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Chronic Chagas' heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine
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DOI: 10.1007/s10741-010-9211-5
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- Muñoz-Saravia, S.G., Haberland, A., Wallukat, G. et al. Heart Fail Rev (2012) 17: 45. doi:10.1007/s10741-010-9211-5
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Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10–30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease.
KeywordsAutoantibodiesChagas' heart diseaseHeart markerInflammation markerOxidative stress markerTrypanosoma cruzi
Chagas' disease (American: trypanosomiasis) is an endemic parasitic disease that mainly occurs in Latin American countries and is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi).1
Both female and male triatomine bugs are able to transmit T. cruzi throughout their lifetimes (up to 2 years). Besides humans, more than 100 mammals, including dogs, cats, rats, sloths, armadillos and bats, are known to be parasite reservoirs. Due to triatomine bug cannibalism, T. cruzi can also be spread throughout triatomine populations. In contrast, birds and reptiles do not carry T. cruzi. Once infected with T. cruzi, subjects become lifelong parasite carriers and pass through several stages of the disease.
In 1987 [6], it was reported for Brazil that the treatment of all symptomatic Chagas' disease patients (pacemaker implantation and surgical intervention) might require 750 million US dollars per year. For the time interval between 1979 and 1981, it was estimated that death caused by Chagas' disease resulted in a loss of working power of about 259,152 years.
Consequently, initiatives and control programs were started that include primary initiatives for interrupting the domestic and peridomestic transmission cycles by chemical control of the vectors, animal reservoirs and infected humans, and initiatives for improving housing conditions and health education.
In order to prevent parasite transmission via blood bottles prepared from subjects who are infected—which is one of the main non-vector routes of transmission—blood donors began being screened for T. cruzi antibodies. Prospectively, in view of the likely number of subjects already infected, it will become increasingly necessary to implement strategies for the effective prevention and treatment of symptomatic Chagas' disease patients. In order to follow such strategies, earlier diagnosis, improved monitoring of the progress of chronic Chagas' disease and optimal treatment guidance are prerequisite elements. In our view, and considering the economical and logistical options available in endemic areas, laboratory medicine could, in particular, possess the potential to guarantee the implementation of such strategies.
Europe is colonized by different subfamilies of the triatomine bug, including species of the Triatominae subfamily. Among these, T. rubrofasciata is known to be a T. cruzi carrier in Latin America. However, there is no indication of T. cruzi transmission by triatomine bugs in Europe.
As summarized [8], various species of flea, fly, bedbug, mosquito and lice have been suggested as possible candidates for T. cruzi transmission. Ticks (Ixodida) were seen as another potential vector for T. cruzi in Europe. Some tick subspecies can carry T. cruzi; however, there is presently no indication that ticks are able to transfer T. cruzi to humans.
Annual death (thousand)
Cases of infection (million)
Annual incidence (thousand)
Population at risk (million)
Distribution (countries)
Due to continuous rural–urban migration, Chagas' disease, which historically is a disease of poor, rural areas, became widespread throughout urban centers, such as Sao Paulo with about 300,000 infected individuals and Rio de Janeiro and Buenos Aires with more than 200,000 infected individuals [13].
International tourism is another route for the worldwide spread of Chagas' disease. Other routes of infection by T. cruzi include diaplacental and/or perinatal transfer from the mother to her fetus [23]. Outside Latin America, one case of congenital transmission of T. cruzi has been documented in Spain [24].
The vicious cycle of Trypanosoma cruzi infection
However, particular genetic variations in the parasite and also in the host are thought of as being responsible for regional differences in the incidence of this disease [25, 26].
Acute Chagas' disease
In a small number of patients, especially children, hepatosplenomegaly, myocarditis and meningoencephalitis are seen. The mortality rate due to acute Chagas' disease is 2–6%, which is mainly attributed to myocarditis and meningoencephalitis [2–4, 10, 28]. The low rate of mortality in the acute stage is certainly the reason for the lack of detailed histopathological information about acutely infected patients. The few data available originate from an 18-month-old boy and a 4-month-old girl who both died after the infection [4]. Amastigotes were found in the testis and ovaries. Moreover, T. cruzi was also found in mononuclear phagocytes.
Mechanisms of parasite control
Both humoral and cellular immune responses participate in parasite control, but the highly complex interactions are far from close to being clarified [29]. More severe signs of infection were shown in B-cell-deficient mice compared to their wild type, which indicates that the humoral immune response is an essential player in the fight against T. cruzi. On the other hand, a concert of CD8+ T cells and macrophages, as well as interferon-γ (IFN-γ) secretion, also seems to be essential. In this context, the perforin-/granzyme-dependent killing of infected cells and FAS-mediated apoptosis must be considered [30]. Furthermore, in reaction to the infection, macrophages produce IL-12, which is an inducer of resistance against T. cruzi [31].
Other important players in parasite defense are cytokines, which regulate the immune response as well as T. cruzi replication [32], and NO [33, 34], due to its cytotoxic properties. Among the cytokines, IFN-y and TNF-α are dominant in parasite defense. Consequently, anti-IFN antibodies cause an increase in parasitemia and mortality. Mice that were deficient for the IFN-y receptor and inducible NO synthetase (iNOS) showed an increased infection risk [35–37]. The protective effect of TNF-α was concluded from experiments that used TNF-R1FcIgG3 transgenic mice, which were found to be more sensitive toward T. cruzi infection than the corresponding wild-type mice [38].
However, no complete parasite elimination has been observed. There is evidence that CD8+ T cells only partially control the infection and that they can lose their activity [39]. Immune suppression elements that directly come from T. cruzi could contribute to the ineffectiveness of the immunological system in parasite control.
Such incomplete parasite eradication combined with the molecular mimicry by T. cruzi antigens of human antigens of the heart and intestine might be the reason for the induction of an autoimmune response after T. cruzi infection. Autoimmune activities are increasingly thought to be one of the main reasons for the manifestation of life-threatening complications in a distinct proportion of chronically infected patients.
Chronic Chagas' disease
The result of incomplete parasite control is the life-long persistence of the parasite and, therefore, patients with chronic infections. This can be demonstrated by anti-T. cruzi antibody positivity and—by using modern analytical equipment such PCR techniques—by parasite detection in patient tissue samples [40, 41]. Despite this permanent parasitic load, the asymptomatic phase of chronic Chagas' disease can be differentiated from the symptomatic stage (Fig. 3).
Asymptomatic chronic Chagas' disease (latency stage, indeterminate stage)
Patients in the asymptomatic stage (indeterminate phase) are symptomless. The heart and gastrointestinal tract have no distinct pathological findings when ECG, sonography and radiological examinations are used. Asymptomatic patients are only diagnosed by chance or by screening for T. cruzi antibodies, for example in the case of enrollment into the blood donor system or in preparation for surgery. The asymptomatic stage might be interrupted by episodes showing unspecific characteristics of acute infection. In particular, patients with immunosuppressive disorders, such as HIV-positive patients, show such episodes [2, 3, 42].
Small focal inflammatory lesions have been detected in tissue samples of the heart, skeletal muscle and gastrointestinal tract from asymptomatic patients [43–45].
Symptomatic phase
Of the chronically infected patients [1–5, 10], one-third become symptomatic, sometimes only after decades. Among these subjects, up to 90% develop Chagas' heart disease. The others present with gastrointestinal disease, mainly megacolon and megaesophagus, and alterations in the peripheral nervous system. A certain proportion of patients manifest both cardiac and gastrointestinal diseases. Genetic variability has been discussed as being responsible [25, 26, 46], but this debate has not yet been concluded [47]. With respect to the relationship between HLA polymorphism and the manifestation of chronic Chagas' disease, associations were observed between distinct HLA alleles and an increased risk of developing of chronic Chagas' disease in some studies [48, 49], but others denied finding any relationships [50].
Chagas' heart disease
Chagas' heart disease becomes manifested in men and women with a comparable frequency, and it mainly begins between the ages of 30 and 50 years. Abnormalities found in ECG and/or echocardiography are early indications of the development of Chagas' heart disease. In line with the diagnostic options available in endemic areas, however, cardiac arrhythmia found by Holter ECG examination is often the first indication of the development of Chagas' cardiomyopathy in chronically infected patients who, from an anamnestic and clinical viewpoint, are clearly thought to be in the asymptomatic stage [51]. Among the potential blood donors who attended the St. Bárbara hospital in Sucre, Bolivia, who were symptomless but were diagnosed during blood donor screening as suffering from chronic Chagas' disease, as detected by T. cruzi antibody positivity, we found that one-quarter of these patients presented with distinct ECG indications for Chagas' heart disease (unpublished data). Of the typical ECG abnormalities in chronic Chagas' heart disease, indicating the diagnostic importance of the ECG [52], right bundle branch block, left anterior hemiblock, ventricular extrasystoles, sinus bradycardia, auricular fibrillation and complete atrioventricular block were found to be the most frequent ones with increasing severity of the disease [2, 4, 27]. According to practical recommendations for the evaluation of newly diagnosed patients with chronic Chagas' disease based on T. cruzi antibody positivity [53], patients should undergo a medical history interview, a physical examination and a resting 12-lead ECG with a 30-second lead rhythm strip. In the case of normality, examination should be repeated annually. Where Chagas' heart disease is diagnosed, comprehensive cardiac evaluation is recommended, which should include Holter ECG examination, echocardiography [54, 55] and exercise testing. It was previously suggested that cardiac MRI is useful in the diagnosis and management of chronic Chagas' disease [56, 57]. From clinical view, myocarditis, thromboembolic events, sudden cardiac death and congestive heart failure are typical of advanced Chagas' heart disease. However, about 30% of Chagas' heart patients die from sudden cardiac death without any characteristic signs of advanced Chagas' heart disease being been found before.
