text:
Journal of the American College of Cardiology
Identification of Protein Disulfide Isomerase as a Cardiomyocyte Survival Factor in Ischemic Cardiomyopathy
Author + information
- Received February 20, 2007
- Revision received May 7, 2007
- Accepted June 4, 2007
- Published online September 11, 2007.
Author Information
- Anna Severino, PhD⁎,
- Mara Campioni, BSc†,
- Stefania Straino, BSc‡,
- Fadi N. Salloum, PhD§,
- Nina Schmidt, BSc∥,
- Ulrike Herbrand, BSc∥,
- Stilla Frede, BSc∥,⁎⁎,
- Gabriele Toietta, PhD‡,
- Giuliana Di Rocco, PhD¶,
- Rossana Bussani, MD#,
- Furio Silvestri, MD#,
- Maddalena Piro, MD⁎,
- Giovanna Liuzzo, MD⁎,
- Luigi M. Biasucci, MD⁎,
- Pasquale Mellone, MD†,
- Florinda Feroce, MD†,
- Maurizio Capogrossi, MD‡,
- Feliciano Baldi, MD†,
- Joachim Fandrey, PhD∥,⁎⁎,
- Michael Ehrmann, PhD∥,
- Filippo Crea, MD⁎,
- Antonio Abbate, MD§ and
- Alfonso Baldi, MD†,⁎ (alfonsobaldi{at}tiscali.it)
- ↵⁎Reprint requests and correspondence:
Dr. Alfonso Baldi, Department of Biochemistry, Pathology Section, Second University of Naples, Via L. Armanni 5, 80138 Naples, Italy.
Objectives The aim of the study was to analyze the molecular mechanisms activated during postinfarction remodeling in human hearts.
Background The molecular mechanisms of initial response to ischemic insult in the heart and the pathways involved in compensation and remodeling are still largely unknown.
Methods Up-regulation or down-regulation of gene expression in the human viable peri-infarct (vs. remote) myocardial region was investigated by complementary deoxyribonucleic acid array technology and confirmed at a single-gene/protein level with reverse transcriptase polymerase chain reaction and immunohistochemistry. An in vitro model of cardiomyocyte hypoxia in HL1 cells was used to validate anti-apoptotic effects of the candidate gene/protein and to assess the associated downstream cascade. Finally, a mouse model of myocardial infarction was used to test the in vivo effects of exogenous transfection with the candidate gene/protein.
Results Protein disulfide isomerase (PDI), a member of the unfolded protein response, is 3-fold up-regulated in the viable peri-infarct myocardial region, and in a postmortem model, its expression is significantly inversely correlated with apoptotic rate and with presence of heart failure (HF) and biventricular dilatation. Induced PDI expression in HL1 cells conferred protection from hypoxia-induced apoptosis. Adenoviral-mediated PDI gene transfer to the mouse heart resulted in 2.5-fold smaller infarct size, significantly reduced cardiomyocyte apoptosis in the peri-infarct region, and smaller left ventricular end-diastolic diameter versus mice treated with a transgene-null adenoviral vector.
Conclusions These results suggest that PDI promotes survival after ischemic damage and that zinc-superoxide dismutase is one of the PDI molecular targets. Pharmacological modulation of this pathway might prove useful for future prevention and treatment of HF.
Progressive remodeling in ventricular architecture occurs in infarcted and noninfarcted regions, after transmural myocardial infarction (MI). Initially, remodeling is required for maintenance of cardiac output but ultimately leads to left ventricular dysfunction (LVD) and heart failure (HF) (1). Substantial changes in gene expression are required to bring about the profound changes within the ischemic and nonischemic myocardium (2). Experimental studies in animal models of MI have identified several candidate genes whose expression is altered after MI. These include genes involved in the cytoskeleton and contractile apparatus, connective tissue, and in the compensatory response to improve hemodynamics (3). However, owing to the difficulties in obtaining ribonucleic acid (RNA) from infarcted hearts, our knowledge of these events in humans is still limited. Different phenomena occur in MI and are important determinants of HF development: cardiomyocyte loss due to necrosis occurring early during acute MI, apoptosis that might occur in the subsequent days or weeks in the peri-infarcted region and that might play a significant role in expansion of dysfunctional area and therefore in HF development, and fibrosis occurring as replacement of lost myocardium and contributing to myocardial stiffness (4). Experimental animal studies revealing beneficial effects of inhibiting apoptosis support a key role of apoptosis in postinfarction remodeling (5). Therefore, understanding these apoptotic events might provide novel insights into HF and its management. We report that the protein disulfide isomerase (PDI) gene, a member of the unfolded protein response (UPR) regulon, is up-regulated in the viable peri-infarct myocardial region of human hearts within the first days after infarction. The functional consequences of this up-regulation, as demonstrated by in vitro and in vivo models of cardiac hypoxia-ischemia, are a significant decrease in the rate of cardiomyocyte apoptosis and, consequently, in a more favorable ventricular remodeling. These results, for the first time, strongly suggest that PDI plays a key protective role in the myocardium after an infarct and identify PDI as a potential target for future pharmacological treatments.
Postmortem analysis: characteristics of selected cases
Eighteen independent cases were selected at time of autopsy (Department of Pathology, University of Trieste, Italy) according to the following inclusion and exclusion criteria: 1) death occurring 10 to 60 days after acute MI; 2) no evidence of re-infarction at clinical and pathologic assessment; and 3) total occlusion of the infarct-related artery as defined by absence of residual lumen at pathologic examination. All subjects were hospitalized before death. Clinical and pathological characteristics of the subjects are shown Table 1.
Pathological examination and determination of apoptotic cardiomyocytes
Autopsy was performed within 24 h after death in all cases (median 16 h). Gross examination of the hearts and determination of apoptotic cardiomyocytes by co-staining for terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), caspase-3, or muscle-actin were performed as described (6). Tissue specimens (125 to 1,000 mm3) were obtained at sites of MI and in regions of the right ventricle remote from the infarcted area supplied by a patent coronary artery. Specimens were either snap-frozen for RNA extraction or fixed in 10% paraformaldehyde in 0.1 mol/l phosphate-buffered saline. The PDI expression was detected with a rabbit polyclonal antibody anti-PDI H-160 (Santa Cruz Biotechnology, Santa Cruz, California) at 1:200 dilution. Immunohistochemistry and TUNEL scores were performed by 2 pathologists (F.F. and A.B.) unaware of clinical and PDI data.
RNA extraction, complementary deoxyribonucleic acid array analysis and reverse transcriptase polymerase chain reaction (RT-PCR)
Total RNA was extracted from myocardial autoptic samples by using RNeasy Fibrous-Tissue-Extraction-kit (Qiagen, Hilden, Germany). Total RNA was purified with RNeasy mini-columns (Qiagen). Five micrograms of pooled RNAs (from border and remote zones) were used to perform an Atlas Human Cardiovascular array (Clontech, Mountain View, California) analysis. The choice of pooled remote myocardium as comparison was considered essential in order to have an internal (rather than external) control and reduce to the minimum the possibility of postmortem autolysis-related changes. Arrays were scanned with a PhosphorImager and analyzed by ImageQuant 5.0 software (Molecular Dynamics, Sunnyvale, California). The experiment was performed in duplicate, with 2 independent RNA preparations. The PDI up-regulation in the border zone was confirmed by semi-quantitative reverse transcriptase polymerase chain reaction (qPCR) assay on the same pooled RNAs. Two micrograms of total RNA were treated with M-MLV reverse transcriptase (Invitrogen, Carlsbad, California) and amplified with Taq DNA Polymerase (Promega, Madison, Wisconsin). The following oligonucleotides were used: PDI-forward:5′-GGACCACGTCTTGGTGCTGCG-3′, PDI-reverse:5′-GATGACGGCCACCTCGCTGCTGGA-3′, β-actin-forward:5′-AAGAGAGGCATCCTCACCCT-3′, β-actin-reverse:5′-ATCTCCTGCTCGAACTCCAG-3′.
Culture of HL1 cells
HL1 cells are differentiated and proliferating atrial cardiomyocytes derived from mouse AT-1 cells (7). Cells were cultured as described in Claycomb-Medium (JRH Biosciences, Andover, United Kingdom).
Treatment with hypoxic stress
Subconfluent HL1 cultures were kept at 37°C in a humidified sealed chamber (Billups-Rothenburg, Del Mar, California) gassed with 5% carbon dioxide- 95% gaseous nitrogen (5% oxygen) for 24 and 48 h.
Western blot analysis
Immunoblot analysis was performed with rabbit polyclonal antibody anti-PDI H-160 (Santa Cruz Biotechnology) or mouse monoclonal antibody anti–β-actin C-2 (Santa Cruz Biotechnology) at 1:200 dilution.
Isolation of PDI cDNA
Full-length human PDI cDNA was isolated from Phoenix cell line total RNA by RT-PCR. The cDNA was subcloned in P-dominant cDNA (pcDNA) 3.1(+) expression vector with the following oligonucleotides: PDI-forward-BamHI:5′-GATCGGATCCATGCTGCGCCGCGCTCTGCTGT-3′, PDI-reverse-EcoRI:5′-GATCGAATTCTTACAGTTCATCTTTCACAGCTTTCTG-3′.
Site-directed mutagenesis
The point mutants PDI-N (C36/40S) and PDI-C (C383/S387) were generated with a QuickChange site-directed mutagenesis kit (Stratagene, La Jolla, California) on the basis of the long-PCR method. The wild-type PDI (PDI-wt) pcDNA3 was used as a template. The following oligonucleotides were used: PDI-N(1):5′-GGCCAGAGCCTTGGAGTGGCCAGACCAGGGGGCATG-3′, PDI-N(2):5′-CATGCCCCCTGGTCTGGCCACTCTAAGGCTCTGGCC-3′; PDI-C(1):5′-GAGCCAACTGTTTGGAGTGACCAGACCATGGGGCATAG-3′, PDI-C(2):5′-CTATGCCCCATGGTCTGGTCACTCCAAACAGTTGGCTC-3′.
Stable overexpression of PDI-wt and PDI mutants
Transfection of PDI-wt, PDI-N, and PDI-C into HL1 cells was carried out by Lipofectamine (Invitrogen). The PDI-transfected or pcDNA3-transfected cells were selected in the presence of 700 μg/ml G418 for 2 weeks and then maintained in the presence of 300 μg/ml G418. Finally, individual colonies were isolated, expanded, and assayed for the expression of the transfected gene by Western blotting.
Construction of adenoviral vectors
Recombinant adenoviral vectors were constructed with the Ad-Easy system (Stratagene). Viral titers were estimated by serial dilution of the viral stocks in transduced 293 cells and expressed as plaque-forming units/ml (PFU/ml). Viral stocks were negative for presence of replication-competent adenovirus as tested on A549 cells.
Superoxide dismutase activity measurements
Cells were resuspended in TSS (145 mmol/l sodium chloride; 2.5 mmol/l potassium chloride; 10 mmol/l Hepes; 10 mmol/l Glucose; 1.5 mmol/l calcium chloride; 1.2 mmol/l magnesium chloride; pH 7.4) and incubated for 1 min at 37°C. Hydrogen peroxide contents were measured by horseradish peroxidase-enhanced chemiluminescence as described (8).
Flow cytometric analysis
The HL1 cells were fixed in ice-cold 70% ethanol. After resuspension, cells were incubated with propidium iodide (50 μg/ml) and RNaseI (1 mg/ml) for 30 min. Flow cytometry and Expo32 ADC software (Beckman Coulter, Fullerton, California) were used for analysis of sub-G1 DNA content.
Quantitative PCR was done with the Platinum SYBR Green qPCR-superMix-UDG-Kit (Invitrogen) with Rotor-Gene RG3000 from Corbett Research as described (9). The following oligonucleotides were used: mPDI-forward-CAAGTTCTTCAAGAATGGAGACACAGC; mPDI-reverse-TTCTTCAGCCAGTTGACAATGTCATC; mATF6alpha-forward- CGACGTTGTTTGCTGAACTTGGCTA; mATF6alpha-reverse-CTGACTCCCAAGGCATCAAATCC; mBIP-forward-CGATAATCAGCCAACTGTAACAATCAAGG; mBIP-reverse-GGAATTCCAGTCAGATCAAATGTACCC; mGRP94-forward-CACACTAGGTCGTGGAACAACAATTAC; mGRP94-reverse-TCTTGCTACTCCACACGTAGATGG; mEro1-forward-GGTGAACTTGAAGAAGCCTTGTCC; mEro1-reverse-CTTGTAGCTCGCAGACTTAATTCCATCAGG; mPERK-forward-GCGACGGAGCCCGATGACG; mPERK-reverse-GCATCCAGTGCAGCGATTCGTCC; mIRE1a-forward-TCACTGCCGGAAGACGACGTGG; mIRE1a-reverse-CCACAGGACATCCCCAGATTCACTGTCC; mβ-actin-forward-GATTACTGCTCTGGCTCCTAG; mβ-actin-reverse-ACTCATCGTACTCCTGCTTGC.
The housekeeping gene β-actin was used to normalize the results, and cDNA from untreated HL1 cells was used as a reference.
Surgical procedures for in vivo experiments
Experimental procedures complied with the Guidelines of the Italian National Institutes of Health, with the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Academy of Sciences), and were approved by the Institutional Animal Care and Use Committee. Myocardial infarction was induced in 34 C57BL/6 mice (male, 8 weeks of age, Charles-River, Italy) as previously described (10). We set the protocol for in vivo adenoviral-mediated gene transfer as follows: 4 injections, 2 for each side flanking the left coronary artery of adenoviral vectors, were performed into the ventricular wall. The volume of each injection was 2.5 μl (approximate titer 1 × 1010PFU/ml). The size of the heart of animals (8-week-old C56/bl6 mice) hampered both increments in the number of injections and volume for single administration. The chest was closed and mice were allowed to recover. After 48 h animals were re-operated and the left coronary artery was ligated. Sham-operated mice were treated similarly (without adenovirus injection), except that the ligature around the coronary artery was not tied. Animals were killed 1 week after surgery, after echocardiography.
Evaluation of myocardial function in vivo
Echocardiography was performed in 14 conscious mice (7 AdPDI/ green fluorescent protein [GFP]-injected and 7 Adnull/GFP control subjects) with a Sequoia 256c echocardiography device (National Ultrasound, Duluth, Georgia) equipped with a 13-MHz linear transducer as described (10). Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were measured.
Histological and immunohistochemical analysis
After echocardiography, hearts were recovered for histology as described (10). Adenoviral-mediated gene transfer was determined with rabbit polyclonal antibodies for GFP (ABCAM, Cambridge, United Kingdom) and PDI (anti-PDI H-160, Santa Cruz Biotechnology). Apoptosis was detected with co-staining for TUNEL (Apoptag-Oncor, Gaithersburg, Maryland) and muscle actin.
Statistical analysis
Statistical analysis was performed with SPSS 10.1 for Windows (SPSS, Chicago, Illinois). For data obtained from human subjects, quantitative results are expressed as median (interquartile range), because of potential deviations from assumptions of normality. The uncorrected chi-square test or the Fisher exact test was used for categorical variables, when appropriate. Continuous variables were analyzed with Mann-Whitney Uor Wilcoxon rank sum tests for unpaired and paired data, respectively. Correlation between continuous variables was analyzed with the Spearman test. For animal data, quantitative results are expressed as mean ± SE. Continuous variables were analyzed with analysis of variance to compare 3 or more groups and, when p < 0.05, the Student ttest for unpaired data (with Bonferroni's correction) was used to compare 2 of 3 groups at a time. Two-tailed statistical significance was at the 0.05 level.
Apoptosis in human postmortem specimens
Apoptotic cardiomyocytes were detected both in the peri-infarct and remote areas in 18 infarcted hearts. The apoptotic index was significantly higher in the peri-infarct versus remote areas (8.9% [5.1 to 12.6] vs. 0.7% [0.5 to 0.9], p < 0.001). The apoptotic rate both in the peri-infarct and remote areas significantly correlated with increasing cardiac transverse diameter (r = +0.51, p = 0.022; r = +0.48, p = 0.048, respectively) and cardiac weight (r = +0.47, p = 0.042; r = +0.44, p = 0.050, respectively).
PDI is up-regulated after infarction
