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Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 β2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation.
Neutrophils are recruited to inflamed sites, where they are required for microbial clearance. Neutrophil recruitment is a multistep process, which comprises initial tethering and rolling along the vessel wall, firm adhesion to endothelial cells, and eventual extravasation. It involves consecutively various adhesion molecules, including selectins and β2 integrins.1–4
Granules of endothelial cells (Weibel-Palade bodies) and of platelets (α-granules) contain P-selectin. Inflammatory stimuli cause its translocation at the endothelial cell surface. The interaction with the counterreceptor, PSGL-1, prompts leukocyte tethering and rolling and initiates the second phase of the process, firm adhesion. During these events, integrins shift to an active conformation.5–7 Integrin activation depends on the signaling cascade downstream the P-selectin/PSGL-1 interaction.8–10
Platelets adhere and are activated at sites of vascular injury: there, they produce a releasate, some contents of which penetrate and/or interact biochemically with neutrophils. This includes unprocessed free arachidonic acid which can then be transformed into leukotriene A4 and B4.11–14 Furthermore, activated platelets express P-selectin. Platelet P-selectin guarantees the access of leukocytes to perivascular tissues even when dying or severely damaged endothelial cells fail to sustain leukocyte rolling and adhesion.15,16 Indeed, endothelial cells surrounding the lesion release signals that amplify the expression of P-selectin on adhering platelets.17
The P-selectin–dependent interaction of neutrophils and platelets amplifies mutually, promoting the exchange of metabolites and protecting released molecules from plasma inhibitors.14 All together, neutrophil recruitment contributes to local inflammation, defense against invading microbes and possibly tissue repair. Neutrophils could however also play a detrimental role, exacerbating tissue damage.
The interaction between neutrophils and activated platelets also occurs in the blood, yielding cell aggregates, which are hallmarks of acute myocardial infarction, sepsis, and inflammatory and myeloproliferative disorders.18,19 Neutrophils that recognize P-selectin on endothelia and on platelets attached to the vessel wall activate intracellular signaling pathways required to cross the endothelial barrier and enter in the tissue.10 Flowing neutrophils, after recognition of P-selectin on platelets, activate identical intracellular signaling cascades5,20–22 but do not leave the vessels.18 Recognition of P-selectin initiates phagocytosis.23
Here, we describe a cell clearance program downstream platelet P-selectin recognition, which results in platelet phagocytosis and neutrophil degranulation.
BCECF-AM (2′,7′-bis-(2-carboxyethyl)-5(6)-carboxy-fluorescein triacetoxy methyl ester), the pHrodo Phagocytosis Particle Labeling Kit for Flow Cytometry, and the Zenon IgG Labeling Kit were purchased from Invitrogen (Milan, Italy); prostaglandin E1 (PGE1) was from Cayman (Milan, Italy); thrombin receptor agonist peptide-6 (TRAP-6) was from Bachem (Milan, Italy); collagen was from Horm (Milan, Italy); Thrombofix IO test 3 fixing solution was from Immunotech (Instrumentation Laboratories, Milan, Italy); and the FIX & PERM Kit was from Caltag (Turin, Italy). Recombinant chicken annexin A524 was a generous gift of Professor Martin Herrmann (University of Erlangen, Erlangen, Germany). EDTA (ethylenediamine-tetraacetic acid), HEPES (N-2-hydroxyethyl piperazine-N′-2-ethanesulfonic acid), ADP (adenosine diphosphate), fMLP (N-Formyl-Met-Leu-Phe), cytochalasin D, and the other chemicals were from Sigma-Aldrich (St Louis, MO).
Monoclonal antibodies (mAbs) against CD14 (clone RMO52), β2 integrin (CD18, clone 7E4), CD11b/CD18 (αMβ2, also called Mac-1, clone Bear-1), CD42a (platelet glycoprotein Ibα, clone SZ2), CD45 (clone J33), CD61 (platelet glycoprotein IIIa, also called β3, clone SZ21), CD62P (P-selectin, clone CLBThromb/6), CD66b (clone 80H3), CD162 (PSGL-1, clone PL1), MPO (clone CLB-MPO-1), the isotype-matched control (clone 679.1Mc7), and FITC-labeled annexin A5 were from Immunotech (Milan, Italy). The nonblocking, P-selectin–specific AK-4 mAb, anti–mouse CD61 (clone 2C9.G2), anti-CD14 (clone mC5-3), and anti-CD45 (clone 30-F11) and its appropriate isotypic controls were from Becton Dickinson (San Jose, CA).
Venous peripheral blood was obtained upon informed consent from 15 consecutive patients with Segment T elevation acute myocardial infarction within 12 hours from onset of symptoms. Exclusion criteria were as follows: age below 18 or above 75 years, serum creatinine above 2 mg/dL, anemia, history of cancer, or immune-mediated disorders. Venous blood was obtained in parallel from 15 healthy controls. The institutional ethic committee approved the study. Blood was collected in plastic tubes containing sodium citrate, sodium EDTA, N-ethylmaleimide, and aprotinin, processed as described,18 and prepared for flow cytometry and confocal microscopy studies. The institutional ethics committee approved the study and informed consent was obtained from all patients in accordance with the Declaration of Helsinki.
Platelets and neutrophils
Venous blood was collected after informed consent from healthy volunteers, who did not receive any medication for at least 2 weeks. When indicated, blood was collected 4 hours after aspirin (500 mg) ingestion. Blood was drawn with an 18-G needle, dripping freely into open tubes, containing 3.8% sodium citrate (1:9, vol:vol). Neutrophils and platelets were isolated as described5 and resuspended in HEPES-Tyrode buffer (pH 7.4) containing CaCl2 (1 mM). Cells were routinely assessed by flow cytometry using anti-CD14, anti-CD45, and anti-CD61 mAbs to exclude potential contaminations.
Adhesion and phagocytosis
Platelets (2 × 109/mL) were treated at 37°C with TRAP-6 (25 μM, activated platelets) or with PGE1 (5 μM, resting platelets) for 2 minutes. Then, neutrophil suspensions (2 × 107 cells/mL) were added at a physiologic 20:1 platelet-to-neutrophil ratio (100 000 platelets to 5000 neutrophils). Reactions were stopped after 5 minutes and aliquots for the assessment of activation markers were retrieved and maintained at 4°C until analysis. When indicated, cells were preincubated with CLBThromb/6, PL1, SZ2, 7E4, Bear-1, or with the irrelevant isotype-matched 679.1Mc7 mAb at a final concentration of 20 μg/mL. Alternatively, the recognition of anionic phospholipids on platelets was hindered using recombinant chicken annexin A5, as described24 (15 μg/mL, final concentration), or to evaluate the role of divalent cations EDTA was added to neutrophils at a final concentration of 5 mM before cell-to-cell interaction. Cytochalasin D at a final concentration of 20 μg/mL (5 minutes at 4°C) was used to evaluate the role of neutrophil actin polimerization. Alternatively, phagocytosis experiments were carried out in parallel at 4°C and 37°C. Samples were washed to remove noninteracting platelets. Pellets were then fixed and permeabilized in HEPES-Tyrode with the FIX & PERM kit (Caltag), before labeling with PE-conjugated mAb against the CD61 platelet antigen (clone SZ21; Immunotech) and with FITC-conjugated mAb against MPO. Phagocytosis by electron and confocal microscopy was scored on coded samples and expressed as the percentage of neutrophils ingesting platelets. Platelets were considered phagocytosed only when their whole volume was contained within the border of the neutrophil, which is believed to underestimate the extent of phagocytosis. Phagocytosis was also assessed by flow cytometry and expressed as the percentage of neutrophils (ie, cells with a high side scatter within the CD45+ population, comprising > 99% CD66b+ and < 1% CD14+ events; Figure S1A, available on the Blood website; see the Supplemental Materials link at the top of the online article) ingesting platelets. Phagocytosis was identified by the gain of fluorescence associated to the CD61 platelet antigen after neutrophil plasma membrane permeabilization, a treatment that allows the mAb to penetrate calculated as follows: phagocytosing neutrophil percentage = percentage of permeabilized neutrophils positive for the platelet CD61 antigen-associated fluorescence (extracellular + intracellular platelets) − percentage of intact neutrophils positive for the platelet CD61 antigen-associated fluorescence (extracellular platelets only; Figure S1B). When indicated, extracellular adherent platelets were removed by incubation with 0.25% trypsin/EDTA solution for 2 minutes at 37°C.
In preliminary experiments, purified platelets were stimulated with either ADP (5 μM), collagen (1 μg/mL), or TRAP-6 (25 μM). When platelets were stimulated before the challenge with resting neutrophils, platelet phagocytosis was similar with all stimuli. However, at the concentrations we used, ADP or collagen failed to induce platelet-neutrophil adhesion in whole blood samples. Collagen and ADP directly activate neutrophils.25 We therefore verified the down-regulation of the PSGL-1 receptor (a bona fide event associated to neutrophil activation) after 60 seconds; that is, before platelet P-selectin expression (Table S1). Indeed, both ADP and collagen, but not TRAP-6, significantly down-regulated PSGL-1 expression as effectively as the positive control for neutrophil activation, fMLP (Table S1). We therefore selected TRAP-6 to study the platelet-neutrophil interaction: this peptide has the extra bonus, compared with the whole thrombin molecule, not to activate the coagulation cascade. It thus represents a suitable choice for use in whole blood samples.26 For confocal microscopy, samples were fixed, permeabilized, and labeled. Primary antibodies were labeled with Zenon IgG Labeling Kits: Alexa Fluor 488 (green), Alexa Fluor 594 (red), or Alexa Fluor 674 (pink). DAPI was used for counterstaining of nuclei. Labeled samples were washed and plated to glass coverslips before analysis with a Leica TCS SP2 Laser Scanning Confocal Microscope, objective 63× (numeric aperture [NA], 1.4). In selected experiments, the percentage of phagocytosing neutrophils was evaluated in parallel by flow cytometry and confocal microscopy; cells with discrete round fluorescent inclusions were scored as those that had ingested platelets. Sample preparation and electron microscopy were performed as described.5 When indicated, adhesion and phagocytosis were assessed in whole blood, without any previous cell isolation or sample manipulation. In these experiments, whole blood samples were treated with TRAP-6 (25 μM final concentration, activated platelets) or PGE1 (5 μM final concentration, resting platelets). After 5 minutes, samples were processed for flow cytometry or confocal microscopy; parallel aliquots were cleared by centrifugation for 1 minute at 16 000g. Released MPO concentration was assessed by enzyme-linked immunosorbent assay (ELISA) using a commercial kit (Enzyme Immunoassay; Bioxytech MPO/Oxis International, Portland, OR).
To further characterize the features of the phagocytic vesicles, platelets were labeled with the cell-permeant, dual-excitation ratiometric pH indicator BCECF-AM before interaction with neutrophils. Measurements were carried out by determining the pH-dependent emission intensity by flow cytometry (detected at 535 nm) when the dye is excited at approximately 490 nm versus the emission intensity when excited at its isobestic point of approximately 440 nm, following the manufacturer's instruction. To verify that the observed acidification of platelets was dependent on their internalization within a bona fide sealed phagocytic vacuole, the pHrodo Phagocytosis Particle Labeling Kit (Invitrogen, Milan, Italy) was used according to the manufacturer's instructions. As a positive control, Escherichia coli labeled and processed exactly as platelets were used.
Activation of platelets and neutrophils
Anionic phospholipids exposure was assessed by PE-conjugated CD61-specific mAb and FITC-conjugated annexin A5.27 Results were expressed as the percentage of annexin A5+ events in the whole CD61+ platelet population. To determine P-selectin expression, platelets were simultaneously fixed (Thrombofix18), labeled with FITC-conjugated mAb against CD61 and PE-conjugated against P-selectin, and analyzed by flow cytometry in purified platelet suspensions as well as in whole-blood samples. Results were expressed as the percentage of CD61+ platelets that express P-selectin. An Alexa 488–labeled irrelevant isotype control mAb was used to assess the background fluorescence. When indicated, MPO expression was assessed using specific mAbs. Neutrophil expression of Mac-1, PSGL-1, MPO, platelet/neutrophil aggregates, and intracellular platelet antigen were assessed by flow cytometry using conjugated mAbs. Results are expressed as the mean of fluorescence intensity (MFI) associated to the specific fluorochrome-labeled mAb or as the percentage of positive cells.
Clotting assay
Activated platelets at a concentration of 100 000 cells/μL were incubated for 1 minute at 37°C alone or in the presence of an equal volume of neutrophils, at a neutrophil-to-platelet ratio of 1:20, 1:10, or 1:5. Neutrophils at the 1:5 ratio were either untreated or pretreated with cytochalasin D to prevent actin-based cytoskeleton assembly. Normal human plasma (100 μL) was added for 1 minute, followed by an equal volume of a 25 mM CaCl2 solution. The coagulation time was determined.
Plate flow adhesion assay
Neutrophil interaction with adherent platelets under physiologic flow was investigated in a parallel plate flow chamber, as described.10 Platelets (3 × 107/mL) were allowed to adhere to a glass slide previously coated with aminopropyltriethoxysilane (APES; Sigma-Aldrich). Platelet-coated slides were washed and served as the chamber's bottom plate. The chamber (width, 1.4 cm; height, 0.250 mm) was placed in a thermoregulated Plexiglas box maintained at 37°C by an electric heating element. Neutrophils (5 × 106 cells/mL in medium containing 0.1% BSA) were perfused through the chamber over the platelet surface at a shear stress of 2 dyn/cm2 for 2 minutes. The chamber was then perfused with medium alone for an additional 10 minutes at 20 dyn/cm2. Adherent neutrophils were observed by contrast phase video microscopy with a 20×/0.40 NA objective (Olympus, Munich, Germany). Images were continuously recorded (Pro-Series video camera, high-performance CCD camera; Media Cybernetics, Silver Spring, MD). Firmly adhered neutrophils were quantified in the last 20 seconds of flow using ad hoc software for image analysis (Image Pro-Plus for Windows; Media Cybernetics).
Time-lapse videomicroscopy
Platelets were labeled with the BCECF-AM intracellular dye. Fluorescence was acquired by exciting at 488 nm and emission was recorded at 560 nM. Platelet-associated fluorescence abates once platelets are internalized and reach an acidic environment. BCECF-loaded platelets were activated with TRAP-6 and placed on slides (final volume 500 μL). Immediately after, autologous neutrophils were added (500 μL) and time-lapse images were acquired at 37°C for 5 minutes at 5-second intervals. Microscopy was performed with a Leica TCS SP2 laser scanning confocal. When indicated, platelets were treated with annexin A5 (15 μg/mL, final concentration) immediately before challenge with neutrophils.
In vivo injection and clearance of activated platelets
Whole blood from female C57BL/6N mice (Harlan, Correzzana, Italy) was obtained by cardiac puncture and collected in syringes containing Na citrate, EDTA, and PGE1. Mouse platelets were isolated and activated as described.26 Platelets (500 000) were resuspended in the presence of PGE1 to prevent further activation (final concentration 4 μM) or activated with thrombin (final concentration 0.5 U/mL). Thrombin was then inactivated by addition of hirudin (0.5 U/mL). Platelets were injected in the tail vein. After 1, 2, 3, and 24 hours animals were killed and blood retrieved as noted. Blood samples were fixed and lysed, washed twice, treated with the FIX & PERM Kit and incubated with anti–mouse CD61, anti-CD14, and anti-CD45 mAbs or appropriate isotypic controls. Neutrophils were identified within the CD45+ population by their forward scatter characteristics. In preliminary experiments, platelets were labeled with the intracellular dye BCECF before injection. All procedures were performed according to protocols approved by the animal care and use committee of the Fondazione San Raffaele del Monte Tabor (IACUC344) and communicated to the Ministry of Health and local authorities according to Italian law.
Statistical analysis
The data are presented as the mean plus or minus the standard error of the mean (SEM) unless otherwise stated. All statistics were calculated using PRISM version 2.0 (GraphPad Software, San Diego, CA), using analysis of variance (ANOVA) followed by multiple pairwise comparison tests, with differences being considered significant for P values less than .05.
Phagocytic clearance of human platelets in vivo: clinical evidence
We first analyzed the interaction between platelets and neutrophils in patients with early acute myocardial infarction, because in these patients both circulating platelets and neutrophils are substantially, although transiently, activated.28–30
We observed that platelets from 15 consecutive patients with acute myocardial infarction had a significant increase in the expression of P-selectin and in the percentage of circulating platelet-neutrophil aggregates, as detected by flow cytometry, compared with healthy controls (Table 1). Moreover, neutrophils had a reduced intracellular expression of MPO, and up-regulated the Mac-1 β2 integrin (Table 1). In all patients, a fraction (31.2% ± 7.5%) of circulating neutrophils were completely devoid of intracellular MPO.
The analysis by electron microscopy of neutrophils purified from the blood of acute myocardial infarction patients indicated that phagosomes contained large particulate corpuscles, whose size and morphology was compatible with internalized platelets (Figure 1A-F). Confocal microscopy analysis confirmed that neutrophils, including those circulating as aggregates, contained intracellular platelet antigens, as assessed by staining with the antiplatelet glycoprotein Ib alpha mAb after permeabilization (Figure 1G-I, Table 1). Interestingly, neutrophils with adherent and/or intracellular platelets had an apparently lower, or absent, content of MPO (Figure 1G-I).
Phagocytic clearance of human platelets: in vitro determinations
Freshly purified platelets, activated with TRAP-6, were readily ingested by resting neutrophils after a 5-minute interaction assay at a 20:1 platelet-to-neutrophil ratio, which is representative of the circulating blood, as easily evinced by electron microscopy. Several platelets closely adhering to neutrophils were evident, partially enveloped by pseudopods extending from the neutrophil plasma membrane, that ultimately encircle and engulf platelets, most of which can be traced into phagocytic vacuoles (Figure 2). Adherent or internalized platelets were not detectable when neutrophils were cultured alone (Figure 2B) or challenged with resting platelets (Figure 2C). The semiquantitative assessment indicated that a substantial fraction of neutrophils phagocytosed autologous activated platelets (Figure 2A). In contrast, less than 5% neutrophils internalized nonactivated platelets (Figure 2A).
