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Currently there are few studies characterising the nature and aetiology of human schistosome-related inflammatory processes. The aim of this study was to determine the relationship between Chitinase 3-like 1 (CHI3L1), also known as YKL-40, a molecule associated with inflammatory processes, and schistosome infection, morbidity and systemic cytokine levels.
Serological levels of CHI3L1 and a panel of cytokines (IFN-y, IL-4/5/6/9/10/13 and 17) were measured in two Zimbabwean populations resident in a high and low schistosome infection area. CHI3L1 levels were related to schistosome infection, haematuria status and cytokine levels after allowing for confounding variables. The effect of antihelminthic treatment with praziquantel on CHI3L1 levels was determined in 246 participants 6 weeks post-treatment.
CHI3L1 levels increased with age in both areas but were significantly higher in the high infection areas compared to the low infection area. CHI3L1 levels were also higher in infected compared to uninfected individuals with this difference being significant in the youngest age group. Curative antihelminthic treatment resulted in a significant decrease in CHI3L1 levels. Of the cytokines, only IL-10 and IL-17 had a significant association with CHI3L1 levels, and this association was negative.
Serum CHI3L1 levels differ between infected and uninfected people before and after antihelminthic treatment. The greatest difference occurs in the youngest age group, in keeping with the period when schistosome-related pathological processes are initiated. Following from previous studies in non-infectious diseases showing that CHI3L1 is a biomarker for the inflammatory process, this study suggests that the potential for CHI3L1 as a biomarker for schistosome-related pathology should be explored further.
Author Summary
Over 100 million people, mainly living in sub-Saharan Africa, are infected with the blood fluke Schistosoma haematobium. Morbidity includes anaemia, malnutrition, impaired cognition and physical growth as well as pathology of the urogenital tract. Urogenital morbidity is initiated by eggs laid at the site of infection causing mechanical damage and leading to haematuria, or blood in the urine. Eggs also secrete antigens, triggering a protective granuloma to form around the eggs which can lead to fibrosis and organ failure. Currently there are few non invasive markers of schistosome-related pathology hampering diagnosis and evaluation of control programmes. Chitinase 3-like 1 (CHI3L1) has been associated with several inflammatory disorders involving tissue remodelling. In this study we assessed the levels of CHI3L1 in a group of individuals from a schistosomiasis endemic area in Zimbabwe. We showed that CHI3L1 is elevated in schistosomiasis infected individuals over uninfected individuals, with the strongest association seen in the youngest age group who have a shorter history of schistosome infection. Treating individuals with a drug that eliminates the adult worm leads to a decrease in CHI3L1 in infected individuals. These results suggest that the potential for CHI3L1 as a biomarker for schistosomerelated pathology should be explored further in different human populations.
Citation: Appleby LJ, Nausch N, Bourke CD, Rujeni N, Midzi N, Mduluza T, et al. (2012) Chitinase 3-Like 1 Protein Levels Are Elevated in Schistosoma haematobium Infected Children. PLoS Negl Trop Dis 6(11): e1898. https://doi.org/10.1371/journal.pntd.0001898
Editor: Stephen John Davies, Uniformed Services University, United States of America
Received: January 25, 2012; Accepted: September 25, 2012; Published: November 8, 2012
Copyright: © 2012 Appleby et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the World Health Organisation (www.who.org); the Wellcome Trust (http://www.wellcome.ac.uk/) [grant number WT082028MA]; the Thrasher Foundation (http://www.thrasherresearch.org/) to [FM]; and by the Medical Research Council (http://www.mrc.ac.uk) [grant number G0600818 to JEA, PhD studentship LJA-544 to LJA]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Urogenital schistosomiasis, caused by the blood fluke Schistosoma haematobium, is one of the world's most prevalent human parasitic diseases. Morbidity includes anaemia, malnutrition, impaired memory cognition and physical growth [1], and immune-mediated pathology in the urogenital tract, the kidneys and ureters [2]. Immunopathology commences with the laying of eggs in the blood vessels at the site of infection where they cause damage to the bladder walls and genital tissues in the form of lesions in blood vessels and tissues leading to the common symptom of haematuria. Antigens secreted by these eggs induce a Th2 response, involving secretion of interleukin-4 (IL-4), IL-5 and IL-13 [3], [4] and the eventual development of granulomas [5], [6]. Resolution of the granuloma involves deposition of collagen and extra-cellular matrix components, which are the source of fibrosis [5], [7], [8]. In young children infected with S. haematobium egg deposition is associated with more acute inflammatory symptoms, visible haematuria, anaemia and a high egg output in what is known as the active stage of disease [7]. This progresses with age to an inactive stage characterised by a drop in urine egg counts as fewer eggs are excreted but more become trapped and calcified in tissues. It is during the inactive stage of disease that signs of extensive and sometimes irreversible fibrotic pathology can be detected [7], while in those still acquiring active infection most of the schistosomiasis associated morbidity is reversible upon antihelminthic treatment [9]. Schistosome control programmes aim to reduce morbidity by reducing infection intensity and their success is monitored through egg counts [10], [11]. However, egg counts as a measure of disease burden can be misleading as the relationship between morbidity and infection intensity can be non linear, for example there can be a discrepancy between an individual with a high worm burden displaying less pathology than an individual with a low worm burden [10], [12]. Haematuria, has been used in numerous studies as both a marker for infection and onset of pathology [10], it is particularly effective in detecting infection in younger age groups. However, haematuria can have a low sensitivity rate [13]. Ultrasonography provides a more reliable method for assessing pathology in schistosomiasis infection [10] but operational logistics, such as the requirement for trained personnel and a consistent power source, make it an unsuitable tool for large scale or rural field studies [14]. In addition, despite its effectiveness in detecting late stage disease, ultrasound can fail to detect the earlier pathological changes associated with infection mediated inflammation [15]. Identification of biomarkers that can detect early pathological changes related to schistosomiasis infection, and changes associated with treatment, would provide an invaluable tool in monitoring schistosome control programmes [11].
Chitinase-like proteins are a characteristic feature of multiple helminth infection models [16], [17]. Chitinase 3-like 1 (CHI3L1), also known as human cartilage glycoprotein 39 (HCgp-39), and YKL-40, is a human chitinase-like chitin-binding lectin with no chitinase enzymatic activity [16], [17]. It is expressed by numerous cell types and has been associated with collagen and extra-cellular matrix formation [18] as well as with a wide range of diseases characterised by inflammation and tissue remodelling including asthma, arthritis, numerous cancers and liver fibrosis [19], [20], [21]. Recently CHI3L1 has also been linked to schistosome related hepatic fibrosis with S. japonicum infection [22]. In order to evaluate the potential of CHI3L1 as a pathology marker in urogenital schistosomiasis, and to investigate the nature of pathological changes associated with infection, the association of serum CHI3L1 levels with schistosome infection status, prevalence and history of exposure to infection was determined in individuals from three villages in rural Zimbabwe with differing levels of S. haematobium endemicity. Comparing villages of different endemicity allows a comparative approach separating the effects of history of schistosome infection from current infection levels, both factors that can potentially influence CHI3L1 levels [23]. The effect of curative antihelminthic treatment on CHI3L1 was determined in a post-treatment follow-up focussed on the village with highest endemicity. In addition we assessed the protein's relationship with a panel of systemic cytokines encompassing the range of Th1, Th2, Th17 and T-regulatory responses associated with schistosome infection and pathology (see [24], [25] for review), thus allowing CHI3L1 levels to be related to the immune environment in the host relative to their immune phenotype.
Materials and Methods
Ethical Statement
The study was conducted in the Mashonaland East Province of Zimbabwe where S. haematobium is endemic. Ethical approval was received from the University of Zimbabwe's Ethics Review Board (UZERB) and the Medical Research Council of Zimbabwe (MRCZ), and permission to conduct the study was obtained from the Provincial Medical Director. The study design, aims and procedures were explained in the local language, Shona, prior to enrolment. Written consent was obtained from participants or their guardians prior to taking part in the study.
Study area and population
The study was conducted within schools, recruiting school children and community members from three villages and details are described elsewhere [26]. Of the three villages Magaya (17°37′21″S 31°54′36″E) and Chipinda (17°41′46″S 31°56′03″E) are considered high infection areas (HIA) for schistosome infection, while Chitate (17°39′45″S 31°53′21″E) is a low infection area (LIA) as defined by the World Health Organization (WHO) [11]. The area has a low prevalence of soil transmitted helminths [27], and the residents are subsistence farmers with frequent contact with infected water for purposes of bathing, washing and collecting water. Plasmodium falciparum is the predominant species of malaria in Zimbabwe, and in this region malaria transmission is largely unstable in nature, classified as low and sporadic [28], [29], giving a low prevalence of co-infection between schistosome infection and Plasmodium infection in the study population.
Sample collection
From each participant a stool and urine specimen was collected on three consecutive days and examined microscopically. Urine samples were examined for S. haematobium infection and stool samples were examined for S. mansoni and soil transmitted helminths using standard techniques [30], [31]. Urine samples from children were examined for visible haematuria and designated positive when haematuria was observed or negative when no haematuria was observed. Macrohaematuria was confirmed on a different urine sample by dipstick (Uripath, Plasmatec, UK). 5 ml venous blood was collected and processed using routine methods to collect serum which was frozen at −20°C prior to freighting to Edinburgh for serological assays. Following parasitology sample collection, participants were offered treatment with the antihelminthic drug praziquantel at the recommended dose of 40 mg/kg of body weight and treatment efficacy was checked 6 weeks later during follow-up parasitology and serological surveys. Treatment of the three communities was staggered by 6 weeks for the purpose of an untreated control group except in the case of heavily infected people as defined by the WHO [11].
