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Sample records for challenge induces ifng

  1. IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

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    Sampaio Elizabeth P

    2007-04-01

    Full Text Available Abstract Background Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL and also the influence of this SNP in the secretion of IFN-γ in vitro. Methods Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR. Leishmania-induced IFN-γ production on peripheral blood mononuclear cell (PBMC culture supernatants was assessed by ELISA. Results There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers. Conclusion Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.

  2. Eomesodermin promotes interferon-γ expression and binds to multiple conserved noncoding sequences across the Ifng locus in mouse thymoma cell lines.

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    Fukuoka, Natsuki; Harada, Misuzu; Nishida, Ai; Ito, Yuko; Shiota, Hideki; Kataoka, Takao

    2016-02-01

    The T-box transcription factors T-bet and eomesodermin (Eomes) have been shown to regulate the lineage-specific expression of interferon-γ (IFN-γ). However, in contrast to T-bet, the role of Eomes in the expression of IFN-γ remains unclear. In this study, we investigated the Eomes-dependent expression of IFN-γ in the mouse thymoma BW5147 and EL4 cells, which do not express T-bet or Eomes. The ectopic expression of Eomes induced BW5147 and EL4 cells to produce IFN-γ in response to phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM). In BW5147 cells, Eomes augmented luciferase activity driven by the Ifng promoter encoding from -2500 to +113 bp; however, it was not increased by a stimulation with PMA and IM. A chromatin immunoprecipitation assay showed that Eomes bound to the Ifng promoter and conserved noncoding sequence (CNS) -22 kb across the Ifng locus with high efficacy in BW5147 cells. Moreover, Eomes increased permissive histone modifications in the Ifng promoter and multiple CNSs. The stimulation with PMA and IM greatly augmented Eomes binding to CNS-54, CNS-34, CNS+19 and CNS+30, which was inhibited by FK506. These results indicated that Eomes bound to the Ifng promoter and multiple CNSs in stimulation-dependent and stimulation-independent manners. PMID:26749212

  3. Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi.

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    Guilmot, Aline; Bosse, Julie; Carlier, Yves; Truyens, Carine

    2013-01-01

    We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+) T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56(bright) NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells), while CD56(dim) NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates.

  4. Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi.

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    Aline Guilmot

    Full Text Available We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+ T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56(bright NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells, while CD56(dim NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates.

  5. Administration of interferon-g to pregnant rats reverses the depressed adjuvant-induced arthritis of their chronically Trypanosoma cruzi-infected offspring

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    Didoli G.

    1999-01-01

    Full Text Available We demonstrated that administration of interferon gamma (IFN-g to the inbred "l" strain of pregnant rats conferred partial resistance on their offspring to challenge with Trypanosoma cruzi. We now examine if this intervention also modifies the reportedly immunodepressed cellular responses which occur during chronic infection. Offspring were born to mothers undergoing one of the following procedures during gestation: subcutaneous injections of recombinant rat IFN-g, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating (IFN-Mo; infection with 106 trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-g treatment as given to the former group (TcIFN-Mo; the same protocol except that physiological saline was injected instead of IFN-g (Tc-Mo; injection of physiological saline only (control-Mo. All offspring groups (N = 8-10/group were infected at weaning and were assessed 90 days later for their adjuvant-induced arthritic response or levels of major T cell subsets in spleen and lymph nodes. TcIFN-Mo and IFN-Mo offspring showed a reestablished arthritic response, which remained within the range seen in controls. Immunolabeling studies on parallel groups of 90-day-infected offspring showed that the inverse CD4/CD8 cell ratio that is usually seen in lymphoid organs from these chronically infected rats (median 0.61 appeared to have recovered in the TcIFN-Mo and IFN-Mo groups (median 1.66 and 1.78, respectively and was not different from uninfected controls (1.96. These studies indicate that early stimulation with IFN-g is able to reverse the immunosuppressive state that is usually present during the chronic period of the experimental infection.

  6. IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population.

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    Shen, Chen; Jiao, Wei-Wei; Feng, Wei-Xing; Wu, Xi-Rong; Xiao, Jing; Miao, Qing; Sun, Lin; Wang, Bin-Bin; Wang, Jing; Liu, Fang; Shen, Dan; Shen, A-Dong

    2013-09-01

    Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-γ), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case-control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including -1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-γ expression) in the extrapulmonary

  7. La proteína asociada a SLAM (SAP regula la expresión de IFN-g en lepra The SLAM-associated protein (SAP regulates IFN-g expression in leprosy

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    María F. Quiroga

    2004-10-01

    Full Text Available La inmunidad protectora contra Mycobacterium leprae requiere IFN-g. Los pacientes con lepra tuberculoide producen localmente citoquinas Th1, mientras que los pacientes lepromatosos producen citoquinas Th2. La molécula linfocitaria activadora de señales (SLAM y la proteína asociada a SLAM (SAP participan en la diferenciación celular que conduce a producción de patrones específicos de citoquinas. A fin de investigar la vía SLAM/SAP en la infección por M. leprae, determinamos expresión de ARN mensajero (ARNm de SAP, IFN-g y SLAM en pacientes con lepra. Observamos que la expresión de SLAM correlacionó en forma directa con la expresión de IFN-g, mientras que la expresión de SAP correlacionó inversamente con la expresión de ambas proteínas. Así, nuestros resultados indican que SAP interferiría con las respuestas de citoquinas Th1 mientras que SLAM contribuiría con la respuesta Th1 en lepra, señalando a la vía SLAM/SAP como potencial blanco modulador de citoquinas en enfermedades con respuestas Th2 disfuncionales.Tuberculoid leprosy patients locally produce Th1 cytokines, while lepromatous patients produce Th2 cytokines. Signaling lymphocytic activation molecule (SLAM and the SLAM-associated protein (SAP participate in the differentiation process that leads to the production of specific patterns of cytokines by activated T cells. To investigate the SLAM/SAP pathway in M. leprae infection, we determined the expression of SAP, IFN-g and SLAM RNA messenger in leprosy patients. We found a direct correlation of SLAM expression with IFN-g expression, whereas the expression of SAP was inversely correlated with the expression of both SLAM and IFN-g. Therefore, our data indicate that SAP might interfere with Th1 cytokine responses while SLAM expression may contribute to Th1 responses in leprosy. This study further suggests that the SLAM/SAP pathway might be a focal point for therapeutic modulation of T cell cytokine responses in diseases

  8. TNF, IL12B, and IFNG Gene Polymorphisms in Serbian Patients with Psoriasis

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    Popadic, Svetlana; Savic, Emina; Markovic, Milos; Ramic, Zorica; Medenica, Ljiljana; Pravica, Vera; Spuran, Zorica; Trajkovic, Vladimir

    2015-01-01

    Background Psoriasis is a common chronic inflammatory skin disease with a strong genetic basis. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (ILs) such are IL-12 and IL-23, and interferon gamma (IFN-γ) are released from various inflammatory and resident cells, and have been implicated in the initiation/maintenance of inflammation. Certain alleles of the aforementioned cytokines may be associated with disease susceptibility/severity. Objective To investigate the association of three common functional gene polymorphisms, namely TNF -308 G/A (rs1800629), IL12B (encoding the p40 subunit of IL-12/23) +1188 A/C (rs3212227), and IFNG +874 T/A (rs2430561) with psoriasis development and severity in Serbian patients. Methods We genotyped 130 patients with psoriasis (26 of whom also had psoriatic arthritis) and 259 controls; rs1800629 and rs3212227, and rs2430561, by real-time PCR assay. Results The TNF GG genotype was detected at a higher frequency in patients with psoriasis compared to control subjects (OR, 1.420; 95% CI, 0.870~2.403) without statistical significance (p=0.191). Lack of the TNF G allele was associated with lower psoriasis severity (p=0.007). The IL12B AC genotype was underrepresented in the patients with psoriatic arthritis compared to healthy subjects (OR, 0.308; 95% CI, 0.090~1.057; p=0.049). The distribution of the rs2430561 allele and genotype frequencies was similar between patients with psoriasis and controls. Conclusion Our study demonstrates an effect of the rs1800629 on psoriasis severity, and a marginal impact of the rs3212227 on susceptibility to psoriatic arthritis. Collectively, our results obtained in a Serbian cohort expand current knowledge regarding individual predisposition to psoriatic disease. PMID:25834350

  9. Thalidomide protects mice against LPS-induced shock

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    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  10. Polymorphisms on IFNG, IL12B and IL12RB1 genes and paracoccidioidomycosis in the Brazilian population.

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    Carvalho, F M C; Busser, F D; Freitas, V L T; Furucho, C R; Sadahiro, A; Kono, A S G; Criado, P R; Moretti, M L; Sato, P K; Shikanai-Yasuda, M A

    2016-09-01

    Paracoccidioidomycosis (PCM) is a systemic chronic mycosis, endemic in Latin America, especially Brazil, and is the eighth leading cause of death among chronic and recurrent infectious diseases. PCM infection is characterized by the presence of Th1 immune response; the acute form, by a mixed Th2/Th9, while the chronic form is characterized by Th17/Th22 profiles. The occurrence and severity of human PCM may also be associated with genetic factors such as single nucleotide polymorphisms (SNP) on cytokines encoding genes. We investigated the association between these polymorphisms and the different clinical forms of PCM. We included 156 patients with PCM (40 with the acute form, 99 with the chronic multifocal and 17 with the chronic unifocal form) and assayed their DNA samples for IFNG +874 T/A SNP by PCR-ARMS (Amplification Refractory Mutational System), IL12B +1188 A/C SNP on 3' UTR and IL12RB1 641 A/G SNP on exon 7 by PCR-RFLP (Restriction Fragment Length Polymorphism). We found similar genotypic and allelic frequencies of the investigated SNPs among the clinical forms of PCM. Considering male patients, the IL12RB1 641 AA genotype was more frequent in the chronic multifocal form while heterozygosis was in the chronic unifocal form of PCM (p=0.048). Although our data suggest that the AA genotype (IL12RB1) may be associated with the more disseminated chronic disease, more patients of the chronic unifocal PCM group need to be analyzed as well as the secretion patterns of IFN-γ combined with the IL-12Rβ1 expression for a better comprehension of this association. PMID:27223631

  11. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy

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    Patty eSachamitr

    2014-04-01

    Full Text Available Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumour associated antigens (TAA are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focussed on the administration of autologous monocyte-derived dendritic cells (moDC pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumour infiltrating lymphocytes (TIL as a source of TAA-specific cytotoxic T cells (CTL. Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross-present exogenous TAA to the CD8+ T cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS cells as well as minor subsets of DC with therapeutic potential, including CD141+XCR1+ DC, capable of cross-presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  12. Screening elite winter athletes for exercise induced asthma: A comparison of three challenge methods

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    Dickinson, JW; Whyte, GP; McConnell, AK; Harries, MG

    2006-01-01

    The official published version can be obtained from the link below. Background: The reported prevalence of exercise induced asthma (EIA) in elite winter athletes ranges from 9% to 50%. Many elite winter athletes do not report symptoms of EIA. At present there is no gold standard test for EIA. Objective: To establish the efficacy of screening for EIA and examine the role of the eucapnic voluntary hyperventilation (EVH) challenge and laboratory based and sport specific exercise challeng...

  13. IL-2 AND IFN-g, BUT NOT IL-4 SECRETION BY PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC ARE RELATED TO CD4+ T CELLS AND CLINICAL STATUS IN BRAZILIAN HIV-1-INFECTED SUBJECTS

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    Marisa A. HONG

    1998-11-01

    Full Text Available It has been reported that production of IL-2 and IFN-g, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV- infected patients and normal subjects, were detected. The patients with CD4+ T cell counts g production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or >500 cells/mm3 also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-g release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells >500 cells/mm3 showed increased levels of IL-2 and IFN-g, than individuals with CD4+ T cells g production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.

  14. Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages

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    Nagarkar, Deepti R.; Bowman, Emily R.; Schneider, Dina; Wang, Qiong; Shim, Jee; Zhao, Ying; Linn, Marisa J.; McHenry, Christina L.; Gosangi, Babina; Bentley, J. Kelley; Tsai, Wan C.; Sajjan, Umadevi S.; Lukacs, Nicholas W; Hershenson, Marc B.

    2010-01-01

    Human rhinovirus is responsible for the majority of virus-induced asthma exacerbations. To determine the immunologic mechanisms underlying rhinovirus-induced asthma exacerbations, we combined mouse models of allergic airways disease and human rhinovirus infection. We inoculated ovalbumin-sensitized and challenged BALB/c mice with rhinovirus serotype 1B, a minor group strain capable of infecting mouse cells. Compared to sham-infected, ovalbumin-treated mice, virus-infected mice showed increase...

  15. Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer

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    Williamson Anna-Lise

    2003-01-01

    Full Text Available Abstract Background The failure of specific types of human papillomaviruses (HPV to raise effective immune responses may be important in the pathogenesis of cervical cancer, the second most common cancer in South African women. Polymorphisms of a number of cytokine genes have been implicated in inducing susceptibility or resistance to cancers caused by infectious agents owing to their role in determining host immune response. Polymorphisms of IL-10 and IFN-γ genes are believed to influence the expression and/or secretion levels of their respective cytokines. Methods and Results In this study, women with histologically proven cancer of the cervix (n = 458 and hospital-based controls (n = 587 were investigated for bi-allelic -1082 (A/G polymorphisms of IL-10 and the bi-allelic +874(A/T polymorphisms of IFN-γ. In addition, the distributions of the allelic frequencies were stratified in both the African and mixed race population groups of South Africa. We found striking differences in the allele distribution of IFN-γ (X2 = 0.02 among the two ethnic groups. A significant increase in the allele distribution of the IFN-γ AA genotype was found in the African group compared to the mixed population group (OR, 0.5; 95% CI, 0.2–1.0. For IL-10 there were no significant allelic differences between the two South African ethnic groups. Furthermore, when the ethnic groups were combined the IL-10 allelic frequencies in the combined South African data were similar to those observed in an Oriental population from Southern China and in an Italian population. However, the allele frequencies of the IFN-γ genotype among the two South African ethnic groups were different when compared to an Italian Caucasoid group. While crude analysis of these data showed both statistically significantly increased and diminished risks of cervical cancer among high producers of INF-γ and low producers of IL-10 respectively, these associations were no longer significant when the

  16. Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

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    Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

    2016-05-01

    We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

  17. Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects

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    Ihlemann, Nikolaj; Rask-Madsen, Christian; Perner, Anders;

    2003-01-01

    cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained......An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential...... during intra-arterial infusion of serotonin to elicit endothelium-dependent, NO-specific vasodilation and during sodium nitroprusside (SNP) infusion to elicit endothelium-independent vasodilation. Subjects were examined before (fasting) and 1 and 2 h after an oral glucose challenge (75 g) with serotonin...

  18. Inducible nitric oxide synthase after sensitization and allergen challenge of Brown Norway rat lung

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    Fang Liu, Shu; Haddad, El-Bdaoui; Adcock, Ian; Salmon, Michael; Koto, Hiro; Gilbey, Tom; Peter J. Barnes; Fan Chung, K

    1997-01-01

    We studied the effects of ovalbumin (OA) sensitization and challenge on inducible nitric oxide synthase (iNOS) gene and protein expression in Brown-Norway rats in vivo.By use of Northern analysis, a 4.4-kb iNOS mRNA transcript was weakly observed in control rat lung but there was a 3 fold increase in lungs sensitized to OA alone (P

  19. No Association of IFNG+874T/A SNP and NOS2A-954G/C SNP Variants with Nitric Oxide Radical Serum Levels or Susceptibility to Tuberculosis in a Brazilian Population Subset

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    Ana Cristina C. S. Leandro

    2013-01-01

    Full Text Available Tuberculosis (TB is one of the most common infectious diseases in the world. Mycobacterium tuberculosis infection leads to pulmonary active disease in approximately 5–10% of exposed individuals. Both bacteria- and host-related characteristics influence latent infection and disease. Host genetic predisposition to develop TB may involve multiple genes and their polymorphisms. It was reported previously that interferon gamma (IFN-γ and nitric oxide synthase 2 (NOS2 are expressed on alveolar macrophages from TB patients and are responsible for bacilli control; thus, we aimed this study at genotyping single nucleotide polymorphisms IFNG+874T/A SNP and NOS2A-954G/C SNP to estimate their role on TB susceptibility and determine whether these polymorphisms influence serum nitrite and NOx- production. This case-control study enrolled 172 TB patients and 179 healthy controls. Neither polymorphism was associated with susceptibility to TB. NOS2A-954G/C SNP was not associated with serum levels of nitrite and NOx-. These results indicate that variants of IFNG+874T/A SNP and NOS2A-954G/C SNP do not influence TB susceptibility or the secretion of nitric oxide radicals in the study population.

  20. Bangpungtongseong-san, a traditional herbal medicine, attenuates chronic asthmatic effects induced by repeated ovalbumin challenge.

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    Lee, Mee-Young; Shin, In-Sik; Jeon, Woo-Young; Shin, Nara; Shin, Hyeun-Kyoo

    2014-04-01

    Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucus secretion, which can lead to chronic and obstinate asthma and can obstruct pulmonary function. In this study, the effects of Bangpungtongseong-san water extract (BPTS) on airway remodeling were examined using a murine model of bronchial asthma induced by ovalbumin (OVA) challenge. We focused on the effects of BPTS on the regulation of chronic asthma. BALB/c mice were randomly assigned to 5 groups, some of which were sensitized and challenged with OVA for 4 weeks. After the final ovalbumin challenge, typical asthma-like morphological changes were observed in the lung tissue with hematoxylin and eosin staining, periodic acid-Schiff, as well as with Masson's trichrome staining. The levels of transforming growth factor-β1 (TGF-β1) and Smad3 were assessed by immunohistochemistry and western blot analysis. The expression levels of vascular endothelial growth factor (VEGF) and adhesion molecules, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were also detected by western blot analysis. Our results revealed that BPTS reduced the OVA-induced increase in the infiltration of leukocytes, mucus hyperplasia and collagen deposition. Compared with the OVA-challenged group, the BPTS group had lower expression levels of adhesion molecules, TGF-β1, Smad3 and VEGF proteins in the lung tissues. The results of the current study suggest that BPTS prevents asthma airway remodeling in chronic asthma by inhibiting the activation of the TGF-β1-Smad3-signaling pathway, as well as the expression of VEGF and adhesion molecules. BPTS may thus be a potential drug for the treatment of patients with changes that occur in the airways due to severe asthma. PMID:24535550

  1. Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

    Directory of Open Access Journals (Sweden)

    Thiago B Kirsten

    Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

  2. Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges

    Indian Academy of Sciences (India)

    Zi-Bing Jin; Satoshi Okamoto; Michiko Mandai; Masayo Takahashi

    2009-12-01

    Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative diseases. We also discuss the challenges of using this technology in the retinology field.

  3. Vaccination with the Defined Chlamydial Secreted Protein CPAF Induces Robust Protection Against Female Infertility Following Repeated Genital Chlamydial Challenge

    OpenAIRE

    Murthy, Ashlesh K.; Li, Weidang; Guentzel, M. Neal; Zhong, Guangming; Arulanandam, Bernard P.

    2011-01-01

    We previously have shown the efficacy of recombinant (r) chlamydial protease-like activity factor (CPAF) vaccination against hydrosalpinx development following primary genital chlamydial challenge. In this study, we evaluated further the protection induced by rCPAF vaccination against infertility. Following primary challenge, fertility levels were not significantly different between the mock- and CPAF-vaccinated and Chlamydia alone challenged mice. However, following secondary genital chlamyd...

  4. Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-08-05

    TNF blockers have rarely been associated with haematological complications; however, there are scattered case reports of marked neutropenia with their use and necessitating in their withdrawal. We would like to report a series of five patients who developed neutropenia with etanercept use; however, all these patients were re-challenged with etanercept with a mean follow up of 30 months. These patients developed neutropenia within 2 months of starting etanercept. Two patients were eventually taken off etanercept; one of them needed switching to a different form of TNF blockers, and the second patient is in clinical remission with low-dose corticosteroids. All our patients continued to have mild-moderate degree of neutropenia; however, they are being monitored very closely and they are enjoying complete disease remission. It was interesting to note that none of our patients had increased infections during the re-challenge phase, even though they had grade 2 to grade 4 neutropenia. We have re-challenged these patients without any clinical complications, revealing that patients with mild to moderate neutropenia can be safely exposed to TNF blockers as long as they are monitored with regular cell count checks. Although largely noted to be clinically insignificant in our patient series, the potential of drug-induced neutropenia in causing higher rate of infections do exist. Careful clinical and hematologic monitoring is the best way to recognize this adverse event.

  5. Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice.

    Directory of Open Access Journals (Sweden)

    Kristin L Griffiths

    Full Text Available Interleukin (IL-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermore, we find that cholera toxin, delivered mucosally along with BCG, further enhances IL-17 production by CD4(+ T cells over mucosal BCG alone both in the lungs and systemically. This boosting effect of CT is also observed using a vaccine regimen of BCG followed by the candidate vaccine MVA85A. Using a murine Mycobacterium tuberculosis (M.tb aerosol challenge model, we demonstrate the ability of cholera toxin delivered at the time of a priming BCG vaccination to improve protection against tuberculosis disease in a manner at least partially dependent on the observed increase in IL-17. This observed increase in IL-17 in the lungs has no adverse effect on lung pathology following M.tb challenge, indicating that IL-17 can safely be boosted in murine lungs in a vaccine/M.tb challenge setting.

  6. Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations.

    Science.gov (United States)

    Grass, Juliane; Kirschbaum, Clemens; Miller, Robert; Gao, Wei; Steudte-Schmiedgen, Susann; Stalder, Tobias

    2015-03-01

    Hair cortisol concentrations (HCC) are assumed to provide a stable, integrative marker of long-term systemic cortisol secretion. However, contrary to this assumption, some recent observations have raised the possibility that HCC may be subject to acute influences, potentially related to cortisol incorporation from sweat. Here, we provide a first detailed in vivo investigation of this possibility comprising two independent experimental studies: study I (N=42) used a treadmill challenge to induce sweating together with systemic cortisol reactivity while in study II (N=52) a sauna bathing challenge induced sweating without systemic cortisol changes. In both studies, repeated assessments of HCC, salivary cortisol, cortisol in sweat and individuals' sweating rate (single assessment) were conducted on the experimental day and at a next-day follow-up. Results across the two studies consistently revealed that HCC were not altered by the acute interventions. Further, HCC were found to be unrelated to acute salivary cortisol reactivity, sweat cortisol levels, sweating rate or the time of examination. In line with previous data, cortisol levels in sweat were strongly related to total salivary cortisol output across the examined periods. The present results oppose recent case report data by showing that single sweat-inducing interventions do not result in acute changes in HCC. Our data also tentatively speak against the notion that cortisol in sweat may be a dominant source of HCC. Further, our findings also indicate that HCC are not subject to diurnal variation. This research provides further support for hair cortisol analysis as a marker of integrated long-term systemic cortisol secretion.

  7. The Significance of Gastric Juice Analysis for a Positive Challenge by a Standard Oral Challenge Test in Typical Cow's Milk Protein-Induced Enterocolitis

    OpenAIRE

    Hwang, Jin-Bok; Song, Jeong-Yoon; Kang, Yu Na; Kim, Sang Pyo; Suh, Seong-Il; Kam, Sin; Choi, Won Joung

    2008-01-01

    This study was performed to investigate the significance of gastric juice analysis (GJA) as a diagnostic criterion of a positive challenge in a standard oral cow's milk challenge (OCC) to confirm typical cow's milk protein-induced enterocolitis (CMPIE). Data from 16 CMPIE patients (aged 14 to 44 days) were analyzed. A standard OCC was openly executed using 0.15 g/kg of protein. Three symptoms (vomiting, lethargy, and bloody or pus-like stool), and four laboratory findings (GJA [3 hr], changes...

  8. Prevalence of Exercise-Induced Bronchospasm by laboratory exercise challenge among Ragunan Sport School athletes

    Directory of Open Access Journals (Sweden)

    Ignatio Rika

    2008-03-01

    Full Text Available Exercise-induced bronchospasm (EIB is a common condition among adolescent athletes. There has been no study examining the prevalence of EIB among adolescent athletes in Indonesia. This study aimed to get the prevalence of EIB among Ragunan Sport School athletes by laboratory exercise challenge. Subjects performed static cycle ergometer exercise (Monark, Sweden to reach minimal workload of 90% maximal heart rate. Force expiratory ventilation (FEV₁ was examined by spirometry (Minato AS-PAL, Japan at minute 0, 5, 10 and 20 post exercise. The EIB was defined as a decline of FEV₁ as much as 10% or more from baseline value. Room temperature and humidity were 28°C-31°C and 74%-82% respectively. There were 168 athletes from 12 sport types who participated in this study. Among them, 23 athletes (13.7% were EIB positive. The highest percentage of EIB was in taekwondo (54.5%. Sixteen athletes with EIB (70% were from less asthmogenic sports. Athletes with EIB consisted of 17 (17.5% females and 6 (8.4% males. In conclusion, the prevalence of EIB among adolescent athletes was moderately high, and was more prevalent in female. More over, laboratory exercise challenge could elicit EIB in less asthmogenic sport. (Med J Indones 2008; 17: 33-6Keywords: adolescent athlete, asthmogenic sports

  9. Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges

    Science.gov (United States)

    Xiao, Bin; Ng, Huck Hui; Takahashi, Ryosuke; Tan, Eng-King

    2016-01-01

    Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an ‘in vivo’ platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the ‘ideal’ neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced. PMID:26833176

  10. Mutant Brucella abortus membrane fusogenic protein induces protection against challenge infection in mice.

    Science.gov (United States)

    de Souza Filho, Job Alves; de Paulo Martins, Vicente; Campos, Priscila Carneiro; Alves-Silva, Juliana; Santos, Nathalia V; de Oliveira, Fernanda Souza; Menezes, Gustavo B; Azevedo, Vasco; Cravero, Silvio Lorenzo; Oliveira, Sergio Costa

    2015-04-01

    Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of the Brucella membrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed that B. abortus Δmfp::kan and Δomp19::kan deletion mutant strains have reduced persistence in vivo in C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a Δmfp::kan or Δomp19::kan strain expressing green fluorescent protein (GFP) approximately 80% or 65% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments. B. abortus Δomp19::kan was attenuated in vivo but had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the Δmfp::kan strain had a lower virulence in these same mouse models. Furthermore, Δmfp::kan and Δomp19::kan strains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the Δmfp::kan strain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a Δomp19::kan strain induced protection similar to that of RB51. Thus, these results demonstrate that Brucella Mfp and Omp19 are critical for full bacterial virulence and that the Δmfp::kan mutant may serve as a potential vaccine candidate in future studies. PMID:25644010

  11. Mutant Brucella abortus Membrane Fusogenic Protein Induces Protection against Challenge Infection in Mice

    Science.gov (United States)

    de Souza Filho, Job Alves; Martins, Vicente de Paulo; Campos, Priscila Carneiro; Alves-Silva, Juliana; Santos, Nathalia V.; de Oliveira, Fernanda Souza; Menezes, Gustavo B.; Azevedo, Vasco; Cravero, Silvio Lorenzo

    2015-01-01

    Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of the Brucella membrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed that B. abortus Δmfp::kan and Δomp19::kan deletion mutant strains have reduced persistence in vivo in C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a Δmfp::kan or Δomp19::kan strain expressing green fluorescent protein (GFP) approximately 80% or 65% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments. B. abortus Δomp19::kan was attenuated in vivo but had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the Δmfp::kan strain had a lower virulence in these same mouse models. Furthermore, Δmfp::kan and Δomp19::kan strains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the Δmfp::kan strain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a Δomp19::kan strain induced protection similar to that of RB51. Thus, these results demonstrate that Brucella Mfp and Omp19 are critical for full bacterial virulence and that the Δmfp::kan mutant may serve as a potential vaccine candidate in future studies. PMID:25644010

  12. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Yu Fen Samantha Seah

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases.

  13. Tuberculous Drug-induced Liver Injury and Treatment Re-challenge in Human Immunodeficiency Virus Co-infection

    Science.gov (United States)

    Costiniuk, Cecilia T.; Gosnell, Bernadett I.; Manzini, Thandekile C.; Du Plessis, Camille N.; Moosa, Mahomed Yunus S.

    2015-01-01

    Background: Tuberculosis drug-induced liver injury (TB-DILI) is the most common adverse event necessitating therapy interruption. The optimal re-challenge strategy for antituberculous therapy (ATT) remains unclear, especially in human immunodeficiency virus (HIV) co-infected individuals in high-prevalence settings such as South Africa. Objective: To determine the incidence of and risk factors for the recurrence of TB-DILI with different ATT re-challenge strategies. Materials and Methods: We conducted a retrospective chart review of patients managed for TB-DILI from 2005 to 2013 at King Edward VIII Hospital in Durban, South Africa. Relevant clinical and laboratory data at the presentation of TB-DILI, time to recovery of liver function, method of ATT re-challenge and outcome of re-challenge were documented. Results: 1016 charts were reviewed, and 53 individuals with TB-DILI (48 HIV-co-infected) were identified. Following discontinuation of ATT, the median time to alanine aminotransferase normalization was 28 days (interquartile range 13-43). Forty-two subjects were re-challenged (30 regimen re-challenges and 12 step-wise re-challenges). 5 (12%) cases of recurrent TB-DILI were noted. Recurrences were not associated with the method of re-challenge. Conclusion: Based on the data available, it appears that full ATT can be safely restarted in the majority of subjects with a recurrence of DILI occurring in about 12% of subjects. The method of re-challenge did not appear to impact on the risk of recurrence. Ideally, a prospective randomized trial is needed to determine the best method of re-challenge. PMID:26752869

  14. Prospects and challenges of induced pluripotent stem cells in equine health

    Directory of Open Access Journals (Sweden)

    Francesc Xavier eDonadeu

    2015-11-01

    Full Text Available Pluripotent stem cells (PSCs hold, through the capacity to differentiate into virtually all body cell types, unprecedented promise for human and animal medicine. PSCs are naturally found in the early embryo, and in rodents and humans they can be robustly harvested and grown in culture in the form of embryonic stem cells (ESCs, however the availability of ESCs from horses is limited. ES-like cells named induced pluripotent stem cells (iPSCs can be derived in vitro by transcription factor-mediated reprogramming of adult cells. As such, iPSCs can be generated in a patient-specific manner providing unmatched potential for tissue transplantation and in vitro disease modelling. In humans, clinical trials using iPSC-derived cells are already taking place and the use of in vitro iPSC models has identified novel mechanisms of disease and therapeutic targets. Although to a more limited extent, iPSCs have also been generated from horses, a species in which, after humans, these cells are likely to hold the greatest potential in regenerative medicine. Before a clinical use can be envisioned, however, significant challenges will need to be addressed in relation to the robust derivation, long-term culture, differentiation and clinical safety of equine iPSCs. Towards this objective, recent studies have reported significant improvement in culture conditions and the successful derivation for the first time of functional cell types from equine iPSCs. Given the wide range of exciting applications they could have, it is hoped future research will make the biomedical promise of iPSCs a reality not only for humans but also horses.

  15. Exertional-induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test

    Directory of Open Access Journals (Sweden)

    Mostafa Ghanei

    2015-01-01

    Full Text Available Introduction: Exertional-induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper- responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET and the response to methacholine challenge test (MCT in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO 2 (volume oxygen in patients with positive methacholine test (20.45 mL/kg/min was significantly lower than patients with negative MCT (28.69 mL/kg/min (P = 0.000. Respiratory rates per minute (RR and minute ventilation in the group with positive MCT (38.85 and 1.636 L were significantly lower than the group with negative methacholine test (46.78 and 2.114 L (P < 0.05. Also, the O 2 pulse rate in the group with negative methacholine test (116.27 mL/beat was significantly higher than the group with positive methacholine test (84.26 mL/beat (P < 0.001. Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic

  16. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    Science.gov (United States)

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  17. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    Science.gov (United States)

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release. PMID:10184318

  18. Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Lazo, Laura; Marcos, Ernesto; Martín, Jorge; Suzarte, Edith; Castro, Jorge; Romero, Yaremis; Guillén, Gerardo; Hermida, Lisset

    2016-02-01

    There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.

  19. Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis

    OpenAIRE

    Mna, Amira Ben; Souissi, Asmahene; Halouani, Slim; El Euch, Dalenda; Zahani, Alia; Kchir, Nidham; Zaraa, Ines; Mokni, Mourad

    2016-01-01

    Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate [1]. Since then, few cases of methotrexate-induced skin ulcers in patients...

  20. Increased response to oxidative stress challenge of nano-copper-induced apoptosis in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Pengjuan; Li, Zhigui; Zhang, Xiaochen; Yang, Zhuo, E-mail: zhuoyang@nankai.edu.cn [Nankai University, College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation (China)

    2014-12-15

    Recently, many studies reported that nanosized copper particles (nano-Cu, the particle size was around 15–30 nm), one of the nanometer materials, could induce nephrotoxicity. To detect the effect of nano-Cu on mesangial cells (MCs), and investigate the underlying mechanism, MCs were treated with different concentrations of nano-Cu (1, 10, and 30 μg/mL) to determine the oxidative stress and apoptotic changes. It was revealed that nano-Cu could induce a decreased viability in MCs together with a significant increase in the number of apoptotic cells by using cell counting kit-8 assay and flow cytometry. The apoptotic morphological changes induced by nano-Cu in MCs were demonstrated by Hochest33342 staining. Results showed that nano-Cu induced the nuclear fragmentation in MCs. Meanwhile, nano-Cu significantly increased the levels of reactive oxygen species, especially increased the levels of H{sub 2}O{sub 2}. It also decreased the activity of total SOD enzyme. In addition, when pre-treated with N-(2-mercaptopropionyl)-glycine, the cell apoptosis induced by nano-Cu was significantly decreased. These results suggest that oxidative stress plays an important role in the nano-Cu toxicity in MCs, which may be the main mechanism of nano-Cu-induced nephrotoxicity.

  1. An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice

    Science.gov (United States)

    Pasquevich, Karina A.; Ibañez, Andrés E.; Coria, Lorena M.; García Samartino, Clara; Estein, Silvia M.; Zwerdling, Astrid; Barrionuevo, Paula; Oliveira, Fernanda S.; Seither, Christine; Warzecha, Heribert; Oliveira, Sergio C.; Giambartolomei, Guillermo H.; Cassataro, Juliana

    2011-01-01

    As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4+ T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a

  2. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  3. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism.

    Science.gov (United States)

    Duivenvoorde, Loes P M; van Schothorst, Evert M; Derous, Davina; van der Stelt, Inge; Masania, Jinit; Rabbani, Naila; Thornalley, Paul J; Keijer, Jaap

    2015-06-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-invasive challenge test that measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. To test whether OxR can be used to reveal early diet-induced health effects, we exposed mice to a low-fat (LF) or high-fat (HF) diet for only 5 days. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and epididymal white adipose tissue (eWAT) and serum markers for e.g. protein glycation and oxidation. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR; however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. Cumulatively, OxR is a promising new method to test food products on potential beneficial effects for human health. PMID:24974902

  4. CHALLENGE WITH ATYPICAL ANTIPSYCHOTIC DRUGS IN RISPERIDONE INDUCED NEUROLEPTIC MALIGNANT SYNDROME: A CASE REPORT

    OpenAIRE

    Mendhekar, D.N.; Jiloha, R.C.; M M Mehndiratta; War, L.

    2002-01-01

    There are several reports available on neuroleptic malignant syndrome (NMS) associated with risperidone but when a more stringent criterion is applied there are only a few. Report on challenge and rechallenge with various atypical antipsychotic drugs in re-emergence of post NMS psychosis is scanty. Our aim of presenting this is to highlight the differential response of various atypical antipsychotic drugs in the treatment of post NMS psychosis. This paper reports a young male with mild mental...

  5. S-nitrosoglutathione supplementation to ovalbumin-sensitized and -challenged mice ameliorates methacholine-induced bronchoconstriction

    OpenAIRE

    Foster, Matthew W.; Yang, Zhonghui; Potts, Erin N.; W Michael Foster; Que, Loretta G.

    2011-01-01

    S-nitrosoglutathione (GSNO) is an endogenous bronchodilator present in micromolar concentrations in airway lining fluid. Airway GSNO levels decrease in severe respiratory failure and asthma, which is attributable to increased metabolism by GSNO reductase (GSNOR). Indeed, we have found that GSNOR expression and activity correlate inversely with lung S-nitrosothiol (SNO) content and airway hyperresponsiveness (AHR) to methacholine (MCh) challenge in humans with asthmatic phenotypes (Que LG, Yan...

  6. Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis.

    Science.gov (United States)

    Mna, Amira Ben; Souissi, Asmahene; Halouani, Slim; El Euch, Dalenda; Zahani, Alia; Kchir, Nidham; Zaraa, Ines; Mokni, Mourad

    2016-01-01

    Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate. Since then, few cases of methotrexate-induced skin ulcers in patients with mycosis fungoides have been published. We report an additional patient with erythrodermic mycosis fungoides who developed cutaneous ulcerations as a sole manifestation of methotrexate toxicity.

  7. Challenges in pulmonary fibrosis · 4: Smoking‐induced diffuse interstitial lung diseases

    OpenAIRE

    Wells, Athol U; Nicholson, Andrew G.; Hansell, David M

    2007-01-01

    Smoking‐induced diffuse interstitial lung processes include respiratory bronchiolitis, respiratory bronchiolitis‐associated interstitial lung disease (RBILD), desquamative interstitial pneumonia (DIP) and Langerhans' cell histiocytosis. The histological, radiological and clinical features of respiratory bronchiolitis, RBILD and DIP are reviewed, with particular reference to management issues; Langerhans' cell histiocytosis is covered elsewhere in this series of articles. Possible relationship...

  8. Adaptive response in zebrafish embryos induced using microbeam protons as priming dose and X-ray photons as challenging dose

    International Nuclear Information System (INIS)

    In the studies reported here, a high-linear-energy-transfer (high-LET)-radiation dose was used to induce adaptive response in zebrafish embryos in vivo. Microbeam protons were used to provide the priming dose and X-ray photons were employed to provide the challenging dose. The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to control and accurately quantify the number of protons at very low doses, viz., about 100 μGy. The embryos were dechorionated at 4 h post fertilization (hpf) and irradiated at 5 hpf by microbeam protons. For each embryo, ten irradiation points were arbitrarily chosen without overlapping with one another. To each irradiation point, 5, 10 or 20 protons each with an energy of 3.4 MeV were delivered. The embryos were returned back to the incubator until 10 hpf to further receive the challenging exposure, which was achieved using 2 Gy of X-ray irradiation, and then again returned to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed that 5 to 20 protons delivered at 10 points each on the embryos, or equivalently 110 to 430 μGy, could induce radioadaptive response in the zebrafish embryos in vivo. (author)

  9. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  10. Targeting the Microbiota to Address Diet-Induced Obesity: A Time Dependent Challenge

    OpenAIRE

    Clarke, Siobhan F.; Murphy, Eileen F.; O’Sullivan, Orla; Ross, R Paul; O’Toole, Paul W; Shanahan, Fergus; Cotter, Paul D.

    2013-01-01

    Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac+), with metabolic improvement ac...

  11. Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges

    OpenAIRE

    Payne, Heather; Adamson, Andrew; Bahl, Amit; Borwell, Jonathan; Dodds, David; Heath, Catherine; Huddart, Robert; McMenemin, Rhona; Patel, Prashant; Peters, John L; Thompson, Andrew

    2013-01-01

    To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. A systema...

  12. Predator-induced physiological responses in tadpoles challenged with herbicide pollution

    OpenAIRE

    Pablo BURRACO, Lidia Jiménez DUARTE, Ivan GOMEZ-MESTRE

    2013-01-01

    Predators induce plastic responses in multiple prey taxa, ranging from morphological to behavioral or physiological changes. In amphibians, tadpoles activate plastic responses to reduce predation risk by reducing their activity rate and altering their morphology, specifically tail depth and pigmentation. Furthermore, there is now evidence that tadpoles’ defenses are modified when predators combine with other stressful factors such as pollutants or competitors, but our knowledge on the physiol...

  13. Predator-induced physiological responses in tadpoles challenged with herbicide pollution

    OpenAIRE

    Burraco, Pablo; Jiménez-Duarte, Lidia; Gómez-Mestre, Iván

    2013-01-01

    Predators induce plastic responses in multiple prey taxa, ranging from morphological to behavioral or physiological changes. In amphibians, tadpoles activate plastic responses to reduce predation risk by reducing their activity rate and altering their morphology, specifically tail depth and pigmentation. Furthermore, there is now evidence that tadpoles' defenses are modified when predators combine with other stressful factors such as pollutants or competitors, but our knowledge on the physiol...

  14. Challenges in Modelling of Lightning-Induced Delamination; Effect of Temperature-Dependent Interfacial Properties

    Science.gov (United States)

    Naghipour, P.; Pineda, E. J.; Arnold, S.

    2014-01-01

    Lightning is a major cause of damage in laminated composite aerospace structures during flight. Due to the dielectric nature of Carbon fiber reinforced polymers (CFRPs), the high energy induced by lightning strike transforms into extreme, localized surface temperature accompanied with a high-pressure shockwave resulting in extensive damage. It is crucial to develop a numerical tool capable of predicting the damage induced from a lightning strike to supplement extremely expensive lightning experiments. Delamination is one of the most significant failure modes resulting from a lightning strike. It can be extended well beyond the visible damage zone, and requires sophisticated techniques and equipment to detect. A popular technique used to model delamination is the cohesive zone approach. Since the loading induced from a lightning strike event is assumed to consist of extreme localized heating, the cohesive zone formulation should additionally account for temperature effects. However, the sensitivity to this dependency remains unknown. Therefore, the major focus point of this work is to investigate the importance of this dependency via defining various temperature dependency profiles for the cohesive zone properties, and analyzing the corresponding delamination area. Thus, a detailed numerical model consisting of multidirectional composite plies with temperature-dependent cohesive elements in between is subjected to lightning (excessive amount of heat and pressure) and delamination/damage expansion is studied under specified conditions.

  15. Disulfiram-induced de novo convulsions without alcohol challenge: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    Ranganath Ramarao Kulkarni

    2015-01-01

    Full Text Available Seizure induction by disulfiram (DSF an adverse effect of therapeutic dosages of DSF is less understood. In our prospective case series of eight subjects with alcohol dependence a temporal, dose-dependent, and reversible epileptogenic potential due to DSF was noted. Mean duration of onset of first seizure was 2.13 ± 1.13 weeks after initiation of DSF therapy (125-500 mg/day with no other detectable causes of seizures. Presence of alcohol withdrawal seizures (50%, DSF-induced hypertension (HTN (37.5%, psychosis (12.5% were noted, that may suggest common neurobiological underpinnings like dopamine-beta-hydroxylase inhibition. Various types of DSF-induced generalized seizures (tonic-clonic, 62.5%; myoclonic and tonic-clonic, 25%; myoclonic, 12.5% were effectively managed by halving initial DSF dose (37.5% even after cessation of antiepileptics, or stopping DSF (37.5%. Presence of alcohol withdrawal seizures, DSF-induced HTN/psychosis during DSF therapy may be early risk factors for dose-dependent and reversible adverse effect of DSF therapy - seizure induction, emphasizing caution.

  16. Addressing the Numerical Challenges Associated With Laser-Induced Melt Convection

    Science.gov (United States)

    Weston, Brian; Nourgaliev, Robert; Delplanque, Jean Pierre; Anderson, Andy

    2015-11-01

    We present a new robust and efficient numerical framework for simulating multi-material flows with phase change. The work is motivated by laser-induced phase change applications, particularly the selective laser melting (SLM) process in additive manufacturing. Physics-based simulations of the laser melt dynamics requires a fully compressible framework, since incompressible flow solvers are inefficient for stiff systems, arising from laser-induced rapid phase change. In this study, the liquid and solid phases are both modeled with the compressible Navier-Stokes equations. The solid phase has an additional combined variable viscosity and drag force model to suppress the velocity in the solid. Our all-speed Navier-Stokes solver is based on a fully-implicit, high-order reconstructed Discontinuous Galerkin method. A Newton-Krylov based framework is used to solve the resulting set of non-linear equations, enabling robust simulations of the highly stiff compressible Navier-Stokes equations. We demonstrate the method's capabilities for phase change on several different melting and freezing configurations, including a three-dimensional laser-induced melt convection problem. Future model enhancements will incorporate material evaporation and rapid solidification.

  17. Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

    Directory of Open Access Journals (Sweden)

    Noam Cohen

    Full Text Available Mice are exceedingly sensitive to intra-peritoneal (IP challenge with some virulent pneumococci (LD50 = 1 bacterium. To investigate how peripheral contact with bacterial capsular polysaccharide (PS antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1 The PS co-localized with MHC molecules on the BMDC surface; 2 PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3 Type-specific resistance to lethal IP challenge was manifested only after day 5; 4 Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5 Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6 Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

  18. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  19. Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

    Institute of Scientific and Technical Information of China (English)

    Raúl J Andrade; Mercedes Robles; Alejandra Fernández-Casta(n)er; Susana López-Ortega; M Carmen López-Vega; M Isabel Lucena

    2007-01-01

    Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and postcommercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice.To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be finetuned as further information is collected.

  20. Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges.