To better characterize the platelet-neutrophil interaction that resulted in platelet clearance, as assessed by electron microscopy (Figures 2, 3D) we developed a flow cytometric method (Figure S1) that was dependent on incubating isolated human neutrophils with purified autologous platelets, either resting or activated. Neutrophils were readily resolved from platelets by physical characteristics and expression of the CD66b marker. Neutrophil-associated platelet fluorescence (CD61 platelet glycoprotein IIIa antigen; Figure 3A,B,F) and MPO content (Figure 3E,F) were then assessed. To discriminate between adherence and ingestion, permeabilized and nonpermeabilized samples were processed in parallel. The fluorescence in nonpermeabilized samples depends on platelets that adhere to the surface of neutrophils. After permeabilization, the fluorescence depends on both platelets that were ingested (intracellular) or that adhered to the neutrophil membrane (extracellular; Figure 1). Results obtained by flow cytometry were in keeping with those obtained by electron microscopy and confocal microscopy (Figure 3).
Neutrophils readily ingested platelets (Figures 2,3). To rule out possible artifacts, we removed extracellular platelets by trypsin/EDTA, after phagocytosis. As expected, adherent platelets were not detectable anymore, whereas those internalized were unaffected (Table 2). In contrast, internalization abated when the neutrophil-platelet interaction was carried out at 4°C (ie, at a temperature that does not permit actual phagocytosis), even if adhesion was partially conserved (Figure 4). Confocal microscopy clearly indicates that phagocytosis associates with loss of extracellular platelets. The phagocytosis was also greatly inhibited when the actin-based cytoskeleton was disrupted by treatment with cytochalasin D (Figure 4). Time-lapse videomicroscopy, carried out using platelets prelabeled with an intracellular red fluorescing reagent (BCECF-AM), further confirmed that neutrophils internalized whole platelets (Videos S1,S2).
The degree of phagocytosis was dependent on platelet activation. Typically, after a 5-minute interaction, greater than 30% of human neutrophils (37.1% ± 4.4%) ingested activated autologous platelets, compared with only 5.2% ± 3.3% of neutrophils challenged with resting platelets (Figures 2A,3,4). Time-lapse videomicroscopy shows that neutrophils interacting with activated adherent platelets under arterial shear stress also extensively phagocytosed; their extreme motility in these conditions enables recognition and clearance not only of adherent, immediately interacting, platelets but also of bystander platelets (Video S3, Figure 4). Once internalized, BCECF-AM–labeled platelet-associated fluorescence abated (Videos S1, S2), suggesting that they have reached an acidic compartment. To verify this issue, BCECF-AM–labeled platelet-associated fluorescence was monitored by flow cytometry in conditions in which neutrophils adhere to and phagocytose platelets, or in which these events are abrogated (ie, at 4°C). Emission at approximately 535 nm (FL2) revealed the intracellular acidification of BCECF-AM–labeled platelets. This was prevented when neutrophils were incubated with resting platelets or with activated platelets at 4°C (Figure 5). We confirmed that platelet acidification took place in a bona fide sealed phagosome by the rhodamine-based pHrodo, which is nonfluorescent at neutral pH. Neutrophils acquired a bright-red color, indicative of acidic environment (Figure 5): the pattern was similar when platelets or killed bacteria (E coli) were used as phagocytic substrates (not shown).
Flow cytometry shows that neutrophils interacting with activated (but not with resting) platelets had a significantly reduced MPO content compared with neutrophils alone (Figures 3E,F and 4). The observation is in keeping with the relative low MPO content of the neutrophils from patients with acute myocardial infarction that had internalized platelets (Figure 1G-I). Interestingly, neutrophils that had degranulated upon interaction with activated platelets, but not those that interacted with resting platelets, were not any more able to further up-regulate Mac-1 expression when exposed fMLP, the best-characterized neutrophil agonist (Table 3).
Phagocytic clearance of activated platelets in vivo: experimental animal model
To further verify the in vivo relevance of these observations, we injected purified platelets, either activated or resting, in the tail vein of C57BL/6 mice. Blood was retrieved at different times after injection (1, 2, 3, and 24 hours). Figure 6 shows that, within the first hour, most circulating neutrophils became engaged in the clearance of activated platelets. The fraction of circulating neutrophils with internalized platelets returned to background levels at 24 hours (Figure 6A), when injected platelets had been cleared. We failed to observe significant increase over the background levels when mice were injected with nonactivated platelets (Figure 6B) or with vehicle alone (Figure 6C).
Role of phosphatidylserine, P-selectin/PSGL-1 interaction, and β2 integrin
The results described in the previous paragraph indicate that moietie(s) expressed by platelets upon activation are critical to trigger their clearance. P-selectin and phosphatidylserine, which both increased on platelet outer surface after activation (Table 1, Figure S2), are promising candidates.31–33 Annexin A5 binds to exposed phosphatidylserine residues, thus inhibiting the events downstream of its recognition, including phagocytic clearance.24 When activated platelets were treated with annexin A5, the phagocytosis abated (percentage of neutrophils phagocytosing platelets from 37.1% ± 4.4% to 5.1% ± 1.2%, P < .001). Annexin A5 in contrast did not significantly modify the percentage of neutrophils with adherent platelets (from 25.6% ± 3.0% to 20.1% ± 3.3%; Figure 7). We also failed to significantly interfere with platelet adhesion to neutrophils under flow conditions (Table 2, Figure 8; Video S4). Moreover, annexin A5 did not influence the MPO depletion induced by activated autologous platelets (from 52.9 ± 5.8 to 26.3 ± 2.1 MF1 for neutrophils challenged with activated platelets, and to 30.6 ± 2.6 MF1 for neutrophils challenged with activated, annexin A5–treated platelets; Figure 7). These results indicate that by hindrance with the recognition of phosphatydylserine we dissect the events linked to platelet adhesion and phagocytosis, thus revealing that neutrophil degranulation is dependent on adhesion.
Divalent cations, which are necessary for selectin- and integrin-mediated adhesion,34 were also required. Platelet adhesion, platelet phagocytosis, and MPO release were virtually abrogated when EDTA was added to activated platelets before interaction with neutrophils (the percentage of neutrophils with adherent platelets decreased from 25.6% ± 2.0% to 6.8% ± 1.2%; the percentage of neutrophils that phagocytosed platelets from 37.1% ± 4.4% to 0.7% ± 0.4% and MPO content from 26.3 ± 1.1 to 55.8 ± 6.2 MPO-MF1; P < .001 for both adhesion and phagocytosis, P < .001 for MPO release; n = 6; Figure 7).
To determine whether P-selectin was involved, we used mAbs blocking either P-selectin or its counterreceptor on neutrophils, PSGL-1. Both adhesion and internalization abated in treated samples, and MPO depletion was prevented (the percentage of neutrophils with adherent platelets decreased from 27.1% ± 1.5% to 3.7% ± 0.4%, the percentage of neutrophils that phagocytosed platelets from 36.1% ± 2.7% to 3.5% ± 1.2%; MPO content from 25.7 ± 3.4 to 60.5 ± 4.5 MF1, respectively, upon P-selectin blockade; the percentage of neutrophils with adherent platelets decreased to 9.5% ± 2.2%, the percentage of neutrophils that phagocytosed platelets to 1.6 ± 1.1 and MPO content to 47.9 MF1 upon PSGL1 blockade). The difference with results obtained in the presence of irrelevant isotype-matched mAb was statistically significant (P < .001, n = 6; Figure 7). These results further support the role of the P-selectin/PSGL-1 interaction in the cell-to-cell interaction and unequivocally implicate this pathway as a master regulator of platelet phagocytosis.
P-selectin/PSGL-1 interaction promotes Mac-1–dependent homotypic neutrophil aggregation and neutrophil/platelet aggregation,5,35 a mechanism dependent on cytoskeletal rearrangement and Mac-1 clusterization. Neutrophils expressed the Mac-1 molecule and up-regulated the surface expression of the molecule when challenged with activated platelets (Figure S2). Blocking mAbs against the common β2 chain (CD18) or against the αM chain of the integrin significantly inhibited both platelet adhesion to neutrophils (from 27.1% ± 1.5% to 13.4% ± 3.2% with anti-CD18 mAb, n = 11, and to 19.0% ± 1.2% with the anti–Mac-1 mAb, n = 6; differences with the control isotype-matched mAb were significant, P < .001) and phagocytosis (n = 6, from 36.1% ± 2.7% to 11.7% ± 4.7% in the presence of anti-CD18 mAb and to 12.4% ± 3.7% in the presence of anti–Mac-1 mAb, P < .001 versus cells treated with the irrelevant mAb). The MPO release, although reduced, was not significantly affected by Mac-1 blockade (Figure 8). The glycoprotein Ibα interacts with Mac-1 expressed on activated leukocytes:36 its blockade did not exert a significant effect in this system (Figure 8). The results indicate that the Mac-1 integrin is required for the firm adhesion of neutrophils to platelets, and suggest that this event is required for eventual platelet internalization. In agreement, prevention of the rearrangement of the actin-based filament network at 4°C or its disruption by cytochalasin D abrogated platelet clearance by neutrophils (Figure 4).
We studied in a parallel set of experiments the interaction between neutrophils and platelets in whole-blood samples.37 This approach avoids potential artifacts due to cell isolation procedures, and maintains during the assay the physiologic array of plasma cofactors and opsonins. At 5 minutes after platelet activation, the fraction of neutrophils with adherent platelets shifted from 2.13% plus or minus 0.6% to 32.0% plus or minus 5.7% (n = 5; P < .001), and the fraction of neutrophils that phagocytosed platelets from 3.4% plus or minus 1.4% to 42.7% plus or minus 5.7% (Figure S3A). Intracellular MPO content significantly decreased (from 101.3 ± 37.1 to 60.0 ± 23.1 MF1, n = 5; P < .001; Figure S3B), with a consensual increase in the plasma concentration of the soluble protein (from 3.8 ± 1.0 ng/mL to 14.6 ± 2.0 ng/mL, n = 5; P < .001; Figure S3B). These results indicate that events associated to platelet adhesion and phagocytosis by neutrophils occurs in the blood (ie, in the physiologic environment where circulating cells interact).
Blocking mAbs against P-selectin and Mac-1, reduced adherence, phagocytosis, and MPO release (Figure S3). Results with recombinant annexin A5 were in keeping with those obtained using isolated cells, because phosphatidylserine exposure was required for internalization of platelets; its hindrance did not alter the release of MPO, further supporting the contention that phagocytosis and degranulation are not causally linked.
To address the role of cyclooxygenase pathway, experiments were performed using samples from donors before and 4 hours after ingestion of acetylsalicylic acid. The treatment did not influence either activated platelet adhesion to neutrophils or their phagocytic clearance (Figure S4). Finally, we evaluated whether phagocytosis by neutrophils influenced the acceleration of the coagulation time due to activated platelets, which physiologically represent a source of anionic phospholipids. Table 4 shows that the interaction with neutrophils significantly reduces the procoagulant activity of activated platelets. The action of neutrophils was dose-dependent, because it increased in direct proportion to the phagocyte-to-platelet ratio and was due to active phagocytosis, because it was abrogated by treatment with cytochalasin D (Table 4).
These experiments document an active pathway culminating in the clearance of activated platelets by neutrophils in vitro and in vivo, involving release of the content of the azurophilic cytoplasmic granules and active phagocytosis. The clearance comprises an adhesion step, which depends on the interaction between P-selectin and its counterreceptor on neutrophils, PSGL-1, and on the activation of the β2-integrin Mac-1. Active internalization is a second step, which is selectively abrogated by interference with the recognition of phosphatidylserine. Neutrophils that have phagocytosed platelets can be traced with relative ease in the circulating blood of patients with acute myocardial infarction who have high platelet P-selectin expression (Table 1). Depletion of neutrophil MPO across the coronary inflamed vascular bed is a well-characterized event in patients with severe unstable angina38,39 where it is unrelated to myocardial ischemia, chronic atherosclerotic burden, or to passage through the ischemic myocardium or culprit unstable lesions.39 The findings of the present study raise the possibility that the interaction between circulating activated platelets and leukocytes is mechanistically involved in such depletion.
The mechanisms controlling the removal of platelets from the circulation are poorly identified, even if the phagocytosis of effete, activated platelets possibly contributes. Extensive thrombosis, such as that which occurs during disseminated intravascular coagulation, causes thrombocytopenia, most likely because of incorporation of platelets into the small thrombi that are eventually cleared by local phagocytes.40 Even in more physiologic conditions, platelet activation would occur on injured vessel walls, and the activated platelets could be rapidly sequestered at these sites.
Autoantibodies accelerate the removal of platelets by Fc receptor–bearing phagocytes in patients with autoimmune thrombocytopenia,41 and microbial products, including bacterial endotoxin, enhance phagocytosis.42,43 Cooling primes reinfused human platelets for activation, and Mac-1 is responsible for rapidly decreasing platelet counts, preventing the induction of thrombosis by primed platelets.44 Interestingly, and in good agreement with our data on a key role of β2 integrin in the phagocytic clearance of platelets, Mac1−/− mice have an increased concentration of circulating platelets compared with wild-type littermates.44 Platelet activation in the circulating blood is a relatively common event, which results in a swift up-regulation of their adhesive45 and prothrombotic properties.46,47 The activation of circulating platelets is indeed directly associated with the risk of thrombosis; it is quite clear that several homeostatic mechanisms physiologically quench their capacity to activate the coagulation system.
The activation of circulating platelets, besides triggering their accelerated turnover, results in the cross-talk with monocytes and neutrophils.48 Our finding that the interaction with activated platelets prompts a phagocytic program is in keeping with previous observations, for which neutrophils that interact with platelets phagocytose bacteria more readily than unbound neutrophils.49
We did not observe any effect of aspirin, which eliminates thromboxane from the platelet releasate and substitute more free, unprocessed arachidonic acid as well as the hydroxy acid12-hydroxyeicosatetraenic acid. The lack of detectable differences in the presence or the absence of thromboxane apparently rules out the participation of the cyclooxygenase pathway in the results.
It is tempting to speculate that the ability of neutrophils to adhere and to selectively internalize activated platelets, expressing phosphatidylserine and P-selectin, is a mechanism to maintain the normal blood fluidity by sequestering a circulating potentially dangerous substrate, which would induce thrombi formation.50 Indeed, it has been previously clearly shown that neutrophils down-regulate platelet function.50
Neutrophils are the more abundant circulating phagocytes, and could represent an inborn circulating clearance system. A "tether and tickle" mechanism controls the clearance of other particulate substrates, like aged red blood cells, phosphatidylserine-containing liposomes, and apoptotic cells. In these models, bridging receptors function by tethering the apoptotic cell to the phagocyte, whereas the recognition of phosphatidylserine is required to transduce signals that initiate the uptake. Our data are at least partially consistent with this model. Indeed, annexin A5, forms a 2-dimensional crystalline lattice on membrane anionic phospholipids, thus hindering their recognition by leukocytes.24 The ensuing selective blockade of phosphatidylserine abolishes internalization, but does not apparently interfere with adhesive interactions.
The P-selectin/PSGL-1 engagement is required for platelet adhesion to neutrophils. Moreover, it is necessary for integrin transactivation, assembly of the phagosome, and neutrophil degranulation.5,10,21,22,51,52 Therefore, platelet adhesion and neutrophil degranulation are simultaneously blocked in our system by the antibodies for P-selectin and PSGL-1.
All together, we propose that tethering is achieved via P-selectin recognition, leading to MPO release, and activating β2 integrins for internalization; if the tethered substrate was a phosphatidylserine-expressing platelet, phagocytosis swiftly removes the activated platelets, which represent a template for thrombin formation, from the circulating blood.31,46,47
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Supplementary PDF file available online.
Contribution: N.M. designed and performed experiments, discussed the experimental strategy, and wrote the manuscript; P.R.-Q. discussed the experimental strategy and wrote the manuscript; V.E. and L.T. provided vital reagents and supervised the experiments of electron microscopy and of phagocytosis under flow conditions; A.P. performed experiments under flow conditions; C.C. carried out image analysis; A.C. and M.T.S.B. contributed to the establishment of the mouse model of platelet clearance; D.C. selected patients and organized clinical data; A.M. discussed the experimental strategy; and A.A.M. defined the experimental strategy, supervised experiments, and wrote the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Norma Maugeri, Clinical Cardiovascular Research Laboratories, University Vita-Salute San Raffaele, via Olgettina 58, 20132 Milan, Italy; e-mail: maugeri.norma{at}hsr.it or normamaugeri2003{at}yahoo.it.
We thank Martin Herrmann (University of Erlangen, Erlangen, Germany) for generously providing unlabeled recombinant annexin A5, Roman Polischuk (Laboratory of Membrane Traffic, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy) for excellent electron microscopy, Alessio di Pentima (Laboratory of Membrane Traffic, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy) for skillful technical assistance, and Anca Dragomir (Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden) for kind advice on electron microscopy.
This work was supported by the MIUR (Ministero dell'Istruzione dell'Università e della Ricerca; PRIN 2005; FIRB 2003), the EC (EVGN network), the Fondazione per il Cuore, the Associazione Italiana Per La Ricerca Sul Cancro (AIRC), and the Ministero della Salute.
The online version of this article contains a data supplement.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.
- Submitted September 25, 2008.
- Accepted February 10, 2009.
- © 2009 by The American Society of Hematology