Inclusion/Exclusion Criteria
In order to be included in this study participants had to meet the following criteria: 1) be lifelong residents of the study area to allow age to be used as a proxy for history of exposure to schistosome infection, 2) have provided at least two urine and two stool samples on consecutive days for parasite detection, 3) have provided a blood sample for serological assays, 4) not have previously received antihelminthic treatment, 5) be negative for co-infections (malaria, intestinal helminths, S. mansoni and HIV). From an initial number of 2000 individuals, a total of 859 individuals 2–86 years old, 642 from the HIA and 217 from the LIA, met these criteria. The post-treatment study focused on the HIA where there was a higher prevalence of infection. To be included in the post-treatment study individuals had to meet the criteria above and be confirmed egg negative 6 weeks post-treatment or remain untreated for the control group. 246 participants (110 treated and 136 untreated) fulfilled these criteria and formed the follow-up cohort.
Serological assays
Serum levels of CHI3L1 were quantified using an ELISA kit from R&D Systems (Cat DY2599, Minneapolis, USA), following the manufacturer's instructions. Systemic levels of IL-10, IL-17, IFN-γ, IL-13, IL-4, IL-5 and IL-6 were measured by ELISA as previously described [32], [33]. All serological assays were performed in duplicate with a positive control on each plate.
Statistical analysis
Statistical analyses were conducted using the statistical package SPSS version 14.0. To describe the age profiles of schistosome infection and CHI3L1 protein, an analysis of variance (ANOVA) was performed using infection intensity (eggs/10 ml urine) and CHI3L1 levels (ng/ml) log transformed (log10(x+1)). The independent variables were age categorised into 6 groups as shown in Table 1. Following these analyses, age was re-categorised to reflect the changing dynamics of rising (2–10 years), peaking (11–20 years) and declining (21+years) infection. Using these age groups the effect of schistosome infection (infection intensity (log transformed (log10(x+1)) or infection status (infected vs. uninfected)) and age group on CHI3L1 protein was determined by ANOVA after allowing for the effects of sex and village of residence through sequential sums of squares. The interaction between infection and age groups was also tested. To determine if CHI3L1 levels were higher in children with visible haematuria, the positive cases were matched with age, sex and infection intensity matched controls and the data analysed by t-test.
The effect of antihelminthic treatment on CHI3L1 levels was analysed using a repeated measures ANOVA followed by posthoc analysis within each age group. In order to relate systemic cytokine to CHI3L1 levels the number of cytokine variables was reduced using factor analysis. Individual cytokine responses (square-root transformed) with no rotation were used to extract uncorrelated principal components (PC) accounting for a significant proportion of variance in the data (eigenvalues greater than 1) and with a factor loading of >0.5 or <0.5 for one or more of the original cytokine variables. The PCs arising from this procedure were then used in a partial correlation (controlling for age group, sex and residential area) relating the PCs to CHI3L1 levels with the 2-tailed p value from the correlation being reported. P values in all statistical tests were considered significant if p≤0.05.
Levels of schistosome infection and CHI3L1 vary with residential area and age
After accounting for sex schistosome infection intensity and prevalence were significantly higher in the HIA (mean infection intensity = 27 eggs/10 ml urine, prevalence = 40%) compared to the LIA (prevalence = 11.1%; mean infection intensity = 2.7 eggs/10 ml urine) (F1,858 = 55.158, p<0.001). The schistosome-age profiles differed in the two residential areas resulting in a significant age group*residential area effect (F5,858 = 2.446, p = 0.033) giving rise to the 'peak shift' [34]; whereby the infection peak occurred at a higher intensity and at an earlier age in the HIA compared to the LIA (as shown in Figure 1A). Overall, after accounting for sex, CHI3L1 levels were also significantly higher in the HIA (mean, 59.9 ng/ml; SEM, 2.03) compared to the LIA (mean, 49.1; SEM 5.15), (F1,858 = 59.722, p<0.001). In both villages CHI3L1 levels rose significantly with age group as shown in Figure 1B and Table 2, but no peak shift occurred in CHI3L1 levels.
Age profiles for the study areas, shown as circles for the high infection area and squares for the low infection areas. Bars represent standard error of the mean. A. Infection intensity exhibiting a peak shift between the two villages. B. Chitinase 3-like 1 protein showing no peak shift between the two villages.
CHI3L1 levels are elevated in infected individuals, and in haematuric cases
CHI3L1 levels were higher in infected vs. uninfected people, after allowing for the confounding effects of age and residential area, with this difference being significant in the youngest age group (Table 2, Figure 2). Interestingly, infection intensity, when analysed in the same model, did not significantly affect CHI3L1 levels (F1,858 = 2.016, p = 0.156). The pattern was maintained, though was not significant, in the older age groups. Comparison of CHI3L1 levels in 34 children aged 6–16 years showed a higher level of CHI3L1 in the children with visible haematuria compared to the infection matched children who were not presenting with haematuria (t = −1.1662; df = 32; p = 0.053) as shown in Figure 3. Neither the mean age nor the mean infection intensity was significantly different between these 2 groups (t = 0.067; df = 32; p = 0.947 for age, and t = −0.595; df = 32; p = 0.556 for S. haematobium infection intensity).
Figure shows mean levels of CHI3L1 protein (log10(x+1)). Uninfected individuals (open) compared to infected (solid). Bars represent standard error of the mean. P-values are obtained from posthoc tests after taking into account residential area. Significant p-values are indicated in bold.
CHI3L1 levels according to haematuria status. P values are obtained from t-test on age, sex and infection status matched individuals.
Praziquantel treatment is associated with a decrease in CHI3L1 level
To address the question of whether CHI3L1 is associated with infection, 246 participants from the HIA were followed up for 6 weeks post-treatment. All treated individuals included in this study were negative for infection 6 weeks post-treatment, as determined by egg counts. In treated people, mean CHI3L1 levels declined significantly from 63.7 ng/ml (SEM, 3.06) pre-treatment to 48.2 ng/ml (SEM, 4.75) post-treatment (p<0.001). In contrast, there was no significant change in mean CHI3L1 levels in the untreated group (47.3 ng/ml; SEM = 2.18 at baseline, and 52.3 ng/ml; SEM = 3.52 6 weeks later, p = 0.855). Partitioning the cohort by age group showed that the post-treatment decline was significant in the youngest age groups (2–10 year olds: F53 = 23.942, p<0.001; 11–20 year olds F51, = 4.161, p = 0.047), while there was no significant change in the oldest age group (F6 = 3.25, p = 0.146) (Figure 4).
Mean CHI3L1 expression within an untreated (n = 136) and a treated population (n = 110) by age group. Week 0 (open), 6 weeks later (solid), bars represent standard error of the mean. Significant p-values from posthoc ANOVA are indicated in bold.
CHI3L1 has a negative relationship with IL-10 and IL-17
The data reduction procedure conducted on the 8 cytokines returned 4 main PCs summarised in Table 3. PC1, accounting for the largest variation in cytokine levels, was composed of Th2-type cytokines (IL-4, IL-5 and IL-9). PC2 was composed of T-regulatory (IL-10) and Th17 (IL-17A) type cytokines. PC3 was composed of IL-13, and PC4 was a pro-inflammatory grouping composed of the Th1 cytokine IFN-γ and the innate cytokine IL-6. Correlating the extracted PCs from the factor analysis with CHI3L1 while controlling for sex, age group, infection area, and infection status revealed a negative association between PC2 and CHI3L1 levels (r = −0.184, p = 0.037). All other PCs showed no significant correlation with CHI3L1 levels PC1 (r = −0.006, p = 0.934), PC3 (r = 0.028, p = 0.755), and PC4 (r = −0.112, p = 0.206).
Infection with schistosome parasites causes a host inflammatory response responsible for much of the disease-associated pathology [3], [4], [5]. As CHI3L1 has been associated with numerous other inflammatory and type-2 diseases we investigated the relationship between CHI3L1 levels and schistosome infection in a population naturally exposed to S. haematobium [19], [20], [21].
Our study presents the first comparative analysis of CHI3L1 levels in human populations who are of the same ethnicity and socioeconomic status but differing helminth endemicity. Similar to reports from non-schistosome endemic areas, CHI3L1 showed a significant increase in levels with increasing age [35], a pattern reported to be due to an increasing level of background inflammation associated with ageing and the onset of age-related diseases [35], [36]. In this study we demonstrated that overall levels of CHI3L1 are higher in the HIA compared to the LIA across all age groups. As the populations are similar in ethnicity and in exposure to other common infections such as Plasmodium, the only differing characteristic being exposure to schistosome infection [37], this result suggests that the difference in schistosome infection may contribute to differences in CHI3L1 levels and is supported by the observation that schistosome infected people had higher levels of CHI3L1 than uninfected people, independent of residential area. Furthermore CHI3L1 levels were reduced following elimination of adult worms from the body via curative antihelminthic treatment [38], determined via egg count and the disappearance of visible haematuria. Taken together these observations suggest that CHI3L1 levels are related to current levels of infection. The significant interaction between age and infection status with the difference between schistosome-infected and uninfected people being the most apparent in the youngest age group is consistent with a dynamic relationship between infection status and CHI3L1 levels as people age. Other factors confounding the relationship between CHI3L1 and infection status pre- and post- antihelminthic treatment, such as the onset of age-related diseases [35] requires further investigation.
A previous study of schistosome related pathology has suggested that it is infection status rather than infection intensity that is related to pathology [12]. Our results are consistent with this observation in that it was infection status rather than intensity that was associated with CHI3L1 levels. Accordingly, the change in CHI3L1 on clearing infection was not related to pre-treatment infection intensity (data not shown).
