in mice and elicits functional TB antibodies in standard membrane feeding assays in 90% of the immunized mice. Our data provide a clear perspective on the clinical development of a Pfs48/45-based TB malaria vaccine.Proceedings of the National Academy of Sciences 04/2008; 105(11):4301-5. · 9.81 Impact Factor
Top Journals
Leiden University Medical Centre
Leyden, South Holland, Netherlands
- Department of Medical Microbiology
Radboud University Medical Centre (Radboudumc)Nymegen, Gelderland, Netherlands
Fraunhofer USA Center for Molecular Biotechnology (FhCMB)Delaware, United States
Radboud University Nijmegen
Nijmegen, Provincie Gelderland, Netherlands
- • Department of Medical Microbiology
- • Nijmegen Centre for Molecular Life Sciences
- • Department of Molecular Biology


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Gado Gado HTP7016 Teardrop Engraved Backplate Pull, Antique Brass
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This Teardrop Engraved Backplate Pull by Gado Gado International is available in an antique brass finish.
5 3/4" elegant teardrop pull on engraved backplate.
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TVMuse > Movies > # > 22 Bullets (2010)
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- Blockbuster: 22 Bullets - Buy or rent Rent, buy, or download over 100,000 movies including new release movies at Blockbuster.com. Your source for movie reviews, trailers, ratings, and more. blockbuster.com
- 22 Bullets - Rotten Tomatoes September 9, 2010. Ellen E Jones. Total Film. An unremarkable French thriller .... A product of Luc Beeson's Europa Corp stable of films, 22 Bullets plays to type ... rottentomatoes.com
- 22 Bullets - Movie Trailers - iTunes This film is a work of fiction inspired by real-life events in the world of the Marseille mafia. ... 22 Bullets. Go to Movie. Charly Matteï has turned his back on his life as an outlaw. For the last three ... Jason Goodyer, Little White Lies, 09.02. 2010. apple.com
- Film review: 22 Bullets | Film | The Guardian 2 Sep 2010 ... 22 Bullets PR. Catherine Shoard. Thursday 2 September 2010 17.05 EDT ... How would it feel to be peppered with bullets by hitmen hired by ... theguardian.com
- 22 Bullets Trailer | Movie Trailers | Contactmusic.com 22 Bullets, Trailer. Director Richard BerryYear 2010Genre(s) Action, Adventure. After living a life of crime, Charly Mattei decides to leave his past behind him and ... contactmusic.com
TVMuse Recommends
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Bullets, Blood & a Fistful of Ca$h (2006)
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Junior Member
Was recently in ranked queue and these errors keep popping up.. Made me lose 20 elo, now i know it's not a big deal but it's annoying. How do i fix this? Please help. Thank you in advance
© 2014 Riot Games, Inc. All rights reserved. Riot Games, League of Legends and PvP.net are trademarks, services marks, or registered trademarks of Riot Games, Inc.


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What Do the Shrinking Kidney Symptoms Warn Us
Shrinking kidney is closely related with the long-term renal diseases, among which Chronic Pyelonephritis is the main leading of kidney shrinkage. In the early stage, there are no shrinking kidney symptoms to warn the patient. Most often, the patient find out their shrinking kidney in the exam for another condition. Once some symptoms occur, the patients should pay attention to some dangers.
What are the shrinking kidney symptoms?
◆ High blood pressure. With the aggravation of the patient's condition, high blood pressure is more likely to occur to warn him that his kidney has been damaged.
◆ Feet or face swelling. Too much fluid and sodium will build up in the small blood vessels, when glomeruli filtration is damaged. As a result, feet or face swelling occurs easily.
◆ Nausea, vomiting and fatigue. As the wastes and toxins build up in the body, the patient will often feel nausea, vomiting and fatigue. In addition, the patient loses his weight quickly.
◆ Hematuria. It is another shrinking kidney symptom to warn the person some problems, such as urinary tract infections.
If these symptoms occur, you should do some tests to detect whether your kidney has begun to shrink. The diagnosis of your shrinking kidney is very important, because it can warn us many problems in your kidney.
What do the shrinking kidney symptoms warn us?
Shrinking kidneys usually accompany with some kidney function loss. When the kidney begins to shrink, renal insufficiency or chronic renal failure must happen. Many kidney diseases can lead to shrinking kidney, and shrinking kidney in turn aggravates the kidney disease. Therefore, you should get prompt test to determine your kidney disease and then receive the correct treatment, in order to prevent further damage, when the above symptoms appear. If left untreated, it is likely to develop renal failure.
If some shrinking kidney symptoms have happened on you, you should adopt some measures immediately. The earlier you get the treatment, the easier your disease can be reversed.
Tag: Living With Kidney Disease
Previous:Four Ways to Lower Creatinine