However, the severity of heart disease does not correlate with the occurrence of parasite DNA. This is a clear sign that direct heart damage in relation to parasite load and inflammation is not the only mechanism that must be considered. It is assumed that both the parasite and the host exert an influence on the pathogenesis of Chagas' heart disease [60].
Comparable with the findings in asymptomatic patients but more pronounced in symptomatic patients, the histopathological pattern of the heart shows nests of focal inflammation with T cells and varying numbers of B cells and macrophages, diffuse interstitial fibrosis and a disturbed morphology of the myocytes. The conduction system in the heart also shows alterations [61–63].
The often apically aneurysmatic Chagas' heart is thought to be the cause of thrombus formation, which may lead to thromboembolic events in the brain and lungs and which are thought of as being responsible for the high rate of sudden death in Chagas' heart disease. However, the main life-threatening complication of chronic Chagas' disease is the continuous progress toward severe heart failure. Nearly 60% of patients die due to cardiomyopathy.
Chagas' gastrointestinal disease (megaesophagus and megacolon)
Malnutrition caused by swallowing problems and regurgitation leading to weight loss, as well as obstipation, accompanied by abdominal pain, marks the progress of chronic Chagas' disease to megaesophagus and megacolon. Radiological investigation employing barium as the contrast agent can be used for early diagnosis; however, a simple radiological investigation is often sufficient.
The nerve system in chronic Chagas' disease
The damage to the parasympathetic nervous system may be the main driver of alterations in the vegetative nervous system in chronic Chagas' disease [64]. It is assumed that the damage to the parasympathetic nervous system starts in the acute phase and proceeds into the chronic phase. The central nervous system, however, is mostly affected during the acute phase of the disease. Rare cases of changes in the psyche of chronically infected Chagas' patients are also a sign of nerve damage during the chronic phase of the disease [2].
Therapy in the acute stage concentrates on the elimination of the parasites, preferably by using Nifurtimox and Benznidazol [3, 18, 65]. While Nifurtimox has to be taken for between 50 and 120 days, Benznidazol is administrated for up to 60 days. However, some T. cruzi strains can develop resistance against the drugs. Consequently, only 50% of treated patients are responders to Nifurtimox and Benznidazol. Furthermore, the existing drugs show enormous potential for toxic side effects, which manifest in the liver and as an allergic reaction, mainly after long-term administration.
In contrast, a wide range of therapeutic possibilities are available after the manifestation of Chagas' heart disease, which are based on common heart failure therapies including drug treatment and pacemaker and cardioverter-defibrillator implantation. Heart transplantation is the only therapeutic option in some cases [2, 18]. As is the case for cardiomyopathy in general, cell-based therapy is being increasingly discussed for Chagas' cardiomyopathy [57].
Considering the increasing acceptance of an autoimmune background in the pathogenesis of the life-threatening complications of chronic Chagas' disease in general, but especially for Chagas' heart disease (see the section "Pathogenesis of symptomatic chronic Chagas' disease"), new treatment regimes similar to those generally used in autoimmune diseases, such as treatment with anti-inflammatory drugs and immunosuppressive drugs, could become increasingly important. Another promising option would be the inhibition or elimination of the high percentage of pathogenetic autoantibodies found in chronic Chagas' heart disease [66, 67]. It has been shown for patients with dilated cardiomyopathy and also recently suggested for patients with Chagas' cardiomyopathy that a significant benefit could be achieved if the autoantibodies against the beta 1-receptor were eliminated by immunoabsorption [68–71]. Since the current immunoabsorption techniques for beta 1-receptor autoantibodies in DCM are based on the elimination of the whole IgG fraction, they might be suitable for chronic Chagas' disease patients carrying autoantibodies against the beta 1-receptor and also for those carrying autoantibodies against the beta 2- and muscarinergic 2-receptors. However, cost factors and logistical reasons might be the limiting factors preventing the wide use of immunoabsorption techniques for chronic Chagas' disease in the near future. The blockade of autoantibodies by specific peptides, homologs to the autoantibody targets of the corresponding receptors, could be an alternative which is presently under investigation [72] with respect to DCM patients, with the focus on inhibiting beta 1-receptor autoantibodies. Recently, we selected chemical antibodies named aptamers for specific neutralization of the autoantibodies found in patients with DCM and Chagas' heart disease [73]. This finding could possibly open the door to a totally new treatment strategy. Whatever strategy of autoantibody-directed therapy is administered to patients with Chagas' heart disease in the future, asymptomatic but autoantibody-positive patients should be included in the treatment.
Pathogenesis of symptomatic chronic Chagas' disease
Different hypotheses have been formulated with respect to the pathogenesis of symptomatic chronic Chagas' disease. However, these hypotheses are clearly more detailed for Chagas' heart disease. This mirrors the greater amount of data available on Chagas' heart disease because of its more frequent occurrence. However, the majority of the pathogenetic data found on Chagas' heart disease can also be used to explain the main aspects of the gastrointestinal manifestation of chronic Chagas' disease.
Chagas' heart disease
As extensively summarized [29, 74], several hypotheses have been formulated based on the direct response of the immune system to the parasites in the tissues, as well as on the interactions between inflammatory, immunological and autoimmunological mechanisms.
A. Primary damage of the neuronal system
The key event in this hypothesis is the denervation of the autonomous parasympathetic system in the heart. This neuronal damage could be induced in the acute phase of the disease, and the resulting lesions might accelerate in the chronic stage.
B. Cardiomyocyte toxicity due to T. cruzi and/or T. cruzi-derived products
The myocytolysis of host cells following intracellular infection has been documented for the acute stage, and it could also potentially be of some significance in Chagas' heart disease. It was first assumed that parasites could secrete cytotoxic products in 1955. However, with respect to the generally low parasite titer in the chronic stage, direct parasite cytotoxicity and/or the cytotoxicity of parasite-derived products should be of only limited relevance. This could change for immunosuppressed patients and/or those with a high parasite titer.
C. Parasite-induced microvascular alteration
This hypothesis is based on the assumption that—without producing cell lysis—parasites interact with essential metabolic reactions in microvascular cells. Inhibited protein synthesis and changed Ca homeostasis are only some of the interactions documented that can cause hypoperfusion. The subsequent hypoxic/ischemic damage of cardiomyocytes might then produce chronic inflammatory conditions in the heart which drive Chagas' heart disease.
D. Polyclonal B-cell activation
Immunosuppression and autoimmune processes following the disruption of normal immune regulation by polyclonal B-cell activation could support pathogenetic events.
E. Persistent T. cruzi antigens
Antigens might trigger T-cell-mediated responses of the delayed-type hypersensitivity cells or cytotoxic cells, leading to damage in the host's infected and/or bystander cells.
F. Autoimmunity induced by T. cruzi-specific antigens or by host antigens
Autoimmunity might result from T. cruzi antigen-associated molecular mimicry, as well as from bystander activation.
Presently, none of these listed hypotheses claim exclusivity. Because of the low quantity of parasites in the myocardium of patients with Chagas' heart disease, the development of autoimmunity is increasingly accepted as a key event in its pathogenesis.
In the bystander activation, parasites produce pro-inflammatory conditions with the release of cytokines, NO/peroxynitrite and chemokines, which together with intracellular parasite replication result in cardiomyocyte damage and the liberation of autoantigens and cryptic epitopes. Such autoantigens and cryptic epitopes, normally inaccessible to the host's immune system, are now recognized by autoreactive T cells. The T cells are activated in parallel and proliferate to perpetuate the immune response against the heart structures.
Cross-reactivity of Trypanosoma cruzi and human antigens favoring molecular mimicry (adapted from [75])
Human antigens
T. cruzi antigens
Sulphated glycolipid
Neuronal 47-kD protein
Heart and skeletal muscle
Microsomal fraction
Smooth and striated muscle
150-kDa protein
Cardiac myosin heavy chain
B13 protein
Sacroplasmatic reticulum antigen (SRA)
Microtuboli-associated protein (MAP) (brain)
28-kD lymphocyte membrane protein
55-kD membrane protein
23-kD ribosomal protein
23-kD ribosomal protein
Beta 1-adrenoreceptor, M2 muscarinic receptor, M2 cholinergic receptor, cardiac
Ribosomal P0, P2ß and 150-kD protein
Cardiac muscarinic acetylcholine receptor
The G-protein-coupled receptors and their functional autoantibodies that were suggested as driving the pathogenesis of heart and circulatory diseases adapted from [77]
AAB effect
Corresponding epitope
Loop 1, 2
Dilated cardiomyopathy
Loop 1, 2
Loop 1, 2
Chagas' disease
Loop 2
Chagas' disease
Loop 2
Allergic asthma
Loop 3
Loop 2
Malignant hypertension
Loop 2
Vascular renal rejection
Loop 2
Chagas' disease
Loop 2
Dilated cardiomyopathy
Loop 2
Systemic lupus erythematodes
Loop 2
Myasthenia gravis
N-terminal extracellular domain
Rassmussen's encephalitis, non-inflammatory focal epilepsy, catastrophic epilepsy
aa 372–386
Graves disease
Extracellular domain, conformational epitope
G-protein-coupled receptors belong to the superfamily of heptahelical transmembrane proteins. About 80% of all receptors belong to this receptor family. In animals and humans, GPCRs participate in the perception of senses, in inflammatory processes, chemotaxis, endo- and exocytosis, cell growth and differentiation. They are also involved in the regulation of metabolism. The effects of glandular hormones, tissue hormones and neurotransmitters such as catecholamines, glucagon, endothelin, angiotensin, acetylcholine, serotonin and others are mediated via GPCRs. G-protein-coupled receptors sense signal molecules outside the cell. The resulting change in receptor conformation activates the G-protein that—depending on its type—modulates the cAMP or phosphoinositol pathway to translate the outside signal into an internal cellular response.