A human Cardiovascular Array was used to compare the RNA transcripts from 2 different pools: 1 from samples obtained in the peri-infarct region and 1 from a remote area. The PDI gene was up-regulated 3-fold in the RNA extracted from the peri-infarct areas. Semiquantitative RT-PCR was performed on the same pooled RNAs to confirm differential expression (Fig. 1A).Immunohistochemical analysis of PDI expression on all human samples confirmed the up-regulation of PDI at the protein level in the peri-infarct areas (Figs. 1B and 1C). Finally, co-staining for PDI and TUNEL showed that most of the cardiomyocytes over-expressing PDI were TUNEL negative (Fig. 1D).
PDI expression, cardiomyocyte apoptosis, and cardiac remodeling
The PDI was expressed in the peri-infarct areas in all 18 patients investigated but only in 7 in the remote regions (100% vs. 39% of remote regions, p < 0.001). Expression in peri-infarct regions was mild in 3 cases (17%), moderate in 5 (28%), and intense in the remaining 10 cases (55%). The intensity of PDI expression was significantly inversely correlated with the apoptotic rate (r = −0.55, p = 0.021). In the 10 cases with intense PDI expression the apoptotic rate was significantly lower (7.1% [1.4 to 9.0] vs. 12.0% [9.1 to 14.1], p = 0.012) (Fig. 1E) than in the 8 cases with mild or moderate expression (Fig. 1E) (Table 2).Interestingly, subjects with intense PDI expression were less likely to be suffering from stage-C New York Heart Association functional class IV congestive HF (30% vs. 88%, p = 0.025) (Fig. 1F) and to have biventricular enlargement at postmortem examination (20% vs. 88%, p = 0.015) (Fig. 1G).
PDI is over-expressed in vitro under hypoxic conditions and protects cardiomyocytes from apoptosis
Murine HL1 cells were subjected to hypoxic stress, and proteins were extracted at various time points. The PDI protein level increase was detected by Western blot analysis (Fig. 2A).These data suggest that the over-expression of PDI is physiologically relevant and might be beneficial for cells to survive hypoxic conditions. To test this hypothesis, we investigated the functional consequences of PDI over-expression after hypoxic stress in cardiomyocytes. Wild-type PDIas well as 2 enzymatically inactive point mutants, PDI-N[C36/40S] and PDI-C[C383/S387], mapped in 2 thioredoxin-like domains located in the N-terminal and C-terminal regions of the protein (Fig. 2B), were over-expressed in HL1 cells. Increased levels of PDI in transfected cells were verified by Western blot analysis. Stable transfectants were subjected to hypoxic stress, and apoptotic rates were measured by flow cytometric (FACS) analysis. Over-expression of PDI was able to significantly decrease the apoptotic rate in normoxic and hypoxic cardiomyocytes at 24 h and 48 h, respectively (p < 0.001). Over-expression of both enzymatically inactive point mutants rather increased the number of apoptotic cells compared with the control in normoxic and hypoxic conditions at 24 h and 48 h (p < 0.001) (Fig. 2C). These data indicate that the enzymatic activity of PDI specifically protects cells from undergoing apoptosis in hypoxic conditions.
Influence of hypoxia on various genes involved in endoplasmic reticulum stress response
We used total RNA of hypoxia-treated HL1 cells to analyze by qRT-PCR the expression levels of PDI as well as of selected folding catalysts, transmembrane kinases, chaperones, and transcription factors known to be involved in the unfolded protein response of the endoplasmic reticulum (ER) (Fig. 3A).The PDI, Ero1, GRP94, and ATF6-alpha were significantly up-regulated (n = 4, p < 0.05) after exposure to hypoxia. For Ero1 and ATF6-alpha the expression level increased with duration of hypoxia. The expression level of IRE1-alpha increased significantly (p < 0.05) after 48-h exposure to hypoxia but not after 24 h. The messenger ribonucleic acid (mRNA) level of PERK did not significantly change, whereas the level of binding protein (BIP)-mRNA decreased under influence of hypoxia. These results provide independent confirmation for the observed up-regulation of PDI during hypoxia. In addition, the co-upregulation of Ero1 supports the notion that the enzymatic activity of PDI protects cardiomyocytes after hypoxic stress. We have also repeated the qPCR experiments with cells over-expressing PDI. These data indicated that over-expression of PDI did not significantly change the expression of the tested genes, suggesting that the detected effects of PDI over-expression are direct (data not shown).
Superoxide dismutase-1 is a target of the anti-apoptotic action of PDI
To obtain initial insights into protective mechanisms supported by PDI, we investigated whether the anti-apoptotic effects of PDI were caused by its protective action on superoxide dismutase (SOD)-1 (11). The SOD activity was determined by measuring the release of hydrogen peroxide (H2O2) generated during the dismutation of 2 superoxide anions. The HL1 cells over-expressing PDI showed a significantly higher H2O2release than HL1 cells transfected with the vector alone (Fig. 3B). Therefore, PDI was able to protect SOD-1 activity, when over-expressed in HL1 cells.
Protective effects of PDI over-expression in the in vivo acute MI mouse model
The PDI was over-expressed in an in vivo mouse model of MI by injecting adenoviral vectors expressing both PDI and GFP (AdPDI/GFP) into the hearts, before the infarction. As a control, infarcted hearts injected with transgene-null, GFP-expressing adenoviral vectors (Adnull/GFP) or hearts from sham-operated animals were used. Thirty-one mice were killed at day 7: 13 in the AdPDI/GFP group, 12 in the AdGFP group, and 6 in the sham-operated group.
Efficiency of the viral infection by GFP expression and increased myocardial PDI expression in AdPDI/GFP-injected mice were verified by Western blots and immunohistochemistry (Figs. 4Aand 4B). Interestingly, infarct size was significantly smaller in AdPDI/GFP-treated mice, determined as reduced circumferential extension (18 ± 1% vs. 43 ± 1%, p < 0.001) and as transmural extension (30 ± 2% vs. 89 ± 1%, p < 0.001) assessed in the mid-ventricular section (Figs. 4C and 5Ato 5D). The apoptotic rate in the peri-infarct region was also significantly reduced (1.0 ± 0.1% vs. 3.0 ± 0.1%, p < 0.001; p < 0.001 vs. sham operated animals [apoptotic rate 0.01 ± 0.001%]) (Figs. 4D, 5E, and 5F).
In vivo assessment of the remodeling pattern with transthoracic echocardiography confirmed a more favorable pattern in AdPDI/GFP-treated mice. Compared with sham operated mice, Adnull/GFP-treated infarcted mice had significantly greater LVEDD (p < 0.001) and LVESD (p < 0.001). Compared with AdGFP animals, AdPDI/GFP mice had significantly smaller LVEDD (2.50 ± 0.02 mm vs. 3.11 ± 0.06 mm, p = 0.009), similar to that in sham-operated animals (2.49 ± 0.01 mm, p = 0.95) (Fig. 4E). A trend toward lower LVESD values in AdPDI/GFP versus Adnull/GFP-treated mice was also found (1.31 ± 0.01 mm vs. 1.54 ± 0.03 mm, p = 0.054) (Figs. 4E and 4F). Finally, we did not find significant differences in the left ventricular fractional shortening between AdPDI/GFP and Adnull/GFP-treated mice (data not shown).
These data clearly indicate that PDI is over-expressed after hypoxia due to infarction and that this over-expression reduces infarct size and adverse remodeling, thus suggesting that PDI plays a key role in myocardial response to ischemia and in postinfarction cardiac remodeling and dilatation.
The molecular mechanisms causing remodeling after MI are still incompletely understood. As a consequence, most therapeutic approaches to limit injury after infarct, such as pharmacological manipulation and coronary revascularization, are based on the observation of a better clinical outcome associated with myocardial reperfusion or reduced cardiac work (1). Complex interactions between pro-apoptotic and pro-survival factors occur in the region bordering the infarct and remote myocardium for days to weeks after the ischemic event and the apoptotic rate is correlated with worse clinical outcome (12). In the current study, we have identified PDI as a key factor of the survival pathway. The PDI belongs to a family of proteins involved in the UPR system (13), which is activated by stresses that interfere with protein folding in the ER. Failure to eliminate misfolded proteins in the ER leads to cell death via apoptosis, and a variety of human disorders are related to ER stress (14). The role of UPR in ischemic diseases has been studied to a limited extent in the brain (15), tumor cells (16), and the ischemic heart, suggesting a contribution to counteract/repair ischemic damage (17–19).
Our data suggest a significant protective effect of PDI in human infarcted hearts mediated by a reduction of apoptotic rate and by prevention of cardiac remodeling. This association is in agreement with the hypothesis that also in humans the ER stress response is activated to counteract ischemic heart insults. Therefore, we tested the protective effects of PDI in in vitro and in vivo models of hypoxia and ischemia. The in vitro studies suggest that the enzymatic redox function of PDI (i.e., the catalysis for disulfide bond formation) is responsible for the observed protective effects. Accordingly, forced expression of enzymatically inactive point-mutants PDI C36/40S and PDI C383/S387 had no protective effects but rather resulted in an increase of apoptotic rate. These data indicate that both thioredoxin-like domains are critical for this protective function against hypoxic stress, which is in agreement with data obtained with glial cells (20). This model is further supported by the observation that Ero1, which re-oxidizes reduced PDI, is also strongly up-regulated after hypoxia. The induction of PDI and Ero1 is mediated by the transmembrane kinase Ire1 that is also up-regulated under these conditions. Because several other elements of the UPR, such as Grp94/Hsp90 and the transcription factor ATF6, are also up-regulated, we propose that this system plays an important role in the response to ischemia.
Both reduced oxygen supply during coronary occlusion and the oxidative stress associated with reperfusion cause protein folding problems in the ER, because disulfide bond formation requires oxygen and can be compromised by reactive oxygen species. Over-expression of PDI is expected to counteract such problems. Indeed, significant superoxide generation occurs in cardiomyocytes both during ischemia and during reperfusion (21). Over-expression of SOD-1, which efficiently dismutases superoxide, prevents postischemic injury in the heart, attenuating both apoptosis and the inflammatory response during ischemia (22). Interestingly, it has been demonstrated that PDI is over-expressed in familial amyotrophic lateral sclerosis, acting as a survival factor through physical interaction with SOD-1 (11). This interaction prevents SOD-1 aggregation and consequently neuronal degeneration. Our findings of increased SOD activity in myocardiocytes over-expressing PDI are in line with these reports and suggest that over-expression of PDI might protect myocardial tissue from apoptosis, mediated by superoxide, through increased SOD activity.
We analyzed the effects of forced PDI expression in a mouse model of ischemic heart disease. The PDI over-expression was associated with a marked reduction of infarct size, with a significant reduction of cardiomyocyte apoptosis in the peri-infarct region, and prevention of cardiac dilatation, as determined in vivo both by transthoracic echocardiography and by pathological analysis of explanted hearts. Interestingly, we did not find significant differences in the ejection fractional shortening between AdPDI/GFP- versus Adnull/GFP-injected mice. This was probably due to the short window of time (1 week) after the infarction. Indeed, the initial increase of cardiac volumes serves the purpose of preserving the ejection fraction; only late cardiac dilation becomes a mechanism of disease resulting in a reduction of ejection fraction and development of HF (23).
The role of apoptosis in the pathophysiology of HF has been demonstrated, and the potential for preventing ischemic cardiomyopathy and HF by inhibiting apoptosis is promising. Our results from postmortem human hearts and in vitro and in vivo models of hypoxia and ischemia point out a pivotal role for PDI in the programmed survival pathway that promotes cell survival after infarction leading to more favorable cardiac remodeling. The resulting working model for cardiomyocytes close to the ischemic region proposes that PDI acts both on the hypoxic and oxidative stresses, by contributing to the correct protein folding in cooperation with ERO-1 and by modulating the activity of SOD-1. When this molecular mechanism is amplified in cardiomyocytes by over-expression of PDI, the programmed survival pathway is strongly ameliorated, resulting in effective prevention of adverse cardiac remodeling. Pharmacological modulation of this pathway might prove useful for future prevention and treatment of HF.
This work was supported by grants from Second University of Naples, FUTURA-onlus (Rome, Italy), and the Istituto Italiano di Medicina Sociale (IIMS) to Dr. Baldi, and Deutsche Forschungsgemeinschaft grants FA 225/20-2 to Dr. Fandrey and EH 100-11-1 to Dr. Ehrmann.
- Abbreviations and Acronyms
- heart failure
- left ventricular dysfunction
- left ventricular end-diastolic diameter
- left ventricular end-systolic diameter
- myocardial infarction
- protein disulfide isomerase
- qPCR
- quantitative reverse transcriptase polymerase chain reaction
- Received February 20, 2007.
- Revision received May 7, 2007.
- Accepted June 4, 2007.
- American College of Cardiology Foundation
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*Best Price Guarantee – due to a price control bond between Bohol tour providers. Add-on is free of booking charge and payable at the hotel.
Step 1
Select Dates
Step 2
Select Rooms
Step 3
Select Add-Ons
Walk-in Watersports Inquiry
Caloy Incon (*not for Room Inquiries)
(+63) 917 324 2217 (Globe)
(038) 510-6191
Resort Room Inquiry
Marjorie Apilat
(+63) 915 469 8515 (Globe)
(+63) 0999 929 8119 (Smart)
(038) 537-9342
Online Package Reservation
Frequently Asked Questions
1) How do I get to Loboc River Watersports?
If you are coming from Tagbilaran city or from Panglao Island, head towards Loboc town.
By Car or Taxi
You can rent a taxi from Tagbilaran to Loboc. Rate starts at Php 600. Panglao island to Loboc's rates start at Php 1000.
By Jeep or Bus
You can also take the jeepney or bus. The jeepney terminal going to Loboc is situated in front of Island City Mall (ICM). The bus terminal is located in front of Dao Public Market which is very close to Island city Mall (ICM). The jeepney and bus fare going to Loboc ranges from Php25 to Php28.
Loboc River Watersports Landmark
When you reach a Caltex gas station around Camayaan, Loboc. 70 meters from that stop by the signage on the left that says Loboc River Resort. The paddling center is within Loboc River Resort and is a 100 meter walk from there.
2) I have no experience in Stand Up Paddle Boarding, can I join the tours?
Yes, all Stand Up Paddle Board tours begins with an introductory lesson by our guide. It is very easy to learn the sport. Loboc River is known to be one of the cleanest and safest river in the Philippines. The river water is flat and calm which is very good for beginners.
3) How safe is the Stand Up Paddle Board Tour?
Stand Up Paddle Board tours are all guided tours that begins with an introductory lesson. Our assigned tour guides are well trained and they are familiar with the river because they are from the local community. We have a policy to limit 1 tour guide to every 5 persons but we also add more tour guides depending on the age or the experience of the paddlers. We provide complete equipment (board, paddle, leash, (PFD) Personal Floating Device or lifevest)