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Win a golden ticket and meet the Oompa Loompas of Solfest. . . .
Published at 07:54, Friday, 20 April 2012
Five lucky youngsters will get to meet the Oompa Loompas at the Solfest music festival in a Charlie and the Chocolate Factory-inspired competition.
Organisers of the three-day event at Tarns, near Aspatria, between August 24 and 26, have released five golden tickets which will give a youngster and accompanying adult free entry to the event and a host of treats.
There are various ways the tickets can be won – registering on the festival's mailing list, a draw from tickets purchased, plus competitions and other events as Solfest draws near.
The Saturday of the event will be fancy-dress day, and festival-goers are urged to dress up as Roald Dahl characters.
Ben Durkan, festival chairman, said: "We've got a fantastic reputation as a family-friendly festival and we wanted to pick a fancy dress theme that encapsulated that.
"As Roald Dahl transcends generations, we thought it was perfect.
"We thought golden tickets were an excellent way to entice people with families to join our mailing list or give the festival a go."
To join the mailing list, go to www.solfest.org.uk
Highlights of the festival will include Adam Ant & The Good, KT Tunstall, Big Country and Billy Bragg.
Tickets, at £95 for adults, £65 for 12 to 16-year-olds and £25 for six to 11-year-olds, can be bought at the Times & Star, 21-23 Oxford Street, Workington.
Published by http://www.timesandstar.co.uk
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7 Spices With Surprising Health Benefits
Cinnamon comes from the bark of a tropical evergreen tree and has one of the highest antioxidant values of any spice. The spice has been shown to reduce inflammation, lower blood sugar and blood triglyceride levels, alleviate nausea and increase sensitivity to insulin as an aid in fat burning. It's also a good source of manganese, iron and calcium.
While cinnamon is an incredibly healthy and nutritious spice, it's often hard to branch out from the most common uses: coffee, cookies, muffins and desserts. But there are healthier ways to reap the benefits of this magical spice: pour it over oatmeal, yogurt or cottage cheese, stir it into peanut butter or protein shakes and sprinkle it on sweet potatoes or carrots. Cinnamon also kills bacteria, so the next time you get a cut, you can actually sprinkle the spice on the wound.
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Resources and Publications
Resource and Publication
Draft legislation on consumer privacy offer many opportunities for improvement.
Open innovation is becoming an increasingly important form of innovation and requires new firm strategies.
Don't like Facebook's privacy policy? Then don't use it. But don't ask government to run...
Is the demand of American and European consumers for organic foods a good thing? In this WebMemo ITIF looks...
The re-authorization of the America COMPETES Act will help foster innovation and American global...
With increasing employment is the number one goal in Washington, policy makers should look to IT as a major...
If self-service technology were more widely deployed, the economy would be approximately $130 billion larger...
ITIF reviews the evolution of the Internet economy into a transformational part of daily life and a trillion...
ITIF outlines eight ideas to improve the U.S. innovation system.
ITIF identifies strengths and weaknesses of the open government initiative and recommends how to make more...
Piracy in TV is increasing, as just about every Emmy-nominated show suffers from illegal downloads.
Corporate tax reform is an economic competitiveness issue.
The "right to be forgotten" may have led to more privacy concerns than intended.
The U.S. manufacturing sector has been losing jobs at an alarming rate since 2000.
Since 1999, the United States has suffered a 13 percent decline in triadic patent filings.
Slow US productivity growth reinforces the need for more public investment in R&D.
The renewal of African Growth and Opportunity Act presents an opportunity to strengthen it.
The U.S. must create a more competitive tax code to drive domestic investment and global competitiveness.
China's efforts to promote domestic IT production by harassing U.S. companies needs to be met with a strong response.
DOJ should rework the ASCAP and BMI consent decrees to assist in modernizing the way music copyrights are licensed in the digital age.
Doug Brake participated in the MMTC's Telecom Act Rewrite and the Potential Benefits to MWBEs and...
Daniel Castro will speak about the NSA's impact on the economy, information security, and Internet freedom at...
Stephen Ezell presented on advanced manufacturing at a NIST VCAT meeting.
How Canada's Policies Impact American Innovation and Competitiveness
This panel discussion investigated methods for speeding the path from research to market.
Matthew Stepp gave a speech at the 2013 Regional Meeting of the Federal Laboratory Consortium in Leesburg, VA.
Daniel Castro will speak at a webinar for the Association of Public Data Users on "Public Policy...
Stephen Ezell participated in a panel on Electronic Commerce and Data Privacy at the Frontiers of Economic...
Robert Atkinson presented on IT policy issues at this event sponsored by the Copenhagen Business School.
A panel of experts discusses the truths and misconceptions of the DCMA.
ITIF Comments to the New York State Department of Financial Services on the Proposed BitLicense Framework
ITIF proposes comments for the New York Department of Financial Services on the BitLicense Framework.
NHTSA should hold off on a DSRC mandate until spectrum questions are resolved.
ITIF Submits Comments to the National Science Foundation Regarding a National Privacy Research Strategy
The U.S.government should support research to address pressing privacy and security concerns.
The AT&T-DirecTV merger is in the public interest.
Val Giddings testifies before the New Jersey State Assembly on GMO labeling.
Labeling legislation is driven by fear, ideology and commercial interests not on a concern for consumers or...
ITIF responds to the Administration's request for comments on the Strategy for American Innovation.
ITIF files comments on effective universal service under a new Communications Act.
ITIF argues the FCC should develop flexible regulations under section 706.
ITIF cautions the FCC against encouraging inefficient use of public resources on municipal broadband...
Conventional economics provides an increasingly poor guide for economic policy and should be replaced by an evolutionary economics framework.
Rob Atkinson contributed the chapter "Public Policy, Innovation and New Technologies" to the textbook "Guide to U.S. Economic Policy."
Robert Atkinson contributed the chapter "Innovation in Cities and Innovation by Cities" for the book "Creating Competitiveness: Entrepreneurship and Innovation Polices for Growth."
In a chapter for the new book Practicing Sustainability, Rob Atkinson wrote about sustainability from an innovation economics perspective.
"Innovation Economics: The Race for Global Advantage." This new book delivers a critical wake-up call: a fierce global race for innovation advantage is under way and the United States is running the risk of losing.
Daniel Castro contributed a chapter titled "U.S. Federal Cybersecurity Policy" in the book "Cybersecurity: Public Sector Threats and Responses."
Rob Atkinson contributed a chapter titled chapter "Who's Who in Internet Politics" for the book "The Next Digital Decade: Essays on the Future of the Internet."
Supply-Side Follies: Why Conservative Economics Fails, Liberal Economics Falters, and Innovation Economics is the Answer
Supply-Side Follies methodically debunks the common assumptions of conservative economics and demonstrates why it is a flawed doctrine that is setting up the U.S. for a major economic downturn in the near future.
Taking into account the historical record, the book discusses the shortcomings of prevailing liberal and conservative economic doctrines and lays out a new growth economics agenda aimed at maximizing the productivity and innovation-enhancing forces of the New Economy.


