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In November 2015, Amazon opened its first physical, real-life bookstore, called Amazon Books, right on its home turf of Seattle.
Since then, Amazon has opened two more bookstores in San Diego and Portland, Oregon, and has just unveiled plans to open a new shop in Midtown Manhattan.
The latest bookstore will be located inside the Shops at Columbus Circle, a high-end shopping center near Central Park. Two more stores are now being planned for Chicago and Dedham, Massachusetts, according to The Wall Street Journal.
While I was in Seattle in August, I made sure to stop by the original Amazon Books to check it out. I don't necessarily love Amazon, but I love books, and I am willing to play along with its ever-ambitious plans to conquer the world of commerce. Cheaper is cheaper, after all.
When my colleague Aly Weisman stopped by Amazon Books last December, she found that while she liked it for the most part, she hated the core concept of the store: The books don't have a listed price; you have to use your phone and scan to see the most current price. But I had the complete opposite reaction. I thought it was great, in a way that only Amazon could make possible. Take a look and see what I mean: | 2023-09-10T01:26:29.851802 | https://example.com/article/3854 |
Sant'Agostino alla Zecca
Sant Agostino alla Zecca, also known as Sant'Agostino Maggiore is a church in central Naples, Italy.
Originally granted to the Augustinian monks by Robert I of Anjou in 1259. The church underwent extensive reconstruction in the Baroque period by Bartolomeo Picchiati. Its name derives from its location near the former mint. Since the 1980 Irpinia earthquake, it has been closed and is in a poor state of conservation. The interior has frescoes of Giacinto Diano in the Sacristy.
Sources
entry on church
Degrading interiors
External links
Agostino alla Zecca
Agostino alla Zecca | 2024-01-03T01:26:29.851802 | https://example.com/article/8816 |
Ramal do Montijo
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Ramal do Montijo, originally called Ramal de Aldegallega or Ramal de Aldeia Galega, the former name of Montijo, is a closed railway line which connected Pinhal Novo to Montijo, in Portugal. It was opened on 4 October 1908 and closed in 1989.
See also
List of railway lines in Portugal
List of Portuguese locomotives and railcars
History of rail transport in Portugal
References
Sources
Category:Railway lines in Portugal | 2023-08-17T01:26:29.851802 | https://example.com/article/2691 |
Recent Blog Articles
The Family Excerpt Two
I have been truly blessed to have such a wonderful family. When it came time to finally put
words to paper, I couldn’t leave them out, in fact, they all became fair game.
The following is an excerpt from my new book…
ENJOY AN EXCERPT FROM MY BOOK,
INSPIRED BY MY FAMILY
The Phone is Going to Ring
Having been back stage at major musical productions, I have seen all that goes into “putting on a show.” Props are especially important and the position of prop master is critical to a production. Props are assigned to a specific place on a specific prop table. There are prop lists that are checked, double checked and tripled checked, every night. Once, while I was singing in Italy, my costume required me to wear beautiful gold and blue jewelry. There was a prop assistant assigned to my necklace, bracelet and earrings. Her only job was to ensure that I wore them on stage and then they were returned to their proper place.
I attended a performance with my cousin, Kim and when the curtain opened, there was a phone on one of the tables in the scene. I whispered to my cousin, “That phone is going to ring.” She looked at me perplexed and then about half way through the scene, there was a phone call for one of the major characters. I knew that every prop has a meaning and a purpose and I knew that the phone on the table is on a prop list, and has an assigned place on a prop table, and I knew there was one person responsible for the phone being on stage and making its way back to the prop table, and if someone is going to all that trouble, the phone is going to ring.
This is how I look at students with learning disabilities. I see the phone that is going to ring but only because I have had the opportunity to be back stage in the world of special education and I have seen firsthand how it all works. My cousin didn’t even notice the phone on the table and why would she? She has never been back stage. My cousin represents the general education teachers who have been thrust onto the stage of special education without warning, without permission, without consultation, without training and without resources. They need our help because whether they are prepared for it or not, they are major characters in this production, the phone is ringing, and the call is for them. | 2023-11-07T01:26:29.851802 | https://example.com/article/2952 |
Introduction {#S1}
============
Extracellular vesicles (EVs) can be harvested from cell culture supernatants and from all body fluids. They can be roughly classified based on their size and subcellular origin as exosomes (70--150 nm in diameter) which are released when multivesicular bodies fuse with the plasma membrane ([@B1]), or microvesicles (100 nm to 1 µm in diameter) which are formed by the outward budding of the plasma membrane ([@B2], [@B3]). In addition to these different EV subtypes, nowadays it is accepted in the field that there is likely to be a much higher degree of EV heterogeneity at multiple levels also within each subentity \[reviewed in Ref. ([@B4])\]. As of now, no specific surface markers discriminating exosomes from microvesicles have been identified, and only a few EV surface markers have been reliably linked to specific cell sources. However, there is accumulating evidence that the protein composition and surface signature of EVs is likely dependent on the cell-type releasing them, the cell's activation status and multiple other parameters. It can also be assumed that single cells release several functionally and phenotypically different types or classes of EVs ([@B5]--[@B12]). In general, addressing questions of heterogeneity in EV-containing samples has been challenging, mainly due to the small size of EVs and the lack of qualified, robust, and rapid methods to analyze multiple parameters of single EVs. However, the identification of specific vesicular surface markers will be of great relevance to further understand the molecular content and related functions of subsets of EVs, to identifying potential EV subsets with a defined therapeutic activity, and to uncovering and defining specific disease-related biomarkers.
Particularly within recent years, technical advancements have led to the development of new approaches enabling the analysis of EVs at the single vesicle level \[reviewed in Ref. ([@B13])\]. Many of those methods are based upon light scattering, electron microscopy, fluorescence detection, or structural analysis ([@B12], [@B14]--[@B17]). Furthermore, a plethora of dedicated flow cytometric approaches have been developed and refined for single EV counting and phenotyping ([@B6], [@B18]--[@B24]), or for single EV sorting ([@B25], [@B26]). Several guidelines and protocols have been published in recent years with the aim to educate researchers and make the field aware of potential pitfalls, measurement artifacts like swarm detection and background caused by antibodies or lipoproteins ([@B20], [@B21], [@B27]--[@B40]). However, the widespread application and use of single EV analysis by flow cytometric methods is still hampered by the above-mentioned challenges, pitfalls, and ambiguities, and by the limited availability of appropriate instrumentation. Furthermore, single EV analysis requires time-consuming operations which in turn require extensive flow cytometric expertise for sample preparation, acquisition, and data analysis.
To overcome such issues, relatively simple bead-based protocols relying on the capture of EVs on antibody-coated beads with flow cytometric read-outs have been used to probe for the presence of candidate EV surface markers ([@B22], [@B41]--[@B45]). Of note, a recent validation study of a bead-based protocol showed a clear correlation between mean fluorescence intensities and EV contents ([@B46]). Moreover, a bead-based assay including 39 different antibody-coated multiplexed bead populations was recently described and used to assess and identify EV surface markers with clear differential expression between different blood cell type EVs by using conventional flow cytometry ([@B10]).
Here, we have critically investigated this novel multiplex bead-based flow cytometric assay and hereby present its methodological optimization and validation. During the course of our experiments we have optimized and explored different sample- and assay-related parameters in terms of detection limit, range of detection and reproducibility. We further provide different kinds of experimental examples to address basic but essential parameters for the assessment of EV surface signatures such as differential EV isolation protocols and storage conditions. Thus, we show that this multiplex bead-based flow cytometric assay, which could be applied in most laboratories, allows for reproducible detection of EV surface marker expression in various EV-containing sample types in a semi-quantitative manner. We conclude that this now validated assay will help EV researchers and support new discoveries in different areas of interest in the EV field.
Materials and Methods {#S2}
=====================
Cells and Cell Culture {#S2-1}
----------------------
Unless indicated otherwise, cell lines were cultured in the following media: HEK293T cells were cultured in DMEM (containing Glutamax-I and sodium pyruvate; 4.5 g/L glucose; Invitrogen) supplemented with 10% FBS (Invitrogen), 1× Antibiotic-Antimycotic (Anti-Anti; ThermoFisher Scientific). Immortalized, human bone marrow-derived mesenchymal stromal cells \[hTert + mesenchymal stromal cell line (MSCs)\] ([@B47]) were cultured in RPMI-1640 (containing Glutamax-I and 25 mM HEPES; Invitrogen) supplemented with 10% FBS (Invitrogen), 10^−6^ mol/L hydrocortisone (Sigma) and 1× Anti-Anti. PANC-1 cells ([@B48]) were cultured in DMEM/F12 (containing 2.5 mM [l]{.smallcaps}-glutamine, 15 mM HEPES) supplemented with 10% heat-inactivated FBS (Invitrogen). IGROV1 cells ([@B49]) were cultured in RPMI-1640 (containing Glutamax-I and 25 mM HEPES; Invitrogen) supplemented with 10% heat-inactivated FBS (Invitrogen). All cell lines were grown at 37°C, 5% CO~2~ in a humidified atmosphere. For some experiments, media was changed to OptiMEM (Invitrogen) 48 h before harvest of conditioned media (CM) as described before ([@B50]). Unless indicated otherwise, all CM samples were directly subjected to a low speed centrifugation step at 500 × *g* for 5 min followed by a 2,000 × *g* spin for 10 min to remove larger particles and cell debris. FOLR1 cell surface expression on PANC-1 and IGROV1 cell lines was assessed by staining with APC-conjugated anti-human FOLR1 monoclonal antibodies (R&D Systems, clone 548908) *via* flow cytometry. Further details on sample processing are provided in Table S2 in Supplementary Material.
Isolation and Culture of Human Hematopoietic Progenitor Cell Subsets {#S2-2}
--------------------------------------------------------------------
Human umbilical cord blood (UCB) was obtained from donors at the University Hospital Essen, Germany, after informed written consent according to the Declaration of Helsinki. The experimental usage of UCB samples was approved by the local ethics commission. Mononuclear cells were isolated by Ficoll (Biocoll Separating Solution, Biochrom) density gradient centrifugation and highly enriched for human hematopoietic CD34+ stem/progenitor cells as described previously ([@B51], [@B52]). For flow cytometric cell sorting of MPP-, LMPP-, and EMP-enriched hematopoietic progenitor subfractions, freshly isolated CD34+ cells were labeled with the following antibodies: anti-CD34-APC-AF750 (Beckman Coulter, clone 581), anti-CD45-BV510 (BD Biosciences, clone HI30), anti-CD133/1-APC (Miltenyi Biotec, clone AC133), anti-CD45RA-BV711 (BioLegend, clone HI100), and anti-CD38-BV786 (BD Biosciences, clone HIT2) antibodies as described before ([@B52]). Dead cells were excluded by 7-AAD (Beckman Coulter) staining. Cells were sorted using a FACSAria IIIu cell sorter (BD Biosciences) to a purity above 99.5%. Sorted cells were seeded at a density of 25,000 cells/300 μL in 48-well plate and cultured in a humidified atmosphere at 37°C and 5% CO~2~ in IMDM (Lonza) supplemented with 20% FBS (Biochrom), 100 U/mL penicillin, and 100 U/mL streptomycin (Life Technologies) and with FLT3L, SCF, and TPO each at 10 ng/mL final concentration (all Miltenyi Biotec). CM were harvested after 4 days. Further information on sample processing and storage is provided in Table S2 in Supplementary Material.
Cerebral Spinal Fluid (CSF) Samples {#S2-3}
-----------------------------------
Cerebral spinal fluid samples included in this study were derived from patients who underwent a lumbar puncture for clinical purposes at Neurology department at Karolinska University Hospital, Stockholm Huddinge, Sweden. Written informed consent was obtained from all subjects in accordance with the Declaration of Helsinki. This study was approved by the Regional Ethical Review Board in Stockholm, Sweden. All CSF samples were pre-cleared by 400 × *g* for 10 min and subsequent 2,000 × *g* centrifugation for 10 min, and filtered through 0.22 µm syringe filters with cellulose acetate membrane (VWR). Further information on sample processing and storage is provided in Table S2 in Supplementary Material.
Human Blood Samples {#S2-4}
-------------------
The prospective clinical studies 02-C-0064, 04-C-0257, and 09-C-0195 were approved by the Institutional Review Board of the National Cancer Institute (NCI; MD, USA). Informed consent was obtained from all donors. For the data presented in this study, plasma and serum samples were processed as follows: 6 mL samples of blood from healthy volunteers were isolated in heparin and serum-separating tubes. The blood was spun at 2,500 × *g* for 20 min twice with the platelet poor plasma being isolated. Samples were then either frozen at --80°C or kept at 4°C, and run through size exclusion chromatography (SEC) columns (single qEV columns, IZON, New Zealand) according to the manufacturer's recommendations were indicated.
Mouse Experiments {#S2-5}
-----------------
Female NMRI mice with a bodyweight around 20 g were intravenously (tail vein) injected with 2 × 10^11^ hTert + MSC-EVs in 100 µL PBS. Blood was sampled by heart puncture 1 min and 30 min after injection and collected into PST-tubes (BD Biosciences) according to manufacturer's instructions. Samples were depleted from cells by centrifugation at 2,000 × *g* for 10 min. Plasma samples were subjected to 0.22 µm filtration, and 120 µL filtered plasma was transferred to the MACSPlex Exosome assay. The animal experiments were approved by the Swedish Local Board for Laboratory Animals. The experiments were performed in accordance with the ethical permissions granted, and designed to minimize the suffering and pain of the animals.
Isolation of EVs From Cell Culture Supernatant {#S2-6}
----------------------------------------------
Several different EV isolation protocols, and variations or combinations thereof, were applied in this study in order to compare the detectable EV surface signatures in respective fractions with the MACSPlex Exosome flow cytometry assay. See Table S2 in Supplementary Material for detailed information how EVs were prepared for which experiment. Generally, CM was pre-cleared first by a low speed centrifugation step (500--900 × *g* for 10 min) followed by centrifugation at 2,000 × *g* for 10--20 min to remove larger particles and debris. Unless indicated otherwise, samples were subsequently filtered through syringe (VWR) or bottle top filters (Corning, low protein binding) with cellulose acetate membranes (0.22 µm pore size) to remove any larger particles. To purify EVs with differential UC CM samples were either first subjected to centrifugation at 10,000 × *g* for 30 min or directly subjected to UC at 110,000 × *g* for 90 min to pellet the EVs. A second washing step was performed in both cases by resuspending the EV pellet in 25 mL of PBS and another 90 min of UC at 110,000 × *g*. 10,000 and 110,000 × *g* centrifugation steps were performed at 4°C using the Beckman Coulter Type 70 Ti rotor in a Beckman Coulter L-80 ultracentrifuge. To concentrate EVs *via* tangential flow filtration (TFF) CM was diafiltrated with at least two times of the initial volume of PBS and concentrated to 20 mL using the KR2i TFF system (SpectrumLabs) equipped with modified polyethersulfone hollow fiber filters with 300 kDa membrane pore size (MidiKros, 370 cm^2^ surface area, SpectrumLabs) at a flow rate of 100 mL/min (transmembrane pressure at 3.0 psi and shear rate at 3,700 s^−1^). To concentrate CSF samples with starting volumes of 20--30 mL, smaller versions of the same filter type (MicroKross, 20 cm^2^, SpectrumLabs) were used to diafiltrate and concentrate samples down to 1 mL manually. To further purify EVs *via* bind-elute SEC (BE-SEC) pre-concentrated CM samples were loaded onto BE-SEC columns (HiScreen Capto Core 700 column, GE Healthcare Life Sciences), connected to an ÄKTAstart chromatography system (GE Healthcare Life Sciences) as described previously ([@B50]). All settings were chosen according to the manufacturer's instructions. Briefly, the EV sample was collected according to the 280 nm UV absorbance chromatogram and concentrated to a final volume of 500 µL by using an Amicon Ultra-15 10 kDa molecular weight cut-off spin-filter (Millipore).
Nanoparticle Tracking Analysis (NTA) {#S2-7}
------------------------------------
Nanoparticle tracking analysis ([@B15], [@B53]) was applied to determine particle size and concentration of all samples. All plasma/serum samples were characterized by NTA with a NanoSight LM10 instrument (Malvern, UK), equipped with a 405 nm LM12 module and EMCCD camera (DL-658-OEM-630, Andor). Video acquisition was performed with NTA software v3.2, using a camera level of 14. Three 30 s videos were captured per sample. Post-acquisition video analysis used the following settings: minimum track length 5, detection threshold 4, automatic blur size 2-pass, maximum jump size 12.0. All other samples were characterized with a NanoSight NS500 instrument equipped with NTA 2.3 analytical software and an additional 488 nm laser. At least five 30 s videos were recorded per sample in light scatter mode with a camera level of 11--13. Software settings for analysis were kept constant for all measurements (screen gain 10, detection threshold 7). All samples were diluted in 0.22 µm filtered PBS to an appropriate concentration before analysis.
Western Blotting {#S2-8}
----------------
HEK293T cells and hTERT + MSCs were collected and counted using trypan blue 0.4% (Invitrogen, Thermo Fisher Scientific) in a Countess II FL automated cell counter (Invitrogen, Thermo Fisher Scientific). 2 × 10^6^ cells were pelleted at 300 × *g* for 5 min, washed once with cold PBS and pelleted at 300 × *g* for 5 min. The cell pellet was lysed with 100 µL of RIPA buffer, kept on ice, and vortexed five times every 5 min. The cell lysate was then spun at 12,000 × *g* for 10 min at 4°C and the supernatant was transferred to a new tube and kept on ice. Cells and particles were mixed with buffer containing 0.5 M dithiothreitol, 0.4 M sodium carbonate (Na~2~CO~3~), 8% SDS, and 10% glycerol, and heated at 65°C for 5 min. The samples were loaded onto a NuPAGE Novex 4--12% Bis-Tris Protein Gel (Invitrogen, Thermo Fisher Scientific) and run at 120 V in NuPAGE MES SDS running buffer (Invitrogen, Thermo Fisher Scientific) for 2 h. The proteins on the gel were transferred to an iBlot nitrocellulose membrane (Invitrogen, Thermo Fisher Scientific) for 7 min using the iBlot system. The membrane was blocked with Odyssey blocking buffer (LI-COR) for 60 min at RT with gentle shaking. After blocking, the membrane was incubated overnight at 4°C or 1 h at RT with primary antibody solution \[1:1,000 dilution for anti-Alix (ab117600, Abcam) and anti-Tsg101 (ab30871, Abcam); 1:2,000 dilution for anti-CD9 (ab92726, Abcam)\]. The membrane was washed with PBS supplemented with 0.1% Tween-20 (PBS-T, Sigma) five times for every 5 min and incubated with the corresponding secondary antibody (LI-COR) for 1 h at RT (1:15,000 goat anti-mouse IRDye800CW or 680LT to detect Alix; 1:15,000 dilution goat/anti-rabbit IRDye800CW or 680LT to detect CD9, Tsg101). The membrane was washed with PBS-T for five times within 25 min, twice with PBS and visualized on the Odyssey infrared imaging system (LI-COR).
Generation of Stable Cell Lines {#S2-9}
-------------------------------
Codon-optimized DNA sequences coding for human CD63 (Uniprot accession number P08962) and the fluorescent proteins mNeonGreen ([@B54]) (GenBank accession number AGG56535.1), mCardinal ([@B55]) (GenBank accession number KJ131552), E2-Crimson ([@B56]) and Cerulean ([@B57]) (GenBank accession number AJD87366.1) were synthesized (Integrated DNA Technologies) as gene fragments and cloned downstream of the CAG promoter into the pLEX vector backbone using EcoRI and NotI. To generate the different constructs expressing respective fluorescent proteins fused to the C-terminus of CD63, fluorescent protein coding sequences (CDS) were subcloned into pLEX-CD63 using SacI and NotI. Next, the complete CDS of the different CD63-fluorescent protein fusions were cloned into the lentiviral p2CL9IPwo5 backbone downstream of the SFFV promoter using EcoRI and NotI, and upstream of an internal ribosomal entry site-puromycin resistance cDNA cassette (see Figure [5](#F5){ref-type="fig"}A). All expression cassettes were confirmed by sequencing. Lentiviral supernatants were produced as described previously ([@B58]). In brief, HEK293T cells were co-transfected with p2CL9IPw5 plasmids containing CD63 fused to the respective fluorescent proteins, the helper plasmid pCD/NL-BH, and the human codon-optimized foamyvirus envelope plasmid pcoPE ([@B59]--[@B61]) using the transfection reagent JetPEI (Polyplus, Illkrich Cedex). 16 h post transfection gene expression from the human CMV immediate-early gene enhancer/promoter was induced with 10 mM sodium butyrate (Sigma-Aldrich) for 6 h before fresh media was added to the cells, and the supernatant was collected 22 h later. Viral particles were pelleted at 25,000 × *g* for 90 min at 4°C. The supernatant was discarded and the pellet was resuspended in 2 mL of Iscove's Modified Dulbecco's Media supplemented with 20% FBS and 1% P/S. Aliquots were stored at −80°C until usage. To generate stable cell lines, HEK293T cells were transduced by overnight exposure to virus stocks and passaged at least five times under puromycin selection (Sigma; 6 µg/mL). The expression of respective CD63-fluorescent protein fusion constructs was confirmed *via* flow cytometry and fluorescence microscopy for all established cell lines (data not shown).
Bead-Based Multiplex Exosome Flow Cytometry Assay {#S2-10}
-------------------------------------------------
Different sample types were subjected to bead-based multiplex EV analysis by flow cytometry (MACSPlex Exosome Kit, human, Miltenyi Biotec) ([@B9], [@B10]), with details regarding sample preparation and normalization summarized in Table S2 in Supplementary Material. Unless indicated otherwise, EV-containing samples were processed as follows: Samples were diluted with MACSPlex buffer (MPB) to, or used undiluted at, a final volume of 120 µL and loaded onto wells of a pre-wet and drained MACSPlex 96-well 0.22 µm filter plate before 15 µL of MACSPlex Exosome Capture Beads (containing 39 different antibody-coated bead subsets) were added to each well. Generally, particle counts quantified by NTA, and not protein amount, were used to estimate input EV amounts. Filter plates were then incubated on an orbital shaker overnight (14--16 h) at 450 rpm at room temperature protected from light. To wash the beads, 200 µL of MPB was added to each well and the filter plate was put on a vacuum manifold with vacuum applied (Sigma-Aldrich, Supelco PlatePrep; −100 mBar) until all wells were drained. For counterstaining of EVs bound by capture beads with detection antibodies, 135 µL of MPB and 5 µL of each APC-conjugated anti-CD9, anti-CD63, and anti-CD81 detection antibody were added to each well and plates were incubated on an orbital shaker at 450 rpm protected from light for 1 h at room temperature. Next, plates were washed by adding 200 µL MPB to each well followed by draining on a vacuum manifold. This was followed by another washing step with 200 µL of MPB, incubation on an orbital shaker at 450 rpm protected from light for 15 min at room temperature and draining all wells again on a vacuum manifold. Subsequently, 150 µL of MPB was added to each well, beads were resuspended by pipetting and transferred to V-bottom 96-well microtiter plate (Thermo Scientific). Flow cytometric analysis was performed, unless indicated otherwise, with a MACSQuant Analyzer 10 flow cytometer (Miltenyi Biotec; see Table S1 in Supplementary Material for acquisition parameters) by using the built-in 96-well plate reader. All samples were automatically mixed immediately before 70--100 µL were loaded to and acquired by the instrument, resulting in approximately 7,000--12,000 single bead events being recorded per well. FlowJo software (v10, FlowJo LLC) was used to analyze flow cytometric data. Median fluorescence intensity (MFI) for all 39 capture bead subsets were background corrected by subtracting respective MFI values from matched non-EV buffer or media controls that were treated exactly like EV-containing samples (buffer/medium + capture beads + antibodies). GraphPadPrism 6 (GraphPadPrism Software, La Jolla, CA, USA) was used to analyze data and assemble figures. To generate heatmaps of data, flow cytometric data were gated in FlowJo with gated data being exported to comma separated files, which were subsequently imported into MATLAB (v9.3.0, Mathworks Inc.) for further analysis and data visualization. In order to compare data from the MACSQuant and FACS Symphony flow cytometers, the log10 transformed ratios of capture beads + EVs + Ab over their respective controls (capture beads + ab) was compared, rather than using background subtraction, which allowed for comparison despite axis scaling differences.
Results and Discussion {#S3}
======================
Detection of EV Surface Signatures With a Multiplex Bead-Based Flow-Cytometry Assay {#S3-1}
-----------------------------------------------------------------------------------
In this study, we aimed to systematically evaluate and explore the capabilities of a recently described ([@B10]) multiplex bead-based flow cytometry assay platform for EV research. In its current form, this assay comprises 39 hard-dyed capture bead populations (4 µm diameter), each of them coated with different monoclonal antibodies against 37 potential EV surface antigens or two internal isotype negative controls. All bead populations can be identified and gated based on their respective fluorescence intensity according to the assay documentation provided by the manufacturer (Figure S1 in Supplementary Material). After incubation with EV-containing samples, bulk bead-captured EVs can subsequently be detected by counterstaining with APC-labeled detection antibodies against the tetraspanins CD9, CD63, and CD81, which are often referred to as common EV surface markers. In this study, we mostly used a mixture of all three antibodies (pan tetraspanin) in order to cover most EVs being present in respective samples. This assay hence relies on the detection of single capture beads, whereby each antibody-coated bead can capture multiple EVs. Bead-captured EVs for each bead, and subsequently for each bead population, can then indirectly be detected through the cumulative signal of multiple fluorescence-conjugated antibodies that bind to respective epitopes on the bulk bead-captured EVs.
First, the EV content of HEK293T-derived pre-cleared CM was analyzed following overnight capture and pan tetraspanin detection (Figure [1](#F1){ref-type="fig"}A). Raw APC MFI values for each capture bead population were background corrected by subtracting corresponding MFI values obtained from media controls (capture beads + detection antibodies) subjected to the same protocol as samples (capture beads + EVs + detection antibodies; Figures [1](#F1){ref-type="fig"}B,C). The FITC and PE channels of a MACSQuant Analyzer 10 flow cytometer equipped with 405, 488, and 638 nm lasers were used to identify capture bead populations (Figure [1](#F1){ref-type="fig"}B; Figure S1 and Table S1 in Supplementary Material). When analyzing samples on flow cytometers equipped with additional green lasers, e.g., the Beckman Coulter Cytoflex S instrument, we observed a slightly different appearance of the bead populations when using respective channels designated for FITC Vs. PE detection (Figure S2A in Supplementary Material, left panel). However, by using more suitable filter sets for bead identification, a similar bead distribution to that from an instrument lacking a green laser could be achieved (Figure S2A in Supplementary Material, right panel).
{#F1}
Particularly four bead populations, i.e., CD9, CD63, CD81, and CD29, were detected as strongly positive in HEK293T CM, which was confirmed *via* backgating (Figures [1](#F1){ref-type="fig"}B,C). Other markers detected at intermediate- to low-positive APC fluorescence intensity levels comprised mainly CD24, CD41b, CD49e, CD146, and MCSP. Markers such as CD3, CD105, or CD326 were detected at very low levels after background correction (Figure [1](#F1){ref-type="fig"}C). Of note, most quantitative data in this study are plotted by using segmented linear axis scales, however, very low values might be better represented by logarithmic or alternatively segmented linear axis scales (Figure S2B in Supplementary Material). For improved comparability of plots with different axis scaling, we have included an arbitrary dotted line at an APC MFI value of 1 for all plots throughout this study, though it should be noted that this does not reflect an objective threshold for marker positivity.
These results confirm that this multiplex bead-based assay is sensitive enough to detect EV surface marker presence in pre-cleared, otherwise unfractionated CM samples. These data clearly indicate the expression of the abundant tetraspanin markers CD9, CD63, and CD81 and of the integrins CD29 and CD49e on HEK293T-derived EVs. Of note, this sandwich assay can only detect EVs that fulfill both of the following criteria: (1) EVs must be positive for at least one of the antigens detected by the antibody-coated capture bead populations, which include CD9, CD63, and CD81 and (2) EVs need to be positive for CD9, CD63, or CD81 when the pan tetraspanin detection cocktail is used. Generally, the results obtained from this assay could be influenced by several factors, including cross-linking of beads by single EVs binding to more than one bead population (see gating on single beads in Figure S1 in Supplementary Material), and thus should be interpreted not as a single vesicle quantification, but rather as a semi-quantitative bulk assessment of the general repertoire of EV surface marker expression, i.e., EV surface signatures, in an EV-containing sample. However, compared to Western blot, which similarly involves probing for antibody binding to one protein in a bulk format, this assay ultimately requires the binding of two antibodies to a single EV, which should result in more sensitive and more specific robust detection, while diminishing the possibility that a given positive signal is derived from free protein rather than intact EVs. Importantly, if the hypothetical surface markers A and B are detected as positive in this assay in a given sample, one cannot conclude if EVs in the sample are all positive for A and B, or if some are positive for A and negative for B and *vice versa*. Instead, this assay can be used to judge if a given marker is positive in a sample, while single EV analyses *via* dedicated flow cytometric assays would be required to detect EV heterogeneity within one sample. However, in contrast to most other more dedicated flow cytometry based methods for EV surface marker analysis, this multiplex bead-based assay can be run on most classical flow cytometers equipped with blue and red lasers and requires less-extensive expertise in flow cytometry.
Evaluation of the Assays Range of Detection Through Assay Input Titration {#S3-2}
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Considering the principle of this multiplex bead-based assay, the strength of any signal detected with APC-conjugated detection antibodies strongly depends on the number of EVs added to the assay. While previous reports relied on defining EV inputs by protein amounts ([@B9], [@B10]), the ratio of EVs to total protein content of a given sample will be dependent on the purity of the sample, which in turn can vary drastically depending on which isolation method was used and subsequently purity was achieved ([@B63]). Thus, we next aimed to define EV input numbers as particle counts based on NTA. EVs were isolated from HEK293T-derived CM with a differential centrifugation protocol which is classically used to enrich for exosomes ([@B64]) (Figure [2](#F2){ref-type="fig"}A; Table S2 in Supplementary Material). NTA-based calculated EV doses between 5 × 10^5^ and 5 × 10^8^ were used as input for the multiplex bead-based flow cytometry assay. As expected, signal intensities for all positively stained bead populations, but not internal isotype control bead populations, were decreasing with decreasing EV input, with almost no detectable signals at an input dose of 5 × 10^5^ EVs (Figures [2](#F2){ref-type="fig"}B,C). Though the presence of the tetraspanin markers CD9, CD63, and CD81 could be clearly detected already at doses of 5 × 10^6^ EVs, less abundant markers like CD29, CD41b, and CD49e required approximately 10-fold higher EV inputs for reliable detection. At the highest dose tested (5 × 10^8^), several markers are negative or near background at lower doses were detected as positive, e.g., CD24, CD146, MCSP, and ROR1, in addition to rather unexpected markers, e.g., the hematopoietic surface marker CD45, and the NK cell marker CD56 (NCAM) (Figures [2](#F2){ref-type="fig"}B,C).
{#F2}
This dataset shows that NTA-based EV quantification is suitable for defining EV input doses for this assay. These results further imply that the range of detection of this assay depends on the abundance of markers and the detail of information a given experiment aims to achieve. If semi-quantitative assessment of only highly abundant markers is needed for a given EV-containing sample, then the EV input can be less than for experiments aiming to cover the whole EV surface signature present in a sample. Furthermore, the minimum amount of EVs required will not only be dependent on the EV input dose but also on the abundance of the marker and the sensitivity of the flow cytometer used. Generally, it appears that an EV input between 1 × 10^8^ and 1 × 10^9^ should be suitable for cell culture media-derived EVs. However, given that different cells might release different quantities of EVs with different surface marker composition, unknown samples should be titrated or measured at different dilutions, if possible. In addition, this data further demonstrates that the lack of reliable detection of signal from a bead population does not necessarily mean that a certain marker is not expressed, it could just be expressed at such low levels, or only on a minor subset of EVs in a sample, such that the signal would be below the limit of detection of this assay, on the instrument used, for this sample. Conversely, signals for markers being detected at low levels close to background also may relate to unspecific binding or background, e.g., the above-mentioned detection of the hematopoietic marker CD45 on HEK293T EVs. On the other hand, if an EV surface marker is detected in this assay, and if its signal increases with increasing sample input, this strongly suggests that this marker is expressed on EVs in this sample.
Evaluation of Assay Variability {#S3-3}
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Aiming to further standardize this assay and optimize assay parameters related to sample preparation and assay protocol, we next compared different basic assay protocols. HEK293T-derived EVs were isolated *via* ultrafiltration, more specifically TFF with subsequent 10 kDa spin filtration (Figure [3](#F3){ref-type="fig"}A; Table S2 in Supplementary Material). Subsequently, isolated EVs were analyzed at input doses of 5 × 10^8^ EVs per assay with three different protocols. The default protocol used throughout this study is based on 0.22 µm 96 well filter plates which are used for all steps including over-night incubation with capture beads, staining (1 h) with detection antibodies and washing steps. This default protocol was compared to a shortened protocol version (1 h incubation with capture beads instead of over-night) and to a protocol in which all steps were performed in standard microcentrifuge tubes instead of a filter plate. All volumes and EV/reagent amounts were otherwise kept constant, and measurements were done in triplicates for all three protocols in order to evaluate respective assay variability (Figure [3](#F3){ref-type="fig"}B; Figure S3 in Supplementary Material). When using the protocol with a shorter bead capture + EV incubation time, we generally observed lower APC MFI values for all positive bead populations when compared to over-night incubation. In contrast, performing all steps of the assay protocol in tubes rather than filter plates led to consistently higher APC MFI values for all detected markers (Figure [3](#F3){ref-type="fig"}B; Figure S3 in Supplementary Material). When comparing replicates done with the same respective protocol variant, highly consistent results with low variability were observed in all cases (Figure [3](#F3){ref-type="fig"}C; Figure S3 in Supplementary Material).
{#F3}
Generally, the results indicate that EV surface signature detection and quantification are relatively consistent and reproducible when assay parameters are kept constant, at least for EV samples derived from HEK293T cell culture supernatant. The trend toward lower MFI intensities detected when the capture bead incubation step is reduced from over-night to 1 h indicates incomplete binding of EVs to capture beads. However, abundant markers were still detectable and most EV surface marker signals were still comparable. Thus, this shortened protocol would be applicable for screening or experiments that do not require optimized detection. Though, if markers with lower abundance are to be detected accurately, the over-night incubation step would be preferred. The consistently increased signals detected when performing the assay protocol in tubes are probably related to different mixing conditions during the incubation steps or differences of bead adhesion to plastic surfaces. We further studied sample stability after completing the capture and staining protocol and obtained highly similar results when performing flow cytometric data acquisition directly or after storing the sample one week at 4°C, even though the total beads acquired for such measurements of leftover samples were lower in most cases (Figure S4 in Supplementary Material). This indicates that the time between assay preparation and data acquisition is not highly critical as long as the samples are kept at 4°C and protected from light. Taken together, all protocols applied are valid and lead to similar results, with robust and reproducible EV surface signature quantification independent of the protocol used for this multiplex bead-based assay.
Stepwise Evaluation and Monitoring of Different EV Isolation Protocols {#S3-4}
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Our results indicate that this multiplex bead-based flow cytometry assay can be used to assess EV surface marker signatures in both unprocessed CM samples and in samples following EV enrichment by different isolation protocols (Figures [1](#F1){ref-type="fig"}--[3](#F3){ref-type="fig"}; Table S2 in Supplementary Material). While the presence of abundant markers on HEK293T-derived EVs appeared rather consistent, we observed slight differences regarding their ratio when comparing CM (Figure [1](#F1){ref-type="fig"}), EVs isolated *via* differential ultracentrifugation (UC; Figure [2](#F2){ref-type="fig"}) and EVs isolated *via* ultrafiltration (Figure [3](#F3){ref-type="fig"}). For example, CD49e was detected at higher levels than CD41b in CM (Figure [1](#F1){ref-type="fig"}C) and filtration-isolated EVs (Figure [3](#F3){ref-type="fig"}B), while the opposite was observed in UC-isolated EVs (Figure [2](#F2){ref-type="fig"}B). Differential UC-based protocols are classically used in the field, and recently were reported to have potentially negative effects on the intactness of EVs ([@B65]--[@B68]). Thus, different alternative isolation protocols, e.g., based on TFF or SEC, have been established in recent years ([@B50], [@B67], [@B69]). Furthermore, there is accumulating evidence for the existence of different types of EVs in terms of density, size, and surface phenotype ([@B10]--[@B12], [@B70]). Since every EV isolation protocol might have a certain bias toward subsets of EVs, we next aimed to evaluate the use of this multiplex bead-based EV assay to analyze different EV-containing fractions throughout an isolation process.
HEK293T-derived CM was derived from cells incubated with either serum-free (SF; Figures [4](#F4){ref-type="fig"}A,C) or serum-supplemented (SS) medium (Figure [4](#F4){ref-type="fig"}B). Respective medium controls did not show substantial background signals, indicating that FBS-derived bovine EVs do not cross-react with the antibodies used in this assay (data not shown). Both CM samples were subjected to the same classical differential centrifugation protocol (Figures [4](#F4){ref-type="fig"}A,B), and SF CM was further processed by using a protocol based on TFF and subsequent bind-elute SEC (BE-SEC) which was recently described by our group ([@B50]). Samples were taken at different steps before, during and after the isolation process, and all samples were analyzed with the multiplex bead-based assay with standardized assay input doses of 1 × 10^8^ particles. Generally no major differences between samples were detected in terms of presence/absence of EV surface markers (Figure [4](#F4){ref-type="fig"}). Compared to SF cultures, SS CM samples and downstream fractions showed consistently lower signals for all markers (Figure [4](#F4){ref-type="fig"}B). This probably relates to the presence of FBS-derived EVs that affect NTA-based EV quantification, and/or that HEK293T cells secreted less EVs when cultured in this medium. Furthermore, it appeared that the 10,000 × *g* centrifugation step before UC resulted in a reduced abundance of CD49e per EV when compared to CM or 0.22 µm filtrated samples (Figures [4](#F4){ref-type="fig"}A,C). Results from samples purified *via* BE-SEC indicated enriched CD24 expression on EVs purified in this way, when compared to unpurified CM or samples post TFF only (Figure [4](#F4){ref-type="fig"}C). However, such minor differences in less abundant EV markers cannot be a valid basis to draw final conclusions on without further validation. Thus, based on this dataset we cannot conclude if, and which, isolation methods introduce distinctive bias toward certain phenotypic EV subsets. In summary, we can, however, conclude that the multiplex bead-based assay is suitable to assess the EV surface marker composition in various EV-containing samples with highly variable purities throughout an EV isolation process, indicating that this assay can also be valuable for in-process monitoring of EV isolation and fractionation protocols, or for screening.
{#F4}
Assay Compatibility With Fluorescently Labeled EVs {#S3-5}
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Fluorescent labeling of EVs is often applied to further study EVs, especially in the context of cellular uptake, release or *in vivo* biodistribution. Toward this, we and others have previously labeled EVs with fluorescent proteins by expressing respective CD63 fusion proteins in producer cells ([@B8], [@B50], [@B71]). Here, we aimed to evaluate the compatibility of EVs labeled with different fluorescent proteins in this assay. Thus, we cloned four different lentiviral constructs facilitating the expression of CD63 fused to either mNeonGreen, mCardinal, E2Crimson, or Cerulean and generated HEK293T cell lines stably expressing each fusion construct (Figure [5](#F5){ref-type="fig"}A). Labeling of EVs with mNeonGreen, with its fluorescence mainly detected in the FITC channel similar to classical GFP, resulted in increased green fluorescence being detected especially for the CD9, CD63, and CD81 beads and thus interfered with identification of the respective bead populations (Figure [5](#F5){ref-type="fig"}B; Figure S6C in Supplementary Material). Thus, the use of green fluorescent proteins is not recommended. Labeling of EVs with the far-red fluorescent proteins mCardinal or E2Crimson facilitated detection of some EV surface markers without any further labeling with detection antibodies. Detected signals were generally much lower than those stained with detection antibodies, with slightly higher signals for E2Crimson-labeled EVs than for mCardinal-labeled EVs. The main markers detected comprised CD9, CD63, CD81, CD24, and CD29, which were all confirmed to be present on HEK293T EVs above (Figure [5](#F5){ref-type="fig"}C; Figures S6D,E in Supplementary Material). While far-red fluorescent proteins will surely not be compatible with the use of APC-conjugated detection antibodies in this assay, they could be of interest as a positive control, reference or to facilitate a more unbiased, non-antigen-dependent detection. The relatively low signals are probably mainly caused by their suboptimal excitation with the equipped 635 nm red laser, since both mCardinal and E2Crimson have an excitation peak around 605 nm and would thus probably be detected at higher signal intensities with a more suitable laser setup ([@B55]). Signals from Cerulean-labeled EVs were mainly detected for CD9, CD63, CD81, and CD29 in the VioBlue channel without notable fluorescence spillover from or to the APC channel (Figure [5](#F5){ref-type="fig"}D; Figures S6F,G in Supplementary Material), suggesting that the use of Cerulean-labeled EVs appears to be fully compatible with this assay in its original form. These results demonstrate that this multiplex bead-based assay facilitates EV surface marker detection with more than one color. This suggests an interesting approach to providing further information about co-expression of EV surface markers in heterogeneous samples. These examples further demonstrate that fluorescently labeled EVs, in this case generated through expression of CD63-fusion constructs in EV producer cells, can be used with the multiplex bead-based assay when appropriate controls are included. This approach should be extended with further validation for lipophilic fluorescent dyes and by applying differently labeled antibodies against different antigens to enhance assay resolution for detection of EV subpopulations.
![Assay compatibility with fluorescently labeled extracellular vesicles (EVs). **(A)** Schematic outline of the lentiviral vector used. Abbreviations: CMV, CMV promoter; SD, splice donor; LTR, long terminal repeat; SA, splice acceptor; RRE, Rev responsive element; cPPT, central polypurine binding tract; SFFV U3, U3 promoter of the spleen focus forming virus; IRES, internal ribosomal entry site; puroR, puromycin resistance cDNA; WPRO, woodchuck hepatitis virus post-transcriptional regulatory element optimized, modified after Wiek et al. ([@B62]). **(B)** Capture bead distribution after overnight incubation with unmodified or CD63-mNeonGreen EVs. **(C)** Capture bead signals in the APC channel after incubation with EVs labeled with far-red fluorescent proteins (mCardinal and E2-Crimson). **(D)** Signals detected in APC and VioBlue channels for unstained and stained (pan tetraspanin) CD63-Cerulean EVs. See Figure S6 and Table S2 in Supplementary Material for further details.](fimmu-09-01326-g005){#F5}
Differential EV Surface Marker Detection on EVs Derived From Different Cell Types {#S3-6}
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Currently, in addition to different EV subtypes being defined based on their origin as exosomes or microvesicles, it is commonly accepted that there is a much higher degree of EV heterogeneity also within these two subgroups. The EV content, including the protein and surface marker composition, is probably strongly dependent on the cell source, the cell's activation status, and multiple other parameters ([@B5], [@B7], [@B9], [@B10], [@B72]). Since the knowledge about EV subtype and cell source-specific EV surface markers is still rather limited, we next aimed to explore both the use of the multiplex bead-based assay for the analysis of EV heterogeneity within one EV sample, and for the comparison of EVs derived from different cell types.
Extracellular vesicles were isolated from HEK293T cells and an immortalized MSC line, and input amounts were standardized to 5 × 10^8^ EVs per assay. For detection, either the anti-CD9/CD63/CD81 (pan tetraspanin) detection antibody mix or respective single anti-tetraspanin antibodies were used in order to compare EV surface signatures in detail between both cell sources (Figure [6](#F6){ref-type="fig"}A). With pan detection, CD63, CD81, CD29, and CD49e were clearly positive on EVs of both cell lines. Of note, the expression of CD9, CD146, CD326, MCSP, and ROR1, was detected on HEK293T EVs but not on MSC-EVs (Figures [6](#F6){ref-type="fig"}B,C). Subsequently, when using anti-CD9 detection antibodies, we observed a complete lack of signal detection for MSC-EVs, while there was a clear signal on HEK293T EVs (Figures [6](#F6){ref-type="fig"}D,E). Robust signal detection was observed with anti-CD63 or anti-CD81 detection antibodies on both MSC- and on HEK293T EVs (Figures [6](#F6){ref-type="fig"}F--I).
{#F6}
We further observed strong variations in signal intensities for the CD9, CD63, and CD81 bead populations when using the same respective antibodies for single detection (Figures [6](#F6){ref-type="fig"}D,F,H). These variations were most likely caused by limitations in specific antibody epitopes per EV, e.g., signals from EVs that were captured on anti-CD63 beads have less CD63 epitopes available or accessible for detection with anti-CD63 detection antibodies. However, some markers, such as CD29 or CD49e, were detected with all three single detection antibodies on HEK293T EVs (Figures [6](#F6){ref-type="fig"}D,F,H), and with anti-CD63 and anti-CD81 antibodies on MSC-EVs (Figures [6](#F6){ref-type="fig"}G,I). On the other hand, CD49e as well as CD146, MCSP, and ROR1 were detected at highest levels on HEK293T EVs when using anti-CD81 antibodies for detection, indicating that those surface markers on HEK293T EVs are co-expressed more frequently on CD81 positive EVs (Figure [6](#F6){ref-type="fig"}H).
In summary, this dataset shows that the multiplex bead-based assay is suitable to detect heterogeneity within one EV sample, and can also be a valuable tool for comparing EVs from different cell sources. However, a reliable comparison will only be possible if input amounts are standardized to comparable EV input doses, and if EVs are prepared according to similar EV isolation protocols. As discussed above, the absence of signal for a marker might indicate its low abundance under the detection threshold and does not necessarily mean it is not present, as it may just be below the limit of detection for the assay. Although in this case, with CD9 being present at high levels on HEK293T-derived EV samples and not detectable at all on MSC-EVs, even when using anti-CD9 antibodies as a detection probe, it is tempting to conclude that EVs from this particular MSC line are indeed negative for CD9. In fact, EVs derived from a primary MSC line have previously been reported to be positive for CD63 and CD81 but negative for CD9 ([@B73]). Western blot analysis confirmed this result, with detectable CD9 signals on HEK293T EVs but not on MSC-EVs (Figure S7 in Supplementary Material). Yet, in this case 5 × 10^9^ HEK293T EVs were required to detect CD9 by WB (Figure S7 in Supplementary Material), while 5 × 10^6^ HEK293T EVs were sufficient to robustly detect CD9 in the multiplex bead-based assay (Figure [2](#F2){ref-type="fig"}). Thus, the CD9 levels on MSC-EVs from this particular cell line could indeed just be much lower than on HEK293T EVs and below the detection limit of both methods. Of note, CD9 was detected in whole cell lysate of both HEK293T and MSCs (Figure S7 in Supplementary Material). Proteomic profiling of EVs from both HEK293T and this MSC line further did not show any detectable CD9 in MSC-EVs but in HEK293T EVs, while CD63 was detected in both (data not shown, manuscript in preparation). Further validation with other MSC lines, other antibody clones and other, more sensitive methods will be required to further clarify this. CD9 is often referred to as a common EV marker ([@B11], [@B74]--[@B76]), but was recently reported to be negative on EVs derived from human primary NK cells, while being highly positive on platelet-derived EVs ([@B10]). This further underlines that the tetraspanins CD9, CD63, and CD81 might not be as homogenously distributed on all EVs as previously proposed.
Usage of Custom Detection Antibodies to Analyze EV Surface Expression {#S3-7}
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In the default format, this multiplex bead-based assay is used with detection antibodies against single or multiple tetraspanins. Since these are commonly found on most EVs, they can be assumed to be highly abundant when detected in combination. In order to ensure that most EVs are detected, this would also be recommended for experiments aiming to assess the general and complete surface signature of a given EV preparation. However, the question of if a certain candidate surface marker is present on EVs from a given sample will likely be a recurring question in many situations when doing EV research. Thus, we wondered if other markers with potentially lower abundance than tetraspanins would be suitable as detection antibodies in this assay.
The presence of folate receptor alpha (FOLR1) on EVs that shuttle folate into the brain has been reported before ([@B77], [@B78]). Here, we aimed to evaluate the use of anti-FOLR1 antibodies to probe EVs derived from either the pancreatic ductal adenocarcinoma cell line PANC-1, which does not express FOLR1 on its surface, or the ovarian adenocarcinoma cell line IGROV1, which does (Figure [7](#F7){ref-type="fig"}A). When subjecting pre-cleared CM from both cell lines to the multiplex bead-based assay with pan tetraspanin detection, EVs from both cell lines showed robust expression of abundant markers like tetraspanins, the integrins CD29 and CD49e, and other markers like CD326/EpCAM (Figure [7](#F7){ref-type="fig"}B). However, when using APC-conjugated anti-FOLR1 antibodies for detection in the same samples, while we did not detect any signals for PANC-1 EVs, we observed clear signals on IGROV1 EVs for the CD9, CD63, CD81, and EpCAM capture bead populations (Figure [7](#F7){ref-type="fig"}C). This indicates that EVs derived from IGROV1 cells but not PANC-1 cells do express FOLR1 on their surface, and that those EVs co-express tetraspanins and EpCAM. To determine whether further markers are co-expressed, the EV input dose would have to be increased and single anti-tetraspanin antibodies for detection would have to be applied. However, this dataset clearly shows that pre-cleared CM can generally be used to verify if a candidate marker is present on EVs in a given sample, and to gain information on which markers included in the assay are predominantly co-expressed.
{#F7}
In principle, the following requirements for the detection of a candidate antigen or surface marker of interest on the surface of EVs of a given sample will apply: (i) the antigen has to be abundant enough in the tested EV sample to be detected in this assay, (ii) an (ideally APC- or AlexaFluor647-) conjugated antibody is required, (iii) any background signal introduced by that antibody in buffer controls (capture beads + a\*ntibody) has to be lower than the true positive signal derived from the sample (capture beads + EVs + antibody), and (iv) the candidate surface marker would have to be co-expressed on the same EVs with at least one of the 37-specific EV surface markers probed for by the capture bead populations, otherwise it would not be picked up.
Analysis of EV Surface Signatures in Biological Fluids {#S3-8}
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Due to the potential relevance of EV surface signatures in the context of diagnostic application, their robust and specific assessment in biological fluids, such as CSF, blood, urine, or saliva is of great importance. Even though the focus of this study clearly lies in evaluating the multiplex bead-based assay for the analysis of cell culture-derived EVs, we also wanted to explore the use of this assay to analyze EVs in human CSF, plasma, and serum samples and share our experiences here. Furthermore, we wished to address the question how data from such analyses of larger sets of samples could be visualized, how results from different instruments compared, and how data could be normalized between such sample sets.