To determine if CHI3L1 levels differ in people with visible signs of pathology, we compared levels of the protein in children who had visible haematuria to age and infection intensity matched controls confirmed negative for haematuria. We showed that within infected children, CHI3L1 levels were higher in haematuria positive compared to haematuria negative individuals, suggesting that elevated CHI3L1 levels are associated with infection and morbidity in S. haematobium infection. Further studies expanding on the numbers of individuals assessed for haematuria and CHI3L1 levels will be required to confirm this association.
The inflammatory immune response associated with schistosomiasis infection is modulated by adult schistosome worms as well as by the egg antigens [39]. Treatment with PZQ kills the adult schistosome worms and removes their recently laid eggs [40], eliminating the source of inflammation. The decrease in CHI3L1 levels in the treated group may therefore be related to a reduction in inflammatory processes associated with schistosome infection and egg laying, and support previous studies in liver disease that suggests CHI3L1 levels are a bio-indicator of early phases of fibrogenesis [21]. However, while CHI3L1 is associated with inflammation, as yet, its precise function remains unknown. In mice, for instance, inflammatory signals induced by LPS and IFN-γ can both stimulate and inhibit chitinase like protein (CLP) expression in a context dependent manner [41]. As the function of these CLPs is elucidated, it may be possible to make a more educated assessment as to why CHI3L1 is downregulated on clearance of schistosome adult worms.
To determine if elevated CHI3L1 levels are a marker of schistosome-related immunopathology, further studies with larger numbers of people with defined levels of pathology (assessed using current standard markers of schistosome- related immunopathology such as ultrasonography) are necessary. Furthermore, in order to resolve the mechanism behind the observed elevation as well as the relationship between CHI3L1 levels and infection status in the different age groups mechanistic studies on both human and mouse models will be required. One possible explanation is that this could be due to differences in the stage of the pathological processes that the hosts were experiencing, with the younger individuals being at a stage of disease where lesion repair and granuloma formation is actively occurring [7], [9]. Given the lack of significant difference in CHI3L1 levels in infected vs. uninfected individuals in the older age groups, it is unsurprising that treating these individuals does not result in a significant reduction in their CHI3L1 levels. Older individuals have had a lifetime of exposure to infection, and may be experiencing more advanced pathology associated with inactive disease including bladder calcification and a drop in egg excretion [7], [9], as well as a higher background level of CHI3L1 associated with age [35]. There were no macrohaematuria cases observed post-treatment and this is consistent with other studies reporting a reversal/clearance of pathology [42]. These previous studies also reported that the groups experiencing the greatest reduction in morbidity following PZQ treatment are the younger age groups where infection levels are rising but who are not yet suffering from irreversible schistosome pathology [42].
In determining the systemic cytokine environment in the participants relative to CHI3L1, we showed that levels of the measured Th1 and Th2 cytokines were not associated with CHI3L1 levels, perhaps due to the cytokines acting locally at sites of infection [2], but there was an inverse association between CHI3L1 and levels of IL-10 and IL-17A. IL-10 can dampen a damaging pro-inflammatory response [43] and has previously been associated with schistosome infection levels [44] where it can limit pathology during infection as is suggested in the case of bladder pathology [45]. IL-17A is primarily regarded as a pro-inflammatory cytokine and has been found to be associated with numerous inflammatory diseases [46]. Despite being reported to have a role in the schistosome mediated pathological process in murine studies [47], a previous study of people resident in the same region showed less systemic IL-17A levels in S. haematobium infected people compared to uninfected individuals [32], and here we describe a negative association with CHI3L1 levels and systemic IL-17A. The relevance and implications of our cytokine findings for CHI3L1 levels in schistosome infection and for schistosome-related pathology remains to be determined in mechanistic studies.
Our study investigated CHI3L1 in a single infection setting; it will be interesting to see if the same relationship with infection status pre- and post- treatment is also observed in S. mansoni infection where there is no existing marker for early morbidity [10]. Indeed, in order to fully evaluate CHI3L1 as a potential pathology marker the study must be extended to other settings, including co-infections and differing ethnic populations, and the results compared to existing and candidate pathological markers.
Overall, our study has demonstrated that CHI3L1 levels are associated with schistosome infection status regardless of cumulative history of exposure to infection. Moreover, CHI3L1 is higher in people showing clinical signs of urogenital schistosomiasis (haematuria) compared to infected people presenting no haematuria. Antihelminthic treatment results in a significant reduction of CHI3L1 levels coinciding with the removal of adult schistosome worms. Both before and after curative treatment the difference in CHI3L1 between infected and uninfected people is greatest in the youngest age group where infection levels are rising rapidly, indicating not only a potential mechanism for schistosomiasis associated pathological processes, but also of an early onset of these pathological processes. The associations between CHI3L1 and schistosome infection warrants further investigation to determine the utility of CHI3L1 as a diagnostic marker for schistosome related morbidity as well as a tool for evaluating the impact of S. haematobium control programmes.
We are grateful for the co-operation of the Ministry of Health and Child Welfare in Zimbabwe, the Provincial Medical Director of Mashonaland East, the Environmental Health Workers, nursing staff at Chitate and Chitowa Clinics and Murehwa Hospital, residents, teachers and school children in Magaya, Chitate and Chipinda Schools. We also thank members of the National Institutes of Health in Zimbabwe and the Biochemistry Department at University of Zimbabwe for technical support.
Author Contributions
Conceived and designed the experiments: FM LJA TM NM. Performed the experiments: CDB FM LJA NM NN NR TM. Analyzed the data: FM LJA. Wrote the paper: FM LJA JEA. Designed the study: FM TM NM. Contributed to fieldwork: LJA NN NR CDB TM NM FM. Contributed to final version of the manuscript: LJA NN NR CDB TM NM FM JEA.
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- 27. Midzi N, Sangweme D, Zinyowera S, Mapingure MP, Brouwer KC, et al. (2008) The burden of polyparasitism among primary schoolchildren in rural and farming areas in Zimbabwe. Trans R Soc Trop Med Hyg 102: 1039–1045.
- 28. Mabaso ML, Vounatsou P, Midzi S, Da Silva J, Smith T (2006) Spatio-temporal analysis of the role of climate in inter-annual variation of malaria incidence in Zimbabwe. Int J Health Geogr 5: 20.
- 29. Hay SI, Guerra CA, Gething PW, Patil AP, Tatem AJ, et al. (2009) A world malaria map: Plasmodium falciparum endemicity in 2007. PLoS Med 6: e1000048.
- 30. Katz N, Chaves A, Pellegrino J (1972) A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 14: 397–400.
- 31. Mott KE (1983) A reusable polyamide filter for diagnosis of S. haematobium infection by urine filtration. Bull Soc Pathol Exot Filiales 76: 101–104.
- 32. Milner T, Reilly L, Nausch N, Midzi N, Mduluza T, et al. (2010) Circulating cytokine levels and antibody responses to human Schistosoma haematobium: IL-5 and IL-10 levels depend upon age and infection status. Parasite Immunol 32: 710–721.
- 33. Joseph S, Jones FM, Kimani G, Mwatha JK, Kamau T, et al. (2004) Cytokine production in whole blood cultures from a fishing community in an area of high endemicity for Schistosoma mansoni in Uganda: the differential effect of parasite worm and egg antigens. Infect Immun 72: 728–734.
- 34. Woolhouse ME (1998) Patterns in parasite epidemiology: the peak shift. Parasitol Today 14: 428–434.
- 35. Bojesen SE, Johansen JS, Nordestgaard BrG (2011) Plasma YKL-40 levels in healthy subjects from the general population. Clinica Chimica Acta 412: 709–712.
- 36. Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, et al. (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2: 8.
- 37. Rujeni N, Nausch N, Bourke CD, Midzi N, Mduluza T, et al. (2012) Atopy Is Inversely Related to Schistosome Infection Intensity: A Comparative Study in Zimbabwean Villages with Distinct Levels of Schistosoma haematobium Infection. Int Arch Allergy Immunol 158: 288–298.
- 38. Utzinger J, Keiser J, Shuhua X, Tanner M, Singer BH (2003) Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials. Antimicrob Agents Chemother 47: 1487–1495.
- 39. Jacobs W, Bogers J, Deelder A, Wery M, Van Marck E (1997) Adult Schistosoma mansoni worms positively modulate soluble egg antigen-induced inflammatory hepatic granuloma formation in vivo. Stereological analysis and immunophenotyping of extracellular matrix proteins, adhesion molecules, and chemokines. Am J Pathol 150: 2033–2045.
- 40. Liang YS, Coles GC, Doenhoff MJ, Southgate VR (2001) In vitro responses of praziquantel-resistant and -susceptible Schistosoma mansoni to praziquantel. Int J Parasitol 31: 1227–1235.
- 41. Mylonas KJ, Nair MG, Prieto-Lafuente L, Paape D, Allen JE (2009) Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing. J Immunol 182: 3084–3094.
- 42. Koukounari A, Gabrielli AF, Toure S, Bosque-Oliva E, Zhang Y, et al. (2007) Schistosoma haematobium infection and morbidity before and after large-scale administration of praziquantel in Burkina Faso. J Infect Dis 196: 659–669.
- 43. Del Prete G, De Carli M, Almerigogna F, Giudizi M, Biagiotti R, et al. (1993) Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 150: 353–360.
- 44. Mutapi F, Winborn G, Midzi N, Taylor M, Mduluza T, et al. (2007) Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-gamma, IL-4, IL-5 and IL-10 with age. BMC Infect Dis 7: 139.
- 45. King CL, Malhotra I, Mungai P, Wamachi A, Kioko J, et al. (2001) Schistosoma haematobium-induced urinary tract morbidity correlates with increased tumor necrosis factor-alpha and diminished interleukin-10 production. J Infect Dis 184: 1176–1182.
- 46. Iwakura Y, Nakae S, Saijo S, Ishigame H (2008) The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev 226: 57–79.
- 47. Rutitzky LI, Bazzone L, Shainheit MG, Joyce-Shaikh B, Cua DJ, et al. (2008) IL-23 is required for the development of severe egg-induced immunopathology in schistosomiasis and for lesional expression of IL-17. J Immunol 180: 2486–2495.