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Superintendent announces resignation
Superintendent Jon Abrams of LCSD #2 announced he will resign at the end of the current school year.
Superintendent Jon Abrams of LCSD #2 announced he will resign at the end of the current school year.
Star Valley and Cokeville schools scored above the state and national average in most categories according to a national accreditation team.
The Afton Airport construction project cost $3 million with two-thirds of that total coming from the Federal Aviation Administration (FAA).
Travelers may experience some delays on U.S. Highway 89 as crews install rock mesh on hillsides to help prevent rock slides.
The decision by a U.S. District Court Judge on wolves in Wyoming has been met with opposition by Wyoming leaders from the Governor to the U.S. Senate.
Lincoln County has been singled out for efforts to keep juvenile detainees out of contact with adults in lock up, citing the experience can be damaging to underage offenders.
According to LCSD #2 Transportation Director, Ryan Lyman, there are instances of "red-light" violations every day in Star Valley as motorists pass school buses with flashing lights.
According to Chris Jones of the National Weather Service station in Riverton, Star Valley saw a record amount of rain in August.
Lincoln County ranks as one of the lowest in Wyoming for women getting a mammogram for early protection.
The Game & Fish has suspended all sales of gray wolf licenses at the current time.


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CFPB oversight hearing June 10 in Senate Banking
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CFPB oversight hearing June 10 in Senate Banking
June 4, 2014 – The Senate Banking Committee is set to hear testimony from CFPB Director Richard Cordray on the bureau's semiannual report to Congress during a June 10 oversight hearing.
semiannual report
addresses CFPB's consumer protection activities, progress in implementing rules, the bureau's operating expenses and more. The report shows CFPB had spent $125.7 million through March 31 – the end of the second quarter of fiscal 2014 – for compensation and benefits for 1,365 employees. It says it spent a total of $297 million carrying out its statutory authorities.
NAFCU, in monitoring this hearing, will focus on any discussion related to transparency in CFPB operations, the bureau's handling of consumers' sensitive data and financial services complaints, and enforcement activities.
Related Links
CFPB semiannual report to Congress
QM, student loan bills near House action


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Listen Live
View the full closings list.
No places in Dayton are currently reporting closings or delays.
in Entertainment
A look at the Hollywood headlines that made history.
in National, World
The number of troops in Afghanistan next year will be larger than originally thought to fill a gap left in the NATO mission.


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I have noticed that some younger typically hipster fools about are into those big hole ear piercings…it took about bit of research but I have found out that they are pofficially called "flesh tunnels" or scalpelling.
Scalpelling┬Āis a┬Ābody art┬Āprocedure similar to┬Ābody piercing┬Āfor the creation of decorative perforations through the skin and other body tissue, and is most commonly used as a replacement for or enhancement of┬Āear piercing. Whereas piercing is typically performed with a hollow piercing needle or an┬Āear piercing instrument, scalpelling is performed by using a┬Āscalpel┬Āto cut a slit into the skin. Unlike┬Ādermal punching, no flesh is removed.┬ĀThe technique can immediately produce holes with a larger diameter than can be achieved by piercing. This is a more rapid means of accommodating larger┬Āgauge┬Ājewellery than┬Āstretching, a technique whereby piercings are enlarged by inserting gradually larger jewellery. Scalpelling is performed to quickly achieve a large-gauge piercing, when┬Āscar tissue┬Āis preventing further stretching, if tissue has thinned to the point where further stretching could cause it to break, or to combine two closely placed piercings into one hole.
I simply don't get it…what is the point? What sort of fool does this?


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Book a Tee Time at Casta del Sol Golf Course
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Our renowned 18-hole, par 61 golf course features two distinct tees, water play on 8 holes, and a variety of challenges that appeal to both beginning golfers and advanced golfers looking to refine their short game.
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Shopping List: September 26th, 2011
|By: Lisa J.
It's almost time to say farewell to September, but not before we squeeze in one last Shopping List poll! Take a look at the bags above and pick your favorite (I know, it's a tough decision this week!) by voting below. The bag that receives the most votes will be the focus of a lookalike (not fake, mind you) shopping spree. You can also tell us why you love or don't love the competition in the comments section below!
You Also Might Like:
posted: September 26th, 2011
Emilio Pucci Canvas Print Cosmetic Bag
BCBGMAXAZRIA Feather Clutch
Lacey Days Skull Clutch
Deux Lux Tate Mini Crossbody Wallet
category: Fendi Handbags, Other designer Handbags, Shopping List Polls