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By Chris Schultz
Winsted-Lester Prairie Journal & Howard Lake-Waverly Herald, Minn.
Feb. 2, 2004
New trail may be established in our area
Can you imagine a new recreational trail being established in our area in the next few years.
A trail, that if done right, would link up with the Luce Line, and create a great loop for bikers, hikers, snowmobile riders, horseback riders and potentially ATV users.
That could be the case. The old rail line that runs from the western suburbs through Mayer, New Germany, Lester Prairie, and Silver Lake was abandoned some time ago, and now the decision has been made to remove the rails.
Some activists in Hennepin County are already proposing the corridor be turned into a DNR recreational trail similar to the Luce Line Trail.
In our area, there hasn't been much play on the subject yet, but the idea seems to be well received.
If the old line is turned into a trail, and several links to the Luce Line Trail are established, creating a variety of loops and distance options, our area could boast one of the best recreational trail systems in the state.
A trail system of that type would be great for local users, and could be a boom to our local small town economies.
Right now, with the issue, or idea, still in the infant stages, there doesn't seem to be a solid reason why the corridor shouldn't be turned into a trail.
It's a safe bet some negatives or opposition will arise. However, the issue is well worth pursuing.
Moving down the trail a bit, before anyone starts ripping out rails, plans should be made to preserve all the bridges and passes so they don't have to be replaced with new ones if the corridor is turned into a trail.
New bridges and over passes became an expensive venture in the development of the Luce Line and other trails in the state.
Howard Lake Fish Derby
The Howard Lake Sportsmen's Club will host it's 58th annual Fishing Derby Saturday, Feb. 7, from 2 to 4 p.m. on Howard Lake.
The grand prize in this year's drawing is a deluxe Ice Buddy fish house on wheels.
The fish house is on display at Joe's Sport Shop and Hardware in Howard Lake.
Along with the many contests, prizes from many area merchants are given away every five minutes.
Tickets are available at Joe's and from club members.
All proceeds go the Howard Lake Sportsmen's Club and are used for local conservation efforts.
Short-term Sacrifice, Long-term Gain
From the DNR
Short-term sacrifice, long-term gain. That is often the way it is with wildlife management.
Take the case of the hen turkey, for example.
There's a patch of native prairie grasses just across the parking lot at our regional headquarters on the outskirts of New Ulm.
The hen figured it would be a good place to make a nest. And so she did.
That patch of prairie, however, was in dire need of a fire to rejuvenate it.
And so one day last spring, some DNR folks held a prescribed burn.
Not long after the flames began crackling and creeping across that stand of grasses, the hen turkey took flight to escape the fire.
That afternoon, the black ashes still smoldering, she returned to search for her nest.
I admit to a certain sense of melancholy as I watched her wander about. She soon found her way back to the area from where she had earlier taken flight.
Back and forth and in circles she moved, stopping occasionally as if trying to figure it all out.
After perhaps a half hour, she ambled away and disappeared back into the wooded ravine.
Would she find another place to re-nest? Maybe.
Over the spring and summer, that patch of prairie responded beautifully to the fire.
Instead of sparse, thin patches of grasses, by late summer there was a thick, vibrant stand of big and little bluestem, Indiangrass and side-oats grama waving in the breeze.
Next spring there may well be another turkey hen or two nesting in that prairie.
And, judging from recent events, it will probably produce some pheasants.
For much of this winter, that prairie has been providing a perfect roosting area for pheasants.
Now, you typically don't see more than an occasional pheasant around here.
The ravines of the Cottonwood and Minnesota rivers are more suitable for deer, turkeys and other assorted woodland types than pheasants.
But close to thirty pheasants have come from who knows where to take winter refuge in that tangle of native grasses.
And come spring, the odds are good that there will be a bunch of little pheasants scurrying about there.
Early this winter, that same patch of prairie hosted one of the largest flocks of tree sparrows our resident naturalist said he has ever seen.
Tree sparrows nest in the north and spend their winters here in prairie, eating grass and wildflower seeds and spending the night nestled down in the tall grass for cover.
The hen turkey's nest was sacrificed, yes. But in exchange, there will be many more turkeys, pheasants and other wildlife produced there than would have been had that fire not been set.
Such exchanges are not always well understood, or accepted.
It's not uncommon to receive calls from upset citizens when the DNR is conducting spring burns.
There is, for example, a fellow I know who has converted substantial portions of his farm into outstanding wildlife habitat.
He has enrolled the land into several programs, including the Conservation Reserve Program (CRP), Conservation Reserve Enhancement Program (CREP), and Reinvest in Minnesota (RIM).
He understands the value of periodic burns. Yet, last year he refused to allow a parcel to be burned because it was during the nesting season.
Prescribed burns are generally set in the spring, when most prairie plants are still dormant and cool-season, non-native grasses are actively growing.
These spring fires can damage the undesirable cool-season grasses while leaving the desirable, dormant plants untouched.
Fire removes accumulated dead plant material, allowing sunlight to more quickly warm the blackened soil, and helps keep trees from taking over the prairie.
Forb seed germination is stimulated and within a few days after fire, native plants begin to sprout.
In short, spring fires are most helpful for these flowers, forbs and grasses.
Once spring green-up is underway, it becomes much more difficult to get an effective burn.
More attention has been focused in recent years on the public and private benefits of protecting and re-establishing grasslands (such as improved water quality) in the once abundant tallgrass prairie region of the U.S.. And public understanding of the need to use fire as a management tool is increasing.
However, with less than one percent of the original prairie now remaining, and more grasslands being converted to cropland, it is more important than ever that what little prairie does remain is managed well.
The future of grassland-dependent wildlife species from prairie chickens to upland plovers depends on it.
For sure, a spring burn will destroy some nests that year. But in subsequent years, that burn will pay dividends that will far out-weigh one spring's loss.
Short-term sacrifice, long-term gain.
DNR begin the trail designation, forest reclassification process
From the DNR
Next week, the Department of Natural Resources will present six off-highway vehicle trail designation plans to the public for review after completing state road and trail inventories in about a third of Minnesota's 58 State Forests.
The trail inventories are the first step in designating motorized trails in Minnesota State Forests as directed by the 2003 Minnesota Legislature.
Trail designation plans identify which trails will be open or closed to motorized and non-motorized used in the future.
"With drafts of the first six proposed trail designation plans complete, we are ready to seek and consider public comment on the plans and move forward with implementation," said Brad Moore, DNR assistant commissioner of operations.
Completing this work is the first step in better managing OHV use in Minnesota State Forests.
Legislation enacted in 2003 requires all state forests be classified as either "limited" or "closed."
The limited classification allows OHV use only on roads and trails that are posted open leaving the rest of the forest closed to motorized use.
A closed classification means that no OHV use is allowed.
There are 45 state forests classified as managed that must be reclassified over the next few years as either limited or closed.
The former managed classification was less restrictive.
The new legislation also requires that state forest roads and trails be inventoried and evaluated for their potential to support motorized use.
The information collected will form the basis for designating trails and reclassifying managed forests.
The first public meetings in this multi-year process will be scheduled in April.
Visit www.dnr.state.mn.us/ohv for the latest information and public meeting notices or call (888) MINNDNR or (651) 296-6157.
Minnesota conservation officer tales
From the DNR
Officer Lee Alderson (Cloquet) was called to a car-deer accident on I-35 near Cloquet.
The deer was badly injured and had to be destroyed.
There was an element of mystery surrounding this occurrence. Someone had covered the deer with a blanket!
Conservation Officer Jeff Johanson (Osakis) was issuing a citation to an angler for fishing with more than two lines.
CO Johanson asked if the person had ever been cited for a game and fish violation.
The reply was, "Kermit got me 25 years ago for the same thing."
Kermit Peterson was the game warden in the Osakis area in the '60s and '70s and is also CO Johanson's grandfather.
CO Julie Olson (Princeton) reports enforcement action was taken for minor consumption of alcohol.
The two minors were "tipping a few" while ice angling.
They stated they were, "just leaving." When the driver was asked what he was driving, he walked out of the fish house and could not remember where he had parked the truck.
The truck was just to the side of the house. A sober driver was called for the pair.
CO Joyce Kuske (Little Falls) and CO Paul Kuske (Pierz) report adding two new hopefuls to the ranks of conservation officers.
Joyce gave birth to twin boys on Jan. 2.
A DNR firearms safety instructor even got into the act. Gary Hebler drove Joyce to the hospital while Paul was returning from an afternoon hunting trip.
CO Brad Schultz (Center City) notes that anglers have again fallen into sloppy fish measuring habits on area special regulation lakes.
He heard statements such as, "it looked pretty close," or "I thought it was OK."
Measurement lessons are expensive.
During his normal course of duties, Conservation Officer Bruce Lawrence (Pine City) found an ice angler using one too many lines.
The angler explained that he was using the extra line to try to retrieve his cell phone, which he said he had accidentally dropped down his ice hole.
Turned out this was no wrong number. The angler had an underwater TV camera and showed Lawrence the cell phone resting in 15 feet of water.
No answer on whether the angler was able to connect with his cell phone of not.
CO Tim Jenniges (Windom) watched a portable fish house go sailing across an area lake with a SUV in hot pursuit.
The SUV caught up with the fish house after a half-mile chase and proceeded to take it back to the point of origin by holding onto it through the driver's window.
Minutes later the same fish house escaped again and went sailing across the lake.
This time after the SUV caught up with it, it was folded up, and placed in the back end of the vehicle before being transported back.
CO Scott Staples (Carlton) assisted the Cloquet PD with a snowmobile fleeing case.
Charges are pending on a juvenile who was pulling one of his friends on a sled.
When attempting to stop the operator, he fled on the machine leaving his friend behind.
The friend gave all the information on who the operator was.
CO Dan Cogswell (Grand Rapids) reports checking out a complaint of two field dressed deer dumped on posted land on Baich Road near Trout Lake.
The deer (large buck and a fawn) appeared to be from deer season.
Only the head was taken from the buck, the meat and hide were still intact on both deer.
They probably hung in someone's shed and were forgotten, except the bragging rights for the rack.
Any information on this can be relayed through the TIP line (1-800-652-9093) or contact the Grand Rapids DNR enforcement office at (218) 327-4117.
DNR Question of the Week
From the DNR
Q: I recently received my boat license renewal form. In addition to the usual fees, I noticed there is a $5 exotic species surcharge, what is this for?
A: The $5 surcharge on watercraft licenses, which is paid once every three years, is the primary source of funding for DNR efforts to curb the spread and reduce the harm caused by of aquatic exotic species such as Eurasian watermilfoil, zebra mussels, purple loosestrife, and Asian carp.
A state statue allows the DNR Exotic Species Program to use the surcharge for many activities including control, public awareness, law enforcement, monitoring, and research of nuisance aquatic exotic species.
An annual report describing how the funds are used is available at: http://files.dnr.state.mn.us/ecological_services/exotics/annualreport.pdf.
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text:
Maren Higbee
Maren is a seasoned producer and writer – having experience working with TV networks, large corporations, and agencies. Some of her most favorite career highlights include working on The Deadliest Catch, Oprah's Big Give, and Jockeys. After many years in the industry, she decided to update her skills and is slated to get her Masters in Digital Communications from the University of Washington in June of 2015.
Though originally from the Pacific Northwest, the desire to work in production and film took her to the East Coast to pursue her education in that field. Upon graduation, she immediately moved to the pulse of the L.A. scene to follow her dream of writing and directing films. Her adaptable style and creative nature got her into quickly learning new skills like crafting pitch packets, writing branded content, developing budgets, overseeing project timelines, and managing vendor relationships.
After a few years working on a variety of projects, she found herself entrenched in the brand new Reality TV business. Maren's passion for telling others' true-to-life stories inspired her to write a fictional novel as a reflection of actual occurrences in her life as a single, successful professional. What she calls her labor of love has become her most recent success by publishing a book, 'Lana Fray and the Grand Plan' released in 2014.
Her main project at the moment is an enterprise business talk show for Microsoft called Modern Workplace – which has been nominated for two Emmy Awards in its 2014 season.
Maren is a native of Seattle where she resides with her husband, Brandon, and her four-legged furry love, Napoleon. In her spare time, she enjoys wine tasting, long walks outdoors, and – if you get her on the right day – she'll even go skydiving.