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I have a Lenovo IdeaPad Y580 that I'm planning on dual booting with. I want to use Ubuntu 13.04, but on the daily builds download page there is only "PC (Intel x86) desktop image" listed for intel, and "64-bit PC (AMD64) desktop image" listed for AMD CPUs. Is there no 64bit for intel? should I just use the 32bit? Or should I just download 12.10 instead?

subset: commoncrawl


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|Home >> Course Descriptions >> College of Arts and Sciences
|Introduction to Sociology
|Three semester hours.
|A scientific approach to the study of the cultural and social basis for human behavior, including the impact of societal groups and organizations on personal identity, feelings and behavior. Topics for special focus include the individual impact of ethnicity, social class, gender, religion, family structure, peer groups, complex organizations, mass media and educational, political and economic systems.
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SAS is No. 1 in advanced and predictive analytics market share, says analyst report
SAS also leads in market share for analytic data integration software
SAS again tops all predictive and advanced analytics suppliers and data integration suppliers, according to the IDC report, IDC Worldwide Business Intelligence and Analytics Tools Software Market Shares, 2016: Here Comes the Cloud.[1]
SAS held a 30.5 percent market share for 2016 in the advanced and predictive analytics category, well over twice the market share of the next-closest competitor. SAS has led in this category since IDC started tracking the market in 1997. SAS has demonstrated continued growth every year in the category, with 2016 showing a 5 percent revenue growth.
"SAS has been able to retain authority in the advanced and predictive analytics market and continue to grow year over year," said Dan Vesset, Group Vice President of Analytics and Information Management at IDC. "This is not an easy feat given the rise in the number of competitors entering the market. SAS' deep roots in advanced analytics and commitment to R&D are two things that help SAS stay at the top of the category."
In addition, IDC ranked SAS as the 2016 market share leader for analytic data integration software with 21.9 percent market share.[2]
With 2016 revenue of $3.2 billion, SAS reinvests about twice the average of major technology firms back into R&D – 26 percent in 2016, a strategy designed to foster innovation. SAS has offices in 58 countries around the globe with a worldwide customer base of 83,000.
See all the newest SAS® Analytics offerings, running on the SAS Platform. The platform is built on a strategy of using analytical insights to drive business actions, and supports and accelerates every phase of the analytics life cycle – from data to discovery to deployment.[1] Doc # US42072417, June 2017
[2] IDC, Worldwide Analytic Data Management and Integration Software Market Shares, 2016: Growth Across Market Segments(Doc # US42755917, June 2017)
About SAS
SAS is the leader in analytics. Through innovative software and services, SAS empowers and inspires customers around the world to transform data into intelligence. SAS gives you THE POWER TO KNOW®.


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clickeryphoto necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 101 diseños de 20 diseñadores freelance.
Clickery Photography
We are a super fun photography company based out of Southern California, but we travel outside of California for many weddings out of the year. Weddings make up most of our clients, but we do shoot family and school portraits as well. Our style is a fantastic fusion of old school portraiture and artistic photojournalism. We have a blast with our clients and are looking to rebrand ourselves to really reflect our style.
Our target audience is women between the ages of 20-45.
Our primary market consists of brides, and recently engaged couples.
We are looking for a unique design. We are not opposed to any type of camera graphic used but we do want it to be original. We like earth tones and nature elements but are not opposed to other colors. We are looking for something that can appeal to women since most of our clients are brides, so we ask that the logo not be overly masculine. Please do not use stock photos or clip art. We are not very excited by monograms since they seem so serious.
We are really looking for something outside of the box. We want something fun and exciting :)
We would be using our logo for business cards, letterhead, advertising and of course, our website. We would like the logo in cmyk vector eps and rgb psd.
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


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"It's PopMart that stands the test of time to a much greater degree than Zoo TV." — Willie Williams
November 8: Auckland
November 9: Auckland
November 12: Brisbane
November 15: Melbourne
November 19: Adelaide
September 6: Mexico City
June 28: Hydra
May 25: Bangor
December 24: Dublin
December 5: Miami
October 20, 1981: Tiffany's, Leeds, England
October 20, 1984: Palais De Sports, Toulouse, France
October 20, 1987: Carver-Hawkeye Arena, Iowa City, IA
October 20, 1989: Entertainment Center, Sydney, Australia
October 20, 2005: MCI Center, Washington, DC, DC
October 20, 2009: University of Phoenix Stadium, Glendale, AZ
See more concerts in the Mexico City area.
Attendance: 94,326 (Capacity: 94,326)
We have 1 reviews and 12 photos from this show.
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Did we mention fun? A few outside-the-box ideas for engaging your team.
If you could switch jobs with anyone in your organization for a day, who would it be and why? I recently posed this question to a colleague and without a moment's pause, he immediately responded that he would switch places with our beloved common room hostess. He joked he would love to be paid to brew coffee and make small talk, but on a more serious note, expressed jealousy of her capacity to build relationships with members of many different divisions in the company.
My spontaneous question spawned an electrifying conversation in the office. One individual wanted to spend a week working with our fellows program, mentoring young professionals, while another wanted to be editor-at-large for a week, with time and freedom to explore a variety of topics of interest. Their excitement at even just a hypothetical situation, such as an office job swap, underlined that there are many creative, small things managers can do to improve engagement without having to launch a full-scale engagement initiative.
Rather than throw numbers on engagement trends at you, we thought we'd bring you four fun, outside-the-box ways to improve engagement in your office. It's Friday after all! Some are bizarre, some surprising and some might just give you a more highly engaged workforce.
1) Job Swap
A job swap has employees switch duties for a day, or week in more ambitious offices. It not only allows employees to explore new elements of the organization, but also helps facilitate greater communication and understanding of the challenges each position faces. You'll be surprised by what people choose, and learn more about your employees' interests. The momentary change of pace and break from routine will likely be welcomed by participants as well.
This idea is perhaps the most ambitious; after all, business still needs to be accomplished. To facilitate such a swap, have employees spend a short time, no more than half an hour, explaining what needs to be accomplished in that day. But heed the words of General Patton, "Don't tell people how to do things, tell them what to do and let them surprise you with their results." Not only will this activity engage your workforce, but you may just find a new, improved way of achieving the mission.
2) DJ Day
There are numerous studies showing the positive effects of listening to music while working, and headphones and earbuds are now nearly as essential to a productive workday as a computer mouse. But why not cut out the isolation created by headphones but still keep the music, just for a day or half day? Rather, have employees take turns playing music for the office, or allow employees to send in song requests. Many of us work in shared office spaces, and are all listening to music simultaneously anyway.
This activity is great not only because it livens up the office space, but also helps create a more communal and laid back office culture. I've had personal experience with this activity in several offices, all to rave reviews. Employees get to share a little about their own music tastes, which helps build relationships and create a positive culture, two important drivers behind employee engagement. Appointing a DJ or using a social DJ site such as turntable.fm are good options to facilitate the logistics of shared music.
3) No Shoes in the Office
We promise the smell isn't that bad! This is a personal favorite of Government Executive's Director of Research and Analysis and Excellence in Government Executive Editor, Bryan Klopack. The effectiveness of this idea lies in its simplicity. Work routines can become just that, routine. Changing one small bit of a routine, however, can be as unsettling as reworking the whole routine (think the uncanny valley effect for routines). A small change such as taking our shoes off in the office can throw our minds out of their routine as well, opening them up to new innovative thoughts and perspectives. Allowing employees to take off their shoes in appropriate circumstances can also create a more relaxed atmosphere. Sometimes the smallest changes lead to the biggest ideas.
Read the post we wrote this summer about how declaring opposite day can supercharge your office culture.
4) Informational Interviews
Have you ever wondered what it is that a colleague of yours does? Mark Micheli, Editor of Excellence in Government, has often wondered aloud what our Talent and Culture Advisor's responsibilities include. He's not quite sure what that position entails but he's pretty certain it's a fascinating one. It's for this reason he's such a big fan of informational interviews. Without burdening himself or anyone else too greatly, he gets the opportunity to learn about other roles within an organization and build new relationships.
Informational interviews are also helpful for new hires, giving them an opportunity to learn about the organization at a rapid pace from many angles. Managers can easily encourage interviews by either explicitly expressing support or even creating a simple system of rotating interviews with time set aside for employees to learn a little bit about how coworkers they may not interact with on a daily basis help advance the organization's mission.
Fostering relationships, broadening horizons, and creating a positive, fun office culture are some simple ways that managers can improve engagement without massive initiatives.
We've shared some of the ways Government Executive tries to engage its employees, do you have any unique practices you use to engage yours? Feel free to share your thoughts in the comments or in Government Executive's agency engagement survey. Over 20,000 managers have taken the survey, but we'd like to hear from more!
Click here to take GovExec's five-minute survey on employee engagement.
Image via Darren Baker/Shutterstock.com
NEXT STORY: What Does the Ideal Work Environment Look Like?