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Experian demands constant innovation and nimble response to markets to maintain its profi tability and competitive edge. Its IT infrastructure team must support its developers' eff orts to meet the business' aggressive time-to-market requirements. A cloud-based infrastructure-as-a-service model for Experian's test and development environments will allow developers to quickly and fl exibly self-provision IT resources when they need them. Business Impact were: Provisioning times, already slashed from weeks to days through virtualization, now further cut to minutes; Developers can more easily collaborate; business units can leverage IT builds from other lines of business; Private cloud and VMware vShield security functionality ensure IT resources are controlled
"VMware vCloud technology will allow Experian to offer an internal, selfservice cloud to our development organization, leading to faster project turnaround and better levels of IT service."
Extreme Networks
Extreme Networks Aims to Migrate Oracle ERP to VMware Platform Network solutions firm consolidates datacenters, progresses to Oracle and desktop virtualization
"Virtualization works well for us. We don't shy away from virtualizing mission-critical applications, such as Oracle, in production as well as in test environments. VMware technology has proven itself."
Based on VMware vSphere, Facilicom virtualised almost all its servers, including the company-critical SAP systems. VMware offers Facilicom more control over the central server environment which supports all the operational applications.
"With VMware vSphere and vMotion it's a lot easier to transfer or upgrade applications. Now everything happens more quickly and with less downtime. Distributing server loads is also easier. That's really useful when deploying applications which need a lot of CPU power temporarily. We are also hardware-independent and the environment is scalable enough to keep growing."
Finanz Informatik
"The VMware TAM program is both profitable and beneficial for a large company such as Finanz Informatik. Through its detailed insight into a company, the TAM program can provide a better VMware-internal picture of the impact a problem is having on a customer."
First Marblehead Corporation
First Marblehead Teams With VMware Professional Services To Migrate A Datacenter Without Lifting A Server
"VMware Professional Services helped us pull off a major Datacenter migration with a very lean team. The consultant who handled our engineering tasks contributed dozens of innovative ideas for solving problems and leveraging the VMware platform."
Florida Atlantic University College of Engineering and Computer Science
Focus on Green IT Leads Innovative Engineering School to VMware Virtualized Desktop Environment
"Virtualization is the key to providing the most cost- and energy efficient IT environments, and VMware is the leader in virtualization. That's why we chose it as a long-term partner for the College."
Florida Hospital
Implement VMware Infrastructure 3.5 To Facilitate IT Management, Improve Application Performance And Availability, Enhance Disaster Recovery, And Reduce Server Hardware, Maintenance, And Energy Costs
"Anything with Cerner in the title is like throwing the ace of spades on the table. If anything goes wrong with these applications, people all over the organization start to yell and scream. Cerner software is part of the infrastructure that Florida Hospital spent 60 million dollars on, in order to provide a safer environment for our patients and to comply with rigorous HIPAA standards for ensuring the security and privacy of healthcare information. Our Cerner applications our hosted by Cerner, and the fact that they ESX servers speaks volumes about our faith in VMware."
Foley & Lardner LLP
Global legal services leader Foley & Lardner LLP has adopted virtual desktops and bring-your-own-device (BYOD) innovation to enhance end-user productivity across their far-flung operations.
"The ease of mobility and some of the productivity gains [from VMware View] make a big difference. The quicker we can get access to people and information for our attorneys, no matter where they are and no matter what the device they're using, is really important today. That does provide some additional benefit for our attorneys, when it comes to delivering the best possible service we can to our clients."
French Fire Department
French Fire Department has been using VMware for past 7 years because of its flexibility and ease of use. Franck Sauve shares his experience working with VMware products to support for their mission critical operations. He explains how Horizon View has helped fire helpline operators to keep their systems working all the time, while, vCenter Operations manager has helped him to plan and provide directions on the budget spent and has simplified IT operations with hardware.
FrieslandCampina Hungária Zrt.
Targets set with regard to virtualisation • Increasing the availability of services • Improving the response times and effectivity of IT operations • Avoiding the need to increase the floor space rented in the data centre of the hosting service provider, establishing an in-house server room • Decreasing the costs of operation Results achieved with VMware's solution • no shutdowns due to malfunction • maintenance and improvements without restricting the services • due to remote supervision, a smaller operational staff perform tasks • almost 80 virtual servers • 11 blade servers at two sites • 75 percent hardware resource utilization • hardware purchases decreased by 75 percent • cessation of data centre rentals • establishment of in-house server room with an investment return of three years
"The virtualisation solution of VMware proved to be an excellent choice in every respect. Since it was introduced, we had no shutdowns due to any malfunction, we have been able to perform developments during continuous service in a way transparent to the users, while our hardware procurements and operatings costs fell significantly."
Frimley Park Hospital NHS Foundation Trust
Frimley Park Hospital has virtualized all of its A&E department desktops using VMware View technology, creating a secure and easy to manage unified system, which has resulted in time savings and a drop in energy bills.
"We pride ourselves in providing our patients with the best possible care and so keeping abreast of the latest innovations and developments is vital to our success. When we virtualised our ED department's desktops we freed up the IT team's and clinical staff's time, paved the way for major energy savings and improved security across the board"
Frontier Communications Solutions
Learn why Frontier Communications Solutions chose VMware Zimbra to deliver a unique and integrated communications system to their customers.
"If email is a strategic asset, you need to have control over it. . . . Zimbra has allowed us to control it."
FUJIFILM Medical Systems USA
Fujifilm Medical Systems Rolls Out SaaS Offering of Synapse® PACS, Synapse RIS, Disaster Recovery and Remote Image Archiving to Customers
"Many health care providers, in particular, smaller hospitals and specialized clinics, don't have the necessary capital to invest in infrastructure or IT staff to support their PACS and medical information management systems. By providing Synapse PACS, Synapse RIS, data storage and archive as managed services, we're satisfying a need that many of our customers had. Plus, we've created opportunities to attract new customers who might otherwise not have considered our Synapse products."
Fulton Financial Corporation
Fulton Financial Corporation Replaces VMware ESX With Vmware ESXi Due To Its Ultra-Thin Footprint, Improved Security And Reliability
"We were up to about 125 patches per quarter with ESX. Now that we're running ESXi, I guess we do about three patches per quarter. So that's made a huge difference for us."
Fulton Financial Corporation
VMware vSphere Creates A Virtual Platform That Allows IT Services To Be Delivered Quickly And Easily, With Lower Costs And Administration
"Our VMware deployment has helped us to enhance our operations not just from a server management standpoint, but from a business continuity standpoint as well. It's helped us do a lot more with less, which is huge in this economy."
VMware vFabric Enterprise Ready Server Delivers Seamless Server Upgrades And Management To Candystand.com
"Comparing the time between using ERS vs. doing everything ourselves, including downloading source and compiling different versions of Apache, Tomcat and everything else, ERS reduces our administrative time on application servers by 75%."
Future Group
Future Group deployed a virtualized infrastructure incorporating VMware vSphere™ and VMware ESXi™ running on Sun server hardware. The guest virtual machines are now running on 10 Sun Fire X4450 servers, leaving plenty of capacity within the Future Group datacenter to sustain future growth.
"Thanks to VMware, we have eliminated the constraints on our datacenter real estate and facilities while providing plenty of capacity to support future growth."
Gainesville State College
Virtual Desktops Open a World of Possibilities for Gainesville State College
"Our basic need was to provide a 24x7 technical lab with campus and remote access for our students. But virtual desktops open a world of possibility. We use them to create GIS labs for middle-school students."
Gateway Bancorp
Financial Institution Sees Virtualization As A Gateway Towards Superior Service
"By helping to provide us with excellent uptime for our applications, the VMware and Intel virtualization solution has been a huge benefit for our company as a whole."
Georgia Institute of Technology Distance Learning and Professional Education
Top Research University Gains Flexibility with VMware View
"For me personally, desktop virtualization means I can access my desktop wherever I go—from my home office or traveling in China, India or anywhere. For DLPE as an organization, desktop virtualization opens doors to innovative new customer services and worldwide collaboration."


