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At Apex, we focus on each student's lifelong success as principled and insightful leader of business and society. We aim to accomplish this purpose by emphasizing on rigorous coursework with experience, individual growth through team work, connections with alumni and corporate houses, and time tested values with innovation. All these have set us apart from others.
Apex is a small but well integrated collaborative community of students, faculty, staff and alumni with a common goal of academic excellence and professional success. And, our individual attention to each student has enabled us to create a unique learning opportunity and experience, and life long relationship with each other.
Apex graduates are contributing to local and global service firms, leading corporations and innovative new ventures.
Our people, facilities, and location have made Apex a place with unlimited opportunities for intellectual and personal growth for students and faculty alike.
Founded in 2000, Apex today is the college of choice among students seeking management education at undergraduate and graduate level.
Inspired by our well-recognized success by society, and with the continuous support of all our stakeholders, we are highly motivated to dedicate ourselves in building human capital. Always.
We stress on personal integrity and responsibility as they are the essential qualities for leadership. We foster a high level of integrity among all our students, faculty and staff through our policies, actions and teaching. We encourage everyone to make decisions and act with integrity.
We strive for excellence in everything we do by setting high standards for our programs, students, faculty, staff and ourselves as an organization.
We admire individual and intellectual difference among our students, faculty and staff. We respect ourselves and others and honor each person in our community as an individual.
We believe in and appreciate the value of diversity of cultures and opinions in society. We include and treat all kind of diversities as a source of learning. We attempt to create an environment where the values of diversity are understood, nurtured and rejoiced.
We encourage our college community to understand and develop a global perspective of business and act accordingly by staying connected with the world at large.
Located in Baneshor, Kathmandu.


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Become an Illegal Immigrant
Published: Monday, August 25, 2014 at 4:13 a.m.
Last Modified: Monday, August 25, 2014 at 4:13 a.m.
Let me get this straight. If you're an illegal immigrant from Central America, or anywhere for that matter, you get food stamps, subsidized housing, free medical and education too. Now, President Barack Obama wants to throw $3.7 billion your way.
I'm a veteran who can't find work because my résumé says I like hard work and long hours. I keep my college degree in my bathroom next to my toilet paper.
I'm facing foreclosure on my home because I can't find a lender who will refinance or assume my chump-change $62,000 mortgage. Federal programs such as HARP and Springboard can't help me because I have the audacity to live in a mobile home.
I live in the land of the free, but it's only free if you're an illegal immigrant. How do I become an illegal immigrant? Renounce my citizenship? Or should I just not push one on my phone?
Plant City
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subset: commoncrawl


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Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene have been identified in patients with heritable pulmonary arterial hypertension (PAH); however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT) Balb/c/Byj mice were exposed to house dust mite (HDM) allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP) was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR) to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations.
Citation: Mushaben EM, Hershey GK, Pauciulo MW, Nichols WC, Le Cras TD (2012) Chronic Allergic Inflammation Causes Vascular Remodeling and Pulmonary Hypertension in Bmpr2 Hypomorph and Wild-Type Mice. PLoS ONE 7(3): e32468. doi:10.1371/journal.pone.0032468
Editor: James West, Vanderbilt University Medical Center, United States of America
Received: December 12, 2011; Accepted: January 31, 2012; Published: March 9, 2012
Copyright: © 2012 Mushaben 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 research was funded by National Institutes of Health Grants U19A170235 (G.K.H.), HL097135 (T.L.C. and G.K.H.), HL102107 (W.N. and T.L.C.), HL07752 (T32; E.M.M.), and AHA 740069N (T.L.C.). 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.
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by vascular dysfunction and remodeling. Arterial remodeling causes increased pulmonary vascular resistance, resulting in sustained pulmonary artery pressures that lead to right ventricular hypertrophy and subsequently death due to right-sided heart failure [1]–[9]. Although PAH is a rare disease, once diagnosed, life expectancy is generally less than three years in adults [4], [6] and less than 1 year in children [10] without therapeutic interventions. Despite intense investigation into the pathogenesis of PAH, the etiology remains unclear and present therapies only slow disease progression [2], [4], [10].
Some insight into the pathogenesis of PAH has come from the discovery that heterozygous mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2) are present in many patients with heritable pulmonary arterial hypertension (PAH) and some patients with idiopathic PAH [1], [11]–[15]. The BMPR2 gene encodes the bone morphogenetic protein receptor type II (BMPR-II), which is a member of the transforming growth factor-β superfamily and plays a critical role in embryogenesis, apoptosis, cell growth, and cell differentiation. Upon ligand binding, the type I BMP receptor is activated by BMPR-II, causing phosphorylation and activation of downstream signaling molecules, Smads 1, 5 and 8 [16]–[19]. While approximately 70% of patients with heritable PAH have mutations in the BMPR2 gene, the disease penetrance is low, with some reports showing that only ∼10–20% of family members with BMPR2 mutations actually develop symptomatic PAH [1], [5]–[7], [13], [14]. As a result, it has been suggested that other genetic and/or environmental factors may be necessary for clinical expression of PAH in individuals with BMPR2 mutations [14].
PAH is known to occur in diseases in which inflammation is a cardinal feature (i.e. autoimmune diseases and HIV infection), leading to the suggestion that inflammation may be an important mediator or trigger of pulmonary arterial remodeling [3], [20]. In addition, data from patients with PAH have demonstrated increases in inflammatory cells in the vicinity of remodeled vessels, as well as elevated levels of pro-inflammatory cytokines such as IL-1β and IL-6 [2], [20]–[22]. Experimental studies in mice and rats have shown that inflammatory models such as chronic hypoxia [23], [24], monocrotaline [21], [25], [26], and allergic asthma (ovalbumin, Aspergillus fumigatus, house dust mite) [3], [27], [28] all develop varying degrees of vascular remodeling. These data further support a role for inflammatory pathways in vascular remodeling and disease, however, the exact involvement of these pathways remains poorly defined.
Given the potential role of inflammation in vascular remodeling [3], [21], [23]–[27] and the development of PAH in patients with BMPR2 mutations [1], [11]–[15], we hypothesized that chronic inflammation would trigger more severe arterial remodeling and PAH in mice with reduced BMPR-II signaling. To address this question we utilized Bmpr2 hypomorph mice, as Bmpr2 null mice die during early gastrulation [29]. Bmpr2 hypomorph mice have a deletion in exon 2 (hereafter referred to as Bmpr2 ΔE2 mice) that encodes half of the extracellular ligand-binding domain of the receptor [30]. This deletion results in reduced BMPR-II signaling [30] similar to that seen in patients with BMPR2 mutations [4]. Bmpr2 ΔE2 mice that are homozygous for the hypomorphic allele die during mid-gestation with cardiovascular and skeletal defects: however, mice that are heterozygous for the hypomorphic allele develop into adulthood with no apparent abnormalities [30]. In this study, we exposed wild-type (WT) and Bmpr2 ΔE2 mice to the aeroallergen, house dust mite (HDM), for 7 or 20 weeks to induce chronic inflammation, as previous studies had reported vascular remodeling in WT mice following such a protocol [27]. Muscularization of pulmonary arterioles and right ventricular systolic pressures (RVSP) were measured to assess the severity of vascular remodeling and PAH after chronic inflammation in both groups. Additionally, airway hyperreactivity (AHR) was assessed as part of the allergic response and to assess airway function since a study had reported reduced BMPR-II expression in the airways of patients with asthma [31]. Vascular remodeling and mild PAH developed after 20 weeks of HDM in both Bmpr2 ΔE2 and WT mice; however, there was no difference between these groups. Interestingly, AHR was more severe after 20 weeks of HDM exposure in Bmpr2 ΔE2 mice compared to WT, demonstrating a phenotypic difference in these mice. These results suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of Bmpr2 mutations. The exaggerated AHR in Bmpr2 ΔE2 mice suggests a potential role for this pathway as a modifier of chronic allergic airway disease.
Genotype Analysis of DNA from Bmpr2 ΔE2 Mice
To verify the genotype of the mice, PCR of tail DNA from WT and Bmpr2 ΔE2 mice was performed using primer probe sets specific for both the WT and hypomorph alleles. WT and Bmpr2 ΔE2 mice were distinguishable by the amplification of a 450-bp fragment for the hypomorph allele (Figure 1A).
A: Tail DNA from mice carrying the wild-type (WT) and/or the Bmpr2 hypomorph (ΔE2) alleles were genotyped by PCR using the primers Bmpr2 MT Neo R1 to detect the hypomorph allele (ΔE2 450 bp) and Bmpr2 WT R2 to detect the WT allele (WT 230 bp). PCR products were run on a 4% agarose gel containing ethidium bromide and photographed. B: Western blot analysis of P-Smad1/5, a downstream mediator of BMPR-II signaling, was decreased by approximately 50% after HDM exposure compared to saline controls (n = 5 mice/group). *P<0.05 vs saline.