    Science.gov (United States)

    Payne, Heather; Adamson, Andrew; Bahl, Amit; Borwell, Jonathan; Dodds, David; Heath, Catherine; Huddart, Robert; McMenemin, Rhona; Patel, Prashant; Peters, John L; Thompson, Andrew

    2013-11-01

    • To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. • Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. • A systematic literature review was undertaken to evaluate the evidence for preventative measures and treatment options in the management of cancer treatment-induced HC. • There is a wide range of reported incidence due to several factors including variability in study design and quality, the type of causal agent, the grading of bleeding, and discrepancies in definition criteria. • The most frequently reported causal factors are radiotherapy to the pelvic area, where HC has been reported in up to 20% of patients, and treatment with cyclophosphamide and bacillus Calmette-Guérin, where the incidence has been reported as up to 30%. • Mesna (2-mercaptoethane sodium sulphonate), hyperhydration and bladder irrigation have been the most frequently used prophylactic measures to prevent treatment-related cystitis, but are not always effective. • Cranberry juice is widely cited as a preventative measure and sodium pentosanpolysulphate as a treatment, although the evidence for both is very limited. • The best evidence exists for intravesical hyaluronic acid as an effective preventative and active treatment, and for hyperbaric oxygen as an equally effective treatment option. • The lack of robust data and variability in treatment strategies used highlights the need for further research, as well as best practice guidance and consensus on the management of HC. PMID:24000900

  1. Vaccination with Enzymatically Cleaved GPI-Anchored Proteins from Schistosoma mansoni Induces Protection against Challenge Infection

    Directory of Open Access Journals (Sweden)

    Vicente P. Martins

    2012-01-01

    Full Text Available The flatworm Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease that occurs throughout the developing world. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control schistosomiasis is through immunization with an antischistosomiasis vaccine combined with drug treatment. In the search for potential vaccine candidates, numerous tegument antigens have been assessed. As the major interface between parasite and mammalian host, the tegument plays crucial roles in the establishment and further course of schistosomiasis. Herein, we evaluated the potential of a GPI fraction, containing representative molecules located on the outer surface of adult worms, as vaccine candidate. Immunization of mice with GPI-anchored proteins induced a mixed Th1/Th2 type of immune response with production of IFN-γ and TNF-α, and low levels of IL-5 into the supernatant of splenocyte cultures. The protection engendered by this vaccination protocol was confirmed by 42% reduction in worm burden, 45% reduction in eggs per gram of hepatic tissue, 29% reduction in the number of granulomas per area, and 53% reduction in the granuloma fibrosis. Taken together, the data herein support the potential of surface-exposed GPI-anchored antigens from the S. mansoni tegument as vaccine candidate.

  2. Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

    Directory of Open Access Journals (Sweden)

    Siobhan F Clarke

    Full Text Available Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac(+, with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac(+ treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac(- administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.

  3. Induced pluripotent stem cell (iPS) technology: promises and challenges

    Institute of Scientific and Technical Information of China (English)

    MIGUELA Esteban; GAN Yi; QIN DaJiang; PEI DuanQing

    2009-01-01

    In 2006,an article published in Cell by Shinya Yamanaka took by surprise the stem cell research community.By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells,the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state.These cells,baptized iPS (induced pluripotent stem) cells,were immediately recognized as a ground-breaking discovery.Subsequently,the same authors and other groups reported a similar achievement with human fibroblasts.Two years later,the number of top quality papers on iPS is astonishing,and interest in the scientific community has risen to a fever pitch.But although iPS has the potential to revolutionize Regenerative Medicine,important questions still remain unanswered.Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS,and trying to improve the technique to make it suitable for the clinic.In this review article we briefly discuss the past,present and future of iPS,with emphasis on urgent issues to be solved.

  4. Recent Advances in NSAIDs-Induced Enteropathy Therapeutics: New Options, New Challenges

    Directory of Open Access Journals (Sweden)

    Yun Jeong Lim

    2013-01-01

    Full Text Available The injurious effects of NSAIDs on the small intestine were not fully appreciated until the widespread use of capsule endoscopy. It is estimated that over two-thirds of regular NSAID users develop injury in the small intestinal injuries and that these injuries are more common than gastroduodenal mucosal injuries. Recently, chronic low-dose aspirin consumption was found to be associated with injury to the lower gut and to be a significant contributing factor in small bowel ulceration, hemorrhage, and strictures. The ability of aspirin and NSAIDs to inhibit the activities of cyclooxygenase (COX contributes to the cytotoxicity of these drugs in the gastrointestinal tract. However, many studies found that, in the small intestine, COX-independent mechanisms are the main contributors to NSAID cytotoxicity. Bile and Gram-negative bacteria are important factors in the pathogenesis of NSAID enteropathy. Here, we focus on a promising strategy to prevent NSAID-induced small intestine injury. Selective COX-2 inhibitors, prostaglandin derivatives, mucoprotective drugs, phosphatidylcholine-NSAIDs, and probiotics have potential protective effects on NSAID enteropathy.

  5. rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

    Science.gov (United States)

    Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

    2014-09-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.

  6. Predator-induced physiological responses in tadpoles challenged with herbicide pollution

    Institute of Scientific and Technical Information of China (English)

    Pablo BURRACO; Lidia Jiménez DUARTE; Ivan GOMEZ-MESTRE

    2013-01-01

    Predators induce plastic responses in multiple prey taxa,ranging from morphological to behavioral or physiological changes.In amphibians,tadpoles activate plastic responses to reduce predation risk by reducing their activity rate and altering their morphology,specifically tail depth and pigmentation.Furthermore,there is now evidence that tadpoles' defenses are modified when predators combine with other stressful factors such as pollutants or competitors,but our knowledge on the physiological responses underlying these responses is still scarce.Here we study physiological responses in Pelobates cultripes tadpoles exposed to a natural predator (larvae of the aquatic beetle Dytiscus circumflexus),non-lethal concentrations of herbicide (glyphosate,0.5 mg/L and 1.0 mg/L) or both factors combined.We measured corticosterone levels,standard metabolic rate,oxidative damage (TBARS) and activity of antioxidant enzymes,and immune response (via leukocyte count).Tadpoles reduced their corticosterone concentration by ca.24% in the presence of predator cues,whereas corticosterone did not change in the presence of glyphosate.Two enzymes involved in antioxidant response also decreased in the presence of predators (14.7% and 13.2% respectively) but not to glyphosate.Herbicide,however,increased the number of neutrophils and reduced that of lymphocytes,and had an interaction effect with predator presence.Standard metabolic rate did not vary across treatments in our experiment.Thus we show a marked physiological response to the presence of predators but little evidence for interaction between predators and low levels of herbicide.Multiple assessment of the physiological state of animals is important to understand the basis and consequences of phenotypic plasticity.

  7. Predator-induced physiological responses in tadpoles challenged with herbicide pollution

    Directory of Open Access Journals (Sweden)

    Pablo BURRACO, Lidia Jiménez DUARTE, Ivan GOMEZ-MESTRE

    2013-08-01

    Full Text Available Predators induce plastic responses in multiple prey taxa, ranging from morphological to behavioral or physiological changes. In amphibians, tadpoles activate plastic responses to reduce predation risk by reducing their activity rate and altering their morphology, specifically tail depth and pigmentation. Furthermore, there is now evidence that tadpoles’ defenses are modified when predators combine with other stressful factors such as pollutants or competitors, but our knowledge on the physiological responses underlying these responses is still scarce. Here we study physiological responses in Pelobates cultripes tadpoles exposed to a natural predator (larvae of the aquatic beetle Dytiscus circumflexus, non-lethal concentrations of herbicide (glyphosate, 0.5 mg/L and 1.0 mg/L or both factors combined. We measured corticosterone levels, standard metabolic rate, oxidative damage (TBARS and activity of antioxidant enzymes, and immune response (via leukocyte count. Tadpoles reduced their corticosterone concentration by ca. 24% in the presence of predator cues, whereas corticosterone did not change in the presence of glyphosate. Two enzymes involved in antioxidant response also decreased in the presence of predators (14.7% and 13.2% respectively but not to glyphosate. Herbicide, however, increased the number of neutrophils and reduced that of lymphocytes, and had an interaction effect with predator presence. Standard metabolic rate did not vary across treatments in our experiment. Thus we show a marked physiological response to the presence of predators but little evidence for interaction between predators and low levels of herbicide. Multiple assessment of the physiological state of animals is important to understand the basis and consequences of phenotypic plasticity [Current Zoology 59 (4: 475–484, 2013].

  8. Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk.

    Science.gov (United States)

    Raschi, Emanuel; De Ponti, Fabrizio

    2015-07-01

    Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities. PMID:26167249

  9. Progress and Future Challenges of Human Induced Pluripotents Stem Cell in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2011-08-01

    Full Text Available BACKGROUND: Less than a decade ago the prospect for reprogramming the human somatic cell looked bleak at best. It seemed that the only methods at our disposal for the generation of human isogenic pluripotent cells would have to involve somatic cell nuclear transfer (SCNT. Shinya Yamanaka in August 2006 in his publication (Cell promised to change everything by showing that it was apparently very simple to revert the phenotype of a differentiated cell to a pluripotent one by overexpressing four transcription factors in murine fibroblasts. CONTENT: Mouse and human somatic cells can be genetically reprogrammed into induced pluripotent stem cells (iPSCs by the expression of a defined set of factors (Oct4, Sox2, c-Myc, and Klf4, as well as Nanog and LIN28. iPSCs could be generated from mouse and human fibroblasts as well as from mouse liver, stomach, pancreatic, neural stem cells, and keratinocytes. Similarity of iPSCs and embryonic stem cells (ESCs has been demonstrated in their morphology, global expression profiles, epigenetic status, as well as in vitro and in vivo differentiation potential for both mouse and human cells. Many techniques for human iPSCs (hiPSCs derivation have been developed in recent years, utilizing different starting cell types, vector delivery systems, and culture conditions. A refined or perfected combination of these techniques might prove to be the key to generating clinically applicable hiPSCs. SUMMARY: iPSCs are a revolutionary tool for generating in vitro models of human diseases and may help us to understand the molecular basis of epigenetic reprogramming. Progress of the last four years has been truly amazing, almost verging on science fiction, but if we can learn to produce such cells cheaply and easily, and control their differentiation, our efforts to understand and fight disease will become more accessible, controllable and tailored. Ability to safely and efficiently derive hiPSCs may be of decisive importance to

  10. Effect of smoking on the levels of TNF-α and IFN-g in sera and BALF in patients with chronic obstructive pulmonary disease%吸烟对慢性阻塞性肺疾病患者血清及肺泡灌洗液中肿瘤坏死因子-α及干扰素-γ的影响

    Institute of Scientific and Technical Information of China (English)

    张念; 徐清; 陈菁; 杨硕; 刘梦琳; 聂红; 孙洁民

    2012-01-01

    Objective To investigate the effects of smoking on the levels of TNF-a and IFN-g in sera and BALF in patients with chronic obstructive pulmonary disease (COPD). Methods Patients enrolled were divided into 4 groups; normal control group, non-smoking COPD group, smoking COPD group, and smoking cessation COPD group. Levels of TNF-a and IFN-g in sera and BALF in all the patients were determined. Results Levels of TNF-a and IFN-g in sera and BALF in patients with COPD in acute and stable periods were higher than those in normal control group (P < 0.05). Levels of TNF-a and IFN-g in BALF in acute and stable periods in smoking COPD group were significantly higher than those in non-smoking COPD group and smoking cessation COPD group (P < 0.05). Conclusions Patients with COPD present enhanced systemic and airway inflammation mediated by TNF-a and IFN-g in both acute and stable phases. Smoking COPD patients present significantly enhanced airway inflammation, which seems be lowered after smoking cessation.%目的:评价吸烟对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者急性期、稳定期血清及肺泡灌洗液中肿瘤坏死因子-α(TNF-α)及干扰素-γ(IFN-γ)的影响.方法:分别测定正常对照组、非吸烟COPD组、持续吸烟COPD组及戒烟COPD组患者急性期、稳定期血清及肺泡灌洗液中TNF-α及IFN-γ的水平,并对各组血清及肺泡灌洗液中TNF-α及IFN-γ水平分别进行比较.结果:COPD患者无论在急性期还是稳定期,肺泡灌洗液中TNF-α水平较正常对照组高(P<0.05).其中,持续吸烟的COPD患者肺泡灌洗液中TNF-α水平较非吸烟COPD组及戒烟COPD组高(P<0.05).急性期及稳定期COPD患者血清中TNF-α水平较正常组高(P<0.05).急性期及稳定期COPD患者血清及肺泡灌洗液中IFN-γ水平均较正常组高(P<0.05).其中,持续吸烟的COPD患者肺泡灌洗液中IFN-γ水平较非吸烟COPD及戒烟COPD患者均高(P<0.05).结论:COPD

  11. Concentrations of plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in induced sputum of asthma patients after allergen challenge.

    Directory of Open Access Journals (Sweden)

    Marcin Moniuszko

    2011-04-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 are involved in tiisue remodeling and repair processes associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challenge on concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. Thirty HDM-AAs and ten healthy persons (HCswere recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoides pteronyssinus (Dp and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputum was induced 24 hours before (T0 and 24 hours (T24 after the challenge. Concentration of uPA and PAI-1 in induced sputum were determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151 Âą 96 pg/ml and PAI-1 (4341 Âą 1262 pg/ml concentrations were higher than in HC (18.8 Âą 6.7 pg/ml; p=0.0002 and 596 Âą 180 pg/ml; p<0.0001; for uPA and PAI-1 respectively. After allergen challenge further increase in sputum uPA (187 Âą 144 pg/ml; p=0.03 and PAI-1 (6252 Âą 2323 pg/ml; p<0.0001 concentrations were observed. Moreover, in Dp challenged, but not in saline challenged HDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters were found in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways. Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodeling and play an important role in the development of bronchial hyperreactivity.

  12. Differential RNAi responses of Nicotiana benthamiana individuals transformed with a hairpin-inducing construct during Plum pox virus challenge.

    Science.gov (United States)

    Montes, Christian; Castro, Álvaro; Barba, Paola; Rubio, Julia; Sánchez, Evelyn; Carvajal, Denisse; Aguirre, Carlos; Tapia, Eduardo; DelÍ Orto, Paola; Decroocq, Veronique; Prieto, Humberto

    2014-10-01

    Gene silencing and large-scale small RNA analysis can be used to develop RNA interference (RNAi)-based resistance strategies for Plum pox virus (PPV), a high impact disease of Prunus spp. In this study, a pPPViRNA hairpin-inducing vector harboring two silencing motif-rich regions of the PPV coat protein (CP) gene was evaluated in transgenic Nicotiana benthamiana (NB) plants. Wild-type NB plants infected with a chimeric PPV virus (PPV::GFP) exhibited affected leaves with mosaic chlorosis congruent to GFP fluorescence at 21 day post-inoculation; transgenic lines depicted a range of phenotypes from fully resistant to susceptible. ELISA values and GFP fluorescence intensities were used to select transgenic-resistant (TG-R) and transgenic-susceptible (TG-S) lines for further characterization of small interfering RNAs (siRNAs) by large-scale small RNA sequencing. In infected TG-S and untransformed (WT) plants, the observed siRNAs were nearly exclusively 21- and 22-nt siRNAs that targeted the whole PPV::GFP genome; 24-nt siRNAs were absent in these individuals. Challenged TG-R plants accumulated a full set of 21- to 24-nt siRNAs that were primarily associated with the selected motif-rich regions, indicating that a trans-acting siRNAs process prevented viral multiplication. BLAST analysis identified 13 common siRNA clusters targeting the CP gene. 21-nt siRNA sequences were associated with the 22-nt siRNAs and the scarce 23- and 24-nt molecules in TG-S plants and with most of the observed 22-, 23-, and 24-nt siRNAs in TG-R individuals. These results validate the use of a multi-hot spot silencing vector against PPV and elucidate the molecules by which hairpin-inducing vectors initiate RNAi in vivo. PMID:24964777

  13. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

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    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  14. Concentrations of plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in induced sputum of asthma patients after allergen challenge

    Directory of Open Access Journals (Sweden)

    Krzysztof Kowal,

    2010-04-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 are involved in tiisue remodeling and repairprocesses associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challengeon concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. ThirtyHDM-AAs and ten healthy persons (HCswere recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoidespteronyssinus (Dp and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputumwas induced 24 hours before (T0 and 24 hours (T24 after the challenge. Concentration of uPA and PAI-1 in induced sputumwere determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151±96 pg/ml and PAI-1(4341±1262 pg/ml concentrations were higher than in HC (18.8±6.7 pg/ml; p=0.0002 and 596±180 pg/ml; p<0.0001; foruPA and PAI-1 respectively. After allergen challenge further increase in sputum uPA (187±144 pg/ml; p=0.03 and PAI-1(6252±2323 pg/ml; p<0.0001 concentrations were observed. Moreover, in Dp challenged, but not in saline challengedHDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters werefound in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways.Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodelingand play an important role in the development of bronchial hyperreactivity.

  15. Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response.

    Science.gov (United States)

    Uzonna, Jude E; Späth, Gerald F; Beverley, Stephen M; Scott, Phillip

    2004-03-15

    Long-term immunity to Leishmania may require the continued presence of parasites, but previous attempts to create attenuated parasites that persist without causing disease have had limited success. Since Leishmania major mutants that lack lipophosphoglycan and other secreted phosphoglycans, termed lpg2-, persist indefinitely in infected mice without inducing any disease, we tested their ability to provide protection to virulent L. major challenge. In response to leishmanial Ag stimulation, cells from lpg2--infected mice produced minimal levels of IL-4 and IL-10, as well as very low levels of IFN-gamma. Nevertheless, when BALB/c mice infected with lpg2- parasites were challenged with virulent L. major they were protected from disease. Thus, these findings report on attenuated parasites that may be used to induce long-term protection against leishmaniasis and indicate that the immunity induced can be maintained in the absence of a strong Th1 response. PMID:15004184

  16. Initiating rain water harvest technology for climate change induced drought resilient agriculture: scopes and challenges in Bangladesh

    Directory of Open Access Journals (Sweden)

    Hasan Muhammad Abdullah

    2015-12-01

    Full Text Available Bangladesh is primarily an agrarian economy. Agriculture is the single largest producing sector of the economy since it comprises about 18.6% of the country's GDP and employs around 45% of the total labor force. The performance of this sector has an overwhelming impact on major macroeconomic indicators like employment generation, poverty alleviation, human resource development and food security. The agriculture sector is extremely vulnerable to disaster and climate induced risks. Climate change is anticipated to aggravate the frequency and intensity of extreme weather events in Bangladesh. Drought is one of the major setbacks for the agriculture and its development. Therefore, disaster and climatic risk, especially drought management in agriculture is a major challenge for Bangladesh in achieving sustainable agricultural development. There are some regions in Bangladesh where every steps of agriculture from field preparation to ripening of crops dependents on rainfall. Consequently, drought affects annually 2.5 million ha in kharif (wet season and 1.2 million ha in dry season. Water is a natural resource with spatial scarcity and availability. Additionally, Cross-country anthropogenic activities caused a severe negative impact on water resources and eco-systems of Bangladesh in the recent years. The rivers and cannels dry up during the dry season and make the people completely dependent on groundwater (Abdullah, 2015. Accordingly the contribution of groundwater as a source of irrigation has increased and surface water has declined. It is now inevitable to look for alternate water source for agriculture. Water harvest technologies (WHTs can play an important role in this regard. WHTs can provide an additional source of water for crop production at the most critical stages of the growing season, thereby increasing yields and food security. The study is consists of drought scenario analysis, GIS based drought mapping and systematic literature

  17. A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers.

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    Rachel A Gibson

    Full Text Available BACKGROUND: Transient receptor potential vanilloid type 1 (TRPV1 is a non-selective cation channel widely expressed in skin tissues, and peripheral sensory nerve fibres. Activation of TRPV1 releases neuropeptides; the resulting neurogenic inflammation is believed to contribute to the development of pruritus. A TRPV1 antagonist has the potential to perform as an anti-pruritic agent. SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against cloned TRPV1 human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies. OBJECTIVES: To select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm engagement of the TRPV1 antagonistic action of SB705498 and assess whether the dose selected has an effect on itch induced by two challenge agents. METHODS: A clinical study was conducted in 16 healthy volunteers to assess the effects of 3 doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB705498 had an effect on challenge agent induced itch. RESULTS: Following capsaicin challenge the greatest average reduction in area of flare was seen for the 3% formulation. This dose was selected for further investigation. Itch intensity induced by two challenge agents (cowhage and histamine was assessed on the Computerised Visual Analogue Scale. The difference in average itch intensity (Weighted Mean Over 15 Mins between the 3% dose of SB705498 and placebo for the cowhage challenge was -0.64, whilst the histamine challenge showed on average a -4.65 point change. CONCLUSIONS: The 3% topical formulation of SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. SB705498 is unlikely to be of symptomatic

  18. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism

    NARCIS (Netherlands)

    Duivenvoorde, L.P.M.; Schothorst, van E.M.; Derous, D.; Stelt, van der I.; Masania, J.; Rabbani, N.; Thornalley, P.J.; Keijer, J.

    2015-01-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-in

  19. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  20. A DNA vaccine directed against a rainbow trout rhabdovirus induces early protection against a nodavirus challenge in turbot

    DEFF Research Database (Denmark)

    Sommerset, I.; Lorenzen, Ellen; Lorenzen, Niels;

    2003-01-01

    encoding the capsid protein of AHNV revealed no protective properties against the nodavirus challenge. Histological examination of muscle tissue sections from the vaccine injection site showed that the DNA vaccine against VHSV triggered a pronounced inflammatory response in turbot similar to what has...

  1. Immersion exposure of rainbow trout (Oncorhynchus mykiss) fry to wildtype Flavobacterium psychrophilum induces no mortality, but protects against later intraperitoneal challenge

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Brudeseth, B.E.; Wiklund, T.;

    2010-01-01

    .e. bathing in high titres of non-attenuated isolates of F. psychrophilum, was able to induce immunity to a subsequent ip challenge. Immersion in live bacteria for 30 or 50 min caused no mortality and protected a major fraction of the fry against challenges 26 and 47 days later with RPS values of 88.2 and 60......Flavobacterium psychrophilum, the causative agent of RTFS or rainbow trout fry syndrome, causes high mortality among hatchery reared rainbow trout (Oncorhynchus mykiss) fry in Europe and the USA. Despite several attempts, no efficient vaccines have yet been developed, the main obstacle being that...... the fry have to be vaccinated very early, i.e. around 0.2–0.5 g, where RTFS usually starts to give problems in the fish farms. Consequently, only oral or bath vaccines are relevant. Immersion of fry in inactivated or attenuated bacteria has resulted in RPS values of less than 50%. However, the results...

  2. Brucella suis S2, brucella melitensis Rev. 1 and Brucella abortus S19 living vaccines: residual virulence and immunity induced against three Brucella species challenge strains in mice.

    Science.gov (United States)

    Bosseray, N; Plommet, M

    1990-10-01

    Live attenuated Brucella suis S2 vaccine was compared to living vaccines B. abortus S19 and B. melitensis Rev. 1 in mice. Residual virulence was estimated by ability to multiply and persist in spleen and lymph nodes. Immunogenicity was estimated by spleen counts of control and vaccinated mice challenged either with the reference B. abortus 544 strain or with virulent B. melitensis H38 and B. suis 1330 strains. S2 vaccine had lower residual virulence; expressed as 50% recovery time, persistence was 4.3 weeks, compared to 7.1 and 9.0 weeks for S19 and Rev. 1 vaccines. Immunity induced by the three vaccines was similar 45 days after vaccination. At 150 days, immunity by S19 and Rev.1 was still similar against the three challenge strains. In contrast, immunity induced by S2 had declined against the B. melitensis strain. Thus, a recall vaccination may be required for vaccination of sheep to confer a long-lasting immunity. PMID:2123586

  3. Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide.

    Science.gov (United States)

    Cubillos, Carolina; de la Torre, Beatriz G; Jakab, Annamaria; Clementi, Giorgia; Borrás, Eva; Bárcena, Juan; Andreu, David; Sobrino, Francisco; Blanco, Esther

    2008-07-01

    The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptide-immunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

  4. Challenges in the development of an immunochromatographic interferon-gamma test for diagnosis of pleural tuberculosis.

    Directory of Open Access Journals (Sweden)

    Claudia M Denkinger

    Full Text Available Existing diagnostic tests for pleural tuberculosis (TB have inadequate accuracy and/or turnaround time. Interferon-gamma (IFNg has been identified in many studies as a biomarker for pleural TB. Our objective was to develop a lateral flow, immunochromatographic test (ICT based on this biomarker and to evaluate the test in a clinical cohort. Because IFNg is commonly present in non-TB pleural effusions in low amounts, a diagnostic IFNg-threshold was first defined with an enzyme-linked immunosorbent assay (ELISA for IFNg in samples from 38 patients with a confirmed clinical diagnosis (cut-off of 300 pg/ml; 94% sensitivity and 93% specificity. The ICT was then designed; however, its achievable limit of detection (5000 pg/ml was over 10-fold higher than that of the ELISA. After several iterations in development, the prototype ICT assay for IFNg had a sensitivity of 69% (95% confidence interval (CI: 50-83 and a specificity of 94% (95% CI: 81-99% compared to ELISA on frozen samples. Evaluation of the prototype in a prospective clinical cohort (72 patients on fresh pleural fluid samples, in comparison to a composite reference standard (including histopathological and microbiologic test results, showed that the prototype had 65% sensitivity (95% CI: 44-83 and 89% specificity (95% CI: 74-97. Discordant results were observed in 15% of samples if testing was repeated after one freezing and thawing step. Inter-rater variability was limited (3%; 1 out of 32. In conclusion, despite an iterative development and optimization process, the performance of the IFNg ICT remained lower than what could be expected from the published literature on IFNg as a biomarker in pleural fluid. Further improvements in the limit of detection of an ICT for IFNg, and possibly combination of IFNg with other biomarkers such as adenosine deaminase, are necessary for such a test to be of value in the evaluation of pleural tuberculosis.

  5. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

    Directory of Open Access Journals (Sweden)

    Franklin R Toapanta

    2016-06-01

    Full Text Available A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD- 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h and/or microbiological (S. Typhi bacteremia endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD- was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml of TD volunteers during disease days and increase in plasmablasts (PB during the recovery phase (>day 14. Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21 and gut homing (integrin α4β7 molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

  6. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease

    Science.gov (United States)

    Toapanta, Franklin R.; Bernal, Paula J.; Fresnay, Stephanie; Magder, Laurence S.; Darton, Thomas C.; Jones, Claire; Waddington, Claire S.; Blohmke, Christoph J.; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.; Sztein, Marcelo B.

    2016-01-01

    A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6–9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans. PMID:27300136

  7. Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs.

    Science.gov (United States)

    Wex, Eva; Bouyssou, Thierry

    2015-01-01

    Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.

  8. Bacillus subtilis PB6 improves intestinal health of broiler chickens challenged with Clostridium perfringens-induced necrotic enteritis.

    Science.gov (United States)

    Jayaraman, Sathishkumar; Thangavel, Gokila; Kurian, Hannah; Mani, Ravichandran; Mukkalil, Rajalekshmi; Chirakkal, Haridasan

    2013-02-01

    Necrotic enteritis (NE) is an enterotoxemic disease caused by Clostridium perfringens that results in significant economic losses, averaging damage of $0.05 per bird. The present study investigated the influence of a dietary supplement, Bacillus subtilis PB6, on performance, intestinal health, and gut integrity against C. perfringens-induced NE in broiler birds. Bacillus subtilis PB6 (ATCC-PTA 6737) is a natural strain isolated from healthy chicken gut that has been shown in in vitro to produce antimicrobial substances with broad activity against various strains of Campylobacter and Clostridium species. The animal study was conducted on broiler chickens (Cobb 400) for the period of 35 d using a completely randomized design. The experimental design included 3 treatments groups. Each treatment group contained 6 replicates, 3 male and 3 female, with 12 birds in each replicate. The 3 treatment groups were an uninfected control, an infected control, and an infected group supplemented with B. subtilis PB6 at 500 g/t of feed, containing 5 × 10(11) cfu/kg. Necrotic enteritis was induced in the broiler birds via oral inoculation of 30,000 oocysts of mixed strains of Eimeria species on d 14 followed by C. perfringens (10(8) cfu/mL) on d 19 through 21 of trial. The birds were analyzed for BW gain, mortality, feed conversion ratio (FCR), intestinal lesion score, intestinal C. perfringens counts, and villus histomorphometry. The infected control group showed markedly thickened mucosa, hemorrhages, intestinal lesions, and ballooning of intestine. The supplementation of B. subtilis PB6 reduced the FCR (P < 0.05) and intestinal C. perfringens counts significantly (P < 0.05) compared with the infected control group. It was also observed that B. subtilis PB6 improved villi length by 10.88 and 30.46% (P < 0.05) compared with uninfected and infected control groups, respectively. The group supplemented with B. subtilis PB6 significantly (P < 0.05) increased the villi length to crypt

  9. The bovine viral diarrhea virus E2 protein formulated with a novel adjuvant induces strong, balanced immune responses and provides protection from viral challenge in cattle.

    Science.gov (United States)

    Snider, Marlene; Garg, Ravendra; Brownlie, Robert; van den Hurk, Jan V; van Drunen Littel-van den Hurk, Sylvia

    2014-11-28

    Bovine viral diarrhea virus (BVDV) is still one of the most serious pathogens in cattle, meriting the development of improved vaccines. Recently, we developed a new adjuvant consisting of poly[di(sodium carboxylatoethylphenoxy)]-phosphazene (PCEP), either CpG ODN or poly(I:C), and an immune defense regulator (IDR) peptide. As this adjuvant has been shown to mediate the induction of robust, balanced immune responses, it was evaluated in an E2 subunit vaccine against BVDV in lambs and calves. The BVDV type 2 E2 protein was produced at high levels in a mammalian expression system and purified. When formulated with either CpG ODN or poly(I:C), together with IDR and PCEP, the E2 protein elicited high antibody titers and production of IFN-γ secreting cells in lambs. As the immune responses were stronger when poly(I:C) was used, the E2 protein with poly(I:C), IDR and PCEP was subsequently tested in cattle. Robust virus neutralizing antibodies as well as cell-mediated immune responses, including CD8(+) cytotoxic T cell (CTL) responses, were induced. The fact that CTL responses were demonstrated in calves vaccinated with an E2 protein subunit vaccine indicates that this adjuvant formulation promotes cross-presentation. Furthermore, upon challenge with a high dose of virulent BVDV-2, the vaccinated calves showed almost no temperature response, weight loss, leukopenia or virus replication, in contrast to the control animals, which had severe clinical disease. These data suggest that this E2 subunit formulation induces significant protection from BVDV-2 challenge, and thus is a promising BVDV vaccine candidate; in addition, the adjuvant platform has applications in bovine vaccines in general.

  10. A single immunization with HA DNA vaccine by electroporation induces early protection against H5N1 avian influenza virus challenge in mice

    Directory of Open Access Journals (Sweden)

    Chen Jianjun

    2009-02-01

    Full Text Available Abstract Background Developing vaccines for the prevention of human infection by H5N1 influenza viruses is an urgent task. DNA vaccines are a novel alternative to conventional vaccines and should contribute to the prophylaxis of emerging H5N1 virus. In this study, we assessed whether a single immunization with plasmid DNA expressing H5N1 hemagglutinin (HA could provide early protection against lethal challenge in a mouse model. Methods Mice were immunized once with HA DNA at 3, 5, 7 days before a lethal challenge. The survival rate, virus titer in the lungs and change of body weight were assayed to evaluate the protective abilities of the vaccine. To test the humoral immune response induced by HA DNA, serum samples were collected through the eye canthus of mice on various days after immunization and examined for specific antibodies by ELISA and an HI assay. Splenocytes were isolated after the immunization to determine the antigen-specific T-cell response by the ELISPOT assay. Results Challenge experiments revealed that a single immunization of H5N1 virus HA DNA is effective in early protection against lethal homologous virus. Immunological analysis showed that an antigen-specific antibody and T-cell response could be elicited in mice shortly after the immunization. The protective abilities were correlated with the amount of injected DNA and the length of time after vaccination. Conclusion A single immunization of 100 μg H5 HA DNA vaccine combined with electroporation was able to provide early protection in mice against homologous virus infection.

  11. A preliminary study of the effects of individual response to challenge tests and stress induced by humans on learning performance of weaned piglets (Sus scrofa).

    Science.gov (United States)

    Brajon, Sophie; Laforest, Jean-Paul; Schmitt, Océane; Devillers, Nicolas

    2016-08-01

    This study investigated whether individual behavioural characteristics of piglets and stress induced by experience with humans can influence learning performance. After weaning, piglets received a chronic experience with humans to modulate their emotional state: rough (ROU), gentle (GEN), or minimal (MIN) experience. Simultaneously, they were trained on a discrimination task. Afterward, their behaviour during challenge tests was assessed. The first learning step of the task involved associating a positive sound cue with a response (approach a trough) and success of piglets depended mostly on motivation to seek for reward. Although the experience with humans did not have direct effect, the degree of fear of handler, measured based on their reactivity to a human approach test, was related to motivation to seek rewards and learning speed of this first step in stressed ROU piglets, but not in MIN and GEN piglets. In contrast, the second learning step was more cognitively challenging, since it involved discrimination learning, including negative cues during which piglets had to learn to avoid the trough. Locomotion activity, measured during an open-field test, was associated with performance of the discrimination learning. To conclude, fearfulness towards humans and locomotion activity are linked with learning performance in relation to task complexity, highlighting the necessity to take into account these factors in animal research and management. PMID:27246576

  12. The challenges of green nanotechnology

    OpenAIRE

    Miguel de la Guardia

    2014-01-01

    Nanomaterials have great impacts on life sciences; however, these advanced materials may induce inadvertant consequences. Thus, this editorial will highlight the futuristic challenges ingreen nanotechnology.

  13. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  14. Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge

    International Nuclear Information System (INIS)

    Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX-HA-hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8+ T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.

  15. Vaccination with recombinant adenoviruses expressing the peste des petits ruminants virus F or H proteins overcomes viral immunosuppression and induces protective immunity against PPRV challenge in sheep.

    Directory of Open Access Journals (Sweden)

    José M Rojas

    Full Text Available Peste des petits ruminants (PPR is a highly contagious disease of small ruminants caused by the Morbillivirus peste des petits ruminants virus (PPRV. Two recombinant replication-defective human adenoviruses serotype 5 (Ad5 expressing either the highly immunogenic fusion protein (F or hemagglutinin protein (H from PPRV were used to vaccinate sheep by intramuscular inoculation. Both recombinant adenovirus vaccines elicited PPRV-specific B- and T-cell responses. Thus, neutralizing antibodies were detected in sera from immunized sheep. In addition, we detected a significant antigen specific T-cell response in vaccinated sheep against two different PPRV strains, indicating that the vaccine induced heterologous T cell responses. Importantly, no clinical signs and undetectable virus shedding were observed after virulent PPRV challenge in vaccinated sheep. These vaccines also overcame the T cell immunosuppression induced by PPRV in control animals. The results indicate that these adenovirus constructs could be a promising alternative to current vaccine strategies for the development of PPRV DIVA vaccines.

  16. Immunization with Individual Proteins of the Lrp/AsnC Family Induces Protection Against Brucella melitensis 16M Challenges in Mice

    Directory of Open Access Journals (Sweden)

    Xinhui eWang

    2015-10-01

    Full Text Available Brucellosis is one of the most common zoonoses worldwide. Subunit vaccines are promising for the prevention of human brucellosis. In our previous protective antigen screening studies, we identified a new protective antigen, BMEI0357, which belongs to the Lrp/asnC protein family, a conserved transcriptional regulator in bacteria that is absent in eukaryotes. In the present study, the Brucella genome annotation was screened and a total of 6 proteins were identified as members of the Lrp/AsnC family. Lrp/AsnC proteins have 2 domains that are conserved among the family members. However, sequence similarities between these proteins ranged from 9% to 50%, indicating high sequence heterogeneity. To test whether proteins of this family have similar characteristics, all 6 proteins were cloned and expressed in Escherichia coli. The recombinant proteins were purified and their protective efficacy was evaluated in BALB/c mice challenged with Brucella melitensis 16M. The results show that all 6 Lrp/AsnC proteins could induce a protective immune response against Brucella melitensis 16M. Antibodies against the Lrp/AsnC proteins were detected in the immunized mice. However, levels of antibodies against these proteins were relatively variable in human brucellosis sera. Taken together, our results show that these 6 proteins of the Lrp/AsnC family in Brucella could induce protective immune responses in mice.

  17. IFNB1/interferon-ß-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Ejlerskov, Patrick; Liu, Yawei;

    2013-01-01

    of survival pathways leading to treatment resistance. Defects in autophagy, a conserved cellular degradation pathway, are implicated in numerous cancer diseases. Autophagy is induced in response to cancer therapies and can contribute to treatment resistance. While the type II IFN, IFNG, which in many aspects...... differs significantly from type I IFNs, can induce autophagy, no such function for any type I IFN has been reported. We show here that IFNB1 induces autophagy in MCF-7, MDAMB231 and SKBR3 breast cancer cells by measuring the turnover of two autophagic markers, MAP1LC3B/LC3 and SQSTM1/p62. The induction...... of autophagy in MCF-7 cells occurred upstream of the negative regulator of autophagy MTORC1, and autophagosome formation was dependent on the known core autophagy molecule ATG7 and the IFNB1 signaling molecule STAT1. Using siRNA-mediated silencing of several core autophagy molecules and STAT1, we provide...

  18. Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.

    Directory of Open Access Journals (Sweden)

    Mark R Soboleski

    Full Text Available BACKGROUND: The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1 highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca influenza viruses from 1977 or recombinant adenoviruses (rAd expressing 1934 nucleoprotein (NP and consensus matrix 2 (M2 (NP+M2-rAd. Antibodies against the M2 ectodomain (M2e were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. CONCLUSION/SIGNIFICANCE: Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.

  19. Aspects of T Cell-Mediated Immunity Induced in Mice by a DNA Vaccine Based on the Dengue-NS1 Antigen after Challenge by the Intracerebral Route.

    Science.gov (United States)

    Oliveira, Edson R A; Gonçalves, Antônio J S; Costa, Simone M; Azevedo, Adriana S; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M A; Alves, Ada M B

    2016-01-01

    Dengue disease has emerged as a major public health issue across tropical and subtropical countries. Infections caused by dengue virus (DENV) can evolve to life-threatening forms, resulting in about 20,000 deaths every year worldwide. Several animal models have been described concerning pre-clinical stages in vaccine development against dengue, each of them presenting limitations and advantages. Among these models, a traditional approach is the inoculation of a mouse-brain adapted DENV variant in immunocompetent animals by the intracerebral (i.c.) route. Despite the historical usage and relevance of this model for vaccine testing, little is known about the mechanisms by which the protection is developed upon vaccination. To cover this topic, a DNA vaccine based on the DENV non-structural protein 1 (pcTPANS1) was considered and investigations were focused on the induced T cell-mediated immunity against i.c.-DENV infection. Immunophenotyping assays by flow cytometry revealed that immunization with pcTPANS1 promotes a sustained T cell activation in spleen of i.c.-infected mice. Moreover, we found that the downregulation of CD45RB on T cells, as an indicator of cell activation, correlated with absence of morbidity upon virus challenge. Adoptive transfer procedures supported by CFSE-labeled cell tracking showed that NS1-specific T cells induced by vaccination, proliferate and migrate to peripheral organs of infected mice, such as the liver. Additionally, in late stages of infection (from the 7th day onwards), vaccinated mice also presented reduced levels of circulating IFN-γ and IL-12p70 in comparison to non-vaccinated animals. In conclusion, this work presented new aspects about the T cell-mediated immunity concerning DNA vaccination with pcTPANS1 and the i.c. infection model. These insights can be explored in further studies of anti-dengue vaccine efficacy. PMID:27631083

  20. Transcutaneous immunization with toxin-coregulated pilin A induces protective immunity against Vibrio cholerae O1 El Tor challenge in mice.

    Science.gov (United States)

    Rollenhagen, Julianne E; Kalsy, Anuj; Cerda, Francisca; John, Manohar; Harris, Jason B; Larocque, Regina C; Qadri, Firdausi; Calderwood, Stephen B; Taylor, Ronald K; Ryan, Edward T

    2006-10-01

    Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], 50 mug) on days 0, 19, and 40. Mice immunized with TcpA alone did not develop anti-TcpA responses. Mice that received transcutaneously applied TcpA and CT developed prominent anti-TcpA immunoglobulin G (IgG) serum responses but minimal anti-TcpA IgA. Transcutaneous immunization with CT induced prominent IgG and IgA anti-CT serum responses. In an infant mouse model, offspring born to dams transcutaneously immunized either with TcpA and CT or with CT alone were challenged with 10(6) CFU (one 50% lethal dose) wild-type V. cholerae O1 El Tor strain N16961. At 48 h, mice born to females transcutaneously immunized with CT alone had 36% +/- 10% (mean +/- standard error of the mean) survival, while mice born to females transcutaneously immunized with TcpA and CT had 69% +/- 6% survival (P < 0.001). Our results suggest that transcutaneous immunization with TcpA and an immunoadjuvant induces protective anti-TcpA immune responses. Anti-TcpA responses may contribute to an optimal cholera vaccine.

  1. Aspects of T Cell-Mediated Immunity Induced in Mice by a DNA Vaccine Based on the Dengue-NS1 Antigen after Challenge by the Intracerebral Route

    Science.gov (United States)

    Oliveira, Edson R. A.; Gonçalves, Antônio J. S.; Costa, Simone M.; Azevedo, Adriana S.; Mantuano-Barradas, Marcio; Nogueira, Ana Cristina M. A.

    2016-01-01

    Dengue disease has emerged as a major public health issue across tropical and subtropical countries. Infections caused by dengue virus (DENV) can evolve to life-threatening forms, resulting in about 20,000 deaths every year worldwide. Several animal models have been described concerning pre-clinical stages in vaccine development against dengue, each of them presenting limitations and advantages. Among these models, a traditional approach is the inoculation of a mouse-brain adapted DENV variant in immunocompetent animals by the intracerebral (i.c.) route. Despite the historical usage and relevance of this model for vaccine testing, little is known about the mechanisms by which the protection is developed upon vaccination. To cover this topic, a DNA vaccine based on the DENV non-structural protein 1 (pcTPANS1) was considered and investigations were focused on the induced T cell-mediated immunity against i.c.-DENV infection. Immunophenotyping assays by flow cytometry revealed that immunization with pcTPANS1 promotes a sustained T cell activation in spleen of i.c.-infected mice. Moreover, we found that the downregulation of CD45RB on T cells, as an indicator of cell activation, correlated with absence of morbidity upon virus challenge. Adoptive transfer procedures supported by CFSE-labeled cell tracking showed that NS1-specific T cells induced by vaccination, proliferate and migrate to peripheral organs of infected mice, such as the liver. Additionally, in late stages of infection (from the 7th day onwards), vaccinated mice also presented reduced levels of circulating IFN-γ and IL-12p70 in comparison to non-vaccinated animals. In conclusion, this work presented new aspects about the T cell-mediated immunity concerning DNA vaccination with pcTPANS1 and the i.c. infection model. These insights can be explored in further studies of anti-dengue vaccine efficacy. PMID:27631083

  2. Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

    Science.gov (United States)

    Peters, S E; Paterson, G K; Bandularatne, E S D; Northen, H C; Pleasance, S; Willers, C; Wang, J; Foote, A K; Constantino-Casas, F; Scase, T J; Blacklaws, B A; Bryant, C E; Mastroeni, P; Charles, I G; Maskell, D J

    2010-01-01

    In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4(+) and CD8(+) T cells and B lymphocytes in the spleen and reduced infiltration by CD11b(+) cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

  3. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo.

    Science.gov (United States)

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M; Werling, Dirk

    2015-11-17

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a "proof of concept" vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage.

  4. Uncertain translation, uncertain benefit and uncertain risk: ethical challenges facing first-in-human trials of induced pluripotent stem (ips) cells.

    Science.gov (United States)

    Fung, Ronald K F; Kerridge, Ian H

    2013-02-01

    The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes.

  5. Featherweight Challenge

    Science.gov (United States)

    Love, Tyler S.; Ryan, Larry

    2012-01-01

    As science, technology education, and engineering programs suffer budget cuts, educators continue to seek cost-effective activities that engage students and reinforce standards. The featherweight challenge is a hands-on activity that challenges students to continually refine their design while not breaking the budget. This activity uses one of the…

  6. Prevention of tri-nitrobenzene of sulfonic acid-induced colitis in chicken by using extract of Aloe vera

    Directory of Open Access Journals (Sweden)

    Motamed Elsayed Mahmoud

    Full Text Available Aim: Aloe vera, species of succulent plant in the genus Aloe, has multiple clinical activities and used routinely to accelerate wound healing. The present study was designed to investigate the anti-inflammatory effect of Aloe vera extracts (AVE in vitro and in vivo. Materials and Methods: The effect of crude AVE on inducible nitric oxide production by LPS/IFNg-stimulated cultured macrophages was evaluated. The therapeutic effect of administering crude Aloe vera extracts (100 mg/kg b.w. on the development of tri-nitrobenzene of sulfonic acid (TNBS-induced colitis (40 mg/kg b. w. in chicken was also investigated. Chicken is a valuable model for this purpose because it showed preference to bitter taste of Aloe vera. Diverse clinical pictures of the colitis including weight loss, diarrhea and histopathological changes were evaluated. Results: Nitrite production by LPS/IFNg-stimulated macrophages was maximally reduced by adding of AVE (100 μg/ml. This result suggests a direct inhibitory effect of AVE on the inflammatory cells. Chicks treated orally with AVE showed improvement of the histological signs with no inflammatory cell infiltrates and reduction of myeloperoxidase (MPO activities when compared with colitis control group. AVE pretreatment ameliorated significantly the clinical and histopathological severity of the TNBS-induced colitis; decreased body weight loss and diarrhea and increased survival. Conclusion: It was concluded that oral administration of AVE represents a valuable therapeutic approach for the treatment of colitis in chicken. [Vet. World 2012; 5(8.000: 469-476

  7. The challenges of green nanotechnology

    Directory of Open Access Journals (Sweden)

    Miguel de la Guardia

    2014-03-01

    Full Text Available Nanomaterials have great impacts on life sciences; however,these advanced materials may induce inadvertant consequences.Thus, this editorial will highlight the futuristic challenges in green nanotechnology.