text:
|Oracle® Database Utilities
10g Release 1 (10.1)
Part Number B10825-01
|View PDF
The chapters in this part describe the use of external tables.
Chapter 13, " External Tables Concepts"
This chapter describes basic concepts about external tables.
Chapter 14, " The ORACLE_LOADER Access Driver"
This chapter describes the
ORACLE_LOADER access driver.
Chapter 15, " The ORACLE_DATAPUMP Access Driver"
This chapter describes the
ORACLE_DATAPUMP access driver, including its parameters, and information about loading and unloading supported datatypes.


text:
It's a good idea to grab tissues before hitting play on a video George Strait recently recorded for one of his biggest little fans.
The Fort Worth Star-Telegram reports that the country music legend sent well-wishes and love this week to Bella, a 10-year-old from Midland, who was reportedly given two weeks left to live.
According to an Oct. 5 Facebook video posted by Damon Cole, a Fort Worth police officer behind the organization Heroes & Cops Against Childhood Cancer, Bella has undergone numerous surgeries in her lifetime due to a host of health problems.
"First thing Bella asks for when she comes through from anesthesia is George Strait," Cole says in the video. "That's the impact that man has had on her."
In his video message, Strait says he hopes she feels better soon and that he's praying for her.
"I just want you to know that I'm thinking about you, and thank you for listening to me and liking my music," Strait says, as a wide smile grows across his face. "It makes me very happy."
"Anyway, darlin' I hope you get better real soon and, remember, I love you," Strait says.
Strait has been a longtime supporter of children's charities through the Jenifer Strait Memorial Foundation, which he and his wife Norma founded in 1986 following the death of their 13 year-old daughter.
Cole coordinated the video message by reaching out for contacts over social media; he spearheaded a GoFundMe campaign for Bella's family to travel comfortably to Disneyland.
According to his Facebook page, Cole says as a police officer, he often finds himself dealing with children who are scared. He had a Superman logo sewn into his bulletproof vest, so that he could share his "secret" with them.
"Every child should know that a police officer is always there to help them through anything," he writes. "The best way to get that message across is to build up a trusting relationship with them."
In 2012, when he was working for Dallas Police Department, Cole began dressing up as a variety of superheroes and visiting children in hospitals, he writes, and he hopes to visit children in all 50 states.
You can help support his mission by purchasing a t-shirt through this fundraiser or through Cole's Heroes & Cops Against Childhood Cancer GoFundMe account.