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Mandy necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 247 diseños de 64 diseñadores freelance.
Images Unveiled is owned by a husband and wife team. The master photographer is myself, Mandy. Our business must appeal to females from 18 up to their late 30s. Our studio is about 50% weddings, 25% families and babies portraits and 25% Seniors. We will need this logo to reproduce well at both large and small sizes. It will appear online, collaterals and some banners and packaging.
Images Unveiled
We need a brand ID mark with a possible tagline that will resonate with our female target audience. We are marketing to brides and moms 90% of the time. Our work is trendy, young, fresh and playful. We want our logo to reflect these traits along with communicating that we are a high end studio. The logo will be used on our website, slideshows, viral marketing, videos, callaterals, letterhead, banners and gift packaging. Basically any materials or mediums where we would present our brand to the client.
- Please see our current website to see our style of photography. http://www.imagesunveiled.com
- We are open to other colors but want the colors to be trendy and modern.
- A mark that reproduces well online or in print.
- We are looking for a logo that combines an icon and or graphic element/s with Images Unveiled Studio.
No camera icons- No crazy fonts that are hard to read
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


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By Laura Mathews
"The farmers went to court two years ago for justice and we aren't going home until we get justice. " – Jim Gerritsen, President of the Organic Seed Growers and Trade Association.
An individual farmer in Indiana lost his case against Monsanto this week, but optimism exists that a group of organic seed growers may yet get a solid second shot for justice and protection from the biotech behemoth.
May 13th, the Supreme Court unanimously ruled in favor of Monsanto ending a suit filed by 75-year-old Indiana farmer Vernon Bowman. Bowman purchased seeds including Monsanto RoundUp ready soybean from a grain elevator. His case revolved around the argument that he purchased the seed from the grain elevator and that act itself was legal. A doctrine called patent exhaustion was used to support Bowman's position.
A separate case against Monsanto – one that we here at Baker Creek Heirloom Seeds participate in – is still undecided and very different. We are plaintiffs in the Organic Seed Growers and Trade Association suit against Monsanto. OSGATA lost the first round when the case was dismissed in the Federal District Court in New York City, but filed an appeal with the US Court of Appeals. Oral arguments were presented in January.
Jim Gerritsen, organic farmer from Maine and President of OSGATA, was not discouraged by the Bowman vs Monsanto decision both because of the broad differences between the cases and the length of time the Court of Appeals has been considering the OSGATA vs Monsanto suit.
"Monsanto seems to be the one that should be sweating at this point," said Gerritsen and explained it was a positive indication that the justices had been considering the appeal for 4 months. If the appeal had no validity, it could have been easily and quickly dismissed.
OSGATA initiated the suit in hope of securing protection from harassment and unjust lawsuits for organic farmers who ardently avoid use of Monsanto products. As it stands, organic growers can have their crops contaminated by Monsanto GMO pollen and still be subject to prosecution. Monsanto admits to filing more than 150 aggressive lawsuits against family farms since 1997. More than 500 farms a year are 'investigated' by Monsanto.
Gerritsen expects OSGATA vs Monsanto to be decided very soon. I had the pleasure to speak with Gerritsen after his presentation at the Slow Money National Gathering a few weeks ago. Slow Money is an organization that promotes financial investments that benefit soil fertility and work to solve food insecurity. They facilitate the meeting of forward thinking farmers and investors. Here is the conversation I had with Gerritsen;
LM – Given the resources Monsanto has, it seems their motivation behind harassing farmers must be something other than financial. What reasons do you think are behind Monsanto's bullying of farmers?
Gerritsen – Essentially, GE crops are all about control. If you gain sufficient control, you then have access to unlimited financial gain. Carlo Petrini (Founder of Slow Food and Terre Madre) just very eloquently said that there is more to life than the striving for money. I don't think the folks at Monsanto got that memo.
Monsanto considers itself stronger when it's able to create this air of intimidation in rural America and I think that's not how you behave in a democracy. That's not how you treat honest farmers.
LM – Speaking of democracy, what do you make of the recent so-called Monsanto Protection Act?
Gerritsen – Monsanto needs to work on being a better citizen in this country and treat their fellow citizens with respect, and treating the democratic process with respect, which does not mean inserting preferential treatment into financial bills like the continuing resolution. That was blatantly unconstitutional, blatantly unfair, and blatantly unconstitutional. And if Monsanto wants the respect of the people, they need to play by the rules and not place themselves above the law.
It is a preposterous notion that they can get their friends in congress to give them protection from the judiciary – which is the people's ability to find redress. We have a separation of powers and should this bill ever be challenged, it absolutely would be thrown out.
We're grateful the bill will be sunsetting on September 30, 2013, with this temporary continuing resolution and it's important that congress not make this mistake again. The peoples last recourse for justice is the court system. That's why the farmers (OSGATA) have gone to court. We seek to gain protection we have not been able to gain otherwise.
LM – I interviewed someone recently who said even (long term biotech advocate) Secretary of Agriculture Tom Vilsack believes Monsanto overstepped with the Monsanto Rider.
Gerritsen – Any high school kid taking their first class in civics knows that Monsanto overstepped. Unconstitutional is unconstitutional. It is my understanding that Secretary Vilsack has asked council within the USDA to look into the constitutionality of this (Monsanto rider) and he should be commended for that.
It would have been better if President Obama would not have signed this into law.
LM – I was told they couldn't separate the rider from the rest of the appropriations bill.
Gerritsen – Then veto the whole thing.
It comes down to integrity. Either you have integrity or you don't and when you're told you can't do something… Well… that's not how I look at it. You simply do what you need to do. And when things are wrong, you make the decision and you bear the consequences and in my book, (signing the bill) was the wrong decision. In my book, he now needs to fulfill his promise from 2007 to have labeling of GMO foods. It's what the American people want. It's what the public will get. And with 80 to 90 percent of the public in favor of labeling, Obama could be a hero by fulfilling his promise.
LM – What do you think it will take to get the general public riled-up enough about the rider that they take action and really put pressure on legislators?
Gerritsen – Maybe turn off the TV.
LM – Well, yes, but the bill sunsets in September, that doesn't give us much time to get people animated about the issue.
Gerritsen – I just got a letter from the Organic Caucus in Congress and they are up on this and working with the appropriations committee to ensure that the Monsanto Protection Act does not make its way into further appropriations bills.
LM – Do you have a sense the average citizen is increasingly concerned about the role of Monsanto and big ag in the food system?
Gerritsen -Oh, absolutely. I think there's been a seed change in people's attitude about GE crops in the last 24 months.The prop 37 campaign in California was a landmark event and the only way the biotech corporations were able to win was to blatantly lie and fool the voters, which tells me that they have so little faith in the technology – the biotech technology – that they felt they couldn't win if they told the truth so they created tremendous lies to win the election.In effect, I think, they have mobilized people nationwide who were already so unhappy with biotech and big ag activity and behavior, and that's why you see now that 37 states are developing labeling initiatives.
We hope to see efforts in Maine, Vermont and Connecticut succeed. Efforts in the state of Washington are looking very hopeful as well.
LM – Is the state approach to labeling more impactful than a national effort?
Gerritsen – Everybody can see how dysfunctional our federal government is, and it's not that I don't think the fact that some leading congressmen in the last week have introduced a GE labeling bill, isn't good, but that will only come about because of pressure the states are putting on them.
LM – How has Monsanto responded to the state initiatives?
Gerritsen – In the state of Maine, Monsanto sent lobbyist who called supporters of labeling 'luddites'. That kind of disrespect of citizens is not the way to engage the public in a positive manner. It brings disrespect upon Monsanto and maybe they don't care, but hard-working Mainers – 91% who want labeling – should not be insulted when they are simply carrying out the democratic process.
LM – Back to OSGATA vs Monsanto. What are developments with the appeal OSGATA filed in January?
Gerritsen – We are expecting a ruling any day now. It was heard by a three justice panel in the Federal Court of Appeals and we need at least two in our favor in order to resolve the case favorably. If we should lose the case, we do have the option of appearing before the US Supreme Court.
The farmers went to court two years ago for justice and we aren't going home until we get justice.
LM – I know this is a difficult question to answer, but do you have a gut sense of how it will turn out?
Gerritsen – The only thing I know that's harder than deciding how justices are going to rule, is deciding when a cow is going to birth her calf. And I've learned to never predict when a cow is going to have that calf.
LM – How has involvement in this case changed your life?
Gerritsen – We've never been so far behind in shipping seed potato orders as we are this spring. There are only so many hours in a day and I'm grateful for my family who have picked up the slack for my being involved in the lawsuit and GMO labeling bills.
But the point is, this is the opportunity of democracy. To the extent that we want to celebrate the freedom we have in this country, we have to get involved. Every person has a role to play and I'm happy to play that role.
LM – You might also be behind in shipping, in part, because so many more people are growing food.
Gerritsen – Yes. The last four to five years have been the best for seed companies since World War II and that's a good sign. More people are growing gardens. People who have had gardens are expanding them. People are becoming more serious about growing food for their families and sometimes, they grow enough extra that they can sell at farmer's markets. So I think this trend is a great demonstration of our self-reliance and I think that's really positive for our country.
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The fight, that GMO's have brought into the bakaycrds of farmers, isn't just a fight for the farmers, but all people who consume the potentially dangerous and unmonitored foods that are being forced down American throats. Other countries have woken up to these dangers and have outright banned the import of any GMO crops. One example is the wheat crop that was being developed in Austraila that was found to potentially cause liver damage in humans. Imagine if such a crop had been created here in the US where GMOs are not tested as well as they need to be. People would have died. The GMO industry is all about squeezing money out of everyone regardless of the damage done to naturally developed crops. What I want to know is why hasn't the EPA stepped up and started it's own investigation of this issue? Who knows what potential risk the natural ecosystems and species are facing.
How can someone participate in this? How can one join in? I don't own a farm, but I definitely want to join in.