When analyzing pre-cleared CSF samples, we consistently observed expression of CD9, CD63, and CD81 and CD133/Prominin1 in samples from all donors. However, other markers were detected consistently in all samples but were near background levels, i.e., CD8, CD14, CD31, CD41b, CD44, CD105, and MHC class II (HLA-DRDPDQ) (Figure [8](#F8){ref-type="fig"}A, data not shown). This probably related to relatively low EV concentrations in CSF compared to cell culture supernatant (data not shown). To gain more information on whether markers with lower abundance in CSF are specifically expressed, we further concentrated EVs from CSF samples and used approximately 3- and 10-fold more EVs as assay input. Most markers expressed at low levels showed higher intensities in more concentrated samples (e.g., CD8, CD31, CD44, CD105, and MHC class II), while some markers, i.e., CD3, CD14, CD41b, or CD62P did not show any consistent signal increase with increased input doses (Figure [8](#F8){ref-type="fig"}A). This indicates that interpretation of EV surface markers close to background levels generally requires further validation by running samples at different dilutions. We further investigated the stability of EV surface signatures when analyzing pre-cleared, unprocessed CSF samples, and observed reproducible results for the same CSF sample analyzed freshly or after storage at −20°C for up to 2 months (Figure S8 in Supplementary Material), indicating that freezing does not have a major impact on the EV surface signature of CSF samples as detected by this multiplex bead-based assay.
{#F8}
Next, we compared different basic sample-related parameters by analyzing human blood-derived samples, i.e., plasma and serum, at different input amounts (10^8^--10^10^/assay), different EV purities and fresh Vs. frozen samples. Initial experiments were performed on a FACS Symphony instrument (Figure S9A in Supplementary Material), and the pan tetraspanin-APC intensities for each bead population were visualized on heatmaps (Figure [8](#F8){ref-type="fig"}B; Figure S10 in Supplementary Material). When comparing non-purified plasma samples with samples purified by SEC, we observed much higher pan tetraspanin detection signals in non-purified samples, though signals were also elevated for the internal negative control bead populations, especially for the REA-control bead population (Figures S8B and S10 in Supplementary Material). This indicates that, compared to experiments with cell culture-derived EV samples, analysis of biological samples with this assay requires optimized sample purification and further validation, since background or unspecific signals can occur. Furthermore, we did not observe any consistent difference between plasma and serum samples (Figure [8](#F8){ref-type="fig"}B; Figures S10 and S11 in Supplementary Material), or, as observed for CSF, between plasma and serum samples subjected to a freeze-thaw cycle, indicating that EV surface markers are not notably affected by freezing plasma or serum (Figure S10 in Supplementary Material).
For further comparison and validation, the same frozen plasma and serum samples were analyzed using the MACSQuant instrument with the same defined input amounts, and we observed highly comparable results. Results from CSF samples were included in the corresponding heatmaps for further comparison (Figure [8](#F8){ref-type="fig"}B; Figures S11 and S12 in Supplementary Material). Normalization of results from both instruments enabled us to conclude that the plasma and serum samples analyzed on both instruments showed clear similarity in the markers detected as positive, particularly when comparing plasma and serum samples at an input dose of 1 × 10^9^ EVs. Results from the MACSQuant showed a greater degree of variation in terms of scale, but less variation than observed in expression when compared to the FACS Symphony (Figure [8](#F8){ref-type="fig"}B; Figure S12 in Supplementary Material). In summary, efforts were taken to minimize variables that could potentially introduce variation, but many are unavoidable due to sample, antibody, and bead handling and preparation, or instrument design differences. While this multiplex bead-based assay is very useful for understanding the general repertoire of EV surface marker expression, it is by no means a completely quantitative analysis technique and, therefore, has limitations that should be understood in order to draw appropriate conclusions from the obtained results. Comparisons between the FACS Symphony and MACSQuant instruments were made possibly by using the ratio of control to EV-captured beads, rather than using background subtraction, due to lack of positive controls. Future inter-instrument comparisons may benefit by converting arbitrary unit scales to molecules of equivalent soluble fluorophore (MESF) using MESF beads to account for instrumental sensitivity and scaling differences that can arise.
Taken together, in terms of detected EV surface signatures in CSF Vs. blood-derived samples, further validations with additional samples will be required in order to make clear statements about which markers are generally positive on EVs from most donors and which markers are more variable. CSF samples contained lower EV concentrations and much lower background levels than plasma/serum samples. CD9, CD63, and CD81 expression was observed at high levels for both EVs from CSF and from blood. Further markers with high abundance on CSF EVs were the T cell marker CD8, MHC class II, and CD133, with especially CD8 and CD133 being much higher on CSF-EVs than blood EVs (Figures [8](#F8){ref-type="fig"}A,B; Figure S11 in Supplementary Material). The presence of MHC-II on CSF-EVs was reported before ([@B79]), and expression of the stem/progenitor cell marker CD133/Prominin1 on EVs in CSF was first described in 2008 ([@B80]), with a more recent study proposing its dose-related association with several neurological diseases ([@B81]). Due to relatively high signals observed for internal negative control bead populations for plasma/serum EVs, at this point it is difficult to identify surface markers unequivocally positive on blood EVs with this multiplex bead-based assay in its current form. It appears that especially the REA control capture bead population which is coated with a recombinant isotype control antibody against keyhole limpet hemocyanin somehow binds to molecules present in plasma/serum, but not in CSF or cell culture supernatant. However, the highest signal intensities above background levels for plasma/serum samples were obtained for CD24, CD29, CD42a, CD62P, and CD69 (Figure [8](#F8){ref-type="fig"}B; Figure S11 in Supplementary Material). In general, further optimization and analysis of more samples from defined donor groups will be required to explore potential disease associations of specific EV surface marker combinations.
Detection of Human EVs in Mouse Plasma Following Intravenous Injection {#S3-9}
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Within the past few years, there have been rapidly accumulating reports about the therapeutic potential of EVs, and especially of MSC-derived EVs. Treatment with MSC-EVs has been reported as being beneficial and safe in several animal studies, and also in the first case in man ([@B82]--[@B85]). However, the mode of action of EVs in such therapeutic settings is still poorly understood, in part because it is technically challenging to track the biodistribution of EVs over time. Different labeling techniques, e.g., labeling of EVs with lipophilic dyes, fluorescent proteins, or luciferase-based approaches have been applied to study the biodistribution of EVs injected in mouse models over time ([@B8], [@B67], [@B86], [@B87]). Several of these studies have shown that following injection, EVs are rapidly cleared from the blood circulation and mostly accumulate in liver and lungs. However, each labeling technique is associated with different limitations, such as the risk of merely tracing the dye or fluorophore. The use of chimeric proteins with a luminescent or fluorescent tag fused to an EV sorting moiety has the advantage of high specificity and lowered risk of signal from non-EV elements. However, this specificity may also be disadvantageous, since it will only reflect the EV population carrying the respective EV sorting domain. Thus, since it is challenging to follow EVs over time, or to detect if specific EV subsets behave differently in terms of biodistribution or targeting after injection, any assay that can be used to gain additional information in such mouse models will be helpful to further understand EV heterogeneity, biodistribution, targeting, and function.
Since this multiplex assay should be rather specific for detection of human EVs, we hypothesized that it could also be useful for the analysis of non-manipulated, human EVs after injection into a mouse. Thus, we isolated EVs from an immortalized human MSC line, injected doses of 2 × 10^11^ EVs/mouse intravenously and took blood samples after 1 min, 30 min, and later time points (Figure [9](#F9){ref-type="fig"}A, data not shown). Plasma samples from these mice were then transferred without further dilution to the multiplex bead-based assay with pan tetraspanin detection. We did not observe any signals from plasma samples from non-injected mice, but could observe clear EV detection after 1 min and lower signals 30 min after injection of treated mice (Figure [9](#F9){ref-type="fig"}B). The surface markers detected accurately 1 min after injection (Figure [9](#F9){ref-type="fig"}C) reflected the surface markers present on MSC-EVs that were directly analyzed at different doses (Figure [9](#F9){ref-type="fig"}D). Plasma samples taken 30 min after injection showed drastically reduced signals (Figures [9](#F9){ref-type="fig"}C,D) and were below the limit of detection for this assay 1 h after detection and at later time points (data not shown). In this experiment, we also tried to use the exact injection dose of 2 × 10^11^ EVs as input dose for the multiplex bead-based assay for comparison, without taking the dilution of EVs in mouse blood into account; however, this resulted in massive background signals also for the internal negative control bead populations (Figure S13 in Supplementary Material).
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Detection of injected human extracellular vesicles (EVs) in mouse plasma. **(A)** Female NMRI mice were injected intravenously at doses of 2 × 10^11^ human mesenchymal stromal cell line-EVs/mouse. Blood was collected 1 or 30 min post injection by heart puncture. Plasma from two to three mice for each time point was analyzed in the multiplex flow-cytometry assay by using a pan tetraspanin mix of CD9/CD63/CD81-APC antibodies. **(B)** Representative dot plots and **(C)** quantification of detected bead populations from analyzed plasma samples from both time points compared to a plasma sample from a non-injected mouse. **(D)** The same EV preparation was analyzed directly at assay input doses of 10^9^ and 10^8^ EVs for comparison. See Figure S13 and Table S2 in Supplementary Material for further details.
Taken together, this proof-of-concept experiment shows that this multiplex bead-based assay can facilitate the specific detection of native, non-manipulated human EVs, and their surface signatures from the blood of EV-injected mice. In accordance with previous findings, we observed that most EVs are cleared from the circulation rapidly. Though, this approach requires further optimization in order to gain deeper insight into which tissues different subsets of EVs are targeted to. Such data would greatly complement other biodistribution or pharmacokinetic studies, which normally rely on bulk fluorescence or luminescence signals and fail to assess surface signatures. Furthermore, this approach could potentially be a powerful tool to detect otherwise non-manipulated EVs in stem cell or cancer xenograft studies.
Detection of EV Surface Signatures in Material Derived From Rare Primary Human Hematopoietic Progenitor Subsets {#S3-10}
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As in many other fields, a role for EVs in intercellular communication has also been proposed in context of communication between hematopoietic stem and progenitor cells (HSPCs) and bone marrow niche cells or leukemia cells. The disruption of this communication axis has been hypothesized to contribute to leukemia development ([@B88]--[@B90]). Since a general understanding of EV subtypes and the identification of specific EV surface markers will be essential to studying and understanding cell-to-cell communication processes within the hematopoietic compartment, we aimed to evaluate if this multiplex bead-based assay would be sensitive enough to assess EV surface signatures from subsets of rare cells like HSPCs, with low total cell numbers and low supernatant volumes available.
To analyze if subsets of hematopoietic progenitor cells secrete different qualities or classes of EVs, we sort-purified HSPC fractions known to be enriched for multipotent (MP), lympho-myeloid (LM), and erythromyeloid (EM) progenitor cells ([@B52]) (Figure [10](#F10){ref-type="fig"}A; Figures S14A,B in Supplementary Material) and cultured these fractions at doses of 25,000 cells per 48 well in 300 µL medium for 4 days, respectively. All CM were not filtered at time of harvesting due to low volumes, but cleared from cells and debris/large vesicles by low speed centrifugation before analysis with pan tetraspanin detection (Figure [10](#F10){ref-type="fig"}A; Table S2 in Supplementary Material). Medium controls were included and treated exactly like samples (Figure [10](#F10){ref-type="fig"}A). The medium controls showed considerable signals which were corrected for by using the respective MFI values from this control for background subtraction (Figure [10](#F10){ref-type="fig"}B). Generally, the signals derived from all samples were high enough above background to facilitate the identification of several markers as clearly expressed at differential levels on MP-, LM-, and EM-derived EVs (Figures [10](#F10){ref-type="fig"}B,C). While some markers like CD29 and CD44 could be identified at rather high and similar levels on EVs derived from all three subsets, several markers were found at clearly higher levels or were detected exclusively on EM-derived EVs, e.g., CD9, CD49e, CD105, and ROR1. On the other hand, the marker CD133 was found to be consistently higher on MP- and LM-derived EVs (Figures [10](#F10){ref-type="fig"}C,D; Figures S14C,D in Supplementary Material), which is likely due to the fact that the MP and LM HSPC EVs were derived from cells expressing high levels of CD133 on their surface, while EM progenitors express CD133 at much lower levels (Figure S14B in Supplementary Material) ([@B52], [@B58]). When comparing the results from two independent experiments, all trends in EV surface marker expression level variation between MP, LM, and EM-derived EVs were highly similar (Figures S14C,D in Supplementary Material).
######
Analysis of extracellular vesicles (EVs) secreted by subsets of human hematopoietic stem/progenitor cells. **(A)** Human umbilical cord blood-derived hematopoietic stem and progenitor cell (HSPC) subtypes were purified *via* flow cytometric cell sorting, seeded in 48-well plate at doses of 25,000 cells per well in 300 µL medium and cultured for 4 days before supernatants were harvested, pre-cleared by centrifugation, and analyzed in the multiplex bead-based assay. Medium controls were included for all conditions and treated exactly like samples. **(B)** Dot plots showing raw data for medium control and supernatants from multipotent (MP), lympho-myeloid (LM), and erythromyeloid (EM) HSPC subset-derived supernatants. **(C)** EV surface signatures for EVs from the three HSPC subsets, background corrected by subtraction of medium control. **(D)** Expression of selected markers detected in conditioned medium derived from the HSPC subsets. Data from one out of two independent experiments are shown. See Figure S14 and Table S2 in Supplementary Material for further details.
Taken together, this dataset shows that this multiplex bead-based assay facilitates the analysis of experiments from limited cellular material and low supernatant volumes with high reproducibility. We can further conclude that this assay enables the detection of both similar and also consistently differential expressed surface markers on EVs from different HSPC subsets, which in turn indicates that the overall surface signature of EVs derived from all three subsets is different. Finally, further optimization and more dedicated single vesicle analysis will be required to properly validate differences detected between EVs from these HSPC subtypes.
Concluding Summary and Outlook {#S3-11}
------------------------------
In summary, we have comprehensively evaluated and optimized a multiplex bead-based flow cytometric assay that can be used to robustly detect EV surface signatures in a semi-quantitative way. More specifically, the results presented in this study demonstrate that this assay facilitates EV surface marker detection in different types of samples in a very specific and reproducible way. To our knowledge, this is the first study that comprehensively evaluates the methodological details of a flow cytometric method for EV surface marker detection that does not need dedicated instrumentation or extensive operator expertise. Of note, the specificity is primarily based on the need for two antibodies to bind one EV in order to detect any signal, which makes this assay both biased and much more specific and sensitive compared to other classical bulk-based methods to detect EV proteins, such as Western blot. We believe that the EV field will benefit greatly from these kinds of assays and thus we share our experiences here, and give recommendations about sample- and acquisition-related parameters and required controls, which in the end will depend on the type of scientific questions asked. Of note, as with most analytic methods within the EV field, this assay should be considered as complement to other analytic EV tools, e.g., NTA, in order to draw valid conclusions. We demonstrate potential applications for this assay to include the comparison of isolation methods, as an in-process monitoring tool, for the identification of EV surface markers in a given sample and comparison of different samples, as an additional read-out for *in vivo* pharmacokinetics and biodistribution experiments, and for the assessment of EVs in samples with low volume or low EV counts.
In general, the detection of EV surface signatures on cell culture-derived EVs appears to be specific and reproducible. In this study, a few markers were detected robustly on EVs derived from all cell lines (CD63, CD81, CD29, CD49e), and several other markers were detected at least on one cell line tested. Many capture bead populations included in this assay are coated with antibodies against specific blood cell-related antigens and did not show detectable signals for cell culture-derived EVs here. Of note, the specificity of EV binding to the CD9, CD63, and CD81 capture beads has been previously evaluated by antibody blocking experiments ([@B10]), and most capture bead populations have been detected as positive in EV samples derived from respective blood cell subsets (e.g., CD19 and CD20 detection for B cell EVs, CD2, CD8, and CD56 for NK cell EVs, and CD42a, CD61, and CD62P for platelet-derived EVs) before ([@B9], [@B10]). Still, future studies should aim to further validate the specificity of other antibodies included in this assay, e.g., by analyzing further cell sources or by blocking experiments. In addition, the analysis of biological fluids, at least of blood-derived EVs, requires further technical optimization and clarification. For example, it remains unclear why the internal control bead populations react with plasma/serum EVs. However, we feel the overall potential to use this robust, multiplexed bead-based flow cytometric assay to generate a snapshot of EV surface signatures in clinically relevant samples with 37-specific markers will be of considerable interest, especially after additional disease-specific EV-associated biomarkers have been identified.
Furthermore, the data obtained in this study clearly underlines that this multiplex bead-based EV flow cytometry kit can not only quantify robust EV surface signatures in a given sample but is also useful for comparing differentially expressed surface markers between samples. It thereby facilitates the identification of heterogeneities between different EV sources, which may lead to the identification of EV markers being specific for certain cell types. The combination of this rather robust and fast approach with more dedicated methods to validate candidate surface markers distinguishing EV subpopulations (i.e., single EV flow cytometric analysis or sorting) would pave the way to studying the function of EV subsets, which will be of the highest relevance to furthering our understanding of their molecular content and related functions.
Future optimization of such an assay and application within the field should aim to identify new EV surface markers, but especially also of validated detection antibodies, more suitable reference materials for controlling experimental parameters and background, and further exploration of the limit of detection in terms of absolute molecules per capture bead needed on a respective instrument to show signals above backgrounds levels for a certain sample type. Finally, the validation of additional fluorescent probes that can be applied in such assays alone or in combination, e.g., the addition of two or more differently labeled detection antibodies to one sample, will add further depth to our knowledge of marker co-expression.
Ethics Statement {#S4}
================
Human UCB was obtained from donors at the University Hospital Essen, Germany, after informed written consent according to the Declaration of Helsinki. The experimental usage of UCB samples was approved by the local ethics commission. CSF samples included in this study were derived from patients who underwent a lumbar puncture for clinical purposes at Neurology department at Karolinska University Hospital, Stockholm Huddinge, Sweden. Written informed consent was obtained from all subjects in accordance with the Declaration of Helsinki. This study was approved by the Regional Ethical Review Board in Stockholm, Sweden. Human blood samples: the prospective clinical studies 02-C-0064, 04-C-0257, and 09-C-0195 were approved by the Institutional Review Board of the National Cancer Institute (NCI; MD, USA). Informed consent was obtained from all donors. The animal experiments were approved by the Swedish Local Board for Laboratory Animals. The experiments were performed in accordance with the ethical permissions granted, and designed to minimize the suffering and pain of the animals.
Author Contributions {#S5}
====================
OW, SEA, and AG conceived the idea and designed the experiments. AG wrote the manuscript and assembled the figures. OW, RB, JW, AZ, DH, GC, BG, JN, and SEA assisted in manuscript writing. OW, RB, JW, AZ, FM, UF, BE, X-ML, GC, MG, DM, CW, MBr, DG, and AG cloned plasmids, generated cell lines, performed flow cytometric cell sorting, cultured cells, and/or isolated EVs. OW, UF, and DG performed the *in vivo* experiments. BE isolated the CSF samples. AG acquired most flow cytometric EV analysis data and performed most of the data analysis. JW and JJ acquired flow cytometric data and analyzed data from biological fluid samples. GC performed Western blot analysis. OW, RB, JW, AZ, FM, UF, DH, BE, X-ML, GC, MBr, DG, BG, JN, JJ, SEA, and AG contributed general intellectual input on the experimental design, contributed to data analysis, and/or discussed the results. BE, HH, MBj, and BG contributed to relevant materials and expertise. All authors reviewed the manuscript and approved its final version.
Conflict of Interest Statement {#S6}
==============================
OW, JN, SA, and AG are consultants for and have equity interests in Evox Therapeutics Ltd. All other authors declare that no potential conflict of interest exists.
The authors would like to thank the MedH Flow Cytometry Facility at Karolinska Institutet, Stockholm headed by Iyadh Douagi for their support. The authors further would like to thank all patients and donors for their consent to provide biological samples for research, and all funding bodies for their financial support.
**Funding.** GC is supported by a Karolinska Institutet Doctoral grant. JN is supported by a postdoctoral grant from Hjärnfonden (Swedish brain foundation). SA is supported by the Swedish Research Council (VR-Med and EuroNanoMedII), Evox Therapeutics, Karolinska Institutet Faculty, Wibergs Stiftelse, SSF-IRC, Vinnova, and the Swedish Society of Medical Research (SSMF).
Supplementary Material {#S8}
======================
The Supplementary Material for this article can be found online at <https://www.frontiersin.org/articles/10.3389/fimmu.2018.01326/full#supplementary-material>.
######
Click here for additional data file.
[^1]: Edited by: Miroslaw Kornek, Universitätsklinikum des Saarlandes, Germany
[^2]: Reviewed by: Alissa Weaver, Vanderbilt University, United States; María Yáñez-Mó, Universidad Autonoma de Madrid, Spain
[^3]: ^†^These authors have contributed equally to this work.
[^4]: Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology
| 2024-03-28T01:26:29.851802 | https://example.com/article/1416 |
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We are turning ourselves into Pavlov’s bitch and if informed consent is a joke, democracy is a myth.
For me, it’s all about journalistic integrity and a well-informed populace. I’m ecstatic whenever any media outlet does some legitimate journalism. That being said, the Fourth Estate tends to give a very skewed narrative, and to some people, it can be incredibly damaging. I’ve met people who will link a John Oliver clip and say “so much this,” rather than engaging in an actual discussion. The obvious truths, that they seem to believe they’re a gatekeeper to, are something they are completely unable to even explain; let alone debate. “I’m not here to educate you,” they’ll tout, exclaiming victory over the ignorant bigot. Frankly, it’s pathetic — it’s deflection at its finest. The uninformed not only believe that they’re enlightened, they brandish their ignorance as a weapon!
Honestly, it’s a constant battle to find truth. Everyone has an agenda, and some are better than others at hiding theirs. I don’t hide mine whatsoever: I want people to be well-informed, happy and not live as slaves (either intellectually, physically or spiritually) unless they so choose. I could namedrop /pol/, and sardonically ask “see how redpilled I am?” but /pol/ has its own biases, mantras and dogmas. I’m a writer, and to truly write a subject takes an incredible amount of research, if you take your work seriously. It takes a lot of time and effort, and I guarantee you — almost everyone willing to spoon-feed you information is trying to use you. Don’t listen to pseudo-intellectual gatekeepers — just listen to the voice deep inside yourself that calls “bullshit” when something seems deceitful.
Fox is sadly a better source of information than MSNBC, HuffPo and Buzzfeed. If you compare the amount of opinion pieces to actual journalism you’ll see what I mean. MSNBC president Phil Griffin even said his channel was “not the place” for breaking news — “Our brand is not that.” On the three days that Pew examined MSNBC was 85% opinion pieces and 15% actual journalism, Fox was 55% commentary and 45% factual reporting, and CNN was 46% discussion of the narrative and 54% news. The fourth estate has becoming a mouthpiece for government propaganda first, and a vector of journalism second. They may as well take a money shot on the face of anyone who can’t tell that they’re in bed together — it’s that obvious.
The only person you need to prove anything to in this life is yourself. As Robert Anton Wilson was apt to say: “on a planet that increasingly looks like a maximum security prison, the only intelligent choice is to plan a jail break.” I’m just trying to lead us away from totalitarian authoritarianism, and that’s something very easy to slip into; when many people get all of their information from a single centralized source — a handful of multinational conglomerates that work together and share goals. Decentralization has the benefit of not having the same asshole, putting on five different masks, sell you the same bullshit; it allows people to make up their own minds a bit more. It’s a few echelon’s above “alternatives” that have the same goals as the mainstream, but is still below being told the truth from the start. In this age, Bob Marley wouldn’t be singing “tell the children the truth”, he’d be screaming it!
As my teacher Bill Cooper would say: “listen to everyone, read everything, don’t trust anything unless you can prove it with your own research.” The only way to truly be right is to admit when you’re wrong or don’t know. The mysteries of this universe will not betray themselves to lazily groping hands! There is absolutely no shame in admitting that you don’t know everything and sometimes need help, in fact, it’s quite liberating to admit your biological, human, limitations. The belief that you’re meant to be illuminated the moment you’re born is just intended to keep you in place. Generally, when someone tries to tell you the real truth, they’re just trying to control you. I am as cynical as Diogenes. I expect you to question me. In fact, I hope you do and that everyone else does too. Life is a game, and it’s time to start playing to win.
After World War II, and the inherent association with the Nazis, the word “propaganda” was replaced with “public relations”, because it was more palatable to Jane and John Q. Citizen. The usage of “journalism” instead of “public relations” is identical; especially considering how badly the fourth estate has failed to create informed consent among the populace. There have been many different ways of describing the power that language has over the human mind, but I prefer the Discordian view and would simply ask you: “have you seen the Fnords?” It’s an absurdist rendition of the power of psychological conditioning; and the ability to overcome a lifetime of it. Fnord mindwashing is “one step beyond Pavlov”, in that the word leads to activation syndrome, repressing ever seeing it and attributing the anxiety to wherever it’s found. In The Illuminatus! Trilogy (Robert Anton Wilson and Robert Shea, 1976, p255), one of the characters is taught to see the Fnords by the protagonist, and he sees them after every argument made by a Senator, in a news story about the increased use of gasmasks among New Yorkers (after every distressing chemical fact) and in a feature story about the endless saber rattling between the United States and Russia. To see the Fnords is to be able to control your fight or flight response, so that it can’t be abused by those who mean to control you. The social justice cult and the media both abuse Pavlov’s work – Fnord is almost their entire vocabulary!
One cannot think logically and emotionally at the same time, as many studies have shown. In this day and age, most of us live in something like a constant Posttraumatic Stress Disorder, with our fight or flight response being manipulated by power hungry sociopaths. They don’t want your money (they laugh at people who think Fed notes are valuable), they want your soul! I only realized this after seeing the Fnords and learning to cope with the PTSD acquired from a car accident. Statistically speaking, I shouldn’t have had the chance to try and walk off eight broken bones. This comparison is slightly anecdotal, but no less valid because it led to the realization that the same mechanism made me scream (both inside my head and aloud), cry, and pray to gods that I didn’t even believe in to make it end, right now. Any time I was in a moving vehicle was no different than the Fnord. It’s the same mechanism that fuels trigger words (literal Fnords) and the overtly emotional response people sometimes give to purely logical questions like: should someone who has committed so many crimes, so obviously, actually be respected as a presidential candidate? Should the fourth estate, which props up her corpse, be held accountable for their countless atrocious deceits?
My mentor, Aldous Huxley, once said in one of his later lectures in 1962: “There will be, in the next generation or so, a pharmacological method of making people love their servitude, and producing dictatorship without tears, so to speak. Producing a kind of painless concentration camp for entire societies. So that people will in fact have their liberties taken away from them, but will rather enjoy it, because they will be distracted from any desire to rebel by propaganda or brainwashing, or brainwashing enhanced by pharmacological methods. And this seems to be the final revolution.” This is what the New World Order really is. The angry man yelling about water filters and male enhancement pills, who panicked a myriad of people on New Year’s Eve 1999 by saying that Russia had launched ICBM’s, is a shill. Alex Jones is the Horseshoe Theory equivalent of the social justice cult. He makes a living by making people so terrified that they buy his sensationalist exaggerations and ridiculous products. His lexicon contains nothing but Fnords and water filters.
This undeserved esteem for man, this kind of suicidal naivety and apathy, couldn’t have been fostered in any other epoch — and it is deadly. We are turning ourselves from the obedient unquestioning sheep into the extinct, and soon to be forgotten, Dodo. We are allowing our nervous systems to be brute-forced by maniacal psychopaths whose Great Work is to become literal gods on Terra, and rule over us all. We are rapidly approaching Huxley’s “Final Revolution” and nobody seems to care. We are receiving propaganda instead of journalism and most salivate, begging for more. We are turning ourselves into Pavlov’s bitch and if informed consent is a joke, democracy is a myth. | 2024-05-01T01:26:29.851802 | https://example.com/article/7709 |
Q:
When and how does HashMap convert the bucket from linked list to Red Black Trees?
I was going through java 8 features and found out that hashmaps use a red black tree instead of a linkedlist when the number of entry sets on the bucket increases.
However, doesn't this require the key to be Comparable or some ordering of the keys to exist and how does this work ? When does this conversion actually happens and how ?
A:
When there are at least 8 entries (TREEIFY_THRESHOLD) in a single bucket and the total number of buckets is more then 64 (MIN_TREEIFY_CAPACITY) then that single bucket will be transformed to a perfectly balanced red black tree node.
There is also the shrinkage that you should be aware of (if you want) that happens when you remove entries (UNTREEIFY_THRESHOLD == 6).
You are correct that keys should be Comparable - but that is not always required, it is good if they are (in case they have the same hashCode), but in case they are not, this is used:
static int tieBreakOrder(Object a, Object b) {
int d;
if (a == null || b == null ||
(d = a.getClass().getName().
compareTo(b.getClass().getName())) == 0)
d = (System.identityHashCode(a) <= System.identityHashCode(b) ?
-1 : 1);
return d;
}
So the className as a String is used for comparison and if that fails too, then System.identityHashCode is used (Marsaglia XOR-Shift algorithm) to decide the left and right.
To answer you question when this happens - when resize is called. When you have to resize your HashMap - there are some things happening; like the number of buckets increases by a factor of two (one more bit is taken into consideration where an entry will move or not) or a certain bucket is transformed to a tree. This process (again if you really care) is pretty slow, some people say that a Java HashMap is "sloooooooow, then is fast fast fast; then it's sloooooo, then it's fast fast fast" (I still see this as mocking, but there are PauselessHashMap implementations).
This brings two interesting points. First is choose the correct size of your Map initially (even a rough estimation will do), i.e.:
new HashMap<>(256); // choosing the size
this will avoid some resizes.
The second one is why transforming to a Tree is important (think database indexes and why they are BTREE...). How many steps it would take you to find an entry in a perfect tree that has INTEGER.MAX_VALUE entries (theoretically). Only up to 32.
| 2023-11-03T01:26:29.851802 | https://example.com/article/2660 |
220 Apartments for rent in Sandy Springs, GA
"I have a dream that one day on the red hills of Georgia, the sons of former slaves and the ..."I have a dream that one day on the red hills of Georgia, the sons of former slaves and the sons of former slave owners will be able to sit together at the table of broth...Read Guide >
"I have a dream that one day on the red hills of Georgia, the sons of former slaves and the sons of former slave owners will be able to sit together at the table of brotherhood." (-Martin Luther King, Jr.)
In 2005, Sandy Springs became the third-largest city in U.S. history to become incorporated. Located just north of I-285, Sandy Springs is a big part of the reason Metro Atlanta is the third-largest Metropolitan area in the South. Although the recent incorporation might be the most noteworthy tidbit about Sandy Springs, the relatively new city is located smack-dab in the middle of a cultural salad bowl. With a population exceeding 94,000, Sandy Springs is the largest suburb of Atlanta, and is one of the most affluent cities in the Metro Atlanta area. Eight years removed from incorporation, Sandy Springs is set to experience a slew of change over the next decade by way of infrastructure, taxes, and maybe even a school system overhaul. Although Sandy Springs hasn't yet built up the culture and diversity that characterizes much of the Metro Atlanta area, you're always just a short drive away from a complete change of scenery should you want it.
Having trouble with Craigslist Sandy Springs? Can't find that special apartment for rent on Apartment Finder or Zillow? Apartment List is here to help!
Each of the various neighborhoods of Sandy Springs has a different feel, different attractions and amenities, and (of course) will have a different impact on your wallet. Here's a quick guide to the major 'hoods to help you narrow it down:
Perimeter Center: Centered around the second biggest mall in Georgia and the largest medical center in the state, Perimeter Center is a commercial hub filled with offices, retailers, condos, restaurants, and--last but not least--apartments. With three MARTA (rail system) stations and a number of taxi services, the Perimeter Center is the easiest part of Sandy Springs to navigate without a car. $$$$
Riverside: This neighborhood is located along the Chattahoochee River. As a result, it’s one of the most affluent areas in Metro Atlanta. It’s more dominated by luxurious houses than apartments for rent. $$$$
Downtown: Downtown Sandy Springs will soon see some of the most dramatic effects of the Sandy Springs incorporation. Recently, City Council members approved a plan to renovate the area to the tune of $350,000. The funds will help construct a municipal complex, a street grid pattern, and more. So the area will look more like--you know--downtown. $$$ (This will probably go up soon)
Dunwoody Panhandle: Although the Panhandle still has plenty of opulent homes, Roswell Road offers a diverse spread of apartment complexes. Williamsburg at Dunwoody and the Dunwoody Village offer up plenty of shopping options. $$$
North Springs: If you have made it this far in the guide, you probably get the picture--Sandy Springs is pretty pricey! North Springs still offers plenty of high-priced lavish apartments, however, it also features some of the most affordable rental options in the city. $$
You'll be checking your smartphone's weather app every morning in Sandy Springs, because the weather here turns faster than Atlanta Braves fans. Although the winters aren’t particularly harsh, some of the warmest days don’t fall far from the coldest ones. Also, since the city is not the best at dealing with icy conditions, one solid night of snow can shut down the entire Metro-Atlanta area. Summers live up to the “Hotlanta” moniker, so keep an eye out for local public pools, or make friends who have their own. Although there will be a few days per year where you should avoid the heat altogether, there are also plenty of afternoons with perfect sunbathing conditions.
Due to a sub-par "developing" system, a never ending list of road and construction work, and the distance between some of the more popular parts of the metro area, it helps to have a car that you feel comfortable driving in for long periods of time--and to have your favorite tunes cued up on your smartphone alongside that weather app. Metro Atlanta’s infamous traffic puts the average commute time for workers at an average of 30.6 minutes, according to recent Census data. That’s enough to earn the seventh spot on the list of worst commutes in the country. A 30-minute drive can quickly turn into an hour-long sit in traffic on a bad day, making the comfy car and good tunes extra essential.
Those who don’t mind spending a little extra time in the car will find plenty of things to do. The Georgia Dome, the Georgia Aquarium, and other downtown Atlanta attractions are just over 20 minutes away. A trip to hang out with the hipsters of Little Five Points and East Atlanta will take about 25 minutes. Looking for ethnic food? Take a 15-minute drive over to Buford Highway for a seemingly endless selection of restaurants serving up authentic grub from every corner of the world. | 2024-06-10T01:26:29.851802 | https://example.com/article/3510 |
Natural products are substances produced by microbes, plants, and other organisms. Microbial natural products offer an abundant source of chemical diversity, and there is a long history of utilizing natural products for pharmaceutical purposes. One such compound is FR901228 isolated from Chromobacterium and has been found to be useful as an antibacterial agent and antitumor agent (see, for example, Ueda et al., U.S. Pat. No. 7,396,665).
However, secondary metabolites produced by microbes have also been successfully found to have uses for weed and pest control in agricultural applications (see, for example, Nakajima et al. 1991; Duke et al., 2000; Lydon & Duke, 1999; Gerwick et al., U.S. Pat. No. 7,393,812). Microbial natural products have been also successfully developed into agricultural insecticides (see, for example, Salama et al. 1981; Thompson et al., 2000; Krieg et al. 1983). Sometimes, such natural products have been combined with chemical pesticides (see, for example, Gottlieb, U.S. Pat. No. 4,808,207).
Burkholderia
The Burkholderia genus, β-subdivision of the proteobacteria, comprises more than 40 species that inhabit diverse ecological niches (Compant et al., 2008). The bacterial species in the genus Burkholderia are ubiquitous organisms in soil and rhizosphere (Coenye and Vandamme, 2003; Parke and Gurian-Sherman, 2001). Traditionally, they have been known as plant pathogens, B. cepacia being the first one discovered and identified as the pathogen causing disease in onions (Burkholder, 1950). Several Burkholderia species have developed beneficial interactions with their plant hosts (see, for example, Cabballero-Mellado et al., 2004, Chen et al., 2007). Some Burkholderia species have also been found to be opportunistic human pathogens (see, for example, Cheng and Currie, 2005 and Nierman et al., 2004). Additionally, some Burkholderia species have been found to have potential as biocontrol products (see for example, Burkhead et al., 1994; Knudsen et al., 1987; Jansiewicz et al., 1988; Gouge et al., US Patent Application No. 2003/0082147; Parke et al., U.S. Pat. No. 6,077,505; Casida et al., U.S. Pat. No. 6,689,357; Jeddeloh et al., WO2001055398; Zhang et al., U.S. Pat. No. 7,141,407). Some species of in this genus have been effective in bioremediation to decontaminate polluted soil or groundwater (see, for example, Leahy et al. 1996). Further, some Burkholderia species have been found to secrete a variety of extracellular enzymes with proteolytic, lipolytic and hemolytic activities, as well as toxins, antibiotics, and siderophores (see, for example, Ludovic et al., 2007; Nagamatsu, 2001).
Oxazoles, Thiazoles and Indoles
Oxazoles, thiazoles and indoles are widely distributed in plants, algae, sponges, and microorganisms. A large number of natural products contain one or more of the five-membered oxazole, thiazole and indole nucleus/moieties. These natural products exhibit a broad spectrum of biological activity of demonstrable therapeutic value. For example, bleomycin A (Tomohisa et al.), a widely prescribed anticancer drug, effects the oxidative degradation of DNA and uses a bithiazole moiety to bind its target DNA sequences (Vanderwall et al., 1997). Bacitracin (Ming et al., 2002), a thiazoline-containing peptide antibiotic, interdicts bacterial cell wall new biosynthesis by complexation with C55-bactoprenolpyrophosphate. Thiangazole (Kunze et al., 1993) contains a tandem array of one oxazole and three thiazolines and exhibits antiviral activity (Jansen et al., 1992). Yet other oxazole/thiazole-containing natural products such as thiostrepton (Anderson et al., 1970) and GE2270A (Selva et al., 1997) inhibit translation steps in bacterial protein synthesis. More than 1000 alkaloids with the indole skeleton have been reported from microorganisms. One-third of these compounds are peptides with masses beyond 500 Da where the indole is tryptophan derived. The structural variety of the remaining two-thirds is higher, and their biological activity seems to cover a broader range, including antimicrobial, antiviral, cytotoxic, insecticidal, antithrombotic, or enzyme inhibitory activity. | 2024-01-21T01:26:29.851802 | https://example.com/article/4922 |
Win every hand of go fish! The cards are secretly marked on the back. With the stripped effect, you can have a spectator select a card and instantly find it in the deck. A trick deck that looks ordinary. | 2024-01-10T01:26:29.851802 | https://example.com/article/5592 |
### “回国避疫”和“中国式撤侨”的真相
------------------------
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<div><img alt="" class="aligncenter wp-post-image" src="https://i.epochtimes.com/assets/uploads/2020/03/008FotoJet-1-600x400.jpg"/>
<div class="red16 caption">
近日陆媒宣传“回国避疫”，但接待大厅里人员稀少，各省分流工作人员很闲。（视频截图）
</div>
</div><hr/>
#### [翻墙必看视频（文昭、江峰、法轮功、八九六四、香港反送中...）](https://github.com/gfw-breaker/banned-news/blob/master/pages/link3.md)
<div><p>
【大纪元2020年03月16日讯】（大纪元记者李新安报导）随着中共宣传“疫情清零”，网上也传出海外华人“
<ok href="https://www.epochtimes.com/gb/tag/%E5%9B%9E%E5%9B%BD%E9%81%BF%E7%96%AB.html">
回国避疫
</ok>
”的消息。那么真实的情况是如何呢？
</p>
<p>
日前，网上一段视频打出字幕，“感受一下今天回国的人有多少？”但视频镜头只停留在取行李的传送带上。另一段相关视频显示，在出站大厅里，设有各省接受登记回国人员的摊位，但看不到有什么人登记，身穿防护服的工作人员无所事事。
</p>
<p style="text-align: center;">
</p>
<p>
而有一段视频背景音显示，有人从日本落地上海第一天，（在机场留观处）等了差不多12个小时，被告知要隔离。拍摄视频的女生在网上表示，是因为看抖音才决定回国的，现在后悔了。
</p>
<p>
另一段视频显示，英、法的中国留学生由于学校关闭因此返回中国，在上海下飞机后被扣留在发热病区两天两夜，不让回家，也不安排房间休息。视频中警察的警号为057526。
</p>
<p>
一名留学生与警察交涉，“我们这些负责任的人被关在这边，冒着被传染的风险，这么多人，都是很危险的情况，还要关在里面，饭两天没吃了，觉也没睡。我们这怎么搞啊？住宿也没有地方安排，要我坐大巴直接回家了，现在这个安排不合理啊。”
</p>
<p>
留学生们表示，他们没有发烧，医生没有给他们诊断证明，也不告诉他们CT和血检结果。
</p>
<p>
</p>
<blockquote class="twitter-tweet">
<p dir="ltr" lang="zh">
在中国宣布机器：中国安全，外国水生火热的宣传下，大量留学生组团回国。这几个英国留学生到机场就被隔离，滞留浦东医院，没饭吃，没有休息的地方！据说所有法国学生都会回来，很好！以后国内的病毒爆发，都算输入性病例，栽赃到你们身上，全部扫厕所，批斗！
<ok href="https://t.co/2uy4ECv7Nu">
pic.twitter.com/2uy4ECv7Nu
</ok>
</p>
<p>
— 冷山时评 (@goodrick8964)
<ok href="https://twitter.com/goodrick8964/status/1238915820417200128?ref_src=twsrc%5Etfw">
March 14, 2020
</ok>
</p>
</blockquote>
<p>
<p>
还有人在网上发布了被隔离的现场视频，居住环境很差，窗户是密封的、打不开，门被铁链锁着，推开的一点门缝是唯一通风的地方。卫生间不能洗澡、不能洗衣服。
</p>
<p style="text-align: center;">
</p>
<h4>
中共政府称没有考虑撤侨
</h4>
<p>
武汉疫情在中国爆发后，各国政府纷纷
<ok href="https://www.epochtimes.com/gb/tag/%E5%8C%85%E6%9C%BA%E6%92%A4%E4%BE%A8.html">
包机撤侨
</ok>
。而当疫情蔓延海外，在日本、韩国、意大利、伊朗等国爆发后，中共政府除了网上宣传，却没有任何撤侨举动。
</p>
<p>
3月6日，中共驻意大利使馆网站发布发言人称，“未听说使馆考虑包机‘撤侨’”。疫情蔓延，“不流动是最大的安全，居家是最好的防护”。
</p>
<figure class="wp-caption aligncenter" id="attachment_11943542" style="width: 450px">
<ok href="http://i.epochtimes.com/assets/uploads/2020/03/ii_meitu_1.jpg">
<img alt="" class="size-medium wp-image-11943542" src="http://i.epochtimes.com/assets/uploads/2020/03/ii_meitu_1-450x276.jpg"/>
</ok>
<br/><figcaption class="wp-caption-text">
中共驻意大利使馆网站发布发言人称，未听说使馆考虑包机“撤侨”。
</figcaption><br/>
</figure><br/>
<p>
3月7日，中共驻英国使馆发言人也称，“目前驻英使领馆没有安排包机的计划。”
</p>
<p>
仅有在3月3日第一架包机从伊朗直飞兰州，《环球网》报导称，一名居住在德黑兰的华人表示，“不过这不是撤侨，而是商业包机。愿意回国的华人需要报名，并支付相关费用。”
</p>
<p>
而在中共驻美大使馆官网上连对撤侨的回应都看不到。
</p>
<h4>
境内境外待遇不同
</h4>
<p>
中共驻日本大使馆3月9日消息称，“目前，国内多地已规定从日本、韩国、意大利、伊朗等国入境人员需隔离14天。”
</p>
<p>
而在中国境内，人们只要绕开湖北就不用隔离。
</p>
<p>
访民朱先生于3月1日坐飞机从温州到北京上访，他告诉记者，当时温州已经解封，凭“绿码”（手机健康码）出行。“我打了市民12345热线，确定可以进北京，不需要隔离。湖北省的要隔离，其它省市不用。就是住酒店有点麻烦，好多酒店不愿接待，找了一家小旅馆一天500元。”
</p>
<p>
也有河南网友致电广东珠海某社区，工作人员证实，坐飞机返回广州不用隔离，“自己开车只要经过湖北回来一律集中隔离，酒店5000块钱自费”。并表示这是省里发的文件规定，不想被隔离的话，可以绕过湖北省。如果坐火车也不得停靠任何湖北境内站点。
</p>
<h4>
撤侨是假 甩锅是真
</h4>
<p>
中国公民力量运动发起人杨建利博士在接受大纪元采访时表示，武汉疫情发生以来，姑且不论中国死了多少人，经济遭受多大损失，仅从中国的形象来讲，受到严重的打击。中共政府开始利用手中的权力，调动社会资源，想把形象树立起来，做一切可能的事情进行维稳。
</p>
<p>
“因为形象上的损失直接造成权力上的不稳定。所以后期它从宣传上把自己打造成一个大国战疫，近期又出现了中国的武汉病毒传染到全世界的现象，造成中国人一种恐慌，世界上会不会给中国带来更多病例？中共就抓住这个时机开始造形象，劝滞留海外的中国人回中国，这是它的一种公关措施。”他说。
</p>
<p>
杨建利指出，实际上这种措施收效是非常有限的，回去的人非常少。推特上无非就是几张照片，因为即使目前在任何一个比较落后、贫穷的国家，只要不是被某种政治正确的概念束缚住，仅仅是从最常识的判断，人们都会觉得比回中国要安全。
</p>
<p>
“毕竟病毒是发生在中国，目前中国遭受病毒袭击的人数最多。更何况现在中国的情况到底怎么样？未来还会不会发生更大的危机？中共政府在逼着大家复工，复工以后会不会复发？一般来讲，你不失去常识判断，没有特殊原因，不会回中国的。”杨建立预测，人们不仅不会回中国，疫情过去以后，世界各地对中国旅行解禁，中国将会有一个新的移民潮。
</p>
<p>
他表示，身边也有一些来美国留学、工作、旅游的，都是在中国较优越阶层家庭的成员，没有一个说马上要回国去。“可能是像韩国、意大利、伊朗这些疫情爆发严重而且也的确出现了一些缺陷的地方，有些人回去了。我没有听说美国、加拿大、澳大利亚等等这些地方有什么中国人要回去避疫。”
</p>
<p>
杨建立指出，中共政府不管它做任何的形象、动作，有一条就可以测验它的真假，如果中共高官包括最高层领导人，下大力气把他自己的公子、千金小姐或者其他亲戚，想办法给接回中国去，那才真正的说明他们是真的是觉得在美国不安全了。但是从目前的情况来看，中共政府和官员根本没有下任何力气来做这些事情。
</p>
<p>
值得注意的是，中国式“撤侨”才刚刚开始，就有医护人员站出来宣称，另一场大战已经打响，发现接连不断的境外输入病例，让中国的疫情再度紧张，批判有些华人华侨恶意隐瞒病情，已被立案调查，将付出代价⋯⋯
</p>
<p>
对此，网友表示，“中共用请君入瓮的把戏，将复工引起病毒再次扩散的责任，让听党话跟党走的海外华侨背锅。”“中共打得一手好牌，没病的回来交钱，有病的回来背锅。”
</p>
<p>
前桂林电视台记者、中国社民党秘书长曾节明认为，中共的文革式“抗疫”外宣，骗得大批海外中国留学生、华侨误以为“中共国抗疫风景独好”，纷纷回国躲避瘟疫，结果一下飞机就被集体关了起来，吃不饱睡不好，反而大大增加了被传染的风险；中共当局把复工和假清零造成的疫情反弹，归咎于归国华人，煽动对海归华人的仇恨。
</p>
<p>
责任编辑：林琮文 #
</p>
</p></div>
<hr/>
手机上长按并复制下列链接或二维码分享本文章：<br/>
https://github.com/gfw-breaker/banned-news/blob/master/pages/nsc413/n11943372.md <br/>
<a href='https://github.com/gfw-breaker/banned-news/blob/master/pages/nsc413/n11943372.md'><img src='https://github.com/gfw-breaker/banned-news/blob/master/pages/nsc413/n11943372.md.png'/></a> <br/>
原文地址（需翻墙访问）：https://www.epochtimes.com/gb/20/3/16/n11943372.htm
------------------------
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If you are looking for a home with the perfect balance of convenience, tranquility and updates, look no further! 2430 Woodside Road is a spacious story and a half home sitting on nearly an acre of land complete with both wooded areas and manicured outdoor living spaces. Not only is this property convenient to all that St. Matthews and Brownsboro Road have to offer but it also offers park-like perks including a perfect sledding hill for the kids and access to a hiking trail that leads to Locust Grove. Enter through the bright and inviting foyer, which flows into each room on the first floor. The kitchen is spacious and equipped with professional grade stainless steel appliances, beautiful marble countertops and storage space galore. The first floor also offers a well-appointed Owner's suite , a large formal living room and a formal dining room which leads into the stunning sun room, perfect for casual family living or entertaining. The second floor boasts three sizable bedrooms, one with an en suite bathroom, the laundry room and an additional full bathroom. In the basement, there is approximately 600 sq ft finished with a family room and half bathroom, and about 700 sq ft unfinished, that serves as a mud room and second laundry room. Come see all that this home has to offer!
Copyright 2017 Metro Search, Inc. All rights reserved. The data relating to real estate for sale on this web site comes in part from the Internet Data Exchange Program. Real estate listings held by IDX
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The Broker providing these data believes them to be correct, but advises interested parties to confirm them before relying
on them in a purchase decision. Information deemed reliable but is not guaranteed. | 2024-03-07T01:26:29.851802 | https://example.com/article/9968 |
Q:
Enforce file upload size on Heroku?
Got a Rails app on Heroku. I want to limit the size of a file upload if possible. The file is processed as a StringIO object, so the file contents will be processed in memory (have no need to write an intermediate file to a filesystem).
Ordinarily, I would limit upload size on the web server. But with Heroku, what options are there? I realize I could go with a Flash uploader, but I'm hoping to avoid requiring Flash on the client, if at all possible.
A:
Heroku limits the request entity to some small size (30MB), and also limits all request/response cycles to 30s. Both are hard rules and must be lived with.
Rails by default spools file uploads to disk and translates them to Tempfile instances before handing them off to your application.
| 2024-01-08T01:26:29.851802 | https://example.com/article/7901 |
Q:
Disable Cmd-w on MacOS Catalina
Cmd-w closes the current window on MacOS Catalina. This conflicts with my muscle memory of using M-w in Emacs.
I looked at Disable Command-W in the terminal, but the accepted answer does not work on MacOS Catalina.
How do you disable Cmd-w?
A:
Like in old versions, it be can't removed. The work around is the same: the system default can be overridden to a new key combination. The hotkey must be associated with a context menu item name (ie. an app specific menu item). The name must match exactly.
Systems apps use the name Close to mean close window, along with iTerm2. Some other apps use the more verbose Close Window. Remap both to get decent app coverage. Note that some apps may use other unique names that mean close window. Separate entries will have to be made for these apps to remap it globally.
Navigate to System Preferences -> Keyboard.
Select the Shortcuts tab, then App Shortcuts in the left pane.
Select the + at the bottom of the window to add a new shortcut.
To remap it globally, select All Applications in the Application field. To change Cmd-w on a specific application instead of globally, select that instead.
Set Menu Title to Close. It is case sensitive and must match exactly.