Because of the central role of GPCRs in the regulation of metabolism, it is not surprising that altering GPCR-dependent signal transduction results in a wide variety of pathogenetic consequences. Agonistically acting autoantibodies are thought to drive GPCR- dependent pathogenetic events.
Autoantibodies against G-protein-coupled receptors in Chagas' heart disease
Basic data and percentages of positivity for autoantibodies (AAB) against beta 1-adrenergic, beta 2-adrenergic and muscarinergic 2 receptors (beta1-AAB, beta2-AAB, M2-AAB) of 228 Chagas' disease patients and 29 healthy subjects [67]
n (male/female)
29 (9/20)
96 (26/70)
57 (34/23)
30 (11/19)
45 (21/24)
Age (years), median (min/max)
30 (19/61)
30 (18/82)
47 (18/82)
46 (19/78)
54 (29/81)
AAB positivity (%)
Beta1-/M2-AAB or beta2-/M2-AAB
Categories of cardiomyopathy (%)
This frequency clearly parallels the epidemiological data on the incidence of Chagas' heart disease in chronically infected patients.
In symptomatic patients, positivity for beta1-AAB was found in 75% of the cases. Nearly all cases had beta2-AAB and M2-AAB positivity. After subdividing the symptomatic patients, beta1-AAB and M2-AAB were found in nearly all patients with cardiomyopathy. In contrast, only 38% of the cardiomyopathy patients had beta2-AAB. Of the megacolon patients, 90% were positive for all receptors. Patients suffering from cardiomyopathy and megacolon carried all three receptors with a frequency of nearly 100%.
There is now growing evidence that AABs are also pathogenetic substrates of Chagas' heart disease, particularly beta1-AAB. This is not least because of the similarities between Chagas' heart disease and dilated cardiomyopathy (DCM). Both patient groups carry a high percentage of beta1-AAB. Consequently, a "cross talk" [81] was suggested between the beta1-AAB found in Chagas' heart disease and the beta1-AAB found in DCM, which means that the results from animal experiments and human studies that focused on the latter case can consolidate the beta1-AAB-associated history of the former. Most important were the experiments that showed cardiomyopathy-typical heart alterations [82, 83] following the transfer of beta1-AAB to animals. Furthermore, as already indicated before, patients show improvements after the elimination (immunoabsorption) of beta1-AAB [68, 69, 71]. At cellular and subcellular levels, changes in the action potential duration and contractility of cardiomyocytes have been observed following the addition of beta1-AAB and M2-AAB [84, 85]. All three of these antibodies, which are found in Chagas' heart disease, are agonistic. However, depending on the different downstream effects—the activation of adenylate cyclase by beta1-AAB and beta2-AAB and its inhibition by M2-AAB—positive or negative chronotropy are evident. In agreement with this, IgG prepared from the blood of Chagas' patients, which preferentially contains beta1-AAB and beta2-AAB, activates adenylate cyclase and increases cAMP formation in heart cell membranes and cardiomyocytes. This occurs in parallel with increased contractility [86, 87]. However, the effects of IgG prepared from animals and humans have not always been consistent [88].
Activation of the L-type calcium canal is a further characteristic reaction in the presence of beta1-AAB. This might result from the protein kinase A-dependent phosphorylation of the canal protein, but it could also result from a direct interaction between the activated G-protein subunits and the canal proteins [89, 90]. It has generally been accepted that changes in the calcium flow caused by autoantibodies are an essential component in the pathogenesis of myocarditis and dilatative cardiomyopathy [91]. As mentioned already before, alterations in the parasympathetic nervous system are a key event in the pathogenesis of both Chagas' heart disease and gastrointestinal disease. Agonists of the M2-receptor reduce the contractility of the rat atrium, increasing cGMP and reducing cAMP formation [92]. However, it has been suggested that M2-receptor-dependent pathogenetic mechanisms could be more profound in gastrointestinal manifestations. The M2-AAB receptor increases the tonus (basal) at the colon and esophageal strips and reduces cAMP concentration [93, 94].
It has been assumed that the binding of M2-AAB activates pertussis-sensitive G proteins that inhibit adenylate cyclase. Additionally, it has been suggested that M2-AAB induces receptor desensibilization and sequestering, which would support dysautonomia of the colon and esophagus [95]. However, with respect to the high prevalence of M2-AAB in Chagas' heart disease, these AAB receptors should not be underestimated as drivers of cardiomyopathy.
Laboratory medicine
Parasite detection
Trypanosoma cruzi in the circulating blood, especially at a high parasite titer, which is predominantly observed in acute Chagas' disease, are detectable by microscopic examinations of thick or thin blood films stained with Giemsa. In addition, anti-T. cruzi antibodies of the IgM type are detectable during the acute phase of the disease [10, 96]. During the chronic stage, because of the low blood titer, direct parasite detection is more difficult, but PCR-based detection of parasite DNA can also be used in tissue samples [40, 41, 97, 98]. However, chronic Chagas' disease is most frequently diagnosed by the detection of anti-T. cruzi antibodies of the IgG type. The World Health Organization [99] recently initiated a multicentric study to compare the sensitivity and specificity of assays used to detect anti-T. cruzi antibodies in chronic Chagas' patients. Trypanosoma cruzi antibodies of the IgG type were detectable in hemagglutination assays (sensitivity = 88–99%, specificity = 96–100%), particle agglutination assays (97–100, 97–99.5%) and ELISA (94–100, 96–100%). Indirect immunofluorescence (sensitivity 98%, specificity 98%), western blot (100, 100%, respectively), immunoblot (98, 99.5%, respectively) and radioimmunoprecipitation (100, 100%, respectively) served for confirmation. Based on the study data, hemagglutination assays are not recommended for T.cruzi antibody detection in blood donor screening.
Risk assessment for Chagas' heart disease in asymptomatic patients
Up until now, there have been no available laboratory medicine tools for assessing the risk of asymptomatic patients developing Chagas' heart disease. However, a patient's genetic disposition and genetic diversity of T. cruzi could indicate the risk for the development of Chagas' complications [26, 100]. Another hopeful strategy for risk assessment could be based on screening for AABs in asymptomatic Chagas' patients (see the section "Autoantibodies against G-protein coupled receptors in Chagas' heart disease"; Table 4). We recently presented the first preliminary data showing that beta1-AAB, beta2-AAB and probably M2-AAB in particular are early indictors of the risk of asymptomatic Chagas' patients becoming symptomatic [101]. The use of M2-AAB for risk assessment is also seen as a promising strategy by others [92], as its function in driving alterations in the autonomic nervous system [94, 102] has frequently been discussed as being one of the primary steps in the pathogenesis of symptomatic chronic Chagas' disease.
However, in order to verify the strategy of AAB measurement for risk assessment in asymptomatic Chagas' patients, prospective studies enrolling broad cohorts would be indispensable.
Currently, a bioassay is mostly used for AAB measurement [67, 103, 104]. In this assay, cultured neonatal rat cardiomyocytes are the substrate for AABs. The AABs are quantified by monitoring the chronotropic effects induced by the AAB-containing IgG fraction prepared from the patient's blood. The addition of specific antagonists enables the differentiation between beta1-, beta2- and M2-AABs. The beating frequency—as an integral parameter of cell functionality—measured in this bioassay is an advantage as it corresponds to the AAB concentration. Moreover, the bioassay tests beta1-AAB, beta2-AAB and M2-AAB in parallel. However, the limitations of this bioassay include sophisticated assay standardization, a lack of adequate control materials and extensive turnaround times.
There are other cell-based AAB quantification methods. In particular, the quantification of beta1-AAB was performed via cAMP formation in cultured cells that were engineered to express the recombinant receptor protein for beta1-AAB. The quantification of cAMP is then possible using RIA or ELISA technology. Quantifying the formation of cAMP using FRET technology might become important in the future [70, 105].