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|SparkLAN's LoRa IoT Module has Passed LoRa Alliance's LoRaWAN™ Certification
Ensures Interoperation of Long-Range, Low-Power IoT Networks
SparkLAN Communications, Inc., is one of the worldwide leading wireless networking solution providers, today announced that its WLRS-590 LoRa module has passed the LoRa Alliance's LoRaWAN™ Certification Program and all relevant tests in conjunction with the LoRaWAN™ Certification Program and is deemed compliant to it meet the functional requirements of the LoRaWAN 1.0.2 protocol for operation in the 868 MHz band. This ensures that designers can quickly and easily integrate their end devices into any LoRaWAN network. The LoRaWAN standard enables low-data-rate Internet of Things (IoT) and Machine-to-Machine (M2M) wireless communication with long range, a battery long life, and the ability to connect millions of wireless sensor nodes to LoRaWAN gateways.
To learn more about SparkLAN's LoRa products, go to
The launch of an accredited certification program is a key step toward the LoRa Alliance's mission to standardize an open specification for secure, carrier-grade, low-power wide area networks (LPWAN). This certification Program will provide assurance to end customers that their application-specific end devices will operate on any LoRaWAN network, which is a crucial requirement for the global deployment of the IoT using LPWAN.
The WLRS-590 module comes with the LoRaWAN protocol stack, so it can easily connect with the established and rapidly expanding LoRa Alliance infrastructure-including both privately managed local area networks (LAN) and telecom-operated public networks -to create Low Power Wide Area Networks (LPWAN) with nationwide coverage. This stack integration enables the module to be used UART interface.
The WLRS-590 provides them with the ability to secure their network communication using AES128 encryption.
With its scalability, robust communication, mobility and the ability to operate in harsh outdoor environments, the WLRS-590 is well suited for a broad range of low-data-rate wireless monitoring and control designs. Example IoT and M2M applications include: Smart Cities (street lights, parking), Energy Measurement (electricity/ water/ gas smart meters), and Industrial/ Commercial/ Automation (smart factory, security system, lighting of dock).
SparkLAN's WLRS-590 is available now for volume production. For additional information, contact any SparkLAN sales representative or visit SparkLAN's Web site at http://www.sparklan.com
Company information
Founded in 2002, SparkLAN is one of the worldwide leading wireless networking solution providers. Our product mix covers wireless embedded modules, and wireless networking devices, offering a comprehensive line of solutions for M2M connectivity in the highest growing broadband communication application. For more information, please visit www.sparklan.com
Press Contact
Marketing Group
SparkLAN Communications, Inc.


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I'm not sure if there's already an existing term for this, so I'm inventing my own.
(tl;dr: I call them "chameleon questions" because they change every time you submit or edit an answer. If you're already intimately familiar with the phenomenon, please skip past the first set of bullet points to where I ask for recommendations.)
I think many of us have experienced this on occasion:
You open up a narrow-looking question, usually dealing with some specific error message. The question probably contains a snippet of sloppy but not quite awful code; code indicating that the author, typically a new/low-rep user, possibly a Mort, doesn't really know what he's doing. I'm not trying to be condescending here, he's probably very intelligent and hardworking, but in this specific case, he's clearly in way over his head.
However, as a question, it's not really too bad. The goal and problem are both clearly stated. The code is formatted (sort of). Mort was polite and checked his spelling. The question looks answerable, although from a rep perspective* it's an obvious dead-end, it's had maybe 3 views in the past 30 minutes.
So you decide, you know what, this person took the time to write up the question properly, he deserves an answer, put on your good citizen hat and throw him a bone. You slog through the ugly code, find the offending line, direct his attention to it and explain why it's wrong and how it needs to be fixed.
Later, he leaves a comment saying that yes, that was indeed the problem and your answer helped him fix it (great!). Oh, but, now there's another problem (uh-oh...). Something else is broken. After letting out a long sigh, you read the comment and/or edited question, roll up your sleeves, and write up Take 2, hoping that's the end of it.
And of course it's not the end. Now maybe the error is gone, but it's not doing what it's supposed to. If you're anything like me, your patience is now starting to wear thin. It's lousy code and you didn't volunteer to help him rewrite his whole app. And of course, the question still only has 12 views, and nobody has upvoted either the question or your answer, including the person you're helping, so this is turning out to be a genuinely thankless task in all respects. Welcome to "Family Tech Support", Web 2.0 Edition.
* Which is of course just an arbitrary number that none of us care about. Not really, anyway. Not very much, at least.
So, here's where I get to my question. At this point, do you:
Leave a comment, stating as politely as possible that you've done your best to help him answer the original question he asked, and if he has a new problem then he should start a new question? (I did this once, and actually ended up with an accept, but I felt kind of guilty afterwards, I don't think anybody answered his 2nd question).
Bite the bullet and edit your answer a 3rd, 4th, 5th time, however many times it takes to resolve his issue, knowing full well that he may not even remember to accept the answer once you're done? (I may work for free on SO, but that doesn't mean my time is worthless.)
Just abandon the question, hoping that it will force Mort to start thinking for himself?
Something else?
I've tried all three of the above and none of them ever quite feel right. I do want to help, but at the same time there are a lot more "lucrative" questions I could be answering. And I don't mind spending a lot of time on an answer either, if the question is interesting or important to me, but debugging is dull work.
I'd prefer not to reference specific questions here; I'm pretty sure that this is a shared experience, and my objective isn't to point fingers at "misbehaving" members. I'm more looking for some practical advice on how to dig myself out of these pits of despair.
Anybody have any other ideas?


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Expand 4 click carries the TPIC6A595, a chip that combines an 8-bit serial-in, parallel-out shift register with an 8-bit D-type storage register. It's intended for use as a port expander for connecting high-power peripherals. On the output side it has open-drain transistors with output ratings of 50V and 350mA. These are available through eight pins above the mikroBUS socket (D0-D7) with corresponding GND pins on the other side.
The outputs are open-drain transistor with continuous sink capability. For data input, Expand 4 click uses SPI. Additional pins include CLR IN (clear all input shift registers when held Low), EN IN (sets all drain outputs to OFF when held High), and CS (provides the impulse for shifting the data from the shift to the storage register).
This board is designed to use a 5V power supply only.
Note: The picture shows the board with through-hole headers. The board now comes populated with male pin headers already soldered for your convenience (the mikroBUS connection pins only). The board's user manual has yet to be updated to remove the soldering instructions.
You also can connect Click boards to many other popular platforms via these adapters:
In addition, it is royalty-free to add mikroBUS to your own designs. Visit the mikroBUS Category to see the full line of Click boards.