Alterations in BMPR-II Signaling in Response to HDM.
To determine if signaling downstream of BMPR-II was altered in response to HDM, western blot analysis for phosphorylated Smad1/5 (P-Smad1/5) was performed on lung homogenates of saline and HDM exposed WT mice. P-Smad1/5 levels were reduced by approximately 50% in mice exposed to HDM for 20 weeks compared to saline controls (Figure 1B).
Inflammatory cell response and Immunoglobulin Levels after HDM Exposure
Total inflammatory cells were assessed in the BALF. Increases in total inflammatory cell counts were similar in HDM exposed WT and Bmpr2 ΔE2 mice, at both 7 and 20 weeks (Figure 2A). Specific inflammatory cell types were assessed by Diff-Quick staining of cytospins. Representative images are shown in Figure 2B. Total neutrophil and eosinophil numbers were increased after 7 weeks of HDM exposure compared to saline controls. After 20 weeks of HDM, neutrophil and eosinophil numbers were still increased above controls although total eosinophil numbers were lower compared to 7 weeks (Figure 2C). In addition, the percentage of neutrophils and eosinophils were increased in WT and Bmpr2 ΔE2 mice after 7 and 20 weeks of HDM exposure compared to saline controls (Table 1). Lymphocytes percentages were increased only in HDM treated Bmpr2 ΔE2 mice at 7 weeks, but similarly increased in both WT and Bmpr2 ΔE2 at 20 weeks. The percentage of eosinophils was lower and the percentage of neutrophils was increased after 20 weeks of HDM compared to 7 weeks. HDM specific IgG1 and IgE levels were measured after HDM exposure to assess sensitization to the allergen. HDM specific IgG1 and IgE levels were similarly increased in HDM exposed WT and Bmpr2 ΔE2 groups compared to saline controls after 7 (top panels) and 20 (bottom panels) weeks (Figure 3). HDM specific IgG1 was slightly higher (1.3 fold) in WT mice compared to Bmpr2 ΔE2 mice after 7 weeks of HDM exposure, but not after 20 weeks. Increases in HDM specific IgE were similar in WT and Bmpr2 ΔE2 mice at 7 and 20 weeks.
A: Total inflammatory cell counts were increased in BALF in both WT (white bars) and Bmpr2 ΔE2 (ΔE2; black bars) mice after 7 weeks (wk) and 20 weeks of HDM (n = 4–13 mice/group in two independent experiments). *P<0.05 vs saline control, ∧P<0.05 vs saline WT 20 weeks. B: Representative images of cytospins from BALF demonstrating specific inflammatory cell types in the lung after 7 and 20 weeks of saline or HDM exposure. The inset in the top panel shows a high power image of an eosinophil and the bottom panel inset is a representative image of a neutrophil. M = Macrophage, L = Lymphocyte, N = Neutrophil, and E = Eosinophil. Scale bar larger panels = 20 µm. Insets scale bar = 10 µm. C: Changes in macrophage cell numbers were only observed after 20 weeks of HDM and only in BMPR2 ΔE2 mice. Neutrophils and eosinophil numbers were increased in HDM exposed groups at both time points, however, the number of eosinophils was lower after 20 weeks. *P<0.05 vs saline control, ∧P<0.05 vs saline ΔE2 lymphocyte 20 weeks, #P<0.05 vs saline WT macrophage 20 weeks, +P<0.05 vs HDM WT macrophages 20 weeks, @P<0.05 vs HDM WT neutrophil 20 weeks.
Levels of HDM specific IgG1 and IgE were increased in both WT and Bmpr2 ΔE2 mice after 7 weeks (top panels) and 20 weeks (bottom panels) of HDM exposure. At 7 weeks, HDM specific IgG1 levels in WT mice were slightly higher compared to Bmpr2 ΔE2 mice (n = 4–12 mice/group). *P<0.05 vs saline control, ∧P<0.05 vs HDM WT 7 weeks.
Pulmonary Vascular Remodeling
No differences in thickening of the arterial wall of the small pulmonary arteries were detected between saline exposed WT and Bmpr2 ΔE2 mice (Figure 4A). Animals exposed to HDM for 7 or 20 weeks demonstrated increased thickening of the medial layer in small pulmonary arteries (20–150 µm) in both WT and Bmpr2 ΔE2 mice compared to saline controls (Figure 4A). Vessel wall thickness was measured by morphometric analysis as demonstrated in Figure 4B. Morphometric analysis revealed significant increases in wall thickness after HDM exposure; however, they were similar between WT and Bmpr2 ΔE2 mice at 7 and 20 weeks (Figure 4C). Mice exposed to HDM had a higher percentage of fully muscularized vessels compared to saline treated controls at both 7 and 20 weeks (Figure 5B). The percentage of fully muscularized vessels was further increased after 20 weeks of HDM exposure compared to 7 weeks. This pattern of muscularization was similar between HDM exposed WT and Bmpr2 ΔE2 mice at both time points. In addition to the increases in percentages of muscularized vessels, the total number of muscularized vessels (fully+partially together) was increased in HDM exposed mice compared to saline controls (data not shown).
A: α-Smooth muscle actin (α-SMA) staining was performed on lung sections from WT (top) and Bmpr2 ΔE2 (ΔE2; bottom) mice exposed to saline or HDM for 7 or 20 weeks (wk). Thickening of the arterial wall (medial layer) in HDM exposed mice is seen (arrows) at both 7 and 20 weeks. Scale bar larger panels = 200 µm. Insets scale bar = 50 µm. B: Image of α-SMA immunostaining of a pulmonary artery demonstrating the method used to measure arterial wall thickness. For each vessel, external diameter and two wall thicknesses were measured along two different axes. Percent wall thickness was calculated as [(1a+1b)/external diameter]×100. This measurement was performed along each axis. The two axes measurements were averaged together to determine the final wall thickness. C: Percent wall thickness of pulmonary arteries (20–150 µm) was increased 1.5 fold in HDM exposed mice after 7 weeks (wk) and 2 fold in mice exposed to HDM for 20 weeks. Differences between WT (white bars) and Bmpr2 ΔE2 (ΔE2) (black bars) mice exposed to saline or HDM were not significant (n = 5–13 mice/group). *P<0.05 vs saline control.
A: Representative images of α-SMA immunostaining of non-muscular (NM), partially muscularized (PM) [53], and fully muscularized (FM) small arterioles used to determine percent muscularization of vessels after HDM exposure (40×). B: WT and Bmpr2 ΔE2 (ΔE2) mice demonstrated increases in the number of arterioles that were fully muscularized (FM) and fewer arterioles that were non-muscular (NM) compared to saline controls after 7 weeks (wk) HDM (left). The percentage of FM arterioles was further enhanced after 20 weeks of HDM and the proportion of NM arterioles was further reduced. No differences were detected between groups of WT and Bmpr2 ΔE2 mice exposed to saline or HDM (n = 5–13 mice/group). *P<0.05 vs saline control, ∧P<0.05 vs ΔE2 saline PM.
Pulmonary Arterial Hypertension
Right heart catheterization was performed to assess the development of PAH. In animals exposed to 7 weeks of HDM, no increase in right ventricular systolic pressure (RVSP) in either group was detected compared to saline controls (data not shown). Following 20 weeks of HDM exposure, however, RVSP was increased in WT (33.54±1.57 versus 26.34±1.11) and in Bmpr2 ΔE2 (30.41±0.76 versus 26.67±0.51) mice compared to saline controls indicating the development of mild PAH in these animals (Figure 6A). RVSP was not different between HDM exposed Bmpr2 ΔE2 mice and WT mice (30.41±0.76 versus 33.54±1.57). Although RVSP was increased in both HDM exposed WT and Bmpr2 ΔE2 mice after 20 weeks, the RV to LV+S weight ratio was only increased in Bmpr2 ΔE2 mice compared to saline controls (0.31±0.01 versus 0.27±0.01) (Figure 6B). However, there was no difference between the RV to LV+S weight ratio in HDM exposed WT and Bmpr2 ΔE2 mice (0.32±0.02 versus 0.31±0.01).
A: Right ventricular systolic pressures (RVSP) was increased in both WT and Bmpr2 ΔE2 (ΔE2) mice after HDM exposure for 20 weeks compared to saline controls. There was no difference in RVSP between WT and Bmpr2 ΔE2 mice exposed to HDM (n = 4–11 mice/group in two independent experiments). *P<0.05 vs saline control. B: The ratio of RV weight to LV+S weight was only increased in Bmpr2 ΔE2 mice compared to saline controls (n = 4–11 mice/group in two independent experiments). *P<0.05 vs saline control.