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VIDEOGAME BLOG! Part 1
By eroticfishcake 0 Comments
Yeah not the most imaginative title but it's the content that counts (that's not to imply that it'll be good but fuck it.)
Watcha ya been playin' dawg?!
Gran Turismo 5
There's isn't one glaring problem but rather a plethora of smaller problems that layer on top of each other, whether it'll be the messy (but functional) interface or the disappointing track editor that I rarely used. The lack of events is a major pain on the later levels. They could've just imported the events from GT4 with some tweaking here and there. Hell, GT4 even had one-make race events that almost every manufacturer had and they were fun. But instead, GT5 decides to take a small fraction of all those events. It does give you some unique challenges but you can only get the rewards once you've done them which means you're tasked to grinding if you want to get more money/experience to which I may add, levelling up takes much longer then it should. Thankfully, Polyphony have added some seasonal events every Thursday that rewards a lot of money and experience but like the challenges, you only get the rewards once.
The A.I. isn't that much different from GT4. In other words, still pretty crap. There's actually a video circulating around YouTube showcasing the terrible it's stupidity in comparison's to Forza 3's more smarter A.I. Contrary to the video, the A.I. does in fact swerve around to avoid you or let you pass if need be but that's only when you get to higher levels. Having said that, it's still really awful. The problem with the A.I. is that it always feels like it's tied to the racing line and completely ignores any other drivers around them which brings me onto the next problem. B-Spec Mode. What happened to you man? You used to be cool(-ish)! Like those few times when I got too bored to do any endurance races and you stepped in for me but now you've run off and started off a separate career from mine? It's a shame that you're too thick to drive properly so you need me to tell you how to drive but even then you're probably going to ignore me most of the time. Doesn't help when you're too spineless to take any risks or simply trying to overtake the car that YOU'RE CURRENTLY RAMMING THE BACK OF. You twit.
So do I regret spending €280 on this? Not at all. For one thing the game does offer over a thousand cars. Yes, only 200 of those cars are premium and yes the other 800 are just are just hi-def versions of GT4 models but they all still drive perfectly fine thanks to the GT5 wheel and not to mention that they're all internally customisable at the very least which is all I could really care for. I won't deny that some standard cars look awful with their stretched, blurry textures and the fact that the damage modelling isn't too great but hey, I drive using the bonnet view and crashing cars is the last thing I want to do in this game. Premium cars look fantastic and they make a great excuse to show off the games beautiful graphics engine. From the Mercedes-Benz 300SL to the Ferrari F40, taking pictures with the in-game photo function makes it a joy to share your collection.
There are other factors that I can appreciate too. I can listen to my own music instead of that rather awful jazz that they've got quite an abundance of. Go-karting is pretty fun when you've the hang of it. There's different track layouts for the Nürburgring. There's a day/night cycle (which you can only witness on endurance races but still looks awesome. (and hard to see.)) Driving with a wheel feels satisfying and more fun than a controller. Online community seems decent. Finally there's this:
At level 30 you'll unlock the Sebastian Vettlel challenge where you're pitted against his ghost around three different tracks. Both of you driving the Red Bull X2010 car (see above.) Now if you don't know anything about this car let me put it this way, it's a super-F1 car. What's more, it can be built in today's technology. The only problem being is that it's stupidly fast, even around corners thanks to it being a fan-car like the Chapparal 2J. Those challenges are perhaps the hardest races I've ever done and this comes from someone who finished all the Gran Turismo games in his life. But if you do manage to get a bronze medal in all the Vettel challenges then you're in for luck. You get this car. Not just any car though, but perhaps the fastest car you've ever driven in a console racing simulator. This alone is one good reason why I still play this game. It's got so many faults but it's also super quirky in it's design. Most people will hate it and that's perfectly fine but it won't change the fact that I love this game for what it is. The folks over at Polyphony Digital have a great passion for cars as well as their history and their technology and it shows.
P.S: I've never played Forza 3 but I appreciate it for what it is since it's got some great ideas and it is a better game then GT5. To put it simply, GT5 is James May and Forza 3 is Jeremy Clarkson.
P.P.S: This is way longer then I intended so I'll post up my thoughts on the other games later.