  8. Challenging Identities

    DEFF Research Database (Denmark)

    Keydar, Ceglar; Marin, Manuela; Janik, Allan;

    , cultural, and political practices. Notions of national identity and national politics are challenged by European integration, as well as by increasing demographic heterogeneity due to migration, and migrants experience conflicts of identification stemming from clashes between cultural heritage...

  9. Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide▿ †

    OpenAIRE

    Cubillos, Carolina; de la Torre, Beatriz G.; Jakab, Annamaria; Clementi, Giorgia; Borrás, Eva; Bárcena, Juan; Andreu, David; Sobrino, Francisco; Blanco, Esther

    2008-01-01

    The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its t...

  10. Sensitization to and Challenge with Gliadin Induce Pancreatitis and Extrapancreatic Inflammation in HLA-DQ8 Mice: An Animal Model of Type 1 Autoimmune Pancreatitis

    Science.gov (United States)

    Moon, Sung-Hoon; Kim, Jihun; Kim, Mi-Young; Park, Do Hyun; Song, Tae Jun; Kim, Sun A; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo; Kim, Myung-Hwan

    2016-01-01

    Background/Aims The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice. Methods Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation. Results Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadin-challenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs. Conclusions Gliadin-sensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation. PMID:27114422

  11. Logistical challenges

    Directory of Open Access Journals (Sweden)

    Steve Matthews

    2005-07-01

    Full Text Available The impact of the Asian tsunami was unprecedented and the logistical challenges of meeting the needs of those affected were enormous. Had the tsunami happened even five years ago, World Vision would not have been able to respond nearly as effectively as it did.

  12. Ethical Challenges

    Science.gov (United States)

    Morris, Michael

    2004-01-01

    All evaluators face the challenge of striving to adhere to the highest possible standards of ethical conduct. Translating the AEA's Guiding Principles and the Joint Committee's Program Evaluation Standards into everyday practice, however, can be a complex, uncertain, and frustrating endeavor. Moreover, acting in an ethical fashion can require…

  13. Archiving challenges

    OpenAIRE

    Ringersma, J.

    2010-01-01

    Teaching slides on: What is a digital archive? Parties involved in digital archiving Archiving challenges organization of data coherence and persistency access and safety Language archiving software Different users, different needs For: Saami Language Documentation and Revitalization. Winter school, Bodø, Norway

  14. CHALLENGES IN BRONCHIAL CHALLENGE TESTING

    NARCIS (Netherlands)

    Lexmond, A. J.; Hagedoorn, P.; Frijlink, H. W.; de Boer, A. H.

    2013-01-01

    Background: In the adenosine 5'-monophosphate (AMP) bronchial challenge test, AMP is usually administered according to dosing protocols developed for histamine/methacholine. It has never been thoroughly investigated whether these protocols are suitable for AMP as well. Methods: The setup of the two-

  15. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part...... of the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region....

  16. Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

    Directory of Open Access Journals (Sweden)

    Franklin R Toapanta

    2015-06-01

    Full Text Available A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD- 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h and/or microbiological (S. Typhi bacteremia endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-. Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD- were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h. Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.

  17. Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge

    Directory of Open Access Journals (Sweden)

    Bernard eArulanandam

    2011-12-01

    Full Text Available We have shown that immunization with soluble recombinant (r chlamydial protease-like activity factor (rCPAF and a T helper (Th 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia–induced pathological sequelae in the genital tract. In this study, we investigated the use of bone marrow derived dendritic cells (BMDCs pulsed ex vivo with rCPAF+CpG in an adoptive subcutaneous immunization for the ability to induce protective immunity against genital chlamydial infection. We found that BMDCs pulsed with rCPAF+CpG efficiently up-regulated the expression of activation markers CD86, CD80, CD40 and major histocompatibility complex class II (MHC II, and secreted interleukin-12, but not IL-10 and IL-4. Mice adoptively immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN- and enhanced IgG1 and IgG2a antibodies. Moreover, mice immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs exhibited significantly reduced genital Chlamydia shedding, accelerated resolution of infection, and reduced oviduct pathology when compared to infected mock-immunized animals. These results suggest that adoptive subcutaneous immunization with ex vivo rCPAF-pulsed BMDCs is an effective approach, comparable to that induced by UV-EB-BMDCs, for inducing robust anti-Chlamydia immunity.

  18. Immunostimulatory complexes containing Eimeria tenella antigens and low toxicity plant saponins induce antibody response and provide protection from challenge in broiler chickens.

    Science.gov (United States)

    Berezin, V E; Bogoyavlenskyi, A P; Khudiakova, S S; Alexuk, P G; Omirtaeva, E S; Zaitceva, I A; Tustikbaeva, G B; Barfield, R C; Fetterer, R H

    2010-01-20

    Immunostimulating complexes (ISCOMs) are unique multimolecular structures formed by encapsulating antigens, lipids and triterpene saponins and are one of the most successful antigen delivery systems for microbial antigens. In the current study, both the route of administration and the antigen concentration of ISCOMs, containing Eimeria tenella antigens and saponins from native plants, were evaluated in their ability to stimulate humoral immunity and to protect chickens against a challenge infection with E. tenella. Broiler chickens were immunized with ISCOM preparations containing E. tenella antigens and the purified saponins Gg6, Ah6 and Gp7 isolated from Glycyrrhiza glabra, Aesculus hippocastanum and Gipsophila paniculata, respectively. The effects of the route of administration, dose of antigen and type of saponin used for construction of ISCOMs were evaluated for ability to stimulate serum IgG and IgM and to protect chickens against a homologous challenge. A single intranasal immunization was the most effective route for administering ISCOMs although the in ovo route was also quite effective. Dose titration experiments demonstrated efficacy after single immunization with various ISCOM doses but maximum effects were observed when ISCOMs contain 5-10mug antigen. Immunization of birds by any of the three routes with E. tenella antigens alone or antigens mixed with alum hydroxide adjuvant resulted in lower serum antibody and reduced protection to challenge relative to immunization with ISCOMs. Overall the results of this study confirm that significant immunostimulation and protection to challenge are achieved by immunization of chickens with ISCOMs containing purified saponins and native E. tenella antigens and suggest that ISCOMs may be successfully used to develop a safe and effective vaccine for prevention of avian coccidiosis. PMID:19879050

  19. Transgenic Increase in n-3/n-6 Fatty Acid Ratio Protects Against Cognitive Deficits Induced by an Immune Challenge through Decrease of Neuroinflammation

    OpenAIRE

    Delpech, Jean-Christophe; Madore, Charlotte; Joffre, Corinne; Aubert, Agnès; Kang, Jing Xuan; Nadjar, Agnès; Layé, Sophie

    2014-01-01

    Polyunsaturated fatty acids (PUFAs) display immunomodulatory properties in the brain, n-3 PUFAs being able to reduce inflammation whereas n-6 PUFAs are more pro-inflammatory. It has been extensively demonstrated that exposure to a peripheral immune challenge leads to the production and release of inflammatory mediators in the brain in association with cognitive deficits. The question arises whether n-3 PUFA supplementation could downregulate the brain inflammatory response and subsequent cogn...

  20. Measuring Regional and District Variations in the Incidence of Pregnancy-induced Hypertension (PIH) in Ghana : Challenges, Opportunities and Implications for Maternal and Newborn Health Policy and Programs

    NARCIS (Netherlands)

    Antwi, Edward; Klipstein-Grobusch, Kerstin; Asare, Gloria Quansah; Koram, Kwadwo A; Grobbee, Diederick; Agyepong, Irene Akua

    2016-01-01

    OBJECTIVES: The objectives were to assess the quality of health management information system (HMIS) data needed for assessment of local area variation in pregnancy induced hypertension (PIH) incidence and to describe district and regional variations in PIH incidence. METHODS: A retrospective review

  1. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    NARCIS (Netherlands)

    van der Heijden, Roel A.; Bijzet, Johan; Meijers, Wouter C.; Yakala, Gopala K.; Kleemann, Robert; Nguyen, Tri Q.; de Boer, Rudolf A.; Schalkwijk, Casper G.; Hazenberg, Bouke P. C.; Tietge, Uwe J. F.; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complicat

  2. Data Challenges

    CERN Multimedia

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  3. Reduction of porcine circovirus type 2 (PCV2 viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge

    Directory of Open Access Journals (Sweden)

    Seo Hwi

    2012-10-01

    Full Text Available Abstract Background The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01, vaccinated non-challenged (T02, non-vaccinated challenged (T03, and non-vaccinated non-challenged (T04 animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge, the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b. Results A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA and interferon-γ-secreting cells (IFN-γ-SCs in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine. Conclusions The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.

  4. A Lactobacillus rhamnosus strain induces protection in different sites after Salmonella enterica subsp. enterica serovar Typhimurium challenge in gnotobiotic and conventional mice

    Directory of Open Access Journals (Sweden)

    A.H. Mendonça

    2014-04-01

    Full Text Available The ability of a Lactobacillus rhamnosus strain isolated from a healthy breast-fed human newborn to reduce the pathological consequences for the host due to an experimental oral infection with Salmonella enterica subsp. enterica serov. Typhimurium in vivo was determined using gnotobiotic and conventional mice. Conventional mice received 0.1mL probiotic milk (8.0 log colony-forming unit daily for 10 days before the oral pathogenic challenge (5.0 log colony-forming unit. Then probiotic treatment was continued until the end of the experiment. Probiotic treatment in germ-free mice consisted of a single dose of the probiotic milk at the beginning of the experiment and a challenge with S. Typhimurium 10 days later (3.0 log colony-forming unit. A protective effect was observed in both gnotobiotic and conventional animals in terms of histopathologic and morphometric data, but in different anatomical sites. This protection was observed in liver and intestines, respectively, for gnotobiotic and conventional mice. However, S. Typhimurium populations were similar in the feces of both treated and control gnotobiotic mice. We conclude that a protective effect of L. rhamnosus against experimental S. Typhimurium was observed. This protection was not due to the reduction of the population of pathogenic bacteria in the intestine.

  5. Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

    Directory of Open Access Journals (Sweden)

    Freek Cox

    Full Text Available There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV adjuvated with the saponin-based adjuvant Matrix-M (MM can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

  6. Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015.

    Science.gov (United States)

    Satyamitra, Merriline M; DiCarlo, Andrea L; Taliaferro, Lanyn

    2016-08-01

    After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. PMID:27387859

  7. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    Science.gov (United States)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  8. SPS Challenges

    CERN Document Server

    Chapochnikova, Elena

    2008-01-01

    In future the SPS should be able to transfer to the LHC the beam produced by a completely new pre-injector chain and required by the LHC for different upgrade scenarios. The issues related to this extremely challenging task are presented together with some possible ways of overcoming the problems that arise. Besides an increase in injection energy provided by PS2, these measures can include both an SPS vacuum chamber upgrade against the e-cloud and operation with larger longitudinal emittance for beam stability. As a result the power plant of the SPS RF system must be doubled. The SPS upgrade will also need the improvement or replacement of many other machine elements.

  9. A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.

    Science.gov (United States)

    Yendo, Anna Carolina A; de Costa, Fernanda; Cibulski, Samuel P; Teixeira, Thais F; Colling, Luana C; Mastrogiovanni, Mauricio; Soulé, Silvia; Roehe, Paulo M; Gosmann, Grace; Ferreira, Fernando A; Fett-Neto, Arthur G

    2016-04-29

    Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P ≤ 0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria. PMID:27032516

  10. Nasal immunization with mannan-decorated mucoadhesive HPMCP microspheres containing ApxIIA toxin induces protective immunity against challenge infection with Actinobacillus pleuropneumoiae in mice.

    Science.gov (United States)

    Li, Hui-Shan; Shin, Min-Kyoung; Singh, Bijay; Maharjan, Sushila; Park, Tae-Eun; Kang, Sang-Kee; Yoo, Han-Sang; Hong, Zhong-Shan; Cho, Chong-Su; Choi, Yun-Jaie

    2016-07-10

    The development of subunit mucosal vaccines requires an appropriate delivery system or an immune modulator such as an adjuvant to improve antigen immunogenicity. The nasal route for vaccine delivery by microparticles has attracted considerable interest, although challenges such as the rapid mucociliary clearance in the respiratory mucosa and the low immunogenicity of subunit vaccine still remain. Here, we aimed to develop mannan-decorated mucoadhesive thiolated hydroxypropylmethyl cellulose phthalate (HPMCP) microspheres (Man-THM) that contain ApxIIA subunit vaccine - an exotoxin fragment as a candidate for a subunit nasal vaccine against Actinobacillus pleuropneumoniae. For adjuvant activity, mucoadhesive thiolated HPMCP microspheres decorated with mannan could be targeted to the PRRs (pathogen recognition receptors) and mannose receptors (MR) of antigen presenting cells (APCs) in the respiratory immune system. The potential adjuvant ability of Man-THM for intranasal immunization was confirmed by in vitro and in vivo experiments. In a mechanistic study using APCs in vitro, it was found that Man-THM enhanced receptor-mediated endocytosis by stimulating the MR of APCs. In vivo, the nasal vaccination of ApxIIA-loaded Man-THM in mice resulted in higher levels of mucosal sIgA and serum IgG than mice in the ApxIIA and ApxIIA-loaded THM groups due to the specific recognition of the mannan in the Man-THM by the MRs of the APCs. Moreover, ApxIIA-containing Man-THM protected immunized mice when challenged with strains of A. pleuropneumoniae serotype 5. These results suggest that mucoadhesive Man-THM may be a promising candidate for a nasal vaccine delivery system to elicit systemic and mucosal immunity that can protect from pathogenic bacteria infection. PMID:27189136

  11. Scrapheap Challenge

    CERN Multimedia

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  12. CHALLENGES IN MAINTAINING EMOTION REGULATION IN A SLEEP AND ENERGY DEPRIVED STATE INDUCED BY THE 4800KM ULTRA-ENDURANCE BICYCLE RACE; THE RACE ACROSS AMERICA (RAAM

    Directory of Open Access Journals (Sweden)

    Ian M. Lahart

    2013-09-01

    Full Text Available Multiday ultra-endurance races present athletes with a significant number of physiological and psychological challenges. We examined emotions, the perceived functionality (optimal-dysfunctional of emotions, strategies to regulate emotions, sleep quality, and energy intake-expenditure in a four-man team participating in the Race Across AMerica (RAAM; a 4856km continuous cycle race. Cyclists reported experiencing an optimal emotional state for less than 50% of total competition, with emotional states differing significantly between each cyclist over time. Coupled with this emotional disturbance, each cyclist experienced progressively worsening sleep deprivation and daily negative energy balances throughout the RAAM. Cyclists managed less than one hour of continuous sleep per sleep episode, high sleep latency and high percentage moving time. Of note, actual sleep and sleep efficiency were better maintained during longer rest periods, highlighting the importance of a race strategy that seeks to optimise the balance between average cycling velocity and sleep time. Our data suggests that future RAAM cyclists and crew should: 1 identify beliefs on the perceived functionality of emotions in relation to best (functional-optimal and worst (dysfunctional performance as the starting point to intervention work; 2 create a plan for support sufficient sleep and recovery; 3 create nutritional strategies that maintain energy intake and thus reduce energy deficits; and 4 prepare for the deleterious effects of sleep deprivation so that they are able to appropriately respond to unexpected stressors and foster functional working interpersonal relationships

  13. Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar Typhimurium induce cross-reactive immunity and provide cross-protection against heterologous Salmonella challenge

    Science.gov (United States)

    Liu, Qiong; Liu, Qing; Yi, Jie; Liang, Kang; Hu, Bo; Zhang, Xiangmin; Curtiss, Roy; Kong, Qingke

    2016-01-01

    Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine. PMID:27698383

  14. Tachyzoites of Toxoplasma gondii irradiated with 255 Gy induces decrease of cysts and cerebral lesions in mice challenged with cysts of ME-49

    International Nuclear Information System (INIS)

    Toxoplasmosis can cause ocular lesions in normal individuals and several diseases in foetus, HIV infection and transplants. Toxoplasma gondii has a complex life cycle, involving cats, as the definitive host, and warm blood species, as intermediated hosts. The infection occurs by ingestion of food and water contaminated with infected cat faeces, contaminated milk and cheese or raw and undercook meat of the intermediated hosts. To date, there is no commercial vaccine of use in humans. In this work, tachyzoites of T. gondii RH strain were irradiated with 255 Gy and inoculated in C57Bl/6j mice (3 doses, biweekly), after mice were challenged with 1, 5, 10, 20 and 25 cysts of ME-49 by oral gavage. The lesions and cysts in the brain were analyzed in all mice, after 4-week post infection. The mortality was 20% in control mice (ME-49 cysts only) and not one in immunized mice. The number of cysts was high in the control group, but low in immunized 255 Gy mice (n<100). Immunized mice showed less cerebral pathology and necrosis foci. Ionizing radiation is an important tool in the study toxoplasmosis and vaccine development. (author)

  15. Attenuated Salmonella typhimurium delivering DNA vaccine encoding duck enteritis virus UL24 induced systemic and mucosal immune responses and conferred good protection against challenge

    Directory of Open Access Journals (Sweden)

    Yu Xia

    2012-07-01

    Full Text Available Abstract Orally delivered DNA vaccines against duck enteritis virus (DEV were developed using live attenuated Salmonella typhimurium (SL7207 as a carrier and Escherichia coli heat labile enterotoxin B subunit (LTB as a mucosal adjuvant. DNA vaccine plasmids pVAX-UL24 and pVAX-LTB-UL24 were constructed and transformed into attenuated Salmonella typhimurium SL7207 resulting SL7207 (pVAX-UL24 and SL7207 (pVAX-LTB-UL24 respectively. After ducklings were orally inoculated with SL7207 (pVAX-UL24 or SL7207 (pVAX-LTB-UL24, the anti-DEV mucosal and systemic immune responses were recorded. To identify the optimum dose that confers maximum protection, we used different doses of the candidate vaccine SL7207 (pVAX-LTB-UL24 during oral immunization. The strongest mucosal and systemic immune responses developed in the SL7207 (pVAX-LTB-UL24 (1011 CFU immunized group. Accordingly, oral immunization of ducklings with SL7207 (pVAX-LTB-UL24 showed superior efficacy of protection (60-80% against a lethal DEV challenge (1000 LD50, compared with the limited survival rate (40% of ducklings immunized with SL7207 (pVAX-UL24. Our study suggests that the SL7207 (pVAX-LTB-UL24 can be a candidate DEV vaccine.

  16. Responses of three very large inducible GTPases to bacterial and white spot syndrome virus challenges in the giant fresh water prawn Macrobrachium rosenbergii.

    Science.gov (United States)

    Huang, Ying; Jin, Min; Yin, Shaowu; Ding, Zhengfeng; Wang, Wen; Ren, Qian

    2016-04-01

    Interferons (IFNs) are cytokines secreted by cells in response to invasion by pathogens, such as viruses, bacteria, parasites, or tumor cells. Very large inducible GTPases (VLIG) are the latest IFN-inducible GTPase family to be discovered and are the largest known GTPases of any species. However, VLIG proteins from invertebrates have yet to be characterized. In this study, three forms of VLIGs designated as MrVLIG1, MrVLIG2, and MrVLIG3 were cloned from the giant fresh water prawn Macrobrachium rosenbergii. MrVLIG1 has a 5445 bp open reading frame (ORF) encoding an 1814-amino acid protein. The complete nucleotide sequence of MrVLIG2 cDNA is 7055 bp long consisting of a 5757 bp ORF encoding a protein with 1918 amino acids. The full length of the MrVLIG3 gene consists of 5511 bp with a 3909 bp ORF encoding a peptide with 1302 amino acids. BLASTP and phylogenetic tree analyses showed that the three MrVLIGs are clustered into one subgroup and, together with other vertebrate VLIGs, into a branch. Tissue distribution analysis indicated that the mRNAs of the three MrVLIGs were widely expressed in almost all detected tissues, including the hemocytes, heart, hepatopancreas, gills, stomach, and intestine, with the highest expression in the hepatopancreas. They were also detected in the intestine but with relatively low expression levels. Quantitative real-time RT-PCR analysis showed that the mRNA transcripts of the MrVLIGs in the hepatopancreas were significantly expressed at various time points after infection with Vibrio parahaemolyticus and white spot syndrome virus. In summary, the three isoforms of VLIG genes participate in the innate immune response of the shrimps to bacterial and viral infections.

  17. Effects of Slow-stroke Back Massage on Chemotherapy-induced Nausea and Vomiting in the Pediatrics with Acute Leukemia: a Challenge of Controlling Symptoms

    Directory of Open Access Journals (Sweden)

    Mojtaba Miladinia

    2015-12-01

    Full Text Available Introduction Nausea and vomiting are the most common side effects of chemotherapy in the pediatrics with cancer which affect their quality of life. Use of some methods of complementary medicine in leukemia patients is problematic. Because, leukemia patients are at risk of infection and bleeding, therefore the use of acupressure, acupuncture, and deep massage can be risky in these patients. Slow- stroke back massage is applied on the surface of body, so does not have complications. No study has addressed the effect of massage therapy on chemotherapy-induced nausea and vomiting in pediatrics with acute leukemia in the world.  Material and methods This study was a two-group randomized controlled trial (RCT, double blind and repeated measures design. In this RCT, 45 school age children with acute leukemia were placed in the massage and control groups. Before start of the study, at the day of chemotherapy administration (day 1th, only nausea and vomiting were measured. Then during 6 days next (day 2 through 7, the intervention group received 5-minutes Super Smash Bros. Melee (SSBM, immediately before start of each session of chemotherapy. Nausea was measured during chemotherapy, 0.5 h and 3 h after each session of chemotherapy in the two groups. Also vomiting was recorded during 24 h after each session of chemotherapy. Repeated measures ANOVA, Chi-square, and t-test were used for analysis. Results Most of pediatrics were male (58.13%, and suffered from Acute myeloid leukemia (AML (81.7%. The repeated measure analysis showed that in the intervention group, the SSBM reduced progressive mean of nausea severity and frequency of vomit over time. While, this side effects have slightly increased over time in the control group. Conclusion The results of this study are suggesting that SSBM, as a non-pharmacologic, easy and safe method, is effective in controlling Chemotherapy-induced nausea and vomiting (CINV in the pediatrics with acute leukemia.

  18. Responses of three very large inducible GTPases to bacterial and white spot syndrome virus challenges in the giant fresh water prawn Macrobrachium rosenbergii.

    Science.gov (United States)

    Huang, Ying; Jin, Min; Yin, Shaowu; Ding, Zhengfeng; Wang, Wen; Ren, Qian

    2016-04-01

    Interferons (IFNs) are cytokines secreted by cells in response to invasion by pathogens, such as viruses, bacteria, parasites, or tumor cells. Very large inducible GTPases (VLIG) are the latest IFN-inducible GTPase family to be discovered and are the largest known GTPases of any species. However, VLIG proteins from invertebrates have yet to be characterized. In this study, three forms of VLIGs designated as MrVLIG1, MrVLIG2, and MrVLIG3 were cloned from the giant fresh water prawn Macrobrachium rosenbergii. MrVLIG1 has a 5445 bp open reading frame (ORF) encoding an 1814-amino acid protein. The complete nucleotide sequence of MrVLIG2 cDNA is 7055 bp long consisting of a 5757 bp ORF encoding a protein with 1918 amino acids. The full length of the MrVLIG3 gene consists of 5511 bp with a 3909 bp ORF encoding a peptide with 1302 amino acids. BLASTP and phylogenetic tree analyses showed that the three MrVLIGs are clustered into one subgroup and, together with other vertebrate VLIGs, into a branch. Tissue distribution analysis indicated that the mRNAs of the three MrVLIGs were widely expressed in almost all detected tissues, including the hemocytes, heart, hepatopancreas, gills, stomach, and intestine, with the highest expression in the hepatopancreas. They were also detected in the intestine but with relatively low expression levels. Quantitative real-time RT-PCR analysis showed that the mRNA transcripts of the MrVLIGs in the hepatopancreas were significantly expressed at various time points after infection with Vibrio parahaemolyticus and white spot syndrome virus. In summary, the three isoforms of VLIG genes participate in the innate immune response of the shrimps to bacterial and viral infections. PMID:26850335

  19. Energetic challenges

    International Nuclear Information System (INIS)

    Full text: Connecting the 2 billion people who have no access to commercial energy is the most important energy challenge facing the world community. Women and children, primarily in developing countries, spend their days collecting wood or cow dung for fuel for cooking and heating their homes in very inefficient stoves: this both harms the environment and directly threatens the health of their families. Outmoded boilers linked to central heating systems in most of the cities of Eastern Europe and the former Soviet Union pose another challenge. They are inefficient; they lack modern pollution control; and the end use of the heat is not metered, leading to more inefficiency and waste. Both of these problems cry out to the world for investment. Investing in energy solutions in these countries can bring about significant and immediate local environmental improvements, achieve greatly improved energy efficiency, and substantially reduce greenhouse gas emissions. But, energy and environmental policy tends to direct investment towards industrial countries, even though it would have a greater impact on the environment - not to mention the human condition in general - in the developing countries and transition economies. We need a new direction in energy policy. The World Energy Council has studied the needs and we believe a number of our proposed policy recommendations would lead towards greater investment in the countries where it is most needed. The political risk of key energy project investments must be addressed both by the countries seeking outside investment and by the global community at large. The countries must create an investor-friendly climate, which includes the rule of law and recognizes private property rights. The global community can contribute by developing new political risk insurance schemes rewarding the countries that create this climate. Energy must be priced to cover costs and ensure payment. In too many countries, blanket subsidies for energy

  20. Regulatory challenges

    International Nuclear Information System (INIS)

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for the

  1. Regulatory challenges

    Energy Technology Data Exchange (ETDEWEB)

    Austvik, Ole Gunnar

    2003-07-01

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for

  2. Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute to responses that protect mice from Coccidioides immitis infection

    Directory of Open Access Journals (Sweden)

    Woelk Christopher H

    2012-09-01

    Full Text Available Abstract Background Coccidioidomycosis results from airborne infections caused by either Coccidioides immitis or C. posadasii. Both are pathogenic fungi that live in desert soil in the New World and can infect normal hosts, but most infections are self-limited. Disseminated infections occur in approximately 5% of cases and may prove fatal. Mouse models of the disease have identified strains that are resistant (e.g. DBA/2 or susceptible (e.g. C57BL/6 to these pathogens. However, the genetic and immunological basis for this difference has not been fully characterized. Results Microarray technology was used to identify genes that were differentially expressed in lung tissue between resistant DBA/2 and sensitive C57BL/6 mice after infection with C. immitis. Differentially expressed genes were mapped onto biological pathways, gene ontologies, and protein interaction networks, which revealed that innate immune responses mediated by Type II interferon (i.e., IFNG and the signal transducer and activator of transcription 1 (STAT1 contribute to the resistant phenotype. In addition, upregulation of hypoxia inducible factor 1A (HIF1A, possibly as part of a larger inflammatory response mediated by tumor necrosis factor alpha (TNFA, may also contribute to resistance. Microarray gene expression was confirmed by real-time quantitative PCR for a subset of 12 genes, which revealed that IFNG HIF1A and TNFA, among others, were significantly differentially expressed between the two strains at day 14 post-infection. Conclusion These results confirm the finding that DBA/2 mice express more Type II interferon and interferon stimulated genes than genetically susceptible strains and suggest that differential expression of HIF1A may also play a role in protection.

  3. Modulatory effect of cilostazol on tramadol-induced behavioral and neurochemical alterations in rats challenged across the forced swim despair test

    Directory of Open Access Journals (Sweden)

    Noha M. Gamil

    2016-06-01

    Full Text Available Pain-associated depression is encountered clinically in some cases such as cancer, chronic neuropathy, and after operations. Tramadol is an opioid analgesic drug that may modulate monoaminergic neurotransmission by inhibition of noradrenaline and serotonin reuptake that may contribute to its antidepressant-like effects. Clinically, tramadol is used either alone or in combination with other NSAIDs in the treatment of cases associated with pain and depression, e.g. low back pain, spinal cord injury, and post-operative pain management. However, tramadol monotherapy as an antidepressant is impeded by severe adverse effects including seizures and serotonin syndrome. Interestingly, phosphodiesterase-III inhibitors demonstrated novel promising antidepressant effects. Among which, cilostazol was reported to attenuate depression in post-stroke cases, geriatrics and patients undergoing carotid artery stenting. Therefore, this study was carried out to investigate the possible antidepressant-like effects of tramadol and/or cilostazol on the behavioral level in experimental animals, and to examine the neurochemical and biochemical effects of tramadol, cilostazol and their combination in rats, in order to explore the probable mechanisms of action underlying their effects. To achieve our target, male albino mice and rats were randomly allocated into five groups and administered either vehicle for control, fluoxetine (20 mg/kg, p.o., tramadol HCl (20 mg/kg, p.o., cilostazol (100 mg/kg, p.o., or combination of both tramadol and cilostazol. At day 14, mice and rats were challenged in the tail suspension test and forced swim test, respectively. Rats were sacrificed and brains were isolated for determination of brain monoamines, MDA, NO, SOD, and TNF-α. The current results showed that concurrent administration of cilostazol to tramadol-treated animals modulated depression on the behavioral level, and showed ameliorative neurochemical and biochemical effects

  4. Constitutive, but Not Challenge-Induced, Interleukin-10 Production Is Robust in Acute Pre-Pubescent Protein and Energy Deficits: New Support for the Tolerance Hypothesis of Malnutrition-Associated Immune Depression Based on Cytokine Production in vivo

    Directory of Open Access Journals (Sweden)

    Bill Woodward

    2011-01-01

    Full Text Available The tolerance model of acute (i.e., wasting pre-pubescent protein and energy deficits proposes that the immune depression characteristic of these pathologies reflects an intact anti-inflammatory form of immune competence that reduces the risk of autoimmune reactions to catabolically released self antigens. A cornerstone of this proposition is the finding that constitutive (first-tier interleukin(IL-10 production is sustained even into the advanced stages of acute malnutrition. The IL-10 response to inflammatory challenge constitutes a second tier of anti-inflammatory regulation and was the focus of this investigation. Weanling mice consumed a complete diet ad libitum, a low-protein diet ad libitum (mimicking incipient kwashiorkor, or the complete diet in restricted daily quantities (mimicking marasmus, and their second-tier IL-10 production was determined both in vitro and in vivo using lipopolysaccharide (LPS and anti-CD3 as stimulants of innate and adaptive defences, respectively. Both early (3 days and advanced (14 days stages of wasting pathology were examined and three main outcomes emerged. First, classic in vitro systems are unreliable for discerning cytokine production in vivo. Secondly, in diverse forms of acute malnutrition declining challenge-induced IL-10 production may provide an early sign that anti-inflammatory control over immune competence is failing. Thirdly, and most fundamentally, the investigation provides new support for the tolerance model of malnutrition-associated inflammatory immune depression.

  5. Challenges in Maintaining Emotion Regulation in a Sleep and Energy Deprived State Induced by the 4800Km Ultra-Endurance Bicycle Race; The Race Across AMerica (RAAM)

    Science.gov (United States)

    Lahart, Ian M.; Lane, Andrew M.; Hulton, Andrew; Williams, Karen; Godfrey, Richard; Pedlar, Charles; Wilson, Mathew G.; Whyte, Gregory P.

    2013-01-01

    Multiday ultra-endurance races present athletes with a significant number of physiological and psychological challenges. We examined emotions, the perceived functionality (optimal-dysfunctional) of emotions, strategies to regulate emotions, sleep quality, and energy intake-expenditure in a four-man team participating in the Race Across AMerica (RAAM); a 4856km continuous cycle race. Cyclists reported experiencing an optimal emotional state for less than 50% of total competition, with emotional states differing significantly between each cyclist over time. Coupled with this emotional disturbance, each cyclist experienced progressively worsening sleep deprivation and daily negative energy balances throughout the RAAM. Cyclists managed less than one hour of continuous sleep per sleep episode, high sleep latency and high percentage moving time. Of note, actual sleep and sleep efficiency were better maintained during longer rest periods, highlighting the importance of a race strategy that seeks to optimise the balance between average cycling velocity and sleep time. Our data suggests that future RAAM cyclists and crew should: 1) identify beliefs on the perceived functionality of emotions in relation to best (functional-optimal) and worst (dysfunctional) performance as the starting point to intervention work; 2) create a plan for support sufficient sleep and recovery; 3) create nutritional strategies that maintain energy intake and thus reduce energy deficits; and 4) prepare for the deleterious effects of sleep deprivation so that they are able to appropriately respond to unexpected stressors and foster functional working interpersonal relationships. Key Points Completing the Race Across AMerica (RAAM); a 4856km continuous cycle race associated with sleep disturbance, an energy-deficient state, and experiencing intense unwanted emotions. Cyclists reported experiencing an optimal emotional state for less than 50% of total competition and actual sleep and sleep efficiency

  6. GC-MS and NMR analysis of the bioactive compounds from the crude extracts of Waltheria indica and the histopathological changes induced in albino rats challenged with Naja nigricollis venom

    Directory of Open Access Journals (Sweden)

    Philip Ilani

    2016-05-01

    Full Text Available Objective: To develop a characteristic fingerprint of the different chemical compounds of plant by gas chromatography-mass spectrometer (GC-MS and nuclear magnetic resonance (NMR analysis and assess the effect of the crude extract on histological changes induced in Naja nigricollis (N. nigricollis envenomed albino rats. Methods: The coarsely powdered Waltheria indica (W. indica whole plant material was extracted using 70% methanol. GC-MS analysis was carried out using a Shimadzu GC-MS QP 2010 plus system of gas chromatography interfaced to a mass spectrometer. The identification of components was based on National Institute of Standard and Technology-08 and Willey-8 libraries. Hydrogen-NMR spectra of the extracts was performed using Bruker Biospin Avance 400-MHz NMR spectrophotometer with a 5 mm broad inverse probe head, equipped with shielded z-gradient accessories and C-13 NMR hetero-nuclear single quantum correction was carried out using the Brucker’s standard pulse library. The efficacy of the crude extract of W. indica whole plant was tested and the lesions induced in the liver, brain and kidney of albino rats challenged with N. nigricollis were analyzed by light microscopy. Results: The identification of the bioactive compounds from W. indica by GC-MS analysis revealed 41 peaks. A total of 38 compounds were identified with majority having important pharmacological activities that included anti-microbial, anti-cancer, anti-oxidant antiinflammatory, anti-allergenic, anti-ageing, anti-arthritic, larvicidal, anti-convulsant and herbicidal activities. C-13 and hydrogen-NMR analysis of W. indica elucidated key bioactive compounds in the whole plant that were consistent with the classes of bioactive compounds detected by GC-MS analysis. The efficacy of the crude extract of W. indica whole plant in ameliorating histopathological lesions induced in the liver, brain and kidney of albino rats challenged with N. nigricollis venom revealed the

  7. GC-MS and NMR analysis of the bioactive compounds from the crude extracts ofWaltheria indica and the histopathological changes induced in albino rats challenged withNaja nigricollis venom

    Institute of Scientific and Technical Information of China (English)

    Philip Ilani; Nicholas Ajodo; Folashade Adewusi; Samirat Yakubu; Victor Yakubu Cosmos; Ache Eunice; Atonila Kayode Ezekiel; Oshiedu Sarah; Emmanuel Amlabu

    2016-01-01

    Objective:To develop a characteristic fingerprint of the different chemical compounds of plant by gas chromatography-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR) analysis and assess the effect of the crude extract on histological changes induced inNaja nigricollis(N. nigricollis)envenomed albino rats. Methods: The coarsely powderedWaltheria indica (W. indica) whole plant material was extracted using 70% methanol.GC-MS analysis was carried out using a ShimadzuGC-MS QP 2010 plus system of gas chromatography interfaced to a mass spectrometer. The identification of components was based on National Institute of Standard and Technology-08 and Willey-8 libraries. Hydrogen-NMR spectra of the extracts was performed using Bruker Biospin Avance 400-MHzNMR spectrophotometer with a 5 mm broad inverse probe head, equipped with shielded z-gradient accessories andC-13 NMR hetero-nuclear single quantum correction was carried out using the Brucker’s standard pulse library. The efficacy of the crude extract ofW. indica whole plant was tested and the lesions induced in the liver, brain and kidney of albino rats challenged withN. nigricollis were analyzed by light microscopy. Results:The identification of the bioactive compounds fromW. indica byGC-MS analysis revealed 41 peaks. A total of 38 compounds were identified with majority having important pharmacological activities that included anti-microbial, anti-cancer, anti-oxidant anti-inflammatory, anti-allergenic, anti-ageing, anti-arthritic, larvicidal, anti-convulsant and herbicidal activities.C-13 and hydrogen-NMR analysis ofW. indica elucidated key bioactive compounds in the whole plant that were consistent with the classes of bioactive compounds detected byGC-MS analysis. The efficacy of the crude extract ofW. indica whole plant in ameliorating histopathological lesions induced in the liver, brain and kidney of albino rats challenged withN. nigricollis venom revealed the abrogation of tissue degeneration when

  8. Elevated levels of NO in both unchallenged and LPS-challenged C. parvum-primed mice are attributable to the activity of a cytokine-inducible isoform of iNOS.

    Science.gov (United States)

    Smith, S R; Manfra, D; Davies, L; Terminelli, C; Denhardt, G; Donkin, J

    1997-01-01

    Elevated levels of nitric oxide (NO2-/NO3-) were detected in the serum of mice 3-7 days after priming with Corynebacterium parvum (Propionibacterium acnes). The serum NO2-/NO3- response was completely inhibited when C. parvum-primed (C. parrum) mice were treated with N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited when the mice were treated with interleukin-10 (IL-10) and the cytokine was most effective when given in multiple doses beginning on the day of priming. In contrast to L-NMMA and AG, IL-10 had no effect on the serum NO2-/NO3- response when administered to the mice on days 6 and 7 post priming. The inducible isoform of NOS (iNOS) appeared to be responsible for the elevated NO2-/NO3- response in C. parvum mice because iNOS transcripts were readily detected in their livers. Moreover, these transcripts as well as the circulating levels of NO2-/NO3- were dramatically reduced when the mice were treated with anti-tumor necrosis factor alpha (anti-TNF-alpha) or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAbs) during the priming interval. There was a modest increase (less than twofold) in the serum NO2-/NO3- response following a lipopolysaccharide (LPS) challenge to C. parvum mice (C. parvum/LPS mice). LPS had a more dramatic stimulatory effect if the levels of NO2-/NO3- preexisting in C. parvum/LPS mice were reduced by treatment with L-NMMA, AG, or IL-10 before the challenge. Thus the levels of NO2-/NO3- that preexisted in C. parvum/LPS mice appeared to influence their ability to mount a NO2-/NO3- response subsequent to the LPS challenge. The NO2-/NO3- response did not contribute to lethality in C. parvum/LPS mice because anti-TNF-alpha and anti-IFN-gamma mAbs were protective but had no effect on serum NO2-/NO3- levels when administered to mice 24 h before the LPS challenge. PMID:9000533

  9. Cellular and humoral factors involved in the response of rainbow trout gills to Ichthyophthirius multifiliis infections

    DEFF Research Database (Denmark)

    Olsen, Moonika Marana; Kania, Per Walter; Heinecke, Rasmus Demuth;

    2011-01-01

    injected with PBS and subgroups were treated with the immuno-suppressant hydrocortisone before fish were challenged with live theronts. Significant up-regulations of genes encoding IgM, IgT, C3, SAA, IL-8, IL-22 and IFN-g were induced by immunization and challenge. Hydrocortisone treatment had...... a significant down-regulating effect on genes incoding IgT, IgM, CD4, CD8, IFN-g, IL-8 and IL-22 in all groups. Immunohistochemistry, using monoclonal antibodies to detect cellular markers, demonstrated active involvement of CD8, MHC II, IgT and IgM positive cells in gill tissue. Putative T-cells (CD8 positive...

  10. Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host.

    Directory of Open Access Journals (Sweden)

    Jodi L McGill

    Full Text Available Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous-administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild-type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4+ T cell proliferation and IFNγ production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection.

  11. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.

    Science.gov (United States)

    Petecchia, Loredana; Sabatini, Federica; Usai, Cesare; Caci, Emanuela; Varesio, Luigi; Rossi, Giovanni A

    2012-08-01

    Epithelial barrier permeability is altered in inflammatory respiratory disorders by a variety of noxious agents through modifications of the epithelial cell structure that possibly involve tight junction (TJ) organization. To evaluate in vitro whether pro-inflammatory cytokines involved in the pathogenesis of respiratory disorders could alter TJ organization and epithelial barrier integrity, and to characterize the signal transduction pathway involved Calu-3 airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and localization, evaluated by confocal microscopy; (b) apoptotic activity, quantified using terminal transferase deoxyuridine triphosphate nick-end labeling staining; (c) epithelial barrier integrity, detected as transmembrane electrical resistance and expressed as G(T) values; (d) epidermal growth factor receptor (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting. Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ transmembrane proteins. The degree ZO-1 and occludin colocalization was 62±2% in control cultures and significantly decreased in the presence of TNF-a (47±3%), IL-4 (43±1%) and INF-g (35±3%). Although no apoptosis induction was detected following exposure to cytokines, changes in the epithelial barrier integrity were observed, with a significant enhancement in paracellular conductance. G(T) values were, respectively, 1.030±0.0, 1.300±0.04, 1.260±0.020 and 2.220±0.015 (mS/cm²)1000 in control cultures and in those exposed to TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling pathway in cytokine-induced damage was demonstrated by a significant increase in threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min incubation. All these cytokine-induced changes were

  12. Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yang, E-mail: yangshi_xz@126.com; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

    2015-05-22

    Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation.

  13. Developing a Watershed Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    This article presents a watershed challenge that gives students an opportunity to investigate the challenge of using a watershed area as a site for development, examining the many aspects of this multifaceted problem. This design challenge could work well in a team-based format, with students taking on specific aspects of the challenges and…

  14. Fine-tuning synthesis of Yersinia pestis LcrV from runaway-like replication balanced-lethal plasmid in a Salmonella enterica serovar typhimurium vaccine induces protection against a lethal Y. pestis challenge in mice.

    Science.gov (United States)

    Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M; Branger, Christine G; Tinge, Steven A; Curtiss, Roy

    2010-06-01

    A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal DeltaasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain chi9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/P(cro)) (P(R)), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P(BAD) c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of beta-lactamase, and cloned into pYA4534 under the control of the P(trc) promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain chi9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route.

  15. 78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

    Science.gov (United States)

    2013-08-13

    ... SPACE ADMINISTRATION Centennial Challenges 2014 Sample Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot... Robot Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  16. Challenges of Parenting Multiples

    Science.gov (United States)

    ... the American Society for Reproductive Medicine Challenges of Parenting Multiples There are many psychological, social, and economic ... the unique challenges and rewards that come from parenting multiples. For more information on the medical aspects ...

  17. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us ... Only Natural email updates. Enter email address Submit Home > It's Only Natural > Overcoming challenges Overcoming breastfeeding challenges ...

  18. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available A project of the U.S. Department of Health and Human Services Office on Women's Health Skip Navigation ... challenges Overcoming breastfeeding challenges Dealing with lack of family support Is my baby getting enough ...

  19. The Backpack Design Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  20. Energy transition - economic challenge, climate challenge, industrial challenge

    International Nuclear Information System (INIS)

    This document highlights and discusses the different economic, climate and industrial challenges, identifies and discusses the different objectives and main results for a successful energy transition respectively in its relationships with the energy mix (the result is to divide emissions by a factor 4), with governance (the result should be a balanced distribution of energy governance), with energy consumption

  1. Climate challenges, vulnerabilities, and food security

    OpenAIRE

    Margaret C. Nelson; Ingram, Scott E.; Dugmore, Andrew J.; Streeter, Richard; Matthew A. Peeples; McGovern, Thomas H.; Hegmon, Michelle; Arneborg, Jette; Keith W. Kintigh; Brewington, Seth; Spielmann, Katherine A.; Simpson, Ian A; Strawhacker, Colleen; Comeau, Laura E. L.; Torvinen, Andrea

    2015-01-01

    Climate-induced disasters are impacting human well-being in ever-increasing ways. Disaster research and management recognize and emphasize the need to reduce vulnerabilities, although extant policy is not in line with this realization. This paper assesses the extent to which vulnerability to food shortage, as a result of social, demographic, and resource conditions at times of climatic challenge, correlates with subsequent declines in social and food security. Extreme climate challenges are i...

  2. Clinical challenges in mechanical ventilation.

    Science.gov (United States)

    Goligher, Ewan C; Ferguson, Niall D; Brochard, Laurent J

    2016-04-30

    Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non-invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator-induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. PMID:27203509

  3. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

    Directory of Open Access Journals (Sweden)

    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  4. Challenges of Relativistic Astrophysics

    CERN Document Server

    Opher, Reuven

    2013-01-01

    I discuss some of the most outstanding challenges in relativistic astrophysics in the subjects of: compact objects (Black Holes and Neutron Stars); dark sector (Dark Matter and Dark Energy); plasma astrophysics (Origin of Jets, Cosmic Rays and Magnetic Fields) and the primordial universe (Physics at the beginning of the Universe). In these four subjects, I discuss twelve of the most important challenges. These challenges give us insight into new physics that can only be studied in the large scale Universe. The near future possibilities, in observations and theory, for addressing these challenges, are also discussed.

  5. First Aid Challenge

    Science.gov (United States)

    Roman, Harry T.

    2011-01-01

    This article describes a challenge wherein students will be asked to design a portable first aid kit that is normally carried in a recreational vehicle (RV), but can also be hand-carried or backpacked off road for distances of approximately 1-2 miles. This can be a very practical challenge for the students because it touches everyone. Everybody…

  6. Challenge and Change

    Science.gov (United States)

    Mehaffy, George L.