Airway Hyperreactivity
After RVSP measurements were obtained, airway hyperreactivity (AHR) to increasing doses of methacholine was assessed since it had been previously reported that Bmpr2 expression was decreased in asthmatic patients [31]. After 7 weeks of HDM exposure, AHR was similarly increased in both WT and Bmpr2 ΔE2 mice compared to saline controls (data not shown). After 20 weeks of HDM exposure, AHR was increased in both WT and Bmpr2 ΔE2 compared to saline controls. Interestingly though, after 20 weeks, AHR was more severe in the HDM exposed Bmpr2 ΔE2 mice at both 25 mg/ml (2.4 fold) and 50 mg/ml (1.8 fold) methacholine compared to the HDM exposed WT mice (Figure 7).
Bmpr2 ΔE2 mice developed more severe airway respiratory resistance to methacholine after 20 weeks of HDM compared to WT mice (n = 4–12 mice/group). Both HDM groups demonstrated increased airway resistance with methacholine exposure compared to saline controls. *P<0.05 vs saline controls, ∧P<0.05 vs WT HDM.
The present study demonstrates that while mice exposed to the aeroallergen HDM for 7 weeks develop increases in wall thickness and muscularization of pulmonary arterioles, this was not associated with significant increases in RVSP. However, when HDM exposure was extended out to 20 weeks, arterial remodeling was more severe and RVSP was significantly increased, although mild. Despite these increases in RVSP and arterial remodeling, Bmpr2 ΔE2 mice showed similar responses to WT mice, suggesting that reductions in BMPR-II signaling do not predispose for more severe PAH with chronic allergen-induced inflammation. Although vascular changes were similar between Bmpr2 ΔE2 and WT mice, AHR in Bmpr2 ΔE2 mice was more severe after 20 weeks HDM which suggests a potential role for this pathway as a modifier of reactive airway disease.
Previous studies have examined the role of inflammation and chronic hypoxia in the development of PAH in Bmpr2 heterozygous mice (Bmpr2+/−). Zhang et. al. treated Bmpr2+/− mice with adenovirus-delivered 5-lipoxygenase (5-LO), which is known to facilitate inflammation and is increased in patients and animal models of PAH [32], [33]. These studies demonstrated increased RVSP and vascular remodeling in Bmpr2+/− mice compared to WT; however, the degree of muscularization in the 5-LO treated mice was mild [34]. A subsequent study demonstrated that Bmpr2+/− mice treated with combined 5-LO and monocrotaline developed sustained increases in RVSP, thickening of small pulmonary arteries, and perivascular inflammation of the remodeled vessels that was more severe in Bmpr2+/− mice compared to WT [26]. Another study utilizing Bmpr2+/− mice, found that a combination of hypoxia and chronic serotonin infusion increased RVSP, right ventricular hypertrophy, and pulmonary remodeling [35]. In the present study, we utilized HDM, as many people develop allergic responses this common aeroallergen [27], [36], [37]. In addition, Erjefalt et. al. had previously demonstrated that chronic HDM exposure could cause pulmonary vascular modeling in mice after 20 weeks of HDM; however, no direct measures of PAH were reported [27]. Unlike reports mentioned earlier, in the present study, PAH severity was not enhanced in BMPR2 mutant mice compared to WT mice. This discrepancy may be due to the different types of inflammation induced in the previous studies since they primarily elicit Th1 responses and little to no eosinophils [20], [24], [26]. In contrast to previous models, HDM exposure induces the release of Th2 cytokines (interleukin 4 (IL-4), IL-5, and IL-13) and an influx of eosinophils during acute exposures and neutrophils during chronic exposures [27], [38]–[42]. A role for Th2 cytokines in the etiology of vascular remodeling was demonstrated by Grunig et. al. as pulmonary arterial remodeling in OVA and Aspergillus fumigatus exposed mice was reduced in IL-4 deficient mice. Comparing the findings of our study to others, suggests that the type of stimuli may be important in determining whether PAH is more severe or not in BMPR2 mutant mice. In addition, in some of these studies, more than one insult was required for animals with reduced BMPR2 to show any PAH phenotype [26], [35], suggesting that the development of the disease may be multi-factorial. This is consistent with additional genetic and/or environmental factors being necessary to trigger PAH in patients with BMPR2 mutations since the penetrance of the disease is low.
In the present study, we assessed vascular remodeling and RVSP after 7 and 20 weeks of HDM exposure to determine if the changes in arterial remodeling were associated with PAH. In addition, we examined the question of whether a Bmpr2 signaling deficiency in HDM exposed mice would cause more severe pulmonary arterial remodeling changes, since mutations in this gene are found in 70% of patients with heritable PAH. Although increases in arterial muscularization in HDM exposed mice were observed after 7 weeks, RVSP was not increased. However, after 20 weeks of HDM exposure, RVSP was similarly increased in both WT and Bmpr2 ΔE2 mice in conjunction with more severe arterial remodeling. Our data agrees with that of two previous studies which showed that persistent allergic inflammation could induce pulmonary vascular remodeling [3], [27], however; in addition, we were able to detect PAH, although mild. The development of PAH in our model might be partly due to a higher percentage of fully muscularized pulmonary arteries at 20 weeks compared to 7 weeks; however, factors such as vasoconstriction could also be playing a role in the pathophysiology.
Although an increase in the number of inflammatory cytokines, macrophages, T cells, B cells, and chemokines have been observed in patients with PAH, the exact role of these molecules in the disease process is unclear [3], [22], [43], [44]. As previously mentioned, Grunig et al. [3], exposed mice to ovalbumin and Aspergillus fumigatus for extended periods of time, and found that both of these allergens caused pulmonary arterial remodeling; however, increased muscularization of the pulmonary arteries did not correlate with RVSP measurements. A more recent study by Morrell et al. reported severe pulmonary arterial remodeling in the presence of Th1 and Th2 inflammatory responses in a mouse model of schistosomiasis, which is thought to be a common cause of pulmonary hypertension [45]. PAH was not observed in these mice, even though extensive pulmonary arterial remodeling was detected. In contrast to the studies above, we were able to detect increases in RVSP after inducing chronic inflammation in our model of vascular remodeling. Recent reports indicate that both mouse strain and sex can affect the inflammatory responses [46], [47]. It is possible that the strain of mice used (Balb/c/Byj) in this study may have influenced the response to chronic inflammation differently compared to the other studies since mice of a different background were used (C57BL/6) [3], [26], [35]. Although differences in sex have previously been shown to affect the inflammatory response, we were unable to detect any differences in inflammation or RVSP between males and females in our model; however, there was a trend towards higher RVSP in females.
In addition to vascular remodeling and PAH, we also assessed AHR in our model since a study reported decreased BMPR2 in the airways of asthmatic patients, providing evidence for a potential role for the BMPR2 pathway in allergic asthma [31]. Interestingly, in our study, more severe AHR was observed in Bmpr2 ΔE2 mice after 20 weeks of HDM exposure compared to WT mice. These findings offer further support that this pathway may be a modifier of the asthmatic response, although additional studies are needed to address this more extensively. Prior to this study, there had been little evidence suggesting any common features between PAH and asthma. One case report showed both increased pulmonary pressures and reactive airway disease in two patients with congenital heart disease [48]. After long-term treatment of these patients for the asthma symptoms, pulmonary pressures decreased; however, whether these two diseases are linked is unclear. One explanation for the lack of information regarding any connection between these two diseases may be due to the fact that the PAH patient population is small.
In summary, we demonstrated that chronic HDM exposure causes arterial remodeling and PAH in mice, although we were unable to detect any differences in the response between WT and Bmpr2 ΔE2 mice. This suggests that chronic HDM exposure causes vascular remodeling and PAH through mechanisms that may be independent of the BMPR-II signaling pathway. To our knowledge, this is the first study to establish that chronic allergen exposure causes PAH, albeit mild. Additionally, we observed more severe AHR in Bmpr2 ΔE2 mice compared to WT after chronic HDM exposure, suggesting a potential role for Bmpr2 in allergic airway disease.
Ethics statement, animal treatments, and RVSP measurements
Animal protocols and procedures were approved by the Animal Care and Use Committee at the Cincinnati Children's Hospital Research Foundation (Cincinnati, OH) (Protocol Number: 1D02011) and all procedures were performed under anesthesia to minimize suffering. Bmpr2 ΔE2 heterozygous mice were generated by Dr. Karen Lyon's lab (UCLA, Los Angeles) [30]. At Cincinnati Children's Hospital, mice were bred onto a mixed Balb/c/Byj background, since this strain responds well to allergens and is frequently used in allergic inflammatory models. All WT mice used were littermate controls from these breedings.