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March 30 Update: 12:01 a.m. April 11 is now time to remove the studded tires
Posted by Unknown in studded tires, winter preparedness on Wednesday, March 24, 2010
UPDATE 4:30 p.m. Tuesday, March 30: And, so that fickle Mother Nature went and threw us a curveball...Due to the threat of more severe winter weather forecast for the Cascade mountain range, Washington State Department of Transportation officials today extended the deadline to remove studded tires through April 10. Drivers must remove their studded tires by 12:01 a.m., Sunday April 11.
Travel over the mountain pass highways and in typically-snowy Eastern Washington sure has been odd this year. Now, the word "drought" seems to be popping up all over the news.
But first we have to get through the last few weeks of March and into April. April 1, 12:01 a.m. is the deadline to remove your studded tires. In Washington, studded tires are legal Nov. 1 - Mar. 31. You can receive a $124 fine for studded tire use after the deadline.
Studded tires damage the highway, and make it harder to stop on wet or dry pavement. In icy conditions, studded tires add some benefit.
Our forecasts don't call for any large-scale snow or ice storms. (well, oops..that changed today) And next year, please talk to your local tire dealer about alternatives that offer that same ice benefit, are safer and don't damage the highway.
If you are driving into the higher elevations, be prepared as El Nino may bring some typical late March and early April conditions. While good for the summer water supply, those of who have enjoyed some almost 70-degree days may be a little surprised to see snow in the mountains.
Some mountain snow is typical in March and April. Please remember, no one can guarantee bare and wet roads everywhere, all the time. Plan ahead, carry chains and drive for conditions.
On the WSDOT Winter Driving Web site, you can find answers to some questions we receive over and over (FAQ), ways to prepare for winter driving, winter driving tips, plus more about WSDOT's winter roadway operations, snow and ice removal and avalanche control.
This entry was posted on Wednesday, March 24, 2010 at 12:24 PM and is filed under studded tires, winter preparedness. You can follow any responses to this entry through the RSS 2.0. You can leave a response.


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Because of the way message storage is structured in a file-based persistent data store (see File-Based Persistence Properties), disk space can become fragmented over time, resulting in inefficient utilization of the available resources. Message Queue's Command utility (imqcmd) provides subcommands for monitoring disk utilization by physical destinations and for reclaiming unused disk space when utilization drops.
To monitor a physical destination's disk utilization, use the imqcmd metrics dst subcommand:
imqcmd metrics dst -m dsk -t destType -n destMame
This displays the total number of bytes of disk space reserved for the destination's use, the number of bytes currently in use to hold active messages, and the percentage of available space in use (the disk utilization ratio). For example, the following command displays disk utilization information for the queue destination curlyQueue:
imqcmd metrics dst -m dsk -t q -n curlyQueue -u admin
Example 7–5 shows an example of the resulting output.
The disk utilization pattern depends on the characteristics of the messaging application using a particular physical destination. Depending on the flow of messages into and out of the destination and their relative size, the amount of disk space reserved might grow over time. If messages are produced at a higher rate than they are consumed, free records should generally be reused and the utilization ratio should be on the high side. By contrast, if the rate of message production is comparable to or lower than the consumption rate, the utilization ratio will likely be low.
As a rule, you want the reserved disk space to stabilize and the utilization ratio to remain high. If the system reaches a steady state in which the amount of reserved disk space remains more or less constant with utilization above 75%, there is generally no need to reclaim unused disk space. If the reserved space stabilizes at a utilization rate below 50%, you can use the imqcmd compact dst subcommand to reclaim the disk space occupied by free records:
compact dst [-t destType -n destName]
This compacts the file-based data store for the designated physical destination. If no destination type and name are specified, all physical destinations are compacted.
You must pause a destination (with the imqcmd pause subcommand) before compacting it, and resume it (with imqcmd resume) afterward (see Pausing and Resuming a Physical Destination):
imqcmd pause dst -t q -n curlyQueue -u admin imqcmd compact dst -t q -n curlyQueue -u admin imqcmd resume dst -t q -n curlyQueue -u admin
If a destination's reserved disk space continues to increase over time, try reconfiguring its maxNumMsgs, maxBytesPerMsg, maxTotalMsgBytes, and limitBehavior properties (see Physical Destination Properties).


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Minister for Arts, Heritage and the Gaeltacht Jimmy Deenihan has come to an agreement with US businessman Gregg Bemis to allow an investigation at the site of the RMS Lusitania wreckage 13 miles off the coast of Cork.
The Irish Times reports that Minister Deenihan has endorsed plans to begin a broad set of exploration objectives with US businessman Gregg Bemis, who owns the rights to the wreck.
"A general agreement on the objectives of further research planned by Mr Bemis was endorsed by both parties," a statement from Deenihan's department said.
The RMS Lusitania was torpedoed by a German U-Boat a few miles out from the Old Head of Kinsale, Cork in 1915. The ship sank in 18 minutes, and claimed 1,198 lives.
The sinking of the Lusitania was the inciting factor to bring the US into WWI, despite Germany's claim that the ship was a legitimate military target.
Bemis now believes that the proof of whether or not the Lusitania was a military threat may lie within the remaining wreckage of the ship.
Up until last year, Bemis had been engaging in a long-running battle with the Irish State to grant permission to further explore the ship's wreckage. Bemis had won a license in 2007, but it expired in late 2011. During that exploration period, Bemis researched the possibility of a second explosion on the ship which could have accounted for the quick sinking.
Additionally, Bemis was licensed to recover specific artifacts that might add to both his and the State's understanding of the wreck, as well as the life and times of those on board the vessel when it sank.
The State held that more exploration could be harmful to its heritage rights to wrecks in its waters.
However, a statement from Deenihan's department said on April 30, "Both the Minister and Mr Bemis agreed that there is also a need for a greater understanding of the present condition of the wreck and to assess its rate of deterioration over time so that future research can target areas that may be at risk of becoming totally inaccessible or which might reveal information on the key questions surrounding the last moments of the vessel before it sank."
In the license that Minister Deenihan is currently reviewing, Bemis plans to continue forensic investigations into the quick sinking of the ship, as well as continue to gather more artifacts that may be suitable for display in time for the centenary of the sinking. The license would be active for three years.


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Senate road map raises expectations for Obama on world stage
COPENHAGEN -- A Senate blueprint on energy and global warming legislation released yesterday quickly rippled across the Atlantic as all eyes focus on what President Obama can deliver when he arrives here next week at the close of U.N.-led climate negotiations.
The four-page framework from Sens. John Kerry (D-Mass.), Lindsey Graham (R-S.C.) and Joe Lieberman (I-Conn.) offers several broad statements that are at the center of the Copenhagen, Denmark, negotiations and the Obama administration's position.
The senators slightly lowered their sights on greenhouse gas emission limits for 2020, dropping from 20 percent to the same "range" of 17 percent below 2005 levels that the United States has already put on the table. And they pledged to include in their bill long-term financing for developing countries' adaptation, deforestation and technology deployment efforts (see related story).
Reflecting several critical points for moderate lawmakers, the senators also call for "a strong international agreement that includes real, measurable, reportable, verifiable and enforceable actions by all nations."
Observers in Copenhagen and Washington said the Senate efforts raise countless questions in the days and months ahead about whether Obama can really pass a bill -- and in turn keep the momentum going on the U.N. talks that are already in a critical stage in Denmark.
Dirk Forrister, managing director of Natsource and former chairman of the Clinton-era White House Climate Change Task Force, said the 17 percent range for emissions should give diplomats confidence that a unified position is forming in Washington.
"More people will be encouraged as a sign of things beginning to solidify in a consistent direction," Forrister said. "If you have a position by the administration, the House and the Senate that all actually have the same number, that's a good sign."
Elliot Diringer, vice president for international strategies at the Pew Center on Global Climate Change, found reasons for optimism.
"It's a very constructive bipartisan message largely consistent with the president's, and that should give other parties greater confidence that the U.S. will be in a position to deliver on its provisional target," Diringer said. "The greater that confidence, the stronger the prospects for a positive outcome here."
Several Republican opponents of cap-and-trade legislation are scheduled to arrive in Copenhagen next week -- Sen. James Inhofe (R-Okla.) has called the coalition a "truth squad" -- to argue such a bill has no chance to make it into law. Inhofe spokesman Matthew Dempsey said the Kerry-Graham-Lieberman blueprint "should send a clear signal to Copenhagen that the current cap-and-trade legislative efforts in Congress are dead and that prospects for any type of new proposal remain on the drawing board."
Failure on Capitol Hill does have many delegates concerned that the U.N. negotiations could also break down, especially if Obama doesn't have a good backup plan.
"It's very important," Vijai Sharma, India's environment secretary, said of the need to pass a U.S. climate law.
Bill Hare, a scientific adviser to Grenada's delegation who also works for the German Potsdam Institute for Climate Impact Research, said that many countries have been tracking Obama's policies and the Capitol Hill debate.
"The quality of that bill and the way it connects to the international position of the United States is fundamental to the outcome of this process," Hare said. "If the U.S. bill falls over, people in some ways would have to go back to square one in terms of how you designed a system or to see what the U.S. administration is to deal with that. That's quite important."
Expectations have long been high among the international community for Obama following eight frustrating years fighting with the George W. Bush administration. But many in Copenhagen are already signaling displeasure with the Senate blueprint and the prospects for the United States' pledge.
"This framework is an insult to the hundreds of millions of people who are already facing the impacts of climate change, and President Obama can't support this and still claim to be a leader in Copenhagen," said Greenpeace USA executive director Phil Radford.
Lumumba Stanislaus Di-Aping, a Sudanese diplomat who speaks for the Group of 77 developing countries, insisted on a U.S. position that is widely seen as politically impractical.
"We do believe President Obama and his government, the American Congress, the American people, should join the Kyoto Protocol," he told reporters.
State Department climate envoy Todd Stern earlier this week said the Kyoto Protocol is a nonstarter in the United States. But Di-Aping did not back down when asked if he thinks Obama would ever budge from that longstanding policy.
"He has to persuade them," Di-Aping said. "The climate change is not to go away by rejecting what common sense and science tell us what to do because we want to maintain a style of life that's simply maintained by overconsumption."
The Copenhagen negotiations may end up drawing out Obama and Hill leaders on the timing for their efforts.
Although Senate Democrats say they will consider the bill next spring, Obama may face demands from world leaders to be more specific, said Alden Meyer, director of international climate strategies at the Union of Concerned Scientists.
The conference's Danish hosts are trying to line up support on a political agreement that spells out the negotiation schedule for next year, with an end date either in June or next December in Mexico City. Meyer said the United States would soon be pressed into taking a stance on a "real deadline" for negotiations that should be influential back on Capitol Hill.
"In some ways, whatever negotiation mandate that's set here at the end of next week becomes the de facto deadline for completion of the U.S. process," Meyer said, "Otherwise, we're back in the same box, that we come to the next negotiation session trying to get a final deal with the Congress not having acted."
Reporter Robin Bravender contributed from Washington, D.C.
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Hi all,
I need to write a java program that will transfer a Compressed Array from an RS232 port, to a usb flash drive. The main problem I have with this program is I have no idea how to start it.
I am not looking for someone to just give me the answers, but if someone could please point me in the right direction in terms of how to start the project, that will be greatly appreciated!