    2012-01-01

    In the past twenty years, various industries have been forever altered by technology: newspapers, book publishing, the photography business, and many more. Higher education too faces unprecedented challenges primarily driven by rapid changes in technology. To meet these challenges and adapt to these changes, new models are needed. Six challenges…

  7. Science Challenge Day

    Science.gov (United States)

    Siegel, Deborah

    2013-01-01

    Science fairs can be good motivators, but as extracurricular activities, they leave some students behind. However, by staging a Science Challenge Day at school, educators can involve all students in doing everything from choosing activities to judging projects. This article presents a model for running a successful Science Challenge Day. The…

  8. Overcoming Breastfeeding Challenges

    Medline Plus

    Full Text Available ... size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming breastfeeding challenges Dealing with ... it into your life My breastfeeding story Partner resources Subscribe ... at the U.S. Department of Health and Human Services 200 Independence Avenue, S.W. • Washington, DC 20201 ...

  9. Antibodies specific for hypervariable regions 3 to 5 of the feline immunodeficiency virus envelope glycoprotein are not solely responsible for vaccine-induced acceleration of challenge infection in cats

    NARCIS (Netherlands)

    W. Huisman (Willem); E.J.A. Schrauwen (Eefje); S.D. Pas (Suzan); J.A. Karlas (Jos); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2004-01-01

    textabstractIn a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a

  10. Activating Transcription Factor 4 (ATF4)-ATF3-C/EBP Homologous Protein (CHOP) Cascade Shows an Essential Role in the ER Stress-Induced Sensitization of Tetrachlorobenzoquinone-Challenged PC12 Cells to ROS-Mediated Apoptosis via Death Receptor 5 (DR5) Signaling.

    Science.gov (United States)

    Liu, Zixuan; Shi, Qiong; Song, Xiufang; Wang, Yuxin; Wang, Yawen; Song, Erqun; Song, Yang

    2016-09-19

    Tetrachlorobenzoquinone (TCBQ) is a downstream metabolite of pentachlorophenol (PCP). Previously, we demonstrated that TCBQ caused cytotoxicity due to mitochondrial-related apoptosis. Here, we confirmed the upregulation of death receptor 5 (DR5) followed by the construction of the death-inducing signaling complex (DISC). We also detected the activation of the caspase cascade, which was correlated with TCBQ-induced apoptotic cell death in PC12 cells. The upregulation of DR5 included transcriptional activation and de novo protein synthesis in response to TCBQ. We also identified the endoplasmic reticulum (ER) as a new target for the TCBQ challenge in PC12 cells. The protein kinase R-like ER kinase/eukaryotic translation initiation factor 2α (PERK/eIF2α)-mediated activating transcription factor 4 (ATF4)-ATF3-C/EBP homologous protein (CHOP) signaling pathway contributed to the process of TCBQ-induced ER stress. Blocking ATF4, ATF3, or CHOP signaling by gene silencing technology resulted in decreased cell apoptosis after exposure to TCBQ. Finally, NAC ameliorated TCBQ-induced apoptosis and ER stress, which illustrated that TCBQ-induced apoptosis is somehow ROS-dependent. In summary, this study provided important mechanistic insight into how TCBQ utilizes ER stress-related signaling to exhibit pro-apoptotic activity in PC12 cells. PMID:27484784

  11. The challenges of dismantling

    International Nuclear Information System (INIS)

    This document gathers Power Point presentations which address the contexts and challenges of dismantling (legal framework, safety and radiation protection challenges, waste processing industry), and propose illustrations of dismantling challenges (example of operations to prepare EURODIF dismantling and CLIGEET work-group on EURODIF dismantling, examples of dismantling of EDF installations and CLIs' opinion on the dismantling of EDF installations, Brennilis dismantling follow-up performed by the CLI, examples of dismantling of CEA installations and opinion of a CLI on the dismantling of CEA installations)

  12. Challenges of serious games

    Directory of Open Access Journals (Sweden)

    B. Fernández-Manjón

    2015-11-01

    Full Text Available Although educational games have revealed to be a very effective focus in diverse situations, their use in education is still very limited. In this paper we analyse the main challenges concerning educational games that, from our perspective, have to be approached so that the use of this kind of games can be widespread. These challenges are classified in three main dimensions: socio-cultural, educational and technological. Once the challenges are identified, some possible measures are suggested to address or reduce these problems so that the use of educational games may be widespread.

  13. Big Data Challenges

    Directory of Open Access Journals (Sweden)

    Alexandru Adrian TOLE

    2013-10-01

    Full Text Available The amount of data that is traveling across the internet today, not only that is large, but is complex as well. Companies, institutions, healthcare system etc., all of them use piles of data which are further used for creating reports in order to ensure continuity regarding the services that they have to offer. The process behind the results that these entities requests represents a challenge for software developers and companies that provide IT infrastructure. The challenge is how to manipulate an impressive volume of data that has to be securely delivered through the internet and reach its destination intact. This paper treats the challenges that Big Data creates.

  14. Challenging behaviour: a challenge to change.

    Science.gov (United States)

    van Berckelaer-Onnes, I A; van Loon, J; Peelen, A

    2002-09-01

    People with intellectual disability often exhibit severe behavioural problems. Treatment of these problems is frequently very difficult. In The Netherlands, parents, institutes, schools and others can request the services of an independent advisory team with a pool of professionals who have experience with individuals who exhibit challenging behaviour. In this article the methods of the team will be described using a 24-year-old man as an example. The process took almost 7 years. Finally, this man, who had been living full time in one room in total isolation from the rest of the world, fulfilled his heart's desire--visiting the UK by Hovercraft. PMID:12212917

  15. A challenging read

    Directory of Open Access Journals (Sweden)

    Cathy Foley

    2004-11-01

    Full Text Available Andrei Mourachkine uses his new book to argue that superconductivity could be achieved at room temperature and, while his thesis may rest on some unconfirmed evidence, it does challenge preconceptions, says Cathy Foley.

  16. Community Challenge Grantees

    Data.gov (United States)

    Department of Housing and Urban Development — HUD's Community Challenge Grants aim to reform and reduce barriers to achieving affordable, economically vital and sustainable communities. The funds are awarded to...

  17. The Electric Car Challenge.

    Science.gov (United States)

    Diehl, Brian E.

    1997-01-01

    Describes the Electric Car Challenge during which students applied methods of construction to build lightweight, strong vehicles that were powered by electricity. The activity required problem solving, sheet metal work, electricity, design, and construction skills. (JOW)

  18. Brazil World Cup Challenges

    Directory of Open Access Journals (Sweden)

    MANSUR, R.

    2012-12-01

    Full Text Available Overcoming the productivity challenge is the main benefit of the 2014 World Cup for Brazilian people. The sustainable development of our cultural tourism industry will catapult the new middle class growing up rate.

  19. Better Buildings Challenge Overview

    Energy Technology Data Exchange (ETDEWEB)

    None

    2011-06-01

    The Better Buildings Challenge is a national leadership initiative calling on corporate chief executive officers, university presidents, and state and local leaders to make a significant commitment to building energy efficiency.

  20. Overcoming Safeguards Challenges

    International Nuclear Information System (INIS)

    The focus of the 2010 IAEA International Safeguards Symposium was how best, from a technical perspective, to prepare for future verification challenges during this time of change. By bringing together the leading experts in the field from across the world, this symposium provided an opportunity for stakeholders to explore possible solutions in support of the IAEA's nuclear verification mission, and to identify areas where the different stakeholders in the safeguards business can help address these challenges

  1. Optimal challenges in tennis

    OpenAIRE

    Clarke, S. R.; Norman, J.M.

    2012-01-01

    The use of technology in sport to assist umpires has been gradually introduced into several sports. This has now been extended to allow players to call upon technology to arbitrate when they disagree with the umpire's decision. Both tennis and cricket now allow the players to challenge a doubtful decision, which is reversed if the evidence shows it to be incorrect. However, the number of challenges is limited, and players must balance any possible immediate gain with the loss of a future righ...

  2. Challenges in obesity research

    Directory of Open Access Journals (Sweden)

    Andreu Palou

    2013-09-01

    Full Text Available Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  3. Challenges in obesity research.

    Science.gov (United States)

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  4. Challenges in obesity research.

    Science.gov (United States)

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. PMID:24010755

  5. Quantum Randi Challenge

    CERN Document Server

    Vongehr, Sascha

    2012-01-01

    Violations of Bell type inequalities in quantum experiments disprove all relativistic micro causal, classically real models. Desperate attempts at saving classicality retreated to claiming what Shimony calls a conspiracy. It is time to embrace the quantum paradigm instead of being stuck in defending it against positions on par with the belief in divinely planted fossils. However, different from 'quantum-magic' pseudoscience, there is resistance against quantum mechanics among scientific literate audiences, and it is growing. The Quantum Randi Challenge is designed to help scientists and educators discredit local realistic models and related attacks against quantum physics. Its 'Randi-type' properties are ensured via a simple computer game that can be made attractive and understandable to lay people. We introduce the general concept of a 'James Randi type' challenge as a tool for science outreach aimed against the spread of pseudoscience. This is a challenge which, according to the laws of nature as known to s...

  6. Meeting the Challenge

    Directory of Open Access Journals (Sweden)

    T. Reg Bott

    2009-01-01

    Full Text Available The first Chempor Conference held in Lisbon in 1975 under the auspices of the Calouste Gulbenkian Foundation, heralded a regular wide-ranging review of research and development in Portugal and the UK Progressively in later years the Conferences have attracted contributions from other European countries and indeed further afield. There is an increasing awareness of the problems for the environment, notably global warming, brought about by human activities. Recent predictions about the future are dire, particularly regarding food and water for a rapidly growing world population. They represent a substantial challenge to the scientific and technical fraternity. In response to that challenge it is important to keep up to date with technical developments, to meet and keep in touch with coworkers in associated fields, and to cooperate wherever possible. The papers presented at the Chempor and other conferences have made and continue to make a significant contribution to that objective of meeting the challenge.

  7. Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE

    Directory of Open Access Journals (Sweden)

    Tracey L. Papenfuss

    2007-01-01

    Full Text Available Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP as a candidate molecule enriched in peripheral macrophages. In situ hybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extending in vitro observations to in vivo biology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.

  8. British Muslims: A Challenge

    OpenAIRE

    Abdel-Hady, Zakaryya Mohamed [زكريا محمد عبد الهادي

    2007-01-01

    The Muslim community in Britain today face multiple challenges covering a wide range of spectrum from the basic right to exists, fighting the increasing trends of Islamophobia, having equal opportunities, to participate in public life, fully integrate within the society and be a positive member of the community. The recent events of September 11th in the US, July 7th in UK and the more recent row over the ban of the headscarf in UK and other European countries have placed tremendous challenge...

  9. Banff Challenge 2

    CERN Document Server

    Junk, Thomas R

    2011-01-01

    Experimental particle physics collaborations constantly seek newer and better ideas for improving the sensitivity of their searches for new particles and phenomena. Statistical techniques are the last step in interpreting the results of an experiment; they are used to make discoveries (hypothesis testing), and to measure parameters (point estimation). They are also used in the first step - experiment and analysis design. Banff Challenge 2 asks participants to test their methods of disco vering hidden signals in simulated datasets and of measuring the properties of these signals. The Challenge problems are described, and the performances of the submitted entries is summarized, for datasets with and without simulated signals present.

  10. Challenges of ecological restoration

    DEFF Research Database (Denmark)

    Halme, Panu; Allen, Katherine A.; Aunins, Ainars;

    2013-01-01

    on Biological Diversity. Several northern countries are now taking up this challenge by restoring forest biodiversity with increasing intensity. The ecology and biodiversity of boreal forests are relatively well understood making them a good model for restoration activities in many other forest ecosystems. Here...... of the target ecosystem should be established with the need for restoration carefully assessed and the outcome properly monitored. Finally, we identify the most important challenges that need to be solved in order to carry out efficient restoration with powerful and long-term positive impacts on biodiversity...

  11. Challenges facing production grids

    Energy Technology Data Exchange (ETDEWEB)

    Pordes, Ruth; /Fermilab

    2007-06-01

    Today's global communities of users expect quality of service from distributed Grid systems equivalent to that their local data centers. This must be coupled to ubiquitous access to the ensemble of processing and storage resources across multiple Grid infrastructures. We are still facing significant challenges in meeting these expectations, especially in the underlying security, a sustainable and successful economic model, and smoothing the boundaries between administrative and technical domains. Using the Open Science Grid as an example, I examine the status and challenges of Grids operating in production today.

  12. Red wine asthma: a controlled challenge study.

    Science.gov (United States)

    Dahl, R; Henriksen, J M; Harving, H

    1986-12-01

    Drinking red wine may provoke bronchospasm in subjects with asthma. In order to reveal some of the possible agents involved in this reaction, 18 patients with a history of red wine-induced asthma were studied. They received, in a double-blind fashion, red wine with low sulfur dioxide (SO2) and high amine, high SO2 and high amine and low SO2 and low amine content. In each challenge, the wine was administered in stepwise increasing quantities until a total of 385 ml or a fall in peak expiratory flow of greater than 15% was reached. Nine subjects demonstrated a significant fall in peak flow in one or more challenges. In all cases the most severe reaction was observed after the wine with high SO2 content. The study suggests that SO2 is the most important factor in red wine-induced asthma. It is recommended that wine labels provide information on the SO2 content.

  13. MALL: The Pedagogical Challenges

    Science.gov (United States)

    Burston, Jack

    2014-01-01

    In this paper the development of mobile-assisted language learning (MALL) over the past 20 years is reviewed with a particular focus on the pedagogical challenges facing its exploitation. Following a consideration of the definition of mobile learning, the paper describes the dominant mobile technologies upon which MALL applications have been…

  14. Tackling the Unemployment Challenge

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    As the world's largest economy in transition, Chinafaces a severe unemployment challenge. With aworking population of 751 million, China'sunemployment rate stands at more than l O% in urbanareas," including rural surplus laborers, it is astaggering 20%. Since assuming office in March

  15. Asia's new challenges

    DEFF Research Database (Denmark)

    Brach, Juliana; Vang, Jan

    2012-01-01

    Asian countries are currently undergoing significant changes with respect to their role in and interaction with the international economy. Despite their heterogeneity, Asian countries share the common aim to upgrade capacities, skills and capabilities. This paper aims at unpacking the challenges...

  16. The Clay Challenge Continues...

    Science.gov (United States)

    Coy, Mary

    2007-01-01

    It was time for yet another challenge. Bright colored glazes were on hiatus; earth tones and mixed media took center stage. Inspiration was provided this time by the myriad Native American potters from the desert Southwest. The project: create a coil pot that demonstrates interesting form and good artistry and reflects, through symbolism or mixed…

  17. Challenges of Retrenchment.

    Science.gov (United States)

    Mingle, James R.; And Others

    The retrenchment experiences of a variety of institutions--large and small, public and private--are described and evaluated using an extensive spectrum of case studies sponsored by the Southern Regional Education Board. Part One discusses challenges of retrenchment (James R. Mingle) and strategies for the 1980s (David W. Breneman). Part Two,…

  18. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    RODOLFOF.FLORENTINO

    2001-01-01

    Experience in many parts of the developing world has shown that food fortification offers a costeffective and sustainable solution to the problem of micronutrient malnutrition.Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs,govenments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy.On the other hand,formidable challenges still remain in many countries in Asia,constraining the widespread adoption of this strategy,The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making,The governent faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort.Industry faces the challenge of adapting its production system to the requirements of fortification in oreder that they can contribute to social bojectives while pursuing their economic objectives,The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification,as these players in turn face the challenges that confront them.

  19. Fortification Challenges and Needs

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Experience in many parts of the developing world has shown thatfood fortification offers a cost-effective and sustainable solution to the problem of micronutrient malnutrition. Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs, governments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long-term strategy. On the other hand, formidable challenges still remain in many countries in Asia, constraining the widespread adoption of this strategy. The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making. The government faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort. Industry faces the challenge of adapting its production system to the requirements of fortification in order that they can contribute to social objectives while pursuing their economic objectives. The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification, as these players in turn face the challenges that confront them.

  20. Hopes and Challenges

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China tops the medal tally again at the Asian Games but still faces challenges in some events The curtain of the 16th Asian Games has fallen, but the 15 days of exciting competitions will be recorded in the history of the Games.

  1. The Moon Challenge

    Science.gov (United States)

    Fitzsimmons, Pat; Leddy, Diana; Johnson, Lindy; Biggam, Sue; Locke, Suzan

    2013-01-01

    This article describes a first-grade research project that incorporates trade books and challenges misconceptions. Educators see the power of their students' wonder at work in their classrooms on a daily basis. This wonder must be nourished by students' own experiences--observing the moon on a crystal clear night--as well as by having…

  2. Ecommerce: Ongoing Challenges

    Directory of Open Access Journals (Sweden)

    Derek Mohammed

    2010-08-01

    Full Text Available This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  3. Electric Vehicle Battery Challenge

    Science.gov (United States)

    Roman, Harry T.

    2014-01-01

    A serious drawback to electric vehicles [batteries only] is the idle time needed to recharge their batteries. In this challenge, students can develop ideas and concepts for battery change-out at automotive service stations. Such a capability would extend the range of electric vehicles.

  4. Ecommerce: Ongoing Challenges

    OpenAIRE

    Derek Mohammed

    2010-01-01

    This paper examines some of the challenges of online marketing, including the importance of adding online marketing to corporation budgets. A review of the pros and cons of social networking on the Internet, when used as a marketing tool by companies is presented. In addition, new forms of Internet shoppers and new niches for companies are identified

  5. Challenging the Boundaries

    DEFF Research Database (Denmark)

    Nørgaard, Nina

    2004-01-01

    To many people, challenging the boundaries between the traditional disciplines in foreign language studies means doing cultural studies. The aim of this article is to pull in a different direction by suggesting how the interface between linguistics and literature may be another fertile field to e...

  6. Anthropocene Age Wicked Challenges

    DEFF Research Database (Denmark)

    Edgeman, Rick; Wu, Zhaohui

    2015-01-01

    Grand global challenges, including wicked human caused or influenced ones key to sustainability, characterize the Anthropocene Age. Among these are climate change driven by increased methane and CO2 in the atmosphere; consequent global warming and increasing intensity and incidence of extreme...

  7. Challenging and valuable

    OpenAIRE

    Van Hal, J.D.M.

    2008-01-01

    Challenging and valuable Inaugural speech given on May 7th 2008 at the occasion of the acceptance of the position of Professor Sustainable Housing Transformation at the faculty of Architeeture of the Delft University of Technology by Prof. J.D.M. van Hal MSc PhD.

  8. 77 FR 70835 - Centennial Challenges 2013 Sample Return Robot Challenge

    Science.gov (United States)

    2012-11-27

    ... SPACE ADMINISTRATION Centennial Challenges 2013 Sample Return Robot Challenge AGENCY: National... in accordance with 51 U.S.C. 20144(c). The 2013 Sample Return Robot Challenge is scheduled and teams... Robot Challenge is a prize competition designed to encourage development of new technologies...

  9. 76 FR 56819 - Centennial Challenges 2012 Sample Return Robot Challenge

    Science.gov (United States)

    2011-09-14

    ... SPACE ADMINISTRATION Centennial Challenges 2012 Sample Return Robot Challenge AGENCY: National... 42 U.S.C. 2451(314)(d). The 2012 Sample Return Robot Challenge is scheduled and teams that wish to... technologies of interest and value to NASA and the nation. The 2012 Sample Return Robot Challenge is a...

  10. Citrus phytophthora diseases: Management challenges and successes

    OpenAIRE

    Graham, J; Feichtenberger, E.

    2015-01-01

    Phytophthora spp. are present in nearly all citrus groves in Florida and Brazil and phytophthora-induced diseases, especially foot and root rot, have the potential to cause economically important crop losses. Disease-related losses due to root rot are difficult to estimate because fibrous root damage and yield loss are not always directly proportional. Challenges from phytophthora diseases have been addressed in both countries by enacting phytosanitary requirements for production of pathogen-...

  11. Seven challenges for neuroscience.

    Science.gov (United States)

    Markram, Henry

    2013-01-01

    Although twenty-first century neuroscience is a major scientific enterprise, advances in basic research have not yet translated into benefits for society. In this paper, I outline seven fundamental challenges that need to be overcome. First, neuroscience has to become "big science" - we need big teams with the resources and competences to tackle the big problems. Second, we need to create interlinked sets of data providing a complete picture of single areas of the brain at their different levels of organization with "rungs" linking the descriptions for humans and other species. Such "data ladders" will help us to meet the third challenge - the development of efficient predictive tools, enabling us to drastically increase the information we can extract from expensive experiments. The fourth challenge goes one step further: we have to develop novel hardware and software sufficiently powerful to simulate the brain. In the future, supercomputer-based brain simulation will enable us to make in silico manipulations and recordings, which are currently completely impossible in the lab. The fifth and sixth challenges are translational. On the one hand we need to develop new ways of classifying and simulating brain disease, leading to better diagnosis and more effective drug discovery. On the other, we have to exploit our knowledge to build new brain-inspired technologies, with potentially huge benefits for industry and for society. This leads to the seventh challenge. Neuroscience can indeed deliver huge benefits but we have to be aware of widespread social concern about our work. We need to recognize the fears that exist, lay them to rest, and actively build public support for neuroscience research. We have to set goals for ourselves that the public can recognize and share. And then we have to deliver on our promises. Only in this way, will we receive the support and funding we need. PMID:24139651

  12. Seven challenges for neuroscience

    Science.gov (United States)

    Markram, Henry

    Summary Although twenty-first century neuroscience is a major scientific enterprise, advances in basic research have not yet translated into benefits for society. In this paper, I outline seven fundamental challenges that need to be overcome. First, neuro-science has to become “big science” – we need big teams with the resources and competences to tackle the big problems. Second, we need to create interlinked sets of data providing a complete picture of single areas of the brain at their different levels of organization with “rungs” linking the descriptions for humans and other species. Such “data ladders” will help us to meet the third challenge – the development of efficient predictive tools, enabling us to drastically increase the information we can extract from expensive experiments. The fourth challenge goes one step further: we have to develop novel hardware and software sufficiently powerful to simulate the brain. In the future, supercomputer-based brain simulation will enable us to make in silico manipulations and recordings, which are currently completely impossible in the lab. The fifth and sixth challenges are translational. On the one hand we need to develop new ways of classifying and simulating brain disease, leading to better diagnosis and more effective drug discovery. On the other, we have to exploit our knowledge to build new brain-inspired technologies, with potentially huge benefits for industry and for society. This leads to the seventh challenge. Neuroscience can indeed deliver huge benefits but we have to be aware of widespread social concern about our work. We need to recognize the fears that exist, lay them to rest, and actively build public support for neuroscience research. We have to set goals for ourselves that the public can recognize and share. And then we have to deliver on our promises. Only in this way, will we receive the support and funding we need. PMID:24139651

  13. Diagnostic Challenges at SNS

    CERN Document Server

    Plum, M A

    2003-01-01

    The Spallation Neutron Source now being built in Oak Ridge, Tennessee, USA, accelerates an H- ion beam to 1000 MeV with an average power of 1.4 MW. The H- beam is then stripped to H+, compressed in a storage ring to a pulse length of 695 ns, and then directed onto a mercury neutron spallation target. Most of the acceleration is accomplished with superconducting rf cavities. The presence of these cavities, the high average beam power, and the large range of beam intensity in the storage ring, provide unique challenges to the beam diagnostics systems. In this talk we will discuss these challenges and some of our solutions, including the laser profile monitor system, the residual gas ionization profile monitors, and network attached devices. Measurements performed using prototype instrumentation will also be presented.

  14. Mathematical olympiad challenges

    CERN Document Server

    Andreescu, Titu

    2000-01-01

    Mathematical Olympiad Challenges is a rich collection of problems put together by two experienced and well-known professors and coaches of the U.S. International Mathematical Olympiad Team. Hundreds of beautiful, challenging, and instructive problems from algebra, geometry, trigonometry, combinatorics, and number theory were selected from numerous mathematical competitions and journals. An important feature of the work is the comprehensive background material provided with each grouping of problems. The problems are clustered by topic into self-contained sections with solutions provided separately. All sections start with an essay discussing basic facts and one or two representative examples. A list of carefully chosen problems follows and the reader is invited to take them on. Additionally, historical insights and asides are presented to stimulate further inquiry. The emphasis throughout is on encouraging readers to move away from routine exercises and memorized algorithms toward creative solutions to open-e...

  15. Challenges in sexual medicine

    DEFF Research Database (Denmark)

    Cellek, Selim; Giraldi, Annamaria

    2012-01-01

    The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have...... placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain...... several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field...

  16. The challenge of conceiving

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Jørgensen, Ulrik

    2011-01-01

    different or even not very well established ideas of what might be a good design result. We present two mutually supportive approaches to problem identification that we have developed, applied and refined. The first is providing an approach to map the arenas of development that influence the context......One of the big challenges in the CDIO approach to engineering education is the first part focusing on conceiving problems to be handled and eventually solved. Traditional engineering education has been dominated by its focus on technical disciplines emphasising their individual tool box of problem...... the perspective of engineering design challenges where the need for problem identification is obvious to avoid the pitfall to reproduce and piecemeal engineer already existing product or service concepts. Problem identification is not a simple desk research task as it often involves a multitude of actors having...

  17. Challenges in Request Management

    DEFF Research Database (Denmark)

    Sommer, Anita Friis

    2014-01-01

    Request management (RQM) is a new term used for managing customer requests for new products. It is the counterpart to typical product development processes, which has no direct customer involvement. It is essential to manage customer requests in a structured and efficient way to obtain...... profitability. This research study seeks to investigate the challenges of RQM in practice. Existing demand chain management literature is used as a basis for developing a RQM framework. RQM is investigated through an explorative research design in a dyadic B2B case study including a global industrial company...... and its customers. The study provides an insight into a new area of supply chain management, including the process activity flow and challenges involved across the process. Furthermore, the method is dyadic including the customer in the case study, which is rare in related research....

  18. Challenges to Resistance Welding

    DEFF Research Database (Denmark)

    Song, Quanfeng

    simulation of resistance welding has been under development for many years. Yet it is no easy to make simulation results reliable and accurate because of the complexity of resistance welding process. In the 2nd part of the report numerical modeling of resistance welding is reviewed, some critical factors......This report originates from the compulsory defense during my Ph.D. study at the Technical University of Denmark. Resistance welding is an old and well-proven technology. Yet the emergence of more and more new materials, new designs, invention off new joining techniques, and more stringent...... requirement in quality have imposed challenges to the resistance welding. More some research and development have to be done to adapt the old technology to the manufacturing industry of the 21st century. In the 1st part of the report, the challenging factors to the resistance welding are reviewed. Numerical...

  19. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    OpenAIRE

    Varma, S. K.; RAPELLIWAR A; S. Sutradhar; THAWARE P; Misra, A. K.

    2013-01-01

    Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Impro...

  20. Terabit Wireless Communication Challenges

    Science.gov (United States)

    Hwu, Shian U.

    2012-01-01

    This presentation briefly discusses a research effort on Terabit Wireless communication systems for possible space applications. Recently, terahertz (THz) technology (300-3000 GHz frequency) has attracted a great deal of interest from academia and industry. This is due to a number of interesting features of THz waves, including the nearly unlimited bandwidths available, and the non-ionizing radiation nature which does not damage human tissues and DNA with minimum health threat. Also, as millimeter-wave communication systems mature, the focus of research is, naturally, moving to the THz range. Many scientists regard THz as the last great frontier of the electromagnetic spectrum, but finding new applications outside the traditional niches of radio astronomy, Earth and planetary remote sensing, and molecular spectroscopy particularly in biomedical imaging and wireless communications has been relatively slow. Radiologists find this area of study so attractive because t-rays are non-ionizing, which suggests no harm is done to tissue or DNA. They also offer the possibility of performing spectroscopic measurements over a very wide frequency range, and can even capture signatures from liquids and solids. According to Shannon theory, the broad bandwidth of the THz frequency bands can be used for terabit-per-second (Tb/s) wireless communication systems. This enables several new applications, such as cell phones with 360 degrees autostereoscopic displays, optic-fiber replacement, and wireless Tb/s file transferring. Although THz technology could satisfy the demand for an extremely high data rate, a number of technical challenges need to be overcome before its development. This presentation provides an overview the state-of-the- art in THz wireless communication and the technical challenges for an emerging application in Terabit wireless systems. The main issue for THz wave propagation is the high atmospheric attenuation, which is dominated by water vapor absorption in the THz

  1. Energy challenges in Asia

    International Nuclear Information System (INIS)

    Energy challenges represent one of the most important security paradigms in the Asia Pacific region where you have a mixture of growing energy dependency, fuelled by high economic growth, the emergence of new major players like China and India, and a quasi-complete absence of regional regulatory mechanisms to tackle the challenges in a multilateral way. These challenges mostly concern Japan and China, where crucial energy issues are aggravated by power rivalry, historical and ideological issues, and a lack of both economic and political harmony between them. Neither countries are self sufficient in terms of energy needs. This can lead to a shared analysis and common approaches regarding Japan and China concerning this issue. Their cases are. however very different and the solutions applied are related to different world views that are not easily reconcilable. Both countries share common objectives: both want security and stable supply. But there are also big divergences and these divergences could be new sources of conflict and misunderstanding between Tokyo and Beijing. One of the main differences is history related. Both China and Japan are uneasy regarding outside energy dependency. In Japan, memories of the pre-war oil embargo have not disappeared. The oil shocks of the 70's renewed this uneasiness. However, Japan's outside dependency is not new. Tokyo has learned to live with it, finding a system to alleviate this vulnerability in cooperation with its partners, multilateral institutions like the International Energy Agency (IEA). China's outside dependency is new. The country's dependency on oil, which began in 1993, is particularly challenging since the principles of independence, non interference and military autonomy, principles at the core of Maoist foreign strategy, did not completely disappear in spite of China's new policy of reform and opening up. China's leadership, even the fourth generation, did not forget its isolation during the 60's and 70's

  2. CHALLENGES FOR FOREIGN TEACHERS

    Institute of Scientific and Technical Information of China (English)

    DengJing

    2004-01-01

    The learner differences and contrasts between the two cultures involved are important aspects that influence foreign language teaching and learning. The foreign teacher as an outsider of the learner's native culture, inevitably faces quite a few challenges. With the focus on the self-esteem, character types, and motivation of the learner, the paper analyses how these factors influence the foreign teacher's teaching. Relevant solutions are also proposed.

  3. Challenges in Danish VET

    DEFF Research Database (Denmark)

    Aarkrog, Vibe

    2011-01-01

    In Denmark the 95 percent target, meaning that in 2015 95 percent of a youth cohort should complete a youth education programme, is particularly challenging for the vocational educational and training (VET) system. In the article is given a short outline of the significant characteristics of the...... Danish dual VET system as well as of the current central initiatives aimed at reaching the 95 percent target....

  4. Librarianship: A Challenging Profession

    OpenAIRE

    Lalithabai, K K.

    1996-01-01

    Defines librarianship as the art and science of managing recorded knowledge. Observes that in earlier days when the recorded sources of information were limited in number, scholars could be the users as well as managers of libraries. But today’s libraries with torrents of information sources and users on either side makes management a truly challenging task requiring highly specialized knowledge and training in the sophisticated techniques of information handling. Views that in information co...

  5. Cleanroom laboratory challenge overcome.

    Science.gov (United States)

    Quinn, Ronan

    2010-10-01

    Ronan Quinn, managing director of interior construction specialist Ardmac, describes the challenges of building and fitting out a new cleanroom laboratory for blood and bone marrow therapeutic treatment at Our Lady's Children's Hospital Crumlin in Dublin. The "state-of-the-art" facility, which fully complies with the recent EU Directive concerning human tissues and cells, has been well received by the client and end-users alike, but, as he explains, there were many obstacles to overcome during its completion.

  6. South China Sea Challenge

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    China's attempts to solve disputes with ASEAN over the South China Sea help regional peace China's marine economy and security are currently faced with new challenges, requiring careful handling, especially in disputes with ASEAN countries and in promoting common development of the South China Sea. The outcome of how this is dealt with could undoubtedly pave the way for solutions to other oceanic disputes. The South China Sea is located south of

  7. Challenges in Crowd Simulation

    OpenAIRE

    Thalmann, Daniel; Grillon, Helena; Maim, Jonathan; Yersin, Barbara

    2009-01-01

    The purpose of this paper is to identify the problems to solve in order to simulate real-time crowds in a Virtual Environment. We try to classify these problems and study how they have been addressed until now by the research community and our Lab in particular. We then discuss for each problem what are the,future challenges and how to address them.

  8. Gaddafi's Death Poses Challenges

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The death of Muammar Gaddafi marks a new era for Libya.It also poses a huge challenge for Libyan authorities dealing with tribal conflicts.He Wenping,a researcher with the Institute of West-Asian and African Studies at the Chinese Academy of Social Sciences,believes that Libya is in danger of falling into a period of internal strife and tribal conflict.

  9. Sustainability challenges and trends

    OpenAIRE

    De Ridder, M.

    2011-01-01

    In the coming decades, increases in population, income and health will put additional pressures on our planet’s biosphere. To meet the needs of future generations, we need to adapt our ways of living and definitions of economic development. A transition to a more sustainable world is imperative if we want to stop depleting the Earth’s resources more quickly than it can regenerate them. This paper synthesizes current trends and challenges that are relevant for the policy debate on sustainabili...

  10. ATLAS Data Challenge 1

    CERN Document Server

    DC1 TaskForce

    2003-01-01

    The ATLAS Collaboration at CERN is preparing for the data taking and analysis at LHC that will start in 2007. Therefore, in 2002 a series of Data Challenges (DC's) was started whose goals are the validation of the Computing Model, of the complete software suite, of the data model, and to ensure the correctness of the technical choices to be made. A major feature of the first Data Challenge (DC1) was the preparation and the deployment of the software required for the production of large event samples for the High Level Trigger and Physics communities, and the production of those large data samples as a worldwide distributed activity. It should be noted that it was not an option to "run everything at CERN" even if we had wanted to; the resources were not available at CERN to carry out the production on a reasonable time-scale. We were therefore faced with the great challenge of organising and then carrying out this large-scale production at a significant number of sites around the world. However, the benefits o...

  11. IDEOLOGICALLY CHALLENGING ENTERTAINMENT (ICE

    Directory of Open Access Journals (Sweden)

    Dana Lori Chalmers

    2015-09-01

    Full Text Available Ideologically Challenging Entertainment (ICE is entertainment that challenges ‘us vs. them’ ideologies associated with radicalization, violent conflict and terrorism. ICE presents multiple perspectives on a conflict through mainstream entertainment. This article introduces the theoretical underpinnings of ICE, the first ICE production and the audience responses to it. The first ICE production was Two Merchants: The Merchant of Venice adapted to challenge ideologies of the Arab-Israeli Conflict. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views. Each performance included two versions of the adaptation: a Jewish dominated society with an Arab Muslim minority, contrasted with an Arab Muslim dominated society and a Jewish minority. A mixed-methods study of audience responses explored whether this production inspired audiences to shift their ideological views to become more tolerant of differences away from ideological radicalization. Of audience members who did not initially agree with the premise of the production, 40% reconsidered their ideological views, indicating increased tolerance, greater awareness of and desire to change their own prejudices. In addition, 86% of the audience expressed their intention to discuss the production with others, thereby encouraging critical engagement with, and broader dissemination of the message. These outcomes suggest that high quality entertainment – as defined by audience responses to it - can become a powerful tool in the struggle against radicalised ideologies.

  12. Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages.

    Science.gov (United States)

    Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto; Becker, María Inés

    2016-06-01

    Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5 Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages.

  13. Simulating hypoxia-induced acidic environment in cancer cells facilitates mobilization and redox-cycling of genomic copper by daidzein leading to pro-oxidant cell death: implications for the sensitization of resistant hypoxic cancer cells to therapeutic challenges.

    Science.gov (United States)

    Ullah, Mohammad F; Ahmad, Aamir; Bhat, Showket H; Khan, Husain Y; Zubair, Haseeb; Sarkar, Fazlul H; Hadi, Sheikh M

    2016-04-01

    This study was conducted to investigate the mechanism of action involved in the anti-cancer activity of daidzein and identification of cancer specific micro-environment as therapeutic target of this secondary metabolite derived from soy. Our data indicated that daidzein induces cellular DNA breakage, anti-proliferative effects and apoptosis in a concentration-dependent manner. We demonstrated that such a daidzein-induced anti-cancer action involves a copper-dependant pathway in which endogenous copper is mobilized by daidzein and redox-cycled to generate reactive oxygen species which act as an upstream signal leading to pro-oxidant cell death. Further in the context of hypoxia being a resistant factor against standard therapies and that an effect secondary to hypoxia is the intracellular acidification, we show that the anticancer activity of daidzein is modulated positively in acidic pH but copper-specific chelator is still able to inhibit daidzein activity. Moreover, an experimental setup of hypoxia mimic (cobalt chloride) revealed an enhanced sensitivity of cancer cells to the cytotoxic effects of daidzein which was neutralized in the presence of neocuproine. The findings support a paradigm shift from the conventional antioxidant property of dietary isoflavones to molecules capable of initiating a pro-oxidant signaling mediated by reactive oxygen species. Further, the clinical relevance of such an action mechanism in cancer chemoprevention is also proposed. This study identified endogenous copper as a molecular target and acidic pH as a modulating factor for the therapeutic activity of daidzein against cancer. The evidence presented highlights the potential of dietary agents as adjuvants to standard therapeutic regimens.

  14. Challenges in pharmacogenetics.

    Science.gov (United States)

    Cascorbi, Ingolf; Bruhn, Oliver; Werk, Anneke N

    2013-05-01

    The attempt to optimize drug treatment of patients by using evidenced-based medicine considering individual physiological and disease-related conditions is standard of modern medicine. Pharmacogenetics (PGx) has contributed to individualization considering hereditary genetic information; however, increasingly, pharmacogenomics is becoming essential, particularly in relation to modern oncology. New technologies such as next-generation sequencing and rapid development of computational and information sciences will help to better elucidate the consequences of genetic variation, considering also epigenetics and gene-environmental interactions and their translation into clinically relevant individual phenotypes. This review highlights the current challenging and most promising examples of PGx. PMID:23640184

  15. The Biofilm Challenge

    DEFF Research Database (Denmark)

    Alhede, Maria; Alhede, Morten

    2014-01-01

    reveals the significance of biofilms, as evidenced by a dramatic increase in scientific publications on the topic, as well as in publications concerning wounds with biofilms, which reached 600 publications in 2013. Judged from the number of publications, it appears that biofilms play a significant role...... in wounds. However, the impact of biofilms is often debated, because infected wounds were also treated before the concept of biofilms was coined. In this short review, we will address the significance of biofilms and their role in wounds, and discuss the future tasks of the biofilm challenge....

  16. Energy challenges in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Niquet, V.

    2007-07-01

    Energy challenges represent one of the most important security paradigms in the Asia Pacific region where you have a mixture of growing energy dependency, fuelled by high economic growth, the emergence of new major players like China and India, and a quasi-complete absence of regional regulatory mechanisms to tackle the challenges in a multilateral way. These challenges mostly concern Japan and China, where crucial energy issues are aggravated by power rivalry, historical and ideological issues, and a lack of both economic and political harmony between them. Neither countries are self sufficient in terms of energy needs. This can lead to a shared analysis and common approaches regarding Japan and China concerning this issue. Their cases are. however very different and the solutions applied are related to different world views that are not easily reconcilable. Both countries share common objectives: both want security and stable supply. But there are also big divergences and these divergences could be new sources of conflict and misunderstanding between Tokyo and Beijing. One of the main differences is history related. Both China and Japan are uneasy regarding outside energy dependency. In Japan, memories of the pre-war oil embargo have not disappeared. The oil shocks of the 70's renewed this uneasiness. However, Japan's outside dependency is not new. Tokyo has learned to live with it, finding a system to alleviate this vulnerability in cooperation with its partners, multilateral institutions like the International Energy Agency (IEA). China's outside dependency is new. The country's dependency on oil, which began in 1993, is particularly challenging since the principles of independence, non interference and military autonomy, principles at the core of Maoist foreign strategy, did not completely disappear in spite of China's new policy of reform and opening up. China's leadership, even the fourth generation, did not forget its isolation

  17. The New Asian Challenge

    OpenAIRE

    C. Fred Bergsten

    2000-01-01

    The initial postwar challenge from East Asia was economic. Japan crashed back into global markets in the 1960s, became the largest surplus and creditor country in the 1980s, and was viewed by many as the world’s dominant economy by 1990. The newly industrialized countries (Korea, Taiwan, Hong Kong, Singapore) followed suit on a smaller but still substantial scale shortly thereafter. China only re-entered world commerce in the 1980s but has now become the second largest economy (in purchasing ...

  18. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  19. Semantic Web Evaluation Challenge

    CERN Document Server

    2014-01-01

    This book constitutes the thoroughly refereed post conference proceedings of the first edition of the Semantic Web Evaluation Challenge, SemWebEval 2014, co-located with the 11th Extended Semantic Web conference, held in Anissaras, Crete, Greece, in May 2014. This book includes the descriptions of all methods and tools that competed at SemWebEval 2014, together with a detailed description of the tasks, evaluation procedures and datasets. The contributions are grouped in three areas: semantic publishing (sempub), concept-level sentiment analysis (ssa), and linked-data enabled recommender systems (recsys).

  20. Perishable Inventory Challenges

    DEFF Research Database (Denmark)

    Damgaard, Cecilie Maria; Nguyen, Vivi Thuy; Hvolby, Hans-Henrik;

    2012-01-01

    The paper investigates how inventory control of perishable items is managed and line up some possible options of improvement. This includes a review of relevant literature dealing with the challenges of determining ordering policies for perishable products and a study of how the current procedures...... in the retail supply chains. The goal is to find and evaluate the parameters which affect the decision making process, when finding the optimal order quantity and order time. The paper takes a starting point in the retail industry but links to other industries....

  1. New challenges? Well, certainly!

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    New challenges? Well, certainly! With the internationalization of European higher education, teaching and learning through the medium of a foreign language has become more and more widespread in recent years. This requires, of course, that lecturers as well as students have the necessary language......, different cultural backgrounds, different educational backgrounds and be used to a diverse set of didactic traditions and norms. Given this diversity, higher education institutions (HEIs) need to have measures in place to deal with this. Policies and practices must go hand in hand and, more often than not...

  2. Induced Abortion

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  3. Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls. Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge

    DEFF Research Database (Denmark)

    Borg, L; Christensen, J M; Kristiansen, J;

    2000-01-01

    Exposure to nickel is a major cause of allergic contact dermatitis which is considered to be an inflammatory response induced by antigen-specific T cells. Here we describe the in vitro analysis of the nickel-specific T-cell-derived cytokine response of peripheral blood mononuclear cells from 35...... nickel-allergic and 30 non-nickel-allergic individuals. Peripheral blood mononuclear cells were stimulated with 10(-4) and 10(-5) mol/l NiSO4 for 6 days and then additionally with ionomycin and phorbol myristate acetate for 24 h. Culture supernatants were analysed for interleukin-4 (IL-4), IL-5......, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) by quantitative ELISA. The analysis showed that the synthesis of IL-4 and IL-5 but not of IFN-gamma or TNF-alpha was significantly higher in the nickel-allergic individuals. The finding of preferential synthesis of Th2 cytokines...

  4. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  5. Safeguards by Design Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Alwin, Jennifer Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-13

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

  6. Review - China's Environmental Challenges

    Directory of Open Access Journals (Sweden)

    Bill Bleisch

    2013-12-01

    Full Text Available Review of: Judith Shapiro. 2012. China's Environmental Challenges. Cambridge: UK and Malden, MA: Polity Press. Judith Shapiro's latest ambitious work picks up the story of modern China's checkered relationship with the environment at approximately the point where her previous study, Mao's War Against Nature (2001, left off. This latest book sets out to address questions of grave importance to China and to the world. The litany of challenges – poisonous water and toxic air, scarcity of water and other resources, deforestation, soil erosion, loss of biodiversity – seem nearly insurmountable, despite evidence of considerable attention from the Chinese government and from China's public, and despite the rocket-like rise of China's economic power and political influence in the world. Shapiro adds to this list the growing problems with lapses in environmental justice, both within China and passed on to its neighbours and to the countries with which it trades. Not only do growing environmental problems affect China's ability to achieve the government's stated goals of a 'harmonious society' with 'moderate prosperity for all,' but these problems, and the ways that ...

  7. The ALICE Data Challenges

    CERN Document Server

    Baud, J P; Carminati, F; Collignon, M; Collin, F; Divià, R; Durand, J D; Jarp, S; Jouanigot, J M; Panzer, B; Rademakers, F; Saiz, P; Schossmaier, K; Van de Vyvre, P; Vascotto, Alessandro

    2001-01-01

    Since 1998, the ALICE experiment and the CERN/IT division have jointly executed several large-scale high throughput distributed computing exercises: the ALICE data challenges. The goals of these regular exercises are to test hardware and software components of the data acquisition and computing systems in realistic conditions and to execute an early integration of the overall ALICE computing infrastructure. This paper reports on the third ALICE Data Challenge (ADC III) that has been performed at CERN from January to March 2001. The data used during the ADC III are simulated physics raw data of the ALICE TPC, produced with the ALICE simulation program AliRoot. The data acquisition was based on the ALICE online framework called the ALICE Data Acquisition Test Environment (DATE) system. The data after event building were then formatted with the ROOT I/O package and a data catalogue based on MySQL was established. The Mass Storage System used during ADC III is CASTOR. Different software tools have been used to mo...