At 6–10 weeks of age, WT and Bmpr2 ΔE2 mice were exposed intranasally to either 20 µl saline (0.9% NaCl) (vehicle control group) or 25 µg of the allergen, house dust mite (HDM) (Greer Laboratories, Lenoir, NC), dissolved in 20 µl of saline, 3 times per week and for either 7 or 20 weeks. Isoflurane was used to anesthetize the mice during repeated intranasal HDM exposures. At the end of the treatment periods, mice underwent right heart catheterization, as previously described [34]. Briefly, mice were anesthetized with 2.5% isoflurane and remained sedated with ∼2.0–2.25% isoflurane via a nose cone during catheterization. After dissection to expose the right jugular vein, an SPR-671 pressure transducer catheter (Mikro-Tip 1.4F, Millar Instruments, Houston, Texas) was inserted into the jugular vein via a small incision, passed through the right atrium and into the right ventricle where right ventricular systolic pressures (RVSP) were measured. For each mouse, an average of 30 individual RVSP measurements during a 3–5 minute time period were taken and analyzed using the HSE Haemodyn W software (version 18.104.22.168, Harvard Apparatus).
Genotype Analysis
Genotypes were determined by PCR (Figure 1) with the primer Bmpr2 WT R2 to detect the wild-type allele (230-bp) and Bmpr2 MT Neo R1 used to detect the neo cassette, which was inserted in place of exon 2 to generate a hypomorph allele (450-bp). Another primer, Bmpr2 F2, was used as a forward primer for both sets of reactions. Amplification was performed for 34 cycles with 1 minute at 95°C, 1 minute at 56°C, and 1 minute at 72°C. The sequences for the primers were: Primer Bmpr2 MT Neo R1, 5′ CCTTCTATCGCCTTCTTGAC 3′; Primer Bmpr2 WT R2 5′ TTCCCTGATAACAGCCTTCC 3′; Primer Bmpr2 F2 5′ AAGTACACGGTCGCTGTCTTC 3′.
Western Blot Analysis
Western blot analysis was performed on lung homogenates using the following antibodies to assess the levels of phosphorylated Smad1/5 (P-Smad1/5, 1∶1,000; Cell Signaling) and β-tubulin (1∶1,000; Cell Signaling). A goat anti-rabbit secondary antibody (1∶10,000; Calbiochem) was used along with an ECL plus chemiluminescence detection system (GE Heathcare). An LAS4000 imaging system and Multi Gauge 3 software (Fujifilm, Tokyo, Japan) were used to image and quantitate the chemiluminescent signal for each Western blot. Protein loading and transfer efficiency were controlled for each sample by normalizing to β-tubulin.
Airway Hyperreactivity
After RVSP measurements, mice were anesthetized with an intraperitoneal injection of Ketamine/Xylaxine/Acepromazine (4∶1∶1) solution and changes in airway resistance to methacholine were assessed as previously described [49]. Briefly, after a tracheostomy was performed, the mouse was connected to a flexiVent system (SCIREQ, Montreal, QC, Canada). Airway respiratory resistance was measured after nebulization of phosphate buffered saline (1× PBS) (baseline) and then increasing doses of methacholine (12.5, 25, and 50 mg/mL; acetyl-β-methylcholine chloride, Sigma, St. Louis, MO).
Bronchoalveolar lavage
After AHR measurements were performed, bronchoalveolar lavage fluid (BALF) was collected from mice to assess the inflammatory response. Lungs were lavaged three times via a tracheostomy tube with a total volume of 1 ml of 1× PBS as previously described [49]. The BALF was centrifuged (2000 RPM) and the supernatant was removed and used to measure HDM specific IgE and IgG1 levels. Red blood cell lysis buffer (R7757 Sigma, St. Louis, MO) was added to the cell pellet to lyse any red blood cells. Cells were centrifuged again, supernatant removed, and cells resuspended in PBS. Total inflammatory cells were counted using a hemocytometer. Cytospins of the remaining cells were collected on slides for differential cell counts. Inflammatory cell types were determined by Diff-Quick staining (Shandon Lipshaw, Pittsburg, PA) (Figure 2B). Three hundred cells were counted per slide and the percentages of macrophages, lymphocytes, neutrophils, and eosinophils were determined.
HDM specific IgG1 and IgE levels were measured in BALF by ELISA to assess allergic sensitization to HDM as previously described [50]. Briefly, plates were coated with 0.01% HDM in PBS overnight. The following day, plates were blocked with 1% BSA in PBS for 1 hour then coated with samples. Biotin-anti-mouse IgE or IgG1 (Pharmingen, 2.0 µg/ml) was used for capture. Streptavidin-HRP (1∶100, R & D, Minneapolis, MN) was added to detect antibodies and the reaction developed by TMB substrate (1∶1) (BD Biosciences, San Jose, CA).
Immunohistochemistry and arterial remodeling
Lungs were inflation fixed by tracheal installation of 4% paraformaldehyde at constant pressure (25 cmH2O), transferred to 70% ethanol after 24 hrs, cut into three sections, and embedded in paraffin as previously described [51]. Immunostaining for α-smooth muscle actin (α-SMA) was performed on 5 µm paraffin-embedded sections by incubating slides with an α-SMA monoclonal antibody (1∶10,000 dilution, Clone 1A4; Sigma) overnight at 4°C, followed by a goat anti-mouse IgG2a secondary antibody (1∶200, Southern Biotech, Birmingham, AL). A Zeiss Axioplan 2 microscope (Carl Zeiss Microimaging, Thornwood, NY) was used to obtain digital images of the immunostaining. All genotypes and identification numbers of the animals were blinded to the observer, and the images were randomized. Vessel wall thickness was measured on pulmonary arteries with an external diameter ranging from 20–150 µm that were associated with terminal bronchioles and fully muscularized. The total number of vessels measured ranged from 20–56 per group. Metamorph imaging software (v6.2; Universal Imaging/Molecular Devices, Downington, PA) was used to measure the medial wall thickness and external diameter of each vessel. For each vessel, wall thickness and the external diameter were measured twice, along two different axes (Figure 4B). Percent wall thickness was calculated as [(wall 1a thickness+wall 1b thickness)/external diameter 1]×100. This calculation was performed for each axis. Each axis measurement was averaged together to determine the final wall thickness. Four to six vessels were measured for each animal. In addition to wall thickness measurements, percent muscularization of the pulmonary arterioles was also assessed. Small pulmonary arterioles in the terminal bronchial and the alveolar regions were identified and scored for muscularization as previously described [52]. Briefly, vessels were scored as nonmuscular (NM) (<50% muscle around vessel), partially muscularized (PM) [53] (>50% but <100% muscle surrounding the vessel), or fully muscular (FM) (muscle surrounds 100% of vessel) (Figure 5A). Thirty small pulmonary arteries were scored per animal and expressed as a percentage of total vessels counted.
Statistical Analysis
Statistical analysis was performed with Prism 4 software (GraphPad Software, San Diego, CA). Unpaired t-tests, one-way, and two-way ANOVA with Tukey's post-hoc test were used to make comparisons. P<0.05 was considered statistically significant.
Author Contributions
Conceived and designed the experiments: EMM TLC. Performed the experiments: EMM MWP TLC. Analyzed the data: EMM MWP. Contributed reagents/materials/analysis tools: EMM GKH MWP WCN TLC. Wrote the paper: EMM. Gave advice on the study design and interpretation: GKH WCN TLC. Provided feedback on the manuscript and final approval of the manuscript: GKH MWP WCN TLC.
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text:
For Mobility Developers
By CW, managing editor on May 18, 2007
New! Java ME Application Developers Project
The open-source Mobile & Embedded Community team has launched a new project to encourage and assist Java ME application developers in building mobile applications. Find the resources you need—demos, source code, tools, and tips—and learn how to connect with the community.
Java Mobility Podcasts
Check out this new series of podcasts from the java.net Mobile and Embedded Community. You'll find an Introduction to the Community, Report from Brazil, 2007 JavaOne Activities, and an interview with a video ringtone-sharing ISV in Meet Vringo.


text:
- Posted February 2, 2014 by
- peters06
london, United Kingdom
How to Refinance a Bank Home Loan in UK
How to Refinance a Bank Home Loan in UK
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Location: Appalachian Fruit Research Laboratory
Project Number: 8080-21000-023-04
Start Date: Jan 01, 2010
End Date: Dec 31, 2014
Genetic engineering will be utilized to improve traits that have been either impossible or too time consuming to approach through traditional techniques. These traits include the development of dwarfing rootstocks for Pyrus (pear) and Prunus (stone fruits), the development of Plum pox virus resistant stone fruits, the improvement of fruit quality traits including the development of stoneless stone fruits, and the production of early flowering lines for speeding the fruit breeding process. We have developed a rapid high throughput transformation system in plum and a technology for early flowering and fruiting. We will use this system to rapidly test genes of interest. Those of interest will be applied for the improvement of stone fruits, particularly plum, and also pear. The genetically engineered plants developed at EPCOT will be further evaluated at Kearneysville in the greenhouse and field (with appropriate permits). The work at EPCOT is critical to us achieving our research project plan's milestones. The ARS staff at EPCOT is competent, motivated, and experienced. The facilities are good. We feel that achieving the objectives of the five-year-plan will provide not only good scientific information but also will lead us to the development of exciting new products for the pear and stone fruit industries.