Considering the time, cost and capacity of cell-based assays, the development of less costly but well-standardized and more universally available ELISAs seems to be an essential prerequisite for AAB measurement. Whereas the bioassay quantifies AABs by measuring their functionality, ELISAs and RIAs use for the AAB quantification exclusively the AAB binding at small peptides that are homologous to extracellular receptor epitopes recognized by the AABs. ELISAs and RIAs do not indicate the AAB functionality. This might be one of the reasons for previous discrepancies in the results between bioassays and ELISAs [106]. Nevertheless, ELISAs specific for beta1-AAB, beta2-AAB and M2-AAB have been frequently used in different studies [107, 108]. However, to the best of our knowledge, no RIAs or ELISAs for Chagas' disease-relevant autoantibodies against GPCRs are presently commercially available.
Early diagnosis and monitoring of Chagas' heart disease
Heart non-specific markers
With respect to the impact of inflammatory processes in the pathogenesis of the Chagas' heart disease, established inflammation markers should be appropriate for patient monitoring. With the tight connection between inflammation and oxidative stress, the measurement of markers for oxidative stress might be additionally helpful.
Inflammation markers
The typical signs of inflammatory processes are obvious, especially during the acute stage after infection with T. cruzi.
The infection of animals with T. cruzi and experiments based on demonstrating protection against T. cruzi infection by immunization clearly showed that the measurement of cytokines and acute phase proteins has the potential for monitoring Chagas' disease, especially the acute stage of Chagas' disease [109, 110].
If compared acute-phase proteins and the serological profiles in chagasic children [111], the early acute stage only presented an increase in specific anti-T. cruzi IgM; the intermediate acute stage showed high levels of anti-T. cruzi IgM and/or anti-galactose antibodies (anti-Gal; which has been suggested as being an additional marker of the acute phase), as well as high levels of α2-macroglobulin and specific anti-T. cruzi IgG; and in the late acute stage, the IgM level was already low but α2-macroglobulin, CRP, anti-Gal and specific IgG levels were still high. Additionally, increased α2-macroglobulin and CRP levels were shown when healthy controls and acute T. cruzi-infected children were compared [112].
Furthermore, for cytokines such as TNF-α, IL-2, IL-6, IL-8 and IL-12 and soluble receptors such as sIL-2R, sCD8 and sCD4, Chagas' disease–associated changes were reported, especially during the acute phase of the infection [113–116]. The increased IL-2R concentration agrees with findings in a mouse model which showed that IL-2R expression was elevated during immune suppression in the acute phase of infection.
However, inflammation markers such as CRP are also increased in chronic chagasic patients when compared to healthy subjects, especially in those suffering from Chagas' heart disease at an advanced stage. However, the values did not often exceed the CRP cutoff used to diagnose acute inflammation [117].
In our study [118] analyzing healthy controls and patients suffering asymptomatic chronic Chagas' disease or heart and gastrointestinal diseases, CRP and IL-6 were significantly increased, mainly in the patient group suffering heart disease. In this group, CRP and IL-6 were found to be above the inflammation-specific cutoffs in 41 and 71% of the patients, respectively. Additionally, CRP and IL-6 concentrations and the percentage of patients with values above the cutoffs increased with the severity of heart disease. However, we also found a distinct number of patients in the asymptomatic and gastrointestinal groups who presented with CRP and IL-6 concentrations above the cutoffs.
In contrast, another study failed to demonstrate significant CRP changes in Chagas' heart and gastrointestinal diseases compared to healthy subjects and asymptomatic patients, although there a more pronounced variability in the CRP values in symptomatic patients was found [119].
Recently, it was suggested that patients with Chagas' heart disease could be more affected by cytokine release than patients with idiopathic dilated cardiomyopathy. Although this was reflected by IL-6 levels, TNF-α levels were not found to be different between the two groups of diseases. However, for both diseases, the markers were higher than in healthy subjects [120], and the IL-6 level correlated with the outcome. For TNF-α, comparable values, which were clearly higher than those for healthy subjects, were found in asymptomatic patients and in those with Chagas' heart disease presenting with LVEF > 50%. Patients with LVEF < 50% showed even higher values [121]. In addition to this TNF-α relationship with the disease stage, differences between healthy subjects and asymptomatic and symptomatic patients were also seen in nitric oxide levels [122]. In contrast, different TNF-α concentrations between healthy subjects and patients with mild cardiomyopathy were sometimes not evident, whereas differences between mild and severe diseases could be substantiated [123]. Patients suffering from both HIV infection and Chagas' disease showed higher TNF-α and IL-6 levels than patients with HIV infection only [124].
In summary, the acute disease stage is detected by profound changes in the pattern of acute-phase proteins and cytokines, which could be of interest as laboratory medicine tools for patient guidance of this stage. Unfortunately, the data for acute-phase protein and cytokine measurements in chronic Chagas' disease are inconsistent. Consequently, the impact of these markers as laboratory medicine tools for the guidance of chronic Chagas' patients is still restricted, especially for monitoring the progress from the asymptomatic stage to the symptomatic stage.
Oxidative stress markers
Oxidative stress has been defined as a metabolic condition characterized by imbalances in the equilibrium status of the pro-/antioxidant system in favor of pro-oxidants. Under aerobic conditions, the formation of pro-oxidants, often named reactive oxygen species (ROS), is strongly associated with physiological processes. Reactive oxygen species are formed as products or by-products of phagocytosis, uric acid formation via xanthine oxidase and oxidative phosphorylation, as well as in the metabolism of eicosanoids, catecholamines and xenobiotics. After the overstimulation of these processes, which have been reported to occur in many pathophysiological situations including, among others, hypoxia, hyperoxia, ischemia, inflammation and intoxication, ROS can be produced in excess. In this case, ROS react with molecular structures in all major chemical classes found in living cells to realize their toxic potential, ultimately leading to cell death. In particular, the cell-damaging potency of thiol oxidation, lipid peroxidation and DNA degradation has been extensively documented. Hypochlorite and reactive nitrogen species are generated by the reaction of ROS with chloride or NO, accelerating the toxic potency of ROS. Consequently, oxidative stress has been implicated by a growing body of evidence in human diseases including diseases of all major organs and physiological systems [125, 126]. Therefore, it is not surprising that oxidative stress has also been discussed as a pathogenetic factor in heart failure [127], especially also in Chagas' heart disease [128, 129]. With respect to this, treatment with antioxidative agents has been tested to protect patients with Chagas' disease [130].
The inflammatory processes in Chagas' disease seem to be mainly associated with ROS generation. As beneficial processes, ROS production of granulocytes and macrophages contributes to parasite phagocytosis. Therefore, neutrophil granulocytes lose their capability of phagocytosis when their ROS production is inhibited [131]. The excessive activation of macrophages (acute inflammation) or long-term stimulation during chronic infection, as seen in Chagas' disease, has resulted in excessive and uncontrolled ROS production [132, 133].
Mitochondrial damage in Chagas' disease was suggested as a further source of excessive ROS generation, especially in the case of heart affection [134, 135]. Treatment with antioxidant compounds prevented mitochondrial alteration and reduced ROS production [136]. In advanced Chagas' heart disease, hypoxic and ischemic conditions (e.g., via xanthine oxidase–produced ROS) could be further sources of ROS.
The first evidence of oxidative stress in Chagas' disease came from animal experiments, which indicated an increase in oxidative stress during the acute phase of T. cruzi infection. Increased oxidative stress in the serum became visible via the elevation of lipid peroxidation and protein carboxylation products. In parallel, a compensatory increase in the antioxidant capacity was also observed. The acute infection was followed by a time of reduced oxidative stress. However, as with the preceding disease, the chronic stage of Chagas' disease was again accompanied by increased oxidative stress alongside a reduction in antioxidant defense [137–140]. An increasing number of markers have been suggested as laboratory medicine tools to monitor oxidative stress in humans [125, 126]. Among these markers, myeloperoxidase, which is localized in neutrophil granulocytes, monocytes and tissue macrophages, is one of the molecular producers of the hypochlorite needed for parasite defense, but its excess production can be responsible for tissue damage. In cases of excessive stimulation of inflammation cells, myeloperoxidase is released into the serum. In acute coronary syndrome and heart failure, the resulting serum levels of myeloperoxidase are of prognostic value [141]. Elevated myeloperoxidase activity has also been observed in the serum of Chagas' patients [142]. Other markers used in human studies were products of lipid peroxidation, protein oxidation and protein nitration. The measurement of antioxidant defense compounds, such as antioxidant enzymes and non-enzymatic antioxidant compounds, has also been used to assess oxidative stress in Chagas' disease. It was recently demonstrated that increased oxidative stress, as indicated by malone dialdehyde elevation in the plasma, correlated with mitochondrial dysfunction in Chagas' patients [143]. Additionally, in this study, the lower blood activities of antioxidant enzymes (total superoxide dismutase, manganese superoxide dismutase and glutathione peroxidase) and non-enzymatic antioxidant glutathione were found. Decreased antioxidant defense was also demonstrated in other studies [144, 145]. A selenium deficiency was found in chronic Chagas' patients, especially in those with progressed cardiomyopathy [146]. Although selenium is essential for glutathione peroxidase, which is one of the main constituents of the antioxidant defense system, the activity of this enzyme did not decrease in chagasic patients.