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Make sure you like Herbs & Oils World on Facebook to be updated every time we find a fantastic tutorial for exciting and innovative ways you can use herbs and essential oils.
Essential oils not only smell delightful, but the scent of certain essential oils have been found to uplift mood, improve concentration, increase energy, calm and relax, and some oils have even been found to curb hunger cravings.
Diffusing essential oils around your home is the best way to take advantage of their incredible properties while also making your home smell heavenly.
This article reveals the three best ways to make your home smell beautiful with the scent of essential oils.
Method #1
Candle Drops
This is the simplest method to begin to diffuse essential oils around your home. It requires no special equipment – just a non-scented candle and an essential oil of your choice.
Light your non-scented candle and allow to burn for a few minutes or until a pool of melted wax forms. Add two or three drops of your favorite essential oil. Within seconds the beautiful aroma will start to spread around the room.
Method #2
Aromatherapy Oil Burner
Aromatherapy oil burners are a great way to gently spread the scent of essential oils around your home. They are really cheap to buy and they look beautiful in your home as the candle gently flickers away.
All you need to do is fill the bowl up with water, add a few drops of any essential oil you like and place a lighted tea light underneath. The candle gently heats the water vaporising the essential oil and allowing it to diffuse around your home.
If you are looking for an oil burner, then you can't go wrong with this Black Metal Aromatherapy Oil Warmer at under $9. Or perhaps take a look at this three pack of Tulip Fun Flower Oil Warmers if you are looking for something a little different.
Method #3
Electric Diffuser
Electric diffusers and vaporisers are the safest and most effective way to diffuse the scent of essential oils around your home. Since there is no naked flame the diffuser can work all day and night to spread the aromas around your home.
This Ultrasonic Aromatherapy Diffuser uses ultrasound to deliver micron-sized essential oil droplets so fine that within a moment of leaving the diffuser, the cool mist becomes a vapor, incorporated into the atmosphere and spreading evenly throughout your room.
Essential oils are little miracle workers and diffusing their aromas around your home can work wonders for yours – and your families – health. Try out the three methods shared in this blog post and share your favorite method by leaving a comment below.
If you need to add some essential oils to your collection then take a look at this Best Of The Best Essential Oil Gift Set (pictured) which contains fourteen of the most popular essential oils. Alternatively you can purchase all the essential oils you'll ever need (and the highest quality ones at that!) from this page on the Mountain Rose Herbs website.
3 Healthy Food LIES Reveal Why Your Kitchen Is Full Of Fat Storing Ingredients
In this powerful article you'll discover:- How food label lies are causing you to poison your body.
- How avoiding this much maligned food group is actually making you fat!
- How some of the so-called healthiest foods in your kitchen may actually be FAKE!
If you value your health, this may be the most important article you ever read!


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Bajaj Pulsar 200 SS
Bajaj Pulsar 200 SS Preview
At the Auto Expo 2014, Bajaj Auto gave a pleasant surprise byshowcasing the Pulsar SS400 and the CS400.Based on the lines of SS400 (SS- Super Sports) the manufacturer will soon be introducing the faired version of the NS200, whichhas already gained quite a popularity of a performance oriented motorcycle.The upcoming SS200 has been spied testing many times and a few days back spy images of the Pulsar SS200 surfaced again on the web and it created a stir among the bike aficionados. Now according to sources, Bajaj is planning to launch the Pulsar SS200 in the second quarter of this year. The Pune based manufacturer will first launch the Pulsar SS200 and later on will launch its bigger siblings, the Pulsar SS400 and the CS400.
Visually, we can safely expect that the bike will be very similar to the SS400 showcased at the Auto Expo 2014. The spied images also indicated towards the styling of SS400 been carried over to its lower version. The SS200 will be Bajaj's first ever fully-faired Pulsar motorcycle and will alsocome equipped with fuel-Injection unit as standard equipment. The SS200 is expected to be powered by a retuned 199.5 cc, four-stroke, liquid- cooled, single-cylinder, fuel-injected engine which also powers the Pulsar NS200 and produces peak power of 23.52 PS at 9500 RPM and peak torque of 18.3 NM at 8000 RPM. The engine will be mated to a six-speed gearbox. The power from the engine to the rear wheel will be transmitted via a chain set.
Bajaj is already doing well with its motorcycle the Pulsar NS200, which has proved to be among the most successful bikes from the Pune based manufacturer. Bajaj will aim to repeat the success of the NS200 with the SS200. Regarding the pricing of the upcoming Pulsar SS200, Bajaj is more likely to price this upcoming bike slightly higher than the NS200 due to the addition of FI unit and optional ABS.
Soon KTM, the renowned Austrian motorcycle manufacturer is also going to launch its RC series of fully-faired motorcycles in the Indian motorcycle market. So Bajaj has to price this bike quite aggressively to be in the competition, we can expect the pricing of this upcoming motorcycle to be around Rs. 1.25 lakh. Once launched the Pulsar SS200 will compete with Honda CBR250R and the upcoming KTM RC 200.
Leave a Comment
Very nice motorcycles but price around ?????
WHAT is Launching Date in Mumbai & what is the expected on road price... ??
Please let me know exact Launch date of Pulsar 200SS in Mumbai......
Pls infom launching date and exact road on price at karnataka, mangalore
I love that. It's very cool.
I love this bike very much.
Yello color bike ka full picture send kro.
WHAT is Launching Date in UP.& What is top speed this bike.
what is the launch date..?? what is the expected on road price..?
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831-3058 - Wi-Pi Raspberry Pi 802.11n Wireless Adapter
A 802.11n compliant wireless client for your Raspberry Pi installation. Tested with the Raspberry Pi release of Debian Linux. Drivers are built into the Raspberry Pi software release and like most other adapters it supports WPA and WPA2 security features.
Mfr Name: Distributed By MCM
Mfr Number: 2133900
83-16323 - 8Gb Raspberry Pi Operating System
This 8GB Micro SDHC card comes pre-installed with NOOBS Operating System, a system image with 6 different Linux based operating systems optimized to run on the Raspberry Pi.
Mfr Name: Raspberry Pi
Mfr Number: 2428393
83-14403 - Wireless Miniature Keyboard and Mouse for Raspberry Pi
Add a miniature wireless controller to your computer project with this combination keyboard and touchpad.
Mfr Name: Adafruit Industries
Mfr Number: 922
58-16695 - DOPO 9" 4GB 1Ghz Android 4.0 Tablet
The Double Power 9" Capacitive Multi-Touch Screen Tablet M975 keeps you connected with the rest of the world through its built-in WiFi.
Mfr Name: Double Power Technology
Mfr Number: M975
83-14407 - Pi View - HDMI to VGA Converter - For the Raspberry PI board
A high quality, convenient and compact device that converts digital HDMI signals from Raspberry Pi into the analog signals required by the widely used VGA computer displays still commonly in use.
Mfr Number: 2133899
58-17195 - D-Link Wireless-N Network IP Camera (DCS-930L)
D-Link Wireless-N Network Camera
The mydlink-enabled Wireless N Network Camera (DCS-930L) comes with everything you need to quickly add a surveillance camera to your home or small office network. It works right out of the box. Simply connect the cables, plug in...
Mfr Name: D-Link
Mfr Number: DCS-930L
83-14038 - Laptop PC Analyzer Card
Diagnose computer problems quickly and easily with this PC analyzer card.
Mfr Number: TRK-C020018
831-2761 - Wireless N Nano USB Adapter
EW-7811Un is a nano USB wireless adapter that supports maximum range and speed. Despite the size, this tiny USB adapter supports higher data rate of up to 150Mbps when connecting with wireless 802.11n device which is 3 times faster than your normally 11g connectio...
Mfr Name: Edimax
Mfr Number: EW-7811UN
72-1086 - Deluxe Computer ATX Power Supply Tester
ATX Power Supply Tester
The Tenma ATX Power Supply Tester is designed to provide fast convenient verification of proper operation of both 20 pin and 24 pin ATX style computer power supplies.
Mfr Name: Tenma
Mfr Number: 72-1086
83-14037 - PC Analyzer Card with LCD Display
Mfr Number: TRK-C020022
58-16275 - 550W ATX Power Supply
This 550W power supply comes with dual quiet 80MM fans, one on the top and one on the back. The whole body is coated with thick glossy paint for a sleek look in any environment.
Mfr Name: Logisys
Mfr Number: PS550ABK
83-15657-S - 480W Power Supply
This 480W power supply boasts its powerful and quiet performance by installing 120mm ball bearing fan with a 75CFM air flow and 2000RPM speed. The power was integrated with dual SATA connectors, four 4-pin molex connectors, one 20pin+4pin ATX connector and one P4 ...
Mfr Number: PS480A12S
58-17210 - 16X HP DVD Burner
Black bezel
SATA interface
16x DVD read speed
48x CD read speed
16x DVD±R write speed
Buffer underrun protection
Limited quantities
Mfr Name: Hewlett Packard
Mfr Number: BLK-GH80N-DO
83-12835 - 6ft USB A Male to Micro B Male Cable
USB A Male to USB Micro B Male cableUSB 2.0 compliant6' length
Mfr Number: HK-US10/2
831-3085 - T1/E1 Loopback Adapter
The SuperLooper™ T1/E1 Loopback Jack and Plug quickly and easily checks the RX/TX pairs of T1/E1 circuit cables helping a network technician determine if a signal exists or if there are broken or shorted wires within the cabling. It can be plugged directly into a ...
Mfr Name: Smartronix
Mfr Number: ST034LT02-03-001
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Essential Grooming Tools for Winter
Cold is brutal on skin. Keep your armor smooth with these simple remedies.
Cold is brutal on skin. Keep your armor smooth with these simple remedies.
Initial findings by a team at Belgium's Ghent University show that compared with wearing deodorant and even going au naturel, antiperspirant actually spawns larger populations of Actinobacteria,...
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If you've relegated charcoal to the backyard or the water filter, you're missing out.
Five DEET-free options to fend off bugs this summer
Let's face it: the great outdoors is a grimy, buggy, skin-scorching, sweat-inducing place, and a small quiver of personal-care items can make the difference between enjoying the sunset and sticking...
How to cure plantar fasciitis
The FDA regulates sunscreens just like any over-the-counter drug, which means that all those words on the label actually mean something. Here's what you need to know to slather smart.