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text:
Skip to comments.Dragon arrives at space station in historic 1st
Posted on 05/25/2012 8:45:26 AM PDT by mandaladon
click here to read article
And NASA is mere months away from sending a far more sophisticated rover to mars.
But, I seriously doubt that many alive today will ever see 'civilization' becoming space-faring - i.e. establishing colonies on other planets.
It's an astounding website.
I know you've seen this Ron, but others should watch the video at bottom of this post. It's very cool.
Taken during mobility testing, this image is of the Mars Science Laboratory rover Curiosity, Jet Propulsion Laboratory, Pasadena, Calif.
Curiosity lands on the surface of Mars in about 2 months, August, 2012.
I suggest others watch this Mars Science Laboratory Curiosity Rover Animation, about the mission. The video is only 11 minutes long, and well worth the watch.
Enlarge the screen and turn up the volume.
How they are going to get Curiosity onto the surface of Mars
The video which will be sent back from this vehicle traveling around the surface of Mars, will be spectacular.
I'm actually glad that there are two businesses out there working toward these goals. These could be the start of much much more than we realize. With a little experience, these firms may blossom into full blown space access for man as well. Looking forward to the next few years.
slow and steady...pretty cool.
The government will most likely continue to control the boosters. After all, the main difference between an orbital booster and an ICBM is the payload.
I thought they could just send their trash to the giant incinerator in the sky (just jettison it toward the earth and let it burn up in the atmosphere).
Only to the extent of flight authorizations, etc....
Actual technical control of the Falcon 9 during the launch was from Space-X.
I think there are 3, but yes it's good to see some new blood. The old big commercial concerns that have launched most satellites are too slow and set in their ways to do things quickly and cheaply.
That seems to be the difference between firm fixed-price contracts and cost plus contracts.
That does seem to be the case. Thanks Johnny.
BTW, thanks for mentioning there are three. Great.
Uh oh. Space X is doomed...Obama is in da house.
Obama is the anti-Midas. Everything he touches turns to s#it.
Today, young people don't have jobs for life. They have careers for life, and move from job to job, following what they love and, of course, the money.
The guys at Space-X obviously don't have an investment in building an empire. Hell, their control center is commercial computers on office tables.
Overhead stuff, like fancy consoles, adds up, and doesn't add value to getting something launched.
LOL! that pic is taken at the USAF Station in Florida. You don't think Space-X is dumb enough to invite him to their facility do you?
Well said. Extremely well said...
For my money it would be sweet if the first person to land on Mars OWNS it.
Talk about an ego boost. You own the Portland Trailblazers? Hah! I own a friggin' planet. Suck it!
Today was the day that Obama's vision of the American space program was declared a triumph. Look for the MSM to make a big deal of this while our shuttles are now museum pieces.
Dream on. This is all Obama BS. He has destroyed our space program. Folks like Neil Armstrong have been very critical of Obama's vision for our space program. This has nothing to do with free enterprise. It is a scam and part of crony capitalism.
Civilization: The West and the rest is a new show on public television that explains why free enterprise and competition is the reason why the Western World has become the leader and the Eastern world stayed stagnant.
Did my heart a world of good to watch that. That's the real America.
No worries, J. The human race will do what it's always done, and will one day own the stars. Like you said, it's in our genes to go bigger, better, farther. Space X is only just the start.
North American/Rockwell was the prime contractor for the shuttle.
Where were they in funding, designing, operating, and making history today? On the sidelines, because it wasn't big-gov cost plus contract.
I'm glad the old way of doing things is going away. It had it's place, and we stand on the shoulders of giants, but big, ancient aerospace companies can't deal with today's world.
I'm sure there are lots of politics and blah, blah, blah involved.
But to tell the truth, I was so excited about this. The government being out of things maybe the best thing that ever happened. (Much to Barry's consternation)
Move over rover..let SpaceX take over...no pun intended.
4/2011 Russian Resistance to SpaceX Dragon Docking
We will not issue docking permission unless the necessary level of reliability and safety is proven, said Alexei Krasov, head of the human spaceflight department of Roscosmos. So far we have no proof that those spacecraft duly comply with the accepted norms of spaceflight safety.
Of course, it was Russia who stood to gain by blocking SpaceX.
Safety? That's odd, as they seemed to have little regard for safety prior to this.
" In 2006, NASA awarded the company a Commercial Orbital Transportation Services (COTS) contract to design and demonstrate a launch system to resupply cargo to the International Space Station (ISS). On 9 December 2010, the launch of the COTS Demo Flight 1 mission, SpaceX became the first privately funded company to successfully launch, orbit and recover a spacecraft. On 22 May 2012, SpaceX's Falcon 9 rocket carried the unmanned Dragon capsule into space, marking the first time a private company has sent a spacecraft to the space station. The unmanned, cone-shaped capsule became the first privately built and operated vehicle to ever dock to the orbiting outpost"
I'm so glad Obama had the foresight to award this contract in 2006.
The mom and pop space businesses will not be any great saviour to what used to be our preeminent position in space. There are enormous national security issues involved. The Chinese are not going to privatize their efforts.
We will see if SpaceX goes the way of Tesla Motors.
Your response hit the 10 ring.
If you recall, Obama was criticized widely for the dismantling of NASA and its scientific team with mass dismissals. Now Bolden says that those jobs will shift over to the private companies. Obama had it right all along.
This scheduling of this is no accident. I watched the head of NASA today extolling Obama's plan to privatize space exploration.
In 2006, NASA awarded the company a Commercial Orbital Transportation Services (COTS) contract to design and demonstrate a launch system to resupply cargo to the International Space Station (ISS)"
Lurkina.n.Learnin: Im so glad Obama had the foresight to award this contract in 2006.
This fall hes hoping for another term for Obama, the best friend of private space, Musk says. Obama seems to care about inspiring events in the country, Musk says. Romney, on the other hand: Hes got that whole business-school thing going on, which Im not a huge fan of. Its hard to make a business case for inspiration. For now Musk has more immediate worries, like the performance of his rocket with the whole world watching. Isnt he worried hell suffer a Kim Jong-un-like fizzle? Nah, Musk says. Believe him. Elon has huge steel balls, his ex-wife notes on her blog. He truly does.
See my post #85. Musk is a staunch Obama supporter. He will get government contracts and then funnel money back into Obama's campaign coffers. This is just more crony capitalism. It is destroying this country. Government already controls 40% of our economy. This is really not privitization of space any more than the defense industry is private.
Private industry greases their own wheels and contributes when they feel the need.
Ya think this is something new Mr. kabar?
In 2006, NASA awarded the company a Commercial Orbital Transportation Services (COTS) contract to design and demonstrate a launch system to resupply cargo to the International Space Station (ISS)"
Who was President of the United States in 2006 Mr. kabar?
We will not issue docking permission unless the necessary level of reliability and safety is proven,
Ok, I'm a bit slow on the uptake here....the Russians didn't actually prevent Dragon from docking with the ISS, did they? Or, was there some international drama that wasn't closely covered by the press?
Great pic, by the way. Thanks.
Thanks for posting the link to the video. My boys and I just watched the whole thing. Bloody fantastic.
Russian Resistance to SpaceX Dragon Docking
See the date.
Mr Musk may be on the wrong side of the political isle but this is the precursor to a privatized space program. Burt Rutan, Richard Banson and Elon Musk are pioneers. Obama is just a politician patting himself on the back.
As if the temporary Chief Executive of one earthbound country could dictate terms the rest of the planet, for the exploration and exploitation of the entire universal space outside this pitiful little mud ball.
I simply smile in amusement.
#3 son has been keeping us apprised of the developments. He's thrilled that we can get materials to the Space Station without having to pay the Russians to do it.
Perhaps. The next US president could easily reinvigorate our manned and unmanned space programs by executive fiat. No different than what Obama's done.
The American people support our space programs. Obama is just doing the typical hard left thing by squelching those dreams in favor of redirecting US dollars toward the welfare/nanny state. It's not the popular tack, and he will find that out in November.
If Elon Musk has a brain cell in his head, he has to realize how intensely political Obama is. Musk says the wrong thing and his fat NASA contract will go away in a heartbeat. And playing kissy-face with him will open up the possibility of Obama taking his boot off NASA's neck and letting them do some real space exploration. Which will create and even bigger market for Musk.
That doesn't mean he is not a democrat or that he would not vote for Obama. But I doubt even under the best of circumstances could he enjoy the same sort of quid pro quo under Romney. At least I hope not.
Even democrats do good things occasionally. Especially when you can keep them out of Washington.