Set Keyboard Shortcut to the desired key combination. I set it to an obscure value so it's essentially 'disabled'.
Click Add to finalize the key shortcut. The right pane should now show a new entry for Close with your key combination (see the first image for an example).
Add another hotkey entry with Application set to All Applications and Menu Title set to Close Window for additional coverage.
Close the menu.
The change takes effect immediately, including with open apps.
| 2024-04-09T01:26:29.851802 | https://example.com/article/7212 |
Q:
What happens when spring bean definition file loaded into application multiple times?
I am just curious to know when a Spring.xml file loaded into application multiple times into an application using ClassPathXmlApplicationContext. For example if I want to get the services defined in Spring.xml into my claases by creating new instance of ApplicationContext in each class . Does this approach create each time new beans without destroying the previously created beans?Does this creates any memory problems ? When I see in ClassPathXmlApplicationContext API in spring website I found this.Does this refresh creates new bean definition of existing bean by destroying existed one?
ClassPathXmlApplicationContext(String... configLocations)
***Create a new ClassPathXmlApplicationContext, loading the definitions from the given XML files and automatically refreshing the context.***
A:
When the same xml file is loaded several times spring creates the same beans several times. In most cases this does not cause problems except initiation time. But sometimes you can get conflicts. For example if you have bean that is listening to TCP port and then open yet another bean that tries to connect to the same port it fails.
| 2024-07-18T01:26:29.851802 | https://example.com/article/1805 |
Q:
How to inherit correctly field in div
how to inherit correctly field
I inherited a field but did not appear as required, because it is inside a div
<group name="email_template_and_project" position="before">
<group name="sale_condition" string="Sale Conditions">
<label for="warranty" groups="stock.group_production_lot"/>
<div groups="stock.group_production_lot">
<field name="warranty" class="oe_inline"/> months
</div>
<label for="sale_delay"/>
<div>
<field name="sale_delay" attrs="{'readonly':[('sale_ok','=',False)]}" class="oe_inline" style="vertical-align:baseline"/> days
</div>
</group>
</group>
<record model="ir.ui.view" id="view_product_template_es_">
<field name="name">product.template.es.form</field>
<field name="model">product.template</field>
<field name="inherit_id" ref="product.product_template_only_form_view"/>
<field name="arch" type="xml">
<xpath expr="//field[@name='sale_delay']" position="after">
<div>
<field name = 'time_pose' /> hours
</div>
</xpath>
</field>
</record>
A:
<record model="ir.ui.view" id="view_product_template_es_">
<field name="model">product.template</field>
<field name="inherit_id" ref="product.product_template_only_form_view"/>
<field name="arch" type="xml">
<xpath expr="//field[@name='sale_delay']/parent::div" position="after">
<label for="time_pose"/>
<div>
<field name="time_pose" class="oe_inline"/> hours
</div>
</xpath>
</field>
</record>
| 2024-04-16T01:26:29.851802 | https://example.com/article/8019 |
An unfortunate aspect of working in the spirits industry is that everyone always wants to meet for a drink. It’s hard to remember the last time I had a coffee meeting that wasn’t an Irish Coffee meeting. Also, I’m pretty well known as a drinks writer, so when I do go out to the bars and restaurants I’m constantly asked to try drinks that bartenders are working on to get recommendations and suggestions on how to tune them. Now add on top of that the spirits I need to sample to review.
I love my job (who wouldn’t?) but the net effect off all this is that I end up having a lot of alcohol. Sometimes it can get to be too much and I find that I simply need to take a break. Just because I’m not drinking doesn’t mean I can stop meeting people for drinks, or that I have to retreat into my home and wait for my ‘dry’ period to pass.
When I am taking a break from drinking, I often rely on a very simple drink that almost any bar can make, something that is easy to sip with more complexity and flavor than having a soda. Angostura makes perhaps the most well-known bitters in the world, used in most of the key spirit-forward classic cocktails like the Old Fashioned and the Manhattan. Angostura is a mix of herbs, water, sugar, gentian, and spirit that acts like a binding agent in drinks (bringing all the flavors together). Although Angostura is spirit based (and has 44.7% alcohol), the amount you use in a drink is fairly small. I did some measuring and 5 dashes of Angostura equals ¼ tsp which has 0.550 ml of alcohol. To put that in perspective, a low alcohol beer with 3% alcohol would have 7.09 ml of alcohol in an 8 ounce serving, or 14.0ml in a pint. You can get intoxicating qualities from Angostura, but you need to use a full 1-2 ounces.
Since Angostura is packed with flavor, just a little of it can have a big impact on what you are drinking. My favorite non-drink drink is to put 5 dashes of Angostura bitters into soda water. I sometimes substitute Sprite or 7UP if I am looking for something a little sweeter. This easy combination is a wonderful stand-in to drink at a bar when you are taking a break from alcohol. It’s also something that I tend to turn to if I have a cold and need to be out in a social situation where there’s drinking, and again I don’t want to drink.
Angostura is also very easy to find. Not only can you get it at most liquor stores, but I’ve seen it at most grocery stores and even at Target. You can easily create variations of this drink by using different bitters we also recommend: Scrappy’s celery bitters, Brooklyn Hemispherical Meyer Lemon Bitters, Bittermens Grapefruit Bitters and Dr Adam Elmegirab’s Boker’s Bitters. Most bars don’t have the ability to charge you for a bitters and soda water, and in many cases I’ve been handed the bottle of Angostura to add it myself to my drink.
Sometimes you need to take a break from drinking (or you are the designated driver) and with Bitters and Soda you do that without the entire world asking you why you aren’t drinking.
[Read our complete report on Angostura Bitters and go Behind The Scenes to see how they are made] | 2024-07-04T01:26:29.851802 | https://example.com/article/3671 |
Q:
how to pass value from directive to controller
Can anybody give me a simple example on how to exchange data between the directive and controller.
I am a newbie to angularjs and i want to learn how to pass data from cotroller to directive and then back to controller.
I have learnt on how to pass value from controller to directive ,but the poblem is I cant achieve the value from directive back to controller ..can somebody help
html code
<div ng-controller="MyCtrl">
<pass-object obj="obj"></pass-object>
</div>
javascript code
var myApp = angular.module('myApp',[]);
myApp.directive('passObject', function() {
return {
restrict: 'E',
scope: { obj: '=' },
template: '<div>Hello, {{obj.prop}}!</div>'
};
});
myApp.controller('MyCtrl', function ($scope) {
$scope.obj = { prop: "world" };
});
A:
You achieve that through some options like :
1- In case your scope was shared scope, then your directive can access and change the parent scope data directly.
2- In case your scope was isolated scope, you can create a service that you can update and shared it with your controller(s), and your controller(s) can watch the values in that service and act accordingly.
3- In case your scope was isolated scope, another way to pass data back is to assign a method to your directive scope and from the directive you can execute that method and pass your data to controller, one trick you need to pay attention to in this case is that you have to override the arguments of that function when you call the method from the directive.
EDIT:
Because of that point 3 is not straightforward, this code should give you a starting point.
(function(){
angular.module("app", [])
.directive("passObject", function(){
return {
restrict : "E",
template: "<input type='button' ng-click='notifyParent()' value='Notify Parent'></input>",
scope : {
dirParam : "&func"
},
controller: function($scope){
$scope.notifyParent = function(){
if($scope.dirParam){
$scope.dirParam({p1 : 10})
}
}
}
}
})
.controller("mainCtrl", function(){
var vm = this;
vm.myFunc = function(p1){
console.log("This alert is in the main controller, and the value " + p1 + ", I got from the directive");
alert(p1);
}
});
})();
Html code :
<!DOCTYPE html>
<html>
<head>
<script data-require="angular.js@1.4.8" data-semver="1.4.8" src="https://code.angularjs.org/1.4.8/angular.js"></script>
<link rel="stylesheet" href="style.css" />
<script src="script.js"></script>
</head>
<body ng-app="app" ng-controller="mainCtrl as ctrl">
<pass-object func="ctrl.myFunc(p1)">
</pass-object>
</body>
</html>
Hope that helps.
| 2023-11-09T01:26:29.851802 | https://example.com/article/6493 |
Processes of producing unsaturated fatty acids from olefins through unsaturated aldehyde correspond to representative catalytic vapor phase oxidation.
In partial oxidation of olefins, molybdenum oxides, bismuth oxides, and transition metal oxides are used to prepare catalysts. As representative processes, there are a process of preparing (meth)acrylic acid through (meth)acrolein by oxidizing propylene or isobutylene, a process of preparing phthalic anhydride by oxidizing naphthalene or ortho-xylene, or a process of preparing maleic anhydride by partially oxidizing benzene, butylene or butadiene.
In the first step, oxygen, propylene or isobutylene is oxidized by dilute inactive gas, vapor and a predetermined amount of catalyst, mainly preparing (meth)acrolein. In the second step, the (meth)acrolein is oxidized by oxygen, dilute inactive gas, vapor and a predetermined amount of catalyst, thereby preparing the (meth)acrylic acid. Devices performing such processes may be provided such that both steps are performed in one device or in respective devices.
The (meth)acrylic acid is mainly used to prepare (meth)acrylate used as coating materials such as paint, textile auxiliaries, paper, etc. by reacting with alcohol. In addition, high-purity (meth)acrylic acid is used as a raw material of high-hygroscopicity resins, demand for which is rapidly increasing.
In general, metal oxide catalysts are prepared through co-precipitation, hydrothermal synthesis, sol-gel synthesis, physical mixing, etc. The metal oxide catalysts are precipitated into a polyanion, metal oxide or metal hydroxylate form in the reaction processes, and physical characteristics and morphologies of the precipitates depend upon the pH or concentration of an aqueous solution, reaction temperature or aging time, thereby affecting a physical state, particle sizes and crystalline structure.
Examples of ligands that are bonded to oxoanions and transition metal precursors used in catalysts for preparing unsaturated fatty acids include —NH4, —NH2, —NOx, —Cl, —F, —N, —OH (hydroxyl), —SOx, —CO, —COO, —CnHmOx, alkoxide (O-metal), etc. Such ligands may be utilized as an ingredient for controlling catalytic activities by changing physicochemical characteristics of catalysts according to proper control methods as an essential ingredient upon dissolution or purification of metal oxides.
Japanese Patent No. 4295521 as a related art introduces a catalyst preparation technology wherein a catalyst is prepared by powder-coating and firing a bulk carrier. This technology produces an acrylic acid catalyst wherein a reduction ratio of a dry matter is 5 to 40% by mass at a 300° C. atmosphere as a catalyst-drying temperature. Such a preparation method has a relatively high drying temperature and thus change in a catalyst structure is caused, thereby disadvantageously affecting catalytic performance and thus tending to exhibit a low transition rate.
In addition, Korean Patent No. 10-0746971 introduces a catalyst wherein the catalyst includes molybdenum and vanadium, the content of catalyst poison measured by ion chromatography is 10 to 100 ppb, at least one volatile catalyst poison ingredient is additionally included, and acrylic acid is generated through vapor-phase contact oxidation of oxygen molecules and acrolein, and an acrylic acid preparation method including performing catalytic vapor phase oxidation of oxygen molecules and acrolein using the catalyst.
The catalyst is prepared through addition of aqueous ammonia as a catalyst poison ingredient, thereby lowering hot spot temperature and suppressing reaction efficiency decrease accompanied with degradation. Accordingly, an acrolein transition rate may be stably maintained for a long time. However, if a reducing material such as ammonia is present in a catalyst, the material functions as a catalyst poison, thus greatly increasing reaction temperature and activating the catalyst after extended use. Accordingly, a reducing material may be used as a catalyst poison for controlling catalytic activity, but there are considerable difficulties in performing quantitative control during a catalyst preparation process.
In addition, although inorganic salts present in catalyst precursors should be treated such that the amount thereof is decreased during a catalyst preparation process, a reducing material removal process is additionally required due to further addition of inorganic salts. Accordingly, there is a need for technology being simple and having superior reproducibility, which may sublimate, during catalyst calcination, ligands included in a catalyst. | 2024-01-10T01:26:29.851802 | https://example.com/article/6260 |
Classic Combo
Seasonal Selection
For a winter wedding, a delicate bouquet of white and blush pink will create a soft, romantic tone. No matter what time of year you get married, seasonal blooms are always the best choice for the freshest (and generally cheapest) look.
Ruby Red
To keep a red bouquet from casting a Christmas vibe, skip the greenery entirely for a fresh, bold look.
Warm Hues
A gorgeous bouquet highlights the colors of spring with peach and red ranunculus, yellow billy balls, peach roses and chamomile.
High, Low Mix
To save money without sacrificing style, create a bouquet that blends a few large blooms with cheaper filler flowers and greenery. The result will still be stunning, and your wallet will thank you.
Go Green
Striking greenery and flowers with hues that complement the surrounding autumn atmosphere comprise the perfect bouquet for this gorgeous fall wedding. Arrangement by Elder Floral Design
Strings Attached
Multi-colored ribbons add an unexpected dash of whimsy to this gorgeous bouquet.
Sculptural Arrangement
No Frills
For a casual country affair, nothing beats a simple bouquet of baby's breath and wildflowers.
Winter White
Simple and understated, this winter bouquet is a lush combination of white hydrangeas and garden roses.
Pops of Purple
A sultry bouquet made up of liatris, lilies, tulips, roses and daisies is the perfect choice for a wedding in early spring.
Make It Yours
To give your bouquet a personalized touch, consider incorporating a special pin or brooch. The bouquet is a great place to add your "something old."
Out of the Box
Though greenery is a classic filler for wedding bouquets, it never hurts to think outside of the box. Try an airy feather arrangement for a fun and romantic twist.
Totally Textural
To create an interesting, more unique bouquet, combine soft flowers, such as the white peonies featured here, with more textural elements, including gorgeous green succulents and unexpected scabiosa pods. Design by Kia Kreations | 2023-12-08T01:26:29.851802 | https://example.com/article/7707 |
Alternative subcellular locations of keratinocyte basonuclin.
Basonuclin is a zinc finger protein present in the basal cell layer of the epidermis and in hair follicles. Human basal epidermal cells are often heterogeneous with respect to a nuclear or cytoplasmic location of basonuclin and the protein may be concentrated in either compartment. In mouse and rat epidermis, although clusters of basonuclin may be seen in some basal cell nuclei, the protein is mainly concentrated in the cytoplasm. When epidermis whose basal cells contain predominantly cytoplasmic basonuclin is disaggregated and the cells are cultivated in the presence of supporting 3T3 cells, the basonuclin of the growing keratinocyte colonies is strongly concentrated in the cell nuclei. Transfer of the cells to culture medium without supporting 3T3 cells results in a predominantly cytoplasmic concentration of the basonuclin. This translocation is reversible, since addition of supporting 3T3 cells restores most basonuclin to the nucleus. The nuclear location is associated with more rapid cell growth. We conclude that different states of the keratinocyte require greater or less activity of basonuclin, and the subcellular location of the protein is probably related to the magnitude of its action on the cells. | 2023-12-15T01:26:29.851802 | https://example.com/article/1005 |
599 A.2d 333 (1991)
Michael G. ROWE, Individually and as a Selectman and Citizen of Ludlow, Windsor County, Vermont
v.
Dean R. BROWN, Jr., Ludlow Town Manager, and Planning Board and/or Board of Adjustment of Ludlow, Vt.; Herbert VanGuilder & Town of Ludlow.
No. 89-500.
Supreme Court of Vermont.
August 9, 1991.
Motion for Reargument Denied September 13, 1991.
*334 Thomas J. McGovern, Ludlow, for plaintiff-appellant.
Sheilla C. Files of Douglas Richards, P.C., Springfield, for defendants-appellees.
Before ALLEN, C.J., and PECK, DOOLEY and MORSE, JJ.
PECK, Justice.
Plaintiff appeals from a superior court dismissal of his action for damages pursuant to 42 U.S.C. § 1983, the Vermont Constitution and the Vermont Open Meeting statute, 1 V.S.A. §§ 311-314. Plaintiff alleged that he was injured when defendants improperly excluded him from various municipal meetings in Ludlow. We reverse with respect to plaintiff's § 1983 claim and affirm with respect to all other claims.
The complaint alleged that plaintiff was excluded from meetings of the Ludlow Board of Selectmen, the Planning Board, and the Board of Adjustment in 1984 and 1985. Plaintiff named town manager and zoning administrator Brown and selectman VanGuilder as defendants, alleging that they "willfully or maliciously and under color of state law" requested the Planning Board and Board of Adjustment to exclude plaintiff from their meetings. In addition, the complaint alleged that the actions of the defendants violated plaintiff's free speech rights and caused him to suffer fear of bodily harm, personal humiliation and mental anguish. The complaint rested on the Vermont Open Meeting Law and the free speech and due process clauses of the Vermont and the federal constitutions.[1] Plaintiff sought declaratory relief and damages for violation of state statutory and constitutional law and under 42 U.S.C. § 1983 and attorney's fees under 42 U.S.C. § 1988.
In September, 1988, the trial court dismissed plaintiff's federal law claims, holding that plaintiff had no federal first amendment right to attend the meeting in question, nor any due process right to a hearing on his exclusion. Because the court concluded that 42 U.S.C. § 1983 could not be employed to vindicate rights having their source in state law, and because his *335 claim was not supported by federal law, his § 1983 claims were dismissed.
In September, 1989, the trial court dismissed plaintiff's state law claims. The court held that the Open Meeting Law created no private right of action for its enforcement, and that plaintiff had no standing to assert a cause of action under the state constitution. The present appeal followed.
The Open Meeting Law on its face creates rights in favor of all members of the public:
All meetings of a public body are declared to be open to the public at all times, except as provided in section 313 of this title [relating to executive sessions]. No resolution, rule, regulation, appointment, or formal action shall be considered binding except as taken or made at such open meeting, except as provided under section 313(a)(2) of this title. A meeting may be conducted by audio conference or other electronic means, as long as the provisions of this subchapter are met.
1 V.S.A. § 312(a). The statute protects the public interest, and its violation offends the public weal.[2] The enforcement provisions of 1 V.S.A. § 314(b) allow the attorney general "or any person aggrieved by a violation of the provisions" of the law to seek injunctive or declaratory relief. Thus, if a Ludlow citizen sought an adjudication that the municipality misconstrued the statutory provision under which it conducted executive sessions (or otherwise violated the Open Meeting Law), the citizen could seek a declaration that the town was in violation of the statute and could enjoin that violation or seek an additional declaration under § 312(a) with respect to action purportedly taken in an unlawfully conducted meeting.
Plaintiff's § 1983 claim rests in part on the first amendment to the United States Constitution. Plaintiff argues that because, under the Open Meeting Law, the 1984 and 1985 meetings should have been open, under the first amendment, he could not be arbitrarily excluded. The trial court correctly concluded that § 1983 does not create a remedy for the violation of purely state-created rights, as its manifest purpose is to "create[ ] a species of liability in favor of persons deprived of their federal civil rights by those wielding state authority." Felder v. Casey, 487 U.S. 131, 139, 108 S.Ct. 2302, 2307, 101 L.Ed.2d 123 (1988); Williams v. State, 156 Vt. ___, ___, 589 A.2d 840, 849 (1990).[3] However, plaintiff had a federal first amendment right not to be excluded from a forum generally held open to the public. See Perry Education Association v. Perry Local Educators' Association, 460 U.S. 37, 45, 103 S.Ct. 948, 954, 74 L.Ed.2d 794 (1983).
Plaintiff admits that the relevant 1984 meetings were designated executive meetings. Such meetings, which must be approved by vote and are restricted in nature, are not generally held open to the public. See 1 V.S.A. § 313. Thus, plaintiff had no first amendment right to be present. Moreover, the fact that matters may have been considered at the executive sessions which are required under the Open Meeting Law to be considered only at public meetings did not convert those executive sessions into public meetings. Rather, if members of the public body, in violation of 1 V.S.A. § 313, considered at executive sessions matters which should have been considered publicly, they may be liable under the penalty section of the Open Meeting Law, 1 V.S.A. § 314. Plaintiff also alleged in his complaint that he was excluded from a public meeting in July, 1985, however. No facts were developed as to the nature *336 of that meeting; thus, dismissal of the § 1983 claim with respect to the July 1985 meeting was premature.
Plaintiff claims next that the defendants violated his Vermont constitutional right to be present at public meetings. He notes that in passing 1 V.S.A. § 312 the legislature codified the public's constitutional right to attend open meetings. An examination of the legislative history of the statutory scheme in question reveals an intention by the legislature to give meaning to Chapter I, Article 6 and Chapter II, § 8 of the Vermont Constitution. See Open Meetings: Hearings on S.35 Before the Senate General Committee, Forty-Fourth Biennial Session (February 14, 1957) (statement of Senator Fayette).
Regarding Chapter I, Article 6 we have previously stated that it is "a truism of a republican form of government, and provides no private right of action. The remedy contemplated by it is that of popular election." Welch v. Seery, 138 Vt. 126, 128, 411 A.2d 1351, 1352 (1980). In Seery we explained that for enforcement of the constitutional maxim, other than popular election, plaintiffs must avail themselves of the legislative enactments giving effect to Article 6.[4] Similar analysis is warranted under Chapter II, § 8.
Nor has plaintiff stated a claim for damages under Vermont's Open Meeting Law. Although plaintiff's amended complaint sought declaratory and injunctive relief, it is clear that the issues raised on appeal relate solely to the claim for damages. The Open Meeting Law on its face provides no such damages, and plaintiff offers no theory under which this Court may infer that what are in effect private tort remedies are to be implicitly read into the statute. There is no indication of legislative intent, explicit or implicit, to create a private tort remedy. See Cort v. Ash, 422 U.S. 66, 78, 95 S.Ct. 2080, 2087, 45 L.Ed.2d 26 (1975). Moreover, it is not "consistent with the underlying purposes of the legislative scheme to imply such a remedy" for violations of the Open Meeting Law. Id. The legislature might have considered the positive and negative impacts on public bodies of private damage suits for violations of the Open Meeting Law, but plaintiff does not contend that it did so. It can hardly be assumed that such an important provision of the statute, with such broad possible effects, would have been allowed to become law by implication, particularly in light of the very explicit limitations placed on the nature of private relief under § 314(b).[5]
We note that the amended complaint does seek other relief, specifically a judgment "finding that the defendants unlawfully excluded plaintiff from their meetings and ... prohibiting the defendants from excluding this plaintiff, Michael G. Rowe, from public meetings in the future." This is the kind of relief now available under § 314(b).[6] Thus, the trial court erred in stating that "the given [i.e., the sole] remedy for such a violation is prosecution by the state under 1 V.S.A. § 314." But while we do not require plaintiffs to cite a correct statutory remedy if they clearly and adequately describe the relief sought at trial and if that relief is available, plaintiff at bar has not raised this issue on appeal either by reference to statutory authority or otherwise. On the contrary, he has made it plain in his brief that the issues he wishes to present to this Court are his § 1983 claims and "a United States or Vermont Constitutional cause of action" and that he seeks damages to redress *337 "the injury done to his person."[7] Issues not raised on appeal are deemed waived. See In re Smith, Bell & Hauck Real Estate, Inc., 132 Vt. 295, 300, 318 A.2d 183, 187 (1974).
Finally, plaintiff argues that he suffered "a distinct and palpable injury to himself" and that Chapter 1, Article 4 of the Vermont Constitution requires that he be afforded a remedy.[8] The legislature has provided the remedy of injunctive or declaratory relief to a plaintiff whose public right to open meetings has been violated. Article 4 does not afford a plaintiff who chooses not to pursue those remedies additional private tort remedies. See Levinsky v. Diamond, 151 Vt. 178, 197, 559 A.2d 1073, 1086 (1989) (Article 4 has been treated as the Vermont equivalent of the federal due process clause), overruled on other grounds, Muzzy v. State, 155 Vt. 279, 280, 583 A.2d 82, 83 (1990).
Consideration of plaintiff's request for attorney's fees is premature at this juncture in the absence of a final determination of his § 1983 claim.
Reversed with respect to dismissal of plaintiff's § 1983 claim; affirmed in all other respects.
NOTES
[1] Plaintiff had earlier filed a complaint seeking redress as a town selectman, but this Court on January 10, 1988, dismissed that claim as moot since plaintiff at that time was no longer a selectman. We granted leave to file an amended complaint, and that amended complaint is the basis for the present action.
[2] 1 V.S.A. § 311(a) states:
(a) In enacting this subchapter, the legislature finds and declares that public commissions, boards and councils and other public agencies in this state exist to aid in the conduct of the people's business and are accountable to them pursuant to Article VI of the Vermont constitution.
[3] When state laws are enforced in a manner that offends rights, privileges, or immunities guaranteed by the federal constitution and enforceable against the states, § 1983 may be invoked in appropriate cases to redress the federal violation. See Monroe v. Pape, 365 U.S. 167, 180, 81 S.Ct. 473, 480, 5 L.Ed.2d 492 (1961).
[4] In this case the legislative enactment is 1 V.S.A. §§ 311-314.
[5] The legislature did consider allowing courts to "assess against the public body reasonable attorney's fees and other litigation costs reasonably incurred in any case under this section in which the complainant ultimately prevails." H. 91 § 23(c), Fifty-Ninth Biennial Session, Journal of the House of the State of Vermont at 208 (Biennial Session 1987). This provision, however, was not enacted. If the legislature considered but rejected awarding attorney's fees to injured plaintiffs, it is unlikely that it intended to permit recovery for damages.
[6] Section 314(b) was enacted on June 16, 1988, after plaintiff filed his amended complaint but before the trial court decided the case.
[7] The closest plaintiff comes to raising the question of injunctive and declaratory relief is the prayer in the conclusion of his appellate brief that the trial court "order the defendants to answer the second amended complaint and grant plaintiff any further relief the Court deems just and proper under the circumstances of this case." This kind of omnium gatherum might be said to raise all of the issues arising from the complaint, including injunctive and declaratory relief. But the isolated and oblique reference to the complaint does not suffice to revive what is not discussed in the brief. And in any event this Court is not required to undertake a search for error where it is not adequately briefed or supported by the arguments. Tallarico v. Brett, 137 Vt. 52, 61, 400 A.2d 959, 965 (1979).
[8] Article 4 states: "Every person within this state ought to find a certain remedy, by having recourse to the laws, for all injuries or wrongs which he may receive in his person, property or character...."
| 2023-10-03T01:26:29.851802 | https://example.com/article/1808 |
357 S.W.2d 160 (1962)
GRAYSON COUNTY STATE BANK, Appellant,
v.
Robert S. CALVERT et al., Appellees.
No. 10953.
Court of Civil Appeals of Texas, Austin.
April 18, 1962.
Rehearing Denied May 9, 1962.
*161 Brown & Brown, Sherman, for appellant.
Will Wilson, Atty. Gen., Bob E. Shannon, Asst. Atty. Gen., Austin, for appellee.
ARCHER, Chief Justice.
The appellant, Grayson County State Bank, is incorporated under the laws of Texas, and is located at Sherman, Texas. Its principal competitor is a National bank, The Merchants & Planters National Bank of Sherman, incorporated and regulated by the National Bank Act, 12 United States Code, § 21 et seq., 12 U.S.C.A. § 21 et seq.
The State of Texas by virtue of Chapter 12, Title 122A, Revised Civil Statutes of Texas V.A.T.S. places a franchise tax with specified exceptions on every domestic and foreign corporation chartered or authorized to do business in Texas. The appellant paid $2,579.45, its 1961 franchise taxes, and pursuant to Article 7057b, Vernon's Civil Statutes, it filed a written protest, in which it was contended that said tax was unconstitutional as a violation of Article I, Section 8, Constitution of Texas, Vernon's Ann.St. and a violation of the Constitution of the United States which requires that taxes be equal and uniform.
The appellant then filed a lawsuit in the 53rd District Court of Travis County in which it sought to recover the taxes paid under protest. On July 27, 1961, the Court held Chapter 12, Title 122A, V.A.C.S., to be constitutional and found, among other things, that the franchise tax is levied on all State banking institutions chartered and doing business under the laws of Texas, but that it is not levied on National banks chartered under the provisions of the National Bank Act, and which are conducting a banking business in Texas. The Court also found that 12 U.S.C. § 548, 12 U.S.C.A. § 548, permits State legislation to tax National Banks by: (1) taxing the shares of National banks, or (2) including dividends derived therefrom in the taxable income thereof, or (3) taxing associations on their net income, or (4) according to or measured by the net income under certain conditions. The Court also found that the tax levied under Chapter 12, Title 122A, V.A. C.S., is not levied upon any one of the bases enumerated in Title 12 U.S.C. § 548, 12 U. S.C.A. § 548.
Appellant asserts that the main question in the appeal is the correctness of the Court's conclusion of law No. 2, reading:
"That the failure of the Legislatures of the State of Texas to enact laws providing for the levy of franchise taxes upon state banking associations in the manner consented to by the Congress of the United States for the taxation of national banking associations located within the State of Texas does not constitute such discrimination as to violate the provisions of either Article VIII, Section 1 of the Constitution of Texas, or the `equal protection' clause of the Fourteenth Amendment to the Constitution of the United States, or any other provision of either the Constitution of the United States or the State of Texas."
Appellant concludes that the present tax setup is unconstitutional, since the conclusion of the Court must stand on one of two propositions: (1) assuming that there is discrimination resulting in substantial damage, still the Legislature has no duty to avail itself of the options for equalization available under the Federal statute, or (2) no discrimination results from the present tax legislation.
We do not believe that the Trial Court erred in holding that Chapter 12, Title 122A, V.A.C.S., is constitutional and did not violate Article VIII, Section 1, of the Texas Constitution and the Fourteenth Amendment *162 of the United States Constitution, but do believe the statute to be constitutional.
The appellant is a bank, created by the State of Texas, which has paid the franchise tax levied and attacks that tax as being unconstitutional in that it is not levied on National banks created by and regulated by Federal law.
The several States do not have power to tax National banks except as expressly permitted by Congress. First National Bank of Guthrie Center v. Anderson, 269 U.S. 341, 46 S.Ct. 135, 70 L.Ed. 295. The States may tax National banks under any of four alternative methods as prescribed by 12 U.S.C. § 548, 12 U.S.C.A. § 548.
The present franchise tax law is not based on any of the four alternative methods.
The franchise tax as levied is a charge made by the State against a State bank for the privilege granted it of doing business in the State and not on the property or income of the bank, though both are to be regarded in measuring such tax. Houston Oil Co. of Texas v. Lawson, Tex.Civ.App., 175 S.W.2d 716, error ref.
There is no discrimination involved under the decision of Union Bank & Trust Co. v. Phelps, 288 U.S. 181, 53 S.Ct. 321, 77 L.Ed. 687, in which the Court held that the several States lack power to tax National bank shares except as expressly permitted by Congress, and fully discussed the doctrine of such taxation. This holding has been accepted and approved by a number of State Supreme Courts and Federal Courts, among the last of which is the Bank of America National Trust and Savings Association v. Lima, 103 F.Supp. 916 (D.C.Mass.1952).
In Druesdow v. Baker, Tex.Com.App., 229 S.W. 493, judgment adopted by the Supreme Court, it was held:
"The Constitution simply guarantees uniformity and equality of taxation. It does not purport to deal with the mode or manner of accomplishing this purpose, but its mandate has been satisfied when uniformity and equality of taxation has been attained."
The equal protection clause of the Fourteenth Amendment of the United States Constitution and the equal and uniformity requirements of the Texas Constitution upon the taxing powers of the State are substantially similar. Hurt v. Cooper, 130 Tex. 433, 110 S.W.2d 896.
The Constitution requires that tax legislation may classify persons and items for purposes of taxation and are satisfied when such legislation meets two tests: (1) Is the Classification of the tax reasonable? and (2) Within the Class, does the legislation operate equally?
The class created by Chapter 12, Title 122A, V.A.C.S., is composed of all domestic and foreign corporations chartered or authorized to do business in Texas and there is no complaint of inequality within the classification by appellant, but the complaint is that National banks are not taxed by the statute. National banks and State banks are not in the same class; both are banks with differences. A State may not tax National banks without consent of Congress. Owensboro National Bank v. Owensboro, 173 U.S. 664, 668, 19 S.Ct. 537, 43 L.Ed. 850.
A National bank is an agency of the Federal Government and may enter and do business in a State without the State's permission, and a State cannot exact a charge for its doing business there.
The judgment of the Trial Court is affirmed.
Affirmed.
RICHARDS, J., not sitting.
HUGHES, Justice (concurring).
Appellant is a state bank. Its principal competitor is a national bank.
*163 Appellant and its competitor each paid similar ad valorem taxes on real estate and ad valorem taxes based on actual value of its capital stock less the realty ad valorem taxes.
In addition, appellant paid $2,579.45 franchise taxes to the State. Its competitor, the national bank, had it been similarly taxed would have paid the State $6,000.00.
Both appellant and its competitor are in the banking business. It is obvious that appellant competes with the national bank under a severe handicap. The Legislature has the power to rectify the disadvantage under which state banks compete with national banks. The Courts do not have such power. I write this opinion merely to point up the existing inequitable condition.
I concur in the affirmance.
| 2024-03-11T01:26:29.851802 | https://example.com/article/8265 |
Charles Coster
Charles Robert Coster (c. 1837 – December 23, 1888) was an American soldier and public official, who is best known for commanding a brigade at the Battle of Gettysburg.
Early life
Coster was born in New York City, New York. He was the son of John H. Coster and Sarah Adeline (née Boardman) Coster, He was also a first cousin of New York clubman, Harry Coster. His father, better known as a playboy before a businessman, was one of twelve children that married into many prominent families.
His grandfather, John Gerard Coster, came from Haarlem in the Netherlands to the United States shortly after the Revolutionary War and founded the family fortune through the mercantile firm, "Henry A. & John G. Coster".
Military career
On April 17, 1861, just five days after the firing on Fort Sumter, he enlisted as a private in the 7th New York Militia, one of the first regiments to come to the defense of Washington, D.C. at the outbreak of the Civil War. He later enlisted in 1861 at age 24 as a first lieutenant in 12th U.S. Infantry. He served in Brig. Gen. George Sykes's division of V Corps in the Seven Days Battles, being commended by his superiors for his conduct at the Battle of Gaines' Mill on June 27, 1862.
On October 8, 1862, Coster was named colonel of the recently organized 134th New York Volunteer Infantry. By December 31, 1862, the regiment belonged to Col. Orland Smith's 2nd Brigade of Maj. Gen. Adolph von Steinwehr's 2nd Division, XI Corps, Army of the Potomac. Coster's regiment participated in the Battle of Chancellorsville under Brig. Gen. Francis C. Barlow, who had been appointed brigade commander in place of Smith. During May 1863, Coster's regiment joined the 1st Brigade, 2nd Division, under Col. Adolphus Buschbeck. When Buschbeck went on leave on June 10, Coster became brigade commander. In that role he patrolled near Boonsboro, Maryland before marching to Gettysburg, Pennsylvania.
Gettysburg
Maj. Gen. Oliver Otis Howard kept von Steinwehr's division in reserve on the first day of the Battle of Gettysburg, July 1, 1863, positioning it on Cemetery Hill. When the Union right flank north of town began to collapse, Howard permitted von Steinwehr to send Coster's brigade to cover its retreat. These Union troops took a position just north of the town, where they were deployed in a brickyard. The brigade was attacked by superior forces from the Confederate division of Maj. Gen. Jubal Early. Coster's brigade lost most of its 597 casualties in that action. The remainder of the brigade spent the next two days supporting batteries on Cemetery Hill. Howard commended Coster and other senior commanders by name for their courage and devotion to duty in his report on Gettysburg.
After Gettysburg
Later in 1863, Coster resigned his regimental command. On May 18, 1864, he was appointed a provost marshal for the State of New York to serve the Board of Enrollment. Coster resigned that position on April 30, 1865. Thereafter he lived in New York City. On February 28, 1882, he became a federal Pension Agent for the city, resigning effective December 1, 1885. He was also a member of the Grand Army of the Republic.
Personal life
In 1864, Coster was married to Marie Bay James (1841–1904), Marie was the daughter of Augustus J. James of Albany, and the niece of theologian Henry James Sr., which made Marie a first cousin of author Henry James, psychologist William James, and diarist Alice James. Together, Marie and Charles were the parents of four children, including:
William Bay Coster (1867-1918), a banker.
Coster died in New York City on December 23, 1888. He was buried on December 26, 1888.
Memorials
Coster Avenue, part of the Gettysburg Battlefield but within the town itself, has a brigade marker and three regimental monuments. A mural painting on the wall of a neighboring building commemorates the Confederate attack and Coster's defense.
References
External links
Category:1837 births
Category:1888 deaths
Category:Union Army colonels
Category:People of New York (state) in the American Civil War
Category:Year of birth unknown | 2023-09-13T01:26:29.851802 | https://example.com/article/2590 |
#!/usr/bin/env python3
from __future__ import print_function
import os
import re
import sys
from datetime import datetime
from math import ceil
from mtools.util.input_source import InputSource
from mtools.util.logevent import LogEvent
class LogFile(InputSource):
"""Log file wrapper class. Handles open file streams or stdin."""
def __init__(self, filehandle):
"""Provide logfile as open file stream or stdin."""
self.filehandle = filehandle
self.name = filehandle.name
self.from_stdin = filehandle.name == "<stdin>"
self._bounds_calculated = False
self._start = None
self._end = None
self._filesize = None
self._num_lines = None
self._restarts = None
self._binary = None
self._timezone = None
self._hostname = None
self._port = None
self._rs_state = None
self._repl_set = None
self._repl_set_members = None
self._repl_set_version = None
self._repl_set_protocol = None
self._storage_engine = None
self._datetime_format = None
self._year_rollover = None
self._shards = None
self._csrs = None
self._chunks_moved_from = None
self._chunks_moved_to = None
self._chunk_splits = None
# Track previous file position for loop detection in _find_curr_line()
self.prev_pos = None
self._has_level = None
# make sure bounds are calculated before starting to iterate,
# including potential year rollovers
self._calculate_bounds()
@property
def start(self):
"""
Lazy evaluation of start and end of logfile.
Returns None for stdin input currently.
"""
if not self._start:
self._calculate_bounds()
return self._start
@property
def end(self):
"""
Lazy evaluation of start and end of logfile.
Returns None for stdin input currently.
"""
if not self._end:
self._calculate_bounds()
return self._end
@property
def timezone(self):
"""Lazy evaluation of timezone of logfile."""
if not self._timezone:
self._calculate_bounds()
return self._timezone
@property
def filesize(self):
"""
Lazy evaluation of start and end of logfile.
Returns None for stdin input currently.
"""
if self.from_stdin:
return None
if not self._filesize:
self._calculate_bounds()
return self._filesize
@property
def datetime_format(self):
"""Lazy evaluation of the datetime format."""
if not self._datetime_format:
self._calculate_bounds()
return self._datetime_format
@property
def has_level(self):
"""Lazy evaluation of the whether the logfile has any level lines."""
if self._has_level is None:
self._iterate_lines()
return self._has_level
@property
def year_rollover(self):
"""Lazy evaluation of the datetime format."""
if self._year_rollover is None:
self._calculate_bounds()
return self._year_rollover
@property
def num_lines(self):
"""
Lazy evaluation of the number of lines.
Returns None for stdin input currently.
"""
if self.from_stdin:
return None
if not self._num_lines:
self._iterate_lines()
return self._num_lines
@property
def restarts(self):
"""Lazy evaluation of all restarts."""
if not self._num_lines:
self._iterate_lines()
return self._restarts
@property
def rs_state(self):
"""Lazy evaluation of all restarts."""
if not self._num_lines:
self._iterate_lines()
return self._rs_state
@property
def binary(self):
"""Lazy evaluation of the binary name."""
if not self._num_lines:
self._iterate_lines()
return self._binary
@property
def hostname(self):
"""Lazy evaluation of the binary name."""
if not self._num_lines:
self._iterate_lines()
return self._hostname
@property
def port(self):
"""Lazy evaluation of the binary name."""
if not self._num_lines:
self._iterate_lines()
return self._port
@property
def versions(self):
"""Return all version changes."""
versions = []
for v, _ in self.restarts:
if len(versions) == 0 or v != versions[-1]:
versions.append(v)
return versions
@property
def repl_set(self):
"""Return the replSet (if available)."""
if not self._num_lines:
self._iterate_lines()
return self._repl_set
@property
def repl_set_members(self):
"""Return the replSet (if available)."""
if not self._num_lines:
self._iterate_lines()
return self._repl_set_members
@property
def repl_set_version(self):
"""Return the replSet (if available)."""
if not self._num_lines:
self._iterate_lines()
return self._repl_set_version
@property
def repl_set_protocol(self):
"""Return the replSet protocolVersion (if available)."""
if not self._num_lines:
self._iterate_lines()
return self._repl_set_protocol
@property
def storage_engine(self):
"""Return storage engine if available."""
if not self._num_lines:
self._iterate_lines()
return self._storage_engine
@property
def shards(self):
"""Lazily return the shards (if available)"""
if not self._shards:
self._find_sharding_info()
return self._shards
@property
def csrs(self):
"""Lazily return the CSRS (if available)"""
if not self._csrs:
self._find_sharding_info()
return self._csrs
@property
def chunks_moved_to(self):
"""Lazily return the chunks moved to this shard (if available)"""
if not self._chunks_moved_to:
self._find_sharding_info()
return self._chunks_moved_to
@property
def chunks_moved_from(self):
"""Lazily return the chunks moved from this shard (if available)"""
if not self._chunks_moved_from:
self._find_sharding_info()
return self._chunks_moved_from
@property
def chunk_splits(self):
"""Lazily return the chunks split in this shard (if available)"""
if not self._chunk_splits:
self._find_sharding_info()
return self._chunk_splits
def next(self):
"""Get next line, adjust for year rollover and hint datetime format."""
# use readline here because next() iterator uses internal readahead
# buffer so seek position is wrong
line = self.filehandle.readline()
if isinstance(line, bytes):
line = line.decode('utf-8', 'replace')
if line == '':
raise StopIteration
line = line.rstrip('\n')
le = LogEvent(line)
# hint format and nextpos from previous line
if self._datetime_format and self._datetime_nextpos is not None:
ret = le.set_datetime_hint(self._datetime_format,
self._datetime_nextpos,
self.year_rollover)
if not ret:
# logevent indicates timestamp format has changed,
# invalidate hint info
self._datetime_format = None
self._datetime_nextpos = None
elif le.datetime:
# gather new hint info from another logevent
self._datetime_format = le.datetime_format
self._datetime_nextpos = le._datetime_nextpos
return le
def __iter__(self):
"""
Iterate over LogFile object.
Return a LogEvent object for each line (generator).
"""
le = None
while True:
try:
le = self.next()
except StopIteration as e:
# end of log file, get end date
if not self.end and self.from_stdin:
if le and le.datetime:
self._end = le.datetime
# future iterations start from the beginning
if not self.from_stdin:
self.filehandle.seek(0)
# return (instead of raising StopIteration exception) per PEP 479
return
# get start date for stdin input
if not self.start and self.from_stdin:
if le and le.datetime:
self._start = le.datetime
try:
yield le
except StopIteration:
return
states = (['PRIMARY', 'SECONDARY', 'DOWN', 'STARTUP', 'STARTUP2',
'RECOVERING', 'ROLLBACK', 'ARBITER', 'UNKNOWN'])
def __len__(self):
"""Return the number of lines in a log file."""
return self.num_lines
def _iterate_lines(self):
"""Count number of lines (can be expensive)."""
self._num_lines = 0
self._restarts = []
self._rs_state = []
ln = 0
for ln, line in enumerate(self.filehandle):
if isinstance(line, bytes):
line = line.decode("utf-8", "replace")
if (self._has_level is None and
line[28:31].strip() in LogEvent.log_levels and
line[31:39].strip() in LogEvent.log_components):
self._has_level = True
# find version string (fast check to eliminate most lines)
if "version" in line[:100]:
logevent = LogEvent(line)
restart = self._check_for_restart(logevent)
if restart:
self._restarts.append((restart, logevent))
if "starting :" in line or "starting:" in line:
# look for hostname, port
match = re.search('port=(?P<port>\d+).*host=(?P<host>\S+)',
line)
if match:
self._hostname = match.group('host')
self._port = match.group('port')
""" For 3.0 the "[initandlisten] options:" long entry contained the
"engine" field if WiredTiger was the storage engine. There were
only two engines, MMAPv1 and WiredTiger
"""
if "[initandlisten] options:" in line:
match = re.search('replSet: "(?P<replSet>\S+)"', line)
if match:
self._repl_set = match.group('replSet')
match = re.search('engine: "(?P<engine>\S+)"', line)
if match:
self._storage_engine = match.group('engine')
else:
self._storage_engine = 'mmapv1'
""" For 3.2 the "[initandlisten] options:" no longer contains the
"engine" field So now we have to look for the "[initandlisten]
wiredtiger_open config:" which was present in 3.0, but would
now tell us definitively that wiredTiger is being used
"""
if "[initandlisten] wiredtiger_open config:" in line:
self._storage_engine = 'wiredTiger'
if "command admin.$cmd command: { replSetInitiate:" in line:
match = re.search('{ _id: "(?P<replSet>\S+)", '
'members: (?P<replSetMembers>[^]]+ ])', line)
if match:
self._repl_set = match.group('replSet')
self._repl_set_members = match.group('replSetMembers')
# Replica set config logging in MongoDB 3.0+
new_config = ("New replica set config in use: ")
if new_config in line:
match = re.search('{ _id: "(?P<replSet>\S+)", '
'version: (?P<replSetVersion>\d+), ', line)
if match:
self._repl_set = match.group('replSet')
self._repl_set_version = match.group('replSetVersion')
match = re.search(', protocolVersion: (?P<replSetProtocol>\d+), ', line)
if match:
self._repl_set_protocol = match.group('replSetProtocol')
match = re.search('members: (?P<replSetMembers>[^]]+ ])', line)
if match:
self._repl_set_members = match.group('replSetMembers')
# if ("is now in state" in line and
# next(state for state in states if line.endswith(state))):
if "is now in state" in line:
tokens = line.split()
# 2.6
if tokens[1].endswith(']'):
pos = 4
else:
pos = 5
host = tokens[pos]
rs_state = tokens[-1]
state = (host, rs_state, LogEvent(line))
self._rs_state.append(state)
continue
if "[rsMgr] replSet" in line:
tokens = line.split()
if self._hostname:
host = self._hostname + ':' + self._port
else:
host = os.path.basename(self.name)
host += ' (self)'
if tokens[-1] in self.states:
rs_state = tokens[-1]
else:
# 2.6
if tokens[1].endswith(']'):
pos = 2
else:
pos = 6
rs_state = ' '.join(tokens[pos:])
state = (host, rs_state, LogEvent(line))
self._rs_state.append(state)
continue
self._num_lines = ln + 1
# reset logfile
self.filehandle.seek(0)
def _check_for_restart(self, logevent):
if (logevent.thread == 'initandlisten' and
"db version v" in logevent.line_str):
self._binary = 'mongod'
elif logevent.thread == 'mongosMain' and ('MongoS' in logevent.line_str or
'mongos' in logevent.line_str):
self._binary = 'mongos'
else:
return False
version = re.search(r'(\d\.\d\.\d+)', logevent.line_str)
if version:
version = version.group(1)
return version
else:
return False
def _calculate_bounds(self):
"""Calculate beginning and end of logfile."""
if self._bounds_calculated:
# Assume no need to recalc bounds for lifetime of a Logfile object
return
if self.from_stdin:
return False
# we should be able to find a valid log line within max_start_lines
max_start_lines = 10
lines_checked = 0
# get start datetime
for line in self.filehandle:
logevent = LogEvent(line)
lines_checked += 1
if logevent.datetime:
self._start = logevent.datetime
self._timezone = logevent.datetime.tzinfo
self._datetime_format = logevent.datetime_format
self._datetime_nextpos = logevent._datetime_nextpos
break
if lines_checked > max_start_lines:
break
# sanity check before attempting to find end date
if (self._start is None):
raise SystemExit("Error: <%s> does not appear to be a supported "
"MongoDB log file format" % self.filehandle.name)
# get end datetime (lines are at most 10k,
# go back 30k at most to make sure we catch one)
self.filehandle.seek(0, 2)
self._filesize = self.filehandle.tell()
self.filehandle.seek(-min(self._filesize, 30000), 2)
for line in reversed(self.filehandle.readlines()):
logevent = LogEvent(line)
if logevent.datetime:
self._end = logevent.datetime
break
# if there was a roll-over, subtract 1 year from start time
if self._end < self._start:
self._start = self._start.replace(year=self._start.year - 1)
self._year_rollover = self._end
else:
self._year_rollover = False
# reset logfile
self.filehandle.seek(0)
self._bounds_calculated = True
return True
def _find_curr_line(self, prev=False):
"""
Internal helper function.
Find the current (or previous if prev=True) line in a log file based on
the current seek position.