  8. Résultats challenge

    CERN Multimedia

    Club de pétanque

    2015-01-01

    C'est avec un temps magnifique que se disputait pour la deuxième année le Challenge de notre cher ami Patrick DURAND le jeudi 30 juillet 2015. Vingt-six personnes formées en doublettes s'affrontaient pour trois parties .Après des parties très serrées le juge arbitre Claude JOUVE épaulé par Alain PHILIPONA déclarait  vainqueur l'imbattable Claude MACARI suivi de très près par Eric DARMEDRU et à la troisième place Christian JOUVE. La première féminine était Mireille ROCHE. La soirée se clôturait par une succulente paëlla préparée par Jennifer et sa maman Sylvie JOUVE. Rendez-vous à tous pour le jeudi 27 août 2015 pour le challenge Jean-Claude FROT Nos concours sont ouverts à tous les amateurs de pétanque.

  9. Proteomics Technologies and Challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

  10. Rising to the Challenge

    Directory of Open Access Journals (Sweden)

    Xiaoping Li

    2015-06-01

    Full Text Available Writing is recognized as a vital skill in education and the workplace; students in the United States finishing K-12 schooling are expected to be competent writers. Yet, the Nation’s Report Card found that U.S. high school graduates coming into the workforce are particularly deficient in writing skills. Teachers serve as a crucial link in the move to improve literacy skills of K-12 students; however, teachers themselves are underprepared to be writers and writing teachers. Therefore, there is an urgent need to improve teachers’ writing skills and skills of teaching writing to improve K-12 students’ writing skills in the United States. This qualitative study examined the process-based writing project experienced by 22 practicing teachers through their reflective practices in a graduate capstone class. In particular, this study explored the challenges the teachers faced and the lessons they learned through the recursive phases of writing: planning, drafting, revising, editing, conferring, and publishing. The triangulation of the researchers’ field notes, teachers’ daily reflections, and informal interviews between the instructor and the teachers indicated that the challenges the teachers faced and the lesson they learned through the process-based writing project were phase specific. On the completion of the writing project, the participating teachers (a developed a deep understanding of process-based writing; (b learned new skills of planning, drafting, revising, editing, and sharing; and (c were more confident as writers themselves and as writing teachers for their students.

  11. Challenge Based Innovation gala

    CERN Document Server

    CERN. Geneva; Utriainen, Tuuli Maria; Toivonen, Harri; Nordberg, Markus

    2014-01-01

    Challenge Based Innovation gala   There’s a new experiment starting in CERN called IdeaLab where we work together with detector R&D researchers to help them to bridge their knowledge into a more human, societally oriented context. Currently we are located in B153, but will move our activities to a new facility next to the Globe in May 2014. One of our first pilot projects is a 5 month course CBI (Challenge Based Innovation) where two multidisciplinary student teams join forces with Edusafe & TALENT projects at CERN. Their goal is to discover what kind of tools for learning could be created in collaboration with the two groups. After months of user interviews and low resolution prototyping they are ready to share the results with us in the form of an afternoon gala. We warmly welcome you to join us to see the students' results and experience the prototypes they have conceived. The event is in three parts, you are welcome to visit all of them,...

  12. The ALICE Data Challenges

    Institute of Scientific and Technical Information of China (English)

    J.P.Baud; W.Carena; 等

    2001-01-01

    Since 1998,the ALICE experiment and the CERN/IT division have jointly executed several large-scale high throughput distributed computing exercises:the ALICE data challenges.The goals of these regular exercises are to test hardware and software components of the data acqusition and computing systems in realistic conditions and to execute an early integration of the overall ALICE computing infrastructure.This paper reports on the third ALICE Data Challenge (ADC III) that has been performed at CERN from January to March 2001.The data used during the ADC Ⅲ are simulated physics raw data of the ALICE TPC,produced with the ALICE simulation program AliRoot.The data acquisition was based on the ALICE online framework called the ALICE Data Acquisition Test Environment (DATE) system.The data after event building,were then formatted with the ROOT I/O package and a data catalogue based on MySQl was established.The Mass Storage System used during ADC III is CASTOR.Different software tools have been used to monitor the performances,DATE has demonstrated performances of more than 500 MByte/s.An aggregate data throughput of 85 MByte/s was sutained in CASTOR over several days.The total collected data amounts to 100 TBytes in 100.00 files.

  13. The competitive challenge in banking

    NARCIS (Netherlands)

    A.W.A. Boot; A. Schmeits

    2005-01-01

    The increasingly competitive environment poses challenges to bankers. This paper emphasizes relationship banking as a prime source of the banks' comparative advantage. The proliferation of transaction-oriented banking (trading and financial market activities) does however seriously challenge relatio

  14. Offshore northern Europe, the challenges

    International Nuclear Information System (INIS)

    This paper relates to challenges of the offshore activity in the North Sea. It is appropriate to address these challenges in the context of generating values through efficient management of resources, markets, safety and technology, as the challenges lie therein. The petroleum industry is built to turn natural resources into market value, assuring broad benefits to stake holders and shareholders. In the following, the challenges facing the industry the industry offshore Northern Europe is examined on this background

  15. WCET Tool Challenge 2011: Report

    OpenAIRE

    Bonenfant, Armelle; Cassé, Hugues; Bünte, Sven; Fellger, Wolfgang; Gepperth, Sebastian; Gustafsson, Jan; Huber, Benedikt; Islam, Nazrul Mohammad; Kästner, Daniel; Kirner, Raimund; Kovács, Laura; Krause, Felix; De Michiel, Marianne; Olesen, Mads Christian; Prantl, Adrian

    2011-01-01

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC’11) defined two kinds of problems to be solved by the Challenge participants with their tools, WCET problems, which ask for bounds on the execution time, and flow-analysis problems, which ask for bounds on the number ...

  16. Offshore northern Europe, the challenges

    Energy Technology Data Exchange (ETDEWEB)

    Bergseth, S. [Statoil, Stavenger (Norway)

    1996-12-31

    This paper relates to challenges of the offshore activity in the North Sea. It is appropriate to address these challenges in the context of generating values through efficient management of resources, markets, safety and technology, as the challenges lie therein. The petroleum industry is built to turn natural resources into market value, assuring broad benefits to stake holders and shareholders. In the following, the challenges facing the industry the industry offshore Northern Europe is examined on this background

  17. Challenging Fieldwork Situations

    DEFF Research Database (Denmark)

    Bille, Thomas; Østergaard Steenfeldt, Vibeke

    2013-01-01

    understanding on the phenomenon of awkwardness as a natural way for researchers to respond to challenging fieldwork situations. Finally, they propose and unfold mutual interviewing and cooperative analysis as methods of investigating researcher’s subjectivity in facing such situations.......Researching two different work settings, police work and hospice care, the authors experienced a strange sense of discomfort in their bodies during their fieldwork when investigating professional training and work situations, especially in encounters with citizens and patients. In some of those...... situations, the authors withdrew physically or mentally from the situation without wanting to do so, feeling emotionally affected by the uncertainty of the situations, not fully grasping the meaning of what was going on. In a strange way they felt awkwardly detached from their research activities...

  18. Multicore Programming Challenges

    Science.gov (United States)

    Perrone, Michael

    The computer industry is facing fundamental challenges that are driving a major change in the design of computer processors. Due to restrictions imposed by quantum physics, one historical path to higher computer processor performance - by increased clock frequency - has come to an end. Increasing clock frequency now leads to power consumption costs that are too high to justify. As a result, we have seen in recent years that the processor frequencies have peaked and are receding from their high point. At the same time, competitive market conditions are giving business advantage to those companies that can field new streaming applications, handle larger data sets, and update their models to market conditions faster. The desire for newer, faster and larger is driving continued demand for higher computer performance.

  19. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann;

    2015-01-01

    Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study...... was undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  20. Sustainable Consumption: Research Challenges

    DEFF Research Database (Denmark)

    Reisch, Lucia A.; Cohen, Maurie J.; Thøgersen, John;

    The Board of the Swedish Foundation for Strategic Environmental Research (Mistra) decided in October 2015 that a proposal for a funding application call in the research area of “sustainable consumption” should be drawn up. According to the statutes of Mistra, research funded by the foundation...... policy) processes that are underway in Sweden and the rest of the European Union (EU) to tackle these challenges; ► to provide an overview of where the international research frontline is located and the status of Swedish research gaps in the area from an international perspective; ► to propose in detail...... “shall promote the development of strong research environments of the highest international class with importance for Sweden’s future competitiveness. The research shall be of importance for finding solutions to important environmental problems and for a sustainable development of society. Opportunities...

  1. The challenge of implementation

    DEFF Research Database (Denmark)

    Andersen, Karen Heide Hauge

    2015-01-01

    Reaching the students in innovation and entrepreneurship courses is hard, when the courses are a requirement but not included in the main project of the curriculum. It is a major paradox for lecturers, who have never participated in and cannot see the relevance of such course, to implement...... these concepts in daily teaching, as it is strongly encouraged by policy makers and educations. This paper aims to discuss how lecturers experience the challenge of teaching their own discipline while being imposed to embrace and promote innovation and entrepreneurship teaching. Through a single study case...... of the paper: which factors influence the degree of implementation of innovation and entrepreneurship in the individual lecturers’ daily teaching? The paper questions the common approach taken by higher educational institutions whereby lecturers are urged to teach innovation and entrepreneurship with minor...

  2. EOSDIS Customer Support Challenges

    Science.gov (United States)

    Moses, J. F.; Boquist, C. L.

    2006-05-01

    The Earth Observation System Data and Information System (EOSDIS) is a large, complex data system currently supporting over 18 operational NASA satellite missions including the flagship EOS missions: Terra, Aqua, and Aura. The observations collected by these missions are kept at geographically distributed data centers. EOSDIS manages over four petabytes of data accessed by over 200,000 distinct users last year. The data centers distributed more than 37 million Earth science data products during 2005 to a diverse customer community. An important goal for these data centers is to provide an adequate service at a uniform level for the user community to ensure we get the most benefit from our investment in space resources. This paper discusses the challenges, the ways the data centers coordinate among themselves to provide service, and recent results of measuring customer satisfaction with this service.

  3. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    VARMA S. K

    2013-01-01

    Full Text Available Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Improvement in knowledge in pharmacovigilance and communication from the top level to the grass-root level in the health sector will help in proper implementation of the programme. Patient should be educated to report any adverse effects after taking drug and stop relaying on acquiring information related to drugs in web. Proper detection, reporting and analysis would help to implement the programme for the betterment of society.

  4. Challenge Measurements For Authentication

    International Nuclear Information System (INIS)

    Authentication of systems with an information barrier that protects sensitive information is difficult; in particular, the information barrier can allow a hidden switch to be implemented by the system fabricator and operator. The hidden switch is the operator's ability to subvert the measurement system and force it to produce a desired and false result. It is usually discussed in the context of an attribute measurement in which a faked item is presented in place of a real item regulated by an agreement, with the driving motivation being the ability to preserve a stock of valuable items. In simple terms, the hidden switch enables a shell game with assets, and the information barrier protects the switch. This presentation outlines challenge measurements that could be used to detect the implementation of a hidden switch and assist the authentication process.

  5. A specific nanomanufacturing challenge

    Science.gov (United States)

    Kelly, M. J.; Dean, M. C.

    2016-03-01

    For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO® brick scaled down by a factor of 10 n for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

  6. Polyhydroxyalkanoates, challenges and opportunities.

    Science.gov (United States)

    Wang, Ying; Yin, Jin; Chen, Guo-Qiang

    2014-12-01

    Microbial polyhydroxyalkanoates (PHA) have been developed as biodegradable plastics for the past many years. However, PHA still have only a very limited market. Because of the availability of large amount of shale gas, petroleum will not raise dramatically in price, this situation makes PHA less competitive compared with low cost petroleum based plastics. Therefore, two strategies have been adopted to meet this challenge: first, the development of a super PHA production strain combined with advanced fermentation processes to produce PHA at a low cost; second, the construction of functional PHA production strains with technology to control the precise structures of PHA molecules, this will allow the resulting PHA with high value added applications. The recent systems and synthetic biology approaches allow the above two strategies to be implemented. In the not so distant future, the new technology will allow PHA to be produced with a competitive price compared with petroleum-based plastics.

  7. New challenges in gas

    Energy Technology Data Exchange (ETDEWEB)

    Mandil, C. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France); Chabrelie, M.F. [Cedigaz, 92 - Rueil Malmaison (France); Streicher, C. [Prosernat, 92 - Paris la Defense (France)] [and others

    2003-07-01

    New developments in the area of gas treatment will be to a large extent driven by the need to find appropriate solutions to the fundamental need of sustainable development. New gas treatment processes are developed with the aim to minimise contaminant emissions and meet most stringent environmental specifications. A new major challenge for the industry will be to implement new cost effective technologies for reducing CO{sub 2} emissions. Industry has also to minimise its costs, and therefore, in order to ensure at the same time a better protection of the environment and a better safety, it is necessary to innovate. The purpose of this seminar is precisely to identify better the innovations which are required in the area of gas treatment. These proceedings comprise 8 papers and a summary of the contributions to a round-table discussion dealing with the options for CO{sub 2} capture and sequestration. The presentations treat of: the future prospects for the gas industry (M.F. Chabrelie, Cedigaz); the solutions for offshore gas treatment (C. Streicher, Prosernat); gas treatment with membranes (H. Meyer, GTI); the Axens Multibed{sub TM} technology for natural gas treatment (G. Jochem, Axens); the potentials and applications for the Propure co-current contactors (F.P. Nilsen, ProPure); the production of very-sour and super-sour large gas reserves: the new challenges (F. Lallemand, TotalFinaElf); Hybrisol, a new gas treatment process for sour natural gases (F. Lecomte, IFP); and the conception and building of large acid-gas removal units (J. Castel, Technip-Coflexip). (J.S.)

  8. Smart City Architecture: Vision and Challenges

    Directory of Open Access Journals (Sweden)

    Narmeen Zakaria Bawany

    2015-11-01

    Full Text Available The concept of smart city was born to provide improved quality of life to citizens. The key idea is to integrate information system services of each domain, such as health, education, transportation, power grid etc., of the city to provide public services to citizens efficiently and ubiquitously. These expectations induce massive challenges and requirements. This research is aimed to highlight key ICT (Information and Communication Technology challenges related to adaptation of smart city. Realizing the significance of effective data collection, storage, retrieval, and efficient network resource provisioning, the research proposes a high level architecture for smart city. The proposed framework is based on a hierarchical model of data storage and defines how different stakeholders will be communicating and offering services to citizens. The architecture facilitates step by step implementation towards a smart city, integrating services, as they are developed in a timely manner.

  9. Clinical Challenges in Catecholaminergic Polymorphic Ventricular Tachycardia.

    Science.gov (United States)

    Imberti, Jacopo F; Underwood, Katherine; Mazzanti, Andrea; Priori, Silvia G

    2016-08-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disorder associated with exercise- and stress-induced sudden death in young individuals. Although important steps forward have been made in the comprehension and treatment of this disease, several aspects remain unclear. Firstly, from an epidemiological standpoint the actual prevalence of CPVT is still unknown and possibly underestimated. In addition, the diagnostic process remains very challenging and can be supported by genetic analysis in only about half of the cases. Finally, up to one third of CPVT patients continue to present complex arrhythmias despite beta blocker treatment; the role of newer therapeutic options, such as flecainide and left cardiac sympathetic denervation, needs to be further elucidated. All these points constitute challenges for the cardiologist in the management of CPVT patients and fuel research into new diagnostic, prognostic and therapeutic approaches. PMID:26948768

  10. Turner's syndrome: challenges of late diagnosis.

    Science.gov (United States)

    Lee, Marilyn Cheng; Conway, Gerard S

    2014-04-01

    Girls and women with Turner's syndrome who come to medical attention older than 12 years present a challenge of medical management. Puberty is already delayed and some compromises have to be made in adjusting the timing of artificially induced puberty to optimise overall outcome with respect to stature, secondary sex characteristics, and psychosocial endpoints. Additionally, individuals who present with primary amenorrhoea to adult services might miss the opportunity for effective growth hormone treatment. Further, induction of puberty regimens lack an evidence base or even clear guidelines for the timing and dose of oestrogen replacement. We have searched the scientific literature to inform management of Turner's syndrome. PMID:24703051

  11. Safeguards information challenges

    International Nuclear Information System (INIS)

    Full text: Overall, the aim of this paper is to provide the background and the broader vision in which the various information related presentations and posters proposed by the Department find their place, exploring solutions to the challenges faced. At a time when the Agency is expected to be a reference for the assessment of nuclear proliferation threats, providing the international community with independent, impartial, timely and credible conclusions that no declared nuclear material is diverted to non-peaceful purposes and that no undeclared nuclear material or activities exist in States, it has to address major challenges with regard to information. Drawing credible conclusions assumes that all relevant information is accessible and put into relevant context. Because of the legal constraints under which it operates, the limitation of resources for collecting existing but difficult to reach details and simply because of the overwhelming quantity of the information needed to properly evaluate proliferation issues, the Agency has to continually improve the way it collects, processes and internally disseminates safeguards relevant information. Developing a coherent picture of a State's nuclear capability is a complex process based on many experts' assessments and fusion of information. The search for better, broader and deeper information through dedicated collection processes is an ongoing effort aimed at filling the gaps of such pictures. Implementing well selected information collection tools is a sine qua non to render effective the Agency's detection capabilities. Beyond collection, another prerequisite to ensuring that the available information is accessible to those who need to know is the establishment of a proper information system architecture and an efficient set of standard business processes. At the same time, that information must be sufficiently protected by appropriate security measures, particularly at a time when private hacking has become a

  12. Safeguards information challenges

    International Nuclear Information System (INIS)

    The purpose of this paper is to provide the background and broader vision in which the various presentations and posters on information related matters, prepared by staff of the Department of Safeguards, find their place, exploring solutions to the challenges faced. At a time when the IAEA is expected to be a reference for the assessment of nuclear proliferation issues, it faces major challenges with regard to the information needed to provide the international community with independent, impartial, timely and soundly based conclusions regarding the non-diversion of declared nuclear material and the absence of undeclared nuclear material or activities in States. The drawing of such conclusions assumes that all relevant information is accessible and has been put in the relevant context. Unfortunately, because of legal constraints under which it operates, or because of limitations on resources available for collecting existing but difficult to reach facts, or simply because of the overwhelming aspect of the information needed to properly evaluate proliferation issues, the IAEA needs to enhance the way it collects, processes, analyses, evaluates and disseminates safeguards relevant information. The search for better, broader and deeper information through dedicated collection means is an ongoing effort aimed at filling the gaps that constrain the development of the coherent picture that analysts need to be comfortable with the results of complex analyses. Implementation of well-selected information collection tools is sine qua non for effective IAEA verification capabilities. Beyond collection, the establishment of a proper information architecture and documented business processes is a prerequisite for ensuring that the available information is accessible to those with a need to know. At the same time, information must be sufficiently protected by appropriate security measures, particularly when hacking has become an intellectual sport and institutional security

  13. Osteomyelitis: a current challenge

    Directory of Open Access Journals (Sweden)

    Luciana Souza Jorge

    2010-06-01

    Full Text Available Over the last 30 years, the pathogenesis of osteomyelitis has almost been totally elucidated, and many factors responsible for the persistence of this infection have been identified. Numerous antimicrobial agents with distinct spectrums of action, pharmacokinetics, and pharmacodynamics have been used in its treatment. Surgical techniques, including muscle grafts, the Ilizarov technique, and antibiotic bone cements, have been applied. However, bone infections are still a challenge. Despite the importance of isolation and identification of microorganisms to determine the antimicrobial treatment of bone infections, there are few systematic national studies about the etiological profile of these diseases. This article describes the current knowledge of osteomyelitis and summarizes published national data based on the experience of different Orthopedic and Traumatology Services. In general, S. aureus was described as an important etiological agent; however, the difference in design of national studies makes a comparison between the prevalence of bone infection, the associated risk factors, and the different therapeutic approaches difficult. In conclusion, effort is necessary in order to stimulate systematic national studies in different Orthopedics and Traumatology Services to obtain a better consensus on preventive measures and therapies of bone infections.

  14. Challenges in Organ Transplantation

    Directory of Open Access Journals (Sweden)

    Rafael Beyar

    2011-04-01

    Full Text Available Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty.

  15. Challenges in organ transplantation.

    Science.gov (United States)

    Beyar, Rafael

    2011-04-01

    Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty. PMID:23908807

  16. VISIR: Experiences and Challenges

    Directory of Open Access Journals (Sweden)

    Mohamed Tawfik

    2012-02-01

    Full Text Available It is of crucial importance the integration of practical sessions in engineering curricula owing to their significant role in understanding engineering concepts and scientific phenomena. However, the lack of practical sessions due to the high costs of the equipment and the unavailability of instructors has caused a significant declination in experimentation in engineering education. Remote laboratories have tackled this issues providing online reusable and shared workbenches unconstrained by neither geographical nor time considerations. Thereby, they have extremely proliferated among universities and integrated into engineering curricula over the last decade. This contribution compiles diverse experiences based on the deployment of the remote laboratory, Virtual Instrument Systems in Reality (VISIR, on the practices of undergraduate engineering grades at various universities within the VISIR community. It aims to show the impact of its usage on engineering education concerning the assessments of students and teachers as well. In addition, the paper address the next challenges and future works carried out at several universities within the VISIR community.

  17. Challenges in Piaget's legacy.

    Science.gov (United States)

    Bibace, Roger

    2013-03-01

    The publication of After Piaget (Martí and Rodríguez 2012) hopefully triggers a new effort to understand the richness of the efforts of that major psychologist of the 20th century. Piaget was consistently concerned with part/whole relationships throughout his life. He addressed this issue philosophically, epistemologically, and psychologically. Conceptually Piaget struggled with the issue of continuity/discontinuity in development and changed his mind about how to reconcile the discontinuities of stages with his concept of development. I also attribute his variability to the implications of his important work on perception, and to his willingness to get involved in widespread concrete applications of his approach to education including the education of children with special needs; his center for genetic epistemology, and his interest in psychoanalysis. Benefiting from all the authors of After Piaget, I want to point out that Piaget has identified many major issues that will continue to constitute challenges to psychology in this century. These include specifying terms such as 'development;' methodological issues such as sampling both quantitatively in one culture and across cultures; comprehensive inclusion of the psychological processes covered by introductory textbooks in psychology; and conceptual issues such as the relationships among all these parts within a whole. I make a distinction between an 'issue' and a 'problem'--problems have solutions; while issues refer to controversies in science generally as well as in psychology that have persisted for centuries. PMID:22733313

  18. Challenges in Astronomy Education

    Science.gov (United States)

    De Greve, Jean-Pierre

    2010-11-01

    Astronomy is an attractive subject for education. It deals with fascination of the unknown and the unreachable, yet is uses tools, concepts and insights from various fundamental sciences such as mathematics, physics, chemistry, biology. Because of this it can be well used for introducing sciences to young people and to raise their interest in further studies in that direction. It is also an interesting subject for teaching as its different aspects (observation techniques, theory, data sampling and analysis, modelling,?) offer various didactical approaches towards different levels of pupils, students and different backgrounds. And it gives great opportunities to teach and demonstrate the essence of scientific research, through tutorials and projects. In this paper we discuss some of the challenges education in general, and astronomy in particular, faces in the coming decades, given the major geophysical and technological changes that can be deducted from our present knowledge. This defines a general, but very important background in terms of educational needs at various levels, and in geographical distribution of future efforts of the astronomical community. Special emphasis will be given to creative approaches to teaching, to strategies that are successful (such as the use of tutorials with element from computer games), and to initiatives complementary to the regular educational system. The programs developed by the IAU will be briefly highlighted.

  19. [Geriatrics - an interdisciplinary challenge].

    Science.gov (United States)

    Nau, Roland; Djukic, Marija; Wappler, Manfred

    2016-06-01

    The care of elderly patients will continue to challenge the healthcare system over the next decades. As a rule geriatric patients suffer from multimorbidities with complex disease patterns, and the ability to cope with everyday life is severely reduced. Treatment is provided by a multiprofessional geriatric team, and the primary goal is improvement of functional status, quality of life in the social environment and autonomy by employing a holistic approach. In Germany geriatric care is provided by physicians from various medical specialties (e.g. general practitioners, internists, neurologists and psychiatrists). In the training for the subspecialty clinical geriatrics, these specialties enjoy equal rights. Recent efforts to establish a qualification as physician for internal medicine and geriatrics have initiated a discussion to make the suitability for qualification as a geriatrician dependent on the medical specialty. Geriatric patients benefit from multidisciplinary cooperation. Neurologists possess great expertise in the treatment of patients with dementia, depression, delirium, consequences of degenerative spinal cord diseases and vertebral bone fractures, stroke, Parkinson's syndrome, epileptic seizures, vertigo and dizziness, neuropathies, lesions of peripheral nerves and in the multimodal therapy of pain. To function in a position of responsibility in a geriatric department, neurologists need skills in general internal medicine. These are acquired either on a geriatric ward or during specialization as a neurologist by full time secondment to large neurological or interdisciplinary intensive care units. PMID:27167886

  20. Challenges of climate change

    Science.gov (United States)

    Husaini, Amjad M

    2014-01-01

    Kashmir valley is a major saffron (Crocus sativus Kashmirianus) growing area of the world, second only to Iran in terms of production. In Kashmir, saffron is grown on uplands (termed in the local language as “Karewas”), which are lacustrine deposits located at an altitude of 1585 to 1677 m above mean sea level (amsl), under temperate climatic conditions. Kashmir, despite being one of the oldest historical saffron-producing areas faces a rapid decline of saffron industry. Among many other factors responsible for decline of saffron industry the preponderance of erratic rainfalls and drought-like situation have become major challenges imposed by climate change. Saffron has a limited coverage area as it is grown as a ‘niche crop’ and is a recognized “geographical indication,” growing under a narrow microclimatic condition. As such it has become a victim of climate change effects, which has the potential of jeopardizing the livelihood of thousands of farmers and traders associated with it. The paper discusses the potential and actual impact of climate change process on saffron cultivation in Kashmir; and the biotechnological measures to address these issues. PMID:25072266

  1. Ribosomal Antibiotics: Contemporary Challenges

    Directory of Open Access Journals (Sweden)

    Tamar Auerbach-Nevo

    2016-06-01

    Full Text Available Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

  2. Ribosomal Antibiotics: Contemporary Challenges.

    Science.gov (United States)

    Auerbach-Nevo, Tamar; Baram, David; Bashan, Anat; Belousoff, Matthew; Breiner, Elinor; Davidovich, Chen; Cimicata, Giuseppe; Eyal, Zohar; Halfon, Yehuda; Krupkin, Miri; Matzov, Donna; Metz, Markus; Rufayda, Mruwat; Peretz, Moshe; Pick, Ophir; Pyetan, Erez; Rozenberg, Haim; Shalev-Benami, Moran; Wekselman, Itai; Zarivach, Raz; Zimmerman, Ella; Assis, Nofar; Bloch, Joel; Israeli, Hadar; Kalaora, Rinat; Lim, Lisha; Sade-Falk, Ofir; Shapira, Tal; Taha-Salaime, Leena; Tang, Hua; Yonath, Ada

    2016-01-01

    Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of "pathogen-specific antibiotics," in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification. PMID:27367739

  3. Effect of folate deficiency on experimental colitis in mice induced by dextran sodium sulfate%叶酸缺乏对葡聚糖硫酸钠诱导的小鼠实验性结肠炎的影响

    Institute of Scientific and Technical Information of China (English)

    马玉萍; 肖锐; 方维丽; 李海东; 刘文天

    2015-01-01

    Objective To investigate whether folate deficiency cause high expression level of interferon gamma (IFN-γ) resulted from IFN-γ gene ( IFNG) hypomethylation and then promote the pathogenesis and development of ulcerative colitis (UC ) in a dextran sulfate sodium (DSS )-induced experimental colitis model in mice .Methods A total of 24 female BALB/c mice were divided into four groups ,six mice in each group , including folate deficient/DSS+ group , standard diet/DSS+ group , standard diet/DSS - group and folate deficient/DSS- group .At the beginning of the sixth week since fed , the mice of model groups were treated with 5% DSS to establish experimental colitis .By the end of the sixth week ,disease activity index (DAI) of colitis and histological changes were evaluated .The folate level of peripheral blood serum of mice were detected by enzyme-linked immunosorbent assay (ELISA ) . The expression of IFN-γ in colonic mucosa of mice was examined by immunohistochemistry . The methylation level of CpG island in the promoter region of IFNG was determined by methylation specific polymerase chain reaction (MSP) .The t test was used for measurement data .Chi square test was performed for comparison between groups of count data . Spearman correlation analysis was used for correlation analysis .Results The folate levels of peripheral blood serum of folate deficiency/DSS+ group and folate deficiency/DSS- group ((2 .70 ± 0 .19) and (2 .80 ± 0 .25)μg/L) were significantly lower than those of standard diet/DSS+ group and standard diet/DSS- group ((13 .62 ± 0 .38 ) and (13 .52 ± 0 .77)μg/L ,t= -63 .33、32 .27 ,both P< 0 .05) ,resepectively .The expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group and standard diet/DSS+ group were significantly higher than those of folate deficiency/DSS- group and standard diet/DSS- group (χ2 = 22 .18 ,P< 0 .05 ) . And the expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group was also higher than that of

  4. Challenges in publication ethics.

    Science.gov (United States)

    Barbour, V; Astaneh, B; Irfan, M

    2016-04-01

    skill. Finally, the editor needs to deal with the journal's ethical policy when examples of plagiarism, author disputes or other forms of misconduct are evident. Breaches of publication ethics are forms of scientific misconduct that can undermine science and challenge editors, many of whom have little formal training in this field. In this respect, the Committee on Publication Ethics (COPE), founded in 1997 as a voluntary body, has become a central player. COPE provides a discussion forum and advice as well as guidelines for scientific editors with the aim of finding practical ways to deal with forms of misconduct. The Annals is a member of COPE and follows its code of conduct for journal editors. (2) It is a privilege that the current chair of COPE, Dr Barbour, and her colleagues have written this final article in the medical publishing series about challenges in publication ethics. I hope you have found this series useful and enjoyed reading the range of articles we have published from many experts in their fields. JYOTI SHAH Commissioning Editor References 1. Sanders SA , Reinisch JM . Would you say you 'had sex' if…? JAMA 1999 ; 281 : 275 - 277 . 2. Committee on Publication Ethics . Code of Conduct and Best Practice Guidelines for Journal Editors . Harleston, UK : COPE ; 2011 . PMID:26985812

  5. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-10-01

    Full Text Available IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  6. The stem factor challenge

    International Nuclear Information System (INIS)

    One of the most important challenges that still needs to be met in the effort to understand the operation of motor-operated, rising-stem valves is the ability to determine stem factor throughout the valve's load range. The stem factor represents the conversion of operator torque to stem thrust. Determining the stem factor is important because some motor-operated valves (MOVs) cannot be tested in the plant at design basis conditions. The ability of these valves to perform their design basis function (typically, to operate against specified flow and pressure loads) must be ensured by analytical methods or by extrapolating from the results of tests conducted at lower loads. Because the stem factor tends to vary in response to friction and lubrication phenomena that occur during loading and wedging, analytical methods and extrapolation methods have been difficult to develop and implement. Early investigations into variability in the stem factor tended to look only at the tip of the iceberg; they focused on what was happening at torque switch trip, which usually occurs at full wedging. In most stems, the stem factor is better (lower) in the wedging transient than before wedging, so working with torque switch trip data alone led many early researchers to false conclusions about the relationship between stem factor and load. However, research at the Idaho National Engineering Laboratory (INEL) has taken a closer look at what happens during the running portion of the closing stroke along with the wedging portion. This shift in focus is important, because functional failure of a valve typically consists of a failure to isolate flow, not a failure to achieve full wedging. Thus, the stem factor that must be determined for a valve's design basis closing requirements is the one that corresponds with the running load before wedging

  7. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-12-01

    Full Text Available ABSTRACT IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  8. WANO. Development, programs, challenges

    International Nuclear Information System (INIS)

    In the wake of the accident at the Soviet RBMK reactor unit 4 in Chernobyl the nuclear industry founded the World Association of Nuclear Operators (WANO). To this day, the purpose of the organization has been to enhance worldwide cooperation of nuclear industry and, in this way, strengthen the safety and availability of nuclear power plants. Following some first steps after 1986, the charter of the organization was signed at the WANO constituent assembly in Moscow on May 15 and 16, 1989. The member companies thus committed themselves to support WANO's mission. WANO was established for these purposes: ''The mission of WANO is to maximize the safety and reliability of nuclear power plants worldwide by working together to assess, benchmark and improve performance through mutual support, exchange of information, and emulation of best practices.'' The WANO programs developed speedily thereafter. The focus was on peer reviews. In 2000, the first interim objective had been reached: Fifty percent of all member nuclear power plants had undergone peer reviews. In addition, plant-related peer reviews were extended throughout all operator organizations, and corporate peer reviews were developed. The other WANO programs as well, i.e. exchanges of experience, technical support, and performance indicators, exerted more and more influence on industry. Peer reviews covered entire operator organizations, and corporate peer reviews were developed. The worldwide paradigm shift in evaluating the use of nuclear power, and the associated construction programs for new nuclear power plants already in their implementation phase, assigned a new quality to the work of WANO. The organization is preparing a long-term strategy in the face of the challenges to be expected. The ultimate objective of these efforts is to support member organizations from the first preparations of a nuclear power plant project to the end of commercial operation. (orig.)

  9. The WCET Tool Challenge 2011

    DEFF Research Database (Denmark)

    Hanxleden, Reinhard von; Holsti, Niklas; Lisper, Björn;

    Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC'11) dened two kinds...... of problems to be solved by the Challenge participants with their tools, WCET problems, which ask for bounds on the execution time, and ow-analysis problems, which ask for bounds on the number of times certain parts of the code can be executed. The benchmarks to be used in WCC'11 were debie1, Papa...

  10. 78 FR 19742 - Centennial Challenges: 2014 Night Rover Challenge

    Science.gov (United States)

    2013-04-02

    ... environments. Competitors will need to demonstrate high energy density storage systems (>330w-hr/kg) that would... Challenge will be conducted in an ambient Earth environment in a NASA test chamber. The Phase I Challenge..., scientific experimentation, communications, and rover movement. The competitors may store and extract...

  11. The challenges of fusion

    International Nuclear Information System (INIS)

    The new boss of the world's biggest fusion experiment cannot afford to fail. Kaname Ikeda will soon be a name on many physicists' lips. Though the outgoing Japanese ambassador to Croatia and former science administrator is not currently widely known, that will all change when he starts work later this month as director general of the International Thermonuclear Experimental Reactor (ITER). Set to be built at Cadarache near Marseille in southern France - assuming the ITER treaty is ratified - this Euro10bn facility is designed to show that fusion could be turned into a practical energy source.To do so would be huge achievement. Fusion reactors could play a massive role in meeting the world's rapidly growing demand for energy. They promise to be environmentally friendly and relatively safe to operate, while the raw materials they need are plentiful. However, early progress in fusion research led plasma physicists to be over optimistic about this energy source, and a commercial fusion plant remains as far off in the future as it was back in the 1970s. Ikeda therefore has a tough job on his hands, as he readily admits in our interview with him (see p12; print version only). It will be no mean feat to build ITER on time and to budget, and Ikeda will have to draw heavily on his undoubted diplomatic skills to ensure that everyone involved in this complex international project gets on. ITER is hugely ambitious in engineering terms, with vast superconducting magnets needed to confine a deuterium-tritium plasma within a doughnut-shaped 'tokamak' vessel. Numerous technical challenges will have to be addressed to ensure ITER fulfils its goal of releasing more energy than it consumes. These include choosing which material to line the inner wall of the tokamak with, overcoming the accumulation of radioactive tritium on this surface, and controlling the properties of the plasma. Fortunately, such issues are being addressed at the recently upgraded Joint European Torus near Oxford

  12. The environmental challenge.

    Science.gov (United States)

    Sanders, T

    1992-11-01

    We now come to the ultimate question of whether we should be optimistic or pessimistic about our environmental future, and indeed our survival. If we believe human beings to be rational and thus ultimately acting in their own self-interest, there is no reason to believe that the environmental challenges confronting us as individuals and as a society are not resolvable in a manner that allows both economic development and a reasonable quality of life for human beings. Indeed, we see, at least in the developed world, recognition of the magnitude of the problems that we face and movements toward solutions. Yet our nemesis is time. Irretrievable seconds are ticking away as we struggle against ignorance and economic self-interest. Our concern must be not whether we will act, but whether we will act in time to forestall environmental catastrophe for our civilization. The ultimate solution to our environmental problems must come from a fundamental change in the self-serving psychology that produced the tragedy of the commons. Self-interest must be sublimated not only to the greater needs of society, but to the needs of our posterity. The tragedy of the commons can only be avoided if our time horizon shifts from the short- to long-term. In addition, there must be a shift in values from obsession with economic development to concern for the quality of human life. These shifts dictate that in the future our economic, political, and social system must be built upon a foundation of "sustainable" growth. This means that "industries (and nations, for that matter) cannot thrive if they sacrifice future quality of life for present economic gain. In the long run, the principles of economic growth and environmental quality reinforce each other." How do we make this esoteric speculation relevant to our job each day as materiel managers in health care delivery organizations? We can do this by first understanding the problems that we confront and how we are a part of these problems

  13. Interleukin-12 and protective immunity to schistosomes

    Directory of Open Access Journals (Sweden)

    A.P. Mountford

    1998-01-01

    Full Text Available The attenuated vaccine against Schistosoma mansoni induces Th1-mediated protective immunity and we have sought to identify a role for IL-12 in this model. Elevated levels of IL-12 (p40 mRNA were detected in the lymph nodes (LN and the lungs of vaccinated mice, whilst treatment of vaccinated mice with anti-IL-12 antibodies decreased the ratio of IFNg:IL-4 secreted by in vitro-cultured LN cells. However, there was only marginal abrogation of the level of resistance in these mice. Soluble antigens from the lung-stage of the parasite (SLAP appeared to be efficient stimulators of IFNg and IL-12 secretion. These antigens when used to immunise mice in conjunction with IL-12 as an adjuvant, elicited a polarised Th1 response with abundant IFNg secretion but no IL-4. This immunisation regime also induced significant protection against reinfection, whereas inoculation of mice with SLAP alone did not. The induction of a dominant Th1 response using SLAP + IL-12 probably operates via IFNg production by natural killer (NK cells stimulated by IL-12, since in vivo ablation of NK cells using anti-NK1.1 antibody reduced CD4+-dependent IFNg production from cultured LN cells by over 97%. Nevertheless, in mice with a genetic disruption of the IFNg receptor, administration of SLAP + IL-12 induced levels of IFNg equal to those in wild-type mice, thus showing that in this model IL-12 can directly prime T cells independent of IFNg. Clearly, IL-12 has a critical role in protective immunity to schistosomes and it may aid the development of an effective vaccine against this disease

  14. Immune responses induced by a Leishmania (Leishmania amazonensis recombinant antigen in mice and lymphocytes from vaccinated subjects

    Directory of Open Access Journals (Sweden)

    Ana Paula FERNANDES

    1997-03-01

    Full Text Available In the search for Leishmania recombinant antigens that can be used as a vaccine against American Cutaneous Leishmaniasis, we identified a Leishmania (Leishmania amazonensis recombinant protein of 33 kD (Larp33 which is recognized by antibodies and peripheral blood leukocytes (PBL from subjects vaccinated with Leishvacin ®, Larp33 was expressed in Escherichia coli after cloning of a 2,2 kb Sau3A digested genomic fragment of L. (L. amazonensis into the pDS56-6 His vector. Immunoblotting analysis indicated that Larp33 corresponds to an approximately 40-kD native protein expressed in promastigotes of L.(L. amazonensis and L. (Viannia braziliensis. Northern blots of total RNA also demonstrated that the gene coding for this protein is expressed in promastigotes of the major lineages of Leishmania causing American Cutaneous Leishmaniasis. Larp33 induced partial protection in susceptible mouse strains (BALB/c and C57BL/10 against L. (L. amazonensis after vaccination using Bacille Calmette-Guerin (BCG as adjuvant. In vitro stimulation of splenocytes from BALB/c protected mice with Larp33 elicited the secretion of IL-2 and IFN-g, suggesting that a Th1 cell-mediated protective response is associated with the resistance observed in these mice. As revealed by its immunogenic and antigenic properties, this novel recombinant antigen is a suitable candidate to compose a vaccine against cutaneous leishmaniasisA resposta imune induzida por uma proteína recombinante de Leishmania (Leishmania amazonensis de 33 kD (Larp33 foi avaliada em linfócitos de indivíduos vacinados com a Leishvacin® e em camundongos através de vacinação. Larp33 foi expressa em Escherichia coli após clonagem de um fragmento genômico de L. (L. amazonensis de 2,2 kb no vetor pDS56-6His. Larp33 foi reconhecida por anticorpos IgG presentes no soro de indivíduos vacinados com Leishvacin® e induziu proliferação em linfócitos desses indivíduos em níveis comparáveis ao ant

  15. Organizational leadership: meeting the challenge.

    Science.gov (United States)

    Hart, A L

    1994-06-01

    Leadership can be learned. Knowledge of leadership theories can serve as basis for developing skills and techniques. Style, trait, and transformational leadership can be applied in both health care institutions and professional associations. Organizational leadership is challenging, but those challenges can help individual nurses grow in the leadership skills that will continue to be demanded in the ever changing healthcare arena. PMID:8075165

  16. IT Challenges for Space Medicine

    Science.gov (United States)

    Johnson-Throop, Kathy

    2010-01-01

    This viewgraph presentation reviews the various Information Technology challenges for aerospace medicine. The contents include: 1) Space Medicine Activities; 2) Private Medical Information; 3) Lifetime Surveillance of Astronaut Health; 4) Mission Medical Support; 5) Data Repositories for Research; 6) Data Input and Output; 7) Finding Data/Information; 8) Summary of Challenges; and 9) Solutions and questions.

  17. Higher Education Marketing: A Challenge.

    Science.gov (United States)

    Canterbury, Richard

    1999-01-01

    States that similarities between education and other services may not be sufficient to conclude that services marketing methods can be easily transferred to all markets in higher education. Article identifies and discusses why higher education marketing is a particular challenge. Suggests that understanding these challenges can help in making…

  18. Challenges Facing Group Work Online

    Science.gov (United States)

    Chang, Bo; Kang, Haijun

    2016-01-01

    Online group work can be complicated because of its asynchronous characteristics and lack of physical presence, and its requirements for skills in handling technology, human relationships, and content-related tasks. This study focuses on the administrative, logistical and relationship-related challenges in online group work. Challenges in areas…

  19. Challenging high-ability students

    NARCIS (Netherlands)

    Scager, Karin; Akkerman, Sanne F.; Pilot, Albert; Wubbels, Theo; Hafd Onderwijsadvies en training; Leerstoel Vermunt; Faculteit Sociale Wetenschappen; LS Wubbels; Education and Learning: Development in Interaction

    2014-01-01

    The existing literature on indicators of an optimal learning environment for high-ability students frequently discusses the concept of challenge. It is, however, not clear what, precisely, constitutes appropriate challenge for these students. In this study, the authors examined an undergraduate hono

  20. Interior Design: Challenges and Solutions.

    Science.gov (United States)

    School Planning and Management, 1999

    1999-01-01

    Presents solutions to architectural challenges in school interior design; these solutions made the indoor environments more conducive and attractive for learning. Addresses four challenges: making a long corridor look less like a tunnel; maintaining tradition and minimizing cost in a new athletic facility; designing a kindergarten that is secure…

  1. Radioecological challenges for mining

    Energy Technology Data Exchange (ETDEWEB)

    Vesterbacka, P.; Ikaeheimonen, T.K.; Solatie, D. [Radiation and Nuclear Safety Authority (Finland)

    2014-07-01

    In Finland, mining became popular in the mid-1990's when the mining amendments to the law made the mining activities easier for foreign companies. Also the price of the minerals rose and mining in Finland became economically profitable. Expanding mining industry brought new challenges to radiation safety aspect since radioactive substances occur in nearly all minerals. In Finnish soil and bedrock the average crystal abundance of uranium and thorium are 2.8 ppm and 10 ppm, respectively. It cannot be predicted beforehand how radionuclides behave in the mining processes which why they need to be taken into account in mining activities. Radiation and Nuclear Safety Authority (STUK) has given a national guide ST 12.1 based on the Finnish Radiation Act. The guide sets the limits for radiation doses to the public also from mining activities. In general, no measures to limit the radiation exposure are needed, if the dose from the operation liable to cause exposure to natural radiation is no greater than 0.1 mSv per year above the natural background radiation dose. If the exposure of the public may be higher than 0.1 mSv per year, the responsible party must provide STUK a plan describing the measures by which the radiation exposure is to be kept as low as is reasonably achievable. In that case the mining company responsible company has to make a radiological baseline study. The baseline study must focus on the environment that the mining activities may impact. The study describes the occurrence of natural radioactivity in the environment before any mining activities are started. The baseline study lasts usually for two to three years in natural circumstances. Based on the baseline study measurements, detailed information of the existing levels of radioactivity in the environment can be attained. Once the mining activities begin, it is important that the limits are set for the wastewater discharges to the environment and environmental surveillance in the vicinity of

  2. ITER Diagnostics - Technology and Integration Challenges

    International Nuclear Information System (INIS)

    Full text: Diagnostics play a vital role in controlling the plasma and optimizing its behavior. The higher temperatures and densities of the burning plasma drive the need for advances in diagnostic technology. Discussion of such needs is part of a conceptual design review activity in progress at ITER, and supported by experts from the ITER parties. The front-ends of most of these diagnostics will be housed in massive port plugs, which also shield the machine from radiation, and supply cooling to the first wall. Many diagnostics are housed in a single equatorial port plug, presenting new and interesting technical and organizational challenges for developers. Front-end components must tolerate thermally-induced stresses, disruption-induced mechanical loads, stray ECH radiation, radiation damage, and degradation due to plasma-induced coatings. Challenges are amplified due to the difficulty in performing maintenance on these large structures, particularly once they are activated. In the active phase, port plug removal and maintenance will be performed robotically. Such activities benefit from a standardized approach to diagnostic packaging. Motivated by needs to minimize disruption loads on the plugs, to standardize the handling of diagnostic shield modules, and to decouple the parallel design efforts of the many parties developing ITER diagnostics, the packaging of diagnostics has recently focused on 3 vertical shield modules inserted from the plasma side into each equatorial port plug structure. The dimensions and attachment features of these modules are standardized. At the front of each is a detachable first wall element with customized apertures. Examples of developmental needs identified in the conceptual design phase will be given. Progress on front-end integration into port plugs will be described, including qualification test plans. Also discussed will be measures for coping with the neutron loads, the thermal and electromagnetic loads, the ECH loads, and the

  3. Eight challenges in phylodynamic inference

    Directory of Open Access Journals (Sweden)

    Simon D.W. Frost

    2015-03-01

    Full Text Available The field of phylodynamics, which attempts to enhance our understanding of infectious disease dynamics using pathogen phylogenies, has made great strides in the past decade. Basic epidemiological and evolutionary models are now well characterized with inferential frameworks in place. However, significant challenges remain in extending phylodynamic inference to more complex systems. These challenges include accounting for evolutionary complexities such as changing mutation rates, selection, reassortment, and recombination, as well as epidemiological complexities such as stochastic population dynamics, host population structure, and different patterns at the within-host and between-host scales. An additional challenge exists in making efficient inferences from an ever increasing corpus of sequence data.