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A Pop Quiz on Texting and Driving
Take a pop quiz on texting and driving – in time for back-to-school safety.
The sweet lull of summer driving through neighborhood school zones without a care about the mobile device embedded in your hand is coming to an end! But you never text and drive, right?
Now is the perfect time for a short refresher course on cellphone use while driving. Take this pop quiz and see if you're ready to hit the road.
- True or False. Using a cellphone while driving delays driver reaction time equivalent to driving with a blood alcohol level of .08, the legal limit for drunk driving.
- True or False. Drivers holding a mobile device are 4 times more likely to be in a serious accident. People who text while driving are 23 times more likely to be in an accident.
- True or False. An estimated 26 percent of motor vehicle crashes involve drivers distracted by cellphone use.
- True or False. Texas law prohibits anyone under 18 from using a cell phone while driving.
- True or False. In Texas, cellphone use is prohibited in all school crossing zones, school parking lots and drop-off lanes unless the vehicle is stopped or the driver is using a hands-free device.
ANSWERS: All the statements above are true. If you got five out of five correct, congratulations on acing the class in cellphone driver safety. If you got even one wrong, consider yourself schooled.
Distracted driving caused 90,378 traffic accidents in Texas in 2012. 18,468 people were seriously injured and 453 were killed as a result of distracted driving. According to the National Safety Council, cellphone use while driving contributes to 26 percent of vehicle crashes: 21 percent involve drivers using handheld or hands-free devices, and 5 percent involve texting while driving.
Is texting and driving as dangerous as drunk driving?
National Highway Traffic Safety Administration research showed that delay in driver reaction time is equally impaired whether drivers are using a cellphone or legally drunk behind the wheel. Drivers who text while driving were 23 times more likely to have an accident compared to non-texting drivers. The highest rates of cellphone-related accidents involved drivers ages 16 to 24.
LESSON #1: One of the best ways to avoid a car crash and a trip to the emergency department is to never talk or text while driving.
Drive safely! Medical City Healthcare is pleased to offer this community safety message to promote awareness for responsible drivers. Bookmark FastERTX.com to find one of 17 nearby Medical City Healthcare emergency rooms with average wait times posted online.
This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.


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To contribute to this site, see above menu item "About".
These transcriptions may contain human errors.
As always, confirm these, as you would any other source material.
Will of Ellen McGrath
In re Ellen McGrath deceased
This is the last Will and Testament of me, Ellen McGrath [widow of the late William McGrath] of Riverhead, Harbour Grace, Newfoundland. I give devise and bequeath to my son Joseph McGrath all monies that I may have in Bank at the time of my death, after all Testamentary and other charges on my estate have been paid. I also give, devise and bequeath to my said son Joseph, all my right-title and interest in and to the undivided estate of my aforesaid deceased husband. And I hereby nominate and appoint John Casey, Clerk of the District Court, Harbour Grace aforesaid, Executor to this my last Will and Testament at Riverhead, Harbour Grace aforesaid, this thirty first day of January A. D. one thousand nine hundred and eighteen Ellen her X mark McGrath. Signed by the Testatrix as and for her last Will and Testament in presence of us [after being first read over and explained to the said Testatrix] who at her request, in her presence, and in the presence of each other subscribed our names as witnesses hereto. John Casey George Davis.
Correct Charles H. Emerson
(Listed in the margin next to this will the following)
|Note: The wills in those will books are NOT actual wills.
They are hand-written copies of a, "last will and testament," written
by the court clerk, after the death of the testator, when the executor
presented them to the court for probate. The court clerk didn't list
the signatures at the bottom, he (or she) just put them in the book
in whatever order they were in, on the original document, no spacing
most of the time, no punctuation. The originals were kept by the executor.
We who have typed these wills, have made every effort to include all the errors that were on the microfilm, in order to avoid destroying the integrity of the originals, where ever they may be.
Page Contributed by Judy Benson, Alana Bennett, Wendy Weller and Eric Weller
Revised: October 16, 2001 (Ivy F. Benoit)
Newfoundland's Grand Banks is a non-profit endeavor.
No part of this project may be reproduced in any form
for any purpose other than personal use.
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© Newfoundland's Grand Banks (1999-2019)
Hosted by
Your Community, Online!


text:
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Not a business? We provide a range of property, personal and company searches – pay by credit card and receive your results via email.


text: Dawnn: I know you asked for cooking advice, not relationship advice, but I've got to say that I found your post rather disturbing. In fact, I was tempted to check the date to ensure that it was a message from 1998, not 1958! My questions to you (since you brought all this up): 1) How have you and Brian managed to eat together up till now? Haven't you both eaten the things that pleased you? Why must that change because you are getting married? 2) Why does your husband-to-be *expect* (your word) you to do all the cooking and to cater only to his diet? Why can't you share the cooking? Why can't he cook vegetarian dishes for you? 3) You say if he knows food has no fat in it, he'll refuse to eat it (without tasting it). If someone reacted that way to my cooking, I'd be hurt. Is he always so closed-minded and stubborn? Is that how he reacts to everything that isn't exactly his way? 4) You seem to want us to tell you it is ok to lie to him about the food that you plan to put on his plate. Dear, if you can't even discuss FOOD with this guy honestly, how will you be able to talk about the real issues that come up in relationships? Two people in a committed relationship will always have conflicts. Are you going to deal with all of them by deceiving and lying to your husband? I think it is bizarre to plan for a life together by preparing a bunch of lies, or subjects you deem appropriate to lie about. Have you even discussed these food issues with him? Where are the honesty and sharing in your relationship? I am not a marriage counselor, but it might do you both some good to seek counselling before you marry. It sounds like you two have some very basic communication issues, and that certainly doesn't bode well for a long and happy relationship. Wishing you all the best, Annie _____________________________________________________________________ You don't need to buy Internet access to use free Internet e-mail. Get completely free e-mail from Juno at http://www.juno.com Or call Juno at (800) 654-JUNO [654-5866] ------------------------------


text:
August completely snuck up on me. Seriously, where has this year gone? I'm more excited for classes to start again on Monday than my birthday this Saturday. This is how you know you're getting old. Don't have any plans so far, but Hubs did already give me my gift: a complete set of the Harry Potter movies on BlueRay! Let's just say there will be a marathon in our near future.
In other news, I can officially apply for my associates degree. I've completed all the necessary courses and have enough credits to go ahead and grab that sucker on my way to my Bachelors. It's kind of a big deal. I won't be walking in a ceremony or anything, but that little piece of paper means I'm halfway done with my undergrad. And I'll be the first person on my Mom's side of the family to have a college level degree of any kind. Woot!
Also, you've probably noticed the changes around these parts. I stayed up all night last night making this happen. It's kinda cool, I guess. There's a new page and everything. I think the new look has inspired me to pay more attention to this little blog of mine and you'll start to see me around a bit more. I missed it. So guess what that means? DISCOUNTS!
Use the code "BIRTHDAYGIRL" to get 25% off the Mahogany and the Chestnut ad spots through August 31st!
Is your year flying by as fast as mine is?