"""
curr_pos = self.filehandle.tell()
# jump back 15k characters (at most) and find last newline char
jump_back = min(self.filehandle.tell(), 15000)
self.filehandle.seek(-jump_back, 1)
buff = self.filehandle.read(jump_back)
self.filehandle.seek(curr_pos, 0)
if prev and self.prev_pos is not None and self.prev_pos == curr_pos:
# Number of characters to show before/after the log offset
error_context = 300
self.filehandle.seek(-error_context, 1)
buff = self.filehandle.read(curr_pos)
hr = "-" * 60
print("Fatal log parsing loop detected trying to find previous "
"log line near offset %s in %s:\n\n%s\n%s\n"
"<--- (current log parsing offset) \n%s\n%s\n"
% (curr_pos, self.name, hr, buff[:error_context],
buff[error_context:error_context + 1], hr),
file=sys.stderr)
raise SystemExit("Cannot parse %s with requested options"
% self.filehandle.name)
else:
self.prev_pos = curr_pos
if isinstance(buff, bytes):
buff = buff.decode("utf-8", "replace")
newline_pos = buff.rfind('\n')
if prev:
newline_pos = buff[:newline_pos].rfind('\n')
# move back to last newline char
if newline_pos == -1:
self.filehandle.seek(0)
return self.next()
self.filehandle.seek(newline_pos - jump_back + 1, 1)
# roll forward until we found a line with a datetime
try:
logevent = self.next()
while not logevent.datetime:
logevent = self.next()
return logevent
except StopIteration:
# reached end of file
return None
def _find_sharding_info(self):
"""
Iterate over file and find any sharding related information
"""
self._shards = []
self._chunks_moved_from = []
self._chunks_moved_to = []
self._chunk_splits = []
prev_line = ""
for line in self.filehandle:
if isinstance(line, bytes):
line = line.decode("utf-8", "replace")
if self.binary == "mongos":
if "Starting new replica set monitor for" in line:
if "[mongosMain]" in line:
match = re.search("for (?P<csrsName>\w+)/"
"(?P<replSetMembers>\S+)", line)
if match:
csrs_info = (match.group('csrsName'),
match.group('replSetMembers'))
self._csrs = csrs_info
else:
match = re.search("for (?P<shardName>\w+)/"
"(?P<replSetMembers>\S+)", line)
if match:
shard_info = (match.group('shardName'),
match.group('replSetMembers'))
self._shards.append(shard_info)
elif self.binary == "mongod":
logevent = LogEvent(line)
if "New replica set config in use" in line:
if "configsvr: true" in line:
match = re.search(' _id: "(?P<replSet>\S+)".*'
'members: (?P<replSetMembers>[^]]+ ])', line)
if match:
self._csrs = (
match.group('replSet'),
match.group('replSetMembers')
)
if "Starting new replica set monitor for" in line:
match = re.search("for (?P<replSet>\w+)/"
"(?P<replSetMembers>\S+)", line)
if match:
if self._csrs and match.group('replSet') != self._csrs[0]:
self._shards.append((
match.group('replSet'),
match.group('replSetMembers')
))
elif not self._csrs:
self._csrs = (
match.group('replSet'),
match.group('replSetMembers')
)
if "moveChunk.from" in line:
logevent = LogEvent(line)
match = re.search('ns: "(?P<namespace>\S+)".*'
'details: { (?P<range>.*\}).*'
'to: "(?P<movedTo>\S+)".*note: "(?P<note>\S+)"', line)
if match:
time = logevent.datetime
chunk_range = match.group('range')
namespace = match.group('namespace')
moved_to = match.group('movedTo')
note = match.group('note')
if note == "success":
errmsg = None
steps = re.findall('(?P<steps>step \d of \d): (?P<stepTimes>\d+)', line)
else:
match = re.search(':: caused by :: (?P<errmsg>\S+):', prev_line)
steps = None
if match:
errmsg = match.group('errmsg')
else:
errmsg = "Unknown"
chunk_migration = (time, chunk_range, moved_to, namespace, steps, note, errmsg)
self._chunks_moved_from.append(chunk_migration)
if "moveChunk.to" in line:
logevent = LogEvent(line)
match = re.search('ns: "(?P<namespace>\S+)".*'
'details: { (?P<range>.*\}).*.*note: "(?P<note>\S+)"', line)
if match:
time = logevent.datetime
chunk_range = match.group('range')
namespace = match.group('namespace')
# TODO: alter this to find moved from shard name when SERVER-45770 TICKET is added
moved_from = "Unknown"
note = match.group('note')
if note == "success":
errmsg = None
steps = re.findall('(?P<steps>step \d of \d): (?P<stepTimes>\d+)', line)
else:
steps = None
match = re.search('errmsg: "(?P<errmsg>.*)"', line)
if match:
errmsg = match.group('errmsg')
chunk_migration = (time, chunk_range, moved_from, namespace, steps, note, errmsg)
self._chunks_moved_to.append(chunk_migration)
if "Finding the split vector for" in line:
logevent = LogEvent(line)
match = re.search('for (?P<namespace>\S+).*'
'numSplits: (?P<numSplits>\d+)', line)
if match:
time = logevent.datetime
split_range = None
namespace = match.group("namespace")
numSplits = match.group('numSplits')
success = None
time_taken = 0
error = None
self._chunk_splits.append((time, split_range, namespace, numSplits, success, time_taken, error))
elif "splitVector" in line:
logevent = LogEvent(line)
match = re.search('splitVector: "(?P<namespace>\S+)".*,'
' (?P<range>min:.*), max.*op_msg (?P<time_taken>\d+)', line)
if match:
time = logevent.datetime
split_range = match.group("range")
namespace = match.group("namespace")
time_taken = match.group("time_taken")
numSplits = 0
success = True
error = None
self._chunk_splits.append((time, split_range, namespace, numSplits, success, time_taken, error))
elif "Unable to auto-split chunk" in line:
logevent = LogEvent(line)
match = re.search("chunk \[(?P<range>.*)\) "
'in namespace (?P<namespace>\S+)'
' :: caused by :: (?P<error>\S+): ', line)
if match:
time = logevent.datetime
split_range = match.group("range")
namespace = match.group("namespace")
numSplits = 0
success = False
time_taken = 0
error = match.group("error")
self._chunk_splits.append((time, split_range, namespace, numSplits, success, time_taken, error))
elif "jumbo" in line:
logevent = LogEvent(line)
match = re.search('migration (?P<namespace>\S+): \[(?P<range>.*)\)', prev_line)
if match:
time = logevent.datetime
split_range = match.group("range")
namespace = match.group("namespace")
numSplits = 0
success = False
time_taken = 0
error = "Jumbo"
self._chunk_splits.append((time, split_range, namespace, numSplits, success, time_taken, error))
prev_line = line
# reset logfile
self.filehandle.seek(0)
def fast_forward(self, start_dt):
"""
Fast-forward file to given start_dt datetime obj using binary search.
Only fast for files. Streams need to be forwarded manually, and it will
miss the first line that would otherwise match (as it consumes the log
line).
"""
if self.from_stdin:
# skip lines until start_dt is reached
return
else:
# fast bisection path
max_mark = self.filesize
step_size = max_mark
# check if start_dt is already smaller than first datetime
self.filehandle.seek(0)
le = self.next()
if le.datetime and le.datetime >= start_dt:
self.filehandle.seek(0)
return
le = None
self.filehandle.seek(0)
# search for lower bound
while abs(step_size) > 100:
step_size = ceil(step_size / 2.)
self.filehandle.seek(step_size, 1)
le = self._find_curr_line()
if not le:
break
if le.datetime >= start_dt:
step_size = -abs(step_size)
else:
step_size = abs(step_size)
if not le:
return
# now walk backwards until we found a truly smaller line
while self.filehandle.tell() >= 2 and (le.datetime is None or
le.datetime >= start_dt):
self.filehandle.seek(-2, 1)
le = self._find_curr_line(prev=True)
| 2024-07-16T01:26:29.851802 | https://example.com/article/6323 |
Condition
=========
.. currentmodule:: oci.cloud_guard.models
.. autoclass:: Condition
:show-inheritance:
:special-members: __init__
:members:
:undoc-members:
:inherited-members: | 2024-02-21T01:26:29.851802 | https://example.com/article/3111 |
Q:
Why do Chrome and Firefox handle javascript variable set inside jQuery ajax() callback differently?
Using jQuery 1.9.1, calling back to the server to check some data:
$form = $("#form2")
var str = $form.serialize();
status = true;
$.ajax({
type : 'POST',
url : 'check_zip.php',
data : str,
async : false,
success : function (data) {
obj = JSON.parse(data);
var result = obj.result;
status = result;
},
error : function (msg) {
alert(msg);
status = false;
}
});
if (status == "false" || status === false) {
....
I found that Chrome would return status "false" (string) and Firefox would return status false (boolean). Is this expected behavior? I was astonished!
The JSON being parsed is data: "{"result":false}"
typeof(status) is string in Chrome and boolean in FF.
The issue seems to arise here:
var result = obj.result;
status = result;
Because the datatype of result in Chrome is boolean, whereas the datatype of status is string.
A:
Got it. The issue was the missing "var" before the declaration of status.
As @bfavaretto noted below, status is already defined as a global variable. So if I had used a variable named like "ajax_status" I would have been fine without the var or I could have used the "status" variable name, but would have had to make it local (using var).
The following code works like a champ in both FF and Chrome.
$form = $("#form2")
var str = $form.serialize();
var status = true; // <--- change 1 - use "var"
$.ajax({
type : 'POST',
url : 'check_zip.php',
data : str,
async : false,
success : function (data) {
obj = JSON.parse(data);
var result = obj.result;
status = result;
},
error : function (msg) {
alert(msg);
status = false;
}
});
if (status === false) { // <-- change 2 - just use boolean comparison
...
Another way to code this would be
var ajaxreturn = $.ajax({
type : 'POST',
url : 'check_zip.php',
data : str,
async : false,
success : function (data) {
},
error : function (msg) {
alert("Unexpected server response on zip validation");
}
});
var status = false;
try {
obj = JSON.parse(ajaxreturn.responseText);
status = obj.result;
} catch (e) {
status = false;
}
if (status === false) {
...
and probably the best practice would be not to reuse the existing variable name status, so using the second example, this would give
var ajaxreturn = $.ajax({
type : 'POST',
url : 'check_zip.php',
data : str,
async : false,
success : function (data) {
},
error : function (msg) {
alert("Unexpected server response on zip validation");
}
});
var check_status = false;
try {
obj = JSON.parse(ajaxreturn.responseText);
check_status = obj.result;
} catch (e) {
check_status = false;
}
if (check_status === false) {
...
| 2024-06-27T01:26:29.851802 | https://example.com/article/5867 |
"Even though they're missing their hand, (amputees) still have muscle activity from their forearm usually," said Akhtar, who has a PhD in neuroscience as well as a master's degree in electrical and computer engineering, both from U. of I. "If they were trying to make a pinch versus a fist, they'll have different muscle activity going on, and that's enough for us to decipher what they would have wanted to do if their hand was actually there." | 2024-03-04T01:26:29.851802 | https://example.com/article/9206 |
What Takes place After the Lasik Treatment?
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What Takes place After the Lasik Treatment?
After you are totally prepared, the Lasik treatment takes less compared to fifteen minutes to finish for both eyes. This will appear an incredibly brief time to have a long-term change to your vision, and also here Lasik appears nearly too great to be real. Furthermore, most Lasik patients observe improved vision promptly or within a couple of hours after the Lasik treatment has actually been carried out.
This does not suggest that you ought to anticipate to leave of the Lasik clinic with twenty-twenty and also without any have to treat your eyes meticulously for the next a number of days. It additionally means that some Lasik individuals will certainly require more time to see the total results for the Lasik procedure, occasionally as high as six months for their vision to stabilize permanently. Expect excellent vision, and also take the time and take care of the operation to produce its best result.
Generally the Lasik medical professional will offer the post-procedure individual a protective shield for their eyes. He could additionally suggest sunglasses throughout the day if you experience level of sensitivity to light after the Lasik procedure is done.
Lots of clients at the Lasik facilities often obtain eye goes down to keep their eyes moist for a long time after the Lasik procedure is done. Once again, this varies by person as well as by physician, so inquire about your specific scenario, particularly if you are prone to eye dryness on a periodic basis even prior to the Lasik treatment. It might be practical to keep any ceiling fans or other air circulation gadgets off in the family for the initial few days.
A lot of customers could return to work as well as regular day-to-day activities the day after the Lasik procedure is done, and do not need any kind of added assistance from other friends or family participants. Upon waking, boosted vision from the Lasik corrections should currently start to be noticeable.
This boosted vision might not be the end product of the Lasik treatment. The enhancement to nearsightedness after Lasik is normally fast and remarkable, though there might be some troubles in checking out conveniently for the very first couple of days after the Lasik procedure. This is flawlessly normal, and also should clear up prior to the week is out.
Individuals that utilize Lasik to boost their farsightedness normally find a significant improvement the day after the Lasik surgery. It could be that there is a short-term obscuring of objects in the distance, yet this will fix itself. The Lasik physician could advise and also recommend temporary glasses up until vision is maintained if this Full Report problem remains for more compared to a couple of days.
These are all typical post-operative suggests for a Lasik person, in i was reading this order to feel comfortable with exactly what to anticipate after the Lasik treatment. Similar to any medical treatment, get all your concerns addressed by the team of your Lasik center for your individual case.
In addition, most Lasik clients observe boosted vision right away or within a few hours after the Lasik procedure has been carried out.
It likewise implies that some Lasik clients will need even more time to see the complete outcomes for the Lasik procedure, occasionally as much as 6 months for their vision to support permanently. Numerous clients at the Lasik centers frequently get eye goes down to maintain their eyes moist for some time after the Lasik procedure is done. Clients that utilize Lasik to improve their farsightedness usually locate a significant enhancement the day after the Lasik surgical treatment. | 2023-10-18T01:26:29.851802 | https://example.com/article/6367 |
Cartesian bicategories II
A. Carboni, G.M. Kelly, R.F.C. Walters, and R.J. Wood
The notion of cartesian bicategory, introduced by
Carboni and Walters for locally ordered bicategories, is extended
to general bicategories. It is shown that a cartesian bicategory
is a symmetric monoidal bicategory. | 2024-05-08T01:26:29.851802 | https://example.com/article/3083 |
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ECLIPSE Blackoil Reservoir Simulation
4.6
Average client rating (based on 1043 attendee reviews)
The ECLIPSE industry-reference Blackoil simulator offers the most complete and robust set of numerical solutions for fast and accurate prediction of dynamic behavior—for all types of reservoirs and degrees of complexity, structure, geology, fluids, and development schemes. ECLIPSE is a fully implicit, three-phase, 3D, general purpose black-oil simulator that includes several advanced and unique features. In this course, you will discover the various solutions ECLIPSE offers over the entire spectrum of reservoir simulation. This training focuses on understanding ECLIPSE syntax rather than simulation methodology.
Agenda
Topics
Instructors
Audience
Prerequisites
Agenda
Day 1
Module 1- Reservoir simulation overview
o What is reservoir simulation
o An introduction to ECLIPSE
o Interaction with ECLIPSE
Module 2 – Petrel RE as a postprocessor
Module 3 – RUNSPEC section
o RUNSPEC section setup
Start date of the simulation
Basic character of the model
Memory allocation
o RUNSPEC keywords
o SPECIAL topics including parallel processing
Day 2
Module 4- GRID/EDIT sections
o Grid types
o Grid cell property definition
o Local grid refinement
o Transmissibility calculations
Non-neighbor connections
Modeling of geological features such as Pinchouts and unconformities
Module 5 – PROPS section
o Introduction to PVT and the applications
Black oil vs. compositional simulation
o Fluid properties in ECLIPSE BlackOil
Single-phase simulations
Two-phase simulations
Three-phase simulations
Oil/Gas/Water Equations of State
PVT data entry using the relevant keywords
o Additional topics
EXTRAPMS keyword
Multiple PVT types using PVT regions
API tracking implementation: Multiple PVT types using API tracking
o Rock properties: Saturation functions
Rock compaction
Saturation function definition
Saturation endpoint terminology
Saturation families and their keywords
Implementation of endpoint scaling
Day 3
Module 6- REGIONS section
o REGIONS section setup
Reservoir division based on variations in reservoir characteristics
Reservoir division for report purposes
Module 7 – SOLUTION section
o Initialization by equilibration
o Restarts and enumeration
o Aquifer modeling facilities
Numerical aquifers
Fetkovich aquifers
Carter-Tracy aquifers
Flux aquifers
Grid cell aquifers
Day 4
Module 8 - SUMMARY section
o SUMMARY section setup
Types of output mnemonics that can be requested
Module 9 – SCHEDULE section
o SCHEDULE section modes and content
History matching versus prediction
o Well definition and connections to the grid
o VFP curve specification
o Historical well control specification
Day 5
Module 9 - SCHEDULE section
o Prediction well control specification
Transition from history matching to prediction
Economic limit definition
Automatic workovers
Restarts
o Recovery optimization strategies such as
Do nothing base case
Water injection scheme
Voidage replacement scheme
Gas re-injection strategy
Module 10 – Convergence
o Convergence issues and troubleshooting
Convergence reports
Speeding up ECLIPSE
Time stepping controls
Non-linear and linear iterations
Simulator control
Common causes of problems
Treatment of local grid refinements
Convergence checklist
Topics
Understand how a simulator initializes and executes
Define block-centered and corner-point grid geometry
Describe rock and fluid properties
Allocate initial pressure and saturation distribution
Define aquifers
Control wells under history matching and production regimes
Comprehend the ECLIPSE Blackoil file structure
Understand input rules
Specify and edit input and output data
Build and execute a simulation model
Analyze results through post-processing
Instructors
Kamshat Ussenova
Audience
Reservoir engineers, geoscientists, and other technically trained individuals introduced to reservoir engineering who are interested in learning reservoir simulation using ECLIPSE Blackoil simulator | 2023-11-18T01:26:29.851802 | https://example.com/article/6086 |
for d.
0
Let p be (3/1)/(-6 - 1457/(-243)). Let w = 729 + p. Let z be 30*(0 + 2/4). Solve -m + 4*m + z = w for m.
-5
Suppose 2*n = n, g = -n + 6. Suppose g*l - 5*l + 7 = 0. Let b = 9 + l. Solve m + m = -b for m.
-1
Let n(a) = -a**3 - 57*a**2 + 55*a + 112. Let p be n(-58). Solve -6*g - 292 + p = 0 for g.
-1
Let a = -10772 - -10853. Solve a*h - 127*h = -368 for h.
8
Let f(z) = z**3 - z. Let b = -123 + 123. Let r be f(b). Solve -3*v + 4*v = r for v.
0
Let j = -46 - -85. Let g = 44 - j. Suppose -7*x = 2*p - 3*x + 12, -p + g*x + 22 = 0. Solve -4*q = p + 2 for q.
-1
Suppose -3*s + 84 = -5*z + 14, 2*s - 2*z - 52 = 0. Suppose x - 2*i = -7*i - 2, 0 = 3*x - 3*i - s. Solve -6*c = -2*c - x for c.
2
Let s(l) = -l**3 - l**2 - 5*l - 20. Let p be s(-5). Let t = p - 101. Let b be 0/(2/(t - 6)). Solve -5*v + v = b for v.
0
Suppose -21*j + 914 = -745. Let i = j + -69. Solve 16 = 14*f - i*f for f.
4
Let d be 0/(-3) - (2 + -5 - 0). Suppose d*x = o + 34, 2*x + 2*o + 18 = 3*x. Solve 5*q - x*q - 10 = 0 for q.
-2
Let x(k) = k**3 - 2*k**2 - 34*k + 9. Let q be x(7). Solve 369*n - q = 365*n for n.
4
Let v be (62 + -81)/(-2 + 1). Solve 0 = -4*p - 27 + v for p.
-2
Let p(d) = -d**3 - 17*d**2 + 15*d - 12. Let f be p(-18). Suppose 8*v = 15*v - f. Suppose 2*h + 2 = 6. Solve h*k = -4 - v for k.
-5
Let h be 14/(-4) - 47/(-2). Solve -h*a + 21 = a for a.
1
Suppose -4*j + 3*j = 5, 4*m - 1494 = 2*j. Suppose 5*q = -4*w - 0*w + 310, 0 = 5*w - 2*q - m. Let x = w + -60. Solve -4*i = -i + x for i.
-5
Suppose v + 1 = -f - 7, -5*f - 5 = 0. Let q be ((7/2)/v)/(1/(-168)). Suppose 13*z - q = -6. Solve -z*g = -7*g for g.
0
Let m(a) = -4*a + 114. Let i be m(27). Suppose 268*y - 265*y = i. Solve -2*r - y = -4 for r.
1
Let d(u) = 6*u**2 - 25*u - 119. Let t be d(7). Solve -8*l - 64 + 96 = t for l.
4
Suppose 0 = -39*d + 40*d + 2*w + 2, -2*d = 2*w. Solve -d*b = 60 - 70 for b.
5
Let r be (-5 - (-117)/18 - 0)/((-6)/(-28)). Solve 0 = 5*h - r*h + 8 for h.
4
Let m(v) = v**2 + v. Let i(n) = 2*n**2. Let b(f) = -6*i(f) + 11*m(f). Let w be b(7). Solve -3*z + w = 13 for z.
5
Let a = 498 + -466. Solve -13*l = -a - 59 for l.
7
Suppose 3*d = p + 5, 4*p = 6*p + 4*d - 20. Suppose 4*l = 2*l - 2*w - 4, 4*w + 23 = l. Suppose -5*q = 5*t + 15, -l*t + 0*t + 4*q = -12. Solve -p + t = h for h.
-4
Suppose 0*g + g = 3*u - 89, -3*g = u - 13. Let b be (-14)/u*(0 - 2). Solve -t + 4 = -b for t.
5
Suppose -7*c = -20*c + c. Solve 9*w = -c + 27 for w.
3
Suppose 0 = 4*v + 6*b - b + 3, 15 = 3*v - 2*b. Let z(k) = -k**3 - 18*k**2 + 175*k. Suppose r - 17 + 42 = 0. Let f be z(r). Solve f = -q + v for q.
3
Let y be 8160/(-85) - (-1746)/18. Let z = 1 - 1. Suppose 6*w - 4*w = z. Solve w = -d - y for d.
-1
Let s be 5 + (54 + -11 - -4). Solve -s*c - 32 = -44*c for c.
-4
Let c be 6*(1 - 2)*(-265)/318. Solve -c = 31*i + 57 for i.
-2
Suppose -358*l + 327*l = -27466. Solve -l*n = -881*n for n.
0
Let z = -257 + 277. Suppose z*d - 84 = -8*d. Solve d*a + 3 = 9 for a.
2
Let k = -770 + 817. Solve 4*p + 47 = k for p.
0
Let i(w) = -26*w. Let c be (9/(-6) + 2)*4. Let u be i(c). Let a be u/39*(-18)/8. Solve -a*k = 2*k for k.
0
Suppose -14*k + 5049 = -k + 14*k. Solve k - 135 = 13*g for g.
4
Let d = 2720 - 2718. Solve 17*p = -d*p - 38 for p.
-2
Let t be (-1)/2 + 91/(-26). Let k be (t/3)/((-12)/27). Solve 5 = -o + k for o.
-2
Suppose 0 = -42*f + 31*f + 55. Let j be (-4)/(-10) + 26/10. Suppose -f*d - j = p, -5*p - 3*d + 7 = -0*p. Solve 0 = -3*y + p + 4 for y.
2
Suppose -8 = 2*d - 2*m, 2 = -3*d + 4*m - 10. Suppose 0 = -0*b - b. Let v be (9 + d + -4)*b. Solve v*u = -5*u for u.
0
Let r(w) = -5*w**2 - w + 5. Let t(i) = -4*i**2 - i + 5. Let d(s) = 3*r(s) - 4*t(s). Let k be d(2). Solve -2 - k = -z for z.
3
Suppose 0 = 2*m - 5*p + 46, 5 = -m + 2*p - 20. Let f be (4/(-6))/(209/m - -6). Solve -1 - 7 = f*a for a.
-4
Suppose 18*y = 266 + 94. Suppose 2*q - 7*q + y = 0. Let k(h) = -h**3 + 6*h**2 - 4*h. Let a be k(5). Solve x + q = a for x.
1
Let i be 30/5*1 + -3. Suppose -163 = -2*s + 4*t + 23, -i*t + 68 = s. Let w = s + -80. Solve w*m + m = 8 for m.
2
Let b(m) = -6*m - 8. Let r be b(-2). Suppose 0 = o + 3, r*u - 6*o - 102 = -8*o. Solve -30 = -k - u for k.
3
Suppose -5*w + 27 = 2*u - 0, -w + 56 = 5*u. Solve -u*d = 88 - 0 for d.
-8
Let w(o) = o**3 + 2*o**2 - o - 2. Let r(v) = v**3 + 3*v**2 - 4*v + 2. Let z be r(-4). Let p be w(z). Let s be (-26)/(-4) - p/8. Solve -11 - 14 = s*c for c.
-5
Let u(f) = -5*f - 13. Suppose 0 = -2*w + 4*x - 0*x - 14, 4*w = x - 14. Let r be u(w). Let s be (2 - r)/(-1 - 0). Solve s = 7*q - 3*q - 12 for q.
3
Suppose 0 = w + 2*w + 4*g + 12, 2*w - 5*g = 15. Let h = 22010 + -21990. Solve -3*q - 2*q - h = w for q.
-4
Suppose w + 2*c - 68 = 0, 41 = -3*w + 5*c + 234. Suppose -68*o + 8 = -w*o. Solve t - o = -2 for t.
2
Let n be (2/14)/1 + (-1530)/(-315). Suppose p = -u + 6, -u - 21 = -n*p + 3. Suppose 5*j + 3*o = 31, p*j - 28 - 27 = 5*o. Solve 4 + j = 4*x for x.
3
Let s = 132 + -110. Solve -136 = -s*i - 26 for i.
5
Let x(y) = 5*y + 1 - 6 - 3*y - 8. Suppose 21 = -3*m + 6*m. Let d be x(m). Solve -3 - d = u for u.
-4
Let o be (10/(-12)*-3)/(35/112). Solve -20*f + o = -12*f for f.
1
Let l = 36 - 30. Suppose -10*d + 24 = -l*d. Suppose 15 = 3*b + 3*f, 0 = -2*b - 3*f + d + 9. Solve u + 4 + 1 = b for u.
-5
Suppose 443 - 3251 = -117*j. Solve j*g = 8 + 64 for g.
3
Let d(o) = 19*o**2 + o + 2. Let q(k) = 18*k**2 + 2. Let p(j) = -3*d(j) + 2*q(j). Let z be p(-1). Let g = -8 - z. Solve -5*y + g = -y for y.
3
Suppose -212*d = -15053 + 2757. Solve 13 - d = -9*k for k.
5
Suppose -3108*h + 1900 = -3008*h. Solve -11*r - h = -19 for r.
0
Let a = -21 + 126. Let w = 102 - a. Let u be 0*(15/(-5))/w. Solve u = -2*q + q for q.
0
Suppose -3*x + 2*x = 5, 0 = -2*c + 2*x + 22. Let m = -253 + 256. Suppose -m*w = c*w + 4*w. Solve w = -k + 4*k for k.
0
Suppose 0 = 3*u - 47 + 2. Let b be 5/(105/72) + u/(-35). Let d(w) = -w**3 - 6*w**2 - 2*w - 8. Let q be d(-6). Solve -b*t = 19 - q for t.
-5
Suppose -p + f = -18, f + 292 - 240 = 3*p. Solve -p*h - 32 = -33*h for h.
2
Let t = 40 - 32. Let m(y) = -y**3 - 10*y**2 + 9*y - 16. Let c be m(-11). Suppose -2*r + 0*b = -2*b + c, 2*r + 3 = b. Solve r*d = -4*d - t for d.
-2
Let m = 77 - 76. Let y be (25 - 11)/(m*2). Solve 2*a - 10 = y*a for a.
-2
Let i(v) = -v**3 - 4*v**2 + 5*v + 2. Let q be i(-5). Let t(f) = -10*f + 53. Let o be t(8). Let p be (-126)/o*(-12)/(-8). Solve -p*d + 5 = -q*d for d.
1
Let a be 8/2 + (1 - -3). Let y(q) = q**2 - 9*q + 8. Let i be y(a). Let z be (-3)/(-2 + -4)*i. Solve 2*h + 0*h + 2 = z for h.
-1
Suppose 5*y - 9*a - 1481 = -7*a, -3*y + a = -889. Suppose 0 = -40*r + 303 + y. Solve r = -10*w - 15 for w.
-3
Let w be -7 + 4 - (-1 - 4). Let h(l) be the first derivative of -l**3/3 + 15*l**2/2 + 36*l + 38. Let x be h(17). Solve 8 = -w*s - x*s for s.
-2
Let t = 116 - 10. Suppose 7*k - 169 = -t. Solve -k*g + 4*g - 15 = 0 for g.
-3
Let i be ((-12)/(-45)*57)/(40/100). Suppose -3*y - 2*q + 17 = 0, i*y - 39*y - q + 5 = 0. Solve -y = -6*z + 11 for z.
3
Let g(u) = -452*u**3 - 2*u**2 + 8*u + 9. Let y be g(-1). Let p = y - 446. Solve -p*t - 9 = -14*t for t.
1
Let g(d) = d**3 + 8*d**2 - 102*d - 319. Let z be g(-3). Solve 0 = -z*q - 75 + 11 for q.
-2
Suppose 14*t = 15*t - 3. Let o(h) = 3*h**2 - 30*h - 68. Let l be o(-2). Solve t*q = -q - l for q.
-1
Let k = 14639 - 14607. Solve -42 = 5*v - k for v.
-2
Let d = -257 - -261. Suppose -51*f + 53*f = d. Solve 4 = 2*o - f for o.
3
Let y(b) be the second derivative of -b**3/2 - 17*b**2 + 2*b. Suppose -5*j + o = 69, 3*o - 68 = 4*j - o. Let v be y(j). Solve s = v*s + 4 for s.
-1
Let m(x) be the first derivative of -3*x**4/2 + x**3/3 - 2*x + 36. Let h be m(-1). Solve -4 = -h*k + 1 for k.
1
Let h(c) = 5*c**2 + 8*c + 20. Let l be h(-5). Let r = l - 81. Let s = r - 23. Solve 2*f = s + 1 for f.
1
Suppose 16*l + 130 = 18*l. Let h = l - -42. Let a = h + -103. Solve 0 = 2*f - 0 + a for f.
-2
Let y(u) = 162 + 90 - 99 + 41*u + 93. Let d be y(-6). Solve 0*q + 5*q = d for q.
0
Let u be -9 - (-2 + -1 + 2). Let h be (-68)/24*-3 + 4/u. Solve h*m - 2 = 6*m for m.
1
Suppose 10*c - 7*c = 18. Suppose 2*d - c*d = 0. Solve d = 3*k - 1 + 13 for k.
-4
Suppose 3721 = 78*z - 1193. Solve 261*h + z = 268*h for h.
9
Let t(w) = 2*w + 8. Suppose -1 = a, -6*a - 27 = -5*h - 9*a. Let s be t(h). Let n = 21 - s. Solve -8 - n = -3*v for | 2023-12-17T01:26:29.851802 | https://example.com/article/6867 |
-- $ID$
-- TPC-H/TPC-R Global Sales Opportunity Query (Q22)
-- Functional Query Definition
-- Approved February 1998
select
cntrycode,
count(*) as numcust,
sum(c_acctbal) as totacctbal
from
(
select
substring(c_phone from 1 for 2) as cntrycode,
c_acctbal
from
customer
where
substring(c_phone from 1 for 2) in
('13', '31', '23', '29', '30', '18', '17')
and c_acctbal > (
select
avg(c_acctbal)
from
customer
where
c_acctbal > 0.00
and substring(c_phone from 1 for 2) in
('13', '31', '23', '29', '30', '18', '17')
)
and not exists (
select
*
from
orders
where
o_custkey = c_custkey
)
) as custsale
group by
cntrycode
order by
cntrycode;
| 2023-09-20T01:26:29.851802 | https://example.com/article/7275 |
server.port=8081
app.id=SampleApp
apollo.meta=http://localhost:8080
apollo.bootstrap.enabled=true
apollo.bootstrap.namespaces=application | 2023-08-23T01:26:29.851802 | https://example.com/article/1670 |
Q:
Rails 4 - setting associated foreign key value
I have a model called project and another called invite.
The associations are:
Project
has_many :invites
Invite
belongs_to :project
I want to allow users who create projects to send invites to other users to join them in working on the project.
I have a form to create invites as follows:
<%= simple_form_for(@invite, :url => invites_path) do |f| %>
<%= f.hidden_field :recipient_id, :value => get_recipient_id %>
<%#= f.hidden_field :project_id, :value => current_user.profile.project_id %>
<%= f.hidden_field :project_id, :value => @invite.project_id %>
<%= f.label :email %>
<%= f.email_field :email %>
<!-- This field should use :date_picker- but it isnt working -->
<%= f.input :expiry, :as => :date, :label => "When do you need a response to this invitation?" %>
<%#= f.input :expiry, :as => :date_picker, :label => "When do you need a response to this invitation?" %>
<%= f.submit 'Send', :class=>"formsubmit" %>
<% end %>
In the above form, I'm trying to set the project_id value.
In the invites controller, I have:
class InvitesController < ApplicationController
before_action :get_project
def index
@invites = @project.invites
end
def new
# @invite = Invite.new
@invite = @project.invites.build
end
def create
@invite = Invite.new(invite_params)
@invite.sender_id = current_user.profile.id
# @project = Project.find(params[:project_id])
if @invite.save
#send existing user email invitation to join project team
InviteMailer.existing_user_invite(@invite).deliver_later
format.html { redirect_to @project }
@invite.recipient.project.push(@invite.project)
else
@invite.recipient.project.push(@invite.project)
InviteMailer.new_user_invite(@invite, new_user_registration_path(:invite_token => @invite.token)).deliver
end
# oh no, creating an new invitation failed
end
private
# Use callbacks to share common setup or constraints between actions.
def set_invite
@invite = Invite.find(params[:id])
end
def get_project
@project = Project.find(params[:project_id])
end
# Never trust parameters from the scary internet, only allow the white list through.
def invite_params
params[:invite].permit(:email, :project_id, :recipient_id)
end
end
I thought the get_project before action would get the project. Instead, I get an error that says:
undefined method `project_id' for #<Profile:0x007fa179509b60>
Did you mean? project_ids
project_ids=
projects
object_id
The error message points to the hidden field in my form for project_id.
Can anyone see where I'm going wrong?
A:
The problem is with the statement current_user.profile.project_id in one of the hidden form fields.
(The error message points to this code but I don't know why you have commented that line in the post)
The error clearly says that a profile does not have a project_id and a user can have many projects. If you want to access the project_id, you can do something like this.
<%= f.hidden_field :project_id, value: @project.id %>
@project is accessible from the controller through the get_project method.
| 2023-12-29T01:26:29.851802 | https://example.com/article/9392 |
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Designed for easy on, easy off Chromebook 13 personalization that won't leave behind any residue | 2024-03-11T01:26:29.851802 | https://example.com/article/1884 |
U.N. Secretary General urges more aid for people of Mosul
New York, Unired States (Reuters): United Nations Secretary General Antonio Guterres on Friday called on the international community to increase aid to help people fleeing the Iraqi city of Mosul which government forces have been battling to retake from Islamic State.
Iraqi forces have seized back most of the country's second-largest city from the Sunni hardline group in a massive six-month campaign.
But at least 355,000 residents have fled fighting, according to the government, and some 400,000 civilians remain trapped inside the densely-populated Old City where street battles have raged for weeks.
"We don't have the resources necessary to support these people," Guterres told reporters during a visit to the Hassan Sham Camp, one of several centers outside Mosul packed with civilians escaping the fighting.
The U.N. and Iraqi authorities have been building more camps but struggle to accommodate new arrivals with two families sometimes having to share one tent.
"Unfortunately our program is only 8 percent funded," he said, referring to a 2017 U.N. humanitarian response program without giving additional details.
Iraqi forces have won back control of most cities that fell to the group and the militants have been dislodged from nearly three quarters of Mosul but remain in control of its center.
Government positions have reached as close as 500 meters to the al-Nuri Mosque, from where Islamic State leader Abu Bakr al-Baghdadi declared a caliphate spanning parts of Iraq and Syria in July 2014.
Baghdadi and other IS leaders are believed to have left the city but U.S. officials estimate around 2,000 fighters remain inside the city, resisting with snipers hiding among the population, car bombs and suicide trucks targeting Iraqi positions. | 2024-04-07T01:26:29.851802 | https://example.com/article/3748 |
Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety and colonic sensitivity.
Corticotropin releasing factor (CRF) is an important mediator in the stress response. Previous studies in rodent models demonstrated that stress-induced colonic hypersensitivity was inhibited by CRF1 receptor antagonism. As CRF(1)R-deficient mice have (+/+), CRF(1)R (+/-) and CRF(1)R (-/-) mice colonic sensitivity was assessed via a visceromotor behavioural response (VMR) induced by colorectal distension (CRD, 0-60 mmHg). In the CRF(1)R (+/+) mice there was a pressure-dependent increase in the VMR to CRD that was moderately attenuated in the CRF1R (+/-) mice. However in the CRF(1)R (-/-) mice a VMR to CRD was only observed at the highest distension pressure (60 mmHg). A CRF(1)R antagonist, NBI 30775 (30 mg kg(-1) i.p.) significantly decreased the VMR to CRD in CRF(1)R +/+ mice. An identical inhibitory effect of NBI 30775 was observed in 43% of the CRF(1)R +/- mice. This study provides pharmacological and genetic evidence for the importance of CRF(1)R in colonic sensitivity and suggests a link between stress and visceral perception. | 2024-07-16T01:26:29.851802 | https://example.com/article/1481 |
With subtlety & skill, Sean Bean stars in 'Legends'
TONIGHT'S MUST-SEE: "Legends," 9 p.m., TNT. Big and booming, Sean Bean often plays epic figures. He's been Zeus and Odysseus; he's been killed in "Game of Thrones," "Lord of the Rings," "Henry VIII" and more. So viewers might be surprised tonight to see him playing a shy and stuttering killer. Stick around; this series about FBI undercover work provides real range. Steve Harris leads a team that includes Ali Larter, Tina Majorino and Bean … who shows us (as PBS viewers already knew) he has subtlety and skill.
TONIGHT'S MUST-SEE II: "So You Think You Can Dance," 8-10 p.m., Fox. After Michael Jackson's death five years ago, producer/judge Nigel Lythgoe planned a tribute – then had to dump it when the estate wouldn't allow the music. Now, with a new album coming, there's no problem: First, a group number has the eight finalists dance to the new Jackson single, "A Place With No Name." Then each one (with an "all-star" partner) will dance to a Jackson song, classic or new. Half of the eight specialize in contemporary or jazz; the others are a ballerina, a ballroom dancer and two tap-dancers. Last week, the show ousted its "popper," plus contemporary dancer Bridget Whitman.
TONIGHT'S ALTERNATIVE: "Heartbreakers" debut, 10 p.m., Investigation Discovery. "You've seen too many soap operas," a villain says tonight. Maybe we all have, which makes this idea work. "Heartbreakers" often uses actors from soaps (primetime or daytime) and has a heightened style. That makes sense, because these true stories are filled with human absurdity. Tonight, a pastor in Independence, Mo., (Harry Truman's old town) has a decade-plus affair with the wife of his finance chairman. He gets careless, then lethal. Jack Wagner gives him a bigger-than-life feel; Rob Estes and Jamie Luner (who is particularly good) play it straight, in an oddly entertaining hour
"Mystery Girls," 8:30 p.m., ABC Family. Already wildly over-acted, this show brings in RuPaul as a self-obsessed designer. An ostrich-feather bag has disappeared on the day of his fashion show.
"Modern Family," 9 and 9:30 p.m., ABC. The first rerun finds generations linking – Jay teaching manly ways, Cam and Mitchell leading a culture tour. The second is a funny Las Vegas visit by grown-ups.
"Extant," 10 p.m., CBS. Molly (Halle Berry) comes across footage that may show the real reason she was chosen for the solo space mission. Meanwhile, her android son has his first dream.
"The Bridge," 10 p.m., FX. Most of this hour continues the "Bridge" strengths – richly drawn characters in life-and-death situations, with a powerhouse ending. Still, that's harmed by two flaws – the continued obsession with torture, plus a sudden loss of logic: Knowing powerful people want to kill him, why would a man stroll through town alone, carrying the evidence? We'll forgive it, for now.
"Jennifer Falls" season-finale, 10:30 p.m., TV Land. Jennifer (Jaime Pressly) is suspicious when Adam says she and her daughter can move in with him. | 2023-12-15T01:26:29.851802 | https://example.com/article/7920 |
0.15, 5, 25
Sort 2/23, 28538, 3 in descending order.
28538, 3, 2/23
Sort 8, -4, -6, -3, 22 in descending order.
22, 8, -3, -4, -6
Sort -2/13, -13, 6/185.
-13, -2/13, 6/185
Sort -19, -0.5, -2/15, -2/25, 1, -4 in descending order.
1, -2/25, -2/15, -0.5, -4, -19
Sort 1/64, 0.1, -7, 9, -1 in increasing order.
-7, -1, 1/64, 0.1, 9
Sort 2/5, -0.1, 15/42856 in ascending order.
-0.1, 15/42856, 2/5
Sort 0, 10, 14, -5.
-5, 0, 10, 14
Sort -5/2, 4, 1/4, 255, -2 in decreasing order.
255, 4, 1/4, -2, -5/2
Sort -247, 0.4, 0.5, 0.51, 2.
-247, 0.4, 0.5, 0.51, 2
Put 0, -114, 1, 143 in decreasing order.
143, 1, 0, -114
Put 2, 88, 4, -2, -12, -96 in increasing order.
-96, -12, -2, 2, 4, 88
Put -228, -123, -4, 3, -2 in decreasing order.
3, -2, -4, -123, -228
Sort -8/13, 0, -1, -272, 1/6, 1/3 in increasing order.
-272, -1, -8/13, 0, 1/6, 1/3
Put 2, -4, -1.3, 0, 11, 3/8 in decreasing order.
11, 2, 3/8, 0, -1.3, -4
Put 195, -5, -3, -4 in descending order.
195, -3, -4, -5
Sort 165, -5, 54.
-5, 54, 165
Put 1, -394, -223 in increasing order.
-394, -223, 1
Put 0, -1.1, -4, 2/9, -2, 1.6 in descending order.
1.6, 2/9, 0, -1.1, -2, -4
Sort 1/6, 1/3, 3, -39, 44, -0.07.
-39, -0.07, 1/6, 1/3, 3, 44
Sort -910, 0.01, -0.5, 0.5 in increasing order.
-910, -0.5, 0.01, 0.5
Sort -3616, 3, -3, 17 in ascending order.
-3616, -3, 3, 17
Sort 5, 13, 0, 3, -51 in increasing order.
-51, 0, 3, 5, 13
Sort 3/5, 0.14, -70, 5/3 in descending order.
5/3, 3/5, 0.14, -70
Sort 10, 22, 3/5 in descending order.
22, 10, 3/5
Put -4, 961, 0.5, -1, 0.6 in descending order.
961, 0.6, 0.5, -1, -4
Put 3.08, 1/14, 4 in increasing order.
1/14, 3.08, 4
Sort 2/7, 936, -49/2, -6.
-49/2, -6, 2/7, 936
Sort -5, 1, 2/97, 0, 0.5, 2/11 in ascending order.
-5, 0, 2/97, 2/11, 0.5, 1
Put -3, -78/5, -12, -3/4, -4, -2/3 in increasing order.
-78/5, -12, -4, -3, -3/4, -2/3
Sort -1462, 8, 2/5, -0.3, -5.
-1462, -5, -0.3, 2/5, 8
Sort 5, -715, -2, -1108.
-1108, -715, -2, 5
Put 4, 13, -104 in increasing order.
-104, 4, 13
Sort 3, 12, -4, -41, 88, 2 in increasing order.
-41, -4, 2, 3, 12, 88
Sort -0.3, 0.0812, 1/2 in increasing order.
-0.3, 0.0812, 1/2
Sort 5, 7213, 3, -4, 0 in ascending order.
-4, 0, 3, 5, 7213
Sort -4, -9, -1, 4, 234.
-9, -4, -1, 4, 234
Sort 44.9, -1.2, -5, -0.2.
-5, -1.2, -0.2, 44.9
Sort 108, 3/7, 8, 37.
3/7, 8, 37, 108
Put -157440, 5, 2 in decreasing order.
5, 2, -157440
Sort 0, 2, 3, -4, 7.
-4, 0, 2, 3, 7
Put -0.1, -2, 0.06498 in decreasing order.
0.06498, -0.1, -2
Put -58, 2, 1, 0, -104 in decreasing order.
2, 1, 0, -58, -104
Sort 894, -5, -3 in descending order.
894, -3, -5
Put -1177, 5, -1, 0, 2 in decreasing order.
5, 2, 0, -1, -1177
Put 1/3, -5, -0.3, -1, 321, 1 in ascending order.
-5, -1, -0.3, 1/3, 1, 321
Sort 6, 1, -4, 42, -23 in increasing order.
-23, -4, 1, 6, 42
Sort -2, 0, 5, -236, 3.
-236, -2, 0, 3, 5
Sort -2/25, 148, 3, -1/3.
-1/3, -2/25, 3, 148
Put -4983, 5, -22 in descending order.
5, -22, -4983
Put -5, -4, -525, 0 in descending order.
0, -4, -5, -525
Sort 0.1, -7/15, -2/69, -0.1, 3, 5.
-7/15, -0.1, -2/69, 0.1, 3, 5
Sort 1, 0, 27, 3, 5 in increasing order.
0, 1, 3, 5, 27
Sort -59, -15, 0.4, 7, 4/3 in ascending order.
-59, -15, 0.4, 4/3, 7
Sort 1, -173/6, -411 in decreasing order.
1, -173/6, -411
Put 4/5, 0.5, 1.2, 1, -81 in decreasing order.
1.2, 1, 4/5, 0.5, -81
Sort 5/7, 80, 317, -2 in descending order.
317, 80, 5/7, -2
Sort -5, -7, 2, -296, -1 in descending order.
2, -1, -5, -7, -296
Put -32, 4, 2, 3, -4, 55 in increasing order.
-32, -4, 2, 3, 4, 55
Put 0, 19, -6/5, -28, 2, -0.2 in decreasing order.
19, 2, 0, -0.2, -6/5, -28
Put 7, -1, 3, -3, 10, -15 in ascending order.
-15, -3, -1, 3, 7, 10
Sort -172/233, -18, 0.
-18, -172/233, 0
Put 847, -0.5, -51 in decreasing order.
847, -0.5, -51
Put -1840, -6, 4, -26 in decreasing order.
4, -6, -26, -1840
Put 2, 0, 5, -3492, -8 in decreasing order.
5, 2, 0, -8, -3492
Sort -52, 15, 2, -8 in descending order.
15, 2, -8, -52
Put 7, -60, -44, -1, 3 in increasing order.
-60, -44, -1, 3, 7
Sort 4, -1, -2.2, -1/2, -4.
-4, -2.2, -1, -1/2, 4
Sort 6, 5, 7, 27, -5 in descending order.
27, 7, 6, 5, -5
Put 5, 11, 13, 4, 606, 2 in descending order.
606, 13, 11, 5, 4, 2
Sort 18, 10, 11.
10, 11, 18
Sort 7, -10, -4, 18.
-10, -4, 7, 18
Sort 2, -5, 351, -39, -4, -1 in ascending order.
-39, -5, -4, -1, 2, 351
Put -2, 8, -4, -10, -12, 2 in ascending order.
-12, -10, -4, -2, 2, 8
Sort -0.2, 3, -1/4699, 2/7 in descending order.
3, 2/7, -1/4699, -0.2
Put -1, 2, 5148 in increasing order.
-1, 2, 5148
Sort 26, 15, -2, -95, 13.
-95, -2, 13, 15, 26
Sort -4, -0.1, -13, -2, -298/11 in decreasing order.
-0.1, -2, -4, -13, -298/11
Sort 4/179, -1, 27 in ascending order.
-1, 4/179, 27
Put 0.06, 34, 0.4, -0.41, -2/21 in descending order.
34, 0.4, 0.06, -2/21, -0.41
Sort -6, -0.5, 0.161, 5.
-6, -0.5, 0.161, 5
Put 1, -2, 20, -3 in descending order.
20, 1, -2, -3
Put 1667, 11, 5, -4, 1 in descending order.
1667, 11, 5, 1, -4
Put -33, 6, 16 in ascending order.
-33, 6, 16
Put -444, -113, 1 in decreasing order.
1, -113, -444
Sort 10010, -1, 0, -3, -5 in increasing order.
-5, -3, -1, 0, 10010
Sort -5, 28, -34 in ascending order.
-34, -5, 28
Put 0.104, 0.039, -0.4, -16 in ascending order.
-16, -0.4, 0.039, 0.104
Sort 1, -2, -1, -5, 20.
-5, -2, -1, 1, 20
Sort 42617, 0.3, -6, 3/7 in decreasing order.
42617, 3/7, 0.3, -6
Sort -12, 8, 41.
-12, 8, 41
Put -5, 3, 139, 1, 5, -122 in decreasing order.
139, 5, 3, 1, -5, -122
Put -153, -6, 1, -4, 0, 4 in ascending order.
-153, -6, -4, 0, 1, 4
Sort 0.1, -0.56, -0.24, -3/11 in ascending order.
-0.56, -3/11, -0.24, 0.1
Put 2, 211, -2, 4 in ascending order.
-2, 2, 4, 211
Sort 5, -0.1, -0.229, 37, 3.
-0.229, -0.1, 3, 5, 37
Put -3, 2, -162, 1, 0, -11 in increasing order.
-162, -11, -3, 0, 1, 2
Sort 10, 1, -2, 57, 2 in decreasing order.
57, 10, 2, 1, -2
Sort 0.03, 0.059, -0.6, 1.4 in ascending order.
-0.6, 0.03, 0.059, 1.4
Sort -3, -6448, -33, -5 in ascending order.
-6448, -33, -5, -3
Put -35, 14, 11, -4 in decreasing order.
14, 11, -4, -35
Put 4, -208, -4, -8, 3 in decreasing order.
4, 3, -4, -8, -208
Sort 5, -2/7, -454/3, 0.2, 2 in increasing order.
-454/3, -2/7, 0.2, 2, 5
Sort -0.022, 16/19, 2/13 in ascending order.
-0.022, 2/13, 16/19
Put -1461, 5, -3, 21, 3, -1 in descending order.
21, 5, 3, -1, -3, -1461
Put 2, 4, 10/49, 20, -1, -6/5 in descending order.
20, 4, 2, 10/49, -1, -6/5
Sort -4/7, -300, 2, -5 in decreasing order.
2, -4/7, -5, -300
Put 47, -0.3, 3/19, 5, -4, -6 in descending order.
47, 5, 3/19, -0.3, -4, -6
Put 2/27, -7, -0.4, 10, -1/8 in descending order.
10, 2/27, -1/8, -0.4, -7
Sort 22, -42, -4, 0, 5 in descending order.
22, 5, 0, -4, -42
Sort 7022, 0, -1, 9, -3 in descending order.
7022, 9, 0, -1, -3
Sort 0.4, -3, -9, 5/4, 68/105 in descending order.
5/4, 68/105, 0.4, -3, -9
Sort 31, -8, 1/5, -0.1, -3/2.
-8, -3/2, -0.1, 1/5, 31
Put -33, 4, 73 in ascending order.
-33, 4, 73
Sort 9, 2780, -2/7, 1 in increasing order.
-2/7, 1, 9, 2780
Sort -3, -0.06, -1/4, 1.87.
-3, -1/4, -0.06, 1.87
Sort -2, -85, 2, -31, -4 in increasing order.
-85, -31, -4, -2, 2
Sort -4, 55, -1, 57, 2 in increasing order.
-4, -1, 2, 55, 57
Sort -2, 2610, -7/3, 3, -1.8.
-7/3, -2, -1.8, 3, 2610
Sort -3, -57, -2, 21.
-57, -3, -2, 21
Put 0.5, -3, -10, -1393 in ascending order.
-1393, -10, -3, 0.5
Sort -1, 6/5, 5/10932 in increasing order.
-1, 5/10932, 6/5
Sort 25, -201, 9, -3, 4.
-201, -3, 4, 9, 25
Put 4, -5, 0, 323, -2 in descending order.
323, 4, 0, -2, -5
Put -11, -2, 5/72 in increasing order.
-11, -2, 5/72
Put 27.2, -0.3, -2, 9 in descending order.
27.2, 9, -0.3, -2
Put -1, 0.3, 0.5, 192, 1/9, -0.4 in descending order.
192, 0.5, 0.3, 1/9, -0.4, -1
Sort -26, 0, -5, -50, 4 in ascending order.
-50, -26, -5, 0, 4
Sort -7, 0, 2, 3, 44, 4 in ascending order.
-7, 0, 2, 3, 4, 44
Sort 0, -3, -189104.
-189104, -3, 0
Sort 3, -34, -28, -5, -1, -2.
-34, -28, -5, -2, -1, 3
Sort -2, -0.23435, 16.