I wouldn't go that far. Obama has merely slowed or halted it, temporarily. The American people love and believe in our space program. It's one of the few great and positive things that our government does, and people around the world wholeheartedly support it.
The US space program will go on. Obama will not.
I have some personal interest in astronomy and space exploration. I support NASA and private industry like SpaceX.
It's just a shame these things always seem to be politicized. But it seems that's the reality of the political madness here on earth.
Didn't the Puritans run away?
The reality is that the Atlas V, built by Lockheed and Boeing is heavily subsidized by the government. It is just more crony capitalism with cost plus contracts.
The only thing that changed between Space-X and ULA is the procurement process. Space-X can put pounds in orbit for NASA cheaper than Lockheed and Boeing do.
Your old pocket protector cost plus government contracts are gone. It's better and cheaper this way, and NASA gets more bang in space for our dollars.
NASA never built a spacecraft. It's all been private contractors, from day 1.
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text:
Maryellen Hooper is cool.
She killed performing at Montreal's Just For Laughs Comedy Festival both as a solo artist and as a member of The 3 Blonde Moms.
Maryellen has a unique brand of storytelling that includes a verbal quirkiness coupled with a physical humor that punches the funny every time. She's a personal favorite and I believe after you see her you will also make her a favorite of yours. Hooper's style of humor ultimately twice landed her a slot on "The Tonight Show with Jay Leno." She was named Best Female Stand-Up at the 12th annual American Comedy Awards. Her numerous television and radio credits include Lifetime Channel's "Girl's Night Out," A&E's Evening at the Improv, Comedy Central specials and numerous other television appearances. She's a comic's comic, a self-made woman that can outshine any guy when it comes to doing the home improvement thing. Now that I think of it she has this blue collar, down-to-earth sensibility about her which I think is why so many like her so much.
I think Maryellen is well grounded in part because she started out in the blue collar world of being a former "disgruntled" hairdresser. Oh man, does she have some interesting stories talking about who's head she has styled and some of the contacts she made in that line of work. She weaves those experiences into her act as well as her experience working along with her husband on their "fixer-upper" home. That alone is worth the ticket price.
Maryellen also talks a lot about her family life including her being a mother to two adopted, adorable sons. She has more than enough stories in this area that really hits home. In fact, Maryellen describes her material as "just plain silly, fun stuff that everybody can appreciate."
Appearing with Maryellen is Jim McCue, a New Englander who loves comedy so much started the Boston Comedy Festival.
Like every Bostonian he is a diehard Boston Red Sox fan. One year he had to reschedule his comedy festival because it interfered with Sox's playoff games. Obviously, there will be no need to worry about rescheduling this year.
The tall Irishman has been featured on Comedy Central, Comcast Comedy Spotlight, NBC's "Last Comic Standing," and "Roughing It" on NESN. He works in top comedy clubs in the Boston area Las Vegas, New York, Dublin, Montreal, Sydney and Edinburgh. Since 1999 Jim has also entertained U.S. troops at more than 100 bases around the world. An account of his experiences performing for the troops were published in a book he wrote, "Embedded Comedian," which Jim describes as a "field manual for comedians in a war zone."
Jim is a very likable guy with a pleasant, improvisational rapport and is never condescending with the crowd.
Jim rarely turns down a gig even if it seems a little out there. If you go to his website McCue is available for "Anniversaries, Awards Nights, Bachelor Parties, Bachelorette Parties, Banquets, Bar Mitzvahs, Bat Mitzvahs, Birthday Parties, Casinos, Celebrations, Christmas Parties, Church Services, Clubs, Coffee Shops, Community Events, Conventions and Corporate Functions." That's very noble of you, Jim, but let's keep your gig confined to The Improv this week OK?


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We offer guided hunting excursions in both Idaho and California. In Idaho we hunt elk, whitetail, mule deer, bear, mountain lion, wolf and moose. For full details on our hunts in Idaho go to www.clarkforkoutfitters.com.
Our California hunts are for bear with hounds but I may start doing some blacktail deer hunting as well since I have seen some very good blacktail in some of the areas I have been hunting for bear.
I am a full time outfitter and guide who does not have a second career to distract me from providing quality service to my clients. It may interest some to know that I am also a sub-guide in Nevada and am eligible for a Master guides license there which I plan on getting for the 2013 season. I can not make any reservations or sign any hunt agreements for hunts in Nevada until I have my master guides license there but I will be happy to discuss my future plans for guiding in Nevada with anyone who inquires.
I have guided for several years in Nevada and was lucky enough to participate as a friend in the first Nevada bear season in 2011. I hunted with Tyler Yohee and on the second day of our hunt my dogs treed a bear that Tyler harvested, it was a super bear with a skull that ended up with an official score of 20 1/2". I will try to post some pictures with this.
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Do you still guide for bear on CA without dogs?
We are no longer guiding in CA. but we are still doing bear hunts in Idaho with bait and/or hounds.


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Running Thoth 1.7.2 (Mac newsreader) out of Jaguar AND Panther (two
Macs via Router).
Ever so often Thoth just keeps crashing (ISP Adelphia). The
solution that works is to by-pass the router (tried two different
routers- Linksys and Netgear) and hook up one Mac at a time directly to
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But the more interesting question is what goes wrong?
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Any ideas that a novice can understand.
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DU's Living Lakes Initiative was conceived to highlight and correct the poor ecological health of larger marshes and shallow lakes in Iowa. Vital to this effort is support from corporate and foundation partners who are needed to help fulfill the conservation objectives of the Initiative.
"Corporate and foundation funding has helped boost DU's wetland conservation effort as part of the Living Lakes Initiative," said Roger Pederson, DU manager of conservation programs for Iowa. "With the support of partners such as Pioneer, DU will be able to leverage their donations to secure additional federal grants for conservation work in the state."
"Pioneer is committed to helping improve the quality of life in the communities where our customers and employees live and work," said Kelly Monier, Pioneer sales representative. "We focus our philanthropic efforts on organizations, like Ducks Unlimited, that support our strategic focus areas of agriculture, education and farm safety."
Iowa Living Lakes projects currently ongoing include the Otter Creek project in Tama County, which will provide water delivery to a 3,600-acre wildlife area. Recently finished projects in Dickinson County include Diamond Lake, Yaeger Slough and Sidel Marsh. A fourth Dickinson County project, Jemmerson Slough, is about 80-percent complete. Dan Green Slough in Clay County is the next large project on the Living Lakes engineering schedule where DU has completed the survey and initial design work. Four Mile Lake, a 215-acre project in Emmet County, is on the docket to be surveyed next.
Many species of wildlife will benefit from the projects, especially migrating ducks and shorebirds that rely on large wetlands to replenish energy and nutrient reserves depleted during their long flight through Iowa in spring and fall. Several shorebird species and at least one duck species, lesser scaup, are in decline continentally, and it is critical to improve and protect the wetlands they rely upon.
With more than a million supporters, Ducks Unlimited is the world's largest and most effective wetland and waterfowl conservation organization. The United States alone has lost more than half of its original wetlands - nature's most productive ecosystem - and continues to lose more than 80,000 wetland acres each year.
Look for Ducks Unlimited on the World Wide Web at www.ducks.org. Tune into The World of Ducks Unlimited Radio Networ, and watch Ducks Unlimited Television on Versus.
Receive a free DU decal when you signup for our free monthly newsletter.
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President Franklin D. Roosevelt signs the Migratory Bird Hunting and Conservation Stamp Act into law.
First duck stamp, designed by Pulitzer-prize winning editorial cartoonist, Jay N. "Ding" Darling, issued.
Prairie drought peaks.


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Tuesday, November 29, 2011
Starbucks K-Cups
An e-mail is on its way to you now so be sure to check your inbox and spam folder.
114 comments :
Brandie -- I am so SOLD on my Keurig!! I simply love it and when I saw my favorite SB coffees were available, well, I about squealed with delight, lol. My favorite is the Sumatran - very bold and so good.ReplyDelete
Thanks for a chance at your fabulous giveaway :)
I love my Keurig, too - I was thinking the same thing you were...what's the fuss? But having a fresh, perfect cup of coffee every time IS something to make a fuss over!! I love French Roast - and all dark blends and can't wait to try the Starbucks K-cups. Thanks for a great giveaway!ReplyDelete
Brandi, my favorite is Breakfast blend, would love to have a cup of it right now with a piece of your honey bun cake. Made 2 in the last couple of weeks, and they did not last anytime. delishReplyDelete
I like the French Roast. What a great giveaway! :)ReplyDelete
Good morning! Welcome to the Keurig world, Brandi! I am brand new to it myself. My son and I just bought a machine last week. Boy oh boy, are we loving it!ReplyDelete
I wish I could tell you my favorite Starbucks blend but I haven't tried any yet. They didn't have it when I went to the local grocery store (small) to get K-cups. Will have to be on the lookout for them.