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Mary E. Wagner "Mary Lou", 87, of Elyria, went home to be with her Lord and Savior on Monday, October 21, 2013 at EMH Healthcare in Elyria. She was born April 3, 1926 in Lorain.
Mary Lou graduated from Clearview High School in the class of 1944. She made her home in Elyria since 1966. Mary Lou had attended Fellowship Baptist Church in Lorain. She began working at Colson Corporation in Elyria until Saul Gilford establish Gilford Instruments, Oberlin. Mary Lou joined the Gilford family business and became one of the "original ten employees". She held several supervisory positions, and retired in 1988, as a senior assembly technician after thirty years of service. As a young women, she enjoyed playing first base with the Frank's Bakery softball league in Elyria. Mary Lou later joined the Erin-Brew semipro softball team in Cleveland. Her softball and basketball experiences included being part of the state championship teams.
Mary Lou was a member of the Butler Builders of Lorain County. In 1963, she was a part of the Ohio Women's Bowling team that won the state championship. Her hobbies included softball, bowling, golfing and fishing. Mary Lou was known for her generous spirit. She enjoyed the family time spent at her cottage in Huron and the many trips to Kelley's Island.
Being the last of 13 children, she is survived by many nieces and nephews and extended family who she treasured.
She was preceded in death by her brothers, Samuel, Harry Jr., George, Edward, Charles and Wilbur Wagner; her sisters, Grace Fitzgerald, Dorothy Trifiletti, Wilma Strehle, Catherine VanNiel and Francis Wagner; and by her parents Harry F. and Elizabeth Wagner (nee Miller).
Friends may call Friday, October 25, 2013 from 6 to 9 P.M. at the Hempel Funeral Home, 373 Cleveland Ave., Amherst. Funeral services will be held Saturday, October 26, 2013 at 11 A.M. in the funeral home. The Rev. Orlando Collazo, Pastor of Fellowship Baptist Church in Lorain, will officiate. Burial will follow at Ridge Hill Memorial Park, Amherst Township.
The family suggests that memorial contributions be made to Fellowship Baptist Church; 5046 Broadway, Lorain, OH 44052 or to the charity of the donors choice.