-2, -0.23435, 16
Put 1, 13, -18, -1 in increasing order.
-18, -1, 1, 13
Sort -3, 24167, -5 in ascending order.
-5, -3, 24167
Sort 3/8, -0.2, 2/31, 1/5, -1, 2 in descending order.
2, 3/8, 1/5, 2/31, -0.2, -1
Put 5, -1907, 12 in descending order.
12, 5, -1907
Sort 5, 12, 68, 2, -1 in decreasing order.
68, 12, 5, 2, -1
Put -3, -12, -8956, 4 in ascending order.
-8956, -12, -3, 4
Sort -466, 5, -2585 | 2024-06-08T01:26:29.851802 | https://example.com/article/9515 |
Will GOP Rep. Justin Amash win reelection?
Will Joe Biden be the 2020 Democratic nominee?
A student crosses below two flags while entering Antigo High School, Monday, April 25, 2016, in Antigo, Wis. According to police Jakob E. Wagner, 18, opened fire with a high-powered rifle outside of the a prom at Antigo High School ... more >
MILWAUKEE (AP) - The 18-year-old gunman who opened fire on students exiting the prom at his former school in northern Wisconsin was aiming a rifle at a police officer when he was fatally shot, preventing what authorities have said could have been a far worse attack.
The officer who ended the threat was publicly identified for the first time Tuesday as Antigo Police Patrolman Andy Hopfensperger, who had been patrolling the parking lot with two other officers during the dance.
Jakob Wagner was pronounced dead early Sunday at a hospital after the shooting. An 18-year-old male student was struck in the leg and a bullet grazed his date’s thigh as they were leaving. Both are recovering.
Hopfensperger had been “near the victims when they were shot and immediately engaged the shooter, stopping any further threat,” Antigo Police Chief Eric Roller said in a statement.
Roller said previously that his officer “saved a lot of lives” by preventing the suspect from ending up inside the dance.
Landglade County Coroner Larry Shadick confirmed Wagner had taken aim at Hopfensperger. He said the autopsy showed a fatal shot went in through the suspect’s extended left arm and ended up in his chest. “The way this shootout went was just unreal,” Shadick said, explaining that the suspect’s arm would have been outstretched if he were pointing a rifle.
Shadick, citing an ongoing state Justice Department investigation, wouldn’t confirm how many times Wagner had been shot. The toxicology report was pending.
According to a search warrant and supporting affidavit, meanwhile, police seized spent ammunition, a gun sling and journals from Wagner’s home.
Antigo Police Capt. Nate Musolff said in the documents that Hopfensperger fired “as the shooter was actively engaging the kids with the rifle” and that the shooter was hit “multiple times.”
State DOJ spokesman Johnny Koremenos said in an email that it was too early in the investigation to provide details, and authorities haven’t revealed a motive for the attack.
People who knew Wagner have said he was bullied. His mother told The Associated Press on Monday that her son “wasn’t a monster” and that she hopes the tragedy “shines light on bullying and how deeply it affects people.”
Wagner’s family released a statement Tuesday that said his loved ones are “filled with sorrow over the injuries caused to his victims, the position in which the police officers were placed along with the prom goers and their families.”
The statement released by an Antigo funeral home said Wagner’s family realizes “his actions have torn open a wound in our community. We pray for healing.”
According to the documents filed Monday in Langlade County Circuit Court, officers seized several types of spent rounds along with the strap and various journal entries, notes and drawings. They also took electronics, including an iPod, a cellphone and video game systems. Additionally, the records show the seizure of “Notecards Devil In Nature” and “Teen Suicide Reading Materials.”
Hopfensperger is on paid administrative leave, which is routine for officers involved in shootings. He has worked for Antigo Police since January 2013, according to the department’s website. | 2024-06-18T01:26:29.851802 | https://example.com/article/4204 |
I had dinner there about two years ago.It was quite decent, and caters to the crowd in the surrounding buildings.Continental.Food isn't exciting, but well executed.The chef is the owner of the restaurant.Sorry, can't remember what most had, but can't believe that I recall having rack of lamb.
I went there once about 2 years ago. It is a small comfortable place, catering to all the residents of that and nearby buildings. Continental food, everything was good, but I don't remember much more than that. | 2024-05-26T01:26:29.851802 | https://example.com/article/9415 |
Comments on purpurapictures.com
question... My step daughter gets like finger print bruises on her jaw line and purple bruising on her "pinnas" spontaneously. Then they spontaneously disappear... Sometimes a fever will accompany them... What could be causing them?
I had this a few years back.....I thought I had measles or chicken poks....They look just like some of your pictures. Stomach area, arms, and legs. They were terrible looking....What causes this??????
Thank you,
Barbara Shumate :0)
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, or captions are accurate. | 2024-07-13T01:26:29.851802 | https://example.com/article/7497 |
//
// Generated by class-dump 3.5 (64 bit) (Debug version compiled Jun 9 2015 22:53:21).
//
// class-dump is Copyright (C) 1997-1998, 2000-2001, 2004-2014 by Steve Nygard.
//
#import <objc/NSObject.h>
@class MSAsset, NSDate, NSError, NSMutableArray, NSString, NSURL;
@interface ICPSharedPhotoStreamAssetImportRequest : NSObject
{
BOOL _isVideo;
BOOL _hasVideoComplement;
BOOL _hasThumbnailAsset;
BOOL _libraryWasRebuilt;
NSString *_streamIdentifier;
NSString *_assetCollectionIdentifier;
NSString *_locationISO6709String;
long long _state;
MSAsset *_mainAsset;
NSURL *_mainAssetURL;
MSAsset *_videoComplementAsset;
NSURL *_videoComplementAssetURL;
NSString *_videoComplementPairingIdentifier;
MSAsset *_thumbnailAsset;
NSURL *_thumbnailAssetURL;
MSAsset *_miniThumbnailAsset;
NSURL *_miniThumbnailAssetURL;
NSString *_versionIdentifier;
NSError *_error;
CDUnknownBlockType _completionHandler;
NSDate *_creationDate;
unsigned long long _playbackVariation;
NSMutableArray *_importPreparationTasks;
NSMutableArray *_importCleanupTasks;
CDStruct_1b6d18a9 _videoComplementDuration;
CDStruct_1b6d18a9 _videoComplementStillImageDuration;
}
@property(retain) NSMutableArray *importCleanupTasks; // @synthesize importCleanupTasks=_importCleanupTasks;
@property(retain) NSMutableArray *importPreparationTasks; // @synthesize importPreparationTasks=_importPreparationTasks;
@property unsigned long long playbackVariation; // @synthesize playbackVariation=_playbackVariation;
@property(retain) NSDate *creationDate; // @synthesize creationDate=_creationDate;
@property BOOL libraryWasRebuilt; // @synthesize libraryWasRebuilt=_libraryWasRebuilt;
@property BOOL hasThumbnailAsset; // @synthesize hasThumbnailAsset=_hasThumbnailAsset;
@property(copy) CDUnknownBlockType completionHandler; // @synthesize completionHandler=_completionHandler;
@property(retain) NSError *error; // @synthesize error=_error;
@property(retain) NSString *versionIdentifier; // @synthesize versionIdentifier=_versionIdentifier;
@property(retain) NSURL *miniThumbnailAssetURL; // @synthesize miniThumbnailAssetURL=_miniThumbnailAssetURL;
@property(retain, nonatomic) MSAsset *miniThumbnailAsset; // @synthesize miniThumbnailAsset=_miniThumbnailAsset;
@property(retain) NSURL *thumbnailAssetURL; // @synthesize thumbnailAssetURL=_thumbnailAssetURL;
@property(retain, nonatomic) MSAsset *thumbnailAsset; // @synthesize thumbnailAsset=_thumbnailAsset;
@property(retain) NSString *videoComplementPairingIdentifier; // @synthesize videoComplementPairingIdentifier=_videoComplementPairingIdentifier;
@property CDStruct_1b6d18a9 videoComplementStillImageDuration; // @synthesize videoComplementStillImageDuration=_videoComplementStillImageDuration;
@property CDStruct_1b6d18a9 videoComplementDuration; // @synthesize videoComplementDuration=_videoComplementDuration;
@property(retain) NSURL *videoComplementAssetURL; // @synthesize videoComplementAssetURL=_videoComplementAssetURL;
@property(retain, nonatomic) MSAsset *videoComplementAsset; // @synthesize videoComplementAsset=_videoComplementAsset;
@property(retain) NSURL *mainAssetURL; // @synthesize mainAssetURL=_mainAssetURL;
@property(retain, nonatomic) MSAsset *mainAsset; // @synthesize mainAsset=_mainAsset;
@property long long state; // @synthesize state=_state;
@property BOOL hasVideoComplement; // @synthesize hasVideoComplement=_hasVideoComplement;
@property(retain) NSString *locationISO6709String; // @synthesize locationISO6709String=_locationISO6709String;
@property BOOL isVideo; // @synthesize isVideo=_isVideo;
@property(retain) NSString *assetCollectionIdentifier; // @synthesize assetCollectionIdentifier=_assetCollectionIdentifier;
@property(retain) NSString *streamIdentifier; // @synthesize streamIdentifier=_streamIdentifier;
- (void).cxx_destruct;
- (id)description;
- (id)allThumbnailURLs;
- (void)removeThumbnailAssetFiles;
- (id)importInfo;
- (BOOL)allRequiredAssetsPresent;
- (void)invokeCompletionHandler;
- (void)performTasks:(id)arg1 completionHandler:(CDUnknownBlockType)arg2;
- (void)performCleanupTasksWithCompletionHandler:(CDUnknownBlockType)arg1;
- (void)performPreparationTasksWithCompletionHandler:(CDUnknownBlockType)arg1;
- (void)addImportCleanupTask:(CDUnknownBlockType)arg1;
- (void)addImportPreparationTask:(CDUnknownBlockType)arg1;
- (id)initWithStreamIdentifier:(id)arg1 assetCollectionIdentifier:(id)arg2 isVideo:(BOOL)arg3 hasVideoComplement:(BOOL)arg4;
- (id)init;
@end
| 2024-03-04T01:26:29.851802 | https://example.com/article/6462 |
Price
Rating
Other
The Best
We'll only sell what we'd run - suppressors are no different. Amazing devices that make shooting not only more enjoyable but healthier for your ears, they become a huge factor in the functionality of your rifle when attached. Whether noise or accuracy is the primary requirement, we've got you covered!
Unique to Rifles
Due to their unique properties and capabilities, especially in precision shooting, rifles need more from a can than just noise reduction. They need to be tuned to ensure they minimize their affect on a bullet's flight path. This requires exceptional tolerances, repeatability and stability in the method of attachment to the barrel, and consistent effects on trajectory, all in a lightweight package.
All of the suppressors you will find on this page meet these criteria. We only carry the best. If you have any questions, or don't see what you're looking for, give us a call and we'll get you squared away.
AAC 7.62 SDN-6
The AAC 7.62-SDN-6 is a compact fast-attach sound and flash suppressor for 7.62x51mm and 300 AAC BLACKOUT (7.62x35mm) weapons. It is 1.25” shorter than the 762-SD and features a fully welded all-Inconel® baffle stack and front...
Dead Air Key-Mo Mount for Omega / Nomad
Expand the modularity of your Nomad-30. The Key-Mo changes your Nomad-30 from a direct-thread to quick attach, making it compatible with any of our muzzle brakes or flash hiders.
If you’re one of the...
Dead Air Key-Mo Mount for SilencerCo Saker
The Key-Mo changes your Saker ASR to a quick attach, making it compatible with any of Dead Air muzzle brakes or flash hiders.
If you’re one of the many owners of a SilencerCo® Saker and have...
Dead Air Nomad-30
Lightweight. Versatile. Modular. The Nomad-30 exists for the everyday user. Designed to go everywhere you go, mounted on whichever rifle suits your job for the day.
The Nomad-30 is made with 17-4 stainless steel and Grade 5 titanium...
Dead Air Sandman-K 7.62mm QD Mount
Sharing all of the features of the Sandman-S and Sandman-L, while adding only 2.9″ to your muzzle.
The K has the class leading solid weld Stellite® baffle core and detachable front cap,...
Dead Air Sandman-L 7.62mm QD Mount
For those demanding absolute performance the Sandman-L™ delivers. Made and constructed from the same materials as the “S” version, the “L” is only 8.9 inches in length, but offers a...
Dead Air Sandman-S 7.62mm QD Mount
At 6.8 inches in length and a weight of 18.5 oz the Sandman-S™ is the perfect cross-over suppressor for your 5.56mm, 300BLK, and 7.62 platforms, even up to .300 Win Mag.
The QD system is design perfection...
Dead Air Sandman-TI
Looking for ultimate silence from your precision rifle? The Sandman Ti™ is your huckleberry. With its direct thread attachment and titanium tube it’s the perfect fit for your precision rifle, or even for dedicated...
The direct thread half NELSON by Q® was designed with practical shooters in mind. Short, lightweight, and hearing safe, this is a silencer for those who carry their rifle over long distances, or who prefer a compact platform. The half...
The Honey Badger by Q®: Your new Personal Offensive Weapon.
The original Honey Badger was developed at AAC by previous owner and Q CEO, Kevin Brittingham and his R&D team at the request of an elite US special operations group looking...
The Honey Badger by Q®: Your new Personal Offensive Weapon.
The original Honey Badger was developed at AAC by previous owner and Q CEO, Kevin Brittingham and his R&D team at the request of an elite US special operations group looking...
The THUNDER CHICKEN by Q® is the Quickie™ Fast-Attach version of the FULL NELSON™. Equally quiet, durable and accurate, the THUNDER CHICKEN is the perfect solution for shooters with multiple silencer hosts.
Like all... | 2024-03-20T01:26:29.851802 | https://example.com/article/2419 |
Syrian refugees are not the problem in ISIS fight
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Syrian refugees waited to register their names at the Al Zaatari refugee camp in Jordan earlier this month.
By Seth MoultonNovember 23, 2015
ISIS wants to murder more Americans, and it hopes to attack us here at home. Its threats in the aftermath of the Paris carnage made that clear. The question now is how we protect ourselves and, ultimately, defeat this brutal and sophisticated terrorist organization.
Our refugee policy has important implications for our strategy. The congressional furor over accepting Syrian refugees is handing ISIS a propaganda victory while distracting attention from their most likely avenue of attack.
ISIS operates differently from older terrorist organizations like Al Qaeda. Traditionally, terrorist groups have recruited and trained operatives in terror safe havens overseas, such as Syria today and Afghanistan before September 11. When these terror recruits are ready, they are dispatched to infiltrate and attack innocent civilians in other countries.
But that is not the ISIS approach. It mostly recruits over the Internet, using social media to try to radicalize people already embedded in the societies it wishes to target. ISIS has taken this approach even in Europe, where refugees flow freely across borders, meaning that foreign fighters can enter with relative ease.
In the United States, there is no such ease of entry. Here, refugees undergo the strictest screening of any travelers to the country. The process is so exhaustive that it often takes more than two years. So, given a choice between attempting to infiltrate this country by navigating its way through a vigorous and extended vetting process or working to radicalize those already in the United States, where do you think ISIS is concentrating its efforts?
That is why, along with a comprehensive political and military strategy to defeat extremism abroad, our focus must be on preventing ISIS from recruiting to its cause people already on American soil. We need to prevent the radicalization of Americans like the Boston Marathon bombers, who came to the United States as children and lived here for many years before making a violent and abhorrent turn toward extremism.
I voted against the Republican bill to pause the lawful immigration of Syrian refugees for two reasons. First, it did nothing substantive to improve the screening process. Even the director of the FBI opposed it. Second, the legislation completely ignores the greatest threat ISIS poses to America: recruiting terrorists from right under our noses.
Singling out Muslims or Syrians — the very victims of ISIS’s reign of terror — or suggesting that American values apply to them only with caveats, gives ISIS a propaganda tool it can use to recruit more foot soldiers. In other words, “pausing” refugee immigration will not help our national security. Instead, that overreaction might well harm our antiterror efforts.
Although ISIS disciples act like medieval thugs, we must not underestimate them. That means recognizing that they innovate and adapt to our efforts to stop them. Which is why, counterintuitive though it may seem, the reactionary policies some think will protect us could actually put us all at greater risk.
We should not let ISIS win by giving in to fearmongering and changing our values. We must remain steadfast and resolute in who we are as a people and a nation: a beacon of hope for all those “yearning to breathe free.” That is who we have long been. To turn our backs on our heritage and history now is to give ISIS exactly what it wants.
Seth Moulton is a US congressman who represents Massachusetts’ Sixth Congressional District. | 2024-01-16T01:26:29.851802 | https://example.com/article/8495 |
735 N.W.2d 409 (2007)
2007 ND 105
In the Matter of the Application for DISCIPLINARY ACTION AGAINST Douglas D. SLETTEN, A Member of the Bar of the State of North Dakota.
Disciplinary Board of the Supreme Court of the State of North Dakota, Petitioner,
v.
Douglas D. Sletten, Respondent.
No. 20070184.
Supreme Court of North Dakota.
June 27, 2007.
Application for Interim Suspension.
INTERIM SUSPENSION ORDERED.
PER CURIAM.
[¶ 1] On June 25, 2007, an Application for the Interim Suspension of Douglas D. Sletten, a member of the Bar of North Dakota, with supporting documents, was filed under N.D.R. Lawyer Discipl. 3.4, Threat of Public Harm. Sletten was admitted to practice law on October 6, 1980, and is currently licensed to practice law in the courts of North Dakota.
[¶ 2] A complaint has been filed against Sletten which alleges Sletten took approximately three hundred thousand dollars from the Estate of Anita Hopkins. The money was put in Sletten's trust account; Sletten eventually used the money for personal or office use.
[¶ 3] According to an Affidavit filed by Disciplinary Counsel: Sletten acknowledged the misconduct during an interview with Disciplinary Counsel; Sletten also admitted to taking an additional $40,000 held on behalf of another client for his personal or office use; Sletten was not authorized to take the money; and Sletten does not have the ability to pay it back.
[¶ 4] Under N.D.R. Prof. Conduct 1.15(a), Safekeeping Property, a lawyer shall hold property of clients or third persons that is in a lawyer's possession in connection with a representation separate from the lawyer's own property. Absent aggravating or mitigating circumstances, disbarment is generally appropriate when a lawyer knowingly converts client property and causes injury or potential injury to a client. N.D. Stds. Imposing Lawyer Sanctions 4.11, Failure to Preserve the Client's Property.
[¶ 5] Under N.D.R. Lawyer Discipl. 3.4(B), Threat of Public Harm, the court may enter an interim order at any stage of any proceeding immediately suspending the lawyer pending final disposition of the proceeding predicated upon the conduct causing the harm or may order such other action as deemed appropriate. This rule also provides that upon request by counsel or the lawyer after entry of an interim suspension order, the court shall within ten days provide an opportunity for the lawyer to demonstrate that the order should not remain in force.
[¶ 6] ORDERED, Douglas D. Sletten's license to practice law is SUSPENDED effective June 27, 2007, and until further order of this Court, pending final disposition of a disciplinary proceeding predicated upon the complaint filed.
[¶ 7] FURTHER ORDERED, Douglas D. Sletten comply with N.D.R. Lawyer Discipl. 6.3, Notice of Status.
[¶ 8] GERALD W. VANDE WALLE, C.J., DALE V. SANDSTROM, CAROL RONNING KAPSNER, and DANIEL J. CROTHERS, JJ., concur.
*410 [¶ 9] MARY MUEHLEN MARING, J., being unavoidably absent, did not participate in this decision.
| 2023-08-25T01:26:29.851802 | https://example.com/article/3155 |
MONTEVIDEO, March 13 (Reuters) - Uruguay confirmed its first four recorded cases of coronavirus on Friday, the Ministry of Health announced in a tweet.
All four cases were people who had arrived to Uruguay from Milan, Italy between March 3 and March 6, the ministry said, adding that the patients are stable and at their homes. (Reporting by Cassandra Garrison) | 2024-04-12T01:26:29.851802 | https://example.com/article/3569 |
Suicide by couples from the public record.
The aim of this paper was to examine accounts on the public record of suicide by couples, with a view to extending our clinical understanding of such events. A collection of print reports was examined and a web search was conducted. Cases were generally only accepted when the names, ages, locations and method of death of the individuals were provided, along with sufficient detail to convey the rudiments of the social and physical setting. Cases were then arranged into groups and classified using a typology of suicide. Twelve cases were identified which provide valuable insights into the lives of couples who suicide. We found 11 married female-male couples and one female-female couple. A large group (seven couples) was characterized by severe or terminal illness in one or both partners. A small group (three couples) was characterized by serious legal problems. One couple was grieving the loss of an only child, and one example involved a psychotic individual, folie a deux and consequent social stressors. The terminal illness group, the legal difficulties group and the bereaved couple could be classified as 'Type 3 suicide' according to the first author's suicide classification. The case involving the psychotic individual and consequent social stressors could be classified as a combination of Type 1 and Type 3 suicide. Reports on the public record of suicide by couples provide valuable insights into the lives of participants, and their suicides could be grouped (terminal illness, legal difficulties, other) and classified using a typology. | 2024-05-01T01:26:29.851802 | https://example.com/article/1127 |
Sonorous Trail Hoscheid
Sonorous Trail Hoscheid
This Sonorous Trail in Hoscheid, Luxembourg is a hiking trail with 17 stations to make music, listen to nature, and enjoy the surrounding nature. Visitors who are visually impaired can enjoy the different musical features through Braille signs and special tours. | 2023-11-08T01:26:29.851802 | https://example.com/article/5191 |
Vladimir Putin laments Soviet Union ignoring his spy intelligence
Vladimir Putin has admitted for the first time that he spent his stint as a KGB spy in 1980s East Germany conducting industrial espionage against the West, lamenting that the secrets he stole were ignored.
n his most candid comments on the subject to date, the Russian prime minister said that at least part of his job as a KGB agent in East Germany involved acquiring sensitive technological and industrial secrets from the West.
But he told a meeting of the Russian Academy of Sciences that he grew increasingly frustrated as the know-how he passed back to the Soviet Union to help it make good the yawning technological gap with the West went unused.
Mr Putin, who worked as a KGB spy in Dresden from 1985-1990, said he could not understand why Soviet scientists did not use the intelligence he and his colleagues were "acquiring" from the West. | 2023-11-17T01:26:29.851802 | https://example.com/article/8891 |
# Marketo Activity Log Schema
```
https://ns.adobe.com/experience/marketo/activity-marketo-details
```
Marketo specific Activity Log Details
| [Abstract](../../../../abstract.md) | [Extensible](../../../../extensions.md) | [Status](../../../../status.md) | [Identifiable](../../../../id.md) | [Custom Properties](../../../../extensions.md) | [Additional Properties](../../../../extensions.md) | Defined In |
|-------------------------------------|-----------------------------------------|---------------------------------|-----------------------------------|------------------------------------------------|----------------------------------------------------|------------|
| Can be instantiated | Yes | Experimental | No | Forbidden | Permitted | [adobe/experience/marketo/marketo-activity.schema.json](adobe/experience/marketo/marketo-activity.schema.json) |
## Schema Hierarchy
* Marketo Activity Log `https://ns.adobe.com/experience/marketo/activity-marketo-details`
* [Extensibility base schema](../../../datatypes/extensible.schema.md) `https://ns.adobe.com/xdm/common/extensible`
* [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md) `https://ns.adobe.com/xdm/context/activity-log-details`
# Marketo Activity Log Properties
| Property | Type | Required | Defined by |
|----------|------|----------|------------|
| [marketo:activityLog](#marketoactivitylog) | `object` | Optional | Marketo Activity Log (this schema) |
| [xdm:accountID](#xdmaccountid) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmaccountid) |
| [xdm:activityDescription](#xdmactivitydescription) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitydescription) |
| [xdm:activityDueDateTime](#xdmactivityduedatetime) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivityduedatetime) |
| [xdm:activityEndDateTime](#xdmactivityenddatetime) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivityenddatetime) |
| [xdm:activityPriority](#xdmactivitypriority) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitypriority) |
| [xdm:activityStartDateTime](#xdmactivitystartdatetime) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitystartdatetime) |
| [xdm:activityStatus](#xdmactivitystatus) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitystatus) |
| [xdm:activitySubject](#xdmactivitysubject) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitysubject) |
| [xdm:asset](#xdmasset) | `object` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmasset) |
| [xdm:campaign](#xdmcampaign) | `object` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmcampaign) |
| [xdm:division](#xdmdivision) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmdivision) |
| [xdm:entity](#xdmentity) | `object` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmentity) |
| [xdm:highPriority](#xdmhighpriority) | `boolean` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmhighpriority) |
| [xdm:interactionEvents](#xdminteractionevents) | `object` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdminteractionevents) |
| [xdm:isCompleted](#xdmiscompleted) | `boolean` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmiscompleted) |
| [xdm:isDeleted](#xdmisdeleted) | `boolean` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmisdeleted) |
| [xdm:isTask](#xdmistask) | `boolean` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmistask) |
| [xdm:ownerID](#xdmownerid) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmownerid) |
| [xdm:sourceType](#xdmsourcetype) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmsourcetype) |
| [xdm:userID](#xdmuserid) | `string` | Optional | [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmuserid) |
| `*` | any | Additional | this schema *allows* additional properties |
## marketo:activityLog
`marketo:activityLog`
* is optional
* type: `object`
* defined in this schema
### marketo:activityLog Type
`object` with following properties:
| Property | Type | Required |
|----------|------|----------|
| `marketo:activityID`| string | Optional |
| `marketo:attributeValues`| object | Optional |
| `marketo:bypassTrigger`| integer | Optional |
#### marketo:activityID
##### Marketo Activity Unique Identifier
Marketo Activity Unique identifier.
`marketo:activityID`
* is optional
* type: `string`
##### marketo:activityID Type
`string`
#### marketo:attributeValues
##### Attribute Values
undefined
`marketo:attributeValues`
* is optional
* type: `object`
##### marketo:attributeValues Type
Unknown type `object`.
```json
{
"title": "Attribute Values",
"type": "object",
"meta:xdmType": "map",
"additionalProperties": {
"title": "Value defined for each Key",
"description": "Map describing open set of key value pairs which are not composed semantically",
"type": "string"
},
"simpletype": "`object`"
}
```
#### marketo:bypassTrigger
##### Bypass Trigger
Bypass Trigger
`marketo:bypassTrigger`
* is optional
* type: `integer`
##### marketo:bypassTrigger Type
`integer`
## xdm:accountID
### Business Account
Business Account Unique Identifier
`xdm:accountID`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmaccountid)
### xdm:accountID Type
`string`
## xdm:activityDescription
### Activity description
Activity self detailed description
`xdm:activityDescription`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitydescription)
### xdm:activityDescription Type
`string`
## xdm:activityDueDateTime
### Activity Due date time
Due date and time by which the activity should complete
`xdm:activityDueDateTime`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivityduedatetime)
### xdm:activityDueDateTime Type
`string`
* format: `date-time` – date and time (according to [RFC 3339, section 5.6](http://tools.ietf.org/html/rfc3339))
## xdm:activityEndDateTime
### Activity end date time
The date and time when the activity in the form of task/business event got completed
`xdm:activityEndDateTime`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivityenddatetime)
### xdm:activityEndDateTime Type
`string`
* format: `date-time` – date and time (according to [RFC 3339, section 5.6](http://tools.ietf.org/html/rfc3339))
## xdm:activityPriority
### Activity priority
Current priority of the activity
`xdm:activityPriority`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitypriority)
### xdm:activityPriority Type
`string`
## xdm:activityStartDateTime
### Activity Start date time
The date and time when the activity in the form of task/business event got started
`xdm:activityStartDateTime`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitystartdatetime)
### xdm:activityStartDateTime Type
`string`
* format: `date-time` – date and time (according to [RFC 3339, section 5.6](http://tools.ietf.org/html/rfc3339))
## xdm:activityStatus
### Activity Status
Current Status of the activity
`xdm:activityStatus`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitystatus)
### xdm:activityStatus Type
`string`
## xdm:activitySubject
### Subject of the activity
Shortened version of the activityDescription
`xdm:activitySubject`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmactivitysubject)
### xdm:activitySubject Type
`string`
## xdm:asset
### Object asset
Asset details for its type and ID
`xdm:asset`
* is optional
* type: `object`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmasset)
### xdm:asset Type
`object` with following properties:
| Property | Type | Required |
|----------|------|----------|
| `xdm:ID`| string | **Required** |
| `xdm:type`| string | **Required** |
#### xdm:ID
##### Asset ID
Holds Asset Identifier
`xdm:ID`
* is **required**
* type: `string`
##### xdm:ID Type
`string`
#### xdm:type
##### Asset Type
Holds Asset Type
`xdm:type`
* is **required**
* type: `string`
##### xdm:type Type
`string`
## xdm:campaign
### Campaign details
Campaign amd its relevant associated details
`xdm:campaign`
* is optional
* type: `object`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmcampaign)
### xdm:campaign Type
`object` with following properties:
| Property | Type | Required |
|----------|------|----------|
| `xdm:ID`| string | Optional |
| `xdm:member`| object | Optional |
| `xdm:program`| object | Optional |
| `xdm:type`| string | Optional |
#### xdm:ID
##### Campaign ID
Unique identifer for Campaign.
`xdm:ID`
* is optional
* type: `string`
##### xdm:ID Type
`string`
#### xdm:member
undefined
`xdm:member`
* is optional
* type: `object`
##### xdm:member Type
Unknown type `object`.
```json
{
"type": "object",
"properties": {
"xdm:type": {
"title": "Member type",
"description": "Whether the Member is a lead or a contact",
"type": "string"
},
"xdm:ID": {
"title": "ID of the Member",
"description": "Member's ID",
"type": "string"
}
},
"simpletype": "`object`"
}
```
#### xdm:program
undefined
`xdm:program`
* is optional
* type: `object`
##### xdm:program Type
Unknown type `object`.
```json
{
"type": "object",
"properties": {
"xdm:ID": {
"title": "Program ID associated with the campaign",
"description": "Unique identifer for Campaign.",
"type": "string"
},
"xdm:type": {
"title": "Program Type",
"description": "The type of program which is associated with the campaign",
"type": "string"
},
"xdm:step": {
"type": "object",
"properties": {
"xdm:number": {
"title": "Workflow step number",
"description": "Program's Workflow Step Number",
"type": "integer"
},
"xdm:status": {
"title": "Program Workflow Step Status",
"description": "Program's workflow name of the step status",
"type": "string"
}
}
}
},
"simpletype": "`object`"
}
```
#### xdm:type
##### Campaign Type
The type of campaign for which audience is invited
`xdm:type`
* is optional
* type: `string`
##### xdm:type Type
`string`
## xdm:division
### Division of Account Enterprise
name of division of the account
`xdm:division`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmdivision)
### xdm:division Type
`string`
## xdm:entity
### Entity
Holds Entity Name and its ID on which activity action is based upon.
`xdm:entity`
* is optional
* type: `object`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmentity)
### xdm:entity Type
`object` with following properties:
| Property | Type | Required |
|----------|------|----------|
| `xdm:ID`| string | **Required** |
| `xdm:name`| string | **Required** |
#### xdm:ID
##### Entity tuple ID
Holds Entity Tuple's Primary Identifier
`xdm:ID`
* is **required**
* type: `string`
##### xdm:ID Type
`string`
#### xdm:name
##### Entity Name
Holds Entity Name
`xdm:name`
* is **required**
* type: `string`
##### xdm:name Type
`string`
## xdm:highPriority
### Activity is a high priority task
A boolean flag to indicate whether the activity is of high priority
`xdm:highPriority`
* is optional
* type: `boolean`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmhighpriority)
### xdm:highPriority Type
`boolean`
## xdm:interactionEvents
### Interaction Events
collection of various forms of interactions
`xdm:interactionEvents`
* is optional
* type: `object`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdminteractionevents)
### xdm:interactionEvents Type
`object` with following properties:
| Property | Type | Required |
|----------|------|----------|
| `xdm:email`| | Optional |
| `xdm:meeting`| object | Optional |
| `xdm:phoneCall`| | Optional |
#### xdm:email
##### Email interaction
Contextual information captured during any given email message
`xdm:email`
* is optional
* type: reference
##### xdm:email Type
* []() – `https://ns.adobe.com/xdm/common/emailinteraction`
#### xdm:meeting
##### Meeting
Meeting details with location co-ordinates
`xdm:meeting`
* is optional
* type: `object`
##### xdm:meeting Type
Unknown type `object`.
```json
{
"type": "object",
"title": "Meeting",
"description": "Meeting details with location co-ordinates",
"properties": {
"xdm:meetingDetails": {
"title": "Meeting interaction",
"$ref": "https://ns.adobe.com/xdm/common/meetinginteraction",
"description": "Contextual information captured for a online/offline meeting"
},
"xdm:location": {
"title": "Physical location of the event management if meeting is offline ",
"$ref": "https://ns.adobe.com/xdm/context/place",
"description": "Physical location where the meeting is taking place"
}
},
"simpletype": "`object`"
}
```
#### xdm:phoneCall
##### Phone interaction
Contextual information captured during a given phone conversation
`xdm:phoneCall`
* is optional
* type: reference
##### xdm:phoneCall Type
* []() – `https://ns.adobe.com/xdm/common/phoneinteraction`
## xdm:isCompleted
### Activity completed or still open to work on
A boolean flag to indicate whether the activity is completed
`xdm:isCompleted`
* is optional
* type: `boolean`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmiscompleted)
### xdm:isCompleted Type
`boolean`
## xdm:isDeleted
### Activity soft deletion
A boolean flag to indicate whether the activity is soft deleted
`xdm:isDeleted`
* is optional
* type: `boolean`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmisdeleted)
### xdm:isDeleted Type
`boolean`
## xdm:isTask
### Activity is task or business event
A boolean flag to represent whether the activity is a task of Event Management
`xdm:isTask`
* is optional
* type: `boolean`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmistask)
### xdm:isTask Type
`boolean`
## xdm:ownerID
### Ownership of the Activity
The owner which is responsible for completing the task or event management
`xdm:ownerID`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmownerid)
### xdm:ownerID Type
`string`
## xdm:sourceType
### Activity Source Type
The upstream source from where the activity record has been syncronized
`xdm:sourceType`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmsourcetype)
### xdm:sourceType Type
`string`
## xdm:userID
### User who is performing the activity
The user initiating the activity
`xdm:userID`
* is optional
* type: `string`
* defined in [XDM Business Activity Log details](../../../mixins/activity-log/activity-log-details.schema.md#xdmuserid)
### xdm:userID Type
`string`
| 2023-12-08T01:26:29.851802 | https://example.com/article/6872 |
The Unfinished Promise of the Center City Connector
Pioneer Square has the most to potentially lose–but also gain–from the connection of Seattle’s downtown streetcar lines.
During her daily commute into Pioneer Square on Link light rail, Lauren Davis, who is assistant director of ArtXchange Gallery, noticed a change in ridership after the completion of the Capitol Hill and University of Washington stations in 2016.
“The cars are packed,” said Davis. “It’s clear that people in Seattle are hungry for connected transit systems.”
Davis is hopeful that Center City Connector (CCC) will offer Pioneer Square access into another connected system. As the director of a well-established gallery on 1st Avenue just south of S. Jackson Street, Davis knows that customer access is essential to her gallery’s success, and she is tired of listening to customer’s frustrations about “circling for an hour for a park spot.”
“I would personally like to have the CCC in the long run,” said Davis. “If the [streetcar] connector were finished and there were new resources for parking, I think that would be ideal.”
On July 24th Mayor Durkan released a letter explaining her decision to halt construction of the CCC, pending completion of a technical review by the firm KPMG. While the fate of the CCC hangs in the balance, no other neighborhood is waiting for what comes next with as much anticipation as Pioneer Square. Because of the utility work being completed on 1st avenue, the neighborhood has already been living with the painful reality of being stuck in the middle of a major road construction project for several months.
Beloved by its residents and stakeholders, Pioneer Square is a place where people choose to locate their lives and businesses, despite the hardships the neighborhood has faced over the years. Recently, more and more small businesses have been moving into Pioneer Square, transforming the neighborhood into a small business hub.
“Because of the historic preservation and the Alliance for Pioneer Square doing business recruitment, we have a nice balance of businesses,” said Aaron Barthel of Intrigue Chocolate, whose business opened its first storefront in Pioneer Square with help from Community Sourced Capitol and a Kickstarter campaign. “The property owners have bought in and realized that having a dynamic community of small businesses is really what makes a neighborhood a neighborhood.”
Opinions over how much of a benefit the CCC would offer the neighborhood differ, but consensus exists around the fact that sustaining and increasing foot traffic in Pioneer Square is essential to its continued success as a vibrant neighborhood. The vision of Pioneer Square as a neighborhood anchored on a quiet, leafy 1st Avenue bustling with pedestrians has widespread appeal.
“I can see how the CCC fits into that vision of the future,” said Davis, “but it’s unfortunate that what we need to build that [future] completely destroys what it is that we need right now. The current system is relying on the financial resources of business owners, and this is a not a great time for lots of businesses. People don’t have the resources to say, ‘I can have three bad years.’”
But focusing on short-term survival could mean losing out on long-term gains for the Pioneer Square community as a whole. A sea change of density is sweeping over Seattle’s downtown core. A recent report revealed that housing construction in the City of Seattle far outpaces housing construction in the suburbs for the first time in decades. In downtown Seattle alone, 9,390 apartment units are planned and 2,696 units are currently under construction.
“There’s ecosystem to the downtown,” said Lisa Howard of the Alliance for Pioneer Square. “We don’t have large space for residential growth here, so we need those other people coming [to Pioneer Square] to work and to eat and to shop and to visit. As a circulator, the CCC is important. The project has value.”
Co-founder and producing director of Café Nordo Terry Podgorski has no regrets about finding a permanent home in Pioneer Square for Nordo’s “culinarium,” an immersive theater experience that offers a “crossroad between the culinary and performing arts.” However, the construction has been brutal since he and co-founder Erin Brindley located there in 2015.
“It’s been great overall being in Pioneer Square, but it’s a neighborhood going through a lot of change,” said Podgorski. “First they were redoing alleyways and then there was the gas and electrical work on Main [Street]. I think they’ve torn up the roads around us, in particular, the corner of 1st and Main, about five times and three years.”
All of that construction has made discussion of future projects a sensitive topic.
“It’s been tough,” said Christl Marcontell, owner of Kinesthesia Pilates. “This was the year I thought I would get a return on my investment after years of pouring my body and soul into my business.”
Marcontell, who has operated her business in Pioneer Square since 2004 is a believer in Pioneer Square’s potential as a “pedestrian-friendly small business corridor.” In 2015, Marcontell relocated to a storefront location on 1st Avenue with the hope of growing her business and establishing a retail presence. Slim first quarter profits, which she attributes to the impact of construction, has once again left her in a precarious situation.
However, Marcontell remains an ardent supporter of the CCC. “I knew it would be a long process,” said Marcontell. “I want the end of result of a pedestrian-friendly boulevard that will be more attractive to tourists and people traveling with families. The [streetcar] will be easy to jump on and jump off. More people will come down to Pioneer Square.”
Not everyone in Pioneer Square is as supportive. “My business partner [Erin Brindley] is supportive, but I don’t like the [streetcar]. I would have rather seen expanded light rail,” said Podgorski.
Yet even as a critic, Podgorski concedes that the CCC might be advantageous for his business. “I can see the potential benefit of connecting these neighborhoods,” he said. “I’m conflicted because I can see some benefits for our business. Parts of it are a great idea.”
But, the chaos and disruptions that have accompanied construction and the lack of communication between the Seattle Department of Transportation (SDOT), the construction company, and the impacted businesses has affected many small business owners’ perceptions of the project.
“It’s been bad. Right after the construction started, it had a huge damage to our business,” says Lusha Chen of Callus, a lifestyle brand collective from China, which opened a large storefront presence on 1st Avenue last year. “Also for [employees], commuting to work and loading stuff, it’s pretty hard.”
Like Callus, General Porpoise wanted to “be part of a historic neighborhood.” So far, there are no regrets about opening a new storefront on 1st Avenue, despite construction affecting the business’s profits. “On days the construction has been light around us, we see so many faces from the area and people are all around happy to be there,” said Reed McCoy, manager. “But when there is heavy construction around us, we see a large dip in foot traffic on the streets, and few people come in.”
Located on S. Jackson Street across from the terminus for the current First Hill Streetcar, Intrigue Chocolate owner Barthel has lived through the construction process twice now, and he has no doubt that the experience on 1st Avenue has been worse.
“The real utility work was done on 1st Avenue,” Barthel said. “You have the trees. You have the underground sidewalks. You have one hundred year-old infrastructure.”
“I think a lot of people don’t realize that the utility work was necessary regardless of the streetcar,” he added, alluding to the fact that for many people it has been difficult to disassociate the CCC from the invasive utility work, which was planned to be completed before the CCC construction began and not actually connected with the CCC project.
According to transit consultant Jarrett Walker, the problem with the first generation of North American streetcars was “with a few exceptions, they’ve been designed with the attitude that transit function isn’t really the point.”
Streetcars were marketed more for their potential to spur business and construction development than as serious transit tools. Thus many streetcars, including the South Lake Union and First Hill lines in Seattle, were designed to share the road with cars and buses, virtually wiping out their mobility benefits.
However, the CCC was designed to be different. For the 1.1 miles it will run through the downtown core, it will operate on its on own exclusive lane, greatly improving its speed and efficiency.
Somehow, apart from the pro-transit community, this message has simply not gotten out.
“The streetcar on Capitol Hill is really slow and a headache for me,” said Chen. “It creates more car traffic. In China, public transportation is underground. It’s different than here.”
Graphics display the design for how the CCC would run on 1st Avenue. Courtesy of SDOT.
Podgorski was clear that a lack of awareness around the project has hurt its reputation with business owners. He blames the City.
“There’s no signage,” he said. “No signs saying, ‘We’re here and we are trying to improve this for this reason.’ They have show us what the CCC will look like and what the benefits will be.”
Jim Baird, who has owned his residential property overlooking 1st Avenue for over twenty years, also had similar difficulty understanding how the CCC would fit into the “current streetscape and flow of traffic.” As a substantial financial donor to the preservation of trees Pioneer Square, Baird was concerned about how the CCC’s presence might negatively impact the greenery of the street, but confessed that he had “no idea of the plan’s logistics.” After a careful review, he changed his mind. “I’m moderately open to the idea of the streetcar now,” Baird said, “as long as it doesn’t negatively impact the trees.”
The Alliance for Pioneer Square partnered with the City to inform business owners and held meetings early on to spread the word about the CCC. “There’s been more opportunity for knowledge than people have necessarily been able to take advantage of,” said Barthel. Many businesses in Pioneer Square are small and new, and informational outreach can fall off their radar, especially since many business owners need to provide both staffing and management at the same time.
Also, the pain of vanishing profits is real. “When you are hurting, when your business is in pain, that is the part that matters to you in that moment,” said Barthel.
Being situated across from the First Hill streetcar line has broadened Barthel’s perspective. “We did not see an explosion of traffic, but we definitely see a lot more people who live on Capitol Hill coming down to explore Pioneer Square,” said Barthel. “Every time a tourist or business traveler comes in here, and they want to see different parts of the city, I tell them the streetcar stops right there and it can take you places you want to go. I really look forward to directing them to the CCC.”
“I can’t imagine if you connect the streetcars that you wouldn’t just see a massive uptick in ridership,” he added.
Concerns also exist that the CCC will improve transit for tourists, but not for Seattle residents. However, those concerns may also be largely unfounded when it comes to the CCC, especially in regards to providing transit for vulnerable populations.
“I heard early on that there was speculation that it didn’t serve poor people, but there wasn’t any data or backup information about why people thought that,” said Howard. “In Pioneer Square, we have a really high number of low-income residents. To have a system that’s really easy to understand and connects us directly to the hospitals on First Hill, that’s really valuable. Streetcars are also really ADA accessible because it’s really easy to go from the platform onto an even, level car. It removes a lot of the steps of getting on to a bus.”
Reconsider the Process, Not the CCC Project
At the Alliance for Pioneer Square, Lisa Howard is a believer. She is a believer in the future of Pioneer Square, a neighborhood that was hit harder than almost any other in Seattle during the 2008 recession, and one that even now can live up to its historic nickname of “Skid Row.” Howard is also a believer in the CCC, not just as a new mobility tool for Pioneer Square and the Downtown core, but as an opportunity to show that transit can be done well.
At her office in the upper story of a historic building, Howard was effusive about how the recent pause in the CCC project can be used to make the CCC succeed:
We’re absolutely supportive of accountability and the need to address some of the system’s issues that are going on now on a city level. But we also think that this project can be something where our city government takes and implements those changes in accountability and cost-savings and demonstrates that they can do it well… We need to expand transit. The project has already been vetted. They are are uncovering issues, which they will be able to address, and they can implement those changes immediately.
At Intrigue Chocolate’s 600 square foot tasting room on S. Jackson Street, Barthel is sympathetic to small business owners’ worries that their businesses will not survive the additional years of construction. But he is also a believer that the entire construction and impact mitigation process can be rethought to benefit businesses.
Impact mitigation and financial payouts to businesses are difficult topics in Seattle. While the City’s approach has generally been not to give financial payouts, there have been some exceptions, including payments given to impacted small businesses on 23rd Avenue. However, those payments were awarded from federal grant funding and it is unlikely that small businesses in Pioneer Square will be eligible for similar compensation.
In reference to this situation, Barthel said, “There needs to be planning. If the city is unwilling to do business mitigation, they need to do activity mitigation.”
Signs encourage shoppers and dinners to come out despite construction. Photo by author.
The City’s current impact mitigation plans for Pioneer Square are standard. After years of living with construction surrounding his business, Barthel has spent a lot of time thinking about how to keep businesses alive during construction and arrived at the conclusion that what is needed is a creative rethinking of construction zones:
Why not turn the liability on its head? There are so many competitions and festivals when things are made by designers and are donated or made for free. What if we try to make it joyful again? What if rather than just ‘open for business signs’, it becomes an art show, a competition? How can we make the scaffolding not gloomy but turn it into a green arbor with fast growing plants? People aren’t going to want to be there for the noise, but at night it’s quiet. Why not install an arcade of lights? We can make it so people feel safe and want to be here.
Mayor Durkan will need to come to a decision about the CCC soon–staff have indicated October is when she will finally decide (and apparently release the consultant report). While there are many factors to consider, if done correctly, the project can be a model in many ways.
At the moment, though, the small businesses of Pioneer Square need support from the greater Seattle community. For people who want to see the historic neighborhood thrive, it’s important to brave the construction headaches and come out.
“Have breakfast, lunch, or dinner at restaurants. Support our retailers during the day,” said Howard. “There’s still a huge concentration of arts and culture here to enjoy.”
Related
Natalie Bicknell is Senior Reporter at The Urbanist. She is a writer and community college instructor who lives in the Central District with her husband and two dogs. In her research and writing, she is always on the lookout for better ways of creating sustainable, diverse, and vibrant cities. Email her at natalie [at] theurbanist [dot] org. | 2023-10-18T01:26:29.851802 | https://example.com/article/5786 |
Rancho Mirage, CA
Company Name:The Ritz-CarltonCasual Dining RunnerWe make stories like this possible every day. Whether we're helping a budding chef create a favorite meal, or an anxious dad find a camera full of memories, we're proud to welcome our guests to a home away from home. Because at The Ritz-Carlton, we never forget that we are creating guests for life.The Ritz-Carlton, Rancho Mirage, located at 68900 Frank Sintra Drive, Rancho Mirage, CA, 92270 currently has the following opportunity:Casual Dining Runner (15000N2U): Complete closing duties, including storing all reusable goods, breaking down goods, cleaning all equipment and areas, returning equipment to proper locations, locking refrigerators, restocking items, turning off lights, locking doors, and completing daily cleaning checklist. Set up, stock, and maintain work areas. Inspect the cleanliness and presentation of all china, glass, and silver prior to use. Maintain cleanliness of work areas throughout the day, practicing clean-as-you-go procedures. Follow all company and safety and security policies and procedures; report accidents, injuries, and unsafe work conditions to manager; and complete safety training and certifications. Ensure uniform and personal appearance are clean and professional, maintain confidentiality of proprietary information, and protect company assets. Welcome and acknowledge all guests according to company standards. Speak with others using clear and professional language, and answer telephones using appropriate etiquette. Develop and maintain positive working relationships with others, support team to reach common goals, and listen and respond appropriately to the concerns of other employees. Ensure adherence to quality expectations and standards. Reach overhead and below the knees, including bending, twisting, pulling, and stooping. Move, lift, carry, push, pull, and place objects weighing less than or equal to 25 pounds without assistance. Stand, sit, or walk for an extended period of time or for an entire work shift. Perform other reasonable job duties as requested by Supervisors.We invite you to learn more about this position and apply at: https://marriott.taleo.net/careersection/7/jobdetail.ftl?job=15000N2UConnect with us on social media to keep up to date on The Ritz-Carlton news, learn more about our culture, and engage with the Careers team on Facebook.www.facebook.com/marriottjobsandcareershttp://www.linkedin.com/company/ritz-carltonJoin The Ritz-Carlton Ladies and Gentlemen. The Art and Soul of Hospitality.The Ritz-Carlton is an equal opportunity employer committed to hiring a diverse workforce and sustaining an inclusive culture. The Ritz-Carlton does not discriminate on the basis of disability, veteran status or any other basis protected under federal, state or local laws.
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such as signing bonus, supplies, etc. The victim will be instructed to deposit the check and use the money
for any of these reasons and then instructed to send the remaining funds to the fraudster. The check will
bounce and the victim is left responsible.
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Tubular Hell starts playing in the arena.The lights dim as a purple spotlight lights up and follows an approaching Chriso walking slowly down the ramp towards the ring.he climbs the steps into the centre of the ring where he goes down on one knee and strikes the ring with his fist liighting up the arena again.He pulls out a mic from his Overcoat pocket and holds it to the side of his mouth amongst the cheers of fans, he speaks:
Chriso: Last Week......I sent a warning to RIOT!.......I warned them......attack me when i fight SadMan......and the consquences would be deadly........
The fans cheer loudly as Chriso goes on.
You chose not to heed that warning......so now you will witness......the beginning of your suffering......the beginning of the pain.......i will inflict on your very souls!!!
Fans are now deafening chanting Chriso's name.
Now i give you a choice.......stay hidden and prolong your doom......that is to come......or come out to this ring now......each and every one of you......and let the harvesting of the souls......come early!!!
:::Down With The Sickness starts to play over the PA system and out comes none other than War with a gimped up Supreme Knight. War has a mic in his hand and as the music fades out he quickly puts the mic to his mouth.:::
War: Do you always talk like you're doing a monologue of some kind? :::mockingly::: I am the DeadMan. Don't attack me or you will pay with your souls! Guess what, buddy!!! I don't have a soul! I'm a god so I'm on a completely different level than these mere mortals who shiver in their boots when your music plays. I just thought of it. You're a dummy! The reason being, you want all of Riot to come out and meet you in the ring. I have to say that has to be the dumbest move any UFW star has made, but I'll say this. I'll meet you in the ring. You may beat me. Hell, I EXPECT you to win against me. But when you look into MY eyes...You'll see that I don't give two pats on a fat baby's @$$ about whether I win or lose. You know, we can do this back and forth all the lil long day. Flap our gums til they bleed, but it seems like you want a taste of someone from Riot! And I'm happy to oblige. Why don't we go ahead and get this little dance started?