Heart-specific markers
B-type natriuretic peptides (BNP, NT-proBNP) are now well accepted for diagnosing and monitoring heart failure [147]. Therefore, it is not surprising that these markers have already been tested in patients with Chagas' heart disease, where it was found that levels of BNP increase with disease severity [148–155]. In patients with chronic Chagas' disease, characterized by LVEF < 40%, levels of BNP were significantly higher than those in patients with LVEF > 40%. The last patient group was not significantly different from healthy controls [148]. The level of BNP was found to be negatively correlated with the LVEF. Based on a specific BNP cutoff point, left ventricular dysfunction was detected with a high sensitivity, specificity and negative predictive value in chronic chagasic patients [148, 149]. Recently, it was suggested that the combination of ECG and BNP is the best strategy for detecting left ventricular dysfunction in chronic Chagas' patients [156] and that this combination is superior compared to the conventional strategy of ECG and chest X-ray. With respect to the economic and logistics situations in endemic areas, this laboratory medicine–supported strategy was recommended as a first-line strategy in the recognition of LV dysfunction in Chagas' disease.
A further finding for BNP in Chagas' heart disease was that BNP elevation is related to the 6-min walking distance [157]. However, no relationship with the BNP level was found when the exercise capacity of Chagas' heart patients was analyzed [158]. It was recently found in a group of patients with chagasic cardiomyopathy that the BNP level correlated with diastolic function patterns, regardless of the systolic function [159]. Using end points such as death and heart transplantation, BNP predicts the outcome of Chagas' patients [154, 155]. Higher values for the marker NT-pro-BNP were also demonstrated in chagasic patients with heart disease [160–162].
The cardiac troponins I and T (cTnI; cTnT) have become another cornerstone in modern laboratory medicine. Troponins were established as markers for the diagnosis, risk stratification and therapy monitoring of patients with acute coronary syndrome [163]. However, there are numerous other physiological heart stressors, for example exercise [164], general pathologies affecting the heart [165] and cardiac diseases such as stable angina, myocarditis and heart failure [166, 167], that are accompanied by serum cardiac troponin values which are clearly different from those of healthy controls (although they might be below or near the established cutoff values for non-ST elevation infarction).
Many of the conditions associated with the mild cardiac troponin release of "non-necrotic" origin are associated with inflammation. This was recently shown for a runner's cardiac troponin release [168]. With respect to the inflammation background in chronic Chagas' disease, especially that derived from focal inflammation spots and microlesions found in the chagasic heart, we suggest that chronic Chagas' patients with heart disease could present with increased levels of cardiac troponin in their blood. However, there have only been two previous studies and a single patient observation that analyzed cardiac troponin levels in Chagas' heart disease [169–171]. These studies did not indicate a profound relationship between Chagas' heart disease and cardiac troponin release, probably because of the insufficient sensitivity of the assays (below or near the 99th percentile of the reference population). However, the recently available highly sensitive cardiac troponin assays with an almost tenfold increase in sensitivity compared to former assays could supply the platform for renewed activities to establish cardiac troponin measurements as a hopeful tool for the diagnosis, risk assessment and monitoring of chronic Chagas' patients who develop heart injury. Recently, we presented the first data that demonstrated increasing cTnT concentrations in the blood of chagasic patients suffering from mild to severe cardiomyopathy [118]. Compared with healthy controls, asymptomatic Chagas' patients, patients with chagasic gastrointestinal disease and patients with Chagas' heart disease had significantly higher cTnT values, which were correlated with the severity of the cardiomyopathy. Although cTnT was not measurable in the majority of healthy controls, asymptomatic patients and patients with chagasic gastrointestinal disease, i.e., 37% of the patients with Chagas' heart disease, had measurable cTnT concentrations, and 13% showed cTnT values above the cutoff for non-ST elevation myocardial infarction. The lower limit of detection for this highly sensitive assay was the best at distinguishing between patients with and without heart injury. Changes in the levels of CRP and IL-6 were found to be parallel to cTnT changes both in the different Chagas' disease groups and in the cardiomyopathy groups separated by disease severity.
Based on sensitivity and specificity, we agree that laboratory medicine guidance of chronic Chagas' patients is inferior compared to cardiological diagnostics and monitoring especially using echocardiography and, in particular, MRT. However, cardiological diagnostics is cost and labor intensive, dependents on highly qualified staff, and is only available in special centers that are often far from patients' homes; therefore, cardiological diagnostics is attached to important economical and logistics problems that are particularly relevant to its common application in endemic areas of Chagas' disease. In contrast, laboratory medicine enables sampling to be performed where patients are situated and subsequent economical investigations of the samples at highly specialized and automated centers, guaranteeing the highest quality service. Therefore, modern tools of laboratory medicine, such as heart markers, should be used to supplement the diagnosis and monitoring of Chagas' heart disease, especially for increasing the pre-test probability for the cardiological diagnostics.
The disease was named in honour of the Brazilian physician Carlos Chagas (born in 1879 in Oliveira, died in 1934 in Rio de Janeiro) who, in 1909, discovered a new trypanosome species in the intestine of the triatomine bug, which he named T. cruzi in honour of his mentor Oswaldo Cruz. A biographical sketch of Carlos Chagas was recently published in memory of the discovery of T. cruzi 100 years before (Moncayo A (2010) Carlos Chagas: biographical sketch. Acta Trop 115:1–4).
We are grateful to "Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin" and "Europäischer Fonds für regionale Entwicklung" for supporting S.G. Munoz Saravia.


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Escape North!: The Story of Harriet Tubman
Random House, 2000 - Juvenile Nonfiction - 48 pages
An easy-to-read, page-turning account of Harriet Tubman's life--from her childhood in slavery to her years as a conductor on the Underground Railroad to her later work as a suffragette and as a spy in the Civil War. This remarkable true story brings to life one of America's greatest female role models.
What people are saying - Write a review
Review: Step into Reading, Step 4: Escape North! The Story of Harriet TubmanUser Review - Karen Kight - Christianbook.com
This is an excellent book that young kids can read. Every child should be aware of what the different nationalities went through. Read full review
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Common terms and phrases
afraid BEACH PUBLIC LIBRARY beaten Ben and Old blankets Born a Slave bossman Brodas broke broom cabin called Camden climb colored conductor Cook Daddy Ben Daddy Ben's Delaware dogs Early Step ESCAPE NORTH eyes fast fell asleep fields fight find north fly north free the slaves gave Harriet going grades Harriet fell Harriet found Harriet ran Harriet remembered Harriet stood Harriet Tubman hide hunters John jumped learn to read lives long ago looked Maryland Moses moss named never run night North Star north to freedom Old Rit parents Philadelphia plantation Quaker woman readers Reading Books runaways safe house Saturday secret sent shoe silently slave catchers slavery Slaves weren't allowed slept sold song station Step 3 Book Step into Reading stop swamp taught thought back tired tobacco told took tree trip Underground Railroad VIRGINIA BEACH vote wagon wanted Wilmington women woods yarn

subset: commoncrawl


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The Hacker's Lair on Mushu Island attraction, which recently celebrated its long anniversary
It's an island built as a tribute to Boudin -- only with less Mushu and more hackers! Guests can stumble through hacker caves, hide behind hacker bone cages, and jump into graves behind a fort destroyed by budgetary issues!
Please don't try Pirate Mode
© copyright 2011–2016
A Pants Aflame production


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|By PR Newswire
Article Rating:
|April 2, 2014 04:00 AM EDT
KALAMAZOO, Mich., April 2, 2014 /PRNewswire/ -- Ablative Solutions, Inc., a privately-held clinical stage company, announced today that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for its Peregrine System™ Infusion Catheter.
The Peregrine System uses a unique, patent-pending technology to deliver diagnostic and therapeutic agents directly to the perivascular layer that surrounds blood vessels. This region is dynamic and consists of sympathetic nerves, lymphatic vessels, and a rich diversity of cells that can influence blood vessel function, repair and disease. For example, it has recently been shown that overactive sympathetic nerves residing in the perivascular space are associated with hypertension, metabolic syndrome, congestive heart failure and obesity.
"Ablative Solutions is pleased to make the Peregrine System available to clinicians to deliver therapies targeted to the perivascular zone," said Vartan Ghazarossian, PhD, President of ASI.
"Cardiovascular disease can impact so many aspects of patient health," observed Prof. Dr. med. Horst Sievert, Director and Founder of the Cardiovascular Center Frankfurt (CVC Frankfurt). "As we deepen our scientific understanding of the underlying disease processes, advances in technology can facilitate further insight and can aid in the development of better treatments. I am eager to work with the Ablative Solutions team to explore how to incorporate the Peregrine System into clinical practice."
About ASI
Ablative Solutions was founded in 2011 by Tim Fischell, MD, FACC, and David Fischell, PhD, and is headquartered in Kalamazoo, MI, with offices in Menlo Park, CA. Ablative Solutions has developed endovascular catheters that are designed to provide a durable and cost-effective means for the targeted delivery of diagnostic and therapeutic agents to the perivascular space of blood vessels to address life-threatening diseases.