subset: commoncrawl


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|Trad, 1 pitch, 50'
|YDS: 5.11a French: 6c Ewbanks: 22 UIAA: VII+ ZA: 22 British: E3 5c [details]
|Todd Gordon & Cyndie Bransford, 3/90
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|Submitted By:
|Locker on Sep 11, 2005
|Comments on Pump Up the Volume
|Add Comment
|Show which comments —
By Locker
From: Yucca Valley, CA
Sep 12, 2005
rating: 5.11a 6c 22 VII+ 22 E3 5c
|a year or so back I hung all over the bolts trying to get this one. Yesterday we top roped it and again..I flailed!!! This thing is thin and takes smooth movement. It is very much Jtree friction all the way! Easy to set up a top rope inside a little hole in the rocks on top (Tight squeeze however) Most pro works well in the small to medium range. After giving this one a shot redirect rope via bolts to the right and have at Grandpa Gander 5.10cR that some found the start more difficult that this route................over and out! Eee Aww Keeeee!!!
By 72HW Holly
Feb 19, 2008
rating: 5.11a 6c 22 VII+ 22 E3 5c
|Bald like a newborns' butt, thin like a 29 Palms tweaker and fun as heck on TR. Would like to see it led, but man, it's not within my ken to do it! Hung like crazy at the crux, found the key to be using obvious crimps in an un-obvious way and a very helpful right foot micro edge. Way balancey, way frictiony and prolly one of the hardest things I've clawed my way up to date. Highly recommended!
By Chris Owen
From: Big Bear Lake
Mar 17, 2009
rating: 5.11a 6c 22 VII+ 22 E3 5c
|Critical smears and tiny crimps - for quite a few moves made this seem harder than 5.11a to me. Should've picked a nice cold day I guess.