Chriso looks up at War hardly moving.He stares at War for a long period before raising the mic to the side of his mouth again.
Every living being has a soul.......God Souls are just harder to take.......but they are also more satisfying!!!
The fans cheer as Chriso acknowledges War and Supreme.
I offered you the chance......for a massive handicap on me.....but you have elected yourself......to step into the ring.....One on One......With the DeadMan......And THAT......will be the stupidest thing....ever.....heared!!!
Fans Start chanting.Some shout War while Chriso's fans add on the end Rest In Peace!
Very well.....You want to prove yourself to RIOT!......then you and i will have a match.......and when your battered corpse is lying unconcious on the floor......and your soul has left your body......i will come for the rest of your friends.....and they too will soon......REST.....IN.....PEEEEAAACE!!! | 2024-02-14T01:26:29.851802 | https://example.com/article/1515 |
The White House’s new Communications Director Anthony Scaramucci has made his first major decision in his new role by firing an alleged “leaker”, who also happens to be an RNC loyalist, within his department.
Scaramucci told Fox News on Sunday that “We have to get the leaks stopped. If we don’t get them stopped. I’m a businessperson so I will take dramatic action to stop those leaks.”
And if that wasn’t clear enough, he also made an appearance on CBS News and responded to a question from John Dickerson when asked how he would treat leakers by saying “They’re going to get fired. I’m just going to make it very, very clear, okay? Tomorrow I’m going to have a staff meeting. And it’s going to be a very binary thing. I’m not going to make any prejudgments about anybody on that staff. If they want to stay on the staff, they’re going to stop leaking.”
Today, it seems Scaramucci is backing up his statements and starting the process of cleaning up the Communications Department at the White House by firing Assistant Press Secretary Michael Short during Tuesday’s morning staff meeting.
“I’m going to fire everybody, that’s how I’m going to do it,” Scaramucci said to reporters outside of the White House on Tuesday. “You’re either going to stop leaking or you’re going to be fired.”
Politco reported that Scaramucci confirmed his decision to terminate Assistant Press Secretary Michael Short this morning.
Scaramucci confirmed to POLITICO early Tuesday that he planned to start by dismissing assistant press secretary Michael Short at a morning meeting, but that move was apparently delayed.
Short, who initially said Tuesday that he hadn’t yet been informed of any decision, resigned Tuesday afternoon.
Short’s ouster is Scaramucci’s first warning shot to White House aides who have been perceived as disloyal to the president. In an echo of Trump’s not-so-subtle warning to Jeff Sessions about his status as attorney general, Scaramucci’s vow to “fire everybody” is a warning to staffers perceived as leakers.
It appears Short was offered the opportunity to resign before getting fired, as Axios tweeted a confirmation of this decision.
Michael Short worked on the Trump campaign, placed there by Preibus and the RNC, until he jumped ship after the Access Hollywood tapes emerged in October, apparently convinced that Trump no longer stood a chance at winning the election. Like most establishment Republicans, he was proven wrong in November.
Breitbart News reports that Short was only working in the White House because of Reince Preibus’s decision to bring him back onboard, despite quitting in October, and his connection to the RNC.
“He was scorned by many of his colleagues for quitting the Trump campaign, only to rejoin as a White House staffer because of Priebus,” Palmeri wrote of Short.
“In a story often retold by campaign staffers, they arrived at Trump Tower one morning, months before the election, to see Short’s computer left open on his otherwise empty desk. He had quit the campaign that day and never returned.
The next time he was seen by former campaign staffers was in January on their first day in the White House, where some were stunned to learn that they were going to have to work alongside him or for some of the press assistants subordinate to him.”
Michael Short was long suspected to be a leaker and loyal to the former White House deputy chief of staff Katie Walsh, who ironically was also fired due to suspected of being a leaker and who came along with Reince Priebus from the RNC.
Many of the top appointments in the Trump administration came from the direct recommendation of Chief of Staff Reince Preibus, who despite his work on the Trump campaign last year was never considered to be a staunch support of the president’s “America First” message.
Preibus has long been disdained by Trump’s voters, who view him as part of the establishment swamp that should be “drained” from the Trump administration, and government all together.
It appears a trend is emerging within the Trump administration. Those with no connection to the RNC or establishment politicians can be trusted to do the right thing, uphold Trump’s agenda and purge leakers from their positions. Anyone from the RNC, including Reince Preibus, are loyal to their party before the American people and President Trump, which makes them even more dangerous than the anti-American Democrats working to oust Trump from office.
Only those who have no connection to “the swamp” of
politics, including the RNC and Republicans, can held Trump move his agenda
forward. Anyone appointed by the Preibus or the RNC is untrustworthy, and will
jump ship at the first sign of trouble.
Fire Preibus and all RNC appointments, and fire business
people who love America more than their jobs or money. | 2024-03-11T01:26:29.851802 | https://example.com/article/5864 |
Q:
Delphi 2007 and Dynamic Variant Array as Var Parameter
I have a form which allows a use to select a record and this form then returns the ID of the record and an arbitrary number of fields values that the calling form may need. To do this, I have a function which handles creating the select form and passes all the values to and from the calling form:
Function Execute(AOwner: TComponent; AConnection: TADOConnection;
AEditor: String; AButtons: TViewButtons; Var AID: Integer;
Var ARtnVals: Array of Variant): TModalResult;
Var
I: Integer;
Begin
frmSelectGrid := TfrmSelectGrid.Create(AOwner);
Try
With frmSelectGrid Do
Begin
Connection := AConnection;
Editor := AEditor;
Buttons := AButtons;
ID := AID;
Result := ShowModal;
If Result = mrOK Then
Begin
AID := ID;
//VarArrayRedim(ARtnVals, Length(RtnVals)); !! Won't compile
//SetLength(ARtnVals, Length(RtnVals)); !! Won't compile either
For I := 0 To High(RtnVals) Do
ARtnVals[I] := RtnVals[I]; // Causes runtime exception
End;
End;
Finally
FreeAndNil(frmSelectGrid);
End;
End;
The selector form has the following public properties:
public
Connection: TADOConnection;
Editor: String;
Buttons: TViewButtons;
ID: Integer;
RtnVals: Array of Variant;
end;
And in the OK click, I have the following code:
Var
I, Idx, C: Integer;
// Count how many fields are being returned
C := 0;
For I := 0 To Config.Fields.Count - 1 Do
If Config.Fields[I].Returned Then
Inc(C);
// If no fields to be returned, then just exit.
If C = 0 Then
Exit;
// Set the size of the RtnVals and assign the field values to the array.
SetLength(RtnVals, C);
Idx := 0;
For I := 0 To Config.Fields.Count - 1 Do
If Config.Fields[I].Returned Then
Begin
RtnVals[Idx] := aqItems.FieldByName(Config.Fields[I].FieldName).Value;
Inc(Idx);
End;
So, once the user clicks OK to select a record, the RtnVals array is populated with the field values of the fields to be returned. I now need to copy these values to ARtnVals in the Execute function so that they are returned to the calling form.
My question is how do I set the size of the ARtnVals array so that I can copy the fields? SetLength doesn't work like it does in the OK click function above. VarArrayRedim doesn't work either.
A:
When written in a procedure parameter list, this code
Var ARtnVals: Array of Variant
is an open array, and not a dynamic array. An open array cannot be resized. An open array is no use to you here.
Instead define a type for the array:
type
TDynamicArrayOfVariant = array of Variant;
Use that type for your parameter, which is actually best as an out parameter:
function Execute(..., out RtnVals: TDynamicArrayOfVariant): TModalResult;
And then pass the function a TDynamicArrayOfVariant to be populated.
Now you have a dynamic array rather than an open array in Execute, and you can use SetLength to size it.
| 2024-02-16T01:26:29.851802 | https://example.com/article/4430 |
Luka Mijaljević
Luka Mijaljević (born 9 March 1991) is a Swedish footballer who plays for AFC Eskilstuna as a forward.
Personal life
Born in Sweden, Mijaljević is of Croatian descent.
References
External links
Category:1991 births
Category:Living people
Category:Association football forwards
Category:Swedish footballers
Category:Swedish people of Croatian descent
Category:Superettan players
Category:Croatian First Football League players
Category:Örgryte IS players
Category:Utsiktens BK players
Category:NK Istra 1961 players
Category:Landskrona BoIS players
Category:Ljungskile SK players
Category:GAIS players
Category:AFC Eskilstuna players | 2024-03-08T01:26:29.851802 | https://example.com/article/9603 |
Location: National Gypsum Loading Facility, MI (Iosco, County)
The National Gypsum loading facility was located south of Tawas City and was accessed by rail off the Alabaster branch just south of Alabaster Junction. Gypsum aggregate was brought here by rail and truck and loaded into vessels well out into Tawas Bay.
Rock is dumped at this facility to a conveyor system which loads ships 1/3 of a mile out in Lake Huron. The facility is served by the Lake State Railway.
Photo Info/Credit: This GE engine works the National Gypsum loading facility south of Tawas City in 1996. [Mark Anderse] | 2024-06-05T01:26:29.851802 | https://example.com/article/1371 |
Q:
Creating an interval in for frequency table in R
I have a dataframe I've created in the form
FREQ CNT
0 5
1 20
2 1000
3 3
4 3
I want to further group my results to be in the following form:
CUT CNT
0+1 25
2+3 1003
4+5 ...
.....
I've tried using the between and cut functions in dplyr but it just adds a new interval column to my dataframe can anyone give me a good indication as to where to go to achieve this?
A:
Here is a way to do it in dplyr:
library(dplyr)
df <- df %>%
mutate(id = 1:n()) %>%
mutate(new_freq = ifelse(id %% 2 != 0, paste0(FREQ, "+", lead(FREQ, 1)), paste0(lag(FREQ, 1), "+", FREQ)))
df <- df %>%
group_by(new_freq) %>%
mutate(new_cnt = sum(CNT))
unique(df[, 4:5])
# A tibble: 2 x 2
# Groups: new_freq [2]
# new_freq new_cnt
# <chr> <int>
#1 0+1 25
#2 2+3 1003
data
df <- structure(list(FREQ = 0:3, CNT = c(5L, 20L, 1000L, 3L)), class = "data.frame", row.names = c(NA, -4L))
| 2024-01-03T01:26:29.851802 | https://example.com/article/9971 |
<?php
/**
* Ushahidi Post Lock Create Validator
*
* @author Ushahidi Team <team@ushahidi.com>
* @package Ushahidi\Application
* @copyright 2017 Ushahidi
* @license https://www.gnu.org/licenses/agpl-3.0.html GNU Affero General Public License Version 3 (AGPL3)
*/
namespace Ushahidi\App\Validator\Post\Lock;
class Create extends Update
{
protected function getRules()
{
return array_merge_recursive(parent::getRules(), [
'post_id' => [
['not_empty'],
],
]);
}
}
| 2023-09-08T01:26:29.851802 | https://example.com/article/9258 |
Q:
Query unmapped class member
I have my class GreenGroup which inherits from abstract Group. GreenGroup has an unmapped property State that is defined in a partial class.
I have a method GetGreenGroups(GroupFilter filter) that should return a list of GreenGroup objects where the State == filter.State.
public List<GreenGroup> GetGreenGroups(GroupFilter filter)
{
IQueryable<VirtualMachineInfo> result = GetAllGroupsInternal(userContext);
if(filter.OwnerId != Guid.Empty)
{
result = result.Where(g => g.OwnerID == filter.OwnerId);
}
// this is the unmapped property
if(filter.State.IsNotNullOrEmpty())
{
result = result.Where(g => g.State == filter.State);
}
// This will throw Class Member Unmapped exception
return new List<GreenGroup>(result);
}
However, since State is not a field in the database, does that mean I cannot include it in my linq query, but would have to further filter my list after the query returns?
I've looked at a few sites including this one in which the user receives the same exception Class Member unmapped but the field is in their database so it doesn't look like an explicit cast will help me out.
Is my only option to split up the filtering like so?
public List<GreenGroup> GetGreenGroups(GroupFilter filter)
{
IQueryable<VirtualMachineInfo> result = GetAllGroupsInternal(userContext);
if(filter.OwnerId != Guid.Empty)
{
result = result.Where(g => g.OwnerID == filter.OwnerId);
}
var groups = new List<GreenGroup>(result);
if(filter.State.IsNotNullOrEmpty())
{
groups = (from g in groups where g.State == filter.State select g).ToList();
}
return groups;
}
A:
You can use an unmapped field from a partial class in a select clause, but not in a where clause. In the case of the select clause, LINQ to SQL hydrates the entire object and then performs the select projection as necessary. In the case of other clauses (where/order by/etc), the LINQ to SQL engine requires that the columns exist in the database in order to perform the appropriate operation. If you must use the unmapped property in a where clause, you have to force your query from IQueryable to IEnumerable before using the unmapped property. Unfortunately, this requires that the superset be hydrated on the client side and the remainder of the query operation performed client side, which is likely a performance bottleneck. In your example, the final If clause would be something like the following:
IEnumerable<GreenGroup> groups;
if(filter.State.IsNotNullOrEmpty())
groups = (from g in groups.ToEnumerable() where g.State == filter.State select g);
| 2023-11-22T01:26:29.851802 | https://example.com/article/9471 |
Intracellular Regulatory Mechanisms: Regulation in multicellular forms may be an elaboration upon the pattern evolved in microorganisms.
The study of metabolic regulation in microorganisms has revealed several simple but efficient regulatory circuits. In one, the operation of an entire sequence of enzymes is controlled by the activity of the initial enzyme which contains a specific inhibitor site. When this site is combined with the endproduct of the sequence, the catalytic site is rendered inactive. In another, the formation of an entire sequence of enzymes is controlled by means of a cytoplasmic mediator which blocks the transcription of the genetic message (repression) when activated by the endproduct, or which allows the transcription (induction) when activated by the substrate of the first enzyme in the sequence. Additional circuits have been proposed for the regulation of RNA and DNA synthesis. The same regulatory devices could account, in part, for intracellular metabolic control in more complex animal and plant forms. However, superimposed upon these simple control circuits will be found others which take advantage of the greater degree of organization in these cells and of the possibilities for regulating gene function that are provided by the chromosomes. The pattern of proteins with special control sites, such as have evolved in the relatively simple controls found in bacteria, may also be found essential for intercellular controls involving nervous and humoral mechanisms. | 2023-08-24T01:26:29.851802 | https://example.com/article/5810 |
Buffered Solutions Versus Isotonic Saline for Resuscitation in Nonsurgical Critically Ill: Protocol for Cochrane Review.
Fluid resuscitation is one of the most prevalent treatment in critical care. There is not definitive evidence about the best fluid for resuscitation. The aim of this review will be to asses the efficacy and safety of buffered solution versus saline. We will perform an electronic search in Medline, Embase, and Central. Studies will be eligible if they are clinical trials who including critical ill patients. Primary outcomes are mortality and renal failure. All findings will be tabulated and synthesized. We will perform a meta-analysis according to Cochrane Review standards. We will design a summary of findings table. | 2024-05-17T01:26:29.851802 | https://example.com/article/5281 |
Mediated transport of anions in band 3-phospholipid vesicles.
Band 3 protein, extracted from human erythrocyte membranes by Triton X-100, was recombined with egg lecithin/cholesterol mixtures to form small unilamellar vesicles at a yield of 15-20%. These systems exhibited sulfate fluxes which were inhibitable by stilbene disulfonates and other inhibitors. Maximal inhibition could only be obtained when inhibitors were present at both membrane surfaces. Inhibitor constants I50 were higher than in the native membrane. Quantitatively, transport function was retained at least 60%, as related to the amount of protein involved. Sulfate transport in the recombinates resembled transport in the native membrane with respect to temperature dependence (Ea = 29-32 kcal/mol), pH dependence between pH 6.5 and 7.8, and the relationship between new and exchanges fluxes. In contrast to the native cell, concentration dependence was linear up to 80 mM sulfate, which may be indicative of a lowered affinity for the substrate. Lactate transport in these systems, although substantial, was insensitive to stilbene disulfonates as well as to mercurials, indicating that band 3 is not involved in the specific monocarboxylate transfer in the erythrocyte. Anion transport in band 3-lipid recombinates was insensitive to cholesterol between 0 and 27 mol%. Treatment with proteases, while not affecting transport per se, abolished sensitivity to stilbene disulfonate inhibitors. These observations indicate a number of disturbances of band 3 after recombination, in spite of a preservation of the major transport properties. | 2023-11-17T01:26:29.851802 | https://example.com/article/2926 |
Council Pushes Decision On Tree Canopy Bill To June
A decision on controversial legislation that would force homeowners to pay for tree canopy lost in new home or home addition projects won’t come until the summer.
Councilmember Roger Berliner (D-Bethesda-Potomac) said at a meeting of the Transportation & Environment Committee this morning that final recommendations from the Committee to the full Council won’t come until after work on the FY 14 budget is finished.
Leggett and officials from the county’s Department of Environmental Protection proposed the measure as a counter to new home building on existing residential lots they say has meant the loss of much tree canopy in many of Bethesda’s older neighborhoods. In an earlier presentation, they showed satellite imagery of a neighborhood along Fairfax Road from 2002 and 2012 with noticeably less tree cover because of take-down home construction projects.
The bill would require property owners who get rid of tree canopy in any building process that requires a sediment control plan to pay into a county fund. That fund would work to replace that tree canopy nearby using a sliding scale of fees based on the amount of tree canopy lost.
The building industry quickly came out against the proposed fees and council members still want to see how the legislation compares with other jurisdictions.
“I’m pleased that we’ve closed the gaps with our various stakeholders and I think know we are within range of making this happen for our community,” Berliner said. “I’m hoping we are coming to the end.”
The Committee did agree to exempt Park and Planning property from the legislation, which the Department of Environmental Protection did not object.
Also on the table is a credit that would lower the cost of removing tree canopy if a property owner protected 25 percent of the tree canopy on-site or made “unusual” efforts to save trees. Builders opposed to the bill have argued that existing stormwater management laws make it difficult to protect trees even if the builder and property owner would prefer to. | 2024-04-11T01:26:29.851802 | https://example.com/article/7490 |
Association between external pelvimetry and vertex delivery complications in African women.
To assess association between external pelvimetry and delivery complications in vertex presentation. Prospective cohort study of 2,413 pregnant women antenatally measured for height and external pelvimetry in four hospitals of the former Republic of Zaire. Complications during delivery of single fetus weighing 2,000 g or more in vertex presentation. Cut-off values at risk for delivery complications were height and pelvic distances closest to the study population 10th percentile. In univariate analysis, maternal height showed significant relative risk for predicting primary cesarean section for failure to progress: 2.0 (95% CI=1.0-4.1; p=0.050) and vacuum or forceps delivery: 15.7 (95%, CI=6.6-37.5; p<0.001). Selected external pelvic distances showed significant relative risks for predicting the following complications: primary cesarean section for failure to progress, elective repeat cesarean section, vacuum or forceps delivery and spontaneous intrapartum stillbirth. Among pelvic predictors, transverse diagonal (TD) of Michaelis sacral rhomboid area was associated with all of these complications. Intertrochanteric (IT) diameter was associated with three of them. The relative risks ranged from 2.3 (95% CI=1.1-6.3; p=0.030) to 9.6 (95% CI=4.1-22.5; p<0.001) for these strongest predictors. External pelvic distances help to predict vertex delivery complications in African women. The predicted complications are compatible with the cephalopelvic disproportion concept (CPD). After validation of current results in a separate cohort, measurements of IT and/or TD are recommended to improve antenatal screening of women at risk for CPD in limited resources settings. | 2024-01-06T01:26:29.851802 | https://example.com/article/9997 |
Smurfs: The Lost Village (2017)
overview : In this fully animated, all-new take on the Smurfs, a mysterious map sets Smurfette and her friends Brainy, Clumsy and Hefty on an exciting race through the Forbidden Forest leading to the discovery of the biggest secret in Smurf history.Genres : Adventure, Animation, Comedy, FamilyTags : sequel, kids | 2024-01-01T01:26:29.851802 | https://example.com/article/7347 |
This invention relates generally to wireless communication services, and more particularly to push-to-talk and location-based services in cellular telephones.
Due to the pervasiveness of cellular telephones and other wireless communication devices, manufacturers and service providers continue to explore features and/or services that will distinguish their products from their competitors' products. Currently, push-to-talk services and location-based services are particularly popular among consumers.
Push-to-talk services comprise half-duplex voice services where cellular telephones operate similarly to a walkie-talkie. Only one user speaks at a time while all other users listen. To talk, a participant presses a push-to-talk control or button and begins speaking while holding the push-to-talk button. After the participant finishes speaking, he/she releases the push-to-talk button to give other participants a chance to speak.
Location-based services provide cellular telephone users personalized services tailored to their location. These services determine the location of the user using one of several location determining technologies, such as GPS (Global Positioning System). Based on the determined location and other personalized information, the location-based service provides the user with personalized location-specific information. For example, location-based services may provide the user with a list of nearby businesses, directions to a specified location, etc.
Push-to-talk and location-based services currently operate independently on conventional cellular telephones. However, it may be beneficial if manufacturers and/or service providers develop enhanced push-to-talk and location-based services by taking advantage of complementary push-to-talk and location-based operations. | 2024-02-09T01:26:29.851802 | https://example.com/article/7311 |
Potential ameliorative effects of grape seed-derived polyphenols against cadmium induced prostatic deficits.
Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured by western blot. The levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP ameliorated the prostatic oxidative stress and fibrosis induced by CdCl2. GSP also inhibited the over-generation of TGF-β1 and p-Smad3, as well as enhanced the levels of Smad7, Nrf-2, HO-1, γ-GCLC and miR-133a/b. These results showed that GSP could attenuate Cd-induced prostatic deficits. | 2024-05-15T01:26:29.851802 | https://example.com/article/4707 |
Benitez won’t stop Napoli rotation
By Football Italia staff
Rafael Benitez has defended his rotation policy after Napoli’s shock 1-1 draw with struggling Sassuolo in midweek.
“We know that making changes to the starting line up is necessary,” the Spaniard noted. “Especially with so many games so close to each other.
“It’s not a question of starters and reserves for me, everyone can play in my mind. A squad is important if you want to win something at the end of the season.
“We want to be fighting for honours at the end of the year, not win one game by losing players who are tired or injured.”
The Stadio San Paolo boys had won their opening four League games of the campaign before the setback at home in midweek.
“Everyone was expecting the three points against Sassuolo, but the game only ended in a draw. Now I’m expecting a reaction against Genoa tomorrow.
“The side is focused on them right now. We’ll only start to think about Arsenal from Saturday night onwards.”
Benitez hinted that summer signing Duvan Zapata may be handed his debut at Marassi tomorrow.
“I wanted to put him on against Sassuolo, but then I couldn’t. He’s training well and his moment is close. He’s at 100 per cent mentally – I speak to him on a daily basis.”
The former Chelsea boss also insisted he wasn’t worried by the absence of the injured Christian Maggio.
“Giandomenico Mesto is doing well there for now, while Juan Zuniga can be fielded at right-back too.”
Watch Serie A live in the UK on Premier Sports for just £9.99 per month including live LaLiga, Eredivisie, Scottish Cup Football and more. Visit: https://www.premiersports.com/subscribenow | 2024-02-19T01:26:29.851802 | https://example.com/article/9646 |
// Copyright (c) 2016, Baidu.com, Inc. All Rights Reserved
// Use of this source code is governed by a BSD-style license that can be
// found in the LICENSE file.
#pragma once
#include "volum.h"
#include "volum_collector.h"
namespace baidu {
namespace galaxy {
namespace volum {
class TmpfsVolum : public Volum {
public:
TmpfsVolum();
~TmpfsVolum();
baidu::galaxy::util::ErrorCode Construct();
baidu::galaxy::util::ErrorCode Destroy();
//baidu::galaxy::util::ErrorCode Gc();
int64_t Used();
std::string ToString();
private:
baidu::galaxy::util::ErrorCode Construct_();
boost::shared_ptr<VolumCollector> vc_;
};
}
}
}
| 2024-01-31T01:26:29.851802 | https://example.com/article/4552 |
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Gucci Mane Could Face 20 Years For Federal Gun Charges
2013 has been a rough year to be Gucci Mane. His most recent troubles include a public meltdown on Twitter and subsequent arrest for disorderly conduct and possession of marijuana and a handgun. Now CNN reports that according to the U.S. Attorney's Office for the Northern District of Georgia Gucci (né Radric Davis) was charged today in a federal court for two counts of possession of a firearm. Read more below.
'On September 12, 2013, Davis, who was a felon at the time, was found in possession of a firearm,' [a news] release said. 'Then, just two days later, on September 14th, he again possessed a firearm different from the earlier gun. On both occasions, Davis displayed the loaded firearm, acted erratically, and made threats to individuals, including police and his attorney.'
Atlanta police and the Bureau of Alcohol, Tobacco, Firearms and Explosives, who are investigating the incident, applauded the arrest. Atlanta Police Chief George Turner said in a statement, 'We cannot tolerate convicted felons ignoring the law by carrying firearms and endangering our citizens.'
Added U.S. Attorney Sally Quillian Yates, 'This is how people get hurt, and we are committed to ensuring that convicted felons not have guns.'
A federal grand jury indicted Davis on November 19. He made an initial appearance before Magistrate Judge Linda T. Walker and was detained in custody pending trial. Each charge of being a felon in possession of a firearm carries a maximum sentence of 10 years in prison and a fine of up to $250,000. | 2024-07-06T01:26:29.851802 | https://example.com/article/6240 |
et c = 33.0000052 + -33. What is c rounded to 6 decimal places?
0.000005
Let l = -147472.1 - -147455.8566352. Let s = l + 16.64337. Let y = s - 0.4. Round y to six decimal places.
0.000005
Let g = -0.3 - -0.3. Let h = 0 - g. Let d = 0.00000008 - h. Round d to 7 dps.
0.0000001
Let o(f) be the second derivative of 2917*f**4/6 + 2*f**3/3 - 6*f. Let a be o(-6). What is a rounded to the nearest 100000?
200000
Let i = -13 + 12.94. Round i to 1 decimal place.
-0.1
Let y = 10 - 9. Let f = -40473321.99999994 - -40473321. Let h = f + y. What is h rounded to seven decimal places?
0.0000001
Let g = -40.01 + 74.8. Let z = -34.6337 + g. Let i = 0.15 - z. Round i to three decimal places.
-0.006
Let t = 65.906 + -66. Let z = t + 0.0939854. Round z to 6 dps.
-0.000015
Let d = -0.06 + -4.94. Let u = d - -4.999936. What is u rounded to five dps?
-0.00006
Let j = 8.364 - 8.4. What is j rounded to three decimal places?
-0.036
Let s(w) = -w**2 - 3*w - 4. Let g be s(-3). Let u(y) = 11*y**2 - 4 + 25*y**2 + 0*y - 2*y. Let a be u(g). What is a rounded to the nearest one hundred?
600
Let h = -4.5 - 129.5. Let u = h - -134.000089. What is u rounded to 5 decimal places?
0.00009
Let z = 31.7 + 0.3. Let s = z - 32.63. Round s to 1 decimal place.
-0.6
Let o be -300*(5 - 4125/(-9)). Round o to the nearest 10000.
-140000
Let o(d) = d**2 + 11*d + 23. Let a be o(-16). What is a rounded to the nearest one hundred?
100
Suppose -4700 = -2*m + m. What is m rounded to the nearest 1000?
5000
Suppose -3*k + 8072 = -3*g + 278084, 4*g + 179984 = -2*k. What is k rounded to the nearest ten thousand?
-90000
Let z = -0.01456 + 0.015. Round z to four decimal places.
0.0004
Suppose -9 - 6 = 3*h, -2*h - 1210 = 3*q. Round q to the nearest 100.
-400
Suppose -i = -4*n, 5*i - n + 23 = -4*n. Let f(m) = -40*m**2 + 4*m - 4. Let y be f(i). What is y rounded to the nearest one hundred?
-700
Let l(t) = 33999*t**2 + 2*t - 1. Suppose 0 = -4*h - 5*m + 23, 5*m - 10 = h + m. Let b = -1 + h. Let o be l(b). Round o to the nearest 10000.
30000
Let l(r) = -2 - 2 - 1666*r - 2. Let z be l(9). Let s be z/(((-15)/(-132))/(-5)). Round s to the nearest 100000.
700000
Suppose 2*v = -3*v + 19000000. What is v rounded to the nearest 1000000?
4000000
Let b = -5.2132 + 5.2. What is b rounded to three dps?
-0.013
Let k(v) = 503*v**3 - v**2 + v. Let p be k(1). Let q be -4 + p - -1*1. What is q rounded to the nearest 100?
500
Let f = -21.8775 - -22. Let b = f - 0.12. Round b to three dps.
0.003
Let a = -2.1 + 2.10000034. What is a rounded to 7 decimal places?
0.0000003
Let z = 47 - 24. Suppose -z = 3*v + 4*y, -2*v = -3*y + 6*y + 17. Let x be (-1500)/(15/12 + v). What is x rounded to the nearest ten thousand?
-10000
Let r = 164.7968 - 166.9967971. Let a = -3.3 + 1.1. Let f = r - a. Round f to 6 dps.
0.000003
Suppose -3*m - 137 = 82. Suppose 0 = -5*v + 15, -2*v - 114 = -u - 6*v. Let w = u - m. Round w to the nearest 10.
180
Let c = 1724 - 1871.3. What is c rounded to the nearest 10?
-150
Let g = -153 - -153.91. What is g rounded to 1 decimal place?
0.9
Let f = 1590977 - 2980977. What is f rounded to the nearest 100000?
-1400000
Let r = 136.1 + -130. Let h = r + -6.10000029. Round h to seven decimal places.
-0.0000003
Let m(b) = -340001*b**2 - 2*b. Suppose -2*t = 4*k + 17 - 3, -2*t = -k + 4. Let w be m(k). What is w rounded to the nearest one hundred thousand?
-1400000
Let z(c) be the third derivative of 0*c + c**2 + 0 - 529/24*c**4 - 1/6*c**3. Let f be z(1). What is f rounded to the nearest one hundred?
-500
Let n be 0/(-2)*(-8)/(-8). Let r be 9/(4 - 1) - n. Suppose 3*b + 4*h - 6012 = 0, 0*b - r*b - 3*h + 6009 = 0. Round b to the nearest one thousand.
2000
Let n = 4 + -3.99. Let d = -6666 + 6666.0099872. Let i = d - n. What is i rounded to six decimal places?
-0.000013
Suppose -q = -3*q - 3*p - 18585, -q - 5*p - 9275 = 0. Round q to the nearest 1000.
-9000
Suppose 0 = -3*h - 2*h + 50255. Let u = 49051 - h. Round u to the nearest ten thousand.
40000
Suppose 0 = 5*r - 802 + 3992. What is r rounded to the nearest one hundred?
-600
Let z = 7937.052 - 7952. Let p = -15 - z. What is p rounded to 2 decimal places?
-0.05
Let f be (2 + -3)/(2/(-6)). Suppose -s + 297 = -f*r + 13, -2*r - 286 = -s. What is s rounded to the nearest one hundred?
300
Let t = 6 - 3. Let d = t + -2.99999955. What is d rounded to 7 decimal places?
0.0000005
Let t = -1675 - -1674.071. Let a = t - -0.98. What is a rounded to two dps?
0.05
Let t(y) = 3485716*y - 12. Let n be t(7). What is n rounded to the nearest 1000000?
24000000
Let g = 603 + -385. Let m = g + -120. Let z = m + -98.00000126. Round z to 7 dps.
-0.0000013
Suppose 20333223 = 2*d + 66133223. Round d to the nearest 1000000.
-23000000
Let p = -0.05002 + 0.05. Let c = p + 0. Round c to 4 decimal places.
0
Let j = -3 - 0.4. Let g = 3.348 + j. Let z = -0.338 + g. What is z rounded to 1 decimal place?
-0.4
Let v = -222.586 - -223. Let s = -0.4 + v. Round s to two decimal places.
0.01
Let k(t) = 2036*t**3 + 7*t**2 - 6*t + 8. Let d(y) = -2*y - 3. Let i be d(-3). Let w = i + 3. Let q be k(w). Round q to the nearest one hundred thousand.
400000
Suppose 3*t - 2849247 = 12000753. Round t to the nearest one hundred thousand.
5000000
Let t = -4 + 3.8. Let w = 0.19 + t. Let x = -0.0036 - w. Round x to 3 decimal places.
0.006
Suppose -4*x = -8 - 4. Suppose 4*m + 4*l + 0*l - 260012 = 0, 0 = -3*m + x*l + 194991. Suppose a + 4*a - m = 0. Round a to the nearest one thousand.
13000
Let y(j) = -11906*j - 10. Let a be y(-7). Let p(d) = 1 + 0 + 3 + a*d. Let i be p(3). Round i to the nearest 100000.
300000
Let p = -259 + 298.1. Let r = -7.6 + -37.4. Let i = r + p. What is i rounded to zero decimal places?
-6
Suppose -460884 = o + 569116. Round o to the nearest 100000.
-1000000
Let u(z) = 1921*z**2 - 5*z - 3. Let y be u(5). Suppose -5*k - j = -239997, 0*j - j = k - y. Round k to the nearest 10000.
50000
Let t = 225 - 224.9999632. What is t rounded to six decimal places?
0.000037
Let a = -0.2 - -0.1999885. What is a rounded to six dps?
-0.000012
Let j = 93158 - 93277.882. Let z = 120 + j. Let s = -0.1237 + z. What is s rounded to 3 dps?
-0.006
Let r = -10463374 - -17563374. Round r to the nearest one million.
7000000
Suppose 1 = 5*j - 9. Suppose -2*o - o - 2*t = 0, -8 = j*o + 4*t. Suppose -3*m = o*c + 3*c + 175, c + 205 = -4*m. What is m rounded to the nearest 10?
-50
Let b = 24.987 - 25. Let w = b - -0.064. Let y = 0.0706 - w. Round y to 3 dps.
0.02
Let v = -272 - -272.00000247. Round v to 7 dps.
0.0000025
Suppose 0 = -r + 4*r - 30. What is r rounded to the nearest 10?
10
Let f = -20.1 + 20. Let w = f - -0.1004. What is w rounded to 4 dps?
0.0004
Let z = 3 - 5. Let x = -1.999966 - z. Round x to 5 dps.
0.00003
Let y = -1.109485464 + -0.063273324. Let i = y - 7.827241882. Let u = i - -9. What is u rounded to seven decimal places?
-0.0000007
Let l be 293612*(-3)/(6/1). Let t = 94806 + l. What is t rounded to the nearest ten thousand?
-50000
Let h = 0.035 + -0.0350065. Round h to six dps.
-0.000007
Let o be 6573336 + -2*(-3)/(-6). Suppose 2*x + 5*i - 10235991 = 2910670, -x - i + o = 0. Let r = 1373338 - x. Round r to the nearest one million.
-5000000
Suppose 3*u + 0*u = -1116. Round u to the nearest 10.
-370
Suppose 10*d - 179 = 21. What is d rounded to zero decimal places?
20
Suppose 0 = -3*t - 3*a + 3, -5*a = -a + 16. Suppose 0 = 5*d - t*x + 3300010, 7*x = d + 2*x + 660010. Round d to the nearest 100000.
-700000
Let j(y) be the third derivative of -y**5/20 + y**4/6 - 5*y**3/6 - y**2. Let r be j(4). What is r rounded to the nearest ten?
-40
Let r = 0.2 + -0.193. What is r rounded to 2 dps?
0.01
Let i = 8854.104 + -8884. Let a = i + 30. What is a rounded to two dps?
0.1
Let b = 9 + -14. Let a(j) be the second derivative of 20801*j**5/20 + 5*j**4/12 - j. Let d be a(b). Round d to the nearest one million.
-3000000
Let b = 33.32227 - -0.66733. Let c = 34 - b. Round c to 3 dps.
0.01
Let t = -4 - 20. Let q = t - -23.915. Let h = q + 0.08500039. What is h rounded to seven decimal places?
0.0000004
Let y = -50 - 47. Let c = y + 142. Suppose -123 - c = -3*r. What is r rounded to the nearest 10?
60
Let q = -5007 + 16399. Suppose -4*f = -3*x + q, -309 = -x + f + 3489. What is x rounded to the nearest 1000?
4000
Let f be 3 + (3/2)/(21/( | 2024-04-13T01:26:29.851802 | https://example.com/article/9161 |
Naoya Tomita plans to deny stealing camera
Swimmer Naoya Tomita, who was summarily indicted for stealing a camera at last month’s Asian Games in Incheon, South Korea, plans to deny committing the theft, according to an informed source.
Tomita, 25, intends to give an explanation of what happened at a news conference on Nov. 6 in Nagoya.
According to the indictment, he took a camera that had been left behind by a South Korean reporter at Munhak Park Tae Hwan Aquatics Center on Sept. 25. Tomita had gone there to cheer on teammates during practice.
Tomita later admitted to the charge after being questioned by police and reached a settlement with the victim.
Before departing for Japan from Incheon International Airport, Tomita bowed to reporters and said: “I apologize for causing so much trouble. I did not do this.”
According to the source, Tomita now claims that someone else placed the camera inside his carrying bag. | 2023-10-08T01:26:29.851802 | https://example.com/article/5912 |
// Copyright 2015 The Chromium Authors. All rights reserved.
// Use of this source code is governed by a BSD-style license that can be
// found in the LICENSE file.
#include "components/password_manager/core/browser/password_manager_constants.h"
namespace password_manager {
const base::FilePath::CharType kAffiliationDatabaseFileName[] =
FILE_PATH_LITERAL("Affiliation Database");
const base::FilePath::CharType kLoginDataFileName[] =
FILE_PATH_LITERAL("Login Data");
const char kPasswordManagerAccountDashboardURL[] =
"https://passwords.google.com";
const char kPasswordManagerHelpCenterSmartLock[] =
"https://support.google.com/accounts?p=smart_lock_chrome";
} // namespace password_manager
| 2024-02-06T01:26:29.851802 | https://example.com/article/6711 |
The present invention generally relates to polyolefin products such as polyethylene and polypropylene packaging materials for food and beverages. More particularly, this invention relates to reduction of aldehydes in polyolefins by incorporation of additives capable of reacting with these aldehydes.
Polyolefins, particularly polyethylene and polypropylene, are utilized extensively across a wide range of industries in a variety of product forms, including fibers, films, and three-dimensional structures. A particularly important application for polyolefins is containers, especially for food and beverages. Polyolefin materials often are selected for use in food and beverage packages and closures because they are inexpensive, lightweight, easily modified, and impact resistant. Yet despite these advantages, polyolefins can have certain undesirable attributes. For example, they frequently contribute xe2x80x9coff-tastexe2x80x9d to packaged products, particularly sensitive products such as water. This off-taste commonly is referred to as a xe2x80x9cplasticxe2x80x9d off-taste. It would be highly desirable to reduce or eliminate this off-taste from products packaged in polyolefin materials.
One approach that has been taken to mitigate the off-taste problem in the non-polyolefin polymer polyethylene terephthalate (PET) is to incorporate additives that are scavengers for aldehydes that are produced by degradation of the PET itself during heat processing of the polymer. U.S. Pat. No. 4,837,115 to Igarashi discloses incorporating additives of amine-group terminated polyamides and amine-group containing small molecules into PET, wherein the additives selectively react with acetaldehyde (AA) that is generated in the PET. Igarashi teaches that the amine groups are effective because they can react with AA to form imines, where the amine nitrogen forms a double bond with the AA moiety. Igarashi teaches that essentially any amine is effective. Mills (U.S. Pat. Nos. 5,258,233; 5,650,469; and 5,340,884) and Long (U.S. Pat. No. 5,266,416) disclose the use of various polyamides, especially low molecular weight polyamides, while Turner and Nicely (PCT WO 97/28218) disclose the use of polyesteramides. These polyamides and polyesteramides are believed to react with AA in the same manner as described by Igarashi. While these AA scavengers are effective at reducing the AA content of melt-processed PET, they suffer from their own drawbacks. In particular, relatively high loadings of the polyamides are needed to effect significant AA reductions, and a significant yellowing of the PET occurs from incorporation of these amine-containing additives. This coloring is believed to be due to the inherent color of the imine group, which for most applications is undesirable because most polyolefin articles in use today are clear and uncolored.
U.S. Pat. No. 5,663,223 to Teumac discloses using a polymeric liner that includes inorganic sulfites or organic hydrazides as flavor protectant compounds. These compounds are added to scavenge oxygen that otherwise could react with the polymer or additives therein to form off-taste producing aldehydes. Incorporation of these compounds into polyolefins is difficult, however, because these protectant compounds have an extremely low thermal stability. Furthermore, these compounds may themselves contribute to an off-taste in sensitive products, and hydrazides react with aldehydes to form hydrazones, which often are highly colored. Such colors oftentimes are unwanted, as many applications require or desire that the polyolefin packaging be white or clear.
A simple and economical method is therefore needed for reducing aldehyde content in polyolefin products without using aldehyde-scavenging agents that impart an off-taste to products packaged in containers made from polyolefins or that impart a color to such polyolefin containers.
It is therefore an object of the present invention to provide methods for decreasing aldehyde content of products in contact with polyolefin packaging materials.
It is another object of the present invention to provide methods for decreasing aldehyde content in polyolefin materials without coloring the polyolefin materials and without creating another source of product off-taste.
It is a further object of the present invention to provide polyolefin packaging containers which provide a decreased aldehyde content of products contained therein.
Methods are provided for decreasing the aldehyde content in polyolefin materials by combining the polyolefin material with an organic additive compound that reacts with aldehydes to form water and a resulting organic compound. The organic additive compound comprises at least two hydrogen-substituted heteroatoms bonded to carbons of the organic additive compound such that the organic additive compound is reactive with aldehydes present in the polyolefin to form water and the resulting organic compound, which comprises an unbridged five- or six-member ring including the at least two heteroatoms. The resulting organic compound neither imparts an off-taste to food and beverage products in contact with the polyolefin nor discolors the polyolefin.
The organic additive compound can be added at relatively low levels to the polyolefin and still sufficiently decrease the aldehyde content of the polyolefin. The organic additive compound preferably is substantially thermally stable at the melt processing temperature of the polyolefin. Preferred organic additive compounds include anthranilamide, 3,4-diaminobenzoic acid, malonamide, tryptophan, and allantoin.
It has been discovered that the off-taste from beverage and food products packaged in polyolefin materials is in fact largely due to the migration of C8 through C10 aldehydes from the polyolefin into the products, and that these aldehydes typically are the degradation products of various unsaturated additives used as processing aids in the polyolefins. These additives degrade chemically, thermally, or by photo-oxidation to yield these undesirable aldehydes. Examples of processing aid additives are erucic acid derivatives, such as erucamide, which often is used as a processing aid additive due to its efficacy and low cost. Although one might propose eliminating the processing aid additives as a solution to the aldehyde problem, the processing properties provided by the unsaturated additives are important and not readily duplicated. It thus is desirable to continue the use of unsaturated additives while simultaneously minimizing or eliminating the off-taste caused by their degradation. Methods therefore have been developed for substantially decreasing the aldehyde content of processed polyolefins by incorporating low levels of an organic additive compound into the polyolefin, such as during melt processing. The organic additive compound scavenges the aldehyde present in the polyolefin by chemically reacting with the aldehyde.
The Aldehyde-Containing Polyolefin
The present method is useful for removing aldehydes from a variety of polyolefin materials. In preferred embodiments, the polyolefin is polypropylene (PP) or polyethylene (PE). Other useful polymers include polyisoprene, polystyrene, poly(vinyl chloride), and poly(methylmethacrylate). The present method can be used with essentially any polyolefin polymer in which unsaturated additives have been incorporated.
Polyolefins, such as PP and PE, can be processed to form films, sheets, and three-dimensional articles, which can be used as or in packaging containers and closures. As part of the processing of the polyolefin, for example, melt-processing (e.g., extrusion and molding), processing aids typically are added to achieve favorable product properties and/or to improve ease of polymer processing. Representative types of processing aid additives include internal lubricants, external lubricants, and viscosity modifiers. Many of these processing aid additives are unsaturated compounds. Euramide, for example, often is added to polyethylene and polypropylene to act as a lubricant to improve handling and prevent the polymer product from sticking to itself. Other unsaturated additives that may generate the off-taste aldehyde include vegetable oil derivatives and castor oil derivatives. These unsaturated processing aid additives are known to degrade thermally, chemically, or by photo-oxidation to generate aldehydes in the polyolefin material. The aldehydes particularly identified as causing off-taste in products are octanal, nonanal, and decanal (i.e. the C8 through C10 aldehydes).
The Organic Additive Compound
Suitable organic additive compounds effective in the method described herein are characterized as small molecules that include at least two hydrogen-substituted heteroatoms bonded to carbons of the organic additive compound such that the organic additive compound is reactive with aldehyde in the polyolefin to form water and a resulting organic compound comprising an unbridged 5- or 6-member ring including the at least two heteroatoms. Unlike prior art methods that depend on the formation of inherently colored imines, the formation of unbridged 5- or 6-member ring structures do not inherently result in color formation. Moreover, thermodynamics often favor ring formation more than imine formation; therefore, significantly lower amounts of the organic additive compound described herein can effectively decrease the aldehyde content in processed polyolefins.
Heteroatoms capable of reacting with the aldehyde include oxygen (O), nitrogen (N), and sulfur (S). The heteroatoms of the additive compound should have at least one bond to an active hydrogen (H), and in the course of condensing with the aldehyde should split off water. Preferred functional groups containing these heteroatoms include amine (NH2 and NHR), hydroxyl (OH), carboxyl (CO2H), amide (CONH2 and CONHR), and thiol (SH). It is necessary for these functional groups to be sterically arranged so that upon condensation with the aldehyde an unbridged 5- or 6-member ring can be formed. The structural arrangement preferably allows the formation of a six-member ring. Furthermore, it is especially preferred that heteroatoms of the organic additive are attached to a preformed ring or rings. The preformed ring(s) most preferably are aromatic so that the unbridged 5- or 6-member ring of the resulting organic compound is bonded to the aromatic ring.
The organic additive compound preferably is substantially thermally stable at the temperatures required for melt-processing the polyolefin. The organic additive compound also preferably includes functional groups that include the heteroatoms and active hydrogens and that are relatively unreactive toward other additives, if any, present in the polyolefin. High thermal stability and low reactivity to other additives increase the amount of unreacted organic additive compound that is available for condensation with the aldehyde, thus reducing the amount of organic additive compound needed to achieve effective levels of aldehyde scavenging. Compounds with decomposition temperatures greater than 200xc2x0 C. as measured by Thermal Gravimetric Analysis (TGA) are most preferred. Compounds that decompose by intramolecular elimination reactions at temperatures less than about 200xc2x0 C. are less likely to be effective.
Examples of organic additive compounds that satisfy these parameters and that are effective at decreasing the aldehyde content of product in contact with polyolefins include anthranilamide, salicyclamide, salicylanilide, o-phenylenediamine, 3,4-diaminobenzoic acid, 1,8-diaminonaphthalene, o-mercaptobenzamide, N-acetylglycinamide, malonamide, 3-mercapto-1,2-propanediol, histidine, tryptophan, 4-amino-3-hydroxybenzoic acid, 4,5-dihydroxy-2,7-naphthalenedisulfonic acid disodium salt, biuret, 2,3-diaminopyridine, 1,2-diaminoanthraquinone, dianilinoethane, allantoin, 2-amino-2-methyl-1,3-propanediol, pentaerythritol, dipentaerythritol, and poly(vinyl alcohol). Preferred organic additive compounds include anthranilamide, 3,4-diaminobenzoic acid, malonamide, tryptophan, and allantoin. Anthranilamide and 3,4-diaminobenzoic acid are most preferred.
The amount of organic additive compound necessary to achieve the desired decrease in aldehyde content is dependent on which specific additive compound is used and the amount of reduction required. Organic additive compounds that are relatively more effective can achieve greater than 90% reduction in aldehyde content at loadings of between 200 and 500 ppm; additives that are relatively less effective may require addition levels up to 1000 ppm.
Using the Organic Additive Compound
The method of incorporating the organic additive compound into the polyolefin is not critical. For example, the organic additive compound can be dispersed in a liquid carrier which is then mixed with polyolefin pellets immediately before injection molding. The organic additive compound may also be incorporated by spraying a slurry of the additive in water onto the pellets prior to drying. In another embodiment, a melt or suspension of the organic additive compound is injected into pre-melted polyolefin. They also may be incorporated as a masterbatch pellet/pellet blend. The organic additive compound also may be incorporated by making a masterbatch of pellets of the additive compound with polyolefin and then mixing the masterbatch pellets with polyolefin pellets at the desired level before drying and injection.
The following equations illustrate the condensation reaction of suitable organic additive compounds described herein with an aldehyde (octanal) to form water and a resulting compound with an unbridged ring:
In the foregoing equations, X-H and Y-H represent functional groups including at least one active hydrogen represented by H and a heteroatom such as O, N, or S. In equation 3, R1 represents a ring which can be a 5- or 6-member ring and can be aromatic or nonaromatic.
Using the Polyolefin Composition
Containing the Organic Additive Compound
The composition comprising the polyolefin and the organic additive compound is, because of the reduced aldehyde content, particularly suitable for making containers such as a container for use in packaging beverages. With the reduced aldehyde content, the containers impart less of an off-taste to the beverages. This is particularly important for beverages, such as water, which do not have a strong flavor. Particularly preferred polyolefins for use in beverage packaging include polyethylene and polypropylene. Containers can be made with the polyolefin compositions described herein using conventional methods such as injection molding and blow molding. A typical method includes forming a preform with the polyolefin and organic additive compound, and then blow-molding the beverage container. The resulting containers can be used in the manufacture of package beverages according to conventional manufacturing methods. | 2024-02-22T01:26:29.851802 | https://example.com/article/5310 |
How Many Carbs Per Day to Lose Weight?
Determine how many carbs per day to lose weight is required. Most people who want to lose weight usually follow a low carbohydrate diet wherein they eat protein rich foods and limit the intake of foods that contain loads of carbohydrates like pasta, cereal, rice, potatoes, and bread. You need to eat more of nuts, cheese, fish, meat, and vegetables.
Studies reveal that the human body needs carbohydrates to function at its best and so if you eat less carbs, your brain may not function properly. Experts also say that without proper supervision, the diet regimen can make a person more prone to heart diseases and diabetes. Still if you are determined to stick with the low-carb diet, you may lose more in the initial attempt but a lot of people are not able to maintain it because of lack of determination. If you want to succeed, you should be patient and hard working. If you want to find out how many carbs per day to lose weight is needed for your body built, you should work closely with your health care provider. Losing weight can be hard and overwhelming but with the right knowledge, you can succeed and reach your goals.