Happy Keurig'ing! :)
I was given a Keurig machine after my cousin got an upgrade on one. I love it! My favorite SB blend is Caffe Verona, very mellow!ReplyDelete
I just got one at our spouses' club auction two weekends ago -- Dave had had one at his office for the past couple years, so this is a first for us to have one at home.ReplyDelete
Pike's Place Blend is our favorite at the Vollmer house! I've only seen the Starbucks K-Cups at Kohl's here so far...
I love my Keurig! I didn't know Starbucks had their own K-cups though! I buy starbucks coffee for my coffee pot and I love their caramel coffee. MMMMM. Thanks for a great giveaway!ReplyDelete
shugarysweets at yahoo dot com
I LOVE our Keurig, can't imagine life without one ;)ReplyDelete
I am so glad to see that SB came out with a line of K-Cups, would have to say the French Roast is one of my fav!
My Keurig's name is Kerri! And I love her!!! My favorite Starbucks blend is the Kenya blend but it doesn't come in k-cup yet.ReplyDelete
I am not yet fortunate enough to have a Keurig at home but I do have one at work. I absolutely love it and prefer Starbucks coffee to the kind my boss buys....but I can't be too picky since he's the one buying! :) Love the house blend at Starbucks and their white chocolate mocha is my favorite drink! Thanks for another one of your great giveaways!ReplyDelete
Jennifer Kaelin
Colombian blend, for about 8 years now. It's just right!ReplyDelete
- AnonymousNovember 29, 2011 at 9:13 AM
Hi my name is Stephanie and my mother-in-law just got a Keurig brewer and my friend registered for it on her wedding registry. I was skeptical at first but after experiencing my mother-in-law's Keurig, I love it! I also love Starbucks Cafe Estanbul - they don't brew it often but I absolutely love it!! My email address is firstname.lastname@example.com
My favorite blend is the French Roast. Like my dark roast coffee. Would absolutely love one of these!! Thanks for the opportunity to try my luck @ winning one! My email address is: email@example.com
I love my Keurig. I have had it for about 2 yrs. My fave is the House Blend. I love the convenience of making my coffee one cup at a time, any variety that I want. My email is firstname.lastname@example.com
The Breakfast blend is my favorite! Hope I can win some :) my email is: firstname.lastname@example.com
- Nicole Wells email@example.com 29, 2011 at 10:05 AM
I love, love, love my Keurig! Favorite flavor is the House blend. :)ReplyDelete
(You can delete my other comment above. Having issues..lol)
I LOVE my machine,,French Blend is my most favorite,,,what a awesome giveaway,,thanks,,ReplyDelete
I simply adore the seasonal blends, so right now I am enjoying the Christmas blend! We just bought a Keurig a few weeks ago and are still in that learning curve as to what is available and where to get them. Will definitely be picking up some Starbucks k-cups! Thanks for the chance to win!ReplyDelete
I like caffe Verona. I wish the Keurig would get a Carmel macchiato cup. Thanks for the chance at the giveaway.ReplyDelete
I love Verona, always stock up on this blend.ReplyDelete
Jessie C.
tcarolinep at gmail dot com
I love Starbucks' Verona blend, too. It's just a bit sweet and delicious!ReplyDelete
I love their breakfast blend but I'm also a big Sumatra fan :)ReplyDelete
ereaper01 @ gmail.com
I can't believe it that Starbucks has made it to the Kcup. We love ours. I like the breakfast or house blend. Kinipeli1 at gmail. - Loved the post today.ReplyDelete
I usually don't buy starbuck coffee, so i don't have a favorite yet.ReplyDelete
I love the breakfast blend.ReplyDelete
hewella1 at gmail dot com
- AnonymousNovember 29, 2011 at 1:17 PM
Hi my favorite Starbucks is the House Blend.I haven"t bought any for my Keuig but after reading the reviews I sure plan on it.ReplyDelete
I like caffe verona best :)ReplyDelete
littlegray88 at yahoo dot com
We LOVE our Keurig :) and are so excited that Starbucks FINALLY got on the K-cup wagon :P Especially since it seems to be 1 of the only coffees that our little bun-in-the-oven will let me drink :P.ReplyDelete
Love your blog. I need to go make some biscotti now :P
Oh. And I like pretty much all of Starbucks coffee :) When we buy it for at home though, we usually get the House Blend :)ReplyDelete
- Linda BNovember 29, 2011 at 4:30 PM
Have only tried French Roast and Breakfast Blend...can't wait to try other brews!ReplyDelete
Linda B. firstname.lastname@example.com
This comment has been removed by the author.ReplyDelete
I LOVE them ALL!!! I like my coffee hot & i like it iced! I guess you could say i LOVE my Starbucks coffee! I also am in love with my Keurig! Thank you so much for the chance! :)ReplyDelete
I love my Keurig!!! For those days when I only want a single cup it works great, but it's also wonderful when I want more! My favorite is the House Blend.ReplyDelete
House Blend======mmmmmmmmReplyDelete
- AnonymousNovember 29, 2011 at 4:52 PM
I like the Pike place market blend!!Sam AllenReplyDelete
I love the breakfast blend ....also house blend ...hard to decide I love coffee!!ReplyDelete
- AnonymousNovember 29, 2011 at 4:57 PM
Love my Keurig!! So excited that Starbucks has joined the K-cup party!! Caffe Verona is my favorite.ReplyDelete
Michelle Williams
A Keurig is on my Christmas wish list! One advantage: many recipes call for the addition of a little bit of coffee- how great it would be to brew just a cup, use what I need and finish off the rest! Favorite Starbucks- their Christmas blend.ReplyDelete
HAVE HAD MY KEURIG FOR MANY YEARS. WILD BLURBERRY IS TOP ON MY LONG LIST. GREAT FOR JUST HOT WATER TO MAKE TEA. MARY STOTT firstname.lastname@example.com
- angie mccabeNovember 29, 2011 at 5:29 PM
French Roast is my favorite!ReplyDelete
This comment has been removed by the author.ReplyDelete
Love my Keurig. Love Starbucks! Match made in heaven. Favorite blend is Breakfast Blend! Thank you!ReplyDelete
CK Hall
We have had a Keurig for yrs. and really enjoy it.ReplyDelete
My favorite coffee at Starbucks is their Pikes Place... but during the holidays I love their Christmas blend!ReplyDelete
Love Keurig Coffee makers! Makes life so much simpler especially on busy mornings!ReplyDelete
House blend and breakfast blend are great ones!!!
Mary Oxford
Love the house blend...firstname.lastname@example.com
Love my machine. Just bought a mini for the RV. My favorite is Pikes Place.ReplyDelete
Mmmm I'm easy: I just enjoy a good skinny latte when I hit up Starbucks or something pumpkin flavored, if it's the right season. Nice new coffee maker! If the husband and I had one of those I could make myself a cup of flavored goodness in the morning and then make the husband his regular ol' black cup of joe.ReplyDelete
Thanks for the chance! My favorite starbucks blend is the breakfast blend! :)ReplyDelete
deeg131 at gmail dot com
I dont know because I am getting my Keurig for Christmas-a present to myself!!But I love Starbucks peppermint mocha latteReplyDelete
I like them all at different times and diffferent foods occasions.. IU am creature of change so I do not stay with one flavor... I would so love to win once in my life nOT THE WINNING KINDReplyDelete
- Leslie WNovember 29, 2011 at 11:47 PM
I love caramel macchiatos with whipped cream and caramel sauce drizzled on top! Most of the time I make or try to make new combo flavors at home, most have been yummy a few were best poured down the sink, ha!ReplyDelete
- AnonymousNovember 30, 2011 at 6:01 AM
I would have to say that my favorite Starbucks blend is Pike's Place although I do like them all & Starbuck's is really the ONLY coffee I'll drink. firstname.lastname@example.com
- AnonymousNovember 30, 2011 at 6:23 AM
My absolute favorite Starbucks blend is French Roast. ElizabethReplyDelete
- AnonymousNovember 30, 2011 at 7:12 AM
I love the flavored coffees and would enjoy the cute mug also.ReplyDelete
- ChristineNovember 30, 2011 at 7:24 AM
Mmm House Blend! This Mom is addicted to Keurig too. firstname.lastname@example.com
- AnonymousNovember 30, 2011 at 7:25 AM
This contest sounds like fun, please sign me up. My favorite coffe is Starbucks Holiday blend mixed with a little light blend, yummy, gets the blood flowing!ReplyDelete
Pat Sherman
e-mail: firstname.lastname@example.com
Like the intensity of French RoastReplyDelete
I love my Keurig and could never go back to anything else! Right now I'm loving the Holiday blend. You have to try the apple cider k cups - delish!ReplyDelete
Hey Brandy:ReplyDelete
While a coffee lover, I haven't yet bought the Keurig so I would love to win one in your giveaway. Starbucks House Blend is the one that gets me going.