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Is There a Golden Rule for the Stochastic Solow Growth Model ?
This paper analyzes the dependence of average consumption on the saving rate in a one-sector neoclassical Solow growth model with pro-duction shocks and stochastic rates of population growth and depreciation where arbitrary ergodic processes are considered. We show that the long-run behavior of the stochastic capital intensity, and hence average consumption along any sample-path, is uniquely determined by a random fixed point which depends continuously on the saving rate. This result enables us to prove the existence of a golden rule saving rate which maximizes average consumption per capita. We also show that the golden rule path is dynamically efficient. The results are illustrated numerically for Cobb�Douglas and CES production function.
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|Date of creation:
|Contact details of provider:
| Postal: Schönberggasse 1, CH-8001 Zürich
Phone: +41-1-634 21 37
Fax: +41-1-634 49 82
Web page: http://www.econ.uzh.ch/
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References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- Robert J. Barro, 2013.
"Inflation and Economic Growth,"
Annals of Economics and Finance,
Society for AEF, vol. 14(1), pages 121-144, May.
- Robert J. Barro, 1995. "Inflation and Economic Growth," NBER Working Papers 5326, National Bureau of Economic Research, Inc.
- Robert J. Barro, 2012. "Inflation and Economic Growth," CEMA Working Papers 568, China Economics and Management Academy, Central University of Finance and Economics.
- Ambler, Steve & Paquet, Alain, 1994. "Stochastic Depreciation and the Business Cycle," International Economic Review, Department of Economics, University of Pennsylvania and Osaka University Institute of Social and Economic Research Association, vol. 35(1), pages 101-116, February.
- Mirman, Leonard J., 1973. "The steady state behavior of a class of one sector growth models with uncertain technology," Journal of Economic Theory, Elsevier, vol. 6(3), pages 219-242, June.
- Steve Ambler & Alain Paquet, 1992. "Stochastic Depreciation and the Business Cycle Puzzle," Cahiers de recherche CREFE / CREFE Working Papers 8, CREFE, Université du Québec à Montréal.
- Mirman, Leonard J, 1972. "On the Existence of Steady State Measures for One Sector Growth Models with Uncertain Technology," International Economic Review, Department of Economics, University of Pennsylvania and Osaka University Institute of Social and Economic Research Association, vol. 13(2), pages 271-286, June. Full references (including those not matched with items on IDEAS)
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text:
CURTAIN UP | Westport; Maybe Sanjaya Was Channeling Her
By SYLVIANE GOLD
Published: May 27, 2007
BABY boomers will recall the brief but spectacular career of one Mrs. Miller, a matronly soul whose pitiful recordings of rock hits like ''Monday, Monday'' and ''Downtown'' became joke best sellers in the late 1960s. Well, she was just a piker compared to Florence Foster Jenkins, whose tune-free singing in the '30s mangled not only pop songs but also the music of Mozart, Verdi and Gounod.
Like Mrs. Miller, she became a sensation. Unlike Mrs. Miller, she caught the attention of the playwright Stephen Temperley, whose ''Souvenir: A Fantasia on the Life of Florence Foster Jenkins,'' became something of a sensation itself, moving from the Berkshires to Off Broadway to Broadway and earning Judy Kaye a Tony nomination last year.
Ms. Kaye, a superb singer who has to work very hard to sound as bad as Jenkins, brings her portrayal to Westport this week, accompanied by Donald Corren, who created the role of her faithful coach and pianist, Cosme McMoon.
While the play does not stint on the comic absurdity of Florence's devoted but futile pursuit of the musical arts, ''Souvenir,'' directed by Vivian Matalon, is more than a compendium of off-key singing and hideous costumes. Mr. Temperley is equally interested in the relationship between the grandly deluded Jenkins and the increasingly empathetic McMoon.
He starts out working with her strictly for the money. But he soon becomes fascinated: not only can't she hear what she actually sounds like, she doesn't realize people are coming to her concerts to laugh. She lives in a happy bubble of certitude, oblivious to the possibility that she has no talent. Cosme, whose career as a composer is going nowhere, has reason to envy her -- and to wonder whether he has an obligation to tell her the truth.
When Cosme gently suggests that she might not be singing the notes exactly as written, she claims a right to artistic ''latitude.'' The play wants us to think about how funny that really is -- if we believe beauty can exist in the eye of the beholder, isn't it possible that musical beauty can exist in the ear? And if it does, who are we to laugh at it?
''Souvenir: A Fantasia on the Life of Florence Foster Jenkins,'' at the Westport Country Playhouse, 25 Powers Court, May 31 through June 16. Information: www.westportplayhouse.org or (203) 227-4177.
Photo: OFF KEY -- Donald Corren, as Cosme McMoon, and Judy Kaye in ''Souvenir: A Fantasia on the Life of Florence Foster Jenkins.'' (Photo by Sara Krulwich/The New York Times)


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June 12, 2012
A spokesman for EU foreign executive Catherine Ashton, who heads the six-power group in nuclear negotiations with Iran, reported Monday night, June 11, that Tehran is now willing to discuss high-grade uranium enrichment in the next round of nuclear talks in Moscow on June 18-19.
The claim is false. Tehran consistently refuses to discuss its "right to enrichment" and threatened not to turn up for the Moscow session after US Secretary of State Hillary Clinton demanded last week that Iran come to the table with "concrete plans" for curbing uranium enrichment up to 20 percent purity.
Iran has not backtracked: Ashton got nothing new from an hour of tense conversation with senior negotiator Saeed Jalili and had to be satisfied with issuing the noncommittal statement, "The Iranians agreed on the need for Iran to engage on the (six powers') proposals, which address its concerns on the exclusively peaceful nature of the Iranian nuclear program."
Enrichment remained unmentioned – least of all, any reference to the international inspectors' discovery that Iran was enriching uranium up to 27 percent – and the "exclusively peaceful nature" of Iran's nuclear program was endorsed.
From the outset, the talks between the six powers (US, China, Russia, Germany, France and Britain) in Istanbul (April 14) and Baghdad (23.5) and Tehran were falsely presented by the US and the European Union as different from previous diplomacy in that Tehran was now prepared to discuss the controversial aspects of its nuclear program.
This article was posted: Tuesday, June 12, 2012 at 3:09 am


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INDIAN ROCKS BEACH, Fla. - A 50-year-old man is accused of attacking four people with a fillet knife in an Indian Rocks Beach bar.
The Tampa Bay Times reports James Klingbeil was at the Red Lion Pub at closing time Sunday when the bartender refused to sell him alcohol because he was intoxicated.
Pinellas County deputies say Klingbeil walked to a nearby store, bought a knife and returned to the pub. He started arguing with 32-year-old bartender Rebecca Shaeffer again before pulling out the knife and attacking her.
Three bar patrons were injured as they tried to help Shaeffer. The injuries didn't appear to be life-threatening.
Deputies say Klingbeil remains in the Pinellas County Jail on charges including attempted first-degree murder.
Copyright 2013 by The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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Excellent Windows Phone style interface. Vast repository of restaurant and business reviews. Lets you write reviews. Monocle shows augemented reality view. Rewards for checking in to certain businesses.
Doesn't have the "compliment" feature. Can't search phone contact list to add Yelp contacts.
Bottom Line
A beautifully designed app lets you find the best local eateries and businesses.
One of the joys of Yelping is not just finding which local business will best suit your needs, but in contributing to the community. It's a great opportunity to share your discerning taste and expertise with the public. One of the big complaints about the earlier version of the Windows Phone Yelp was that it didn't let you enter reviews; that deficiency has been addressed. From any business page's Reviews panel, you just hit the + at the bottom of the screen.
Five big gray stars at the top let you rate the business (they turn gold when you tap them); below this is the space for you to vent your frustration or sing your praises. Just as in the iPhone app, the review you enter here is a draft, for which you later will have to hit the publish button on the website. It's not a bad idea to let your comments stew a bit before committing them to public view—especially if the venue is a bar!
Interacting with contacts is another joy of Yelp. You can add your Facebook friends and follow other's reviews. You can search for any Yelp users to add as friends, but strangely, the app won't search your phone contact list for users, as the iPhone version does. If you like someone's reviews, you can hit a + sign at the bottom of his profile page (which can include a photo and location), and a pleasant message request that you can send is created. One thing I did miss that's on the iPhone app is the ability to send "compliments" to users whose reviews you like.
Like Foursquare, Yelp lets you "check-in" to any of the establishments reviewed on the service—and even get perks such as discounts for some. You can also earn distinctions: for example, I'm the "Duke" of 46 Bliss Bistro in Queens! The Regulars tab of any place's page shows who's checked in there most recently and most frequently.
Yelping for Joy
There are disappointingly few Windows Phone apps that let you do pretty much everything you can in other platforms—Yelp is not one of these. It's full function, in a beautiful, easy-to-use, and well-designed interface. OK, there are a couple of tiny features you get on the iPhone but not on Windows Phone. But for everything that really matters about Yelp, the Windows Phone app works with aplomb. It's our Editor's Choice for local information apps.


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I was lucky enough to attend the opening of Ruby Chew's latest exhibition "Spitting Image" at Hill Smith Gallery on Wednesday night. I have heard a lot of good things about this new up and coming artist who is an honours graduate from the Adelaide Central School of Art.
oil Archive
Jan Van Dijk is a Queensland artist, and has lived in Brisbane since he was four. His painting style has its roots in street art and is energetic, thick paint envelopes the space. Bright bold colour drags the eye to and fro; each work is a cavalcade of interesting


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ESCONDIDO -- The Escondido Planning Commission approved a motion to add strict guidelines for businesses seeking to occupy the old Kmart site on Mission Avenue on Tuesday but also said they would revisit the guidelines in 120 days.
The commission agreed to a list of 13 businesses that will not be allowed to build on the site. These businesses include storage facilities, pawn shops, funeral parlors, swamp meets and adult entertainment establishments.
Commissioner Frank Lorey amended the initial motion -- made by Commissioner Barry Newman -- to include prohibiting car sales and special events.
The motion passed 6ñ0 with Commissioner Jeffrey Weber absent.
In addition to restricting specific businesses, the commission agreed to revisit the guidelines in 120 days during which time they will work with the city and the current site owners to come up with a list of businesses all parties wish to attract.
The site ñ-- located at 620 W. Mission Avenue -- is currently owned by Escondido Mart Trust, a trust fund representing a private couple, said David Ferguson, the tenant's attorney.
Ferguson spoke before the commission and urged the commission and the city to conduct studies of the site area to develop a plan for bringing new businesses to the area. The site is bordered by Highway 78 to the north, Quince Street to the east, Mission Avenue to the south and Rock Springs Road to the west.
"If we don't know the root cause of the deterioration of the area, how are we going to know how to turn it around?" Ferguson asked.
The commission clearly wants to attract a business that will revitalize the area. Commissioners spoke of attracting a big box retailer such as Costco or Best Buy but Ferguson argued that there was no evidence that a big box retailer is interested in the site due to the small size.
The Kmart site --ñ the only portion of the area currently vacant ñ-- is 9.5-acres while most big box retailers require a minimum of 11-acres, staff reports said.
Ferguson made reference to the old Montgomery Ward site on West Valley Parkway where a 16-screen movie theater and restaurant complex is set to open in December. He also referenced vacant land on La Terraza Boulevard that the city earmarked for hotel development.
"This kind of approach worked with the Montgomery Ward site but on La Terraza, where the city insisted on a hotel, the area is still vacant," Ferguson said. "We want to avoid that situation and match market forces."
Commissioners were sympathetic to the current tenant's need to lease the land.
"I think we need to see more information gathered before establishing a specific plan," Chairwoman Karen Allgeier said. "We need to ask if this is a bigger issue than one site at the corner of Mission and Quince and, in the long term, I think it is."
Ferguson said the current tenants have placed ads in the Wall Street Journal and sent information to 3,000 brokers nationwide since Kmart closed in April. Thus far, the only offer received has been for a swamp meet which the tenant denied.
Escondido Mart Trust currently loses $50,000 per month due to the site vacancy, Ferguson said.