Forward-Looking Statements
This press release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995. Information in this press release, which is not historical, is forward-looking and involves a number of risks and uncertainties. Investors are cautioned not to put any undue reliance on any forward-looking statement. ASI's actual results may differ materially from ASI's historical results of operations and those discussed in the forward-looking statements for various reasons, including, but not limited to ASI's ability to carry out its business plan, successful development and commercial acceptance of its products, ability to fund development necessary for existing products and for the pursuit of new product opportunities, ability to hire required personnel, the risk of whether products result from development activities, protection of ASI's intellectual property portfolio, the risk associated with obtaining the necessary regulatory approvals, the ability to obtain foreign regulatory approvals for products and to establish marketing arrangements in countries where approval is obtained, and other potential factors.
For more information:
Vartan Ghazarossian, PhD
(650) 321-6884
SOURCE Ablative Solutions, Inc.
SYS-CON Events announced today that 910Telecom will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Housed in the classic Denver Gas & Electric Building, 910 15th St., 910Telecom is a carrier-neutral telecom hotel located in the heart of Denver. Adjacent to CenturyLink, AT&T, and Denver Main, 910Telecom offers connectivity to all major carriers, Internet service providers, Internet backbones and ...
Aug. 31, 2016 09:00 PM EDT Reads: 2,073
We are always online. We access our data, our finances, work, and various services on the Internet. But we live in a congested world of information in which the roads were built two decades ago. The quest for better, faster Internet routing has been around for a decade, but nobody solved this problem. We've seen band aid approaches like CDNs that attack a niche's slice of static content part of the Internet, but that's it. It does not address the dynamic services-based Internet of today. It doe...
Aug. 31, 2016 09:00 PM EDT Reads: 308
SYS-CON Events announced today that Numerex Corp, a leading provider of managed enterprise solutions enabling the Internet of Things (IoT), will exhibit at the 19th International Cloud Expo | @ThingsExpo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Numerex Corp. (NASDAQ:NMRX) is a leading provider of managed enterprise solutions enabling the Internet of Things (IoT). The Company's solutions produce new revenue streams or create operating...
Aug. 31, 2016 08:15 PM EDT Reads: 301
Qosmos has announced new milestones in the detection of encrypted traffic and in protocol signature coverage. Qosmos latest software can accurately classify traffic encrypted with SSL/TLS (e.g., Google, Facebook, WhatsApp), P2P traffic (e.g., BitTorrent, MuTorrent, Vuze), and Skype, while preserving the privacy of communication content. These new classification techniques mean that traffic optimization, policy enforcement, and user experience are largely unaffected by encryption. In respect wit...
Aug. 31, 2016 07:45 PM EDT Reads: 1,964
While DevOps promises a better and tighter integration among an organization's development and operation teams and transforms an application life cycle into a continual deployment, Chef and Azure together provides a speedy, cost-effective and highly scalable vehicle for realizing the business values of this transformation. In his session at @DevOpsSummit at 19th Cloud Expo, Yung Chou, a Technology Evangelist at Microsoft, will present a unique opportunity to witness how Chef and Azure work tog...
Aug. 31, 2016 07:15 PM EDT Reads: 240
The Internet of Things can drive efficiency for airlines and airports. In their session at @ThingsExpo, Shyam Varan Nath, Principal Architect with GE, and Sudip Majumder, senior director of development at Oracle, will discuss the technical details of the connected airline baggage and related social media solutions. These IoT applications will enhance travelers' journey experience and drive efficiency for the airlines and the airports. The session will include a working demo and a technical d...
Aug. 31, 2016 07:00 PM EDT Reads: 260
SYS-CON Events announced today that Isomorphic Software will exhibit at DevOps Summit at 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Isomorphic Software provides the SmartClient HTML5/AJAX platform, the most advanced technology for building rich, cutting-edge enterprise web applications for desktop and mobile. SmartClient combines the productivity and performance of traditional desktop software with the simp...
Aug. 31, 2016 06:30 PM EDT Reads: 2,532
Although it has gained significant traction in the consumer space, IoT is still in the early stages of adoption in enterprises environments. However, many companies are working on initiatives like Industry 4.0 that includes IoT as one of the key disruptive technologies expected to reshape businesses of tomorrow. The key challenges will be availability, robustness and reliability of networks that connect devices in a business environment. Software Defined Wide Area Network (SD-WAN) is expected to...
Aug. 31, 2016 06:15 PM EDT Reads: 299
Between the mockups and specs produced by analysts, and resulting applications built by developers, there exists a gulf where projects fail, costs spiral, and applications disappoint. Methodologies like Agile attempt to address this with intensified communication, with partial success but many limitations. In his session at @DevOpsSummit at 19th Cloud Expo, Charles Kendrick, CTO at Isomorphic Software, will present a revolutionary model enabled by new technologies. Learn how business and deve...
Aug. 31, 2016 06:15 PM EDT Reads: 216
DevOps at Cloud Expo – being held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA – announces that its Call for Papers is open. Born out of proven success in agile development, cloud computing, and process automation, DevOps is a macro trend you cannot afford to miss. From showcase success stories from early adopters and web-scale businesses, DevOps is expanding to organizations of all sizes, including the world's largest enterprises – and delivering real results. Am...
Aug. 31, 2016 06:15 PM EDT Reads: 3,626
Developing software for the Internet of Things (IoT) comes with its own set of challenges. Security, privacy, and unified standards are a few key issues. In addition, each IoT product is comprised of (at least) three separate application components: the software embedded in the device, the back-end service, and the mobile application for the end user's controls. Each component is developed by a different team, using different technologies and practices, and deployed to a different stack/target –...
Aug. 31, 2016 05:15 PM EDT Reads: 297
SYS-CON Events announced today that Hitrons Solutions will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Hitrons Solutions Inc. is distributor in the North American market for unique products and services of small and medium-size businesses, including cloud services and solutions, SEO marketing platforms, and mobile applications.
Aug. 31, 2016 05:00 PM EDT Reads: 881
Internet of @ThingsExpo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 19th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The Internet of Things (IoT) is the most profound change in personal and enterprise IT since the creation of the Worldwide Web more than 20 years ago. All major researchers estimate there will be tens of billions devices - comp...
Aug. 31, 2016 04:45 PM EDT Reads: 3,853
Enterprises have forever faced challenges surrounding the sharing of their intellectual property. Emerging cloud adoption has made it more compelling for enterprises to digitize their content, making them available over a wide variety of devices across the Internet. In his session at 19th Cloud Expo, Santosh Ahuja, Director of Architecture at Impiger Technologies, will introduce various mechanisms provided by cloud service providers today to manage and share digital content in a secure manner....
Aug. 31, 2016 04:15 PM EDT Reads: 984
As the world moves toward more DevOps and Microservices, application deployment to the cloud ought to become a lot simpler. The Microservices architecture, which is the basis of many new age distributed systems such as OpenStack, NetFlix and so on, is at the heart of Cloud Foundry - a complete developer-oriented Platform as a Service (PaaS) that is IaaS agnostic and supports vCloud, OpenStack and AWS. Serverless computing is revolutionizing computing. In his session at 19th Cloud Expo, Raghav...
Aug. 31, 2016 04:00 PM EDT Reads: 1,145


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The 5 Most Dangerous Neighborhoods in Wichita Falls
There are good and bad areas to every city. Which Wichita Falls neighborhoods are the most dangerous?
There are good and bad areas to every city. Which Wichita Falls neighborhoods are the most dangerous?
NaDonna Norris, owner of Davenport Grocery on the east side of Wichita Falls, passed away suddenly this past weekend just days shy of her 50th birthday.
'The Texas Bucket List' spent today at Willie's Place filming an upcoming segment at the Wichita Falls restaurant.
When I tell you that political correctness has invaded every aspect of America from your living room to Washington, DC, believe me, it has.
The Resource Center, a service center for the LGBT community in Dallas, is asking the city to cut ties with former Wichita Falls pastor Robert Jeffress after comments he made on a radio show.
Most of America might look forward to Memorial Day because it gives us a three-day break from our hectic work lives and an excuse to grill great gobs of red meat over an open pit, but it's intentions are much nobler.
Greg Stockton of Golden Chick receives the highest honor from the Texas Restaurant Association.
People from Kohl's were so impressed with Candace Payne's hysterical Chewbacca mask video, they showed up at her house with a big surprise!


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Oceanside Harbor battle ended?
Fishing businesses chart courses for zero conflict
Ken Harrison 6:45 p.m., Aug. 23
Sign along Sunset Highway near Portland inviting people to stop at a produce stand & pick up some delectable strawberries!
Image posted by pearljammed
June 3, 2013
Ken Harrison 6:45 p.m., Aug. 23
Ian Anderson 6 p.m., Aug. 23
Matt Potter 4:30 p.m., Aug. 23
Dorian Hargrove 2:30 p.m., Aug. 23
Jay Anderson 1:30 p.m., Aug. 23
Julie Stalmer 11:30 a.m., Aug. 23
Larry Steckling 10 a.m., Aug. 23
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Kapadokya Mediterranean Grill
Location & Contact:
Located on Route 1 south, just south of New Brunswick and North of Princeton; this quaint eatery will feature the best in Mediterranean cuisine!
Once we know when Kapadokya Mediterranean Grill will open we will post it here!
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Dine in or take out, Panico's Brick Oven Pizza is the perfect destination for a casual dinner with f…Read More
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Warm cookies Straight from our oven to your door! Open until 4am on weekends! order online today! …Read More
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120 Albany Street, New Brunswick
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Located in Middlesex County, Ria Mar is one of the few NJ restaurants that has been serving traditio…Read More
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Love me.