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IEEE membership options for an individual and IEEE Xplore subscriptions for an organization offer the most affordable access to essential journal articles, conference papers, standards,
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click on this link:http://dx.doi.org/+10.1063/1.3068186
Co40Fe40B20/MgO single and double barrier magnetic tunnel junctions (MTJs) were grown using target-facing-target sputtering for MgO barriers and conventional dc magnetron sputtering for Co40Fe40B20 ferromagnetic electrodes. Large tunnel magnetoresistance (TMR) ratios, 230% for single barrier MTJs and 120% for the double barrier MTJs, were obtained after postdeposition annealing in a field of 800 mT. The lower TMR ratio for double barrier MTJs can be attributed to the amorphous nature of the middle Co40Fe40B20 free layer, which could not be crystallized during postannealing. A highly asymmetric bias voltage dependence of the TMR can be observed for both single and double barrier MTJs in the as-deposited states and after field annealing at low temperature. The asymmetry decreases with increasing annealing temperature and the bias dependence becomes almost symmetric after annealing at 350 °C. Maximum output voltages of 0.65 and 0.85 V were obtained for both single and double barrier MTJs, respectively, after annealing at 300 °C, a temperature which is high enough for large TMR ratios but insufficient to completely remove asymmetry from the TMR bias dependence.
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Ad Closing: November 10, 2014 | Material Closing: November 18, 2014
Cover Story
Chemical Makers Think Small
By Seán Ottewell, Editor at Large
Companies now are using nanotechnology in a wide variety of ways to improve processes and products. Here's a rundown of some of recent developments that provide large benefits through use technology on the nanoscale.
Maintenance and Operations
Assess Pump Lifecycle Costs
By Robert Lax, ITT PRO Services, and Mike Pemberton, ITT Goulds Pumps
Taking a lifecycle approach to pumps can identify ways to improve system efficiency and reliability of pump and valve subsystems, and thus to reduce energy consumption, lower maintenance costs and enhance process control.
Instrumentation and Control
Targeted Attacks are the New Normal
By Andrew Ginter, Waterfall Security
Threats to plant networks have become more sophisticated, necessitating the continual evolution of cyber security efforts. Hardware, particularly unidirectional security gateways, can play an important role in ensuring security.
Energy Saver
Sustain Energy-Cost-Control Efforts
By Ven Venkatesan, Energy Columnist
Energy cost savings may wane over time unless you invest in ongoing efforts. Follow these five steps to ensure that results are sustained long-term and to help identify new opportunities for energy savings.
For advertising information contact your district manager or Rita Fitzgerald, Production Manager, at 630/467-1300 ext. 468. Send insertion orders to her at Chemical Processing, 1501 E. Woodfield Rd., Suite 400N, Schaumburg, IL 60173; fax 630/467-0197; e-mail firstname.lastname@example.com.