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Home > Home/Education > Numerology Calculator
Getting rid of software like Numerology Calculator can be very difficult due to the size and amount of programs that it installs onto your system. The software contains several parts which occupy large space of you computer. Because Numerology Calculator technically get installed separately they can be notoriously difficult to remove. Now, let me tell you how To Uninstall Numerology Calculator
To uninstall the software you will have to take the usual windows options as it doesn't offer a way to remove it in the 'All Programs' area. Although this is generally safe it does have its downfalls. Like not being able to be automatically delete Numerology Calculator from the system registry. This can cause errors and slowed down computer speeds.
(Completely remove the Numerology Calculator )
If you are still have problems with the software, or if it still hasn't been fully removed then you will have to delve into the system registry and manually delete the Numerology Calculator I would highly recommend that you do not mess around inside this area of your computer as you could end up causing even more problems. If you accidentally remove the wrong file path then your other software that you have installed on your computer could just stop working.
If you don't want to rummage around the system registry then you might need to get Numerology Calculator to do the job for you. The other option is that you hire a professional, but even this can be risky and very pricey. There is a program called the Mighty Uninstaller. This software has been designed specifically for people who don't know a lot about computers, so they can remove corrupted files and Numerology Calculator from the registry automatically. This software is highly praised among IT experts from all over the world.


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The Town of Estes Park has hired Gregory Muhonen to serve as its new Public Works Director. Muhonen will begin work in Estes Park July 28. Town Administrator Frank Lancaster commented, "Greg's extensive experience and dedication to his work will make him a valuable asset to the Town of Estes Park." An outdoor enthusiast and resident of the mountains between Estes Park and Loveland for over 17 years, Muhonen looks forward to serving the Estes Park community. "I believe I possess the mindset and hands-on work ethic that fit well with the multi-tasking environment at the Town of Estes Park," he said. "My wife and I are thrilled for this opportunity to integrate into the community that we have been visiting and bringing guests to for over two decades."
Muhonen holds a Bachelor of Science degree in Civil Engineering from Stanford University and is registered as a professional engineer in Colorado. He has more than 30 years of civil engineering work experience including private land development, land use entitlement review, traffic engineering, municipal policy, and public works capital project design and construction. Since 2012, Muhonen has worked for the City of Loveland supervising the City's transportation Project Management group. He also worked for the City of Loveland from 1989 until 2001, serving as the Senior Transportation Engineer and Development Engineering Manager. In the late '80s Muhonen was the first Construction Engineer for Larimer County, managing all the County's road and bridge construction work, including resurfacing projects on Fish Creek Road and Highway 66 in Estes Park.
In 1993 and 1999, Muhonen won the Employee of the Year award for his work as a civil engineer in the City of Loveland Engineering Division. In 2002, he received the award for Program of the Year from the American Public Works Association for his work on the Larimer County Urban Street Standards. Last week he was honored by the Loveland Public Works Department for his collaborative leadership and timely repairs of the bridge damage caused by the 2013 flood at Sylvan Dale Ranch and at US Hwy 287. Muhonen is also the President and Managing Member of Timber Wind Land, LLC, the company that developed The Springs at Mariana and The Overlook at Mariana in west Loveland.
"I strive to lead by example," said Muhonen. "I hold myself and my team accountable to each other, our community residents, and our leaders to implement the goals and priorities that we collaboratively establish."


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We've seen a lot of pseudodong in our day, but it's about time we went green. From the New York Botanical Garden comes this fine phallic specimen.
Cucurbita moschata is a hardy little plant, able to thrive in the warmer temperatures of the Mid-Atlantic and Southern United States. It includes a number of squashes and pumpkins that are no strangers to the average plate, and it can also look like a penis.
Now go watch some football tonight.


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Say It with Love A6 Folded Card Blank Wedding / Party Invitation Pack of x10
Say It with Love A6 Folded Card Blank Wedding / Party Invitation Pack of x10
from 18.00
DIY Wedding Invitations with a Vintage Inspired look. Folded Blank cards ready for you to print yourself.
This listing is for x10 cards & x10 envelopes. No Text on cover.
Printed on a matt finish 350gsm card, and folded to A6 size. C6 Kraft rustic style envelope included. Cards are sold in lots of 10. White border surround.
Each card is blank inside ready for DIY printing. Assembly not included.
Please note that you do not print directly onto the cards. Instead print your text on a separate sheet and stick inside the card using glue roller tape or double sided tape. Or if you prefer, you can write out your invites directly onto the inside of the card.
Printing templates are emailed with each order to make it as easy as possible for you to set up your printing at home or at the office.
Orders comes packaged in a display box.
Orders are posted by Registered Tracking Post.
Orders taken will be ready in approx 1-2 weeks from payment received.
Please see our policies for more information on our services for Wedding Stationery, or contact us to set up a custom order.
Prices Per Pack of x10 -
€18.00 per pack of x10 for 10 - 40 quantity
€16.00 per pack of x10 for 50 - 90 quantity
€14.00 per pack of x10 for 100 + quantity
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A6 Say It With Love WEDBLANK:
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Ka'anapali is located on Maui, one of the biggest and most beautiful Hawaiian Islands, making it a popular vacation destination. While some visitors to Ka'anapali stay in hotels on the island, there are many accommodations available at a better value. The economical vacation homes on the island will provide you and your family with a great deal more privacy and space. There are a number of rental homes dotted around the island, many that feature striking ocean views.
Many visitors to Ka'anapali won't want to leave their beautiful beachfront homes, but there is plenty to do if you wish to get out for the day. Aloha Bicycle Tours offers a fantastic experience that the whole family can enjoy. This unique bicycle tour gives you the opportunity to cycle down the island's volcano. It is an amazing, once-in-a-lifetime adventure for a good value.
The waters around the island of Maui are crystal clear and beautiful. There is no better way to enjoy them than a relaxing kayak tour. South Pacific Kayaks offers high quality kayak tours that are fun and safe for the whole family. It is the perfect way to spend the day outside of your vacation home.
A number of visitors to Maui choose to dine in their vacation homes, but if you fancy venturing out of your vacation villa in the evenings, the restaurants will not disappoint you. The Lahaina Grill is located at the historic Lahaina Inn just off Front Street and features the "Cake Walk" as its signature dish. Roy's in Kahana is an excellent fusion restaurant that serves up some of the best seafood on the island.
One of the most famous things to do when you are taking a Hawaiian vacation is to go to a Luau. This is a truly traditional dining and entertainment experience. There will be music, traditional hula dancing, and some of the best food that you have ever tasted.
It is no secret that Maui is a high-end island, but there are many affordable vacation rental options. As long as you reserve your vacation villa early, you will not be disappointed.


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ITEC to Represent Swedish Tube- and Pipe-Bending Equipment Manufacturer
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Friday, October 1, 2010
Sweden's Herber Engineering AB, a manufacturer of hydraulic and electric tube- and pipe-bending machines, announced the formation of a strategic partnership with Innovative Tube Equipment Corp. (ITEC), Rockford, IL. ITEC will be Herber's exclusive North American representative for sales, applications engineering, technical support and service, and installation.
See also: Innovative Tube Equipment Corp.
Related Enterprise Zones: Fabrication
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