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By Karen Pierog
(Reuters) - Illinois Governor Pat Quinn on Wednesday said the state must make changes to its pension system and to Medicaid this year, while also insisting that spending cuts alone will not fix the state's budget.
A financial watchdog group recently forecast that Illinois' pile of unpaid bills will quadruple to $35 billion in five years, while Moody's Investors Service cited inaction on pensions and unpaid bills last month when it cut the state's credit rating to A2, the lowest rating level among the states it rates.
"While we have downsized Illinois government more than ever before, we continue to face very difficult decisions to restore financial stability to our state," Quinn, a Democrat, said in his State of the State address to the General Assembly.
Further changes to pensions need to be "meaningful, constitutional and fair to the employees who have faithfully contributed to the system," Quinn said, adding that a pension working group would propose changes that could be enacted this year.
Illinois's unfunded public pension liability of $83 billion, along with escalating costs for Medicaid, the health-care program for the poor funded jointly by states and the U.S. government, have been major factors eroding the state's finances.
The Civic Federation, a Chicago-based government watchdog, had projected a rise in the state's bill backlog to $35 billion if the state fails to address pensions and Medicaid.
Details of the governor's plans may be revealed when he lays out his fiscal 2013 proposed budget on February 22.
In Wednesday's speech, Quinn said the state must take action beyond spending cuts.
"We must build and grow our Illinois economy like never before to keep Illinois moving forward," he said.
Quinn proposed eliminating the state's natural gas utility tax paid by businesses and residents and creating tax credits for taxpayers with children and for businesses that hire military veterans.
State Comptroller Judy Baar Topinka, a Republican, compared those ideas with "putting dessert on the table before the vegetables."
"We must get our fiscal house in order before we can even talk about more tax breaks and incentives," she said in a statement.
(Reporting By Karen Pierog; Editing by Leslie Adler)


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Only I can't find a new apartment for my daughter and myself. the real estate market where we live is in some kind of a crazy bubble and prices have risen 10 to 15% as I have been looking. Not only are there very few places on the market but the bidding for them is very competitive. I lost a bid last week to two all cash offers.
It was hard to lose my marriage, crushing to lose my intact family but now I feel nothing but despair over finding a place to live. As I made Halloween decorations with my DD, 9, and her friend this weekend, it was everything I could do not to cry. I am starting to think that I won't be able to hold it together. For her, at work, at all. I am crying everyday now again just like in the beginning of this shitstorm. I am already taking ativan and ambian.
I am going to have to lower my expectations one more time. It seems too cruel that I now have to choose between a small and dark apartment or one that is very far from our friends, my DDs school, the life we know.
I can brainstorm some more ideas for you if it would help.
And never grow a wishbone, daughter, where your backbone ought to be.
― Sarah McMane
Have you looked at possibly finding somebody to share a place with? That can advantageous for a couple of reasons, 1. cheaper; 2. built in babysitter (sometimes if needed.) I know it's tough, but that's probably what I would do if I had to. Do you have any family/friends that you can stay with for awhile? That could be an option for you. If you want to find a roommate, you can post notices on college bulletins, and be sure to meet any prospective person(s) in a public arena. You can NOT be too careful.
None of this is fair, honestly, you didn't do anything wrong yet you continue to be punished. Keep reading on forgiveness (it's for you not him) and seek anybody you can just sit and vent to, that's what your friends are for. I hope things work out for you.
Status: We're going to try IC one more time.
New place = new memories. I know it is hard but It will be ok.
I know it doesn't seem like it, but you do still have some time to figure things out. Take PPs advice, there are options out there.
And know that where ever you end up, your DD will be fine. You just need to present it to her as an "adventure". Kids are so much more adaptable than we are.
Then a year later, bought something, had money saved and a direction.
For me, I bought a much smaller house in a good neighborhood. I look at is as an investment for my future I'm here for now, and no, it isn't my dream house, but when my kids are older...or I meet a great man and want to marry again, I can sell it for a tidy profit!


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User Manual (ADCP-96-114) that is shipped with the cabinet. Revision History ISSUE DATE REASON FOR CHANGE 05/2007 Original. 1406707 Rev A Pad Mount Frame Installation Instructions ADCP-96-123 • Issue 1 • May 2007 ™ OmniReach FDH 3000 Small Cabinet 21934-A Page Page 1 © 2007, ADC Telecommunications, Inc.
PAGE IDENTIFIER Trademark Information ADC and ADC Telecommunications are registered trademarks of ADC Telecommunications, Inc. OmniReach is a trademark of ADC Telecommunications, Inc. Admonishments Admonishments — in the form of Dangers, Warnings, and Cautions — must be followed at all times.
1, is a stainless steel frame that provides a mounting base 20.80 IN. (52.8 CM) Figure 1. FD3-PMFC06 Dimensions Figure 2 ADCP-96-123 • Issue 1 • May 2007 5.5 IN. (14.0 CM) 12.55 IN. (31.2 CM) 21935-A for the base construction details. Page 3 © 2007, ADC Telecommunications, Inc.
GRAVEL OR EQUIVALANT FILL COMPACTED SOIL 4.0 IN. MIN. (10.2 CM) Figure 2. Constructing the Concrete Pad for the FDH 3000 Small Size Cabinet Page 4 © 2007, ADC Telecommunications, Inc. 36.8 IN. (93.5 CM) 17.5 IN. (44.5 CM) 12.5 IN 4 IN.
CABLE CONDUIT FRONT OF CABINET Figure 4) while the concrete is poured. ADCP-96-123 • Issue 1 • May 2007 Figure 3. The holes ALIGN EDGES OF TEMPLATE WITH EDGES OF PMF 21937-A Figure Figure Page 5 © 2007, ADC Telecommunications, Inc.
When installed, the top of the rod should be located 1 to 2 inches (2.54 to 5.08 cm) below the top of the finished concrete pad. Page 6 © 2007, ADC Telecommunications, Inc. (93.5 CM) F R O...
ADCP-96-123 • Issue 1 • May 2007 Connect the grounding wire to the grounding system. Leave sufficient slack in the grounding wire to allow it to be routed into the cabinet after the cabinet is mounted on the pad. Page 7...
Contents herein are current as of the date of publication. ADC reserves the right to change the contents without prior notice. In no event shall ADC be liable for any damages resulting from loss of data, loss of use, or loss of profits and ADC further disclaims any and all liability for indirect, incidental, special, consequential or other similar damages.


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We're just about to sort Visas for a trip to Kenya and know we need visas for the children. The forms of the High Commission website don't really make it clear who should sign for the child and I'm not sure if they charge for child visas.
Anyone with recent experience? Would it just be easier to get visas on arrival (worried we'll be tired!).


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Times Now : India's greatest Wimbledon ever
Mon, Jul 13, 2015, 01:00 PM
In the history of lawn tennis, for the first time, Indian players have created records. Leander Paes won the mixed doubles event of the Wimbledon Championship partnering with Martina Hingis. It is Paes's 16th Grand Slam trophy. They have registered win against Alexander Peya and Timea Babos, in London. Another Indian tennis star Sania Mirza has made history by becoming the first from the country to win a women's doubles Grand Slam trophy partnering with Martina Hingis of Swiss. On the other hand, youngster Sumit Nagal has registered his name in the history books as he became the only sixth Indian to win a Grand Slam junior title after winning the boys doubles trophy at the Wimbledon championships partnering with Nam Hoang Ly, in London. Also listen to Leander Paes's father about the win.


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Springfield Micro G.I.
I picked one up in a trade. Its in nice shape with only 250 rounds down the pipe. I'm thinking of making this a bit nicer of a gun, but I have some questions. Is this the series 70 or 80 firing system? Can I add an extended bevertail safety, new hammer, and trigger? Also What is the cut for the sites? The first thing that I will be adding is an ambidextrous safety as I am a lefty. As far as value I think I can do all this and still come out even if I ever sell it. I have about 375 total into it. Thanks
What? No pics? :)
Series 70 and 80 are Colts, but Springfield is much like the series 70 firing system, no firing pin block.
Here is the gun porn for ya.
The front sight looks to be a post. No joy for the DIY'er. Rear looks to be a standard GI. Typical hump & bump.
Sights on a "mouse gun" are the least used item and IMHO, irrelevant to accuracy. This is a PD weapon and as such, a point shooter. IOW, a Fight Shooter's gun. If you want to competitive shoot, get a gun with a real barrel!
My best experience for the grip safety is a Wilson "Drop in". It really was a drop-in. (See photo below)
Beavertail Grip Safety | Drop-In | Commander | Blue-Wilson Combat
Changing hammers is not something for the novice to DIY. You can go from crappy trigger pull to full auto in just a few file swipes! BATFE loves those guys and rewards them with a visit to Club Fed.
The Mainspring housing is a simple swap and with the "mouse" gun the addition of a S&A mag-guide adds some much needed purchase real estate. (See photo below)
Smith & Alexander - "The Mag-Guide People"
Call Aaron at Trip Research (877.837.9445) and tell him what gun you have and ask him to build you an 8 round, Gen II Cobra Mag w/base pad. Tripp's are the best 1911 mags on earth and this will also give your pinkie some aforementioned purchase. (Tell Aaron one like canebrake's) Once you use this mag you will be back ordering more. Read this:
Tripps Cobra Magazine Test
My Defender with an 8rd Cobra Mag and Alloy Base Pad for the Officer model 1911.
Hey, you asked.....and I'm Olympic at spending other people's money!
Hint for diy types concerning hammer/trigger/sear stuff:
Use only 1 live round followed by a snap cap or dummy round. This way if you make a booboo you can toss the f'd up part without some holier than thou scum bag calling the batfe on you. A visual inspection over the course of 50 shots or so in that manner will determine if your work is causing a failure
You did get a good deal for $375. I would try to sell it for $450 and add the money you would have used on parts and labor and get a model that already has what you want on it from the factory.
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text:
After a two-year hiatus, a well-known restaurant at the top of a Novato hill has reopened with a slightly altered name and a totally altered look.
Hilltop 1892, previously known as Hilltop Restaurant, officially opened its doors Thursday afternoon under the ownership of Marin native and San Francisco restaurateur Erick Hendricks. The menu of Chef Jack Harris is described as "classic American with a Californian influence."
The building at 850 Lamont Ave., originally constructed in 1892, was a restaurant from the late 1930s until September 2008 and for much of that time was one of Novato's few "destination" restaurants for date nights, prom-goers and those celebrating anniversaries.
The restaurant underwent a major renovation and beautification the past two years and was made compliant with the Americans with Disabilities Act. The most visible upgrades are a disabled-access ramp at the front door and aesthetic touches on the roof that cover mechanical equipment. The sweeping 10-mile views remain the same.
"The town of Novato and all the politicians embraced the project and were really supportive of me," Hendricks said. "There are obstacles in any project, but I found a lot of support from people in town and from the building officials and planners."
Hendricks, working with general manager Dave Keegan, will gradually increase the hours of operation at the restaurant, which seats 150.
"We won't have a full dining room for a while," Hendricks said. "We're not having a grand opening where we're inviting the whole town for dinner. It's a large establishment and there are a lot of working parts inside."
Read more Novato stories at the IJ's Novato section.
Contact Brent Ainsworth via e-mail at firstname.lastname@example.com