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Originally posted 11/24/2014 06:00PM
The police officer who fatally shot an unarmed 18-year-old in Ferguson, Missouri, setting off weeks of ongoing protests, has gotten married.
Originally posted 11/24/2014 12:20PM
A 12-year-old boy shot by police after grabbing what turned out to be a replica gun died from his wounds Sunday, a day after officers responded to a 911 call about someone waving a "probably fake" gun at a Cleveland playground.
Originally posted 11/01/2014 03:20AM
Another 14-year-old girl who was shot by a fellow student at a Washington state high school has died.
Originally posted 10/27/2014 07:55AM
A 14-year-old girl who was wounded when a student opened fire inside a Washington state high school has died, raising the death toll in the shooting to three.
Originally posted 10/24/2014 02:35PM
A student opened fire in a high school cafeteria north of Seattle on Friday, killing at least one person and wounding four other students, officials said. The gunman also died in the attack.
Originally posted 09/15/2014 04:35PM
The family of the man accidentally killed in a shooting mishap by a 9-year-old girl have written her a letter of forgiveness.
Originally posted 09/12/2014 08:30PM
Liza Long used to spend hours using Photoshop to merge various pictures of her four children into one ideal image.
Originally posted 09/12/2014 08:15AM
A teenager convicted of killing three students at an Ohio high school scrambled over a fence to escape a state prison with two other prisoners and was captured nearly six hours later hiding by a church early Friday, authorities said.
Originally posted 08/28/2014 01:00PM
An Arizona gun range has been shuttered indefinitely after a 9-year-old girl accidentally killed her shooting instructor on Monday.
Originally posted 08/24/2014 11:15AM
Hip-hop mogul Suge Knight was shot multiple times early Sunday morning, TMZ reports.
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Panthers Newest Sideline Reporter Jordan Gross
August 18, 2014 4:53 PM
Jay "JayWeezie" Brown
JayWeezie was born and raised right here in Charlotte NC. He attended...Read More
Carolina Panthers
Buy Panthers Tickets
Full Schedule
Upcoming Games
Sunday Dec 14
vs. Buccaneers
Sunday Dec 21
vs. Browns
Jordan Gross talks with Primetime about the Chiefs game from Sunday night. They get into the defensive back field playing better than expected, how Cam Newton looked in his first action this pre-season, and they discuss Jonathon Stewart making his return to the field for the first time.


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Mildelich him gan andswere the milde maide thanne:
Wichewise sold ich bere a child withute manne?
Th angel hir said, Ne dred tee nout;
thurw tholigast sal been iwrout
this ilche thing warof tiding ich bringe;
al manken wurth ibout
thurw thine sweet childinge and ut of pine ibrout.
Wan the maiden understood and th angels wordes herde,
mildelich with milde mood to th angel hie andswerde:
Ure lords thewe maid iwis
ich am, that heer aboven is.
Anentis me fulfurthed be thi sawe
that ich, sith his wil is,
a maid, withute lawe, of moder have the blis.
Th angel went awei mid than al ut of hire sighte;
hire womb arise gan thurw th oligastes mighte.
In hir wes Crist bilok anon,
sooth God, sooth man in fles and bon,
and of hir fles ibore wes at time.
Warthurw us kam good won;
he bout us ut of pine and let him us for slon.
Maiden-moder makeles, of milce ful ibunde,
bid for us him that tee ches, at wam thu grace funde,
that he forgive us sen and wrake,
and clene of evri gelt us make,
and heven-blis, wan ur time to sterve,
us give, for thine sake,
him so heer for to serve that he us to him take.
The gentle maiden then gently answered him:
In what way should I bear a child without a husband?
The angel said to her, Fear not;
for this very thing
whereof I bring news will be done by means of the Holy Spirit;
all mankind will be redeemed
by means of thy sweet child-bearing and brought out of torment.
When the maiden understood and heard the angels words,
she answered the angel gently, with gentle spirit:
I am indeed the bondmaid
of Our Lord, who is above.
May thy saying concerning me be fulfilled,
that I, since it is his will, may as
a maiden, contrary to natural law, have the bliss of a mother.
The angel went away with that altogether out of her sight;
her womb began to swell through the power of the Holy Spirit.
In her Christ was straightaway enclosed,
true God and true man in flesh and bone,
and was born of her flesh at due time.
Whereby good hope came to us;
he redeemed us from torment and let himself be slain for us.
Matchless maiden-mother, fully endowed with compassion,
pray for us to him who chose thee, in whose sight thou didst find
grace, that he forgive us sin and hostility
and make us innocent of every offence,
and when it our time is to die, is give us the bliss of heaven,
and grant us for thy sake
so to serve him here that he may take us to himself.
[Return to top of page]


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Narrow your search
Four-player Push Me Pull You is one of the strangest -- and most mesmerising -- gaming experiences we've ever clapped eyes on.
The dormant smartphone gaming phenomenon is making a triumphant return as a multiplayer title, creator Dong Nguyen confirms.
By translating chat commands into in-game movements and button inputs, more than 12,000 people are haphazardly steering the protagonist of the original GameBoy classic in a chaotic collective effort.
What can Xbox One users expect from next month's update? Microsoft unwraps some of the details, but promises there's still more to come.
A February update will beef up the Kinect's voice recognition, while another one in March will enhance the console's party and multiplayer features.
A new update to Google Play means Android games can now begin to offer turn-based multiplayer modes via the store's built-in gaming system.
The update rolled out to always-online consoles at 1am UK time this morning, and fixes a bunch of minor bugs.
The game is this year's biggest entertainment launch, according to Activision, though the company didn't say how much the game has generated in sales since its early November release.
Sony's cranked up the macho-o-meter for the PlayStation 4's debut TV ad.
Baad-ass! A new patch for the game Goat Simulator adds a pseudo online multiplayer mode so you can headbutt and lick things with all of your pretend goat friends.