- AnonymousNovember 30, 2011 at 7:41 AM
I love Starbucks......my fav is French Roast. Can't wait to try these K-cups in my Keurig!ReplyDelete
- AnonymousNovember 30, 2011 at 7:42 AM
Haven't tried these yet but looooove my Keurig. I think I would like the breakfast blend best. Thanks!ReplyDelete
jstone45601 @ gmail . Com
I too LOVE my Keurig!!! The company is GREAT too! My local grocer has started to carry the K-cups & that makes life so much easier!!ReplyDelete
Hope I'm the WINNER!!
Thank you for sharing your recipe for the ice coffee!!!
- Carie :)November 30, 2011 at 8:38 AM
I love my Keurig and I love Starbucks House Blend its quite balanced and lively at the same time. Happy Everything to Everybody!!ReplyDelete
I never met a Starbucks blend that I didn't like! Right now I am enjoying their Anniversary blend, and waiting to finish this before I break into the Christmas blend!Yummo...ReplyDelete
French roast would be our fave! And we were slow to get on the Kureig wagon, too, but oh so glad we did!!! Thanks for the opportunity!ReplyDelete
rrgoff06 at gmail dot com
Brandie- I was like you.. What's the BIG deal about Keurig??? all of my family and friends had them, so I jumped on board and bought one... well... i will NEVER have to make my own coffee again... MY HUSBAND has taken over the Keurig and greets me every morning with a cup of coffee delivered right to me in the bed!!! How about that!!!! Why did I wait so long to get one???? His favorite -French Roast.. mine Breakfast Blend!!! great post & give-a-wayReplyDelete
Brandie - we have a Cuisinart Keurig brewer. Was excited when Starbucks came out with K-cups! So far the House blend is my favorite, but can't wait to try all the blends!ReplyDelete
Hi! Wow, another great giveaway! Thanks. :)ReplyDelete
My fav Starbucks coffee is the Breakfast Blend and I love, love, love my Keurig and my K-Cups. My hubby got us one for Christmas last year and we LOVE it! Hi from Bama!
I have looked at the Keurig machines but haven't made the change yet! I love the House Blend. :)ReplyDelete
I love my keurig and told myself if it ever quits I will replace it fast! Love starbucks coffee and really enjoy either the morning blend or the house blend, then stir it with a peppermint stick for a nice treat in the wintertime here in the north!ReplyDelete
I finally just got a Keurig last week and I love it. I like the medium blend cause I don't like it strong. Thanks Mary walker.ReplyDelete
Keurig is on Santa's list this year...would love some SB to go with it!ReplyDelete
Keurig is best thing ever to be made, mine is older model (infact when I called the comp about replacement basket to use my own coffee grounds they couldnt believe I still had it, saying man that one is one of the first ones) and when it goes will have another to replace ASAP my favorite coffee is a toss up, french roast or breakfast blend, hmmm depends on my mood, I just cant pick one, I am def going to starbucks site to check out as I was having to buy from QVC and then groc store started to get a few just not ones I like,-- wheather I win or not I have already won the day I got my KeurigReplyDelete
I love my Keurig Coffee maker! I love a dark roast coffee, so French Roast is a great one for me.ReplyDelete
(It is NOT ok to contact this poster with other services or other commercial interests)
I just LOVE, LOVE, LOVE my Starbucks Coffee. My fav is Breakfast Blend and right now I love to put a little peppermint mocha in it first thing of the morning. Helps me get the day started. Could only be made better if I had your apple dumplings to go with it! That would make my day Bah na nas!ReplyDelete
- CynthiaNovember 30, 2011 at 2:58 PM
I love Starbucks, all coffees.ReplyDelete
French Roast, but I am also a big tea drinker and love their Tazo teasReplyDelete
- AnonymousNovember 30, 2011 at 5:21 PM
French Roast - love the machine - daughter loves the hot chocolate - firstname.lastname@example.com Thanks.ReplyDelete
i love the breakfast roast...it what gets me going in the morning. i think the Keurig coffee maker is the best!ReplyDelete
thanks for sharing!
I love my Keurig - French Roast is my favorite.ReplyDelete
- Elise in San franciscoNovember 30, 2011 at 7:42 PM
The Breakfast Blend gets me going. Thanks so much for the give-away!ReplyDelete
Happy Holidays -
I LOVE Starbuck's French Roast! GREAT giveaway!ReplyDelete
Sumatra for sure! I just got a Keurig machine too, it's awesome. Thanks for the contest!ReplyDelete
I love my Starbucks! I enjoy the HouseBlend too. Now is this timing or what? My husband ordered me a new one as my Christmas present just last weekend. I have been hinting ( or maybe it was whining)for one for 2 years! Love to have some Starbucks to enjoy in it! Thanks!ReplyDelete
My favorite Starbucks coffee is Sumatra Extra Bold. TammyReplyDelete
- Shana JonesNovember 30, 2011 at 11:21 PM
My favorite blend is Verona! It's a mixture of italian and the Yukon blend! ;)ReplyDelete
-Shana Jones/ email@example.com
- Susan @ firstname.lastname@example.com 30, 2011 at 11:37 PM
Loving the Thanksgiving Blend and the Christmas Blend...had a half-caff Eggnog Latte today....yummy!! Hope you had a wonderful Thanksgiving...thank you for our blog!ReplyDelete
Oh, how nice! We like the house blend or breakfast blend best! Thanks! ♥♥♥ReplyDelete
I so love Sumatra. I love my coffee dark with a little cream and a little bailey's, lol.ReplyDelete
Starbucks Breakfast Blend. I also go to Starbucks twice a day. Sounds like the Keurig would be a good investment for meReplyDelete
Just got my Keurig too! I love pretty much anything from starbucks:)ReplyDelete
Casey Coleman
I told you it was wonderful! So glad you got one:) My favorite from Starbucks is salted caramel or peppermint mocha.. maybe one day that will be in my k cup. I have not yet tried their k cups, but i am sure they are great. I love iced coffees and am starting to enjoy hot ones too!ReplyDelete
My favorite Starbucks blend is the Caffe Verona! I worked there for almost 5 years, and I still miss the coffee (although, I don't miss going home smelling like it!)ReplyDelete
AnneMarieKaluza (at) Gmail
What an exciting giveaway! I would have to say my favorite is the house blend. MMM! Love love love my coffee!ReplyDelete
I'm not sure if I could live without my Keurig (a little dramatic I know!) I only drink 1 cup of coffe at home before I go to work so the machine is just perfect. Currently I am addicted to pumpkin spice lattes :)ReplyDelete
- AnonymousDecember 2, 2011 at 9:26 AM
My Keurig should be delivered today!! So excited!! My fav at Starbucks is a vanilla bean frappuccino. Yummo!! Another good mix is iced tea, lowfat milk, shot of vanilla. :)ReplyDelete
- Phyllis villarrealDecember 2, 2011 at 9:31 AM
I like the 'French roast'ReplyDelete
We love our Keurig too! My favorite is house blend with some vanilla creamer and splenda.ReplyDelete
My Keurig should arrive today & I'm So excited to try the Starbucks K-cups. My 1st cup of coffee in the morning really starts my day, especially now that cold weather is here. My love the House Blend which is what I get when I go to Starbucks. Can't wait to have it w/o leaving the house. :) Great giveaway!! Love your recipes!!ReplyDelete
Thanks for the giveaway! I love all of the different blends but House has to be my very favorite:)ReplyDelete
I like a variety of their blends, but house blend is my favorite! Thanks so much for the giveaway.... I love you blog and have used several of your recipes. :) firstname.lastname@example.com
We have a Keurig at our house, for our college age daughter. Somehow that "coffee drinking gene" skipped a generation....neither my husband or I drink coffee! She LOVES Starbucks and anything associated with her Keurig. No idea her favorite though, but she'd be thrilled for me to win this! :-)ReplyDelete
This time of year I love the Christmas Blend but usually I buy the House or French Roast. Happy Holidays!! :)ReplyDelete
Breakfast BlendReplyDelete
Starbucks House Blend...and thank you for all the recipes. We have certainly been eating better since I discovered your website! Thanks!ReplyDelete
Can't beat the House BlendReplyDelete
I first discovered kriton when I visited my son in Charlotte. When I returned home I purchased one immediately. I am now on my 3rd brewer and hav given one to the rest of my kids as well. They are ALL hooked. My favorite brew is the Christmas blend.... YuummmyyyyyReplyDelete
This comment has been removed by the author.ReplyDelete
house blend is my favorite!ReplyDelete
Karen Fiore
I really enjoy their French Roast!ReplyDelete
vandango33 at gmail dot com
- Bobbie StropeDecember 4, 2011 at 5:01 PM
I think house blend!ReplyDelete
New comments are not allowed.


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