The reason why a lot of people fail on a low-carb diet is because they were not able to sustain the weight loss using the right strategies. Ideally, you can lose several pounds in a few weeks and in order to maintain it, you will have to stick with the diet regimen no matter what. If you can’t follow the weight loss program, you will only gain more weight. So what are you waiting for? Determine how many carbs per day to lose weight is needed for effective attempts to get rid of excess pounds. Have the right attitude today!
Article Source:How Many Carbs Should i Eat to Lose Weight | 2024-04-09T01:26:29.851802 | https://example.com/article/6441 |
Hyoid apparatus
The hyoid apparatus is the collective term used in veterinary anatomy for the bones which suspend the tongue and larynx. It consists of pairs of stylohyoid, thyrohyoid, epihyoid and ceratohyoid bones, and a single basihyoid bone. The hyoid apparatus resembles the shape of a trapeze, or a bent letter "H". The basihyoid bone lies within the muscle at the base of the tongue.
In humans, the single hyoid bone is an equivalent of the hyoid apparatus.
References
Category:Bird anatomy
Category:Mammal anatomy
Category:Human head and neck | 2023-09-23T01:26:29.851802 | https://example.com/article/6979 |
Gavin Williamson has accused the prime minister of mishandling his sacking as defence secretary, describing it as a "shabby and discredited witch hunt".
Mr Williamson said he wanted a "full and impartial investigation" into the Huawei leak that led to his dismissal, with Scotland Yard having said the disclosure from a National Security Council (NSC) meeting did not breach the Official Secrets Act.
He said: "With the Metropolitan Police not willing to do a criminal investigation, it is clear a proper, full and impartial investigation needs to be conducted on this shabby and discredited witch hunt that has been so badly mishandled by both the prime minister and (senior civil servant) Mark Sedwill."
Were you part of Huawei leak? 'Absolutely not'
Sky News' political editor Beth Rigby said Mr Williamson had "come out all guns blazing" against Theresa May, who was hoping the fallout would "go away" after defending her decision to dismiss him.
Rigby explained: "She had hoped this story would go away, but I think this story will run on into next week.
"We will have to see when everyone goes back to the Commons how this plays out, what are his next moves, how much pressure does he continue to put on prime minister.
"She is already under huge pressure after shocking losses in the local elections. She is under pressure to set out her departure date and now Williamson is coming for her.
"She wants him to shut up and go away and he really won't."
Will PM hand over Huawei leak report?
Some at Westminster had called for a criminal investigation into the leak of a decision to green-light a bid by Chinese telecoms giant Huawei to help build Britain's 5G network, details of which found their way into the media.
Mrs May told Sky News on Friday she has confidence the inquiry that led to Mr Williamson being fired was "properly conducted" after it found "compelling evidence" that he leaked the information.
The prime minister added: "The importance of this was not about the information that was leaked, it was where it was leaked from. This was about the NSC and trust in the NSC."
Williamson case 'a breach of trust' - Gauke
Mr Williamson has asked for a copy of the report that led to his dismissal, but Mrs May refused to answer directly to his plea when asked by Beth Rigby.
"This was an inquiry that was properly conducted, it was conducted in the way that one would expect an inquiry of this sort to be conducted," she said.
"As a result, I took the decision that it was necessary for the then secretary of state for defence to leave his post."
Image: Huawei has become one of the world's leading smartphone manufacturers
There has been no official confirmation from the government that it does plan to allow Huawei to play a key role in the development of 5G in the UK, amid concerns it could enable spying by the Chinese government.
:: Listen to the Sophy Ridge on Sunday podcast on Apple podcasts, Google podcasts, Spotify, Spreaker
Australia, New Zealand and the US are among the Western nations to have barred the company from supplying vital elements of their infrastructure, and Canada could follow suit.
Following reports that the NSC had decided to allow Huawei to be involved in Britain, Downing Street said: "We don't comment on NSC discussions."
The Cabinet Office has discussed the leak with Met Police Assistant Commissioner Neil Basu, who said he had also taken legal advice over the fallout.
Image: Royal Navy reservist Penny Mordaunt replaced Mr Williamson as defence secretary
He said he was "satisfied that the disclosure did not amount to a criminal offence" and that it was not a matter for the police, adding: "Any organisation has the right to conduct an internal investigation into conduct in the workplace. It is not a matter for the police unless a crime is alleged.
"No crime has been alleged by the owner of the material and I am clear that the leak did not cause damage to the public interest at a level at which it would be necessary to engage Misconduct in a Public Office.
"It would be inappropriate to carry out a police investigation in these circumstances."
Image: Theresa May has said she was justified in sacking Mr Williamson
Mr Williamson - who has been replaced as defence secretary by Penny Mordaunt - previously told Sky News he would get the "nicest apology" from the prime minister if a criminal inquiry had gone ahead.
He had been "massively comfortable" with the prospect, adding that he was "visibly shocked" when he was informed of the decision to sack him. | 2023-10-06T01:26:29.851802 | https://example.com/article/9183 |
5 Tips on Beautifying Your Home for a Visitor
The problem is your home. For you, it’s embarrassing in its current condition.
So what do you do?
You beautify it, of course!
1 – Decorate Your Kitchen
Decorate your kitchen. Start rearranging the appliances and determine which arrangement seems most attractive. Consider making it more spacious, too.
Additionally, using fridge magnets is one cool idea. You can also put up framed pictures and quotations on the walls.
2 – Eliminate Odor (Especially In Your Living Room)
Another tip is to eliminate unpleasant smells in your home. If you’re a pet owner, this is a must. Try using aerosol sprays or natural deodorizers.
You should put emphasis on your living room because this is where your visitor may hang out often. Make sure it’s pleasant to be around in.
3 – Renovate Your Bathroom
The third tip is to renovate your bathroom. Take this tip very seriously if you must. While it seems costly, renovating your bathroom is a plus. If your visitor is staying for at least a few hours, she will need to make a trip to the bathroom. In fact, the first thing she does upon arrival might even be to head to your bathroom.
So put up new tiles, wash basins, and a medicine cabinet. Maybe you could even decorate it (with awesome shower curtains and candles) later on. If you don’t want to worry about this, hiring a contractor is always an option.
4 – Buy New Furniture
Does your cabinets have visible chips? Does your couch have holes in it? Do you have a 10-year old TV rack? Do you own a simple wooden table?
If so, buying furniture should be on your list. Shop for new ones, which will make your visitor feel like your home is also her home.
5 – Go for a Modern & Edgy Feel
If your home is an old-fashioned place, spicing things up is a great idea. This time, go for a modern and edgy feel. This gives off the vibe that you’re bold and brave.
So give your home some enthusiasm. Some ways that you can accomplish this are changing the wallpaper, adding high-tech gaming devices and a billiards table, and re-painting your doors.
The Bottom Line
On top of all the above-mentioned tips, remember to maintain the cleanliness of your home. Schedule a day or two in a week to clean your place because this will amplify the beautification that you just did. No one wants to visit a dirty and unorganized home, after all. | 2023-09-11T01:26:29.851802 | https://example.com/article/9841 |
Georgia Man Sank Lotto Fortune into Meth Business
Ronnie Music Jr. was in federal court earlier this month where he pleaded guilty to federal drug trafficking and firearm charges before Chief U.S. District Court Judge Lisa Godbey Wood. In February 2015, the 45-year-old ex-con won $3 million in the Georgia Lottery’s "100X the Money" game. After purchasing the scratch-off ticket from a local deli and collecting his winnings, he then proceeded to invest the money in an ill-advised methamphetamine business—an illicit venture that authorities quickly uncovered.
“I buy tickets every once in a while,” Music said in a Georgia Lottery statement at the time he won. “I couldn’t believe it, and I still don’t believe it yet.” It's even harder to believe that he took his legitimate funds and made them illegitimate, especially because criminals usually work it the other way around. Music pled guilty to conspiring with others to possess and distribute kilograms of crystal meth in Ware County, Georgia, about 240 miles southeast of Atlanta, and elsewhere. The drug venture unraveled when his co-conspirators were busted selling 11 pounds of meth, worth over $500,000, and investigators identified Music as the source of the drugs.
“Defendant Music decided to test his luck by sinking millions of dollars of lottery winnings into the purchase and sale of crystal meth,” U.S. Attorney Ed Tarver, of the Southern District of Georgia, said in a press release. “As a result of his unsound investment strategy, Music now faces decades in a federal prison.” Investigating agents confiscated over $1 million worth of meth, a large cache of firearms and ammunition, several vehicles and $600,000 in cash.
“Dude is crazy for real,” an ex-con, who served time in the feds for a crack conspiracy, tells The Fix. “I mean, you sell drugs to make money and this dude had money and he used it to get himself caught up in an indictment? That is crazy for real. He was doing it backward. Usually drug dealers are trying to buy winning lottery tickets for cash to make their drug money legit. It's a laundering scheme. This dude did it the other way around. Really stupid if you ask me.”
The case was a joint law enforcement investigation that included agents from the ATF, DEA and the Glynn-Brunswick Narcotics Enforcement Team.
Music faces a possible life sentence when he goes in front of the judge again to get his time. | 2023-09-27T01:26:29.851802 | https://example.com/article/9468 |
“I urge you to apologise for the offence you have caused to so many people in appearing to endorse the sentiment expressed by your Labour Colleague. I trust you will immediately demand the resignation of the Labour Council candidate involved.” | 2023-08-26T01:26:29.851802 | https://example.com/article/8881 |
Industry & Mining
A number of factors bode well for Mexico’s industrial sector. Cheap labour costs, proximity to the US market and improving human resources have attracted global firms. The sector in Mexico is making gains in some strategically important areas, and strong performance in the mining, electronics and agri-business segments is driving overall growth. Even as protectionist measures and bilateral trade tensions dominate the headlines, Mexico is strategically positioned to support Chinese manufacturers looking to bypass US tariffs. A number of risks and uncertainties remain for several industrial segments, however. The shortage of oil and natural gas supply, the absence of a government-led policy and criminal activity along supply routes are causes for concern. Still, investors will likely see ample opportunities in Mexico’s strong ties to the global economy, especially the US and China. This chapter contains an interview with Francisco Cervantes, President, National Confederation of Industry Chambers.
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Season 2016 begins with a clash against our supposed traditional rivals, Port Magpies, cough cough, no, the Magpies are well and truly dead it is really Port Power reserves. The game begins at a frantic pace with Josh Donohue kicking the first goal of the season. Port soon reply from a dubious free kick this sets the pattern for the night but then a exquisite pass from Panos to Lewis Johnston who marks and goals in his debut for the ‘Legs; he is swamped.
Stephen, a friend of my son Daniel, who is attending footy for the first time, asks why are the players fighting so much? It is a combination of ill discipline and appalling umpiring. If the umpires had reversed any number of free kicks paid when the fights occurred and gained control in this way it would have helped, but no, bewildering technical free kicks were paid all night resulting in a staggering 72 free kicks paid.
There must be huge amount of fault laid at the hands of the SANFL due to some ridiculous new interpretations including a huge tightening of the holding the ball rule which basically meant any player who was making the ball their object but any sort of pack resulted, that player was being penalized. For goodness sake, where in the hell was protecting the ball player!
The SANFL has also been stupid and incompetent enough to introduce the last touch of the ball before going out of bounds rule and being far stricter on the deliberate out of bounds rule. With the last touch rule on occasions this resulted in the farcical situation of players shepherding the ball hoping it goes out of bounds the ball bouncing at right angles and then having to compete for the ball.
Where in the hell is COMMON SENSE? Pay the first warranted free kick. Also there is not enough footy nous amongst the umpires to understand when a player is trying to attack and the ball accidentally goes out. Don’t pay a free kick, throw the bloody thing in!
As an umpire, I have a appreciation of how hard it is, but the SANFL is going the wrong way about it, picking young kids who can run and teaching them how to umpire I am more convinced than ever you must have played adult footy at some level to umpire it.
Back to the game, but I had to vent!
The first quarter was a even contest with Dougal Howard showing his promise including a freakish snapped goal; Jimmy Toumpas the Power’s recruit from Melbourne and the returning Anthony Wilson are having a enthralling duel. Wilson makes his touches really count with a clever side step and goal. How Wilson with his amazing blistering pace wasn’t looked at by the Crows and then no one else picking him up is bewildering.
The first quarter ends with Port 3 points up in a see-sawing encounter.
The second quarter is similar with Aaron Young on ball, Cam O’Shea and Paul Stewart having their moments but Norwood are more even and have more contributors.
Goals to Davin Ferriera (the Ferrari) and Peter Perfect Persinos give the ‘Legs a 17 point half time lead. Norwood continues to gain the ascendancy in the third quarter with Lewis Johnston being the most dangerous key forward in the game, Alex Georgiou is annihilating John ‘was the future now the dud’ Butcher.
Jace Bode in his first game as joint captain with Georgiou is contributing individually and also with leadership, his instructing with voice impressive, first gamer Lachlan Pascoe re positioning.
An individual highlight of the third quarter was Wilson seemingly coming from the eighth row of the grandstand to spoil a certain easy mark. Geez he was that quick you would have thought it was Usain Bolt. The third quarter ends with the Redlegs holding a commanding 31 point lead.
Port challenge early in the last, but with Norwood down a player thru Simon Phillips being injured and when Sam Baulderstone rolls a ankle, it looks like Port could run over Norwood. Now Baulderstone has been disappointing in that while he has been the victim of some bewildering ruck infringement free kicks, he didn’t adjust his ruck tactics to the umpires’ interpretation of the rule.
Brady Dawe goes on the ball and gets on top of Dougal Howard, Tim Webber and Matt Panos are too good on the ground for Aaron Young, Steven Summerton and Cam O’Shea. Goals to Johnston and then a long bomb from Matt Fuller, returning from the Western Bulldogs, effectively ends the game as a contest. Jarryd Cachia who has also returned from Richmond has been important with his toughness and clean hands. Peter Bampton, after a wretched 2015 ruined by injury, has been lively on ball and at half forward.
The final margin of 25 points flattered Port with only their straight kicking keeping them in the game, so Round 1 ends with the good guys having a comfortable win. The walk back to the car in the rain is joyous, Daniel finds some religious radio which is as bad as tonight’s umpiring. Good Friday starts with Norwood back in their rightful position on the Premiership ladder on top!
Related
Comments
Thanks Book. Ventured out to Doggy Park yesterday for the fabulous 18 goal hammering of Norf. Not too many controversial frees there, but there was, yet again, the usual missed out-on full because the boundary ump was 50 metres off the play and the field ump blind-sided – how are they then meant to correctly interpret the nnew (stupid) rule? I’m still concerned too about the potential of the new ‘medical assessment rule’ – maybe we’ll have to see how it goes.
Lastly, I would normally have attended the toothless v tossers game, but WHY oh WHY did the SANFL schaedule the opening game in direct competition to the Socceroos game (to which I went)?
Grrr.
The last touch of the ball was trialed in an AFL preseason a while back and they decided just that, the players shepherded it out so they`d get the free and hold up the game. Guess what it never happened so why the SANFL have agreed to it is beyond me. I`m also sad that there is very little coverage of the SANFL games this year on radio so that those of us who, like me, once lived in Adelaide and still follow their team can`t get to at least hear it. 7 can only show one game at a time so it means we will only have the print network to know whats happening, is this really the way to go? Young kids in the country may still follow AFL because they get all the coverage but to get to that level they have to start lower down the rungs so please someone at the SANFL put more effort into local footy in our state.
Fully agree with you on the UMPIRING Rulebook, why the hell do they have to tinker with it?If it ain’t broke, DON’T FIX IT! Is it because they wish to emulate the Australian Farnarkling League? Or is it simply some pinhead wanting to make a name for himself in the history of the SANFL?
Even though the SANFL MAGPIES don’t exist anymore, it’s still a sweet feeling to beat the SWAMPIES, no matter WHAT guise they take!
Looking forward to our next encounter with the Power Reserves!
GO LEGS!!!
How on earth did J.Butcher male the Port best player list? The umpiring in the second quarter was ridiculous and I am convinced some umpiring official went into the rooms at half time to tell them to pull their heads in, otherwise Port would have received 60+ frees for the match.
I like the new out of bounds rule, although I’ll reserve judgement to see how it effects close finishes and what leeway they need to give defenders. I also love the rotation cap to 60. Both rules straightened the game up and encouraged long kicking rather than farting around with unnecessary handball.
Good 4 quarter effort from Norwood and encouraging signs for the season ahead.
Great reading again rulebook . The legs looked good for their first hit out . The umpiring was a shocker , we seen a free kick paid for after disposal which was brought back to the kick taker? ? I thought this would be paid down the ground as it was after disposal thus why the free kick was paid in the first place
The umpires had no control of the game, to scared to reverse decisions. One of the worst umpired games i have watched
As for Norwood i like the way we played quick and direct look forward to the North game. Fortis in procella
Good unbiased call Mal, the umpiring was at best ,bizzare.When 2 teams are fighting how does an umpire pull out a free + a 50 metre penalty in the same scuffle? Port had the best of those type of decisions, but the Redlegs were fantastic and deserved to win.
Good write up mal. The umpiring seemed to have a real AFL feel to it which to me stuffed up a hard, typical Norwood port game of footy. The out if bounds rule is just wrong with players sweating off on the bounce of the ball close to the line.
The real positive of the night was a more direct and quicker Norwood side. I think Johnston will be a huge bonus up front as will the welcome return if Wilson and the Ferrari.
Cheers
“Baulderstone has been disappointing.” Have you been reading my report cards from Kadina Memorial High School, Rulebook?
Good to hear that Alex is back in top form and sharing the leadership duties. Hard ask from full back.
Rabs yes personally I thought the game should have been,Good Friday.Jill just staggering that this out of bounds rule has been brought in after it got trialed in the afl pre season years ago common sense was to bin it for ever,and yes I totally agree re publicity v disappointing lack of radio coverage in 2016.Thanks
Breton and Mark appreciated and agree.Graeme and Jamsey I think,Butcher made the bps for the legs on merit.Malcolm the classic was when 1 umpire was reversing a decision ( which would have been the correct call) while the other was paying a 25 meter penalty pure incompetence.Thanks Greg and Joe yes inconsistent and diabolical.Steve our ball movement was good and a huge improvement especially on the 2nd part of 2015.Great stuff PB loved the line and Alex G started the year in fine style. thanks folks
I can’t recall more than 70 free kicks being paid in a match before. I agree the interpretation of holding the ball was red-hot in the first half and the last quarter. For some reason the umps went to a more conventional interpretation in the third quarter. Maybe the extraordinarily high number of greed was due to men in green being concerned that the game was going to get completely out of control. There were many acts of poor self-discipline that cost both teams goals.
Forgetting the umps, Nwd looked impressive. Simon Phillips is an unfortunate out for the team, but we have some quality in the Reserves. Now for the Roosters at Prospect.
A good account Ashy!
Norwood outclassed the magpies and deserved their win.
I really felt the bizarre decisions, inappropriate over corrections and general level of inconsistent interpretations led to an elevated level of animosity in the game.
Another big stat – ripped guernseys!! More than Butcher scored I’d say!
Regardless, the ‘good guys’ won and sit atop the ladder
Thanks Martin and Mike yes there was some poor discipline by both sides but also agree the incompetent, inconsistent and totally bemusing umpiring was a factor.Jane Bode ( mum of Jace) was happy that she did not have to repair,Jaces gurnsey and yes well and truly more ripped gurnseys than,
Butcher touches! thank you
I used to think the SANFL had the right umpiring interpretation for holding the ball etc. If what we saw on Thursday night is going to be the norm well they have taken many steps backward.,absolutely diabolical
Good stuff Rulebook. Was unable to attend but was watching the live stats on the phone. When I saw 20 frees had been paid in the first half of the first quarter I assumed the new last touch rule was being counted and was prevalent. Looks like such a better balanced Redlegs side and that makes it 5 in a row against that Alberton mob and 11 in a row against them at the Parade. Since he got good Baulderstone is scragged at pretty much every ruck contest, yet when he returns the favour he is immediately pinged. Agree he needs to get better in this regard but understand his frustration. Great to have Rabbs back!
Perfect analysis Rulebook. Poor Baulderstone had ruck infringements paid against him for obstructing 3rd up in the ruck. Seriously? Is this an actual rule? Bewildering but Bodes well for the season ahead for the mighty ‘Legs. (pun intended)
Barks yep a huge concern thanks,Dave agreed definitely better balance and while I totally understand,Baulderstones frustration as several were diabolical decisions he must adapt more anc go with. the flow and interpretations each game furthermore there should be a ruck coach for the umpires as the majority have no idea of the art of rucking.Thanks Luke and Raj totally agree.Thankx Smack bewildering to say the least and good pun.Thanks Milts and Damian greatly appreciated and Rabs is a vital recruit and a big out this week.Thanks Raf not a problem.Knackery readers there has been publicity about legs supporters behavior towards the Cornes boys well amazingly I did not even see either of them on the night and while I am not condoning the over the top abuse my mail re Kane is he doesn’t come out exactly smelling like roses from the dispute overall it is disappointing and hopefully doesn’t occur again.
Malcolm loved your review of the match against the Magpies. They fielded a good side so it was impressive the way the Norwood boys dismantled them. They look a lot faster than last year with the inclusions they have this year. Waiting for your report on the North Adelaide match.
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#ifndef _ROS_control_msgs_JointTolerance_h
#define _ROS_control_msgs_JointTolerance_h
#include <stdint.h>
#include <string.h>
#include <stdlib.h>
#include "ros/msg.h"
namespace control_msgs
{
class JointTolerance : public ros::Msg
{
public:
typedef const char* _name_type;
_name_type name;
typedef float _position_type;
_position_type position;
typedef float _velocity_type;
_velocity_type velocity;
typedef float _acceleration_type;
_acceleration_type acceleration;
JointTolerance():
name(""),
position(0),
velocity(0),
acceleration(0)
{
}
virtual int serialize(unsigned char *outbuffer) const
{
int offset = 0;
uint32_t length_name = strlen(this->name);
varToArr(outbuffer + offset, length_name);
offset += 4;
memcpy(outbuffer + offset, this->name, length_name);
offset += length_name;
offset += serializeAvrFloat64(outbuffer + offset, this->position);
offset += serializeAvrFloat64(outbuffer + offset, this->velocity);
offset += serializeAvrFloat64(outbuffer + offset, this->acceleration);
return offset;
}
virtual int deserialize(unsigned char *inbuffer)
{
int offset = 0;
uint32_t length_name;
arrToVar(length_name, (inbuffer + offset));
offset += 4;
for(unsigned int k= offset; k< offset+length_name; ++k){
inbuffer[k-1]=inbuffer[k];
}
inbuffer[offset+length_name-1]=0;
this->name = (char *)(inbuffer + offset-1);
offset += length_name;
offset += deserializeAvrFloat64(inbuffer + offset, &(this->position));
offset += deserializeAvrFloat64(inbuffer + offset, &(this->velocity));
offset += deserializeAvrFloat64(inbuffer + offset, &(this->acceleration));
return offset;
}
const char * getType(){ return "control_msgs/JointTolerance"; };
const char * getMD5(){ return "f544fe9c16cf04547e135dd6063ff5be"; };
};
}
#endif | 2023-10-01T01:26:29.851802 | https://example.com/article/3155 |
---
abstract: 'Two-view triangulation is a problem of minimizing a quadratic polynomial under an equality constraint. We derive a polynomial that encodes the local minimizers of this problem using the theory of Lagrange multipliers. This offers a simpler derivation of the critical points that are given in Hartley-Sturm [@hartley1997triangulation].'
address: 'Hon Leung Lee, Mathematics, University of Washington, Seattle, WA 98195'
author:
- Hon Leung Lee
bibliography:
- 'lee.bib'
title: 'Critical points for two-view triangulation'
---
Introduction
============
Two-view triangulation is the problem of estimating a point $X\in {{\mathbb{R}}}^3$ from two noisy image projections; see [@hartley-zisserman-2003 Chapter 12] for its significance in structure from motion in computer vision. Assuming a Gaussian error distribution, one way to solve the problem is to compute the maximum likelihood estimates (MLE) for the true image point correspondences. After that the point $X\in {{\mathbb{R}}}^3$ can be recovered via linear algebra [@hartley-zisserman-2003]. In this paper we study the above problem of finding the MLEs. According to the discussion in [@aholt-agarwal-thomas] or [@hartley-zisserman-2003 Chapter 12], the problem is formulated as follows.
Consider a rank two matrix $F\in {{\mathbb{R}}}^{3\times 3}$ which is called a [*fundamental matrix*]{} in multi-view geometry. This matrix $F$ encodes a pair of projective cameras [@hartley-zisserman-2003 Chapter 9]. Given two points $u_1,u_2\in {{\mathbb{R}}}^2$ which denote the noisy image projections, we solve the problem $$\begin{aligned}
\label{triangulation}
\begin{split}
\min_{x_1,x_2\in \RR^2} \ & \|x_1 - u_1\|^2_2 + \|x_2- u_2\|^2_2\\
\text{subject to} \ \ & {\widehat}{x}_2^\top F {\widehat}{x}_ 1= 0
\end{split}\end{aligned}$$ where ${\widehat}{x}_k := (x_k^\top \ 1)^\top\in {{\mathbb{R}}}^3$ for $k=1,2$. The equation $ {\widehat}{x}_2^\top F {\widehat}{x}_ 1= 0$ is called the [*epipolar constraint*]{}, which indicates that $x_1$ and $x_2$ are the true image projections under the projective cameras associated with $F$. The minimizers of are the MLEs for the true image correspondences, assuming the error is Gaussian.
In [@hartley-zisserman-2003 Chapter 12] (or [@hartley1997triangulation]) there is a technique for finding the global minimizers of using a non-iterative approach. They use multi-view geometry to reformulate the problem as minimizing a fraction in a single real variable say $t$. Using the Fermat rule in elementary calculus, it turns out that the minimizers can be computed via finding the real roots of a polynomial in $t$ of degree 6.
In this note, we view the problem as minimizing a multivariate quadratic polynomial over one single equality constraint, and then employ the classical method of Lagrange multipliers to locate the potential local minimizers. These candidates are called [*critical points*]{}. For general rank two matrices $F$ and general points $u_1,u_2$, there are six critical points. They can be computed via finding the roots of a polynomial of degree 6 in the Lagrange multiplier. Assuming that a global minimizer exists, the minimizer of can be obtained from the critical points.
Six critical points for two-view triangulation
==============================================
Reformulation of the problem
-----------------------------
Given a fundamental matrix $F\in {{\mathbb{R}}}^{3\times 3}$ and $u_1=\begin{pmatrix} u_{11} & u_{12}\end{pmatrix}^\top$, $u_2
= \begin{pmatrix} u_{21} & u_{22}\end{pmatrix}^\top\in {{\mathbb{R}}}^2$, consider the invertible matrices $W_1 :={\left}( \begin{smallmatrix} 1 & 0 & -u_{11} \\ 0 & 1 & -u_{12} \\ 0 & 0 & 1\end{smallmatrix} {\right})$ and $W_2 :={\left}( \begin{smallmatrix} 1 & 0 & -u_{21} \\ 0 & 1 & -u_{22} \\ 0 & 0 & 1\end{smallmatrix} {\right})$. Note that $\|x_k-u_k\|^2 = \|{\widehat}{x}_k-{\widehat}{u}_k\|^2$. and that problem is equivalent to the problem $$\begin{aligned}
\begin{split}
\min_{x_1,x_2\in \RR^2} \ & \|W_1 {\widehat}{x}_1\|^2_2 + \|W_2 {\widehat}{x}_2\|^2_2\\
\text{subject to} \ \ & {\widehat}{x}_2^\top F{\widehat}{x}_ 1= 0
\end{split}\end{aligned}$$ For all $k=1,2$, the last coordinate of $W_k{\widehat}{x}_i$ equals one. As a result, we let $y_k\in {{\mathbb{R}}}^2$ be such that ${\widehat}{y}_k = W_k {\widehat}{x}_k$. Then is further equivalent to the problem $$\begin{aligned}
\label{t2}
\begin{split}
\min_{y_1,y_2\in \RR^2} \ & {\frac}{1}{2}{\left}( \|{\widehat}{y}_1\|^2_2 + \|{\widehat}{y}_2\|^2_2{\right}) \\
\text{subject to} \ \ & {\widehat}{y}_2^\top F'{\widehat}{y}_ 1= 0
\end{split}\end{aligned}$$ where $F':= W_2^{-\top} F W_1^{-1}= {\left}( \begin{smallmatrix} a & b & c \\ d & e & f\\ g & h & i\end{smallmatrix} {\right})$ is another fundamental matrix.
Derivation of a six degree polynomial
-------------------------------------
Let $G(y_1,y_2) := {\frac}{1}{2}{\left}( \|{\widehat}{y}_1\|^2_2 + \|{\widehat}{y}_2\|^2_2{\right})$ and $H(y_1,y_2):={\widehat}{y}_2^\top F'{\widehat}{y}_ 1$. The Karush-Kuhn-Tucker (KKT) equation for is $\nabla G + \lambda \nabla H = 0$ for some $\lambda\in {{\mathbb C}}$ called the Lagrange multiplier; see any nonlinear programming text e.g. [@bertsekas1999nonlinear]. Unwinding this equation we obtain a linear system in four variables, namely, $$\begin{aligned}
\label{lsls}
\begin{pmatrix}
1 & 0 & \lambda a & \lambda b \\
0 & 1 & \lambda d & \lambda e \\
\lambda a & \lambda d & 1 & 0 \\
\lambda b & \lambda e & 0 & 1
\end{pmatrix}
\begin{pmatrix}
y_{21}\\
y_{22}\\
y_{11}\\
y_{12}
\end{pmatrix}
= -\lambda
\begin{pmatrix}
c\\
f\\
g\\
h
\end{pmatrix}\end{aligned}$$ where $y_k = \begin{pmatrix} y_{k1} & y_{k2}\end{pmatrix}^\top$ for $k=1,2$, and $\lambda$ is the Lagrange multiplier. To acquire the critical points we derive a polynomial equation in $\lambda$. It comes from first expressing $y_k$, $k=1,2$, in terms of $u_1,u_2,F$ and then substituting these expressions into the epipolar constraint $ {\widehat}{y}_2^\top F'{\widehat}{y}_ 1= 0$. Let $A_\lambda$ be the $4\times 4$ coefficient matrix of the above system. One has $$\det(A_\lambda) = (bd-ae)^2\lambda^4 - (a^2+b^2 + d^2 +e^2) \lambda^2 + 1.$$ Define $p_{kl}:= \det(A_\lambda) y_{kl}$ for $k,l=1,2$. By Cramer’s rule one has $$\begin{aligned}
& p_{21} = \lambda[ (bd-ae)(eg-dh)\lambda^3 + (d^2 c+ e^2 c - adf - bef) \lambda^2 + (ag+bh)\lambda-c]\\
& p_{22} = \lambda[ (bd-ae)(ah-bg)\lambda^3 + (a^2 f + b^2 f - acd - bce) \lambda^2 + (dg+eh)\lambda-f]\\
& p_{11}= \lambda[ (bd-ae)(ce-bf)\lambda^3 + (b^2 g + e^2 g - abh - deh) \lambda^2 +(ac+df)\lambda-g]\\
& p_{12}= \lambda[ (bd-ae)(af-cd)\lambda^3 + (a^2 h + d^2 h - abg - deg ) \lambda^2 + (bc+ef)\lambda-h ].\end{aligned}$$ Consider the polynomial $$\begin{aligned}
T & := -\det(A_\lambda)^2 {\widehat}{y}_2^\top F' {\widehat}{y}_1 = - p_2^\top F' p_1\end{aligned}$$ where $p_k := \begin{pmatrix} p_{k1} & p_{k2} & \det(A_\lambda)\end{pmatrix}^\top$ for $k=1,2$. Since $\det(A_\lambda)$ is a quartic in $\lambda$, and $p_{kl}$ is also a quartic in $\lambda$ for $k,l = 1,2$, we know $T$ is a polynomial in $\lambda$ of degree at most 8. By a careful and slightly tedious computation without using any machines, or by using the following [Macaulay2]{} [@M2] code:
[ ]{}
we know the coefficient of $\lambda^7$ is zero. The coefficient of $\lambda^8$ is $$\begin{aligned}
& -(bd-ae)^2 (eg-dh) (ace-abf+baf - bcd + cbd - cae) +\\
& -(bd-ae)^2 (ah-bg)(dce - dbf + eaf - ecd + fbd - fae) +\\
& -(bd-ae)^3 (gce - gbf +haf - hcd + ibd - iae) = (bd-ae)^3 \det(F)=0\end{aligned}$$ since $F$ has rank two. This implies $T$ is a polynomial in $\lambda$ of degree at most six. Here we record the explicit expression of $T$: $$\begin{aligned}
T = \ & (bd-ae)^2 (acg + dfg + bch + efh - a^2 i - b^2 i - d^2 i - e^2 i ) \lambda^6 + \\
& a^{2} c^{2} d^{2} \lambda^{5} + c^{2} d^{4}
\lambda^{5} + 2 a b c^{2} d e \lambda^{5} + b^{2} c^{2} e^{2} \lambda^{5} + 2 c^{2} d^{2}
e^{2} \lambda^{5} + c^{2} e^{4} \lambda^{5} - \\
& 2 a^{3} c d f \lambda^{5} - 2 a b^{2} c d f
\lambda^{5} - 2 a c d^{3} f \lambda^{5} - 2 a^{2} b c e f \lambda^{5} - 2 b^{3} c e f
\lambda^{5} - 2 b c d^{2} e f \lambda^{5} - \\
& 2 a c d e^{2} f \lambda^{5} - 2 b c e^{3} f
\lambda^{5} + a^{4} f^{2} \lambda^{5} + 2 a^{2} b^{2} f^{2} \lambda^{5} + b^{4} f^{2}
\lambda^{5} + a^{2} d^{2} f^{2} \lambda^{5} +\\
& 2 a b d e f^{2} \lambda^{5} + b^{2} e^{2}
f^{2} \lambda^{5} + a^{2} b^{2} g^{2} \lambda^{5} + b^{4} g^{2} \lambda^{5} + 2 a b d e
g^{2} \lambda^{5} + 2 b^{2} e^{2} g^{2} \lambda^{5} + \\
& d^{2} e^{2} g^{2} \lambda^{5} +
e^{4} g^{2} \lambda^{5} - 2 a^{3} b g h \lambda^{5} - 2 a b^{3} g h \lambda^{5} - 2 a b
d^{2} g h \lambda^{5} - 2 a^{2} d e g h \lambda^{5} -\\
& 2 b^{2} d e g h \lambda^{5} - 2
d^{3} e g h \lambda^{5} - 2 a b e^{2} g h \lambda^{5} - 2 d e^{3} g h \lambda^{5} + a^{4}
h^{2} \lambda^{5} + a^{2} b^{2} h^{2} \lambda^{5} + \\
& 2 a^{2} d^{2} h^{2} \lambda^{5} +
d^{4} h^{2} \lambda^{5} + 2 a b d e h^{2} \lambda^{5} + d^{2} e^{2} h^{2} \lambda^{5} +
a^{3} c g \lambda^{4} + a b^{2} c g \lambda^{4} +\\
& a c d^{2} g \lambda^{4} -5 b c d e g
\lambda^{4} + 6 a c e^{2} g \lambda^{4} + a^{2} d f g \lambda^{4} + 6 b^{2} d f g \lambda^{4} +
d^{3} f g \lambda^{4} - \\
& 5 a b e f g \lambda^{4} + d e^{2} f g \lambda^{4} + a^{2} b c h
\lambda^{4} + b^{3} c h \lambda^{4} + 6 b c d^{2} h \lambda^{4} - 5 a c d e h \lambda^{4} +\\
& b c
e^{2} h \lambda^{4} - 5 a b d f h \lambda^{4} + 6 a^{2} e f h \lambda^{4} + b^{2} e f h
\lambda^{4} + d^{2} e f h \lambda^{4} + e^{3} f h \lambda^{4} - a^{4} i \lambda^{4} - \\
& 2 a^{2}
b^{2} i \lambda^{4} - b^{4} i \lambda^{4} - 2 a^{2} d^{2} i \lambda^{4} - 4 b^{2} d^{2} i
\lambda^{4} - d^{4} i \lambda^{4} + 4 a b d e i \lambda^{4} - 4 a^{2} e^{2} i \lambda^{4} - \\
& 2
b^{2} e^{2} i \lambda^{4} - 2 d^{2} e^{2} i \lambda^{4} - e^{4} i \lambda^{4} - 2 c^{2}
d^{2} \lambda^{3} - 2 c^{2} e^{2} \lambda^{3} + 4 a c d f \lambda^{3} + 4 b c e f \lambda^{3} -\\
&
2 a^{2} f^{2} \lambda^{3} - 2 b^{2} f^{2} \lambda^{3} - 2 b^{2} g^{2} \lambda^{3} - 2
e^{2} g^{2} \lambda^{3} + 4 a b g h \lambda^{3} + 4 d e g h \lambda^{3} - 2 a^{2} h^{2}
\lambda^{3} - \\
& 2 d^{2} h^{2} \lambda^{3} - 3 a c g \lambda^{2} - 3 d f g \lambda^{2} - 3 b c h
\lambda^{2} - 3 e f h \lambda^{2} + 2 a^{2} i \lambda^{2} + 2 b^{2} i \lambda^{2} + \\
& 2 d^{2} i
\lambda^{2} + 2 e^{2} i \lambda^{2} + c^{2} \lambda + f^{2} \lambda + g^{2} \lambda + h^{2} \lambda - i.\end{aligned}$$
The six critical points
-----------------------
By solving $T = 0$ for $\lambda$, we get six (complex) solutions (counting multiplicities) for $\lambda$, say $\lambda_1, \ldots, \lambda_6$. Plugging in these six values of $\lambda$ into the linear system , solving the linear system for $y_1$ and $y_2$, and computing $x_1$ and $x_2$, one obtains the critical points for two-view triangulation. If $\det(A_{\lambda_k})\neq 0$ for every $k=1,\ldots,6$ then there are precisely six critical points counting multiplicities.
Now we claim that for general fundamental matrices $F$ and points $u_1,u_2\in {{\mathbb{R}}}^2$, there are six distinct critical points for two-view triangulation. The claim is false if and only if the discriminant of $T$ or the resultant of $T$ and $\det(A_\lambda)$ are zero polynomials. Instead of computing the desired discriminant and resultant which depend on $u_1,u_2$ and $F$, one can find an example of $(u_1,u_2,F)$ such that the discriminant of $T$ and the resultant of $T$ and $\det(A_\lambda)$ take a nonzero value, that is, $\det(A_\lambda)\neq 0$ for every solution $\lambda$ of $T$, and the six critical points obtained are distinct. If we consider the data $u_1 = \begin{pmatrix} 0 & 0 \end{pmatrix}^\top$, $u_2 = u_1$ and $F= {\left}( \begin{smallmatrix} 1 & 1 & 1 \\ 0 & 1 & 1 \\ 1 & 3 & 3\end{smallmatrix}{\right})$, then the polynomial $T$ becomes $-2\lambda^6+6\lambda^5+3\lambda^4-12\lambda^3-3\lambda^2+12\lambda-3$, and there are six distinct complex critical points for the problem ; see Table \[t1\].
$x_{21}$ $x_{22}$ $x_{11}$ $x_{12}$
------------------- ------------------- ------------------ -------------------
$0.0596$ $-0.0321$ $-0.312$ $-0.891$
$-0.0843$ $-2.06$ $-0.438$ $-0.0259$
$-2.42 + 0.0137i$ $-1.02 -1.56i$ $-1.57 + 0.714i$ $-1.246 - 1.51i$
$-2.42 - 0.0137i$ $-1.02 +1.56i$ $-1.57 - 0.714i$ $-1.246 + 1.51i$
$-1.69+0.0226i$ $-0.935 + 0.414i$ $0.748 + 0.169i$ $-0.279 - 0.574i$
$-1.69-0.0226i$ $-0.935 - 0.414i$ $0.748 - 0.169i$ $-0.279 + 0.574i$
: Six critical points for when $u_1=(0 \ 0)^\top$, $u_2=u_1$ and $F=$ .[]{data-label="t1"}
We summarize the discussion in the following theorem.
For general points $u_1,u_2\in {{\mathbb{R}}}^2$ and fundamental matrices $F$, there are six complex critical points for the problem .
Discussion
==========
One can make sense of the critical points for $n$-view triangulation where $n$ is greater than two. The authors in [@stewenius2005hard] (cf. [@hartley-kahl]) computed the number of critical points for 2 to 7 view triangulation are 6, 47, 148, 336, 638, 1081. Draisma et al. [@DHOST] call this list of numbers the [*Euclidean distance degrees*]{} of the multi-view variety associated to 2 to 7 cameras. They conjecture that the general term of this sequence is $$C(n):={\frac}{9}{2}n^3 - {\frac}{21}{2} n^2 + 8n-4.$$ One can apply the Bézout’s theorem to conclude that $C(n)$ has order $n^3$, and our paper verified $C(2)=6$. However a proof of the above general formula is still unknown.
| 2023-11-26T01:26:29.851802 | https://example.com/article/8640 |
Derrotó a San Lorenzo en condición de local luego de 13 años. Ganó en Mendoza después de medio siglo. Quedó a cinco puntos de los líderes y aún tiene pendiente el partido de la segunda fecha ante Newell's, que se disputará el 15 de diciembre. El escenario es otro en Independiente desde que Fernando Berón se hizo cargo del equipo tras la salida de Sebastián Beccacece. Los semblantes son otros en el plantel. Y Juan Sánchez Miño intentó explicar qué fue lo que cambió. "Es difícil modificar mucho en tan poco tiempo. Berón nos dio tranquilidad, hizo mucho hincapié en eso. Desde lo futbolístico creo que al no tener al rival tan adelante estamos aprovechando mejor los espacios" , comentó el lateral izquierdo. Y avisó: "Cambió la energía. Eso ha ayudado a que se nos den los resultados" .
LAS NOTICIAS DEL DEPORTE Recibí la info más importante todos los días Recibir newsletter
Independiente volverá a jugar recién el domingo 1 de diciembre, ante Aldosivi en Mar del Plata . El partido de la próxima fecha contra River se postergó para el 19 de enero ya que el conjunto de Marcelo Gallardo debe disputar la final de la Libertadores. ¿Cómo le cae este parate tan largo al Rojo? "Cuando venís ganando es bueno seguir jugando. Por otro lado, estos días le servirán al técnico para poder trabajar sobre su idea . No hay que relajarse porque todavía estamos en competencia. Debemos aprovechar para trabajar con el fin de que el técnico pueda darle su sello al equipo", remarcó Sánchez Miño.
Mirá también Mirá también Los muchachos Beronistas | 2024-04-09T01:26:29.851802 | https://example.com/article/7181 |
World News Quick Take
Agencies
UNITED KINGDOM
Wedding mistaken for sham
Immigration officials admitted on Friday that they mistakenly raided the wedding of an Italian man and his Chinese bride because they believed the marriage was a sham. Massimo Ciabattini and his bride, Miao Guo, had their big day ruined when border police stormed into their wedding ceremony at a London town hall last week and hauled them out for questioning. The couple had attracted a registrar’s suspicion because Guo’s visa was due to expire soon and they appeared to have difficulty spelling each other’s names. Border officials realized their mistake after questioning the couple and their bridesmaids. The marriage ceremony resumed afterward, the town hall confirmed. To compound officials’ embarrassment, they had invited a journalist from a local newspaper along to witness the raid as an example of their work combating bogus marriages between strangers trying to gain British residency.
KENYA
German cleared of murder
A court has acquitted a German man who was arrested while sleeping with the decomposing body of his Kenyan wife and charged with her murder, court officials said on Friday. The court in the coastal city of Mombasa ruled on Thursday that there was insufficient evidence to convict the man, identified in court documents as Michael Bibcke Robel, 43, from the city of Hamburg, of murdering Esther Elsi Igoki Munyi in December 2009. The court heard how the accused was found sleeping next to his dead, decomposing wife at their home near Mombasa after police were alerted by the smell. The accused had also stabbed himself in the chest in an apparent failed suicide attempt. “It is pertinent that under cross-examination by the defence counsel, the doctor did concede that no obvious injuries were seen on the neck. There was no strangulation,” Judge Maureen Odero said in her ruling. She also ruled that there were no eyewitnesses to the events, and that an autopsy failed to establish the precise cause of death beyond that of asphyxia.
RUSSIA
Squatting for metro tickets
Passengers on the Moscow metro puffed and sweated for a free ride on Friday after Olympic officials unveiled a machine that issues a free ticket as a reward for performing 30 squats. By setting the somewhat embarrassing challenge with a time limit of two minutes, the organizers said they were encouraging people to incorporate “Olympic values” into their commute. It is part of a campaign by the nation’s Olympic Committee that picks projects proposed by the public to “add elements of sport into daily life.” The campaign aims to make Russians healthier so that they do not simply curl up on a couch to watch the events in the Winter Olympics in Sochi in February next year.
RUSSIA
Six found guilty of slaying
A jury has found six men accused of the brutal slaying of a farming family guilty on all counts. The 2010 killing of 12 people, including four children, in the village of Kushchevskaya in the southern Krasnodar region shocked the nation. Several assailants burst into the home of a farmer, killing him, his entire family and their guests. Most of the victims were stabbed to death. The alleged leader of the gang that committed the killings, Sergey Tsapok, was arrested shortly after along with several suspected accomplices. Their trial in the Krasnodar Regional Court began a year ago, and the jury delivered the verdict on Friday. A sentence is expected next week. | 2024-03-12T01:26:29.851802 | https://example.com/article/1918 |
Claire Freeman.
Politicians and planners are being urged to take a long-term view of Auckland's growth and to start realising short-term money injections are not the best options for long-term economic growth and development of the city and New Zealand as a whole.
Four University of Otago academics tackled the vexing and complicated issue of the dominance of Auckland in a lively discussion in front of more than 60 people in Auckland last night.
The second of three University of Otago Winter Symposiums, held in association with the Otago Daily Times, discussed a wide range of topics, from the growth of cities not always assured, the need for a national planning strategy, how South Island health professionals had skills they could pass on to their northern counterparts to reduce inequality and whether businesses could justify moving to Auckland from places like Dunedin purely on a cost basis.
Etienne Nel
Prof Etienne Nel led off the debate explaining how Auckland's ''remarkable growth'' in the past 10 years was seen as being to the detriment of the regions.
There was a view of rural depopulation, rural decline and the rise of ''Zombie towns''.
That was not always the case. Not all small towns were declining and some had significant economic growth, above the national average, he said.
A study from the 1950s identified 10 major United States cities which were growing strongly.
Robin Gauld.
Eight of those cities were no longer growing.
Prof Nel warned of the trend being seen now in Auckland being reversed in the future.
There was a global trend of rural towns declining in population because of various factors.
They were not disappearing, but were examples of a new term called ''right sizing''.
That would happen in New Zealand but there needed to be a holistic view taken to the growth of Auckland.
Sergio Biggeman
New Zealand desperately needed a comprehensive regional policy, he said.
Dr Sergio Biggemann, of the department of marketing, put paid to any notion businesses in the South needed to move to Auckland to be either closer to their market, be part of a cluster or reduce their costs.
The New Zealand market was so small and the country had a history of exporting to grow, right from the first shipment of frozen lamb from Otago.
There was no reason for a Dunedin business to move to Auckland to service a global market, he said.
The cluster phenomenon was incorrect.
Often, like industries did well in certain areas because of the interactions they had with a city and local councils.
And no accounting system was developed enough to accurately compare the costs of doing business either in Dunedin or Auckland.
One Dunedin firm, which Dr Biggemann did not name, serviced its Auckland and global clients more efficiently from Dunedin because of a variety of factors, including its staff not having to travel 90min to work each morning.
Pro vice-chancellor and business school dean Prof Robin Gauld, took a no-nonsense approach to the provision of healthcare in Auckland and providing some solutions to the rising inequality identified by all panellists.
Doctors were the most needed in South Auckland but the area was the least well serviced by GP s while the best served area was the central city.
He advocated Auckland doctors learning from those in places like Ranfurly, Wanaka and Te Anau, where their ''big brains'' ensured they could treat patients with complaints usually treated in an Auckland hospital.
One in four or one in five New Zealanders did not go to the doctor or get prescriptions filled because of cost.
In Auckland, where the cost of living was among the highest in the world, the number of people putting off going to the doctor was likely much higher, he said.
However, there were some ''alternative facts'' from the South Island which were being mainly ignored by the North Island district health boards.
They included the South Island having an IT system operating across five health boards which was set up for less than $10million.
The most important part of the South Island health system was collaboration, something not happening in the north, Prof Gauld said.
Finally, Prof Claire Freeman revealed how insignificant Auckland was on a global scale being 195 on a city ranking and squeezed between a city in Mexico and one in India most people had never heard of.
Prof Freeman wanted a national planning policy established because the country had to go ahead together.
''When we go forward, Auckland will have a major role but it won't have the only role.''
dene.mackenzie@odt.co.nz | 2024-04-26T01:26:29.851802 | https://example.com/article/3044 |
Non-epileptic seizures and child sexual abuse: a critical review of the literature.
Non-epileptic seizures have received a substantial amount of attention in the psychiatric and medical literature, but comparatively little attention from psychologists. Non-epileptic seizures resemble epileptic seizures but lack the physiological symptoms of genuine epilepsy and are psychological in origin. Many authors have emphasized the role that child sexual abuse may play in the etiology of this disorder. In the present paper, we provide a review of 34 studies examining this relationship, followed by a meta-analysis of 19 effect sizes. While our statistical results support the professed link between child sexual abuse and non-epileptic seizures, we suggest that because of research design limitations, it is premature to draw any definitive conclusions regarding a relationship. Eight of these research design limitations are identified and discussed (e.g., the absence of comparison groups; an explicit and public definition of child sexual abuse). Alternatives to a traditional psychoanalytic perspective that emphasizes the role of child sexual abuse in the etiology of NES are presented. Specific recommendations for future research are made and psychologists are strongly encouraged to play a more active role in both researching and treating non-epileptic seizures. | 2023-11-08T01:26:29.851802 | https://example.com/article/3868 |
Abu Zenima
Abu Zenima () is a coastal city in South Sinai Governorate, Egypt. It has an area of .
History
In 2009, a whale 10 metres long and weighing 10 tonnes was found on its Red Sea beach. The minke whale was presumed to have lost its way from the Indian Ocean, and starved due to the relative lack of food. The body was buried in lime, for public health reasons, with the intention of eventually displaying the skeleton in a visitor's centre.
Climate
Köppen-Geiger climate classification system classifies its climate as hot desert (BWh), as the rest of Egypt.
See also
Abou Redis
References
Category:Populated places in South Sinai Governorate | 2023-11-28T01:26:29.851802 | https://example.com/article/7680 |
Q:
Reducing the size of a QMdiSubWindow holding a QLabel with QPixmap
The question statement says it all. I am able to enlarge the QMdiSubWindow (and the pixmap scales UP, i.e. enlarges, appropriately) but I am not able to reduce its size (i.e. scale the image DOWN or shrink). When trying to scale down though, the border handles of the QMdiSubWindow remain rigidly fixed.