  4. Energy challenges. A European answer

    Energy Technology Data Exchange (ETDEWEB)

    Berge, Hans ten [EURELECTRIC, Brussels (Belgium)

    2013-02-01

    The European electricity sector is facing four main challenges: a very challenging investment climate, relatively low electricity demand, the continued expansion of electricity from subsidised renewable energy sources, and the unexpected weakness of the EU Emissions Trading System (ETS). EURELECTRIC's answers to these challenges revolve around a more consistent framework with the ETS as the key driver of decarbonisation, the integration of renewables into the market and a less distortive approach to their development, a renewed focus on energy infrastructure as a means of completing the internal energy market, and an improved strategy for RD and D.

  5. The Leadership Challenge Activities Book

    CERN Document Server

    Kouzes, James M; Biech, Elaine

    2010-01-01

    ACTIVE Learning for Exemplary Leaders. The best leaders are the best learners. This evidence-based truth has been a foundational principle of The Leadership Challenge since it was first published nearly twenty-five years ago. In this new work, bestselling Leadership Challenge authors Jim Kouzes and Barry Posner team up with experiential learning expert Elaine Biech to bring today's leaders over 100 engaging activities designed to expand and accelerate their leadership development efforts. Grounded in The Five Practices of Exemplary Leadership® model, The Leadership Challenge Activities Book in

  6. Challenges in aerospace medicine education.

    Science.gov (United States)

    Grenon, S Marlene; Saary, Joan

    2011-11-01

    Aerospace medicine training and research represents a dream for many and a challenge for most. In Canada, although some opportunities exist for the pursuit of education and research in the aerospace medicine field, they are limited despite the importance of this field for enabling safe human space exploration. In this commentary, we aim to identify some of the challenges facing individuals wishing to get involved in the field as well as the causal factors for these challenges. We also explore strategies to mitigate against these.

  7. Grand Challenges facing Storage Systems

    CERN Document Server

    CERN. Geneva

    2004-01-01

    In this talk, we will discuss the future of storage systems. In particular, we will focus on several big challenges which we are facing in storage, such as being able to build, manage and backup really massive storage systems, being able to find information of interest, being able to do long-term archival of data, and so on. We also present ideas and research being done to address these challenges, and provide a perspective on how we expect these challenges to be resolved as we go forward.

  8. Nuclear energy: meeting the challenges

    International Nuclear Information System (INIS)

    'Nuclear Energy - Meeting the Challenges' was the theme of the 25th Annual Conference of the Canadian Nuclear Society, held in Toronto, Ontario on June 6-9, 2004. The theme has the implication of optimism - that we WILL meet the many challenges needed to overcome if nuclear power is to play a significant role in our energy future. The organizers succeeded in presenting a thorough discussion of the challenges facing the nuclear power industry in Canada with close to 300 delegates attending the three-day event

  9. Challenges in implementing and maintaining osteoporosis therapy

    Directory of Open Access Journals (Sweden)

    Modi A

    2014-08-01

    Full Text Available Ankita Modi,1 Shiva Sajjan,1 Sampada Gandhi2 1Center for Observational and Real-World Evidence, Merck & Co., Inc., Whitehouse Station, NJ, USA; 2School of Public Health, Rutgers University, Piscataway, NJ, USA Abstract: In the United States, an estimated 19% of older men and 30% of older women are at elevated risk of osteoporotic fracture and considered to be eligible for treatment. The burden of osteoporosis is similar in Europe and is projected to rise worldwide, with aging populations and increasing fracture rates accompanying urbanization. Notwithstanding its high prevalence, osteoporosis is often underdiagnosed and undertreated. Moreover, even when the diagnosis is made and the decision is taken to treat, there are remaining challenges in implementing therapy for osteoporosis. Several patient populations are particularly challenging for clinicians to treat and require further study with regard to osteoporosis therapy. These include the very elderly, who face challenges relating to adherence; men, in whom osteoporosis remains under-recognized; patients with glucocorticoid-induced osteoporosis or renal impairment, who are at increased risk of fracture; patients with preexisting gastrointestinal problems who cannot tolerate existing orally administered osteoporosis therapies; and high-risk patients who show inadequate response to therapy. Moreover, poor adherence and poor persistence with osteoporosis medications are common and result in an increased risk of fracture, higher medical costs, and increased hospitalizations. Once the decision to institute therapy is made, patient education about osteoporosis and fracture risk should be provided. This is particularly important for men, who may not be aware that osteoporosis can be a concern. Secondary prevention programs, including fracture liaison services and bone therapy groups, can help to improve adherence to therapy. Further study is needed to guide the treatment of men, the very elderly

  10. Challenge of COPD: Getting Tested

    Science.gov (United States)

    ... please turn JavaScript on. Feature: The Challenge of COPD Getting Tested Past Issues / Fall 2014 Table of Contents Getting Tested Everyone at risk for COPD who has cough, sputum production, or shortness of ...

  11. Refugee status determination: three challenges

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  12. The Humpty-Dumpty Challenge.

    Science.gov (United States)

    Chock, Jan S.

    1995-01-01

    Describes a twist on the egg-drop challenge activity for an 8th grade physical science unit. Students engage in active inquiry and explore the laws of physics, develop critical thinking skills, and practice problem-solving tasks. (NB)

  13. Challenges in Designing Mechatronic Systems

    DEFF Research Database (Denmark)

    Torry-Smith, Jonas; Qamar, Ahsan; Achiche, Sofiane;

    2013-01-01

    Development of mechatronic products is traditionally carried out by several design experts from different design domains. Performing development of mechatronic products is thus greatly challenging. In order to tackle this, the critical challenges in mechatronics have to be well understood and well...... supported through applicable methods and tools. This paper aims at identifying the major challenges, by conducting a systematic and thorough survey of the most relevant research work in mechatronic design. Solutions proposed in literature are assessed and illustrated through a case study in order...... to investigate if the challenges can be handled appropriately by the methods, tools, and mindsets suggested by the mechatronic community. Using a real world mechatronics case, the paper identifies the areas where further research is required, by showing a clear connection between the actual problems faced during...

  14. Challenges in Soft Tissue Engineering

    OpenAIRE

    Yuksel, Eser; Choo, Joshua; Wettergreen, Matthew; Liebschner, Michael

    2005-01-01

    Soft tissue engineering strategies targeting restoration of volume loss have inherent critical challenges as they relate to the problem of restoration of defects with a high volume to surface ratio. We outline the problems associated with the limitations of translational applications regarding soft tissue engineering strategies as follows: cell survival, mechanical challenges: macroenvironment (scaffold collapse and on-the-shelf availability), compositional considerations: microenvironment, i...

  15. Challenges in Kurdish Text Processing

    OpenAIRE

    Esmaili, Kyumars Sheykh

    2012-01-01

    Despite having a large number of speakers, the Kurdish language is among the less-resourced languages. In this work we highlight the challenges and problems in providing the required tools and techniques for processing texts written in Kurdish. From a high-level perspective, the main challenges are: the inherent diversity of the language, standardization and segmentation issues, and the lack of language resources.

  16. Challenges when introducing electronic exam

    OpenAIRE

    Kuikka, Matti; Kitola, Markus; Mikko-Jussi LAAKSO

    2014-01-01

    Time pressures often necessitate the use of more efficient exam tools, such as electronic exams (e-exams), instead of traditional paper exams. However, teachers may face challenges when introducing e-exams in a higher education context. This paper describes what kinds of challenges teachers may face when introducing e-exams, based on experiences in Turku University of Applied Sciences (TUAS) where e-exams have been used since 2012. For this research, the authors used their personal experience...

  17. Conclusion: challenges for the future

    OpenAIRE

    North, D. Warner

    1993-01-01

    The title “Challenges for the Future” implies the challenge to summarize a very complex meeting. Of necessity, I will present a personal impression. My interest is in risk assessment, which I define as a process for summarizing science in support of decision making. Risk assessment is sometimes regarded as arcane numerology, a rigid process of computing risk numbers in which much available science is unused. I am a strong advocate for the broader definition of risk assessment. It is encouragi...

  18. Challenges to Nordic Police Research

    DEFF Research Database (Denmark)

    Holmberg, Lars

    2015-01-01

    The paper will cover three main points: A short description of published police research in the Nordic countries; a somewhat longer discussion of the nature of, and challenges to, Nordic police research and, finally, a critique of the homeliness of research.......The paper will cover three main points: A short description of published police research in the Nordic countries; a somewhat longer discussion of the nature of, and challenges to, Nordic police research and, finally, a critique of the homeliness of research....

  19. Internationalization challenges of Ethiopian SMEs

    OpenAIRE

    Yigzaw, Tamirat

    2014-01-01

    This study was made to find out what the internationalization challenges of Ethiopian small to medium size enterprises (SMEs) are. SMEs play a vital role in the economic development of a country. As the internationalization activities of these SMEs is affected by various factors, a research to identify the challenges that hinder their internationalization activities was made in order to minimize the internationalization problems faced in the future. A detailed literature review related to the...

  20. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity.C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys. At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a global transcriptional variations in kidney tissues, (b morphological changes in the kidneys, (c changes in white and red blood cell count as well as blood levels of urea, and (d changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months.Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these

  1. Challenges in diagnostic accuracy studies in primary care: The fecal calprotectin example

    NARCIS (Netherlands)

    G.A. Holtman (Gea A); Y. van Leeuwen (Yvonne); B.J. Kollen (Boudewijn ); J.C. Escher (Johanna); A. Kindermann; P.F.V. Rheenen (Patrick F Van); M.Y. Berger (Marjolein)

    2013-01-01

    textabstractAbstract. Background: Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodologi

  2. Challenges in diagnostic accuracy studies in primary care : the fecal calprotectin example

    NARCIS (Netherlands)

    Holtman, Gea A.; Lisman-van Leeuwen, Yvonne; Kollen, Boudewijn J.; Escher, Johanna C.; Kindermann, Angelika; van Rheenen, Patrick F.; Berger, Marjolein Y.

    2013-01-01

    Background: Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of ou

  3. The Mock LISA Data Challenges: from Challenge 1B to Challenge 3

    International Nuclear Information System (INIS)

    The Mock LISA Data Challenges are a programme to demonstrate and encourage the development of LISA data-analysis capabilities, tools and techniques. At the time of this workshop, three rounds of challenges had been completed, and the next was about to start. In this paper we provide a critical analysis of the entries to the latest completed round, Challenge 1B. The entries confirm the consolidation of a range of data-analysis techniques for galactic and massive-black-hole binaries, and they include the first convincing examples of detection and parameter estimation of extreme-mass-ratio inspiral sources. In this paper we also introduce the next round, Challenge 3. Its data sets feature more realistic waveform models (e.g., galactic binaries may now chirp, and massive-black-hole binaries may precess due to spin interactions), as well as new source classes (bursts from cosmic strings, isotropic stochastic backgrounds) and more complicated nonsymmetric instrument noise

  4. The Mock LISA Data Challenges: from Challenge 1B to Challenge 3

    CERN Document Server

    Babak, Stanislav; Benacquista, Matthew J; Cornish, Neil J; Crowder, Jeff; Larson, Shane L; Plagnol, Eric; Porter, Edward K; Vallisneri, Michele; Vecchio, Alberto; Arnaud, Keith; Barack, Leor; Błaut, Arkadiusz; Cutler, Curt; Fairhurst, Stephen; Gair, Jonathan; Gong, Xuefei; Harry, Ian; Khurana, Deepak; Królak, Andrzej; Mandel, Ilya; Prix, Reinhard; Sathyaprakash, B S; Savov, Pavlin; Shang, Yu; Trias, Miquel; Veitch, John; Wang, Yan; Wen, Linqing; Whelan, John T

    2008-01-01

    The Mock LISA Data Challenges are a programme to demonstrate and encourage the development of LISA data-analysis capabilities, tools and techniques. At the time of this workshop, three rounds of challenges had been completed, and the next was about to start. In this article we provide a critical analysis of entries to the latest completed round, Challenge 1B. The entries confirm the consolidation of a range of data-analysis techniques for Galactic and massive--black-hole binaries, and they include the first convincing examples of detection and parameter estimation of extreme--mass-ratio inspiral sources. In this article we also introduce the next round, Challenge 3. Its data sets feature more realistic waveform models (e.g., Galactic binaries may now chirp, and massive--black-hole binaries may precess due to spin interactions), as well as new source classes (bursts from cosmic strings, isotropic stochastic backgrounds) and more complicated nonsymmetric instrument noise.

  5. ESTUARINE AND COASTAL CHALLENGES IN CHINA

    Institute of Scientific and Technical Information of China (English)

    陈吉余; 陈沈良

    2002-01-01

    Estuaries and coasts are conjunctions of four spheres (atmosphere, lithosphere, hydrosphere and biosphere) and important matter and energy convergence/divergence zones, where developed economy, dense population and highly intensive exploitation induce adverse environmental changes and serious destruction of resources, which have great impacts on coastal sustainable development, especially as the highly intensive development in river basins has direct and pronounced effects on estuaries and their adjacent coasts. In the new century, China's estuaries and coast are faced with four main challenges: sharp decrease of sediment discharge into the sea, rapid increase of pollution matter into the sea, loss of coastal wetland, and the impacts of global sea level rise on the coastallowlands of China. Therefore, it is undoubtedly very important and urgent to carry out studies on estuarine and coastal environmental changes, in order to resolve the issue of national sustainable development, especially that of rational use of coastal zone resources. ``

  6. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  7. Stable isotope views on ecosystem function: challenging or challenged?

    Science.gov (United States)

    Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

    2010-01-01

    Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

  8. Challenges and counter challenges in HIV/AIDS

    Institute of Scientific and Technical Information of China (English)

    Qingsheng Li; Charles Wood

    2010-01-01

    @@ Since the beginning of the HIV/AIDS pandemic, there has been significant progress in combating the virus.In addition to identifying HIV,1 scientists have developed an array of antiretroviral drugs and successfully converted the once deadly disease into a treatable and chronic condition.2 Nevertheless, this battle is far from over and HIV still outsmarts humans in multiple ways and poses tremendous challenges. Within this context, the Chinese Medical Journal has timely published this special issue on HIV/AIDS, highlighting the ongoing challenges posed by HIV and potential solutions to these problems.

  9. Ecological Challenges for Closed Systems

    Science.gov (United States)

    Nelson, Mark; Dempster, William; Allen, John P.

    2012-07-01

    Closed ecological systems are desirable for a number of purposes. In space life support systems, material closure allows precious life-supporting resources to be kept inside and recycled. Closure in small biospheric systems facilitates detailed measurement of global ecological processes and biogeochemical cycles. Closed testbeds facilitate research topics which require isolation from the outside (e.g. genetically modified organisms; radioisotopes) so their ecological interactions and fluxes can be studied separate from interactions with the outside environment. But to achieve and maintain closure entails solving complex ecological challenges. These challenges include being able to handle faster cycling rates and accentuated daily and seasonal fluxes of critical life elements such as carbon dioxide, oxygen, water, macro- and mico-nutrients. The problems of achieving sustainability in closed systems for life support include how to handle atmospheric dynamics including trace gases, producing a complete human diet and recycling nutrients and maintaining soil fertility, the sustaining of healthy air and water and preventing the loss of crucial elements from active circulation. In biospheric facilities the challenge is also to produce analogues to natural biomes and ecosystems, studying processes of self-organization and adaptation in systems that allow specification or determination of state variables and cycles which may be followed through all interactions from atmosphere to soils. Other challenges include the dynamics and genetics of small populations, the psychological challenges for small isolated human groups and measures and options which may be necessary to ensure long-term operation of closed ecological systems.

  10. Challenged

    Science.gov (United States)

    Manzo, Kathleen Kennedy

    2006-01-01

    The work of librarians can be a lifeline to youths dealing with difficult personal issues, such as family strife, growing up, and sexuality. This paper presents an issue where school library books at Fayetteville High School are questioned because their books are too sexually explicit or mature for teenagers. In the midst of intense media coverage…

  11. Higgs Machine Learning Challenge 2014

    CERN Multimedia

    Olivier, A-P; Bourdarios, C ; LAL / Orsay; Goldfarb, S ; University of Michigan

    2014-01-01

    High Energy Physics (HEP) has been using Machine Learning (ML) techniques such as boosted decision trees (paper) and neural nets since the 90s. These techniques are now routinely used for difficult tasks such as the Higgs boson search. Nevertheless, formal connections between the two research fields are rather scarce, with some exceptions such as the AppStat group at LAL, founded in 2006. In collaboration with INRIA, AppStat promotes interdisciplinary research on machine learning, computational statistics, and high-energy particle and astroparticle physics. We are now exploring new ways to improve the cross-fertilization of the two fields by setting up a data challenge, following the footsteps of, among others, the astrophysics community (dark matter and galaxy zoo challenges) and neurobiology (connectomics and decoding the human brain). The organization committee consists of ATLAS physicists and machine learning researchers. The Challenge will run from Monday 12th to September 2014.

  12. Challenges in future linear colliders

    CERN Document Server

    Chattopadhyay, S

    2002-01-01

    For decades, electron-positron colliders have been complementing proton-proton colliders. But the circular LEP, the largest e/sup -/e /sup +/ collider, represented an energy limit beyond which energy losses to synchrotron radiation necessitate moving to e/sup -/e/sup + / linear colliders (LCs), thereby raising new challenges for accelerator builders. Japanese-American, German, and European collaborations have presented options for the "Future Linear Collider " (FLC). Key accelerator issues for any FLC option are the achievement of high enough energy and luminosity. Damping rings, taking advantage of the phenomenon of synchrotron radiation, have been developed as the means for decreasing beam size, which is crucial for ensuring a sufficiently high rate of particle-particle collisions. Related challenges are alignment and stability in an environment where even minute ground motion can disrupt performance, and the ability to monitor beam size. The technical challenges exist within a wider context of socioeconomi...

  13. Seismological challenges for stellar structure

    CERN Document Server

    Christensen-Dalsgaard, J

    2010-01-01

    Helioseismology has provided very detailed information about the solar interior, and extensive data on a large number of stars, although at less detail, are promised by the ongoing and upcoming asteroseismic projects. In the solar case there remain serious challenges in understanding the inferred solar structure, particularly in the light of the revised determinations of the solar surface composition. Also, a secure understanding of the origins of solar rotation as inferred from helioseismology, both in the radiative interior and in the convection zone, is still missing. In the stellar case challenges are certain to appear as the data allow more detailed inferences of the properties of stellar cores. Large remaining uncertainties in modelling concerns the properties of convective cores and other processes that may cause mixing. As a result of developing asteroseismic signatures addressing these and other issues, we can look forward to a highly challenging, and hence exciting, era of stellar astrophysics.

  14. The Challenge of Prejudice: Counsellors' Talk about Challenging Clients' Prejudices

    Science.gov (United States)

    Spong, Sheila J.

    2012-01-01

    This paper considers the implications for training and practice of counsellors' responses to the notion of challenging clients' prejudices. It explores tensions in counselling discourse between social responsibility, responsibility to the client and responsibility for one's self as counsellor. Three focus groups of counsellors were asked whether a…

  15. Success of Breast Cancer Startup Challenge Inspires Second Challenge | Poster

    Science.gov (United States)

    By Thomas Stackhouse, Joseph Conrad, and Michele Newton, Contributing Writers, and Rosemarie Truman, Guest Writer Sixty-one teams have been accepted into, and are now competing in, the Neuro Startup Challenge, a new collaboration established by the National Institutes of Health (NIH) with The Center for Advancing Innovation (CAI) and Heritage Provider Network, Inc.

  16. ITER safety challenges and opportunities

    International Nuclear Information System (INIS)

    Results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ''ITER is capable of meeting anticipated regulatory dose limits,'' but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. We need much research and development (R ampersand D) and design analysis to establish that ITER meets regulatory requirements. We have a further opportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, we need to overcome three programmatic challenges and three technical challenges. The first programmatic challenge is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of the three key technical challenges is plasma engineering -- burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost. Some design requirements are now too strict; some are too lax. Fuel cycle design requirements are presently too strict, mandating inappropriate T separation from H and D. Heat sink requirements are presently too lax; they should be strengthened to ensure that maximum loss of coolant accident temperatures drop

  17. Challenges and opportunities for REDD+

    DEFF Research Database (Denmark)

    Pasgaard, Maya; Sun, Zhanli; Müller, Daniel;

    2016-01-01

    Reducing Emissions from Deforestation and forest Degradation (REDD+) is a promising mechanism of payments for ecosystem services with the aim to effectively reduce emissions in an efficient and equitable manner. REDD+ is part of the Paris-agreement reached at the UNFCCC COP21 in December 2015...... the opportunities and challenges of REDD+ for achieving effective, efficient and equitable outcomes and co-benefits (3E+). We substantiate our survey results with a literature review. Results suggest that the challenges in achieving the 3E+ relate to the disproportionality between deforestation drivers...

  18. Grand Challenges of Enterprise Integration

    Energy Technology Data Exchange (ETDEWEB)

    Brosey, W.D; Neal, R.E.; Marks, D.

    2001-04-01

    Enterprise Integration connects and combines people, processes, systems, and technologies to ensure that the right people and the right processes have the right information and the right resources at the right time. A consensus roadmap for Technologies for Enterprise Integration was created as part of an industry/government/academia partnership in the Integrated Manufacturing Technology Initiative (IMTI). Two of the grand challenges identified by the roadmapping effort will be addressed here--Customer Responsive Enterprises and Totally Connected Enterprises. Each of these challenges is briefly discussed as to the current state of industry and the future vision as developed in the roadmap.

  19. The Challenges of Becoming Agile

    DEFF Research Database (Denmark)

    Ovesen, Nis

    -five years old, the statement from the 1986-edition of Harvard Business Review seems more true than ever before. Commercial markets are moving faster and faster, and time as a strategic source of competitive advantage is receiving increasing attention (Souza et al., 2004). This is the present condition...... as a potential solution to their struggles with similar challenges. This Ph.D. project is based on case studies of the development environments of seven Danish companies working with the implementation of Scrum. The outcome of the project is an identification and overview of the challenges of implementing...

  20. Understanding the LHC Controls Challenges

    CERN Document Server

    Van den Eynden, M

    2000-01-01

    The analysis, design and construction of the LHC control system is a complex problem which will challenge CERN's capability to provide a modern controls infrastructure fulfilling the stringent operational requirements of this machine. The first part of this talk will review the present LHC project context in which several controls initiatives have already been taken. The second part will try to highlight the important technical aspects and engineering steps involved in the process of defining a control system architecture. The importance of understanding the major LHC operational challenges will be stressed along with some practical proposals and examples on how to conduct such activity with all stakeholders.

  1. Statistical Challenges in Modern Astronomy

    CERN Document Server

    Feigelson, E D

    2003-01-01

    Despite centuries of close association, statistics and astronomy are surprisingly distant today. Most observational astronomical research relies on an inadequate toolbox of methodological tools. Yet the needs are substantial: astronomy encounters sophisticated problems involving sampling theory, survival analysis, multivariate classification and analysis, time series analysis, wavelet analysis, spatial point processes, nonlinear regression, bootstrap resampling and model selection. We review the recent resurgence of astrostatistical research, and outline new challenges raised by the emerging Virtual Observatory. Our essay ends with a list of research challenges and infrastructure for astrostatistics in the coming decade.

  2. The Challenges of Becoming Agile

    DEFF Research Database (Denmark)

    Ovesen, Nis; Dowlen, Chris

    2012-01-01

    During the last decade agile methods have been a vast success in the domain of software development. This paper investigates whether these methods can be successfully transferred to the domain of physical product development in order to address the fundamental challenges of increased marked speed......, development uncertainty and product complexity. The paper compares two cases from industry and education where agile methods are used in physical product development. The comparison between the cases is conducted within five thematic areas, which creates an overview of the challenges that may occur when...

  3. Authenticity and its Contemporary Challenges

    DEFF Research Database (Denmark)

    Bork Petersen, Franziska

    2013-01-01

    In this thesis I investigate what ‘authenticity’ means in a contemporary popular context and how it is used in the staging of bodies. Furthermore, I analyse works of dance and fashion from the past fifteen years with a focus on their strategies of challenging the notion of ‘bodily authenticity...... and by a depiction of 'working hard'. But various techniques also mask the hard work, for example by showing a participant ‘having fun’ performing it. Contemporary works of dance and fashion challenge the problematic implications in the notion of ‘bodily authenticity’. I analyse three strategies of undermining...

  4. The challenges of big data

    Science.gov (United States)

    2016-01-01

    ABSTRACT The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  5. The challenges of big data.

    Science.gov (United States)

    Mardis, Elaine R

    2016-05-01

    The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest.

  6. Vitreous substitutes: challenges and directions

    Institute of Scientific and Technical Information of China (English)

    Qian-Ying; Gao; Yue; Fu; Yan-Nian; Hui

    2015-01-01

    The natural vitreous body has a fine structure and complex functions. The imitation of the natural vitreous body by vitreous substitutes is a challenging work for both researchers and ophthalmologists. Gases, silicone oil, heavy silicone oil and hydrogels, particularly the former two vitreous substitutes are clinically widely used with certain complications. Those, however, are not real artificial vitreous due to lack of structure and function like the natural vitreous body. This article reviews the situations, challenges, and future directions in the development of vitreous substitutes, particularly the experimental and clinical use of a new artificial foldable capsular vitreous body.

  7. The Mock LISA Data Challenges: from challenge 3 to challenge 4

    Energy Technology Data Exchange (ETDEWEB)

    Babak, Stanislav; Petiteau, Antoine; Robinson, Emma L [Max-Planck-Institut fuer Gravitationsphysik (Albert-Einstein-Institut), Am Muehlenberg 1, D-14476 Golm bei Potsdam (Germany); Baker, John G; McWilliams, Sean T; Arnaud, Keith A [Gravitational Astrophysics Laboratory, NASA Goddard Space Flight Center, 8800 Greenbelt Rd, Greenbelt, MD 20771 (United States); Benacquista, Matthew J [Center for Gravitational Wave Astronomy, University of Texas at Brownsville, Brownsville, TX 78520 (United States); Cornish, Neil J; Adams, Matt [Department of Physics, Montana State University, Bozeman, MT 59717 (United States); Larson, Shane L [Department of Physics, Utah State University, Logan, UT 84322 (United States); Mandel, Ilya [Department of Physics and Astronomy, Northwestern University, Evanston, IL (United States); Porter, Edward K [APC, UMR 7164, University Paris 7 Denis Diderot, 10, rue Alice Domon et Leonie Duquet, 75025 Paris Cedex 13 (France); Vallisneri, Michele; Cutler, Curt [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Vecchio, Alberto [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B152TT (United Kingdom); Blaut, Arkadiusz [Institute of Theoretical Physics, University of Wroclaw, Wroclaw (Poland); Bridges, Michael; Feroz, Farhan [Astrophysics Group, Cavendish Laboratory, University of Cambridge, Cambridge CB30HE (United Kingdom); Cohen, Michael [Theoretical Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Gair, Jonathan R., E-mail: Michele.Vallisneri@jpl.nasa.go [Institute of Astronomy, University of Cambridge, Cambridge CB30HA (United Kingdom)

    2010-04-21

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in April 2008, which demonstrated the positive recovery of signals from chirping galactic binaries, from spinning supermassive-black-hole binaries (with optimal SNRs between approx10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with OMEGA{sub gw}(f) approx 10{sup -11}, slightly below the LISA instrument noise.

  8. The Mock LISA Data Challenges: from Challenge 3 to Challenge 4

    CERN Document Server

    Babak, Stanislav; Benacquista, Matthew J; Cornish, Neil J; Larson, Shane L; Mandel, Ilya; Petiteau, Antoine; Porter, Edward K; Robinson, Emma L; Vallisneri, Michele; Vecchio, Alberto; Adams, Matt; Arnaud, Keith A; Błaut, Arkadiusz; Bridges, Michael; Cohen, Michael; Cutler, Curt; Feroz, Farhan; Gair, Jonathan R; Graff, Philip; Hobson, Mike; Key, Joey Shapiro; Królak, Andrzej; Lasenby, Anthony; Prix, Reinhard; Shang, Yu; Trias, Miquel; Veitch, John; Whelan, John T

    2009-01-01

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in Apr 2008, which demonstrated the positive recovery of signals from chirping Galactic binaries, from spinning supermassive--black-hole binaries (with optimal SNRs between ~ 10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Omega_gw(f) ~ 10^-11, slightly below the LISA instrument noise.

  9. The Mock LISA Data Challenges: from challenge 3 to challenge 4

    International Nuclear Information System (INIS)

    The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in April 2008, which demonstrated the positive recovery of signals from chirping galactic binaries, from spinning supermassive-black-hole binaries (with optimal SNRs between ∼10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Ωgw(f) ∼ 10-11, slightly below the LISA instrument noise.

  10. CHALLENGES FACING THE ESP PRACTITIONER

    Directory of Open Access Journals (Sweden)

    SIMION MINODORA OTILIA

    2015-12-01

    Full Text Available The ESP teacher has to face certain challenges in his profession: One of the biggest challenges of the ESP teacher is the fact that he/she lacks the necessary knowledge of the subject to teach Business English, for instance, some researchers believing that such courses should be taught by subject teachers. The task of teaching ESP by ESL teachers is not an easy one. Dudley- Evans and St. John pointed out its complexity, identifying five key roles of the ESP practitioner: teacher, course designer and materials provider, collaborator, researcher and evaluator and this is probably the biggest challenge of the profession. The ESP practitioner has also to be aware of the fact that using a foreign language for workplace or study purposes requires not only linguistic proficiency and knowledge but also knowledge of work –related and disciplinary concepts.Last but not least, another challenge for the ESP practitioner is the use of technology in class, a valuable tool for helping with traditional forms of teaching and for creating new forms of communicating.Thus, the ESP practitioner has many things in common with the teacher of general English: he has to be familiar with linguistic development and teaching theories ,he has to be aware of contemporary ideas related to his position and role and he has to become familiar with the new technologies which can be used to improve his methodology.However,his role is more complex than that of a General English teacher.

  11. Fostering Reflection through Challenging Practica

    Science.gov (United States)

    Nickel, Jodi; Sutherby, Linda; Garrow-Oliver, Susan

    2010-01-01

    This article describes challenging practicum situations that provided three early childhood education students with leadership opportunities to promote best practices in child care centers. Using excerpts from student journals and meetings, the article documents students' initial discouragement at practices observed, inspiration through…

  12. Monitoring challenges and innovative ideas

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, R.V.; Hunsaker, C.T.; Levine, D.A.

    1990-01-01

    Monitoring programs are difficult to design even when they focus on specific problems. Ecosystems are complex, and it is often impossible to predetermine what aspects of system structure or dynamics will respond to a specific insult. It is equally difficult to interpret whether a response is a stabilizing compensatory mechanism or a real loss of capacity to maintain the ecosystem. The problems are compounded in a broad monitoring program designed to assess ecosystem health'' at regional and continental scales. It is challenging in the extreme to monitor ecosystem response, at any scale, to past insults as well as an unknown future array of impacts. The present paper will examine some of the fundamental issues and challenges raised by large-scale monitoring efforts. The challenges will serve as a framework and as an excuse to discuss several important topics in more detail. Following the discussion of challenges, we suggest some basic innovations that could be important across a range of monitoring programs. The innovations include integrative measures, innovative methodology, and creative interpretation. 59 refs., 1 tab.

  13. Challenges in Business System Integration

    NARCIS (Netherlands)

    Hvolby, H.H.; Trienekens, J.H.

    2010-01-01

    Four main frameworks for intercompany relationships (SCOR, CPFR, ISA95 and OAG) are discussed and compared. The link between the frameworks and different supply chain integration applications such as ERP, CRM and VMI are pictured. Finally the state-of-the-art, future state and challenges of the supp

  14. Accountability: new challenges, new forms

    NARCIS (Netherlands)

    C. van Woerkum; N. Aarts

    2012-01-01

    The general call for more accountability, affecting all western institutions, has reached the communication professionals as well. How can they cope with this new challenge? The danger is that they focus mainly on outcomes, so on performative accountability, whereas decisional accountability, meanin

  15. A Water-Service Challenge

    Science.gov (United States)

    Roman, Harry T.

    2011-01-01

    It is important to let students see the value of mathematics in design--and how mathematics lends perspective to problem solving. In this article, the author describes a water-service challenge which enables students to design a water utility system that uses surface runoff into an open reservoir as the potable water source. This challenge…

  16. Kids Camping Takes the Challenge.

    Science.gov (United States)

    James, Vickie L.; Hohnbaum, Claudia

    2002-01-01

    A Wisconsin Girl Scout camp integrated The Healthy Kids Challenge into its program. The camp evaluated policies related to meals, snacks, physical activities, team building, and self-esteem. Staff inservice training resulted in healthier meals on the same budget and developed ownership of the program. Campers and families had opportunities to…

  17. Challenging Sexual Harassment on Campus

    Science.gov (United States)

    Baker, Nancy V.

    2010-01-01

    More than thirty years ago, an administrative assistant at Cornell University first challenged her university's indifference to her boss's sexually predatory behavior. While she did not prevail, her case sparked a movement. Litigation, news stories, and government guidelines defining sexual harassment followed. And universities responded: policies…

  18. The Challenge of Urban Policy

    Science.gov (United States)

    Glaeser, Edward L.

    2012-01-01

    Urbanization almost invariably accompanies development, and the cities of India and China are experiencing spectacular increases in population. The concentration of millions of people in a small mass creates challenges for public policy, especially in the areas of basic infrastructure, public health, traffic congestion, and often law enforcement…

  19. Challenges to 5G standardization

    DEFF Research Database (Denmark)

    Mihovska, Albena D.; Prasad, Ramjee

    2013-01-01

    Interoperable, ubiquitous and dynamic are key objectives for fifth-generation (5G) communication systems and applications. These characteristics are also at the core of the main challenges that researchers, manufacturers, regulators and standardization bodies face when designing targeted strategies...... for the successful deployment of 5G enabling technologies....

  20. Plain language and organisational challenges

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    2014-01-01

    Changing the language in an organization is a major organizational change. In this article, I discuss some of the organizational challenges for one specific language change implementation, taking the stance that language change must be treated as any other organizational change for it to have an ...

  1. The Real Challenge of ESD

    Science.gov (United States)

    Jackson, M. G.

    2011-01-01

    Between the Inter-governmental Conference on Environmental Education at Tbilisi in 1977 and the Fourth International Conference on Environmental Education at Ahmedabad in 2007, our conception of the challenge posed by the global crises of climate change, environmental destruction, social disintegration, poverty, natural resources exhaustion and…

  2. They rose to the challenge!

    CERN Document Server

    Anaïs Schaeffer

    2015-01-01

    The Challenge-Based Innovation programme is a Masters-level initiative developed at CERN in collaboration with many universities around the world. The first programme saw 45 students take part, and their final results were presented at an official "gala" held on 26 February.   On 26 February, after their official presentations, the six CBI teams presented their prototypes to the public in the IdeaSquare building.   As part of the IdeaSquare project, the Challenge-Based Innovation (CBI) programme is based on a very pragmatic question: can the tools and results produced by basic research (like that being carried out at CERN) be used to solve societal problems? If so, how? To answer this question, 45 students from very different professional and cultural backgrounds formed six teams, each with a specific societal challenge to solve (see here). Over a six-month period – from September 2014 to February 2015 – the six teams worked on the challenge in o...

  3. Efficient Audio Power Amplification - Challenges

    DEFF Research Database (Denmark)

    Andersen, Michael Andreas E.

    2005-01-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extens...

  4. Climate Change: Meeting the Challenge

    Science.gov (United States)

    Chance, Paul; Heward, William L.

    2010-01-01

    In "Climate Change: Meeting the Challenge," we conclude the special section by assuming that you have been persuaded by Thompson's paper or other evidence that global warming is real and poses a threat that must be dealt with, and that for now the only way to deal with it is by changing behavior. Then we ask what you, as behavior analysts, can do…

  5. Challenges in a Physics Course

    DEFF Research Database (Denmark)

    Hernández, Carola Hernández; Ravn, Ole; Forero Shelton, Antonio Manu

    2014-01-01

    This article identifies and analyses some of the challenges that arose in a development process of changing from a content-based teaching environment to a student-centred environment in an undergraduate physics course for medicine and biology students at Universidad de los Andes. Through the use...

  6. Efficient audio power amplification - challenges

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Michael A.E.

    2005-07-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extensive research and development are needed is covered. (au)

  7. Climate change challenges for SEA

    DEFF Research Database (Denmark)

    Larsen, Sanne Vammen

    This paper takes a theoretical perspective on the challenges that climate changes pose for SEA. The theoretical framework used is the sociologist Ulrich Beck’s theory of risk society and the aspects that characterise this society. Climate change is viewed as a risk, and the theory is used to derive...

  8. Challenges of blended-learning

    OpenAIRE

    Lugovtsova, Y. D.; Mylnikova, Tatyana Stepanovna

    2014-01-01

    Creation of the virtual environment as an educational resource to increase motivation and inquisition of the students is a great challenge for Russian educational system. The paper considers some issues of blended-learning. Some elements of blended-learning are analyzed through the ways they are implemented in Tomsk Polytechnic University.

  9. The Electric Power Exhibit Challenge

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    A design challenge is all about planning first and understanding the problem before diving in and looking frantically for a solution. Any experienced engineer or designer will tell one to think first and plan the steps before acting. An experienced carpenter friend of the author always said to "take many measurements and cut once." There is great…

  10. Turbulent Dissipation Challenge -- Problem Description

    CERN Document Server

    Parashar, Tulasi N; Wicks, Robert; Karimabadi, Homa; Chandran, S Peter Gary Benjamin; Matthaeus, William H

    2014-01-01

    The goal of this document is to present a detailed description of the goals, simulation setup and diagnostics for the Turbulent Dissipation Challenge $($http://arxiv.org/abs/1303.0204$)$ as discussed in the Solar Heliospheric and INterplanetary Environment $($SHINE$)$ 2013 workshop, American Geophysical Union Fall Meeting 2013 and the accompanying antenna meeting in Berkeley.

  11. NASA Space Rocket Logistics Challenges

    Science.gov (United States)

    Neeley, James R.; Jones, James V.; Watson, Michael D.; Bramon, Christopher J.; Inman, Sharon K.; Tuttle, Loraine

    2014-01-01

    The Space Launch System (SLS) is the new NASA heavy lift launch vehicle and is scheduled for its first mission in 2017. The goal of the first mission, which will be uncrewed, is to demonstrate the integrated system performance of the SLS rocket and spacecraft before a crewed flight in 2021. SLS has many of the same logistics challenges as any other large scale program. Common logistics concerns for SLS include integration of discreet programs geographically separated, multiple prime contractors with distinct and different goals, schedule pressures and funding constraints. However, SLS also faces unique challenges. The new program is a confluence of new hardware and heritage, with heritage hardware constituting seventy-five percent of the program. This unique approach to design makes logistics concerns such as commonality especially problematic. Additionally, a very low manifest rate of one flight every four years makes logistics comparatively expensive. That, along with the SLS architecture being developed using a block upgrade evolutionary approach, exacerbates long-range planning for supportability considerations. These common and unique logistics challenges must be clearly identified and tackled to allow SLS to have a successful program. This paper will address the common and unique challenges facing the SLS programs, along with the analysis and decisions the NASA Logistics engineers are making to mitigate the threats posed by each.

  12. Bioanalysis: challenges and solutions seminar.

    Science.gov (United States)

    Roberts, Andrew

    2011-09-01

    Industry challenges and solutions for bioanalysis were top of the agenda for the Spring Seminar organized by Quotient Bioresearch in Munich, Germany. The seminar was attended by representatives from pharmaceutical and biotechnology organisations across Europe and featured debates and panel discussions from leading industry speakers on new techniques and hot topics, including the latest industry guidelines.

  13. Self Efficacy: Operationalizing Challenge Education.

    Science.gov (United States)

    McGowan, Michael L.

    1986-01-01

    Examines self-efficacy theory and how it can be utilized in describing participant change in adventure/challenge programs. Explores connection between personal experience and how people view ability to function in world around them. Discusses Bandura's theory and interaction of sources of information: performance accomplishment, vicarious…

  14. Challenges to Vocational Teacher Education.

    Science.gov (United States)

    Erickson, Richard C.

    1985-01-01

    Challenges to vocational teacher education include technological change that is sending large numbers of adults back to school; increasing numbers of women, minorities, and handicapped individuals who are seeking employment in nontraditional occupations; vocational preparation for jobs in the information economy; teacher recruitment; and creative…

  15. The Kiki-Bouba Challenge

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Collins, Nick

    2014-01-01

    We propose the “Kiki-Bouba Challenge” (KBC) for the re- search and development of content-based music informa- tion retrieval (MIR) systems. This challenge is unencum- bered by several problems typically encountered in MIR research: insufficient data, restrictive copyrights, imper- fect ground...

  16. The Concrete and Pavement Challenge

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    The modern world is characterized by the extensive use of concrete and asphalt pavement. Periodically, these materials are replaced and the old materials disposed of. In this challenge, students will be asked to develop ways to reuse the old materials. It is important for students to understand how concrete and asphalt are made and applied, as…

  17. Employees’ Organizational Commitment Challenges - a Hotel Industry Perspective

    OpenAIRE

    Carmen Arustei

    2013-01-01

    Hotel industry is confronted with some challenges induced by changing customers’ requirements and by a competitive environment. In this context, front-line employees are a very important determinant of organizational performance. Researchers suggested that organizational performance can be achieved through employee organizational commitment (OC) development. This is the reason why this paper aims to explore employees’ level of OC components from hotel chains, considering a variety of independ...

  18. Organotypic liver culture models: Meeting current challenges in toxicity testing

    OpenAIRE

    LeCluyse, Edward L.; Witek, Rafal P; Andersen, Melvin E.; Powers, Mark J.

    2012-01-01

    Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive respo...

  19. An All-School Library Challenge

    Science.gov (United States)

    Quirk, Connie

    2005-01-01

    The library media center is hosting an all-school team challenge, designed to celebrate reading and library skills. Students could choose from the contest categories like "Lord of the Rings", "Harry Potter", Author Facts Challenge and Opening Lines Challenge for the competition and those students who read more challenging books show their…

  20. Heparin Characterization: Challenges and Solutions

    Science.gov (United States)

    Jones, Christopher J.; Beni, Szabolcs; Limtiaco, John F. K.; Langeslay, Derek J.; Larive, Cynthia K.

    2011-07-01

    Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.

  1. Challenges for Research on Intelligence

    Directory of Open Access Journals (Sweden)

    Earl Hunt

    2013-10-01

    Full Text Available After 100 years of research, the definition of the field is still inadequate. The biggest challenge we see is moving away from a de-factor definition of intelligence in terms of test scores, but at the same time making clear what the boundaries of the field are. We then present four challenges for the field, two within a biological and two within a social context. These revolve around the issues of the malleability of intelligence and its display in everyday life, outside of a formal testing context. We conclude that developments in cognitive neuroscience and increases in the feasibility of monitoring behavior outside of the context of a testing session offer considerable hope for expansion of our both the biological and social aspects of individual differences in cognition.

  2. Antibiotic resistance: An ethical challenge.

    Science.gov (United States)

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper.

  3. Challenges and opportunities in nanomanufacturing

    Science.gov (United States)

    Cooper, Khershed P.; Wachter, Ralph F.

    2011-10-01

    Nanomanufacturing is the fabrication of materials and components with nanoscale features and resolution and their integration into useful engineered systems. Through the precise control of materials and processes at the nanoscale, new features, functional capabilities, and properties, controlled by physics at the nanoscale, may be realized. The challenges for nanomanufacturing are achieving the desired functionality, product quality, process repeatability, production scalability and cost affordability. The ONR Manufacturing Science Program is meeting these challenges though basic research in nano-scale direct digital manufacturing, massively parallel nanoscale processing, and high-throughput (e.g., roll-to-roll) nanofabrication that encourages system-level integration. These concepts along with research examples will be described.