text:
Senator Farley Discusses Fair Issues with NYSAAF Representatives
State Senator Hugh T. Farley (R, C, I – Schenectady) met with representatives of the New York State Association of Agricultural Fairs (NYSAAF) on March 3rd in Albany to discuss the proposed State Budget and funding as well as other legislation pertaining to county fairs. Included in the meeting were (left to right) Will Schultz and Marie McMillen of the Altamont Fair, Frank Griffin and Jeff Townsend of the Saratoga County Fair, and Tom Della Rocco of Altamont Fair. Senator Farley is seated in the middle.


text:
BH T5 Treadmill Review
treadmill Doctor Note :
At $2300, True or Lifefitness would get my attention.
If you can get a $1000 discount, the T5 makes sense. Otherwise, look at other brands.
The BH T5 isn't a bad treadmill. Like many of BH's models, however, it is very overpriced. At $2,299, we'd suggest looking at other options, Lifefitness or True in particular, because the quality of this machine is well below what the price should dictate. If you can get a major discount, meaning $1,000 or more, then it would certainly be worth considering.
The walking area is a good size. The belt measures in at 20" x 57", which is a solid 3" shorter than the standard 20" x 60" walking belt that is found on many of today's treadmills. This should still provide plenty of room for larger users to run on comfortably without altering their stride.
A good motor powers this machine, but you can find cheaper treadmills with greater power producing capabilities if you know where to look. Speeds of up to 12 mph are attainable, so even experienced runners should have no problem challenging themselves.
An okay cushioning system comes on this model. Active Flex Suspension is used to reduce the impact that running has on your joints and back. You can find less expensive treadmills with significantly more forgiving and durable running surfaces.
As far as projected reliability is concerned, this machine is pathetic. You can find plenty of treadmills selling for less than $1,000 that have longer life expectancies than this one has. The quality of parts used is also extremely disappointing in this price range.
The warranty on the BH T5 is good. Labor is covered for 1 year, parts are covered for 10 years, and the motor and frame are covered for life. The warranty is the most price appropriate aspect of this treadmill. Don't let it trick you into believing that it is worth the $2,299 price tag it is associated with.


text:
Have Honda Questions? Ask a Honda Repair Expert.
Hello. Thank you for using Just Answer. I will give my best efforts in answering your question to achieve your full satisfaction. This transmission is a computer controlled unit. This means that the computer controls the shifting of the transmission by using calculations derived from numerous of engine and transmission sensors. If the computer does not have the proper sensor readings, it will place the transmission into a limp mode. This mode generally will be noticed with a D4 flashing light and a transmission shift difference. The shifting of the transmission will be dependent on the problem that the computer has noticed. The fact that the D4 light is flashing will alone tell you that the computer has detected an unusual sensor reading and will limit the trasmission's range of capabilities to protect it from further damage. The problem can be a faulty pressure, speed, engine sensor or a sensor that is actually detecting a problem in the transmission operating characteristics. The first thing to do here is to retrieve the stored trouble codes in the transmission computer. Then, depending on the trouble code(s) the diagnostic procedure will vary widely from that point. Even though these transmissions are known to be problemsome. Internal transmission problems are generally noticed as an progressive onset of numerous symptoms such as slipping, harsh shifts, shudders, and vibration rather than a sudden loss of shifting. An immediate loss of shifting will generally lead me to believe that an electrical/electronic problem is present rather than an internal transmission failure.
This transission is quite sensitive to the fluid quality. So, a clean Honda ATF (ONLY) filled transmission will have a much longer life than a transmission that has never been filled or filled with the incorrect fluid. Fluid drain and refills are generally done every 30K miles or as needed to keep the fluid a nice red color. Brown and discolored fluid will damage the transmission. So, you can check the fluid condition and this will also shed some light on the problem.
The most common problem causing your described symptom is a faulty pressure sensor for the 2nd clutch. There are 4 of these sensors. Since your unit will not shift fast 2nd gear, I would suggest a problem with the 2nd sensor or the 2nd clutch. But again, internal problems are generally noticed as a progressive onset of symptoms in shift quality rather than an immediate loss of shifting.
I strive to provide the best answers possible. If you need further help, have any questions, or need clarification about anything regarding this topic... Please feel free to ask by replying and I will give my best efforts to help you until your full satisfaction is achieved. However, if my answer was helpful and you are satisfied... I ask that you accept my answer so I may be compensated. Experts do not have funds transferred to their account unless the customer accepts. Your satisfaction is my main priority and I strive to provide the best service so please ask if there is anything else I could help you with
They are external to the transmission. If you provide with your VIN#, I can post a location of the sensors/switches if you would like.
This code is for a TCC (Torque Converter Clutch) Mecanical Malfunction. This is indeed the worst case scenario.
1. These transmission had a high failure rate and had a 7 year 100,000 mile warranty extension from Honda (Honda TSB #02-062). Honda has been replacing the transmission at times even if the vehicle has over 100,000 miles. Check fluid level and condition first. 2. If the fluid is OK, then suspect metal contamination in the transmission causing the transmission to slip or a failed seal. The most common problem is the carrier bearing failed and contaminated the transmission with metal. If the shift solenoid is sticking mechanically then where is the metal; coming from? Honda does not suggest solenoid replacement if the vehicle has over 20,000 miles or has been rebuilt once before.
Honda is the best when it comes to standing behind it's products. However, due to the recent geological problems in Japan, the economy worries, and other events... Honda is facing a shortage in parts and is having significant financial difficulties which have spread through out the Japanese vehicle lines. You might have picked the worst time to ask for leniency from Honda. But, you still have a good shot at having some kind of labor reimbusement for the repairs. When speaking with the dealer representatives, be professional, pleasant, and never lose your temper. That will get you NOWHERE fast. Instead, work your way up the dealership leadership ladder until you end up at the Honda customer website. Keep all recurds, names, and times you have spoken with each indivisual as this will aid your case if the dealership kicks your claim back at you. After all, the extended warranty for the transmission is only 7 years. You are past that... so you are asking THEM for help.
You are quite welcome. If you have any further questions regarding this matter, I encourage you to ask. However, I do ask that once fully satisfied with the answers I have provided you Accept so I may be properly compensated. Thanks.


text:
Worcester, Massachusetts: The uncle of the Boston Marathon bombing suspect killed in a gun battle with police has arrived at a funeral home to arrange for his burial.
Ruslan Tsarni and three other men met with Worcester funeral home director Peter Stefan, who said cemeteries in Massachusetts had been unwilling to accept the body.
The men who accompanied Mr Tsarni plan to wash and perform Muslim burial rites on the body of 26-year-old Tamerlan Tsarnaev, Mr Stefan said.
Tsarnaev, who had appeared in surveillance photos wearing a black cap and was identified as Suspect No. 1, died days after the April 15 bombing at the marathon finish line, which killed three people and wounded more than 260 others.
Mr Stefan said he has received calls from people criticising him and calling him "un-American" for being willing to handle Tsarnaev's funeral.
"We take an oath to do this. Can I pick and choose? No. Can I separate the sins from the sinners? No," he said. "We are burying a dead body. That's what we do."
On Sunday, no protesters were gathered outside the funeral home as there had been Friday and Saturday. But several people who drove by the funeral home yelled out their windows, including one man who shouted, "Throw him off a boat like Osama bin Laden!," a reference to the al-Qaeda leader's burial at sea after he was killed by Navy SEALS in a raid on his compound in Pakistan.
Mr Stefan said he hasn't been able to find a cemetery in Massachusetts willing to take the body, but he has received offers to provide a grave and to contribute money toward the funeral expenses from people in other states. Mr Stefan said he plans to ask the city of Cambridge, where Tsarnaev lived, to provide a burial plot, and if Cambridge turns him down, he will seek help from state officials.
Mr Stefan said Tsarnaev's uncle told him he is anxious to bury his nephew.
"They just want to get it over with. They want to get him buried," Mr Stefan said.
Mr Tsarni has denounced the acts that his nephews - Tamerlan and younger brother Dzhokhar - are accused of committing and has said they brought shame to the family and the entire Chechen community. The brothers are ethnic Chechens from Russia who came to the United States about a decade ago with their parents. Both parents returned to Dagestan in southern Russia last year.
Dzhokhar, 19, is in a prison hospital, facing a potential death sentence if convicted of the terrorism plot.