text:
Pages: 1
With regards to this: https://www.archlinux.org/todo/move-fil … -possible/
Make it idiot-proof, and someone will breed a better idiot.
-- Oliver Elphick
frony0, just to clarify - only arch developers and trusted users can submit or update packages in the arch repos. If you feel up to it, you can enable the testing repos, and help that way.
Last edited by tomk (2013-05-25 11:03:09)
remember install AUR binaries into usr/bin, report problems to AUR maintainers an/or propose alt PKGBUILDS
the merge begin with you
Well, I suppose that this is somekind of signature, no?
Pages: 1


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A Winter Haven, Florida couple, 24-year-old Christopher Mahurin and 22 year-old Jenna Lynn Frey, for some reason decided that a Walgreen's women's restroom was a good place to bone last Saturday. I personally would prefer something a bit more intimate with less fecal matter, but I guess different strokes for different folks. Things were presumably going well for the pair until a 6-year-old girl entered the restroom and Mahurin handled the situation in absolutely the worst way possible.
This is when the story turns south for Mahurin. While the pair was still in the stall, a 6 year-old female entered the restroom while her father stood nearby, according to Winter Haven police.
After the victim was inside of the restroom, Mahurin exited the stall completely naked. Mahurin immediately pushed the girl towards the door and she began screaming. The victim's father, who was just outside of the restroom door, heard the screams and entered the restroom to grab his daughter.
I guess the kind of crack decision making and general life skills that lead to Walgreen's bathroom intercourse in the first place also dictate that a good way to deal with unwanted sex interruption is to practically maul a young child bare ass naked. Mahurin was booked with charges of lewd/lascivious behavior, indecent exposure, battery and driving with a suspended license. His girlfriend was to my knowledge not charged with anything because I assume police felt sorry for her and figured having that idiot as a boyfriend was punishment enough.


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Buzzer-beater! MC's Burse banks in 30-footer as time expires in OT
SALIDA — Short of winning the lottery and donating the proceeds to build a new gym, there now officially is nothing Isaiah Burse can do to enhance his athletic legacy at Modesto Christian High School.
It's only been three months since Burse quarterbacked the Crusaders to the state small school bowl championship in Carson, ample imprint for most athletes.
But on Thursday he gave the home folks a moment to cherish, banking home a fadeaway 3-pointer from 30 feet, at the buzzer of overtime, to give MC a 66-63 victory against Arcata.
The win propels the Crusaders (24-8) to the Northern California Division 4 semifinal round Saturday night against Salesian of Richmond, which beat Mission 84-65 on Thursday.
MC saw the game sent into overtime when Arcata guard Conor Byrne banked in a contested 3-pointer with 3.5 seconds left in regulation, then the stunned Crusaders fell behind 60-56 when the Tigers scored the first four points of the overtime.
Ryan Riner scored five points during a 7-0 run that game MC a 63-60 lead, but Byrne again had the dagger. His 3-pointer with 18 seconds left hit the front rim, bounced high into the air and fell through to tie the game 63-63.
Modesto Christian worked the clock, but Burse's 3-pointer hit the rim with three seconds left and bounced out of bounds off an Arcata player.
There was exactly one second left, and Gary Porter called time out to set up the play.
Earlier in the game, MC was faced with a throw-in from the same baseline spot — just to the left of the backboard — and ran a lob to Anthony Pratt that he caught and dunked in one motion. This time, they set up in the same alignment, but the ball wasn't about to be lobbed inside.
"The option was to get Isaiah the ball," Porter said. "We wanted it to look like we were set up for our normal play there, which is a lob over the basket."
Burse broke from the pack, backpedalling beyond the arc on the left side. He caught the ball, made one dribble to his left and rose to get off the shot over two charging Tigers.
As soon as it left his hand, it appeared to be sailing slightly to the left. But instead of caroming off the backboard, it kissed the glass and banked cleanly though the net as the buzzer sounded.
"I've done that before," Burse said. "With one second left I knew I had to shoot fast. I caught the ball, cocked the wrist and let it fly.
"I called the bank. Yes I did, and the coaches heard it. Really, I knew it was going to bank, but I didn't know it was going in."
The shot capped Burse's 19-point effort that almost was for naught against a tall, big and talented Arcata team.
The Tigers (26-6) had a lineup of aircraft carriers, with forward Noah Wheeler and Ryan DeHart, who both are 6-foot-5 and weigh more than 230 pounds. But offensively their strength was in their outside game, where 6-6 shooting guard Jordan Semple (29 points) and Byrne (21 points) had their way.
"Tonight, these guys had me by weight and size," said MC's 6-4 junior center Anthony Pratt, who had 15 points. "It was a challenge, but we got the job done.
"What was so hard was the penetration of their guards. We watched game film, so we saw how well they could shoot. It did surprise me how well they shot down the stretch under pressure."
MC led nearly the entire game, but never by more than six points. A late run by the Tigers forged a 53-53 tie with 45 seconds left in regulation, but senior guard Alden Wampler appeared to have hit the game-winner when he hit a 3-pointer — his third of the game — with 15 seconds left in regulation.
All that did was set the stage for Byrne's improbable bank shot that sent the game into overtime, and then Burse's shot to win it.
"I just have the drive," Burse said. "I'm a competitor and I just don't like to lose. We're going to go as far as we can take ourselves and we have the ability here to win the state."
Bee staff writer Brian VanderBeek can be reached at email@example.com or 578-2300.


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UK death metal trio Binah is coming at us with their debut release, Hallucinating in Resurrecture, in late June/early July on CD through Dark Descent Records and as a standard LP via Me Saco Un Ojo.
The album starts off innocently enough with the intro Into the Psychomanteum. Its haunting sounds attempts to get your ready for what is to come, but nothing can prepare you for the descent into hell you are about to take. From the opening chord of Morbid Obumbration, you realize a few things – that Binah has a sweet tone and that they are heavy as hell.
As Hallucinating in Resurrecture continues, you are treated to some nice death metal hitting on influences such as Autopsy and Morbid Angel among others. They give a nod to classic death metal bands and throw in some hooks of their own interspersed throughout the album.
The lead-off track, Morbid Obumbration, is an opus of sorts coming in at just over 7 minutes. It is riffer madness at its best. There are so many riffs throughout the track, but each one fits just as good as the last one. The song just works together as a whole. At no point do you ever feel like they are adding riffs for the sake of having a longer than normal song. Nothing is forced on the opening track, nor is it forced on any of the other tracks either.
The cover art for Hallucinating in Resurrecture was done by MMonsterbrush.
Binah Lineup:
Aort (Rhythm & Lead Guitars, Bass, Synths)
Ilia R.G. (Vocals, Lead Guitars, Synths)
A. Carrier (Drums)
Hallucinating in Resurrecture Track Listing:
Into the Psychomanteum (Intro)
Morbid Obumbration
A New Rotten Dawn
The Emissary
Absorption into the Unearthly
Eminence of the Sombre (Instrumental)
Hallucinating in Resurrecture
Crepuscular Transcendence
Buried Baptistry (Outro)


text: Got my SourceEast card on Wednesday, so thought I'd give it a try at a local site to be sure it works. Went to Cambridge Park&Ride Madingley Rd. Found the charge points after two laps of the site. Plugged in. Applied SourceEast branded smartcard to SourceEast branded post: 'tag read OK' then 'card not found' and a red flashing light (and no charge). Tried the other post (without plugging in) - same result. Called the phone number on the post (same number on card). 'Source East' answered; said they needed to get someone to call me back. Someone from 'PodPoint' called back; after some discussion of the location, decided it wasn't one of their posts (and indeed it says 'Elektromotive' under the SourceEast branding). Gave me the number for Elektromotive. Called the number; answerphone says they are only open 09:00-17:30 mon-fri and suggests leaving a message if wanting to report a fault. Called SourceEast again and explained that I didn't want PodPoint, it's an Elektromotive site. Said someone would call back. Same guy from PodPoint calls back. Called SourceEast a third time. Different guy. Says the only thing he can do is to get someone to call me back - not sure who it will be as he just dials a number and it's 'automated'. Agree that it's a waste of time. So, just as well I wasn't in desperate need of a charge. Also, these unhelpful helplines were all 0845 numbers - haven't they heard that 0845 numbers for helplines are now illegal?


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Different bollards used in our day to day lives
Let's be honest, if you asked 10 people what a bollard is, 9 out of 10 of them probably wouldn't know. That's because bollards are sold by a select few and it's only a few companies and local municipalities that use them for specific uses. The rest of us barely notice them.
However, once someone points it out to you, or you write a blog post about them, you'll always know what a bollard is, but currently the humble bollard gets a bad rap in terms of publicity. It needs more attention. So here are seven different types of bollards that you might encounter in your day to day lives.
Definition. A bollard is a vertical post from short and stumpy to long and thin. They were used for mooring ships and boats to the quay but today are more commonly used as safety and control measures.
Portable Safety Barriers
Portable safety barriers are barriers that are usually installed for a specific time period, like for sporting events or concerts, allowing for easy crowd and traffic control. They are easy to install and just as easy to remove, making for a convenient short term safety and control measure.
Breakaway Bollards
Breakaway bollards are used to prevent traffic from entering unauthorised areas or parking where they are not supposed to. The important point is that they are deterrents and will break off if hit by a car, so they are not to be used as a strict security measure. The reason they break off is so that emergency personnel can access these areas in case of an emergency, meaning the areas will be blocked off but not inaccessible.
Bell Bollards
Bell bollards are flattish bell-shaped humps designed to allow vehicles to roll around them but keeping them off traffic islands at the same time. They allow cars to perform U-turns and tight turns if need be and cars can semi-mount the bollard without actually driving over them.
Rising Bollards
These are automated bollards which are popular in Europe. They are electronically controlled to allow access to buses and emergency vehicles. The bollards remain visible to the general public but will sink into the ground to allow designated vehicles access before rising magically again to prevent the rest of the public from using those roads. '
Of course there's always the 'smart' drivers who think they can quickly pass over the bollard by following close to the legal vehicles in front of them, only to land up marooned on a rising bollard with some significant damage done to their cars.
Redirective Crash Cushion
These crash cushion bollards are self-restoring and can cushion cars at speeds up to 80km/h. These bollards can withstand a different range of impacts, and are built to last.
Recycled Plastic Bollards
While most bollards are made from iron or steel, there is range of recycled plastic bollards, which are ideal as light and medium markers. These are manufactured from recycled plastic from 100% mixed post-consumer waste, are weather resistant, fire proof, crack resistant and are most commonly used in parks and rural environments.
Waterside Mooring
The original bollard, still as effective today as it was when it was first used, probably over 150 years ago. These waterside mooring bollards are perfect to tie watercraft to and are used in canals, lakes, river and seaside. They are designed to have a mushroom appearance that is a large diameter top so that ropes can be dropped over them and will not easily come loose. They often include a cross rod for additional security for tying the ropes.
If you are looking for bollards of all shapes and sizes, talk to your local bollard specialist.