  4. Smart textiles: Challenges and opportunities

    Science.gov (United States)

    Cherenack, Kunigunde; van Pieterson, Liesbeth

    2012-11-01

    Smart textiles research represents a new model for generating creative and novel solutions for integrating electronics into unusual environments and will result in new discoveries that push the boundaries of science forward. A key driver for smart textiles research is the fact that both textile and electronics fabrication processes are capable of functionalizing large-area surfaces at very high speeds. In this article we review the history of smart textiles development, introducing the main trends and technological challenges faced in this field. Then, we identify key challenges that are the focus of ongoing research. We then proceed to discuss fundamentals of smart textiles: textile fabrication methods and textile interconnect lines, textile sensor, and output device components and integration of commercial components into textile architectures. Next we discuss representative smart textile systems and finally provide our outlook over the field and a prediction for the future.

  5. Embracing the challenge of competition

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, C. [Edmonton Power Inc., Edmonton, AB (Canada)

    1998-07-01

    The new and creative solutions that Edmonton Power is using to meet the challenges of deregulation, competition and demand for customer choice in the electric power industry are discussed. Among these creative initiatives, in 1997 Edmonton Power extended account management services to 850 accounts to deliver commercial and operational analysis of energy consumption and management. Another major focus of effort has been the introduction of time of use (TOU) pricing options to commercial and industrial customers above 150 kWh. This required the installation of the latest hourly metering technology and the establishment of new price plans and contracts. Two major challenges were highlighted: (1) the mismatch between the prices utilities pay at the power pool and what the customer pays at the meter, and (2) the increased volatility of hour to hour price changes are just some of the risks that will have to be resolved under the new market structure.

  6. MR connectomics: Principles and challenges.

    Science.gov (United States)

    Hagmann, Patric; Cammoun, Leila; Gigandet, Xavier; Gerhard, Stephan; Grant, P Ellen; Wedeen, Van; Meuli, Reto; Thiran, Jean-Philippe; Honey, Christopher J; Sporns, Olaf

    2010-12-15

    MR connectomics is an emerging framework in neuro-science that combines diffusion MRI and whole brain tractography methodologies with the analytical tools of network science. In the present work we review the current methods enabling structural connectivity mapping with MRI and show how such data can be used to infer new information of both brain structure and function. We also list the technical challenges that should be addressed in the future to achieve high-resolution maps of structural connectivity. From the resulting tremendous amount of data that is going to be accumulated soon, we discuss what new challenges must be tackled in terms of methods for advanced network analysis and visualization, as well data organization and distribution. This new framework is well suited to investigate key questions on brain complexity and we try to foresee what fields will most benefit from these approaches. PMID:20096730

  7. Terahertz applications: trends and challenges

    Science.gov (United States)

    Robin, Thierry; Bouye, Clementine; Cochard, Jacques

    2014-03-01

    The objective of our work [1] was to determine the opportunities and challenges for Terahertz application development for the next years with a focus on systems: for homeland security and for Non Destructive Testing (NDT). Terahertz radiation has unique abilities and has been the subject of extensive research for many years. Proven concepts have emerged for numerous applications including Industrial NDT, Security, Health, Telecommunications, etc. Nevertheless, there has been no widely deployed application and Businesses based on THz technologies are still in their infancy. Some technological, market and industrial barriers are still to be broken. We summarize the final analysis and data: study of the technology trends and major bottlenecks per application segment, main challenges to be addressed in the next years, key opportunities for THz technologies based on market needs and requirements.

  8. Challenges in pediatric endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Vikas Mittal

    2014-01-01

    Full Text Available We performed endothelial keratoplasty (EK in three eyes of two siblings (2.5 years, male and 3.5 years, female with congenital hereditary endothelial dystrophy (CHED and report the intraoperative and postoperative difficulties. Repeated iris prolapse, apprehension of crystalline lens touch due to positive vitreous pressure, and need for frequent air injections to attach the graft were intraoperative challenges in all three eyes. These were addressed by use of Sheet′s glide instead of Busin′s glide during graft insertion and suturing of main and side ports before air injection. One eye had graft dislocation on second postoperative day due to eye rubbing by the child. Graft was repositioned with air and a venting incision was created. Postoperative examination required repeated general anesthesia. Corneal edema resolved completely in all three eyes. Present case series highlights the possible intraoperative and postoperative challenges and their solutions in pediatric EK for CHED.

  9. Challenges in Complex Systems Science

    CERN Document Server

    Miguel, Maxi San; Kertesz, Janos; Kaski, Kimmo; Díaz-Guilera, Albert; MacKay, Robert S; Loreto, Vittorio; Erdi, Peter; Helbing, Dirk

    2012-01-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneou...

  10. Challenges and Advances in Nanotoxicology

    Directory of Open Access Journals (Sweden)

    Robert L. Tanguay

    2014-08-01

    Full Text Available This Special Issue of Nanomaterials examines the potential for engineered nanomaterials to negatively impact biological systems and highlights some advances in evaluating key areas of their hazard potential. Nanomaterial science is evolving rapidly with the generation of more complex nanostructures with exciting potential applications. Keeping modern toxicology abreast of this innovation to the point that it guides a safer nanotechnology presents an equally exciting and eminently worthwhile challenge. [...

  11. Paraganglioma: a potentially challenging tumor.

    Science.gov (United States)

    Trombetta, Mark; Silverman, Jan; Colonias, Athanasios; Lee, Vincent; Mohanty, Alok; Parda, David

    2008-03-01

    Paragangliomas are usually low-grade neoplasms with a benign natural history. While the treatment of paraganglioma has historically been controversial, surgery and radiotherapy have become standardized as therapies of choice for primary therapy. More recently, stereotactic radiosurgery has been used effectively against this rare tumor. The development of metastatic disease in patients with paraganglioma is an unusual and challenging event. This case report and review describes the specific features of this disease and the multiple therapeutic options.

  12. Challenges for Contextualizing Language Learning

    DEFF Research Database (Denmark)

    Eskildsen, Søren; Rehm, Matthias

    2013-01-01

    To help facilitate language learning for immigrants or foreigners arriving to another culture and language, we propose a context-aware mobile application. To expand on the known elements like location, activity, time and identity, we investigate the challenges on including cultural awareness...... to ensure a better experience-based learning. We present methods used to collect information about everyday activities collected by immigrants or foreigners. This information will help structuring language learning assignments presented through the context-aware mobile application....

  13. Challenges in global genomics education

    Directory of Open Access Journals (Sweden)

    Ashwini de Abrew

    2014-12-01

    Full Text Available In spite of high expectations for the integration of genomics into medicine, it is not clear that health providers are competent to appropriately use new genomic approaches. The issue is further complicated by differences across the globe in terms of educational systems, access to genomic technologies, and priorities in health care. In this commentary we will review some of the major challenges in educating the health provider workforce about genomic medicine.

  14. Feature Selection: Algorithms and Challenges

    Institute of Scientific and Technical Information of China (English)

    Xindong Wu; Yanglan Gan; Hao Wang; Xuegang Hu

    2006-01-01

    Feature selection is an active area in data mining research and development. It consists of efforts and contributions from a wide variety of communities, including statistics, machine learning, and pattern recognition. The diversity, on one hand, equips us with many methods and tools. On the other hand, the profusion of options causes confusion. This paper reviews various feature selection methods and identifies research challenges that are at the forefront of this exciting area.

  15. The challenges of managing migration

    Energy Technology Data Exchange (ETDEWEB)

    Tacoli, Cecilia

    2005-10-15

    Migration and urbanisation are driven by economic growth and social change, but also by deepening inequalities. Managing migration should not be equated with curbing it, as this inevitably reduces migrants' rights. But managing population movement whilst respecting the rights of migrants and nonmigrants, supporting the contribution of migration to poverty reduction and economic growth in sending and receiving areas and reducing the human and material costs of movement means that fundamental challenges need to be addressed.

  16. Asia Confronts Its Inflation Challenge

    Institute of Scientific and Technical Information of China (English)

    Gerard Lyons

    2011-01-01

    @@ Asia is finally waking up to its inflation challenge.Recent weeks have seen a further round of monetary tighten-ing, with a succession of central banks raising interest rates, or taking other measures to put a cap on rising prices.India, in particular, has taken tougher action than before, with a large rate hike, whilst others such as China have again pushed up reserve requirements.

  17. Diagnostic Challenges in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Mahmood Haghighat

    2014-04-01

    Full Text Available 1. The most important challenge in diagnosis of celiac disease is not-performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be aware about uncommon presentations of disease and indications of celiac tests. 2. The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3. The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing for DQ8 and DQ2 should be done. 4. The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN, positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5. In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6. In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7. Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.

  18. Diagnostic challenges in celiac disease

    Directory of Open Access Journals (Sweden)

    M Haghighat

    2014-04-01

    Full Text Available   1-The most important challenge in diagnosis of celiac disease is not- performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be awared about uncommon presentations of disease and indications of celiac tests 2-The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3- The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing  for DQ8 and  DQ2 should be done. 4-The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN , positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5-In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6-In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7-Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.  

  19. Statistical Challenges in Functional Genomics

    OpenAIRE

    Sebastiani, Paola; Gussoni, Emanuela; Kohane, Isaac S.; Ramoni, Marco F

    2003-01-01

    On February 12, 2001 the Human Genome Project announced the completion of a draft physical map of the human genome---the genetic blueprint for a human being. Now the challenge is to annotate this map by understanding the functions of genes and their interplay with proteins and the environment to create complex, dynamic living systems. This is the goal of functional genomics. Recent technological advances enable biomedical investigators to observe the genome of entire orga...

  20. Economic challenges in the Anthropocene

    OpenAIRE

    Musu, Ignazio

    2013-01-01

    The evolution during the Anthropocene is analyzed through the interaction between economic and technological development, characterized by the role of fossil fuels and by the progressive dominance of those with a higher energy and density power. The challenge is how to make the rising demand for economic growth, mainly coming from developing and emerging countries, compatible with the sustainability of the processes concerning the Earth system. Mainly by focusing on the energy-environment cha...

  1. The Challenge of the bespoke

    DEFF Research Database (Denmark)

    Tamke, Martin; Quinn, Gregory; Evers, Henrik Leander;

    2014-01-01

    The Dermoid project, a series of three plywood grid shells, navigates at the interface between parametrically designed architectural spaces and the efficiency and resourcefulness of the simulations that are necessary in order to build them. It highlights the increasingly common challenges...... and conflicts which occur in building practice ranging from design to fabrication and highlights approaches that facilitate implementation in multiple scales of material, element and structure....

  2. Challenges of aircraft design integration

    OpenAIRE

    Kafyeke, F.; Abdo, M.; Pepin, F; Piperni, P.; Laurendeau, E.

    2007-01-01

    The design of a modern airplane brings together many disciplines: structures, aerodynamics, controls, systems, propulsion with complex interdependencies and many variables. Recent aircraft programs, such as Bombardier's Continental Jet program use participants located around the world and selected for their cost, quality and delivery capability. These participants share the risk on the program and must therefore be fully implicated in the design. A big challenge is to provide information on c...

  3. Laser Challenges for Fast Ignition

    Energy Technology Data Exchange (ETDEWEB)

    Zuegel, J.D.; Borneis, S.; Barty, C.; LeGarrec, B.; Danson, C.; Miyanga, N.; Rambo, P.K.; LeBlanc, C.; Kessler, T.J.; Schmid, A.W.; Waxer, L.J.; Kelly, J.H.; Kruschwitz, B.; Jungquist, R.; Moses, E.; Britten, J.; Jovanovic, I.; Dawson, J.; Blanchot, N.

    2006-04-12

    The laser challenges and state of the art in high-energy, solid-state petawatt lasers for fast ignition (FI) research are reviewed. A number of new laser systems are currently under construction or being planned that will facilitate proof-of-principle FI experiments. Recent technological advances in each of the major ultrafast laser subsystems are reported, including chirped-pulse generation and broadband amplification in the front end, high-energy amplification, and pulse compression with adaptive wavefront correction.

  4. Proceedings: International conference Reforestation Challenges

    OpenAIRE

    Vladan Ivetić; Dragica Stanković

    2015-01-01

    This book of Proceedings compiles 35 papers presented by researchers and scientists at The International Conference on Reforestation Challenges. Topics included various aspects of reforestation: 1) Planning and management of reforestation programs; 2) Stocktypes and seedlings quality; 3) Monitoring reforestation successes; 4) Planting and seedling-site interaction; 5) Species, intra-species and seed source selection and 6) Plant health in nurseries and plantations. In addition to country repo...

  5. Challenges when introducing electronic exam

    Directory of Open Access Journals (Sweden)

    Matti Kuikka

    2014-10-01

    Full Text Available Time pressures often necessitate the use of more efficient exam tools, such as electronic exams (e-exams, instead of traditional paper exams. However, teachers may face challenges when introducing e-exams in a higher education context. This paper describes what kinds of challenges teachers may face when introducing e-exams, based on experiences in Turku University of Applied Sciences (TUAS where e-exams have been used since 2012. For this research, the authors used their personal experiences as administrators and teachers of current e-systems used for e-exams in universities in Turku, Finland. Quantitative data were collected by survey from teachers in TUAS (the case study. The learning management systems, Moodle, Optima and ViLLE, and dedicated e-examination systems, Soft Tutor and Tenttis, were also compared to clarify what kind of features are available in order to ease teachers’ work with examinations. The results identified various challenges during e-exam introduction in TUAS. The paper also provides a list of essential services or features for teachers to ease the introduction of e-exams. Among the analysed systems, ViLLE supported most of the required features, and can be used for both learning management and e-examination systems, providing teachers with one single system, which was found to be important to teachers. The key service found by this paper is ‘support for teachers’, which is in line with previous studies.

  6. Challenges of Big Data Analysis.

    Science.gov (United States)

    Fan, Jianqing; Han, Fang; Liu, Han

    2014-06-01

    Big Data bring new opportunities to modern society and challenges to data scientists. On one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity, and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This article gives overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasize on the viability of the sparsest solution in high-confidence set and point out that exogeneous assumptions in most statistical methods for Big Data can not be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions.

  7. Challenges in complex systems science

    Science.gov (United States)

    San Miguel, M.; Johnson, J. H.; Kertesz, J.; Kaski, K.; Díaz-Guilera, A.; MacKay, R. S.; Loreto, V.; Érdi, P.; Helbing, D.

    2012-11-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneous databases; moving from data to dynamical models, going beyond correlations to cause-effect relationships, understanding the relationship between simple and comprehensive models with appropriate choices of variables, ensemble modeling and data assimilation, modeling systems of systems of systems with many levels between micro and macro; and formulating new approaches to prediction, forecasting, and risk, especially in systems that can reflect on and change their behaviour in response to predictions, and systems whose apparently predictable behaviour is disrupted by apparently unpredictable rare or extreme events. These challenges are part of the FuturICT agenda.

  8. CHALLENGES IN CROSS CULTURAL ADVERTISING

    Directory of Open Access Journals (Sweden)

    Yuni Retnowati

    2015-10-01

    Full Text Available At first, marketing practitioners and academics consider standardized approaches to marketing and advertising strategies in globalization, and then some studies proved that the standardization of advertising across culture is not valid. Therefore, cross cultural advertising takes local culture into account when conveying messages in advertisements. Cross cultural understanding is very important in order to produce successful localized advertising that would reflect the cultural values and norms of intended audience. Challenge in cross cultural advertising is the problem of communicating to people of diverse cultural background. Cross cultural solutions are applied in areas such as language, communication style, images and cultural values. Cross cultural advertising is simply about using common sense and analyzing how the different elements of an advertising campaign are impacted by culture and modifying them to best speak to the target audience. Other challenges are determining between standardization and adaptation of cultural values content of advertising when facing different people from diverse cultures. In academic side, the challenge is preparing students to design advertisements that communicate effectively to diverse cultures.

  9. Chemotherapy-induced polyneuropathy

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Vilholm, Ole Jakob

    2014-01-01

    Chemotherapy-induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most...... frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. Therefore, the aim of this MiniReview was to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant...

  10. International Collaboration: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    R. Jay Widmer

    2015-04-01

    Full Text Available Rambam Maimonides Medical Journal 2015 April; 6(2: e0012. ISSN: 2076-9172 Published online 2015 April 29. Special Issue on the Rambam-Mayo Collaboration Guest Editor: John H. Davidson, M.D., M.A.H.L. doi: 10.5041/RMMJ.10196. International Collaboration: Promises and Challenges R. Jay Widmer, M.D., Ph.D.,1 Jocelyn M. Widmer, Ph.D., M.P.H.,2 and Amir Lerman, M.D.1* 1Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN, USA; 2Department of Urban and Regional Planning, College of Design, Construction and Planning, University of Florida, Gainesville, FL, USA Conflict of interest: No potential conflict of interest relevant to this article was reported. * To whom correspondence should be addressed. E-mail: lerman.amir@mayo.edu Copyright: © 2015 Widmer et al. This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract We currently face a myriad of grand global challenges in fields such as poverty, the environment, education, science, and medicine. However, our current means of dealing with such challenges has fallen short, and ingenious solutions are required to overcome the inherent resistance to progress toward ameliorating such difficulties. Here, we highlight the promises and challenges of international collaboration in achieving success toward these trials. We note prior successes in fields such as education, medicine, science, and environmental issues made to date, yet at the same time we do note deficiencies and shortcomings in these efforts. Hence, the notion of international collaboration should be strengthened and encouraged by governments, non-profit organizations, and others moving forward using creative

  11. 75 FR 21044 - Notice of Centennial Challenges 2011 CAFE Green Flight Challenge

    Science.gov (United States)

    2010-04-22

    ... SPACE ADMINISTRATION Notice of Centennial Challenges 2011 CAFE Green Flight Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2011 CAFE Green Flight... Flight Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  12. Addressing verification challenges [International safeguards symposium on addressing verification challenges

    International Nuclear Information System (INIS)

    In his welcome address the Director General of the International Atomic Energy Agency (IAEA), Mr. M. ElBaradei, stated that safeguards activities are probably the most difficult task entrusted to an international organization and to determine all the details of a country's nuclear programme is a daunting challenge that raises a number of questions. There is an increase in nuclear power around the globe as a result of shortages of energy and concerns about energy independence and climate change. On the one hand, this is good, because without energy there is no hope for development on the other hand, however, it means that nuclear know-how and nuclear technology will continue to spread to more and more countries. There is also an increase in the number of countries interested in developing nuclear fuel cycle capabilities: sensitive fuel cycle activities, reprocessing and above all uranium enrichment. It even seems that some countries might be hedging their bets in order to have the know-how should they need to develop their own deterrence. Verifying enrichment or reprocessing facilities is quite difficult, and the so-called conversion time is extremely short. Thus, the IAEA is dealing with what is called 'virtual nuclear weapon States'. The IAEA has been talking for a number of years about the need to develop a new international or multinational approach to the fuel cycle in order to avoid a situation with nine nuclear weapon States and another 20 or 30 States having the capacity to develop nuclear weapons in a very short period of time. There is a need to remember that there is a linkage between nuclear disarmament and non-proliferation. Furthermore safeguards activities, though fundamentally technical in nature, are carried out in a political charged environment. The security dimension - that is, nuclear terrorism - also presents a new challenge, because State systems of accounting for and control of nuclear material are no longer simply tools for safeguards, but

  13. Silicon photonics: some remaining challenges

    Science.gov (United States)

    Reed, G. T.; Topley, R.; Khokhar, A. Z.; Thompson, D. J.; Stanković, S.; Reynolds, S.; Chen, X.; Soper, N.; Mitchell, C. J.; Hu, Y.; Shen, L.; Martinez-Jimenez, G.; Healy, N.; Mailis, S.; Peacock, A. C.; Nedeljkovic, M.; Gardes, F. Y.; Soler Penades, J.; Alonso-Ramos, C.; Ortega-Monux, A.; Wanguemert-Perez, G.; Molina-Fernandez, I.; Cheben, P.; Mashanovich, G. Z.

    2016-03-01

    This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.

  14. PROFESSIONAL MASTER AND ITS CHALLENGES

    Directory of Open Access Journals (Sweden)

    Lydia Masako Ferreira

    2015-01-01

    Full Text Available Objective: To describe the history, origin, objectives, characteristics, implications, the questions of the evaluation form and some examples of the Professional Masters (MP, to differentiate the Academic Master, and identify the challenges for the next quadrennial assessment. Methods: The CAPES site on Professional Masters and documents and meeting area of reports from 2004 to 2013 of Medicine III were read as well as the reports and the sub-page of the area in Capes site. The data relating to the evaluation process and the Scoreboard of the other areas were computed and analyzed. From these data it was detected the challenges of Medicine III for the next four years (2013-2016. Results: The creation of the Professional Master is very recent in Medicine III and no Professional Master of Medicine III course was evaluated yet. Were described the objectives, assumptions, characteristics, motivations, the possibilities, the feasibility, the profile of the students, the faculty, the curriculum, funding, intellectual production, social inclusion, the general requirements of Ordinance No. 193/2011 CAPES and some examples of proposals, technological lines of scientific activities, partnerships and counterparties. The evaluation form of the MP was discussed, the need for social, economic and political intellectual production and the differences with the MA. It was also reported the global importance of the MP and its evolution in Brazil. From the understanding of the MP, Medicine III outlined some challenges and goals to be developed in the 2013-2016 quadrennium. Conclusion: Medicine III understood the MP as a new technological scientific horizon within the strict sensu post-graduate and full consistency with the area.

  15. International migration: a global challenge.

    Science.gov (United States)

    Martin, P; Widgren, J

    1996-04-01

    Trends in international migration are presented in this multiregional analysis. Seven of the world's wealthiest countries have about 33% of the world's migrant population, but under 16% of the total world population. Population growth in these countries is substantially affected by the migrant population. The migration challenge is external and internal. The external challenge is to balance the need for foreign labor and the commitment to human rights for those migrants seeking economic opportunity and political freedom. The internal challenge is to assure the social adjustment of immigrants and their children and to integrate them into society as citizens and future leaders. Why people cross national borders and how migration flows are likely to evolve over the next decades are explained. This report also presents some ways that countries can manage migration or reduce the pressures which force people to migrate. It is recommended that receiving nations control immigration by accelerating global economic growth and reducing wars and human rights violations. This report examines the impact of immigration on international trade, aid, and direct intervention policies. Although migration is one of the most important international economic issues, it is not coordinated by an international group. The European experience indicates that it is not easy to secure international cooperation on issues that affect national sovereignty. It is suggested that countries desiring control of their borders should remember that most people never cross national borders to live or work in another country, that 50% of the world's migrants move among developing countries, and that countries can shift from being emigration to immigration countries. The author suggests that sustained reductions in migration pressure are a better alternative than the "quick fixes" that may invite the very much feared mass and unpredictable movements.

  16. CHALLENGES FOR DIGITAL LITERATURE TEACHING

    Directory of Open Access Journals (Sweden)

    Edgar Roberto Kirchof

    2013-12-01

    Full Text Available This paper addresses some challenges faced by researchers and teachers interested in teaching digital literature in formal educational institutions. Initially, a brief history of digital literature is presented, with emphasis on the first literary experiments with computational language that were carried out still in the 50s, under the mentorship of Max Bense in Germany. In addition, the paper brings forward two movements of digital literature arising after the 50s: thedigital poetry and its relation with avant-garde poetry movements; and the hypertext literature. Finally, the paper presents the results of some educational projects on teaching digital literature conducted in different European universities

  17. University education: Demands and challenges

    Directory of Open Access Journals (Sweden)

    Eduardo Pinos Vélez

    2013-06-01

    Full Text Available This paper presents a study on the current situation prevailing in the Universities from the point of view of a teacher whose academic since its inception has been Salesian, which allows for a “best approach” to young students and where the passion for teaching is clearly influenced by the teachings of one of the greatest teachers, Don Bosco. Also, these teachings are still of great relevance in our time, seek to adopt these methodologies in our workspaces teaching is challenging, where you can suggest new strategies for communication and integration with students and in this way to service the needy, such as programs aid Persons with Disabilities.

  18. Challenging and Reducing Cultural Stereotypes

    Institute of Scientific and Technical Information of China (English)

    黄鸣

    2011-01-01

    Abstract:Anyplace where differences are found leaves room for stereotypes.Each of us hears or makes stereotypical comments every day,and although sometimes it is necessary to make stereotypes in foreign language teaching and learning,we should always be aware of the negative effects of stereotyping people from other cultures when we use them to interpret behavior.This paper defines stereotypes,discusses how they impede communication and then focuses on some ways to challenge and reduce stereotypes in cross-cultural communication.

  19. Nanometrology - challenges for health regulation

    Directory of Open Access Journals (Sweden)

    Jailton Carreteiro Damasceno

    2013-11-01

    Full Text Available The relationship between metrology, nanotechnology and nanoscience and sanitary regulation is discussed from the point of view of its importance and the interrelationship between the themes for the development of products and services involving nanotech-nology. The discussion involves the main techniques for measuring dimensional, chemical and biological properties of materials, and presents some of the challenges for the future. Issues such as processes of standardization and regulation in Europe, U.S. and Brazil are also addressed, providing an overview of how these processes are related to sanitary regulation.

  20. Developmental psychopathology: concepts and challenges.

    Science.gov (United States)

    Rutter, M; Sroufe, L A

    2000-01-01

    The defining features of developmental psychopathology concepts include attention to the understanding of causal processes, appreciation of the role of developmental mechanisms, and consideration of continuities and discontinuities between normality and psychopathology. Accomplishments with respect to these issues are reviewed in relation to attachment disorders, antisocial behavior, autism, depressive disorder, schizophrenia, and intellectual development. Major research challenges remain in relation to measurement issues, comorbidity, gender differences, cognitive processing, nature-nurture interplay, heterotypic continuity, continuities between normal variations and disorders, developmental programming, and therapeutic mechanisms in effective treatments. PMID:11014739

  1. The Challenges of Community Engagement.

    Science.gov (United States)

    Cormick, Craig

    2010-12-01

    Lyons and Whelan provide a useful list of recommendations as to how community engagement on nanotechnology could be improved, which very few people working in community engagement could disagree with. However, as the conclusions of any study are dependent on the data obtained, if more data had been obtained and analysed then different conclusions might have been reached. Addressing the key issues in the paper and providing more data, also allows an opportunity to expand on current issues relating to community engagement on nanotechnology and the challenges it provides for practitioners. PMID:21258427

  2. University education: Demands and challenges

    OpenAIRE

    Eduardo Pinos Vélez

    2013-01-01

    This paper presents a study on the current situation prevailing in the Universities from the point of view of a teacher whose academic since its inception has been Salesian, which allows for a “best approach” to young students and where the passion for teaching is clearly influenced by the teachings of one of the greatest teachers, Don Bosco. Also, these teachings are still of great relevance in our time, seek to adopt these methodologies in our workspaces teaching is challenging, where you c...

  3. Addressing the workforce pipeline challenge

    International Nuclear Information System (INIS)

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need. (authors)

  4. Addressing the workforce pipeline challenge

    Energy Technology Data Exchange (ETDEWEB)

    Leonard Bond; Kevin Kostelnik; Richard Holman

    2006-11-01

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need.

  5. The ambiguous challenge of intranets

    DEFF Research Database (Denmark)

    Thommesen, Jacob

    2003-01-01

    increases with tendencies to cooperate and communicate across organisational boundaries, mainly as a reaction to developments in markets and industrial knowledge base, but also due to the potential provided by computer network. In the third chapter I identify some characteristics of two fundamental intranet...... media, email and the web, partly in the perspective of media richness theory, partly compared with philosophical discussions of classical media. The fourth chapter presents an intranet in a global company, in which problems and challenges related to ambiguity have proven significant....

  6. Cleaning insertions and collimation challenges

    CERN Document Server

    Redaelli, S; Bertarelli, A; Bruce, R; Jowett, J M; Lechner, A; Losito, R

    2015-01-01

    High-performance collimation systems are essential for operating efficiently modern hadron machine with large beam intensities. In particular, at the LHC the collimation system ensures a clean disposal of beam halos in the superconducting environment. The challenges of the HL-LHC study pose various demanding requests for beam collimation. In this paper we review the present collimation system and its performance during the LHC Run 1 in 2010–2013. Various collimation solutions under study to address the HL-LHC requirements are then reviewed, identifying the main upgrade baseline and pointing out advanced collimation concept for further enhancement of the performance.

  7. Challenges of local water governance

    DEFF Research Database (Denmark)

    Munk Ravnborg, Helle; Bustamante, Rocio; Cissé, Abdoulaye;

    2012-01-01

    This article presents the results of comprehensive inventories made of water-related conflict and cooperation occurring in five districts in Africa, Asia and Latin America between 1997 and 2007. Following a description of the conceptual and methodological framework developed for undertaking...... these inventories, the article documents the extent, nature and intensity of water-related conflict and cooperation in the five districts. The article concludes by identifying three challenges relating to the magnitude, complexity and invisibility of local-level conflict and cooperation about water, which efforts...

  8. Challenges in wind farm optimization

    DEFF Research Database (Denmark)

    Larsen, Gunner Chr.

    for the wind turbine modeling, where aeroelastic models are required, and for the wind farm flow field description, where in-stationary flow field modeling is needed to capture the complicated mixture of atmospheric boundary layer (ABL) flows and upstream emitted meandering wind turbine wakes, which together...... dictates the fatigue loading of the individual wind turbines. Within an optimization context, the basic challenge in describing the in-stationary wind farm flow field is computational speed. The Dynamic Wake Meandering (DWM) model includes the basic features of a CFD Large Eddy Simulation approach...

  9. Nonlinear dynamics: Challenges and perspectives

    Indian Academy of Sciences (India)

    M Lakshmanan

    2005-04-01

    The study of nonlinear dynamics has been an active area of research since 1960s, after certain path-breaking discoveries, leading to the concepts of solitons, integrability, bifurcations, chaos and spatio-temporal patterns, to name a few. Several new techniques and methods have been developed to understand nonlinear systems at different levels. Along with these, a multitude of potential applications of nonlinear dynamics have also been enunciated. In spite of these developments, several challenges, some of them fundamental and others on the efficacy of these methods in developing cutting edge technologies, remain to be tackled. In this article, a brief personal perspective of these issues is presented.

  10. Responses to microbial challenges by SLAMF receptors

    Directory of Open Access Journals (Sweden)

    Boaz Job Van Driel

    2016-01-01

    Full Text Available The SLAMF Family (SLAMF of cell surface glycoproteins is comprised of nine glycoproteins and whilst SLAMF1, 3, 5, 6, 7, 8, 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other. Their interactions induce signal transduction networks in trans, thereby shaping immune cell-cell communications. Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development and, T and B cell responses to microbes and parasites. In addition, several SLAMF receptors serve as microbial sensors, which either positively or negatively modulate the function of macrophages, dendritic cells, neutrophils and NK cells in response to microbial challenges. The SLAMF receptor-microbe interactions contribute both to intracellular microbicidal activity as well as to migration of phagocytes to the site of inflammation. In this review, we describe the current knowledge on how the SLAMF receptors and their specific adapters SAP and EAT-2 regulate innate and adaptive immune responses to microbes.

  11. Munchausen syndrome by proxy: ongoing clinical challenges.

    Science.gov (United States)

    Squires, Janet E; Squires, Robert H

    2010-09-01

    In 1977, Roy Meadow, a pediatric nephrologist, first described a condition he subsequently coined Munchausen syndrome by proxy. The classic form involves a parent or other caregiver who inflicts injury or induces illness in a child, deceive the treating physician with fictitious or exaggerated information, and perpetrate the trick for months or years. A related form of pathology is more insidious and more common but also damaging. It involves parents who fabricate or exaggerate symptoms of illness in children, causing overly aggressive medical evaluations and interventions. The common thread is that the treating physician plays a role in inflicting the abuse upon the child. Failure to recognize the problem is common because the condition is often not included in the differential diagnosis of challenging or confusing clinical problems. We believe that a heightened "self-awareness" of the physician's role in Munchausen syndrome by proxy will prevent or reduce the morbidity and mortality associated with this diagnosis. In addition, we believe contemporary developments within the modern health care system likely facilitate this condition. PMID:20639771

  12. Modern climate challenges and the geological record

    Science.gov (United States)

    Cronin, Thomas M.

    2010-01-01

    Today's changing climate poses challenges about the influence of human activity, such as greenhouse gas emissions and land use changes, the natural variability of Earth's climate, and complex feedback processes. Ice core and instrumental records show that over the last century, atmospheric carbon dioxide (CO2) concentrations have risen to 390 parts per million volume (ppmv), about 40% above pre-Industrial Age concentrations of 280 ppmv and nearly twice those of the last glacial maximum about 22,000 years ago. Similar historical increases are recorded in atmospheric methane (CH4) and nitrous oxide (N2O). There is general agreement that human activity is largely responsible for these trends. Substantial evidence also suggests that elevated greenhouse gas concentrations are responsible for much of the recent atmospheric and oceanic warming, rising sea level, declining Arctic sea-ice cover, retreating glaciers and small ice caps, decreased mass balance of the Greenland and parts of the Antarctic ice sheets, and decreasing ocean pH (ocean "acidification"). Elevated CO2 concentrations raise concern not only from observations of the climate system, but because feedbacks associated with reduced reflectivity from in land and sea ice, sea level, and land vegetation relatively slowly (centuries or longer) to elevated 2 levels. This means that additional human-induced climate change is expected even if the rate of CO2 emissions is reduced or concentrations immediately stabilized.

  13. The male beard hair and facial skin - challenges for shaving.

    Science.gov (United States)

    Maurer, M; Rietzler, M; Burghardt, R; Siebenhaar, F

    2016-06-01

    The challenge of shaving is to cut the beard hair as closely as possible to the skin without unwanted effects on the skin. To achieve this requires the understanding of beard hair and male facial skin biology as both, the beard hair and the male facial skin, contribute to the difficulties in obtaining an effective shave without shaving-induced skin irritation. Little information is available on the biology of beard hairs and beard hair follicles. We know that, in beard hairs, the density, thickness, stiffness, as well as the rates of elliptical shape and low emerging angle, are high and highly heterogeneous. All of this makes it challenging to cut it, and shaving techniques commonly employed to overcome these challenges include shaving with increased pressure and multiple stroke shaving, which increase the probability and extent of shaving-induced skin irritation. Several features of male facial skin pose problems to a perfect shave. The male facial skin is heterogeneous in morphology and roughness, and male skin has a tendency to heal slower and to develop hyperinflammatory pigmentation. In addition, many males exhibit sensitive skin, with the face most often affected. Finally, the hair follicle is a sensory organ, and the perifollicular skin is highly responsive to external signals including mechanical and thermal stimulation. Perifollicular skin is rich in vasculature, innervation and cells of the innate and adaptive immune system. This makes perifollicular skin a highly responsive and inflammatory system, especially in individuals with sensitive skin. Activation of this system, by shaving, can result in shaving-induced skin irritation. Techniques commonly employed to avoid shaving-induced skin irritation include shaving with less pressure, pre- and post-shave skin treatment and to stop shaving altogether. Recent advances in shaving technology have addressed some but not all of these issues. A better understanding of beard hairs, beard hair follicles and male

  14. Space Shuttle Star Tracker Challenges

    Science.gov (United States)

    Herrera, Linda M.

    2010-01-01

    The space shuttle fleet of avionics was originally designed in the 1970's. Many of the subsystems have been upgraded and replaced, however some original hardware continues to fly. Not only fly, but has proven to be the best design available to perform its designated task. The shuttle star tracker system is currently flying as a mixture of old and new designs, each with a unique purpose to fill for the mission. Orbiter missions have tackled many varied missions in space over the years. As the orbiters began flying to the International Space Station (ISS), new challenges were discovered and overcome as new trusses and modules were added. For the star tracker subsystem, the growing ISS posed an unusual problem, bright light. With two star trackers on board, the 1970's vintage image dissector tube (IDT) star trackers track the ISS, while the new solid state design is used for dim star tracking. This presentation focuses on the challenges and solutions used to ensure star trackers can complete the shuttle missions successfully. Topics include KSC team and industry partner methods used to correct pressurized case failures and track system performance.

  15. Managing neurocysticercosis: challenges and solutions.

    Science.gov (United States)

    Fogang, Yannick Fogoum; Savadogo, Abdoul Aziz; Camara, Massaman; Toffa, Dènahin Hinnoutondji; Basse, Anna; Sow, Adjaratou Djeynabou; Ndiaye, Mouhamadou Mansour

    2015-01-01

    Taenia solium neurocysticercosis (NCC) is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline). Accurate patients' categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. PMID:26527895

  16. Meeting the Challenges for Agriculture

    Directory of Open Access Journals (Sweden)

    Les Copeland

    2011-06-01

    Full Text Available Ensuring food security is an ongoing global challenge. Many forecasts point to a need to increase food production by at least 70% if we are to feed the world’s projected population of nine billion in 2050. Recent volatility in commodity prices and the general upward trend in the cost of food are indicators that global food systems are now driven by demand rather than supply. There are various reasons for this: greater demand for animal protein with economic growth in developing countries; the continuing increase in world population; competition between food and bioenergy crops for land and water; low inventories of world grain stocks; reduced investment in agricultural R&D; and unfavorable weather resulting in a succession of poor harvests around the world. Increasing production of grains, which are the foundation of the human food supply, will have to be achieved through higher crop yields without boosting inputs of land, water and energy. Meeting community expectations for environmental stewardship and sustainability, and adapting food production to increasingly variable climate, add greatly to the challenge.

  17. Engineering ethics challenges and opportunities

    CERN Document Server

    Bowen, W Richard

    2014-01-01

    Engineering Ethics: Challenges and Opportunities aims to set a new agenda for the engineering profession by developing a key challenge: can the great technical innovation of engineering be matched by a corresponding innovation in the acceptance and expression of ethical responsibility?  Central features of this stimulating text include:   ·         An analysis of engineering as a technical and ethical practice providing great opportunities for promoting the wellbeing and agency of individuals and communities. ·         Elucidation of the ethical opportunities of engineering in three key areas:             - Engineering for Peace, emphasising practical amelioration of the root causes of    conflict rather than military solutions.             - Engineering for Health, focusing on close collaboration with healthcare professionals      for both the promotion and restoration of health.             - Engineering for Development, providing effective solution...

  18. Leadership Challenges in Academic Anesthesiology.

    Science.gov (United States)

    Mets, Berend

    2005-01-01

    The leadership challenge for academic anesthesiology lies in developing leadership at all levels in the department to create a meaningful, equitable, academic environment, with an attractive culture which challenges but supports and mentors individual growth and in so doing retains faculty. Education, research and clinical care, important as they are, are not ends in themselves, but a means to personal fulfillment lending meaning and identity to the individual which would be different from that which might be achieved in a private practice setting. The concepts of leadership from contemporary business literature are reviewed and a framework within which leadership can occur is described. This framework is based on an understanding of the role that the development of a departmental vision plays. This vision should be based on shared values as well as the mission of the department and should draw on the concepts of strategy, and commitment to realize the departmental goals. Based on these ideas, suggestions are made to illustrate how these business concepts might be applied in academic anesthesia departments.

  19. The coffee-time challenge

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The challenge to identify the LEP events displayed on coffee tables in Restaurant 1 (Bulletin 02-03/2010) sparked interest among readers who do not have the opportunity to see them . Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12 Table 13, Table 14, Table 15, Table 16       We have therefore decided to open the challenge to these readers by displaying the events on the web. We are also extending the deadline accordingly to 2 March. There are 16 events in total (in two areas), four from each of the four LEP experiments, and they include examples of different particle decays observed at LEP during its 11 years of operation. The list below indicates the decay channels represented. We are offering a prize of the ATLAS pop-up book, Voyage to the Heart of Matter, for the correct identification of all 16 events.  Entries should indicate the table number corresponding to each of the decays listed. There wi...

  20. Challenges in contemporary academic neurosurgery.

    Science.gov (United States)

    Black, Peter M

    2006-03-01

    Traditionally, the ideal academic neurosurgeon has been a "quadruple threat," with excellence in clinical work, teaching, research, and administration. This tradition was best exemplified in Harvey Cushing, who developed the field of neurosurgery 90 years ago. This paradigm will probably have to change as academic neurosurgeons face major challenges. In patient care, these include increasing regulatory control, increasing malpractice costs, consolidation of expensive care in academic centers, and decreasing reimbursement; in resident teaching, work hour limitations and a changing resident culture; in research, the increasing dominance of basic scientists in governmental funding decisions and decreased involvement of neurosurgeons in scientific review committees; and in administration, problems of relationships in the workplace, patient safety, and employment compliance in an increasingly bureaucratic system. To meet these challenges, the new academic neurosurgeon will probably not be a quadruple threat personally but will be part of a quadruple threat in a department and institution. Neurosurgeons in such a setting will have to work with hospital, medical school, and national and international groups to address malpractice, reimbursement, subspecialization, and training problems; find supplemental sources of income through grants, development funds, and hospital support; lead in the development of multidisciplinary centers for neuroscience, brain tumor, spine, and other initiatives; and focus on training leaders for hospital, regional, and national groups to reconfigure neurosurgery. Collaboration, flexibility, and leadership will be characteristic of the academic neurosurgeon in this new era.

  1. Multiphysics simulations: challenges and opportunities.

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, D.; McInnes, L. C.; Woodward, C.; Gropp, W.; Myra, E.; Pernice, M. (Mathematics and Computer Science); (KAUST and Columbia Univ.); (Lawrence Livermore National Laboratory); (Univ. of Illinois at Urbana-Champaign); (Univ. of Mich.); (Idaho National Lab.)

    2012-11-29

    This report is an outcome of the workshop Multiphysics Simulations: Challenges and Opportunities, sponsored by the Institute of Computing in Science (ICiS). Additional information about the workshop, including relevant reading and presentations on multiphysics issues in applications, algorithms, and software, is available via https://sites.google.com/site/icismultiphysics2011/. We consider multiphysics applications from algorithmic and architectural perspectives, where 'algorithmic' includes both mathematical analysis and computational complexity and 'architectural' includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. We also initiate a modest suite of test problems encompassing features present in many applications.

  2. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi

    2014-01-01

    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  3. Managing voluntary turnover through challenging assignments

    NARCIS (Netherlands)

    Preenen, P.T.Y.; Pater, I.E. de; Vianen, A.E.M. van; Keijzer, L.

    2011-01-01

    This study examines employees' challenging assignments as manageable means to reduce turnover intentions, job search behaviors, and voluntary turnover. Results indicate that challenging assignments are negatively related to turnover intentions and job search behaviors and that these relationships ar

  4. 6 CFR 7.30 - Classification challenges.

    Science.gov (United States)

    2010-01-01

    ... 6 CFR 7.31. ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Classification challenges. 7.30 Section 7.30... INFORMATION Classified Information § 7.30 Classification challenges. (a) Authorized holders of...

  5. Sustainable Materials Management (SMM) Electronics Challenge Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — On September 22, 2012, EPA launched the SMM Electronics Challenge. The Challenge encourages electronics manufacturers, brand owners and retailers to strive to send...

  6. The Challenges of Standardized Planetary Geologic Mapping

    Science.gov (United States)

    Skinner, J. A.

    2015-06-01

    The process and product of creating standardized geologic maps of planetary bodies has been met with particular challenges. Addressing these challenges helps ensure that benchmark contextual geologic map products remain a reliable community resource.

  7. Science solving the XXI century challenges

    OpenAIRE

    USAID. Office of Agriculture and Food Security; EGAT Agriculture and Agribusiness. R&D Management Unit

    2001-01-01

    Presentation describes the government and university partnerships that are taking on the challenges of food insecurity and poverty, challenges to agricultural development and and food security, and expectations in natural resource management.

  8. Challenges in diagnosing tuberculosis in children

    DEFF Research Database (Denmark)

    Rahman, Nadia; Pedersen, Karin Kæreby; Nielsen, Vibeke Rosenfeldt;

    2012-01-01

    Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country.......Clinical investigations of childhood tuberculosis (TB) are challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. We investigated the challenges in diagnosing TB in children in a low-incidence country....

  9. Health Care Challenges in Iran

    Directory of Open Access Journals (Sweden)

    M Davari

    2005-10-01

    Full Text Available All health systems across the world have faced new challenges, which is primarily referable to increasing the cost of health care services as well as growing demands for new and expensive health technologies. The aim of this study is to analyse the main challenges facing the Iranian health system. A review of available governmental and relevant publications about Iranian health care system was undertaken to assess the direction of future healthcare policy. Electronic news agencies, newspapers, and parliament’s electronic news also reviewed to realise policy-makers points of view about the health system. Healthcare services in Iran have had a great success in primary healthcare services in last 25 years, which is mainly attributable to National Health Networks policy. Between 1979 and 2003, average life expectancy at birth increased from 57 to 70 and infant mortality rate fell from 104 to 26 per thousand live births. Active vaccination system, very good distribution and coverage, free end point services, family planning, maternal teaching, and primary referral system are of strong advantages of health networks in Iran. However, the healthcare system is now subject to a range of new pressures that must be addressed. Many of these pressures are common to all health services (rising consumer demands and expectations for expensive new technologies, changing disease patterns, and resources shortage, but some are largely specific to Iran. Financial fairness contribution of the population to health system, responsiveness of health system, overusing new technologies, inadequate integration of health services, and inequitable distribution of the resources are of the main challenges of health system in Iran. In addition, considering demographic changes of the Iranian population in recent decades, which made Iranian population young, potential pressures due to an aging population will reveal in coming years. Many of these pressures relate to policies and

  10. Challenges and Opportunities for Libraries in Pakistan

    OpenAIRE

    Shafiq UR, Rehman; Pervaiz, Ahmad

    2007-01-01

    Abstract: This paper, based on review of literature, observation, and informal conversations, discusses various challenges regarding finance, collection development, ICTs, human resources, library education, library association and research & development faced by library profession in Pakistan. The opportunities to meet these challenges have also been explored. Keywords: Library challenges and opportunities (Pakistan); Librarianship (Pakistan); Library issues; Library profession in Pa...