Love me.
"Almost Seemed An Eternity"
Wisconsin Horizons By Phil Koch.
2546 West Clybourn Street, Milwaukee.
Really like this 💜 (sorry not sorry)
As insurers push large premium increases for 2017 Obamacare plans, some of the steepest hikes have been requested by insurers in crucial swing states that could determine control of the Senate.
In nine of 11 states with competitive Senate races, at least one insurer seeks to hike rates for Obamacare customers by at least 30 percent next year: Highmark Blue Cross Blue Shield in Pennsylvania wants to jack up average premiums by more than 40 percent. In Wisconsin, three insurers have asked for rate hikes of more than 30 percent. In New Hampshire, two of the five carriers want to sell plans with rate increase above 30 percent.
The potential sticker shock — coupled with the likelihood many consumers will have fewer choices next year after major insurers scale back their exchange participation — creates a potential political opening for Republican candidates, especially since the next Obamacare enrollment season starts one week before Election Day.
"People who are feeling it in their pocketbooks are going to be very unhappy about [rate hikes]," said Brian Walsh, a former communications director for the National Republican Senatorial Committee. "You would expect to see this will be part of the campaign messaging for House and Senate Republicans. … If it hasn't started, it will be coming."
Read more here
Hey my name is Savannah ❤ 18 Wisconsin. Looking for friends and maybe a little more. My snapchat is @Savannahiepoo hit me up!
Wisconsin Horizons by Phil Koch
CNN just called the election for Bernie! #FeelTheBern🔥
A camper finds insect eggs under a lily pad in Wisconsin, 1974. Photograph by Steve Raymer, National Geographic Creative
Racine, Wisconsin, 1890
The state of "Fighting Bob" La Follette wouldn't let down the political revolution, I am sure of it.
FOUND: yellow-green male parakeet in Hudson WI in the Ford dealership parkinglot.
He is safe, eating and drinking, and super friendly!
If this is your bird please contact me with photo proof and we will get in contact with you in hudson asap. This little fellow will be coming home to my hospital cage and staying with me until his people are found.
Please signal boost! Even if you don't live in Wisconsin you may have followers who do.
Thank you! Let's hope this sweetie gets home as safe as he found his way to the crazy bird lady!
First lake day of the summer 💦
Say it with me, YES! #Bernie
From yesterday's excursion into the Wisconsin Dells, behold: The dreaded Castle of Error.
Keep voting for my boy Sanders! #Love it!
More from the morel house


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tynauri. Subscribe Subscribed Unsubscribe 43. Loading... Loading... Working... Created playlists. 137 videos Play all Play now; niii - Playlist. 91 videos ... - read more
seqsi Minda shentn, seqsi minda shentn, Georgian, Russian, Translation, human translation, automatic translation. - read more
Please vote if the answer you were given helped you or not, thats the best way to improve our algorithm. You can also submit an answer or search documents about seqsis chveneba minda.


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Students Severely Burned Because of Sunscreen Ban at School
Tiffany Raiford
When 11-year-old Violet and her 9-year-old sister, Zoe, went to school last week for an all-day outdoor school event, no one suspected that they would soon be the subject of national outrage — and all because of a sunscreen ban. The two girls were not permitted to apply sunscreen, despite the fact that both girls were clearly burning under the hot ...
Spicy Gingersnaps to Amaze Your Guests
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I've always loved gingersnap cookies. And my hubby is a serious addict when it comes to cookies of any kind — although these spicy gingersnaps are his absolute favorite! If you're looking for a great recipe to add to your holiday baking repertoire, this is the one you've been looking for. It's delicious, super simple to make, and everyone that ...
Spring Cleaning Tips for REAL Moms
Jae Curtis
I always have to laugh when I see magazine articles about spring cleaning tips for moms. While I totally appreciate the suggestions ("mix baking soda with water for a cleaning paste!"), some of the logistics can be be problematic. For example, I don't know about you, but when I try to clean, my kids follow right behind, pulling out toys and ...
Strawberry Cornbread Recipe
Mandy Fayne
As I was dreaming up my Thanksgiving menu and thinking of a new cornbread to bake, my daughter was busy giving her princesses time outs — she told me they were making a mess (I wonder how she came up with that scenario). I realized the time outs were becoming ineffective once my daughter started asking if she could have a time out. Our new ...
Studies and Articles on Stress in Autistic
State the Obvious
Elizabeth Dunn
Articles on stress say that autistic children can be a big cause for moms, my first thought is, "Well, of course!" Perhaps I've lived in the autism bubble so long that I forget the average person doesn't know what we autism moms go through every day. And while I would love to educate the world about autism and its effects on the
, I need to ...
Songs About Being A Mom - Touch My Heart
There is this song out there that I heard recently by Taylor Swift and I fell in love. I love songs about being a mom. There are some great songs about being a mom out there. I know that a lot of country singers have written them. Taylor Swifts song is Never Grow Up. It's probably one my favorite songs about being a mom. Let me tell you some of ...
Soothing the Ache When a Grandparent Dies
It's difficult when a grandparent dies. Let's face it - here's this person you've looked up to your whole life, who has loved you and nurtured you, and done their best to lovingly spoil you... and suddenly, that person is gone. Knowing how to deal with death of a loved one can be very difficult for adults. I can only imagine how hard it would be ...
Should Mothers Feel Guilt for not Breastfeeding?
When Norton was born, it was no secret: I was not breastfeeding. I had very personal reasons for not breastfeeding that I have shared numerous times in my blog. In a nutshell, all of those infant bonding benefits seemed less likely when there was a very real danger of covering my child with vomiting at every feeding session. I don't feel any guilt ...
Sisters Campaign for a Puppy Via Facebook
Virginia Williams
This cute story is proof that the power of social media should never be underestimated. Two sisters wanted a puppy so badly that they — inspired by a similar Facebook campaign — bet their dad that they could get one million "Likes" on Facebook just by posting a photo of themselves with a poster saying how much they wanted a new dog. If the two ...
Snoring Toddlers May Be More Likely to Misbehave
Leeann Teagno
A new study suggests that snoring in toddlers may make them more prone to behavioral difficulties. According to U.S. News and World Report , the study shows that toddlers who snore persistently are more likely to exhibit problems with attention deficit, hyperactivity, and even depression compared to toddlers who don't. The study, published in the ...
Sleep Disorders Misdiagnosed as ADHD in Kids
Nicole Stevens
Attention Deficit Hyperactivity Disorder (ADHD) appears to be a growing problem in America. Millions of children have been diagnosed with the condition, and the number of kids on stimulant medication to help control symptoms is rising. But several studies suggest that at least in some cases, children diagnosed with ADHD may be suffering instead ...
Specific Learning Disabilities Often Occur in Pairs
Carolyn Buchanan
On average, two to three students per classroom have learning disabilities, says a new study published in a special Education edition of the journal Science . Up to 10 percent of the total population have some type of specific learning disability (SLD) including autism, attention deficit hyperactivity disorder, and dyslexia, and many have more ...
Single Mom's Stress: Playing With Kids Can Reduce Symptoms
Erica Loop
Most moms know that sustained mother-child playtime has tremendous benefits for the child, but what about the parent? A new study claims that single mom's stress may decrease as a result of interacting with their children. According to Reuters , researchers surveyed 2,370 single moms on their perceived stress levels and the amount of time that ...
Sperm May Carry Dad's Stress to Offspring
Carolyn Buchanan
Summary: Dad's exposure to stress may affect the way offspring respond to stressful scenarios, a new study found. Of course, there isn't much you can do about a stressful past, but you can head off present and future stress by being aware, recognizing the symptoms, and applying some stress-reducing strategies to help you, and your mate to better ...
Simple Saliva Test May Predict Violent Behavior in Boys
Carolyn Buchanan
Could it be as simple as a saliva test? A new study suggests that saliva may carry the code to aggressive and violent behavior in young boys: There may be a link between salivary concentrations of particular hormones and aggression. The study led by Drew Barzman, MD, a child and adolescent forensic psychiatrist at Cincinnati Children's Hospital ...
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Very interesting research on Islam-Mahdi-Antichrist & The Mark of the Beast
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Great! Then lets form an allience: Christians, Jews, Atheist, Whites, Blacks nonbelievers. All who have problems with Muslims and dont like the Fascist Koran Can all Join me! And form a Christian Messiah Jesus Liberation Army!
Those who is not with me is against Christ! And those who is with me is with Christ. Lets do something together, i am here saving yall' asses why just sit here and waiting for persecution of the muslim army. Such a wimps!
lol..Round 2 of the Crusades??
religion is the root of all man kinds troubles
Be a part of 144.000 who will slaughter the wicked ones of the face of the earth!!!
No Thank You!
Just ignore those types of posts they can be deceiving and misled. I suggest Haile Menelik search for truth in Lord Jesus Christ only He will wash all your sins away if you truthfully ask Him in prayer in repentance.
Jesus Christ is our Lord and Savior.
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text: This is the place you want to go especially, with our hot August sun. By far the COOLEST on the boardwalk. Nice friendly service and the salted caramel ice cream can't be beat. Truly a nice little respite when you want to get out of the sun and the heat.