text: The embassy attack was in revenge against the 'state of infidelity,' according to an internet site [AFP] "One of the heroes of 'Qaedat al-Jihad' carried out a suicide operation on the morning of Monday," said the statement, signed by Mustafa Abu al-Yazid, one of Al-Qaeda's leaders. 'Infidel state' The attack was "in revenge against the state of infidelity, called 'Denmark', that posted cartoons hostile to the messenger of Allah," the statement read, according to an English translation provided by Site, a US-based group which monitors Islamic militant internet websites and chat rooms. "This operation is a warning to the infidel state and those who ride with it, so that they are deterred from their sin ... and so that they apologise for what they did," Yazid added. Site said the message was posted across several forums. Danish intelligence officials said earlier on Wednesday that the attack had been meticulously planned for a "long time and with precision". Denmark's secret services have sent three experts to Islamabad as part of their investigation. Victims of attack One Danish citizen of Pakistani origin and two Pakistani employees were among the dead in the blast that badly damaged the embassy and the offices of a UN-backed aid agency. Al-Qaeda called for attacks on Danish targets after Danish newspapers ran caricatures of the prophet Mohammed. Danish newspapers first published the controversial cartoons in 2005, sparking violent protests in Pakistan and other Muslim countries. Several dailies reprinted the sketches in February this year. Yazid said al-Qaeda congratulated "the Pakistani mujahideen ... the pioneers of the religious fervor and Islamic zeal, who participated" in the attack. SOURCE: Agencies


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Monday, February 20, 2012 10:00am ET by Newsdesk
Rihanna starts work on new material
Superstar Rihanna has revealed that she is currently working on new material during her stay in London.
The 24-year-old, who is in the capital for tomorrow's Brit Awards where she is nominated for Best International Female, confessed on Twitter that she has set up a makeshift studio in her hotel room in order to record brand new music:
"Brit rehearsal went smoove! Next stop, set up studio in a hotel room. Brits rehearsal was #FAWESOME I'll be turning 24 making mu$ic!!! (sic)"
The news comes in the same week that she is set to release a new remix of Talk That Talk album track, 'Birthday Cake,' which according to its co-producers, Da Internz, features a guest artist that is "gonna shock the world."
The 'We Found Love' hit-maker, who celebrated her birthday today, has acquired a reputation as one of pop's most prolific stars, having released six studio albums in six years.
Watch Rihanna's performance with Coldplay at last week's Grammy Awards below:
Latest 10 Rihanna News Stories


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The Willamette Valley Company's Railroad Division is the industry leader in providing innovative new products and application systems for today's railroads. The Railroad Division's proprietary product, SpikeFast®, has quickly become the most sought-after and reliable product for plugging spike holes. The Railroad Division also offers other railroad tie products for wood and concrete ties, and unique application systems to accurately and consistently apply proven products.
Today's modern railroads face diverse and unique challenges in daily maintenance projects. Let Willamette Valley Company's Railroad Division show you how easy it can be to repair your ties and get the best return on your investment.


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Green Trails Maps
Green Trails Maps, California
$ 13.95
Red Rock Canyon National Conservation Area is a topographic trails map of Red Rock Canyon NCA in the greater Las Vegas area. This map features all the trails with trail names, point-to-point mileages, and trailheads. The obverse side covers the north side and the reverse side covers the south side. The table provides the main trails for Spring Mountain Ranch State Park and Red Rock Canyon National Conservation Area with their trail names, map side, map coordinates, mileage, kilometerage, and trail difficulties for hikers, horseback riders, mountain bicyclists, and those with physical disabilities. Two-sided, self-cover, paper folded map. Projection = UTM Zone 11 Datum = NAD27 Contour Interval = 40' Size:* Folded = 9" x 6"* Unfolded = 18" x 24"
- Topographic Trails Map
- Trail Names, Point-to-Point Trail Mileages, & Trailheads
- Table of Principle Trails


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Taming a long tail
Tidying up a long cast-on tail to be used in seaming later on…
Tidying up a long cast-on tail to be used in seaming later on…
Knitting Needles Conversion Charts showing contemporary US sizes vs UK/Metric size.
Ellen working on her granny stripes blanket (video).
Why don't left-handed knitters have to "reverse everything" in patterns? Here's why…
Video tutorial for making a slip knot directly onto the knitting needle (left-handed knitting)
A little photo tutorial, in which I show you how to knit, hand felt, and stiffen a little trinket box. It's a little fun make, great for getting to grips with felting!
Here's my little pattern/photo guide to making a cute pair of knitted teddy ears that you can use to customise a hat, or anything else! First, you'll need to follow this little written pattern. Abbreviations: k = knit, p = purl, k2tog = … Continued
How many of us find ourselves in this situation?…we find a pattern we like, oh it's beautiful…but…. You add up the cost of all those balls of lovely wool used in the design and almost faint at the outcome! Oh no, … Continued


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A1 Heating Inc
- Electrical, Heating and Plumbing
- Maintenance
At A1 Heating, Residential Heating, Cooling and Indoor Air Quality is our passion. We've had the opportunity to work on dozens of exciting and interesting retrofit projects. We work closely with both our customer and suppliers to find solutions to some very complex, and sometimes challenging applications. We also provide heating and cooling service, maintenance, sales & installation on a wide range of HVAC products in the market today. Servicing all brands! If your home comfort is an issue, we're here help! A1 Heating, proudly serving Trent Hills and surrounding areas
Hot DealsMember to Member DealPrint Coupon
273 13th Line West, Hastings, ON, K0L 1Y0


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More than 200 council workers at borough and county level were disciplined over a three-year period, a Freedom ofInformation request has uncovered.
Responses on disciplinary action taken by the area's local authorities showed 42 Hertfordshire County Council and five Dacorum Borough Council staff members were fully dismissed because of misconduct between 2011 and 2014.
County statistics – which also revealed a total of 190 staff were disciplined with 15 of those resulting in resignation – were taken from March 31, 2011 to April 1, 2014. Conversely Dacorum Borough Council – which revealed there were nine cases of gross misconduct in its neighbourhood delivery department resulting in a final warning being issued – takes its data from November to November, 2011 to 2014.
The county authority employed 8,451 people as of March 2014 – a reduction of 1,939 on overall staff numbers in 2011. Derrick Ashley, county cabinet member for resources, said: "In an organisation of more than 8,000 employees there will inevitably be a few occasions where behaviour is not as it should be and disciplinary measures are necessary.
"Thankfully these occasions are rare – just 0.7 per cent of our staff were involved in disciplinary proceedings over the last three years, and only a tiny fraction had to be dismissed as a result."
Dacorum Borough Council currently employs 740 people, and of the five outright dismissed for their conduct. three were in the housing department and two were from the neighbourhood delivery section.
Group manager for people Matthew Rawdon confirmed the authority deals with staff conduct issues very seriously to ensure customers get the best possible services, adding: "In the infrequent case staff fall short of our conduct expectations, we will take appropriate disciplinary action. We carry out rigorous pre-employment checks to ensure that we employ excellent staff to deliver first-rate services."
See below the full responses to the Gazette's Freedom of Information request:
> Dacorum Borough Council:
Gross misconduct where the outcome was dismissal: 3 Cases in Housing, 2 cases in Neighbourhood Delivery
Misconduct where a first written warning was issued: 9 cases in Housing, 10 cases in Neighbourhood Delivery, 2 cases in Finance and Resources,1 case in Planning, Development and Regeneration area
Misconduct where a final written warning was issued: 3 cases in Neighbourhood Delivery, 1 case in Housing
Gross misconduct where a final written warning was issued: 9 cases in Neighbourhood Delivery
> Herts County Council:
Disciplines by department: 15 in Community Protection, 66 in Children Services, 10 in Environment, 18 in Herts Catering Ltd, 59 in Health and Community Services & Public Health, 22 in Resources & Performance
Types of transgression: 20 of Fraud, 16 of ICT Breach, 115 of Inappropriate Conduct, 9 of Professional Negligence, 19 of Safeguarding Breach, 7 of theft and 6 other
Types of disciplinary action taken: 42 Dismissals, 42 final written warnings, 47 first written warnings, 31 of No Case to Answer, 15 resignations, 10 verbal warnings and 3 other