text:
Contact InformationGood Life Residential Llc
7233 Town Brooke
Middletown, CT 06457
Other InformationEntity Status: Active
Type of Entity: Domestic Limited Liability Company
Entity Creation Date: Mar 31, 2011
Days in Business: 2369 days
Company Description
Good Life Residential Llc is located in Middletown, Connecticut and is listed as an active Domestic Limited Liability Company. Good Life Residential Llc was started on Mar 31, 2011 which was 2369 days ago.
EmployeesEarl Wilson Sr: Manager
Registered AgentMarc A Wilson
None, CT NONE
Edit ProfileEdited: 12/1/2011
To edit this profile, please click here. You will be able to add a custom description, social networks, website, phone number, and many more features to your ISHCC.org profile.
Reviews0 Reviews
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text:
FBI agents on Thursday were at Southwest Secondary Learning Center charter school in Albuquerque as part of an ongoing investigation, FBI spokesman Stephen Marshall said.
The agents were seen loading boxes into two dark-colored vans parked outside the school near Morris and Candelaria during the afternoon.
Marshall said he could "confirm we have agents over there as part of an ongoing investigation," but he would not say what the agency was investigating or whether it involved a specific individual or individuals.
The Journal could not reach principal Al Baysinger on Thursday afternoon. Chief Financial Officer Scott Glasrud did not return a phone call left at the school or on his cellphone Thursday, nor did he respond to an email from the Journal.
Jennifer Chavez, who has been a spokeswoman for the school, said she had no information because her contract with the school expired July 1.
Geneva Schult said she went by the school at about 2:15 p.m. Thursday to sign a form so her son could take one of the school's online courses. She said she saw the vans parked in front of the building.
"I thought 'What are they doing? They can't park there,' " she said. "I walked up to the door and there was a big blue sign that said 'Closed' but it didn't say why or give any other information."
Schult said the door was ajar, and she noticed several file boxes in the lobby and an FBI agent.
She said another man in a dress shirt and tie, who did not identify himself, told her the school would reopen today. The phone at the school went unanswered Thursday and nobody could be reached to confirm when it would reopen.
The campus contains Southwest Primer, Intermediate and Secondary schools that serve students in grades 4-12.


text:
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text:
|2008-06-17, 02:34
|Link #1321
VxR Productions
IT Support
Since i'm not on always nowadays, there's that PM function or just wait for my arrival in IRC, i'll geive you exclusive access to one of OCC/T's Private Sanctuaries...
And speaking of CCS... i'm probably one of few that can think of card combos and OC cards as well
Sword + Illusion + ?? Card = Unlimited Blade Works CCS ver.
I'm not kidding.
I'm working in the TRAP department thought atm.
*points to avatar*
*warps away*
|2008-06-17, 02:50
|Link #1322
Sword Wielding Penguin
It's politics. And politics get wonky.
It would boil down to the Haves and the Have Nots. You've got the supporters, such as the Harlowne Admiralty providing support... And then you've got high ranking officials who have the responsibilities of their positions, but lack either prestige or power that they think should come with it.
The aces have gotten their position by getting the Job Done. Which gains them adoring fans, and good standing. But then you've got the people who abuse the system, who gain their position through well played paperwork games and internal politics. People who think they desserve everything on a silver platter, and have been their longer... and that when some upstart young mages come along that can actually do their jobs right and thus get special treatment... that "It's not fair."
Regius, being non-mage from the start, is borderline of this. He got his position by being a strong politalker, but was genuinly decent at his job. However, the Admiralty generally gets more jobs done, and gets the funding, the prestige, and the special treatment.
Then suddenly along comes RF6... essentially a Ground Jurisdiction force operating on his HOME turf in Cranagan. He was genuinly suprised to discover them operating right under his nose. Where was HE when the paperwork was signed?
You can have plenty of people who love RF6 to death... but there are plenty of backstabbing politically ambitious types who find their own oppertunity for self-profit in breaking them, or lost oppertunity because they jumped in with their special privilages.
I mean, just looking at RF6 offhand, my first thought would be: The only reason that unit is there is freakin Nepotism. I mean, look at the primary supports. Admiral Lindy and Admiral Chrono Harlowne... Mother and son... Who in turn adopted Fate Testarossa... making her their daughter, in a unit they're supporting. Good friends with T. Nanoha, who are all good friends with Y. Hayate.... Who is 'related' to Signum, Vita, Shamal, and Zafira.
Fate's subordinate squad consists of two children she adopted, and Nanoha's squad consists of a person she rescued.
Let's not forget how Hayate ties in with the Harlownes indirectly through another incident.
If I were a self serving sonuva who spotted this... I could probably tear the unit apart with nothing more than a sub-par legal team, just by attacking the nepotism that is rampant. And the only reason they seem to manage to stay in good favor in a buraucracy like the TSAB is because of the results they've had, and the connections they have to the very top tier. (The Three Admirals)
There's any number of reasons some oppertunist punk in the TSAB command structure would hate RF6 and the aces. From spite, to greed, to distrust.
|2008-06-17, 02:55
|Link #1323
Nuclear Fusion
Join Date: Sep 2007
Location: Sky of stone, floor of flame.
Age: 30
Quick question regarding affinity.
I'm aware that a person is normally restricted to one affinity. For argument's sake, though, if I were to try my hand at a believable way for a person to somehow have two (and no more that two), maybe through a loophole I thought of (:3), would there be a way to make that work?
This is for a WIP of mine, and a dual-setup would greatly simplify a problem I have; I really want to make this work somehow.
|2008-06-17, 03:06
|Link #1324
Part-Time TTK & Master
Join Date: Jun 2006
Location: Iwakawa base and Chaldea
Age: 37
tbh, the only reason I'd bring up political backstabbing in my scenarios is to have the camarillas and plotters to get the badass balls-out bitchslap of their life. It happened at my table during a AD&D2 campain, where the player playing the barbarian of the group got so pissed at the political scheming of a courter, it has cost his friends' lifes, that he humiliated the courter in public and dragged him behind his horse until all his skin has been peeled off.
And being the barbarian he is, he killed the courter's family.
|2008-06-17, 04:10
|Link #1327
Adeptus Animus
Join Date: Jan 2007
Age: 29
I think I'm going to take the initiative and drop the Barrier Jacket discussion. It's clear that we will never reach a conclusion on this subject. I for one am perfectly able to accept the barriers and fields that give even a tank top high defensive capabillities (its not a matter of clothing, its a matter of energy).
Now start writing, I want to read FateXAsclei love moments. :3
Baring the silly looking helmet, it doesn't really look all that different from the standard TSAB Air force Jacket. And they leave the arms and legs uncovered by what little hard stuff it has too... and 3 guesses which body parts suffer the most hits in close range combat.
Anyway, I don't see the point of this assault. Tactical competence of the TSAB and RF6 haters are hardly related, however RF6 haters and RF6 supporters are.
Last edited by Keroko; 2008-06-17 at 12:03.
|2008-06-17, 04:21
|Link #1329
Join Date: Nov 2006
Location: Portugal
IMO, Subaru's BJ seems to provide as much defense as Signum's.
Sure, it's a dangerous card, but it doesn't look that powerful, it's just fast...and gradually becomes even faster if not stopped...but powerful...don't think so.
*warps away*
|2008-06-17, 04:40
|Link #1331
Sword Wielding Penguin
Yeah... like an angry new yorker that scout...
That's not how a Chain of Command works. Your superiors immediately above you in your chain of command, and their superiors are the ones who generally control how quickly you will rank up. Good standings with other units and such certainly help. But in the end, it's the unit commander in charge that makes the call.
As an air force agressor, Nanoha could piss off entire ground force battalions and they don't have jack as far as having any say in what the air force general in charge of her does. They can complain, but if the Air Force General likes her, sees she DOES get the job done, and such... he can ignore them.
I think 7arcs just didn't realize what a legal mess that level of Nepotism would have in a highly buraucratic system. I mean, the first thing that screamed it was Lindy waving Chrono off with a hankie. Okay... so mom commands a Warship... and her top ass-kicker onboard is her own son. O_o Okay. Anyone who understands the psychology of command knows that family members reprisent a massive liability to rational thinking in high risk scenarios... And a mother is right there sending her son into a risky situation like it's another day at the park.
|2008-06-17, 04:54
|Link #1332
Part-Time TTK & Master
Join Date: Jun 2006
Location: Iwakawa base and Chaldea
Age: 37
I highly recommend this manga, just to check how the combat choregraphy can be awesome. Not in a "CHARGIN MAH LAZAH" way.
|2008-06-17, 05:12
|Link #1333
Adeptus Animus
Join Date: Jan 2007
Age: 29
Of course, Signum's rank may also be a factor. Signum is an S-rank mage, so she'd be able to put lot more magic to her Barrier Jacket, which would increase its defense higher then Subaru's, simply because she has more energy to spare.
Well... maybe some terrorist ones, or those in shady countries, but lets not go there.
In my opinion 7Arcs quite frankly didn't care about that sort of stuff, so they didn't bother to put it in. And if almost all their fans can swallow it without choking, why complicate things? Sure, a few people who know military and psychology may be bothered by it (and even then only if they take the effort to be bothered by it) but you can't please everyone.
Last edited by Keroko; 2008-06-17 at 05:33.
|2008-06-17, 05:58
|Link #1336
Part-Time TTK & Master
Join Date: Jun 2006
Location: Iwakawa base and Chaldea
Age: 37
|2008-06-17, 06:09
|Link #1338
Part-Time TTK & Master
Join Date: Jun 2006
Location: Iwakawa base and Chaldea
Age: 37
|2008-06-17, 07:09
|Link #1339
Storm Vanguard
Graphic Designer
Join Date: Mar 2008
Location: Type-00
Yeah, I'm glad the Sonic EXA Form is good enough to please some of you. The reason why her barrier jacket has been changed will be explained in the chapters (which I'm gonna start writing soon again).
Fate turning into a tsundere? umm...not really. The reason why she had that face is because she was trying to forget about the dream. She came close but seeing Asclei's face brought it up again which caused her to feel flustered causing her to avoid Asclei and trying her best again to forget about it
What do you want me to draw? I could try but there are somethings that I can't simply sketch unless I'm inspired.
Yeah. I should start writing the ch 2 soon XD (although I'm quite itching to sketch a 21 year old, long haird Hayate). The FatexAsclei love moments will not appear till later though.
|2008-06-17, 07:33
|Link #1340
Join Date: Mar 2008
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