  11. iSTEM: The Aerospace Engineering Challenge

    Science.gov (United States)

    English, Lyn D.; King, Donna T.; Hudson, Peter; Dawes, Les

    2014-01-01

    The authors developed The Paper Plane Challenge as one of a three-part response to The Aerospace Engineering Challenge. The Aerospace Engineering Challenge was the second of three multi-part activities that they had developed with the teachers during the year. Their aim was to introduce students to the exciting world of engineering, where they…

  12. Builders Challenge Quality Criteria Support Document

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-06-01

    This document provides guidance to U.S. home builders participating in Builders Challenge. To qualify for the Builders Challenge, a home must score 70 or less on the EnergySmart Home Scale (E-Scale). Homes also must meet the Builders Challenge Quality Cri

  13. 78 FR 20628 - Wireless Metering Challenge

    Science.gov (United States)

    2013-04-05

    ... challenge specification to spur the development of new, low cost wireless electric metering devices. In... of Energy Efficiency and Renewable Energy Wireless Metering Challenge AGENCY: Office of Energy... (EERE) requests comments on the draft version of the Wireless Power Meter Challenge Specification....

  14. Challenges of the Innovation Project

    Science.gov (United States)

    Hayrapetyan, Ruben

    2010-04-01

    In order to be successful in the modern world a professional needs to be creative, open to innovation, and able to take responsibilities. Innovation and creativity are not skills a person is born with, they have to be taught. However, the course syllabus has almost no room for teaching anything except of standard course topics and even more standard applications. Course project may be a solution to this problem. But being a strong tool for teaching an innovation, such a project is a challenge for both students and instructors. In this talk I will discuss some outputs (both positive and negative) of the innovation project ``Trip to Mars'' given in my ``Differential Equations'' class.

  15. Crowdsourcing. A Citizen Participation Challenge

    Directory of Open Access Journals (Sweden)

    Junia Borges

    2014-05-01

    Full Text Available This paper is a work in progress on Crowdsourcing. First, its concepts and importance are discussed and then its value for citizenship and urban planning. The motivation for participation and the display of geo-tagged information, as well as its possible applications in dynamic spatial temporal issues are presented, as well as its different approaches and applications. Furthermore, Crowdsourcing is discussed when the “ONVCêVIU”, a VGI case study, is presented, revealing its origin, objective, free platform comparison - to select the proper tool to implement, the project’s main challenges, results so far and further steps to be taken. To conclude a short review of the author’s vision about what is to come in the future research.

  16. Multiphysics simulations: Challenges and opportunities

    KAUST Repository

    Keyes, David E.

    2013-02-01

    We consider multiphysics applications from algorithmic and architectural perspectives, where "algorithmic" includes both mathematical analysis and computational complexity, and "architectural" includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. © The Author(s) 2012.

  17. Challenges in anaesthesia for elderly

    DEFF Research Database (Denmark)

    Strøm, Camilla; Rasmussen, L S

    2014-01-01

    The segment of elderly individuals comprises a growing proportion of the global population. Health care systems and health care providers worldwide need to understand the specific challenges related to treatment of this heterogeneous patient population. The process of ageing is complex and under...... constant influence by numerous factors, for which reason the way human age is extremely individual. It is important to understand and acknowledge how elderly differ from younger adults, and how management needs to be modified and tailored to the individual patient in order to improve outcomes. The goal...... of treatment of an elderly patient is not necessarily to increase human longevity regardless of the consequences, but to increase active longevity free from disability and functional dependence. For older people, deterioration in function can be devastating and is often precipitated by a stressful event...

  18. Multiphysics Simulations: Challenges and Opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, David; McInnes, Lois C.; Woodward, Carol; Gropp, William; Myra, Eric; Pernice, Michael; Bell, John; Brown, Jed; Clo, Alain; Connors, Jeffrey; Constantinescu, Emil; Estep, Don; Evans, Kate; Farhat, Charbel; Hakim, Ammar; Hammond, Glenn E.; Hansen, Glen; Hill, Judith; Isaac, Tobin; Jiao, Xiangmin; Jordan, Kirk; Kaushik, Dinesh; Kaxiras, Efthimios; Koniges, Alice; Lee, Ki Hwan; Lott, Aaron; Lu, Qiming; Magerlein, John; Maxwell, Reed M.; McCourt, Michael; Mehl, Miriam; Pawlowski, Roger; Randles, Amanda; Reynolds, Daniel; Riviere, Beatrice; Rude, Ulrich; Scheibe, Timothy D.; Shadid, John; Sheehan, Brendan; Shephard, Mark; Siegel, Andrew; Smith, Barry; Tang, Xianzhu; Wilson, Cian; Wohlmuth, Barbara

    2013-02-12

    We consider multiphysics applications from algorithmic and architectural perspectives, where ‘‘algorithmic’’ includes both mathematical analysis and computational complexity, and ‘‘architectural’’ includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities.

  19. Future challenges in renal transplantation.

    Science.gov (United States)

    Whalen, H; Clancy, M; Jardine, A

    2012-02-01

    There is a worldwide increase in the incidence of end-stage renal disease. Renal transplantation has been shown to be cost effective, prolong survival and provide a better quality of life in comparison to dialysis. Consequently, there has been a steady increase in demand for organs leading to a shortage of available kidneys, and an increase in transplant waiting lists. Renal transplantation is therefore an expanding field with a number of unique future challenges to address. This article outlines strategies that may be employed to expand organ supply in order to meet increased demand. The ethical issues surrounding this are also summarized. Furthermore, we highlight techniques with the potential to minimize peri-transplant injury to the kidney on its journey from donor to recipient. Current and potential future management strategies to optimize graft and patient survival are also discussed. PMID:22361673

  20. HCI challenges in Dance Education

    Directory of Open Access Journals (Sweden)

    K.El Raheb

    2016-08-01

    Full Text Available Dance learning is by nature multimodal, while dance practice presents a wide diversity across genres and contexts. Choreography and artistic contemporary dance performances have been using interactive technologies to support their creative process for several decades. Nevertheless the use of interactive technologies to support dance learning and education is still relatively immature and raises many challenges and interesting questions when it comes to choosing the appropriate human computer interaction methods. In this paper, we present the characteristics of dance teaching and learning in relation to interactive technology and we highlight the points/feedback that dance, as a field of mastering expressive movement, can bring to the design of whole-body interaction experiences.

  1. Eosinophilic ascites: a diagnostic challenge.

    Science.gov (United States)

    Khalil, Hesham; Joseph, Moby

    2016-01-01

    Eosinophilic ascites is a rare feature of eosinophilic gastroenteritis. We would like to highlight this increasingly recognised diagnosis in a case of unexplained ascites. We present a challenging case of a woman aged 25 years who presented with nausea, vomiting, diarrhoea, generalised abdominal pain and swelling 8-week following delivery of her first baby. Her symptoms were primarily aggravated by eating, and she had also noticed postprandial itching and self-limiting generalised rash. She had a strong history of atopy. Physical examination revealed abdominal tenderness and distension with shifting dullness. Urticarial skin rash was noted on the face, neck, chest and abdomen. Routine biochemistry was normal apart from peripheral eosinophilia. Imaging confirmed moderate ascites. Diagnostic paracentesis showed exudative ascites with numerous eosinophils. Histology of the upper and lower gastrointestinal tract showed infiltration of the oesophageogastroduodenal and rectosigmoid mucosa with eosinophils. The patient significantly improved following a course of steroids and six-food elimination diet. PMID:27600059

  2. Islay development flow assurance challenges

    Energy Technology Data Exchange (ETDEWEB)

    Helingoe, Mark; Greder, Hugues

    2010-07-01

    The Islay field is located in the Northern North Sea UK sector in the vicinity of the Alwyn Platforms. This gas condensate Brent structure is planned to be developed subsea with first gas in 2011. The main development challenge for this HPHT field comes from the early expected formation water production which is the source of major hydrate related flow assurance issues. As continuous inhibition is not feasible, Total has progressed a development scenario based on seabed conditioning prior to pipe laying so that water can be collected and temporarily inhibited at specific low points after a shut-down. It is also intended to heat trace the pipeline as a back-up solution to avoid hydrate formation. Heat tracing has so far never been implemented in Subsea developments. The Islay pilot could open the path to a new hydrate management philosophy for future developments. (Author)

  3. Refining in Germany: future challenges

    International Nuclear Information System (INIS)

    Changes in the German petroleum products market regarding volumes and qualities are examined and the impact on refinery costs of regulations reflecting the demands for improvements in the areas of vehicles and fuels, domestic heating, and industry is considered. The demand for petroleum products, diesel and jet fuels, and petrochemicals is discussed along with the introduction of low-sulphur and sulphur-free fuels, new engine designs incorporating deNOx catalysts and requiring sulphur-free fuel, and the tax breaks for sulphur-free fuel. The plans of the VORP company to produce SuperPlus fuel with a maximum 10ppm sulphur, the development of a desulphurisation catalyst, new types of distribution systems, and advanced processes which result in the removal of sulphur without significant reduction in octane number are outlined. Examples of the progress that VORP has made in adapting to the changing and challenging business environment are presented

  4. LNG - the challenge of growth

    International Nuclear Information System (INIS)

    LNG growth prospects - both in the Far East and Atlantic Basin - have never been better. Natural gas is responding strongly to the green momentum and to its clear competitive advantage in power generation. To meet growing demand, the major energy buyers are turning increasingly to large remote reserves of gas which often can only be delivered as LNG. But, the market will decide when and which LNG projects are developed - and the trigger will be price. LNG will compete head-on not only with low priced oil and coal but, in some markets, also with long-haul pipeline gas. This paper outlines regional demand and supply opportunities for LNG and then considers the challenges that the LNG industry must now tackle if it is to realistically expect a larger share of the world's energy market

  5. Ten Challenges for Decision Neuroscience

    Directory of Open Access Journals (Sweden)

    Scott A Huettel

    2010-09-01

    Full Text Available Decision neuroscience research, as currently practiced, employs the methods of neuroscience to investigate concepts drawn from the social sciences. A typical study selects one or more variables from psychological or economic models, manipulates or measures choices within a simplified choice task, and then identifies neural correlates. Using this neuroeconomic approach, researchers have described brain systems whose functioning shapes key economic variables, most notably aspects of subjective value. Yet, the standard approach has fundamental limitations. Important aspects of the mechanisms of decision making – from the sources of variability in decision making to the very computations supported by decision-related regions – remain incompletely understood. Here, I outline ten outstanding challenges for future research in decision neuroscience. While some will be readily addressed using current methods, others will require new conceptual frameworks. Accordingly, a new strain of decision neuroscience will marry methods from economics and cognitive science to concepts from neurobiology and cognitive neuroscience.

  6. Challenges in commercializing biomimetic membranes

    DEFF Research Database (Denmark)

    Perry, Mark; Madsen, Steen Ulrik; Jørgensen, Tine Elkjær;

    2015-01-01

    The discovery of selective water channel proteins—aquaporins—has prompted growing interest in using these proteins, as the building blocks for designing new types of membranes. However, as with any other new and potentially disruptive technology, barriers for successful market entry exist. One...... barriers and challenges associated with introducing biomimetic aquaporin membranes. These include technical issues in membrane production and product testing. Then we discuss possible business models for introducing new technologies in general, followed by a presentation of beach-head market segments...... organization and the technology are at early stages. Often, one faces barriers from both these categories at the same time, which makes it necessary to gain insight of the particular market when introducing a new innovative product. In this review we present the basic concepts and discuss some of these...

  7. Nuclear energy safety - new challenges

    Energy Technology Data Exchange (ETDEWEB)

    Rausch, Julio Cezar; Fonseca, Renato Alves da, E-mail: jrausch@cnen.gov.b, E-mail: rfonseca@cnen.gov.b [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    Fukushima accident in March this year, the second most serious nuclear accident in the world, put in evidence a discussion that in recent years with the advent of the 'nuclear renaissance' has been relegated in the background: what factors influence the use safe nuclear energy? Organizational precursor, latent errors, reduction in specific areas of competence and maintenance of nuclear programs is a scenario where the guarantee of a sustainable development of nuclear energy becomes a major challenge for society. A deep discussion of factors that influenced the major accidents despite the nuclear industry use of the so-called 'lessons learned' is needed. Major accidents continue to happen if a radical change is not implemented in the focus of safety culture. (author)

  8. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P

    2010-01-01

    The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

  9. Nanotechnology for the energy challenge

    CERN Document Server

    2013-01-01

    With the daunting energy challenges faced by Mankind in the 21st century, revolutionary new technologies will be the key to a clean, secure and sustainable energy future. Nanostructures often have surprising and very useful capabilities and are thus paving the way for new methodologies in almost every kind of industry. This exceptional monograph provides an overview of the subject, and presents the current state of the art with regard to different aspects of sustainable production, efficient storage and low-impact use of energy. Comprised of eighteen chapters, the book is divided in three thematic parts: Part I Sustainable Energy Production covers the main developments of nanotechnology in clean energy production and conversion, including photovoltaics, hydrogen production, thermal-electrical energy conversion and fuel cells. Part II Efficient Energy Storage is concerned with the potential use of nanomaterials in more efficient energy storage systems such as advanced batteries, supercapacitors and hydrogen st...

  10. Materials for Space: It's Challenging!

    Science.gov (United States)

    Johnson, Sylvia M.

    2016-01-01

    Space environments place tremendous demands on materials that must perform with exceptional reliability to realize the goals of human or robotic space exploration missions. Materials are subjected to extremes of temperature, pressure, radiation and mechanical loads during all phases of use, including takeoff and ascent, exposure to space or entry into an atmosphere, and operation in a planetary atmosphere. Space materials must be robust and enable the formation of lightweight structures or components that perform the required functions; materials that perform multiple functions are of particular interest. This talk will review the unique challenges for materials in space and some of the specific material capabilities that will be needed for future exploration missions. A description of needs and trends in thermal protection materials and systems will complete the talk.

  11. CHALLENGES OF PERMANENT TEACHER TRAINING

    Directory of Open Access Journals (Sweden)

    María Manuela Valles-Ornelas

    2015-07-01

    Full Text Available The new challenges for teachers and managers require to assume permanent formation as a tool for responding effectively and efficiently to them, different perspective to strengthen from the initial teacher education programs. The research was done in a primary school in the state of Chihuahua. The method used was research action, the question was: How can we encourage the lifelong learning and training of the staff of this school, with the purpose to assist them in these processes to improve the service that the school provides to students. The school group is the center of the process, the cooperative and collaborative work accompanied by educational leadership and persuasive provide better results, and all accompanied by the professional selfinvitation.

  12. Challenging industry conceptions with provotypes

    DEFF Research Database (Denmark)

    Boer, Laurens; Donovan, Jared; Buur, Jacob

    2013-01-01

    . Provotypes are ethnographically rooted, technically working, robust artefacts that deliberately challenge stakeholder conceptions by reifying and exposing tensions that surround a field of organizational interest. The daily and local experience of provotypes aim to stir dialectical processes of reflection...... on how conceptions currently are, and fuel the front end of a development process by speculating how conceptions could be different. In this article we start by making explicit the relation between provotypes, practices of critical design and organizational sense-making. We then illustrate through...... a multi-stakeholder project that concerned the field of indoor climate how provotypes facilitate transfers of user knowledge to industry, and how they contribute to the development of new products and services. We end by framing the role of the design researcher and discuss the politics that are inherent...

  13. Nuclear energy safety - new challenges

    International Nuclear Information System (INIS)

    Fukushima accident in March this year, the second most serious nuclear accident in the world, put in evidence a discussion that in recent years with the advent of the 'nuclear renaissance' has been relegated in the background: what factors influence the use safe nuclear energy? Organizational precursor, latent errors, reduction in specific areas of competence and maintenance of nuclear programs is a scenario where the guarantee of a sustainable development of nuclear energy becomes a major challenge for society. A deep discussion of factors that influenced the major accidents despite the nuclear industry use of the so-called 'lessons learned' is needed. Major accidents continue to happen if a radical change is not implemented in the focus of safety culture. (author)

  14. Challenges in diagnostic accuracy studies in primary care: The fecal calprotectin example

    OpenAIRE

    Holtman, Gea A; Leeuwen, Yvonne van; Kollen, Boudewijn; Escher, Johanna; Kindermann, A.; van Rheenen, Patrick F.; Berger, Marjolein

    2013-01-01

    textabstractAbstract. Background: Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of our choices, using a quality assessment tool for diagnostic accuracy studies (QUADAS-2). Design. The study investigates the diagnostic value of fecal calprotectin for detecting ...

  15. Technical solutions to nonproliferation challenges

    Science.gov (United States)

    Satkowiak, Lawrence

    2014-05-01

    The threat of nuclear terrorism is real and poses a significant challenge to both U.S. and global security. For terrorists, the challenge is not so much the actual design of an improvised nuclear device (IND) but more the acquisition of the special nuclear material (SNM), either highly enriched uranium (HEU) or plutonium, to make the fission weapon. This paper provides two examples of technical solutions that were developed in support of the nonproliferation objective of reducing the opportunity for acquisition of HEU. The first example reviews technologies used to monitor centrifuge enrichment plants to determine if there is any diversion of uranium materials or misuse of facilities to produce undeclared product. The discussion begins with a brief overview of the basics of uranium processing and enrichment. The role of the International Atomic Energy Agency (IAEA), its safeguard objectives and how the technology evolved to meet those objectives will be described. The second example focuses on technologies developed and deployed to monitor the blend down of 500 metric tons of HEU from Russia's dismantled nuclear weapons to reactor fuel or low enriched uranium (LEU) under the U.S.-Russia HEU Purchase Agreement. This reactor fuel was then purchased by U.S. fuel fabricators and provided about half the fuel for the domestic power reactors. The Department of Energy established the HEU Transparency Program to provide confidence that weapons usable HEU was being blended down and thus removed from any potential theft scenario. Two measurement technologies, an enrichment meter and a flow monitor, were combined into an automated blend down monitoring system (BDMS) and were deployed to four sites in Russia to provide 24/7 monitoring of the blend down. Data was downloaded and analyzed periodically by inspectors to provide the assurances required.

  16. Challenges for future energy usage

    International Nuclear Information System (INIS)

    In the last 2000 years the world's population and the worldwide total energy consumption have been continuously increasing, at a rate even greater than exponential. By now a situation has been reached in which energy resources are running short, which for a long time have been treated as though they were almost inexhaustible. The ongoing growth of the world's population and a growing hunger for energy in underdeveloped and emerging countries imply that the yearly overall energy consumption will continue to grow, by about 1.6 percent every year so that it would have doubled by 2050. This massive energy consumption has led to and is progressively leading to severe changes in our environment and is threatening a climatic state that, for the last 10 000 years, has been unusually benign. The coincidence of the shortage of conventional energy resources with the hazards of an impending climate change is a dangerous threat to the well-being of all, but it is also a challenging opportunity for improvements in our energy usage. On a global scale, conventional methods such as the burning of coal, gas and oil or the use of nuclear fission will still dominate for some time. In their case, the challenge consists in making them more efficient and environmentally benign, and using them only where and when it is unavoidable. Alternative energies must be expanded and economically improved. Among these, promising techniques such as solar thermal and geothermal energy production should be promoted from a shadow existence and further advanced. New technologies, for instance nuclear fusion or transmutation of radioactive nuclear waste, are also quite promising. Finally, a careful analysis of the national and global energy flow systems and intelligent energy management, with emphasis on efficiency, overall effectiveness and sustainability, will acquire increasing importance. Thereby, economic viability, political and legal issues as well as moral aspects such as fairness to disadvantaged

  17. Managing neurocysticercosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Fogang YF

    2015-10-01

    Full Text Available Yannick Fogoum Fogang, Abdoul Aziz Savadogo, Massaman Camara, Dènahin Hinnoutondji Toffa, Anna Basse, Adjaratou Djeynabou Sow, Mouhamadou Mansour Ndiaye Neurology Department, Fann Teaching Hospital, Cheikh Anta Diop University, Dakar, Senegal Abstract: Taenia solium neurocysticercosis (NCC is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline. Accurate patients' categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide. Keywords: neurocysticercosis, Taenia solium, epilepsy, headache, albendazole, praziquantel

  18. Challenges in Web Information Retrieval

    Science.gov (United States)

    Arora, Monika; Kanjilal, Uma; Varshney, Dinesh

    The major challenge in information access is the rich data available for information retrieval, evolved to provide principle approaches or strategies for searching. The search has become the leading paradigm to find the information on World Wide Web. For building the successful web retrieval search engine model, there are a number of challenges that arise at the different levels where techniques, such as Usenet, support vector machine are employed to have a significant impact. The present investigations explore the number of problems identified its level and related to finding information on web. This paper attempts to examine the issues by applying different methods such as web graph analysis, the retrieval and analysis of newsgroup postings and statistical methods for inferring meaning in text. We also discuss how one can have control over the vast amounts of data on web, by providing the proper address to the problems in innovative ways that can extremely improve on standard. The proposed model thus assists the users in finding the existing formation of data they need. The developed information retrieval model deals with providing access to information available in various modes and media formats and to provide the content is with facilitating users to retrieve relevant and comprehensive information efficiently and effectively as per their requirements. This paper attempts to discuss the parameters factors that are responsible for the efficient searching. These parameters can be distinguished in terms of important and less important based on the inputs that we have. The important parameters can be taken care of for the future extension or development of search engines

  19. Facing the challenge of multimorbidity

    Directory of Open Access Journals (Sweden)

    Boris Azaïs

    2016-02-01

    Full Text Available Abstract Multimorbidity is a major public health challenge that is rising up the political and health agenda at an accelerated rate. Although the prevalence of multimorbidity increases with age, more than half of the population with multimorbidity are under the age of 65 years [1], with social deprivation a key determinant of multimorbidity in young and middle-aged adults [2,3]. From an individual’s perspective, multimorbidity reduces life expectancy [4–6], decreases physical functioning and quality of life [7], and increases the risk of depression and other mental health disorders [3]. From a healthcare provider’s perspective, multimorbidity is associated with increased health service use, a high risk of emergency and other hospital admissions, high rates of polypharmacy, and spiralling costs [8]. Current health systems, which are typically built around a single-disease framework, are poorly adapted to cope with patients with multimorbidity, who typically experience fragmented healthcare services, leading to potentially inefficient and ineffective care. It is increasingly clear that we need to change our perspective on multimorbidity in order to address it as a specific condition that requires tailored solutions and approaches. The urgent need to tackle multimorbidity in a more strategic, holistic, and cost-effective manner was evident at the 18th European Health Forum Gastein, a leading annual health policy event in the European Union (EU, held in the autumn of 2015. This Forum attracted policymakers, clinicians, health service managers, patients, and a broad range of other stakeholders, all of whom were invited to attend a session entitled “Facing the Challenge of Multimorbidity”. Journal of Comorbidity 2016;6(1:1–3

  20. Correlates of Immunity to Influenza as Determined by Challenge of Children with Live, Attenuated Influenza Vaccine

    Science.gov (United States)

    Wright, Peter F.; Hoen, Anne G.; Ilyushina, Natalia A.; Brown, Eric P.; Ackerman, Margaret E.; Wieland-Alter, Wendy; Connor, Ruth I.; Jegaskanda, Sinthujan; Rosenberg-Hasson, Yael; Haynes, Brenda C.; Luke, Catherine J.; Subbarao, Kanta; Treanor, John J.

    2016-01-01

    Background. The efficacy of live, attenuated live attenuated influenza vaccine(LAIV) and inactivated influenza vaccine(IIV) is poorly explained by either single or composite immune responses to vaccination. Protective biomarkers were therefore studied in response to LAIV or IIV followed by LAIV challenge in children. Methods. Serum and mucosal responses to LAIV or IIV were analyzed using immunologic assays to assess both quantitative and functional responses. Cytokines and chemokines were measured in nasal washes collected before vaccination, on days 2, 4, and 7 after initial LAIV, and again after LAIV challenge using a 63-multiplex Luminex panel. Results. Patterns of immunity induced by LAIV and IIV were significantly different. Serum responses induced by IIV, including hemagglutination inhibition, did not correlate with detection or quantitation of LAIV on subsequent challenge. Modalities that induced sterilizing immunity seen after LAIV challenge could not be defined by any measurements of mucosal or serum antibodies induced by the initial LAIV immunization. No single cytokine or chemokine was predictive of protection. Conclusions. The mechanism of protective immunity observed after LAIV could not be defined, and traditional measurements of immunity to IIV did not correlate with protection against an LAIV challenge.

  1. Correlates of Immunity to Influenza as Determined by Challenge of Children with Live, Attenuated Influenza Vaccine.

    Science.gov (United States)

    Wright, Peter F; Hoen, Anne G; Ilyushina, Natalia A; Brown, Eric P; Ackerman, Margaret E; Wieland-Alter, Wendy; Connor, Ruth I; Jegaskanda, Sinthujan; Rosenberg-Hasson, Yael; Haynes, Brenda C; Luke, Catherine J; Subbarao, Kanta; Treanor, John J

    2016-04-01

    Background.  The efficacy of live, attenuated live attenuated influenza vaccine(LAIV) and inactivated influenza vaccine(IIV) is poorly explained by either single or composite immune responses to vaccination. Protective biomarkers were therefore studied in response to LAIV or IIV followed by LAIV challenge in children. Methods.  Serum and mucosal responses to LAIV or IIV were analyzed using immunologic assays to assess both quantitative and functional responses. Cytokines and chemokines were measured in nasal washes collected before vaccination, on days 2, 4, and 7 after initial LAIV, and again after LAIV challenge using a 63-multiplex Luminex panel. Results.  Patterns of immunity induced by LAIV and IIV were significantly different. Serum responses induced by IIV, including hemagglutination inhibition, did not correlate with detection or quantitation of LAIV on subsequent challenge. Modalities that induced sterilizing immunity seen after LAIV challenge could not be defined by any measurements of mucosal or serum antibodies induced by the initial LAIV immunization. No single cytokine or chemokine was predictive of protection. Conclusions.  The mechanism of protective immunity observed after LAIV could not be defined, and traditional measurements of immunity to IIV did not correlate with protection against an LAIV challenge. PMID:27419180

  2. Ionospheric Challenges for GNSS Based Augmentation Systems

    Science.gov (United States)

    Doherty, P.; Valladares, C. E.

    2007-12-01

    The ionosphere is a highly dynamic physical phenomenon that presents a variable source of error for Global Navigation Satellite System (GNSS) signals and GNSS based operational systems. The Federal Aviation Administration's (FAA) Wide-Area Augmentation System (WAAS) was designed to enhance the GNSS standard positioning service by providing additional accuracy, availability and integrity that is sufficient for use in commercial aviation. It is the first of a number of planned regional Satellite Based Augmentation Systems (SBAS). Other systems in development include the European EGNOS system, the MSAS system in Japan and the GAGAN system in India. In addition, the South American countries are investigating the feasibility of operating an SBAS system in this region. Much of the WAAS ionospheric research and development focused on defining and mitigating ionospheric challenges characteristic of the mid-latitude regions, where the ionosphere is well studied and relatively quiescent. The EGNOS and MSAS systems will primarily operate under a similarly quiescent mid-latitude ionosphere. SBAS system development in South America, India and other low-latitude regions, however, will have to contend with much more extreme conditions. These conditions include strong spatial and temporal gradients, plasma depletions and scintillation. All of these conditions have a potential to limit SBAS performance in the low latitude regions. This presentation will review the effects that the ionosphere has on the mid-latitude WAAS system. It will present the techniques that are used to mitigate ionospheric disturbances induced on the system during severe geomagnetic activity and it will quantify the effect that this activity has on system performance. The presentation will then present data from the South American Low-latitude Ionospheric Sensor Network (LISN) that can be used to infer the ionospheric effects on SBAS performance in the most challenging low-latitude ionospheric environment

  3. Small Space Launch: Origins & Challenges

    Science.gov (United States)

    Freeman, T.; Delarosa, J.

    2010-09-01

    The United States Space Situational Awareness capability continues to be a key element in obtaining and maintaining the high ground in space. Space Situational Awareness satellites are critical enablers for integrated air, ground and sea operations, and play an essential role in fighting and winning conflicts. The United States leads the world space community in spacecraft payload systems from the component level into spacecraft, and in the development of constellations of spacecraft. In the area of launch systems that support Space Situational Awareness, despite the recent development of small launch vehicles, the United States launch capability is dominated by an old, unresponsive and relatively expensive set of launchers in the Expandable, Expendable Launch Vehicles (EELV) platforms; Delta IV and Atlas V. The United States directed Air Force Space Command to develop the capability for operationally responsive access to space and use of space to support national security, including the ability to provide critical space capabilities in the event of a failure of launch or on-orbit capabilities. On 1 Aug 06, Air Force Space Command activated the Space Development & Test Wing (SDTW) to perform development, test and evaluation of Air Force space systems and to execute advanced space deployment and demonstration projects to exploit new concepts and technologies, and rapidly migrate capabilities to the warfighter. The SDTW charged the Launch Test Squadron (LTS) with the mission to develop the capability of small space launch, supporting government research and development space launches and missile defense target missions, with operationally responsive spacelift for Low-Earth-Orbit Space Situational Awareness assets as a future mission. This new mission created new challenges for LTS. The LTS mission tenets of developing space launches and missile defense target vehicles were an evolution from the squadrons previous mission of providing sounding rockets under the Rocket

  4. The challenges of lupus anticoagulants.

    Science.gov (United States)

    Chighizola, Cecilia Beatrice; Raschi, Elena; Banzato, Alessandra; Borghi, Maria Orietta; Pengo, Vittorio; Meroni, Pier Luigi

    2016-01-01

    The term "lupus anticoagulant" (LA) refers to a heterogeneous group of immunoglobulins behaving as acquired in vitro inhibitors of coagulation. These antibodies, namely anti-β2GPI and anti-prothrombin antibodies, induce the in vitro elongation of clotting time interfering with phospholipid-dependent coagulation cofactors. Positive LA is associated with thrombosis and pregnancy complications, providing one of the three laboratory criteria for the classification of the anti-phospholipid syndrome. LA is the strongest predictor of clinical events, especially when associated with other anti-phospholipid antibodies. Much more controversial is the risk conveyed by isolated and weak LA. LA detection is technically laborious, envisaging screening, mixing and confirming tests. Hopefully critical issues in LA detection, such as the interference of anticoagulants, will be overcome, in the next future. PMID:26789237

  5. Gaia and its spectrometric challenge

    International Nuclear Information System (INIS)

    The Gaia program was kicked off at the beginning of 2006 and is now reaching a phase of construction and integration for a launch at the end of 2011, to reach the L2 point several months later. Apart from that industrial activity, the European astronomical community is actively preparing the data treatment and in particular how to extract the astrophysical parameter outputs from the use of the spectrographs on board the satellite. This work consists of the realization of algorithms to extract fundamental parameters of the detected source points with the help of an extensive grid of synthetic spectral libraries. The number of these estimated fundamental parameters and their accuracy depend on the ability of the algorithms to treat the spectra and to compare them with the computed ones, and also on the quality of the synthetic spectra themselves. Then, on the one hand a huge effort is underway to produce these extensive grids of one-dimensional (1D) local thermodynamic equilibrium (LTE) spectra of stars, galaxies, quasi-stellar objects and asteroids, and on the other hand, new physics is tested in the atmosphere model of stars to improve the theoretical libraries. An example of the questions we need to answer is: do we need 3D non-local thermodynamic equilibrium (NLTE) modelling? If yes, the libraries will then be improved by adding corrections checked on dedicated standard stars. Shall we be able to implement this new physics in a reasonable time? This is another challenge.

  6. Northern pipelines : challenges and needs

    Energy Technology Data Exchange (ETDEWEB)

    Dean, D.; Brownie, D. [ProLog Canada Inc., Calgary, AB (Canada); Fafara, R. [TransCanada PipeLines Ltd., Calgary, AB (Canada)

    2007-07-01

    Working Group 10 presented experiences acquired from the operation of pipeline systems in a northern environment. There are currently 3 pipelines operating north of 60, notably the Shiha gas pipeline near Fort Liard, the Ikhil gas pipeline in Inuvik and the Norman Wells oil pipeline. Each has its unique commissioning, operating and maintenance challenges, as well as specific training and logistical support requirements for the use of in-line inspection tools and other forms of integrity assessment. The effectiveness of cathodic protection systems in a permafrost northern environment was also discussed. It was noted that the delay of the Mackenzie Gas Pipeline Project by two to three years due to joint regulatory review may lead to resource constraints for the project as well as competition for already scarce human resources. The issue of a potential timing conflict with the Alaskan Pipeline Project was also addressed as well as land use issues for routing of supply roads. Integrity monitoring and assessment issues were outlined with reference to pipe soil interaction monitoring in discontinuous permafrost; south facing denuded slope stability; base lining projects; and reclamation issues. It was noted that automatic welding and inspection will increase productivity, while reducing the need for manual labour. In response to anticipated training needs, companies are planning to involve and train Aboriginal labour and will provide camp living conditions that will attract labour. tabs., figs.

  7. New challenges for data design

    CERN Document Server

    2015-01-01

    The present work provides a platform for leading data designers whose vision and creativity help us to anticipate major changes occurring in the data design field, and pre-empt the future. Each of them strives to provide new answers to the question, “What challenges await data design?” To avoid falling into too narrow a mind-set, each works hard to elucidate the breadth of data design today and to demonstrate its widespread application across a variety of business sectors. With end users in mind, designer-contributors bring to light the myriad of purposes for which the field was originally intended, forging the bond even further between data design and the aims and intentions of those who contribute to it. The first seven parts of the book outline the scope of data design, and presents a line-up of “viewpoints” that highlight this discipline’s main topics, and offers an in-depth look into practices boasting both foresight and imagination. The eighth and final part features a series of interviews wit...

  8. Astronomy Education Challenges in Egypt

    Science.gov (United States)

    El Fady Beshara Morcos, Abd

    2015-08-01

    One of the major challenges in Egypt is the quality of education. Egypt has made significant progress towards achieving the Education for All and the Millennium Development Goals (MDGs). Many associations and committees as education reform program and education support programs did high efforts in supporting scientific thinking through the scientific clubs. The current state of astronomical education in Egypt has been developed. Astronomy became a part in both science and geography courses of primary, preparatory and secondary stages. Nowadays the Egyptian National Committee for Astronomy, put on its shoulders the responsibility of revising of astronomy parts in the education courses, beside preparation of some training programs for teachers of different stages of educations, in collaboration with ministry of education. General lectures program has been prepared and started in public places , schools and universities. Many TV and Radio programs aiming to spread astronomical culture were presented. In the university stage new astronomy departments are established and astrophysics courses are imbedded in physics courses even in some private universities.

  9. CMS prepares for new challenges

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    One of the world’s largest physics experiments has just had a change in leadership. This is a chance for the collaboration to take stock of the tremendous work done for LS1 and to prepare for the challenges that lie ahead.   From left to right: Kerstin Borras, Tiziano Camporesi and Paris Sphicas. “The keyword is teamwork. That’s the only way you can effectively manage a large number of extremely talented and motivated people,” says Tiziano Camporesi who took the reins of the CMS collaboration at the beginning of the year. The recipe might seem easier on paper than in practice. However, given his 28 years at CERN, two of which he spent as the head of the DELPHI collaboration, Camporesi has extensive experience in managing large scientific collaborations and success in this respect is well within his reach: “I have learned many lessons from the past and I believe that building consensus is instrumental to successful leadership.” The C...

  10. Gastroparesis: Concepts, Controversies, and Challenges

    Directory of Open Access Journals (Sweden)

    Klaus Bielefeldt

    2012-01-01

    Full Text Available Patients with gastroparesis often present a challenge to the treating physician. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also cause significant disruptions to social activities that often center around food. While the definition of gastroparesis focuses on impaired gastric emptying, treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic nature of the illness with a common history of abuse, and coexisting anxiety or depression show parallels with other functional disorders of the gastrointestinal tract. These parallels provided the rationale for some initial studies investigating alternative therapies that target the brain rather than the stomach. This emerging shift in medical therapy comes at a time when clinical studies suggest that gastric electrical stimulation may exert its effects by modulating visceral sensory processing rather than altering gastric motility. Physiologic and detailed anatomic investigations also support a more complex picture with different disease mechanisms, ranging from impaired accommodation to apparent visceral hypersensitivity or decreased interstitial cells of Cajal to inflammatory infiltration of myenteric ganglia. Delayed gastric emptying remains the endophenotype defining gastroparesis. However, our treatment options go beyond prokinetics and may allow us to improve the quality of life of affected individuals.

  11. Intratumoral Pharmacokinetics: Challenges to Nanobiomaterials.

    Science.gov (United States)

    Al-Abd, Ahmed M; Al-Abbasi, Fahad A; Torchilin, Vladimir P

    2015-01-01

    Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. Solid tumor tissue is characterized by high density of vascular bed however; the vast majority of these blood vessels are not functioning. The vast majority of solid tumors can be described as poorly perfused with blood; and anticancer agents need to penetrate/distribute avascularly within solid tumor micro-milieu. Classic pharmacokinetic parameters correlate drug status within central compartment (blood) to all perfused body tissues according to their degree of perfusion. Yet, these classic pharmacokinetic parameters cannot fully elucidate the intratumoral drug penetration/distribution status of anticancer drugs due to the great discrepancies in perfusion between normal and solid tumor tissues. Herein, we will discuss the recently proposed pharmacokinetic parameters that might accurately portray the distribution of anticancer agents within solid tumor micro-milieu. In addition, we will present the new challenges attributed to these new pharmacokinetic parameters towards designing nanobiomaterial drug delivery system. PMID:26027565

  12. Electrolyte materials - Issues and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Balbuena, Perla B. [Department of Chemical Engineering, and Department of Materials Science and Engineering, Texas A and M University, College Station, Texas, 77843 (United States)

    2014-06-16

    Electrolytes are vital components of an electrochemical energy storage device. They are usually composed of a solvent or mixture of solvents and a salt or a mixture of salts which provide the appropriate environment for ionic conduction. One of the main issues associated with the selection of a proper electrolyte is that its electronic properties have to be such that allow a wide electrochemical window - defined as the voltage range in which the electrolyte is not oxidized or reduced - suitable to the battery operating voltage. In addition, electrolytes must have high ionic conductivity and negligible electronic conductivity, be chemically stable with respect to the other battery components, have low flammability, and low cost. Weak stability of the electrolyte against oxidation or reduction leads to the formation of a solid-electrolyte interphase (SEI) layer at the surface of the cathode and anode respectively. Depending on the materials of the electrolyte and those of the electrode, the SEI layer may be composed by combinations of organic and inorganic species, and it may exert a passivating role. In this paper we discuss the current status of knowledge about electrolyte materials, including non-aqueous liquids, ionic liquids, solid ceramic and polymer electrolytes. We also review the basic knowledge about the SEI layer formation, and challenges for a rational design of stable electrolytes.

  13. Plant Biotechnology: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    P.V. Lakshmana Rao

    1996-01-01

    Full Text Available Development of procedures in cell biology to regenerate plants from single cells in any desired quantity provides the prerequisite for the practical use of plant tissue culture and genetic engineering in crop improvement. Such regenerating cell cultures are used for selection of mutants and for DNA transformation experiments. DNA transfer by means of engineered Ti and Ri plasmids has become an established technique for the rapidly growing list of dicotyledonous plants. Considerable success has also been achieved in making gene transfer techniques independent of cell culture methods. These techniques have given the opportunity to create, characterise and select plant cultivars which cannot be obtained by traditional breeding methods. The exploitation of plant cell cultures for production of pharmaceuticals, natural products of commercial importance and mass propagation of high-value crops by automation, have developed into an important industry with considerable potential for future. This paper discusses the recent advances and applications of plant biotechnology in agriculture and industry and the challenges the still exist.

  14. The challenge of patient adherence.

    Science.gov (United States)

    Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; Dimatteo, M Robin

    2005-09-01

    Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician-patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559

  15. Mystery photos: challenge No. 2!

    CERN Multimedia

    Alex Brown, Jens Vigen

    2014-01-01

    In the last issue of the Bulletin, we launched a public appeal for information to identify some CERN pictures that have recently been digitised by the CERN Library. The response has been huge. The story was picked up on many websites and discussion forums all over the Web, and hundreds of people sent in their suggestions. Time for a new challenge.   Many thousands of CERN's archived pictures are currently being scanned and uploaded to the CERN Document Server. While most of these pictures can be matched to existing historical information, many are harder to identify. Following the recent article in the last issue of the Bulletin, we have received submissions in five different languages from a dozen countries. We would like to express our thanks to everyone who has contributed their answers. We have now identified all of the pictures highlighted in the last issue of the Bulletin and we are updating the records accordingly. You can see them all here. To see a complete lis...

  16. Spintronics - achievements, prospects and challenges

    International Nuclear Information System (INIS)

    Spintronics utilizes not only the charge of the electrons but also their spin, or resulting magnetization, to realize functional devices of information technologies. In the last decade, spintronics has become a quickly developing research area for solid state scientists. Already, spintronics (or magnetoelectronics) has revolutionized the market for storage devices. Some predicted advantages of the new emerging technology are the nonvolatility of data storage, the increased speed of data processing, the high storage density, and the low energy consumption. To exploit the full potential of spintronics and facilitate design of novel functional devices, it is necessary to exploit the basic physics and progress materials research to find new materials satisfying particular demands. A general understanding of the structure property relationship is a necessary prerequisite for further development of spintronics. In these three lectures, the most important developments in the field of spintronics will be presented and related to the materials science. In particular, the problems connected to spin current such as, magnetoresistance, giant magnetoresistance (GMR), tunneling magnetorestance (TMR), and spin injection from ferromagnetic material will be discussed. In this context, new magnetic materials such as the half-metallic ferromagnets, colossal-magnetoresistance materials, and ferromagnetic semiconductors will be mentioned. Also the challenges connected to the problem of spin transistor and spin manipulation will be discussed. (author)

  17. Temelin NPP status and challenge

    International Nuclear Information System (INIS)

    In this presentation author deals with the NPP Temelin status and challenge. It was concluded that: - Temelin NPP was modified from the every beginning in order to meat internationally acceptable safety level; - IAEA, US and Western countries safety principles, criteria and requirements are mostly applied; - Number of international safety review missions confirmed this fact; All assessments of the Temelin NPP have been positive and all recommendations were carefully considered and either implemented or other equivalent solution was found. Temelin NPP Halliburton NUS audit in 1992 stated that Temelin can be licensable, but licensibility could not be assured unless the audit team's technical and programmatic recommendations are implemented. ENCONET Consulting (Austria) in 1998 stated that: - After modifications are fully implemented, Temelin NPP will be a much safer plant than originally designed and much more safer than some of the already operating WWER 1000 plants; - The process of compatibility was specifically assured by selecting prudent practices acceptable in the Western countries. IAEA mission on Safety issues resolution (1996) stated that: - It is recognized that the Czech Electric Company (CEZ) has made a large effort to improve the design of Temelin independently of the identification of safety issues by the IAEA

  18. Silicon spintronics: Progress and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Sverdlov, Viktor; Selberherr, Siegfried, E-mail: Selberherr@TUWien.ac.at

    2015-07-14

    Electron spin attracts much attention as an alternative to the electron charge degree of freedom for low-power reprogrammable logic and non-volatile memory applications. Silicon appears to be the perfect material for spin-driven applications. Recent progress and challenges regarding spin-based devices are reviewed. An order of magnitude enhancement of the electron spin lifetime in silicon thin films by shear strain is predicted and its impact on spin transport in SpinFETs is discussed. A relatively weak coupling between spin and effective electric field in silicon allows magnetoresistance modulation at room temperature, however, for long channel lengths. Due to tunneling magnetoresistance and spin transfer torque effects, a much stronger coupling between the spin (magnetization) orientation and charge current is achieved in magnetic tunnel junctions. Magnetic random access memory (MRAM) built on magnetic tunnel junctions is CMOS compatible and possesses all properties needed for future universal memory. Designs of spin-based non-volatile MRAM cells are presented. By means of micromagnetic simulations it is demonstrated that a substantial reduction of the switching time can be achieved. Finally, it is shown that any two arbitrary memory cells from an MRAM array can be used to perform a logic operation. Thus, an intrinsic non-volatile logic-in-memory architecture can be realized.

  19. Challenges in Commercializing Biomimetic Membranes

    Directory of Open Access Journals (Sweden)

    Mark Perry

    2015-11-01

    Full Text Available The discovery of selective water channel proteins—aquaporins—has prompted growing interest in using these proteins, as the building blocks for designing new types of membranes. However, as with any other new and potentially disruptive technology, barriers for successful market entry exist. One category includes customer-related barriers, which can be influenced to some extent. Another category includes market-technical-related barriers, which can be very difficult to overcome by an organization/company aiming at successfully introducing their innovation on the market—in particular if both the organization and the technology are at early stages. Often, one faces barriers from both these categories at the same time, which makes it necessary to gain insight of the particular market when introducing a new innovative product. In this review we present the basic concepts and discuss some of these barriers and challenges associated with introducing biomimetic aquaporin membranes. These include technical issues in membrane production and product testing. Then we discuss possible business models for introducing new technologies in general, followed by a presentation of beach-head market segments relevant for biomimetic aquaporin membranes.

  20. ALICE Holds Up to Challenge

    CERN Multimedia

    2006-01-01

    ALICE's main austenitic stainless steel support structure (the Space Frame) has recently gone through many tests that proved quite challenging: insuring the structure is sound and lowering it horizontally into the ALICE cavern. This structure is constructed to hold the large volume detectors, such as the Time Projection Chamber, Transition Radiation Detector and Time of Flight inside the ALICE solenoid magnet. After the final assembly at CERN, two large mobile cranes were needed for the job of lifting and turning the 14 tonne frame onto its side. Once shifted, it was placed in Building SX2, one of the surface assembly areas designated for ALICE. The structure, which is 8 m in diameter and 7 m long, underwent many tests in its new position. Geometric control tests were performed by measuring each of the 18 cells and placing wooden or metal samples constructed to the same dimensions as the real thing inside the structure. The most important check was the movement of the real Time Projection Chamber from its s...