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Panama Is Coming Again!
March 23, 2007
I don't know if any other international PPC agencies, or individuals, have received their notification, but we received our first one this morning: Yahoo'!'s Panama is coming to the UK! The migration letter is the same one distributed to US advertisers (aside from being slightly anglicized) so there aren't any new developments regarding the migration process. Finally, the USA has an export of epic proportions to volley back at those Brits… of course, The Beatles, Led Zeppelin, the Rolling Stones, and Eddie Izzard are going to be hard to beat, but I think Panama is up for the challenge.
Expanded Text Ads And Other Bing Ads Editor Updates
Pilot access for Expanded Text Ads is now available to Bing Ads users. Get access to the link and learn about other new features in the latest Bing Ads Editor update.
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Where do you go to get the most relevant information in PPC, plus the opportunity to network with the best and brightest the industry has to offer? Why Hero Conf, of course.
3 Questions You Need To Answer Before Beginning Paid Advertising
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Check out these classy folks as they show off their talents!
Pull up your red diaper and go on an adventure with the best talking animal...
Every other Monday, our team of blacksmiths and craftsman build some of you...
dare public
You should see what's in his backpack.
Best Backpack Ever
Stuff keeps falling out the bottom
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Cat backpacks are all the rage right now.
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Those backpacks look like they are having fun.
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at a camp in the city some friends of my picked up some hot swedish backpac...
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Ability to close sales. BS in Management, Sales or Marketing required. Strong track record in building business and increasing sales....
Jun 27 - Los Angeles, CA
Experience in sales is a plus. We're looking for a high-energy call center agent....
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Jul 3 - Carson, CA
A minimum of seven years of experience in Human Resources Business Partner positions with a complex corporation (manufacturing or industrial industry preferred)...
Jun 24 - United States
Oerlikon is a leading high-tech industrial group specializing in machine and plant engineering. The Company is a provider of innovative industrial solutions and...
Aug 23 - United States
Outside Sales Rep - Chemicals Industry (Bilingual Japanese/Eng. Lang.)
International Chemicals Distributor seeks an Outside Sales Representative for their South Bay, LA office. Some sales or business experience desired.Outside sales background is a plus, but not required.Bilingual Japanese/English language skills required.Must be able to travel. This is a full-time, direct hire position with benefits. To apply, please send your resume as a MS Word attachment.In ...
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Torrance - Sales & biz dev
With $29 billion in sales, about 87,000 employees worldwide and operations in 100 countries.We have 66 years leading innovation, quality and commitment to the...
May 18 - United States
Sales Coordinator - Aerospace Industry
A major aerospace firm is seeking a Sales Coordinator for their Torrance office. This candidate will fulfill a variety of support responsibilities ranging from coordinating to taking initial lead in relations to flight operations.
- Bilingual English/Japanese language is a MUST
- Previous customer service experience is a PLUS
- Aircraft experience is a PLUS
This is a full ...
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Gardena - Administrative & office
KONE is an industry leader in Industrial Engineering. In 2015, KONE had annual net sales of EUR 8.6 billion, and at the end of the year close to 50,000...
Aug 25 - Los Angeles, CA
Highest Paid Sales Industry
Industry experience not required if you have a positive attitude and are willing to put in work to learn our system. Former mortgage reps, realtors, financial advisors, attorneys etc. have made very successful transitions into our industry. Write insurance policies on mortgages and final expense policies and make a substantial income doing so. We are looking for both, PART-TIME and FULL-TIME ...
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Pasadena - Sales & biz dev
OEM sales experience:. Ability to analyze markets, identify sales opportunities and develop/execute sales strategies.• Demonstrated communication effectiveness,...
Jul 28 - Pomona, CA
Outsides Sales Rep (Corrugated Box Industry)
International Corrugated Box company seeks an Outside Sales Rep for their LA office.
Bachelor's degree in business or related field preferred.
Outside sales experience in corrugated box industry required.
Must be able to travel.
To apply please send your resume as a Microsoft Word attachment to: [email removed]
In the email subject line please write: BoxSales-ebay-EK
Aug 15 -
Los Angeles - Sales & biz dev
Our complete line of products includes perimeter security solutions for industrial, commercial and residential applications....
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Industrial Sales Repeat Business
Maintain and built relationships with existing and new industrial accounts.Because of online shopping, The packaging industry is on fire. DHL / UPS / FEDX / Amazon trucks are everywherethey are shipping packages. My 60 year old client sells packaging supplies and they are growing. This can be a six figured opportunityBase salary depending on experience$500 monthly car allowanceMedical and ...
Aug 12 -
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Advanced degree in HR management, Organizational Development or Industrial Relations. Bachelor's degree in Human Resources, Industrial Relations, Business...
Aug 26 - Universal City, CA
Regional Sales Manager - Infrastructure & Industry
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Aug 8 -
Los Angeles - Construction & trades
Degreed individuals with industrial sales experience will receive preferential consideration for this well paying long term position....
Jul 13 - South Gate, CA
Sales Manager [Paper Trading Industry Experience]
Sales Manager
Major International manufacturing and trading firm in the paper product industry is seeking a qualified Sales Manager for their Los Angeles / Orange County area location. The Sales Manager will be responsible for increasing current customer sales growth as well as new business development.
Required Qualifications:
- Bachelor's Degree preferred
- 10+ years of sales experience ...
Aug 2 -
Whittier - Sales & biz dev
As manufacturers of paperboard products and industrial point-of-purchase packaging, Smurfit Kappa Orange LLC's goal is to provide all of its customers with...
Apr 29 - Carson, CA
Sales Manager - Industrial Filtration (Los Angeles, CA)
SALES MANAGER – INDUSTRIAL FILTRATIONWe are a 35 year old company in Los Angeles, CA and Austin, TX and manufacture filtration products with a global customer baseThe position is a non-supervisory role and expectation is the successful candidate will be self motivated and able to work as part of a team to develop a profitable sales portfolio in a timely manner. We are lean and non ...
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Los Angeles - Sales & biz dev
Automotive, Information & Communications, Electronics, Environment & Energy, and Industrial Materials. The group companies in North and South America generate...
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Demonstrated knowledge of policy distinctions between gifts, grants and contract mechanisms for industrial support of university programs....
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Sales Manager - 75K to 150K Yearly - Lifeline Wireless Industry
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Culver City - Business & management
Business, Supply Chain, Industrial Engineering or Finance preferred. Update supply requirements by collaborating with the Operations and Sales teams....
Aug 9 - Los Angeles, CA
Sales Executive / Account Manager - Aviation/Ground Support Industry
We are a fast growing, dynamic west coast firm in the Aviation / Ground Support industry, located in the San Fernando Valley, in Los Angeles.Career Description:• Generate new business in the Aviation and Ground Support industries via sales calls and meetings.Qualifications:• Bilingual Required (English & Spanish).• Must be self-motivated, initiative-oriented, energetic, positive, and ...
Jul 26 -
Los Angeles - Sales & biz dev
Industrial Sales Representative
Job profile:Provide sales support for existing customers in the industrial coatings market. Sales calls would be required on owners, buyers, finishing supervisors and engineers. Develop new accounts by improving our relationships with key decision makers. Have working knowledge about liquid coating application and have the ability to work with customers to improve coating properties and ...
Jul 19 -
Los Angeles - Sales & biz dev
Industrial/Manufacturing Sales Representative
Our client is a Global manufacturer of Awnings with a plant in the Los Angeles area and is looking for a hungry and entrepreneurial West Coast Sales Representative to help further develop their dealer base and make a significant contribution to their continued success!WHAT THIS COMPANY OFFERS YOU: Excellent Compensation including base salary + bonusOutstanding BenefitsStrong Growth Potential ...
Jul 14 -
Los Angeles - Sales & biz dev
Jul 13 -
San Fernando - Business & management
Food Industry Sales Representative [Bilingual Japanese/English Lang]
Sales Representative
An international wholesaler/distributor in the seafood industry is seeking a qualified Sales Representative for their Los Angeles area location. This person will be responsible for managing accounts with new and existing clients in the food industry.
Required Qualifications:
- Fluent Bilingual language abilities in Japanese/English languages (speak, read & write)
- 2-3 ...
Jul 5 -
Los Angeles - Sales & biz dev
Sales Representative (Industrial and Commercial Lighting)
Cam-Air, LLC is a premier regional energy consultancy helping businesses reduce lightening expenses and make long-term capital improvements through custom engineered LED retro-fitting in addition to other energy conserving products.We are expanding and developing our sales department to accommodate regional independent territory managers. We provide you with thorough training, and your job is ...
Jul 1 -
Los Angeles - Sales & biz dev
Aug 9 - United States
Hydrotex is looking for dedicated, full time, commercial, industrial field sales representatives (Lubrication Consultant)....
Aug 3 - United States
Fortive is a diversified industrial growth company comprised of global businesses that are recognized leaders in attractive markets....
Jul 15 - United States
OERL) is a leading high-tech industrial group specializing in machine and plant engineering. The new Oerlikon Surface Solutions Segment has around 6,000...
Jul 13 - United States
Minimum twelve years of experience managing the sales process and implementing sales strategies; Company Overview Rockwell Automation, the world's largest...
Jul 12 - United States
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