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- GMR uses geostationary satellites. Downlink signals from this system are visible over large areas of the Earth's surface, especially for someone looking at the sky with a dish antenna.
- GMR handsets use wide-beam antennas. Uplink signals from the handsets are visible from space, not just at the serving satellite, but over really big regions of space, occupied by lots of other satellites.
- Uplink signals from satellite phones are also visible on the ground in a vicinity of the handset, probably at ranges of several kilometers for interceptors with directional antennas. These handsets are easy to detect in a radio environment because they transmit distinctive patterns and are relatively rare (much rarer than cellular handsets, for instance). And any transmitter that can be detected can be located, using any of a number of techniques commonly practiced by most intelligence services.
- The level of air interface security on GMR handsets is probably lower than on cellular handsets. But even if the air interface were absolutely secure, a GMR handset would still be easy to locate by it's distinctive radio signature.
- GMR handsets include GPS receivers and transmit identity and location information to the network operator. These transmissions are completely in the clear, but even if they were encrypted, the network operator would have access to this information.
- GMR encryption is not end-to-end, so the network operator normally has access to plaintext user traffic.
- GMR handsets register with the network periodically, reporting identity and location, even when you are not "using" them.
- Even if a GMR operator, as an organization, is sincerely dedicated to the security and privacy of its customers, it is difficult to completely protect a large organization from infiltration by criminal organizations or state intelligence services, through technical hacking, social engineering, bribery, blackmail, political/religious recruitment, etc.
- Everything I just said about GMR is at least mostly true (if not completely true) of any civilian satellite telecom product and even a lot of military satcom systems.
- Satellite phone users tend to be more interesting than the general population. Because satellite phones are relatively expensive and mostly used by international travelers, the conversations they carry tend to have interesting content, things that the users thought were important enough to spend real money talking about. So, for an intelligence service, eavesdropping on satellite phones is a more effective use of resources than eavesdropping on most other kinds of networks. They get less "mom and pop crap" and a lot more useful information.
- In any given country, the users of satellite phones are mostly foreigners, who are often subject to a lower legal standard for eavesdropping, especially for international telephone calls.
23 February 2012
Some Comments on Satellite Phones
8 comments:
- Anonymous23 February, 2012 16:44
so shd ppl on obsolete technology devices be concerned
even if the location feature has bern turned off?
it has happened to ppl -- blutooth turned off but still actively contled by smarter pplReplies
Mobile is a best way to communicating with any area of the world.Mobile Social networkMosork - Mobile Social Network. Find and connect with friends no matter where they are.Delete
It's not about obsolete technology or the location feature. It's about the fact that you are transmitting a distinctive radio signal.ReplyDelete
- Anonymous24 February, 2012 02:26
Also of interest with the security of sat phones crypto:ReplyDelete
Don't Trust Satellite Phones: A Security Analysis of Two Satphone Standards
Benedikt Driessen, Ralf Hund, Carsten Willems, Christof Paar, Thorsten Holz - IEEE Symposium on Security & Privacy (Oakland), 2012
- Anonymous24 February, 2012 07:34
Thanks for your informed comments.ReplyDelete
As in many other areas of IT security, the movement of packets themselves are as telling as their content.
The phrase "There's someone over there with fancy comms and it's not us" says it all.
It is the same Paul, I talked to him about it just the other day. Great site, I really like it.ReplyDelete
Fta Receiver
Satellite phone are also the best option for the travelers.ReplyDelete
Satellites have become a very big part to many aspects of our everyday lives. Our cellphones, most TV networks, GPS, and so many other things all depend on satellites to function the way they need to. We have come a long way with them over the last few decades, and it makes me wonder how this technology will change in the next couple of decades.ReplyDelete


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Our Homeschooling Year.
We started our first week of homeschooling on Monday the 31st of August.
Shew. It has been a rough few days trying to get the kids back into a routine of actually doing something. Of course I have all kinds of wonderful expectations and fantasies of how each day will go. Days filled with cheerfulness and glorious learning! Curiosity filled kids, bright sunshine…
Annnnd then there's reality.
A screaming toddler creating havoc on purpose to get attention.
A whining five year old who is having trouble learning that the world doesn't revolve around her, and that she needs to control her emotions.
A nine year old who thinks she already knows everything.
Check, check, check, check…adds up to a great day, right?
I wanted to RIP. MY. HAIR. OUT.
I am so burned out after our summer of moving and Igor. I'm having trouble just getting dressed in the morning. It's not depression, it's just something like extreme exhaustion. I need a beach vacation to reset, and I need a week of being waited on hand and foot. No chores, no fighting kids, no responsibilities.
That will never happen. Even one night of full sleep will never happen.
I try not to fixate on all of this wishful thinking. It only leads to frustration and disappointment.
Luckily yesterday, Wednesday, was a bit smoother and the kids were more receptive and interested in learning. Today both girls have done math, and Ada did some reading and phonics work while Rosie read a book to herself.
We've managed to get the week's Latin lesson fully accomplished, and the girls are working on memorizing our homeschool's motto and rules.
I have other things I'm planning on adding into our curriculum for Rosie. We're going to be doing more reading from Ambleside Online's Year 4. I'm still working on planning out that part of our curriculum though. I haven't had a spare second to work on it!
I see no harm in slowly easing into the school year, anyway. As much as I just want to start out and have a perfect day right off the bat we all know that will not realistically happen. Life is messy and imperfect. I'm working on accepting that.
It's a very scary balancing act–doing the regular chores, raising the kids, and accomplishing the best learning ever. ;) I think it will take me years to perfect it, if it ever happens. Though I have to say each year that goes by it's getting easier to balance schooling and chores, even with adding on Ada in kindergarten and a terrifying toddler Henry.
Here's some of what Rosie is going to be doing for the fall term in 4th grade:
Science: Focusing on flying creatures, a Christian curriculum, but yes I also teach her about evolution.
Nature Study: Nature walks outside, one plant a week water color painted with notes in her notebook)
Reading science books including Madam How and Lady Why, The Story Book of Science
Poetry: Yeats, Tennyson,
Bible: The New Testament, starting with studying fruits of the spirit
History: Ancient history starting with the Romans in Story of the World
A Child's History of Architecture
US History starting at the beginning of This Country of Ours
Math: Since there is so much struggle here we're re-doing 3rd grade concepts first
Latin: Latina Christiana Level 1
Beginning Spanish
Literature: Unabridged classics starting with Peter Pan, Mary Poppins, The Jungle Book, Black Beauty, Pollyanna, The Secret Garden, The Railway Children, Robinson Crusoe, and Kidnapped by Robert Louis Stevenson
Short story read alouds by Washington Irving–Paul Revere's Ride, The Legend of Sleepy Hollow, Rip Van Winkle
We're also studying Da Vinci's art and observation notebooks this year, which is pretty fascinating. Rule of thirds is probably one of the most amazing things I have ever learned and I can't wait to explain it to Rosie.
I'm going to add in some geography also. We never finished reading Tree in the Trail last year, so we will squeeze in the completion of that. Minn of the Mississippi also by Holling is up next on the agenda. I saw a really neat idea for how to teach geography by making your own maps, so we may try that at some point during the year. Maybe in the dead of winter…
We're also doing monthly field trips to the zoo for their homeschooler classes. If I can ever gather up enough spare cash I want to get a membership to COSI also. It's a great science/children's musuem. I need to check into their classes.
We've also got some cool class offerings at various local parks to attend. One coming up next week is creeking.
For kindergarten Ada is focusing on learning basic math and reading. She already has a good start, but we're purposefully hammering home the foundations of math and phonics now and making sure there are no gaps. She's learning handwriting too, but she's a perfectionist so I'm not pushing it really hard. We also read lots of good quality children's books. For example we're reading the original Winnie the Pooh stories. She goes on nature walks with Rosie too. I love kindergarten. Such a fun age!
I constantly worry that Rosie isn't learning enough, but recently I helped my neighbor with her homework. She's in 4th grade. It was like what Rosie would have done in first grade. I was shocked. So I feel a little better about things now, haha.


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Ok so I had one blog post last year and I'm not letting that happen again! Its September. Early September. I'm already getting pumped for the new season, and I doubt we'll see snow till November at the Earliest. Praying for an amazing season, lay a solid base maybe in October, very early Nov? Be skiing by Nov 15? Please?! Last year waiting was the worst.
I'm also thinking about going out to A-Basin for a few days if we don't have any snow. If anyone has gone before and has any ideas, please, let me know!
I'm planning out some designs for a backyard rail too so that'll be awesome.
The Fall Semester is underway and its stressin me out. I havent reverted to drawing stick skiers hitting raw jumps over my notes but seriously its only a matter of time. Seriously though I need a 3.5 at least so I gotta do work. Its gonna be tough when things get colder though, right now its still basically summer.
Anyway, thats all I've got for now, my Syracuse Orangemen lost their second game today, this one against Akron... So I think thats it for Greg Robinson has head coach, I dont know when he's gone though, either soon or the end of the season. I still have hope we're gonna pull out a few wins this season though!!
PS: NYS Ski and Board sale at the fairgrounds in Syracuse!! Cant wait! Its Sept 12,13,14.


text:
Customs Central Excise Recruitment 2019 Customs Vibhag Applications form
Customs Central Excise Recruitment 2019 Apply Online For Customs Vibhag Applications form under Clerk, Assistant, Accountant and Inspector Jobs in Customs Central Excise.
Customs Vibhag recruitment 2018 Ministry of Finance, Department of Revenue Directorate of Logistics Central Excise department Online application form Recruitment in 2019 Bharti New Delhi Applications are invited from Indian national by Directorate of Logistics for the following Group's' officers post in the Marine Department under Central Board of Excise & Customs New Delhi on deputation or re-employment basis from the working/Ex-sailors of Indian Navy and Central Government Offices.
Central Excise Department Recruitment 2018-19: The posts are located all over India for Customs Central Excise Recruitment 2019 Patrol Vessels, Customs Marine Workshops and Headquarters. The details of posts, education & other qualifications, number of vacancies and pay scales are as follows:-RECRUITMENT OF ENGINEERS AND SKIPPERS GROUP "B" IN THE CUSTOM MARINE
S.N. 1 Post: Engineer (Hull)
Number of Vacancies: 03
Scale: Rs 7450-225-11500 (pre-revised), PB-2 (9300-34800) GP-Rs.4600/- (Revised)
Eligibility for Deputation: Officers under the Central Government Essential: Degree in Mechanical Engineering or Naval Architecture
S.N. 2 Posts: Engineer (Electrical)
Number of Vacancies:
Scale: Rs 7450-225-11500 (pre-revised), PB-2 (9300-34800) GP-4600/- (Revised) Essential: (i) Degree in Electronics and Telecommunications or Electrical Engineering
S.N. 3 Posts: Engineer (Marine)
Number of Vacancies:
Essential: (i) Degree in Mechanical Engineering; and
(ii) Two years experience on Board a Mechanized Vessel.
(i) Diploma in Mechanical Engineering: and
(ii) Four years experience on Board a Mechanized Vessel
S.N. 4. Post : Skipper
Number of Vacancies:
Essential: Certificate of Competency as second hand of fishing vessel issued by the Mercantile Marine Department of Govt. of India with three years sea experience on board mechanized vessel.
Other eligible candidates for re-employment are required to forward their application as per prescribed Performa containing education, qualification and experience to Directorate of Logistics, Customs & Central Excise, 4th Floor, 'A' Wing, Lok Nayak Bhawan, Khan Market, New Delhi-110511 within 60 days from the date of publication of this advertisement in the Employment News. Marking envelop for Additional Director (Admn.) by indicating clearly post applied for.
Government of India
Ministry of Finance, Department of Revenue
Directorate of Logistics, Customs & Central Excise
4th Floor, 'A' Wing Lok Nayak Bhawan, Khan Market,
New Delhi-110511