The code I am using is as follows:
class PixmapWidget : public QLabel
{
Q_OBJECT
public:
PixmapWidget():
QLabel()
{
_pixmap = QPixmap("path\\to\\image.jpg");
setPixmap(_pixmap);
_layout = new QHBoxLayout();
_layout->setSizeConstraint(QLayout::SetNoConstraint);
setLayout(_layout);
setSizePolicy(QSizePolicy(QSizePolicy::Preferred, QSizePolicy::Preferred));
}
void resizeEvent(QResizeEvent * event)
{
int width = event->size().width();
int height = event->size().height();
setPixmap(_pixmap.scaled(width,height));
QLabel::resizeEvent(event);
}
protected:
QPixmap _pixmap;
QHBoxLayout* _layout;
};
int main()
{
QMainWindow mainWindow;
QHBoxLayout* layout = new QHBoxLayout();
QMdiArea* mdiArea = new QMdiArea();
mainWindow.setCentralWidget(mdiArea);
mainWindow.centralWidget()->setLayout(layout);
layout->setSizeConstraint(QLayout::SetNoConstraint);
QMdiSubWindow* mdiSubWindow = new QMdiSubWindow();
layout->addWidget(mdiSubWindow);
mdiSubWindow->setSizePolicy(QSizePolicy(QSizePolicy::Preferred, QSizePolicy::Preferred));
mdiSubWindow->layout()->setSizeConstraint(QLayout::SetNoConstraint);
DMSQt::PixmapWidget pixmapWidget;
mdiSubWindow->layout()->addWidget(&pixmapWidget);
mainWindow.show();
qapp.exec();
}
A:
Alright, I found the problem. Apparently, I need to set a minimum size on my text label:
Adding:
setMinimumSize(_pixmap.width(), _pixmap.height());
solved the problem.
| 2024-02-13T01:26:29.851802 | https://example.com/article/1272 |
Developer Mobius Digital's wonderful sandbox space exploration adventure Outer Wilds (which was named Eurogamer's favourite game of 2019, don't you know) will be waving goodbye to Epic Games Store exclusivity and hello to Steam on 18th June.
Outer Wilds, if you've not yet had the pleasure, casts players as intrepid adventurers itching to explore the gorgeously compact solar system spinning endlessly above their heads. It's a dreamily realised, deliciously off-kilter place, with its striking, often surreal planets gradually evolving in unexpected ways as time progresses in-game.
Thanks to violent celestial calamity, however, the entire solar system constantly resets every 20 minutes, sending players all the way back to the start, albeit with a headful of crucial new knowledge collected on their previous adventures to the stars. The idea, then, is to slowly pick apart the cosmos' secrets, using previous learnings to be in the right place at the right time, and perhaps even avert disaster when the dying sun goes supernova next time around.
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Eurogamer's Christian Donlan was smitten enough with Outer Wilds' intergalactic delights to award it a Recommended badge in his review last year, and its charms ultimately won over the rest of the team, sufficiently so that it was crowned our favourite game of 2019.
"Outer Wilds is astonishing," enthused Donlan once more in his end-of-year write-up, "in an era in which you'd think that games would be running out of ways to astonish people.
"It gives you a clockwork solar system filled with planets whose evocative names are matched by dynamic, tempestuous, mysterious surfaces. It gives you addled, oxbow interiors filled with secrets, with a trail to follow. It gives you physics and memory and logic and sweetness and, in amidst the emptiness, a sense of camaraderie, of belonging to something folksy and pine-scented and cobbled-together with craft and will."
Those planning to venture forth and uncover Outer Wilds' ancient mysteries and long-forgotten secrets through Steam on 18th June can add it to their wishlist now. | 2023-12-17T01:26:29.851802 | https://example.com/article/5085 |
Supported by the Global Center for Glycogen Storage Disease (GSD) (to D.A.W.), the Ralph & Alice Brown Type VI GSD Research Fund (to D.A.W.), and the Crozet Crusader\'s Fund for GSD Research (to D.A.W.).
Potential conflict of interest: Dr. Weinstein received grants from Nestle/Vitaflo, Ultragenyx, and Moderna. The other authors have nothing to report.
*α*‐SMA
: alpha smooth muscle actin
ALP
: alkaline phosphatase
ALT
: alanine aminotransferase
AST
: aspartate aminotransferase
CCL5/Rantes
: C‐C chemokine ligand 5
Col1a1
: collagen type I alpha 1
Col1a2
: collagen type I alpha 2
Col4a2
: collagen type IV alpha 2
Ctgf
: connective tissue growth factor
Fn1
: fibronectin
FRT
: flippase recognition target
G1P
: glucose 1‐phosphate
GNG
: gluconeogenesis
GSD
: glycogen storage disease
H&E
: hematoxylin & eosin
HSC
: hepatic stellate cell
KOMP
: Knockout Mouse Project
lacZ
: beta‐galactosidase
loxP
: locus of X‐over P1
Mcp‐1
: monocyte chemoattractant protein 1
mRNA
: messenger RNA
PCR
: polymerase chain reaction
*Pygl*
: liver glycogen phosphorylase
Tgf‐*β*
: transforming growth factor beta
Tnf‐a
: tumor necrosis factor alpha
WT
: wild type
Glycogen storage disease type VI (GSD‐VI; MIM\#232700), or Hers disease, is caused by a deficiency or mutation in the human glycogen phosphorylase (*PYGL*) gene, which codes for the metabolic enzyme liver glycogen phosphorylase. GSD‐VI is an autosomal recessive disease that affects approximately 1 in 65,000 to 85,000 live births.[1](#hep41426-bib-0001){ref-type="ref"}, [2](#hep41426-bib-0002){ref-type="ref"} An integral enzyme in glucose metabolism, PYGL catalyzes the rate‐limiting step of glycogenolysis, converting glycogen into glucose 1‐phosphate (G1P). Breakdown of glycogen in the liver requires the step‐wise activation of several cytosolic liver enzymes. Phosphorylase kinase, which phosphorylates liver PYGL, triggers a conformation switch from phosphorylase b (inactive form) to phosphorylase a (active form), which catalyzes the breakdown of glycogen into chains of G1P monomers. Through the addition of the glycogen debranching enzyme, which assists to further cleave α‐1,6 glycosidic linkages, free G1P monomers are converted to glucose 6‐phosphate, which can be released from the liver or shunted into alternative pathways.[3](#hep41426-bib-0003){ref-type="ref"} Additionally, glycogen is processed through the autophagy--lysosomal pathway, mediated by the enzyme acid α‐glucosidase, to produce low quantities of free glucose.[4](#hep41426-bib-0004){ref-type="ref"}
People with GSD‐VI typically present with growth retardation and hepatomegaly early in life. Unlike the more severe form of GSD‐I, patients with GSD‐VI experience mild hypoglycemia.[2](#hep41426-bib-0002){ref-type="ref"} In fact, several clinical reports detail asymptomatic patients with GSD‐VI presenting with isolated hepatomegaly and no prior history of hypoglycemia.[5](#hep41426-bib-0005){ref-type="ref"} While hypoglycemia can be mild in GSD‐VI, blood analyses often demonstrate hyperlipidemia, hepatic transaminase elevation, and hyperketosis.[2](#hep41426-bib-0002){ref-type="ref"}, [5](#hep41426-bib-0005){ref-type="ref"}, [6](#hep41426-bib-0006){ref-type="ref"}, [7](#hep41426-bib-0007){ref-type="ref"}, [8](#hep41426-bib-0008){ref-type="ref"}, [9](#hep41426-bib-0009){ref-type="ref"}, [10](#hep41426-bib-0010){ref-type="ref"} Protein deficiency can occur from over dependence on protein as an alternative fuel and a precursor for gluconeogenesis. As a result of the tendency for ketosis and a low protein concentration, most patients with GSD‐VI benefit from therapy even if severe hypoglycemia is not occurring.
Based on the nonspecific and variable nature of the disease, GSD‐VI is almost certainly underdiagnosed in the general population. There is a paucity of literature on the condition, but severe complications can occur, including liver fibrosis, liver tumors, and cirrhosis.[2](#hep41426-bib-0002){ref-type="ref"}, [7](#hep41426-bib-0007){ref-type="ref"}, [8](#hep41426-bib-0008){ref-type="ref"} In order to better understand the pathophysiology of the condition and develop new therapies, we generated this novel mouse model with a deficiency in the *Pygl* gene that exhibits the metabolic abnormalities and clinical manifestations associated with GSD‐VI.
Materials and Methods {#hep41426-sec-0002}
=====================
Generation of *Pygl*‐Deficient Mice {#hep41426-sec-0003}
-----------------------------------
A *Pygl* knockout allele mouse (*Pygl* ^targeted\ mutation\ 1a\ \[tm1a/+\]^ or *Pygl* ^+/--^, C57BL/6N background) line was created in collaboration with the Knockout Mouse Project (KOMP) Repository (\#CSD23397) at the University of California, Davis, using the "knockout first (promoter driven)" strategy.[11](#hep41426-bib-0011){ref-type="ref"} To generate the knockout allele, a cassette containing flippase recognition target (FRT), locus of X(cross)‐over in P1 (loxP) sequences, engrailed 2 splice acceptor (En2 SA), beta‐galactosidase (lacZ), neomycin, and FRT and loxP sites was inserted in the intron between exon 2 and exon 3 of the *Pygl* gene. The allele of Pygl^tm1a^ was initially in a nonexpressive form with conditional potential. Embryonic stem cells containing the targeted allele (JMN8.4 subline, C57BL/6N background, KOMP repository, *Pygl* H02) were introduced into donor blastocysts (BALB/c). Chimerism of 50% or greater was identified by coat color, and chimeric male mice were bred with C57BL/6N female mice. Desired heterozygous mice from the bred cross (*Pygl* ^tm1a^ allele) were genotyped to confirm germline transmission. For all experiments, heterozygous mating (*Pygl^+/--^*) pairs were used to generate *Pygl*‐deficient mice (*Pygl* ^−/−^). Human and mouse PYGL proteins share 94% of sequence similarity (the Ensembl genome browser [www.ensembl.org](http://www.ensembl.org)).
Animal Studies {#hep41426-sec-0004}
--------------
All animal studies were performed in accordance with the guidelines and approval of the Institutional Animal Care and Use Committee of the University of Connecticut Health Center. All mice were maintained in a pathogen‐free animal facility at 22°C‐24°C under a 12‐hour:12‐hour light--dark cycle in individually ventilated caging systems. Standard rodent chow (Envigo, Madison, WI) and water were provided *ad libitum*. Animals were weaned and separated according to sex at postnatal day 21 and housed in groups of four to five mice. Littermate (*Pygl^+/+^*) animals were used as wild‐type (WT) control mice. Phenotypes evaluated in this study were indistinguishable between male and female mice; therefore, both male and female mice were used in all studies without preference. The mice were classified by age group as young (4‐20 weeks) and old (\>40 weeks). Total number of mice used were young WT (n = 27) and *Pygl* ^−/−^ (n = 36) and old WT (n = 27) and *Pygl* ^−/−^ (n = 13) mice. At the end of the study, mice were fasted for 24 hours before being killed. Liver and kidney weights were expressed as percentage of body weight. The numbers of mice analyzed were young WT (n = 13) and *Pygl* ^−/−^ (n = 24) mice for liver weight and young WT (n = 7) and *Pygl* ^−/−^ (n = 17) mice for kidney weight.
Genotyping {#hep41426-sec-0005}
----------
Tail biopsies were lysed in tail lysis solution (DirectPCR tail lysis; 20 mg/mL proteinase K) at 55°C overnight and then at 85°C for 1 hour. Genotyping was performed using Accupower polymerase chain reaction (PCR) premix (Bioneer, Oakland, CA) tubes. The introduced cassette containing lacZ in intron 2‐3 was identified using the following primer pair: lacZ forward (5′‐TAATCACGACGCGCTGTACT‐3′) and lacZ reverse (5′‐CGGATAAACGGAACTGGAAA‐3′); this was expected to amplify a fragment of 500 base pairs (bp) in the inserted lacZ cassette. The WT allele was identified using the following primer pair: WT forward (5′‐TGCTGAAACACATCAGCACA‐3′) and WT reverse (5′‐ATGTCCAATCCA AGCTGAGG‐3′); this was expected to amplify a fragment of 800 bp in the WT allele. However, if the introduced cassette exists in the DNA, it will fail to amplify the fragment.
Fasting Glucose and Ketone Test {#hep41426-sec-0006}
-------------------------------
Fasting glucose tests and ketone tests were performed at 0, 2, 4, 6, and 24 hours. Blood glucose levels were measured with a blood glucose meter and cuvettes (HemoCue Glucose 201 System; HemoCue, Brea, CA), and blood ketone (β‐hydroxybutyrate) concentration was determined using a blood ketone meter and ketone strips (Precision Xtra; Abbott Laboratories, Abbott Park, IL). Young WT (n = 12) and *Pygl* ^−/−^ (n = 17) mice were used for fasting glucose tests, and young WT (n = 18) and *Pygl* ^−/−^ (n = 18) mice were used in ketone studies.
Hepatic Glycogen and Free Glucose Content Determination {#hep41426-sec-0007}
-------------------------------------------------------
To determine hepatic glycogen and free glucose content, liver tissues from 24‐hour fasted young WT (n = 5) and *Pygl* ^−/−^ (n = 6) mice and old WT (n = 5) and *Pygl* ^−/−^ (n = 6) mice were homogenized. Hepatic glycogen and free glucose content were measured according to the manufacturers\' instructions using a glycogen colorimetric/fluorometric assay kit (BioVision, Milpitas, CA) and a D‐glucose assay kit (Megazyme, Chicago, IL), respectively, and normalized to hepatic protein concentration measured by the bicinchoninic acid (BCA) assay kit from Thermo Fisher Scientific (Louisville, CO).
Hepatic Hydroxyproline Determination {#hep41426-sec-0008}
------------------------------------
To quantify hepatic collagen content, hepatic hydroxyproline was measured using a colorimetric assay kit from BioVision. Briefly, livers from both young and old WT (n = 11) and *Pygl* ^−/−^ (n = 13) mice were homogenized in 100 μL of distilled water. We added 100 μL of 10 N NaOH to the homogenate, incubated this at 120°C for 1 hour, and neutralized the mixture with 100 μL of 10 N HCl. After centrifugation at 10,000*g* for 5 minutes, the hydroxyproline content in the resulting hydrolysate was measured with the SpectraMax i3x (Molecular Devices, Sunnyvale, CA) according to the manufacturer\'s instructions and normalized to the hepatic protein concentration in the homogenate as measured by the BCA assay kit.
Serum Biochemistry {#hep41426-sec-0009}
------------------
To determine serum metabolites, serum was collected from 24‐hour fasted young WT (n = 6) and *Pygl* ^−/−^ (n = 7) mice and analyzed for triglyceride, cholesterol, lactic acid, and uric acid. The colorimetric kits used for serum biochemistry were the cholesterol and uric acid kits from Thermo Fisher Scientific, the triglyceride kit from Sigma‐Aldrich (St. Louis, MO), and the lactic acid kit from Pointe Scientific (Canton, MI). To analyze liver function, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin were determined using the respective colorimetric kits from BioVision.
Histopathology of GSD‐VI {#hep41426-sec-0010}
------------------------
Liver samples from young WT (n = 6) and *Pygl* ^−/−^ (n = 9) and old WT (n = 7) and *Pygl* ^−/−^ (n = 13) mice were fixed in 10% neutral‐buffered formalin and embedded in paraffin using standard methods (Histoserv, Inc., Germantown, MD). Adjacent 4‐5 µm sections stained with hematoxylin and eosin (H&E) and Masson\'s trichrome were evaluated by a certified veterinary pathologist (J.A.S.). Liver sections were also stained by picrosirius red and periodic acid--Schiff for evaluation of collagen and glycogen, respectively.
Immunohistochemical Analysis {#hep41426-sec-0011}
----------------------------
The formalin‐fixed paraffin‐embedded liver sections of young WT (n = 5) and *Pygl* ^−/−^ (n = 6) mice and those of old WT (n = 6) and *Pygl* ^−/−^ (n = 13) mice were sectioned and deparaffinized by xylene. The resulting sections were then incubated in citrate antigen unmasking buffer (Cell Signaling Technology, Danvers, MA) for 10 minutes at 100°C. Endogenous peroxidase activity in tissue sections was quenched with 3% hydrogen peroxide solution. Tissue sections were blocked with normal goat serum, incubated with polyclonal antibody to alpha smooth muscle actin (α‐SMA; Cell Signaling Technology), and followed with the biotinylated secondary antibody in the VECTASTAIN Elite ABC kit (Vector Laboratories). The resulting complexes in sections were visualized with the ImmPACT EQV DAB kit (Vector Laboratories). Tissue sections were also counterstained with hematoxylin (Vector Laboratories). All stained sections were imaged with Laxco\'s LMC 4000 series compound microscope (Laxco, Inc., Mill Creek, WA) using a SeBaCam5c digital camera and SeBaView software (Laxco, Inc.).
Gene Expression Analysis {#hep41426-sec-0012}
------------------------
Total RNA was isolated from liver samples from young WT (n = 9) and *Pygl* ^−/−^ mice (n = 24) and old WT (n = 16) and *Pygl* ^−/−^ (n = 13) mice using TRIzol Reagent (Invitrogen, Carlsbad, CA) and the RNeasy Protect Mini Kit (QIAGEN) according to the manufacturers\' instruction. We synthesized complementary DNA (cDNA) using the iScript genomic DNA Clear cDNA Synthesis Kit (Bio‐Rad Laboratories, Hercules, CA). Messenger RNA (mRNA) expression was quantified by the CFX96 One Touch Real‐Time PCR Detection System (Bio‐Rad Laboratories). Data were analyzed using CFX Maestro software (Bio‐Rad Laboratories) and normalized to mouse ribosomal protein L19 mRNA expression. The PrimePCR quantitative PCR assay primers (Bio‐Rad Laboratories) used are summarized in Supporting Table [S1](#hep41426-sup-0001){ref-type="supplementary-material"}.
Statistical Analysis {#hep41426-sec-0013}
--------------------
Statistical analyses of ketone bodies, serum metabolites, gene expression, hepatic metabolites, and hepatic hydroxyproline were performed using Wilcoxon rank sum tests with SAS, version 9.4 (SAS, Inc., Cary, NC). Box‐and‐whisker plots were generated using GraphPad Prism, version 7 (GraphPad Software Inc., San Diego, CA). Other data were analyzed by unpaired *t* tests using GraphPad Prism, version 7. All tests were two sided.
Results {#hep41426-sec-0014}
=======
Generation of *Pygl‐*Deficient Mice and Presentation of GSD‐VI {#hep41426-sec-0015}
--------------------------------------------------------------
PCR analysis confirmed integration of the internal ribosome entry site:LacZ cassette and floxed promoter‐driven neomycin cassette between exon 2‐3 of the *Pygl* gene (Fig. [1](#hep41426-fig-0001){ref-type="fig"}A,B). Hepatic *Pygl* deficiency was also confirmed by real‐time PCR in young (4‐20 weeks) and old (\>40 weeks) mice (Fig. [1](#hep41426-fig-0001){ref-type="fig"}C). *Pygl* ^−/−^ mice exhibited no significant difference in body weight or physical appearance compared with age‐matched WT mice, although we observed a slight reduction in body weight in old *Pygl* ^−/−^ mice compared to age‐matched WT mice (Supporting Fig. [S1](#hep41426-sup-0001){ref-type="supplementary-material"}). *Pygl* ^−/−^ mice exhibited hepatomegaly with an elevated ratio of liver weight to body weight compared with WT mice, while no significant difference in kidney size and appearance was observed between WT and *Pygl* ^−/−^ mice (Fig. [1](#hep41426-fig-0001){ref-type="fig"}D,E).
{#hep41426-fig-0001}
GSD‐VI Mice Exhibit Excessive Hepatic Glycogen Accumulation and Ketotic Hypoglycemia {#hep41426-sec-0016}
------------------------------------------------------------------------------------
Periodic acid--Schiff staining revealed glycogen accumulation in *Pygl* ^−/−^ mice compared with WT mice (Supporting Fig. [S2](#hep41426-sup-0001){ref-type="supplementary-material"}). Quantification of hepatic glycogen revealed significantly increased glycogen accumulation in young and old *Pygl* ^−/−^ mice compared with age‐matched WT mice (Fig. [2](#hep41426-fig-0002){ref-type="fig"}A). Hepatic glycogen levels in old *Pygl* ^−/−^ mice were about 3‐fold higher than those in young *Pygl* ^−/−^ mice, suggesting hepatic glycogen accumulation with age. Consistent with impaired glycogen breakdown reflected by excessive glycogen accrual, hepatic free glucose levels were significantly decreased in *Pygl* ^−/−^ mice compared with age‐matched WT mice (Fig. [2](#hep41426-fig-0002){ref-type="fig"}B).
{#hep41426-fig-0002}
Patients with GSD‐VI display mild hypoglycemia with elevated blood ketone bodies during fasting.[2](#hep41426-bib-0002){ref-type="ref"}, [12](#hep41426-bib-0012){ref-type="ref"} Consistently, compared with WT mice, *Pygl* ^−/−^ mice displayed lower blood glucose levels at all tested fasting time points except 24 hours of fasting (Fig. [2](#hep41426-fig-0002){ref-type="fig"}C) and displayed elevated blood ketones levels at 2, 4, and 6 hours of fasting (Fig. [2](#hep41426-fig-0002){ref-type="fig"}D), representing ketotic hypoglycemia observed in patients with GSD‐VI. However, we did not witness any hypoglycemic seizures in *Pygl* ^−/−^ mice, a common complication observed during fasting in GSD‐Ia mice.[13](#hep41426-bib-0013){ref-type="ref"} Additionally, analysis of serum biochemistry revealed 24‐hour fasted *Pygl* ^−/−^ mice expressed significantly lower serum levels of triglyceride, cholesterol, and lactic acid compared with WT mice (Supporting Fig. [S3](#hep41426-sup-0001){ref-type="supplementary-material"}).
Histologic Findings in GSD‐VI Mouse Liver {#hep41426-sec-0017}
-----------------------------------------
Examination of H&E stained sections revealed that both young and old *Pygl* ^−/−^ mice had histologic evidence of glycogen accumulation in hepatocytes, with associated moderate enlargement to ballooning of hepatocytes that resulted in inconspicuous hepatic sinusoids (Fig. [3](#hep41426-fig-0003){ref-type="fig"}; Supporting Fig. [S4](#hep41426-sup-0001){ref-type="supplementary-material"}). Eight of 13 old *Pygl* ^−/−^mice had small to large (\>200 cells) aggregates of mononuclear cells associated with blood vessels (Fig. [3](#hep41426-fig-0003){ref-type="fig"}), while none of the WT mice did. Picrosirius red staining and Masson\'s trichrome staining revealed that in 13 old *Pygl* ^−/−^ mice, eight mice had minimal but occasionally mild collagen deposition in the subcapsular, sinusoidal, and/or periportal area of their livers (Fig. [3](#hep41426-fig-0003){ref-type="fig"}D1‐D4,E1‐E4,F1‐F4) compared to old WT mice (Fig. [3](#hep41426-fig-0003){ref-type="fig"}C1‐C4), and one mouse had regionally severe central to central fibrosis with a collapse of the intervening lobular structure (Fig. [3](#hep41426-fig-0003){ref-type="fig"}G1‐G4).
{#hep41426-fig-0003}
Old GSD‐VI Mice Exhibit Elevated Serum Transaminases and Activated Hepatic Stellate Cells {#hep41426-sec-0018}
-----------------------------------------------------------------------------------------
Quantitative analysis of hepatic hydroxyproline level, indicative of collagen content, revealed no significant difference between WT and *Pygl* ^−/−^ mice at both young and old age, although there were some individual variations between old *Pygl* ^−/−^ mice (Fig. [4](#hep41426-fig-0004){ref-type="fig"}A). Elevated serum transaminases has been reported in patients with GSD‐VI.[2](#hep41426-bib-0002){ref-type="ref"} Consistently, serum levels of AST and ALT were elevated in old *Pygl* ^−/−^ mice, indicating liver injury, while there was no significant difference in serum levels of bilirubin and ALP between WT and *Pygl* ^−/−^ mice at both young and old age (Fig. [4](#hep41426-fig-0004){ref-type="fig"}B). Activated hepatic stellate cells (HSCs) play a critical role in liver fibrosis.[14](#hep41426-bib-0014){ref-type="ref"} When HSCs are activated by liver injury, they transdifferentiate into myofibroblasts, which produce and secrete various extracellular matrix proteins, leading to liver fibrosis.[14](#hep41426-bib-0014){ref-type="ref"} To investigate HSC activation in liver, we performed immunohistochemistry of α‐SMA, a marker of activated HSCs. Notably, old *Pygl* ^−/−^ mice displayed increased but variable numbers of α‐SMA‐positive cells in periportal and perisinusoidal areas in their livers compared with old WT mice, while there was no difference between young WT and *Pygl* ^−/−^ mice (Fig. [4](#hep41426-fig-0004){ref-type="fig"}C). Collectively, these results suggest that liver injury in old *Pygl* ^−/−^ mice may activate HSCs, which are responsible for liver fibrosis.
{#hep41426-fig-0004}
Expression Profile of Fibrotic and Inflammatory Genes in GSD‐VI Mice {#hep41426-sec-0019}
--------------------------------------------------------------------
To understand the underlying pathological mechanism in *Pygl*‐deficient mice, hepatic mRNA expressions in young and old WT and *Pygl* ^−/−^ mice were evaluated by quantitative real‐time PCR analysis. Target mRNA markers analyzed were connective tissue growth factor (*Ctgf*) and transforming growth factor β (*Tgf‐β*) related to liver fibrosis; interleukin‐6 (*Il‐6*) and tumor necrosis factor alpha (*Tnf‐α*) related to inflammation; collagen I a1/a2 (*Col1a1/a2*), collagen IV a2 (*Col4a2*), and fibronectin (*Fn1*) related to extracellular matrix; and monocyte chemoattractant protein 1 (*Mcp‐1*), C‐C chemokine ligand 5 (*Ccl5*/*Rantes*), C‐X‐C chemokine ligand 1 (*Cxcl1*/*KC*), and macrophage inflammatory protein 2α (*Mip‐2α/Cxcl2*) related to immune cell recruitment. Hepatic mRNA levels of *Tgf‐β* (*P* \< 0.001), *Tnf‐α* (*P* \< 0.01), and *Ccl5/Rantes* (*P* \< 0.05) along with *Col1a1* (*P* \< 0.001), *Col1a2* (*P* \< 0.05), *Col4a2* (*P* \< 0.001), and *Fn1* (*P* \< 0.01) were elevated in young *Pygl* ^−/−^ mice compared with WT mice (Fig. [5](#hep41426-fig-0005){ref-type="fig"}A). However, examination of H&E, Masson\'s trichrome, and picrosirius red staining (Fig. [3](#hep41426-fig-0003){ref-type="fig"}) showed that increased mRNA expression of these genes in young *Pygl* ^−/−^ mice did not correlate with liver fibrosis. Consistent with pathological phenotypes observed in old *Pygl* ^−/−^ mice (Fig. [3](#hep41426-fig-0003){ref-type="fig"}), we also observed up‐regulated hepatic mRNA levels of *Ctgf* mRNA (*P* \< 0.0001) and *Mcp‐1* (*P* \< 0.001) and *Ccl5*/*Rantes* (*P* \< 0.05), which play important roles in fibrosis and immune cell recruitment (Fig. [5](#hep41426-fig-0005){ref-type="fig"}B).
{#hep41426-fig-0005}
Discussion {#hep41426-sec-0020}
==========
GSD‐VI is an inheritable metabolic disorder characterized by hepatomegaly, mild fasting hypoglycemia, and hyperketosis during fasting.[2](#hep41426-bib-0002){ref-type="ref"}, [5](#hep41426-bib-0005){ref-type="ref"}, [6](#hep41426-bib-0006){ref-type="ref"}, [7](#hep41426-bib-0007){ref-type="ref"}, [8](#hep41426-bib-0008){ref-type="ref"}, [9](#hep41426-bib-0009){ref-type="ref"}, [10](#hep41426-bib-0010){ref-type="ref"} GSD‐VI is frequently underdiagnosed because of its mild phenotype. However, severe complications, including liver fibrosis, liver tumors, and cirrhosis, have been reported in patients with GSD‐VI.[2](#hep41426-bib-0002){ref-type="ref"}, [7](#hep41426-bib-0007){ref-type="ref"}, [8](#hep41426-bib-0008){ref-type="ref"} Currently, there are limited resources available to study this disease besides clinical case reports. Thus, we developed a mouse model with a genetic deficiency of *Pygl* that recapitulates the phenotype reported in human GSD‐VI. Indeed, *Pygl*‐deficient mice exhibit hepatomegaly, excessive hepatic glycogen accumulation, mild fasting hypoglycemia, and elevated blood ketone bodies during prolonged fasting. Furthermore, we show PYGL deficiency leads to progressive accumulation of hepatic glycogen with age and increases the risk of liver damage and inflammation along with collagen deposition in old *Pygl* ^−/−^ mice (Fig. [6](#hep41426-fig-0006){ref-type="fig"}).
{#hep41426-fig-0006}
During fasting periods, the liver plays a critical role in endogenous glucose production through glycogenolysis and gluconeogenesis (GNG).[15](#hep41426-bib-0015){ref-type="ref"} Short‐term fasting activates hepatic glycogenolysis, including liver glycogen phosphorylase‐mediated degradation of glycogen into G1P, which is further metabolized into glucose. Once hepatic glycogen storage is depleted by prolonged fasting, the liver induces GNG, which uses amino acids, lactate, pyruvate, glycerol, and fatty acids to produce glucose. This study shows that *Pygl*‐deficient mice following a fasting challenge display mild ketotic hypoglycemia along with reduced levels of serum metabolites, including triglyceride, cholesterol, and lactic acid, which can be substrates for GNG. Intriguingly, it has been suggested that elevated ketone bodies in ketotic GSDs reflect increased mitochondria fatty acid oxidation, which is elicited by GNG.[16](#hep41426-bib-0016){ref-type="ref"} Therefore, elevated blood ketone bodies and reduced levels of serum metabolites in fasted *Pygl* ^−/−^ mice raise the possibility that *Pygl* deficiency may induce GNG instead of defective glycogenolysis to compensate low glucose production in fasted periods, as suggested.[17](#hep41426-bib-0017){ref-type="ref"}
Distinct hepatic complications have been reported in each type of GSD. Untreated patients with GSD‐I and animal models frequently develop hepatocellular adenoma (HCA) or carcinoma (HCC), while liver fibrosis or cirrhosis was not observed in GSD‐I.[13](#hep41426-bib-0013){ref-type="ref"}, [15](#hep41426-bib-0015){ref-type="ref"} In contrast, liver fibrosis and cirrhosis as well as hepatic tumors have been reported in patients with GSD‐III.[18](#hep41426-bib-0018){ref-type="ref"}, [19](#hep41426-bib-0019){ref-type="ref"} However, it is still unclear which hepatic complications are prevalent in GSD‐VI, although there are a few case reports showing that patients with GSD‐VI develop hepatic tumor, fibrosis, and cirrhosis.[2](#hep41426-bib-0002){ref-type="ref"}, [7](#hep41426-bib-0007){ref-type="ref"}, [8](#hep41426-bib-0008){ref-type="ref"} In this study, we have shown that old *Pygl* ^−/−^ mice are at risk of liver fibrosis while there was no evidence of HCA and HCC in spite of excessive glycogen accumulation.
Hepatic fibrosis is triggered by chronic liver injury caused by viral infection, drugs, toxins, or metabolic disorders.[14](#hep41426-bib-0014){ref-type="ref"} Once HSCs are activated by cytokines and chemokines released by immune cells and damaged hepatocytes, they undergo transdifferentiation into myofibroblasts, which are mainly responsible for collagen deposition in liver fibrosis.[14](#hep41426-bib-0014){ref-type="ref"} In this study, several lines of evidence show that prolonged *Pygl* deficiency leads to the pathological features associated with liver fibrosis. First, *Pygl* ^−/−^ mice displayed age‐dependent excessive hepatic glycogen accumulation, which can damage hepatocytes as well as the liver architecture. It is noteworthy that average hepatic glycogen levels in old *Pygl* ^−/−^ mice are at least 60‐fold higher than those in WT mice. Moreover, we observed liver injury reflected by elevated serum ALT and AST in old *Pygl* ^−/−^ mice. Second, α‐SMA‐positive cells, indicative of activated HSCs, were increased in old *Pygl* ^−/−^ mice compared with age‐matched WT mice. Third, collagen deposition and inflammatory infiltrates associated with hepatic vessels were variably but overall elevated in the livers of old *Pygl* ^−/−^ mice along with up‐regulated hepatic mRNA levels of fibrogenic gene (*Ctgf*) and chemokine genes (*Ccl5/Rantes* and *Mcp‐1*). Based on these results, we suggest that prolonged hepatic *Pygl* deficiency leads to an excessive buildup of hepatic glycogen that can increase the risk of liver damage, inflammation, and fibrosis (Fig. [6](#hep41426-fig-0006){ref-type="fig"}). Additional mechanistic studies are needed to understand the complete metabolic impact of defective glycogen metabolism on hepatic pathogenesis in GSD‐VI.
While the *Pygl*‐deficient mice appear to be an outstanding model for studying GSD‐VI in humans, it is important to note that several differences were identified. Growth retardation, presumably from chronic ketosis, is common in humans, but body weight differences were only identified in aged mice in this study. The severity of hypoglycemia is also worse in humans compared with this mouse model. In humans with GSD‐VI, hyperlipidemia is common, but this is not found in this model. Finally, results from initial fasting studies were similar to those seen in humans, but humans are much more prone to severe ketosis with prolonged fasting. One explanation for the discrepancy may result from the broad spectrum of residual liver glycogen phosphorylase activities in human GSD‐VI patients.[2](#hep41426-bib-0002){ref-type="ref"}, [5](#hep41426-bib-0005){ref-type="ref"}, [9](#hep41426-bib-0009){ref-type="ref"} in contrast to the complete absence of the enzyme activity in the *Pygl* ^−/−^ mouse. A second possibility is a differential dependency on alternative metabolic pathways to compensate low blood glucose. Indeed, GSD‐VI mice exhibit decreased serum levels of lactic acid, triglyceride, and cholesterol that can be used for gluconeogenesis in a prolonged fasting state. Additionally, the difference shown in serum metabolites might result from the varying fasting conditions to collect blood in clinical cases[1](#hep41426-bib-0001){ref-type="ref"}, [2](#hep41426-bib-0002){ref-type="ref"}, [7](#hep41426-bib-0007){ref-type="ref"} compared to the current study.
In summary, our newly generated GSD‐VI murine model faithfully recapitulates the features of human GSD‐VI (Fig. [6](#hep41426-fig-0006){ref-type="fig"}), including hepatic glycogen accumulation, ketotic hypoglycemia, and hepatic collagen deposition, and provides a model to elucidate the mechanisms underlying hepatic complications associated with defective glycogen metabolism.
Supporting information
======================
######
######
Click here for additional data file.
We thank the KOMP Repository at the University of California, Davis, for collaboration and production efforts to generate the *Pygl*‐knockout mice. All funding support was managed by the foundations at the University of Connecticut Health Center and the University of Florida.
| 2023-12-11T01:26:29.851802 | https://example.com/article/7514 |
Q:
Stack Snippets and non-runnable code
Since the introduction of Stack Snippets, I've noticed them showing up frequently with non-runnable code. (I spend most of my time on the google-apps-script tag, which is a server-side js variant. I imagine that node-js folks see the same. Sure enough - it's mentioned in this question for casperjs as well.)
I can see value in Stack Snippets for js variants, for the code tidy-up within the editor and "copy to answer" function. But the "Run" button is prominent & useless.
Is there a way that I can edit a question to leave the snippet in place, but disable the "Run" button?
A:
If it's not a stack snippet (HTML+CSS+JS), don't use the stack snippet feature.
Copying a bog-standard code-sample to the answer is easy enough, the copy-to-answer button is not valuable enough to balance blatant misuse of the feature.
A:
Easily done, but not documented. (Until now, that is!)
Turns out there's zero tolerance on the syntax of the begin comment, therefore you can disable snippet controls by making that comment line invalid. A whitespace violation is enough, but I'm proposing using runnable: false in the hopes that it turns into a feature that only removes the "run" button, leaving the still-useful "copy snippet to answer" button.
<!-- begin snippet: js hide: false runnable: false -->
Other 'typos' that can disable the snippet widget:
remove space after open or before close comment markers
<!-- begin snippet: js hide: false-->
^
any extraneous character
<!-- begin snippet: js hide: false x -->
^
A:
I really like the runnable snippets
I think it's nice to have a replacement for jsFiddle and CodePen and others that were so often linked too. It would be nice if Runnable Snippets could run other kinds of snippets too, but HTML+CSS+JavaScript is as easy as combining them and feeding them to an iframe, so it was the obvious choice to start with.
It's going to be hard to build it for other languages
I think the next step would be excessively harder to build. You'd need a completely different UI to select from a multitude of languages, and you require a big server capacity and complex configuration to run all that stuff. Because once there is a Node.js tool, PHP users will want one too. And eventually you'll be running COBOL code somewhere.
But let's still keep the current one
Personally I'm glad with this feature, and I think it's acceptable that it works only for, basically, client-side web questions, and removing this feature because it is misused doesn't seem the right way to go. After all, new users make mistakes with the normal code snippet button too. That's what new users do, and often it's simple to fix. A small checkbox to mark it as 'Non runnable' could make life easier for those who edit the questions.
And add some features to normal code snippets
But maybe there can be some modification to the snippets inserted by the normal {code sample} button. They could have a 'copy snippet to answer' button as well, and maybe also a possibility to select a language in case the automatic detection failed.
Doing so gives no a richer experience for normal snippets, and an additional simulator for client-side web code, which may in the future be expanded with other languages as well.
| 2024-01-08T01:26:29.851802 | https://example.com/article/8979 |
Objective
=========
To determine ICU-acquired infections and sensibility to antibiotics by an antibiotic therapy policy with a patient-to-patient rotation. We have compared our dates with EPIC study \[[@B1]\].
Design
======
Prospective observational study.
Setting
=======
A 20-bed medical-surgical Intensive Care Unit (ICU).
Patients
========
All patients admitted in ICU from 1-1-1999 to 30-7-1999 and from 16-6-2000 to 16-10-2000, with a length of stay in ICU longer than 24 hours. The infections were diagnosed according to the criteria of the CDC.
Results
=======
371 patients (66.85% males) and 163 patients (63.19% males) fulfilled all criteria in respectives periods. Mean age was 57.71 ± 16.85 years and 57.58 ± 16.56 years. APACHE-II was 14.4 ± 6.2 and 12.5 ± 5.2. Mortality was 12.18% and 12.19%. Patients distribution was: 43% and 46% cardiac surgery, 14% and 15% cardiologic, 9% and 13% neurologic, 9% and 7% traumathology, 10% and 5% pulmonary, 5% and 6% digestive, 10% and 8% others. Mechanical ventilation was need in 74% and 91%, central venous line in 79% and 97%, vesical catheter in 92% and 97%. We diagnosed 145 UCI-acquired infections in 90 patients and 105 UCI-acquired infections in 52 patients. Distribution infections was: respiratory 40% and 39%, urinary tract 28% and 22%, bloodstream 14% and 12%, others 18% and 27%; 152 and 106 germs were isolated: 48% and 45% gram negative, 45% and 45% gram positive, 7% and 10% fungi. Most frequently germs reported in first period were: 15% *S. Aureus*, 12% Enterococci and 11% *E. Coli*; and second period were: 19% Epidermidis Staphylococci, 9% *S. Aureus* and 9% *E. coli*. The differences we found with EPIC are shown in the Table.
EPIC HUC- HUC-
-------------------------------- ------ ------ ------
Rate infections
For pseudomonas aeruginosa 28% 6% 9%
For acinetobacter 9% 0.6% 0%
For fungi 17% 7% 10%
Rate resistance of pseudomonas
To gentamicin 46% 37% 25%
To ureidopenicillin 37% 37% 0%
To ceftazidime 27% 25% 0%
To ciprofloxacin 26% 4% 10%
To imipenem 21% 17% 10%
Rate resistance
Of staphylococci aureus to 60% 4% 30%
methicillin
Of coagulase-negative 70% 91% 88%
staphylococci to methicillin
Of coagulase-negative 3% 0% 0%
staphylococci to vancomycin
Of coagulase-negative 66% 69% 42%
staphylococci to gentamicin
Conclusions
===========
The antibiotic therapy policy with a patient-to-patient rotation can be useful for the control of infectious mape in ICU.
| 2023-08-10T01:26:29.851802 | https://example.com/article/4884 |
The invention is directed to a method for instantaneously monitoring two or more wavelengths of light and an apparatus for effecting the same. More particularly, the invention is an acousto-optic dispersive light filter (AODLF), which is an electronically adjustable spectroscopic device capable of instantaneously monitoring many wavelengths with a fixed RF drive frequency. The present invention has approximately a one octave optical range, the center of which is selected by changing the RF drive frequency. The resolution of the AODLF in the infrared is several thousand, and is also electronically adjustable. The process and apparatus of this invention is particularly useful for the detection and analysis of, for example, short light pulses.
The acousto-optic tunable filter (AOTF) has long been recognized as an effective way to rapidly analyze light with an all solid-state device, over a large spectral bandwidth. Among the advantages of the AOTF are its large angular aperture with good spectral resolution, making it well suited for applications both in the visible and infrared ranges. However, the AOTF is inherently a single-channel device; i.e., in its natural mode of operation, only one wavelength resolution element at a time may be passed, although it is possible to randomly access such elements in times typically on the order of tens of microseconds. This random access time is simply limited by the travel time of the acoustic wave across the optical aperture. Thus, the filtered light falls upon a single detector element, and the spectrum scanning is performed by a linear time sweep of the applied RF power. A typical application of an AOTF as described above is set forth in detail in allowed U.S. patent application Ser. No. 345,123 filed Feb. 2, 1982 and entitled "An Automated Acousto-Optic Infrared Analyzer". This allowed patent application is assigned to the assignee of the subject patent and is incorporated by reference as if set forth in full herein. Such a spectrum scanning operation is satisfactory in the presence of cw or very slowly varying light signals, in which the composition of the light remains essentially constant over a complete sweep duration of the RF range. Complications, however, may arise in the presence of pulsed-light signals, which will go undetected unless the proper acoustic tuning frequency is present in the optical aperture at the instant of the light pulse. Thus, if it is desired to detect the presence of a known optical wavelength, but at an unknown time of arrival, the AOTF must be continuously excited with RF of exactly that frequency. This may be extended to a few wavelengths simultaneously, for which frequencies corresponding to each of the wavelengths must be simultaneously applied to the AOTF. In this case, the determination of which of the several wavelengths may have been detected will require a strategy of frequency dropping over a few pulses. Operation at reduced duty cycle will result in lower detection probability. These difficulties make it desirable to consider possible acousto-optic techniques which are many channel in nature, so that the device will be open to receive all of the wavelength resolution elements simultaneously.
It is, therefore, an object of this invention to provide an acousto-optic dispersive light analyzer which is an electronically adjustable spectroscopic device capable of instantaneously monitoring many wavelengths with a fixed drive frequency and a technique for operating such an acousto-optic device to obtain the aforedescribed results.
The AODLF is functionally very similar to a fixed grating, but there are several important differences which are advantageous in certain applications. The two principal differences are the tunability of the AODLF and its birefringent operation. A conventional grating, being optically isotropic (i.e., no change of polarization of the diffracted light), must be blazed in order to concentrate the diffracted light into a single order; however, the birefringence of the AODLF produces only a single order. Because the fixed grating is isotropic, the angular aperture with a blaze will be more limited than the angular aperture of the AODLF and correspondingly the optical range will also be more limited. A large change in the optical bandcenter of the fixed grating requires a mechanical change in the angle of incidence, while a bandcenter change of the AODLF is accomplished simply by a change in the RF only, with no change in the angle of incidence. Thus, the unique feature which is provided by the AODLF of this invention is the electronic tunability of the grating constant, which allows enhanced flexibility of operation, such as large changes of spectral range. The electronic tunability also easily permits the frequency modulation of the optical signal in order to perform derivative spectroscopy, which may improve the signal-to-noise ratio over that of a constant signal.
It is known that the simplest AO Bragg diffraction of the type used in scanning and deflection can be employed, in principle, to effect a light spectrum analyzer. However, there are serious limitations to this simplistic approach. Ideally, such a device would work in the following fashion. The light to be analyzed is incident on the cell at some fixed angle which will not be varied over the entire spectral range, and with some usably large angular aperture; the acousto-optic cell will be excited with a fixed cw RF so that there will be unity probability of intercept, and at as near 100% efficiency as possible for maximum sensitivity; each wavelength resolution element should emerge from the cell at a different diffracted angle, so that a detector array in the focal plane of the system may be used to analyze the light spatially; the spectral range and the resolution should be electronically controllable so that no mechanical motion is needed to make adjustments for its operation.
In the simplest configuration, the low frequency or Raman-Nath mode of diffraction, the relationship between the optical wavelength, .lambda., the acoustic wavelength, .LAMBDA.=v/f, and the interaction length, l, must satisfy EQU 4l.lambda./.LAMBDA..sup.2 .ident.Q<<1, (1)
where v is the acoustic wave velocity and f its frequency. When this condition is satisfied, for light incident normal to the acoustic wave propagation direction, light is diffracted at the Bragg angle .theta..sub.B into multiple positive and negative orders, n, according to EQU sin n.theta..sub.B =n.lambda./.LAMBDA.=n.lambda.f/v (2)
The resolution of the cell is simply given by N, the number of acoustic wavelengths within the optical aperture, L, so that EQU N=L/.LAMBDA.=Lf/v (3)
and the angular aperture, A, is given by the acoustic wave diffraction spread EQU A=.LAMBDA./l=.lambda./l sin .theta..sub.B ( 4)
A few characteristics can be easily evaluated for the two favorable infrared materials, Tl.sub.3 AsS.sub.3 (TAS) and Hg.sub.2 Cl.sub.2, at an optical wavelength of, say, 5 .mu.m. To satisfy the condition of Q<1 we take l=1 cm for TAS, and 0.5 cm for Hg.sub.2 Cl.sub.2, and an RF of 2.3 MHz for the former and 1.1 MHz for the latter. At such low frequencies, acoustic attenuation is not a limiting factor, and we may make the optical aperture crystal size limited, said 5 cm. The number of resolution elements will then be 110 for TAS and 158 for Hg.sub.2 Cl.sub.2. These characteristics are summarized in Table I.
TABLE I ______________________________________ CHARACTERISTICS OF RAMAN-NATH AO DISPERSION CELL .lambda. = 5 .mu.m, L = 5 cm Material 1(Cm) f(MHz) .theta..sub.B (deg) A(deg) N ______________________________________ TAS 1 2.3 0.63 2.6 110 Hg.sub.2 Cl.sub.2 0.5 1.1 0.91 3.6 158 ______________________________________
There are some serious limitations on utilizing Raman-Nath diffraction in this fashion for optical spectrum analysis. First, since the interaction length l, must be small, it will not be possible for the efficiency to be high at long infrared wavelengths. This is because the RF power requirements increase with the square of the wavelength, and the above values of l will not be large enough even with these efficient materials; compounding this difficulty is the wasting of diffracted light to orders other than the +1, so that the detected light efficiency at a single order can never be high. Second, the presence of multiple diffraction orders restricts the optical bandwidth to one octave, in order that there be no overlap between first and second orders. Third, the Bragg angles are small in comparison with the angular aperture, so that it will be necessary that the input light be highly collimated.
One might hope to avoid these difficulties by operating in the Bragg diffraction mode, for which it is required that the parameter Q>>1. To illustrate the problems that approach leads to, let us assume a factor of 10 increase in RF, for the same values of l. Operation in the Bragg regime requires that the light to be analyzed be incident to the acoustic wave at the Bragg angle, so that the incident light angle must therefore vary with the optical wavelength. If we require the incident light angle to be fixed, the spectral range will be limited by the angular aperture. Some of these considerations are summarized in Table II.
TABLE II ______________________________________ CHARACTERISTICS OF BRAGG AO DISPERSION CELL .lambda. = 5 .mu.m, L = 1 cm Spectral Material 1(Cm) f(MHz) A(deg) Range(.mu.m) N ______________________________________ TAS 1 23 0.26 0.21 220 Hg.sub.2 Cl.sub.2 0.5 11 0.36 0.20 316 ______________________________________
It is apparent that this approach is unsatisfactory due to the very small value of spectral range that results from the small angular aperture. The range can be enlarged by mechanical rotation of the cell to match the Bragg angle as the optical wavelength is changed, but then the device is no longer purely electronic.
The acousto-optic tunable filter (AOTF) which is known generally consists of a transducer plate and a transparent optical medium through which acoustic waves generated by the transducer propagate. The transducer is typically a thin plate of a piezoelectric crystal such as lithium niobate (LiNbO.sub.3) or quartz (SiO.sub.2). The optical medium must be crystalline and possess the appropriate symmetry properties, such as thallium arsenic selenide (Tl.sub.3 AsSe.sub.3). The transducer is operably associated with the optical medium by a bond of high acoustic quality. The operational concept of the AOTF is explained in detail in the article "Tunable Acousto-Optic Filters and Their Application to Spectroscopy", Feichtner, J. D., et al., SPIE Vol. 82, page 106 (1976), the contents of which are incorporated herein by reference. | 2023-12-10T01:26:29.851802 | https://example.com/article/9077 |
A Fairer Way To Tax
So goes one of many libertarian mantras, and it embodies a core principle of liberty. Taxless libertarian nirvana is not, however, lurking around the corner, or on the next block, or even in the same hemisphere, so it’s a philosophical position more than an actual hope for policy. Thus, it behooves libertarians and liberty lovers to actually engage in dialogue on matters of taxation, rather than simply cut ourselves out of the conversation.
One such opportunity presents itself in an idea currently percolating in California: taxing drivers/vehicles on a per-mile basis. Currently, revenue is raised for road maintenance and construction via per-gallon gasoline taxes (plus tolls, plus registration fees and the like). Considered theoretically, such taxes are more “just” than many other taxes we pay, because they are connected to the use of a public good (i.e. roads, bridges, highways). Practically, however, the gasoline tax isn’t as fair or just as it could be, because there is a wide disparity in fuel efficiency, because actual wear-and-tear on the roads is not proportional to fuel consumption, and because the tax applies to gasoline used for non-public-road purposes as well. Consider that a Prius weighs the same as a Chevy Malibu, but gets almost double the mileage. And consider that a Chevy Volt, or a Tesla, or a Nissan Leaf, or any of the other plugin cars on the market pay no gasoline tax. Roads don’t care about how fuel efficient a car traveling on them is. Roads are affected by that car’s weight. An 80,000 lb tractor trailer gets 6 miles to the gallon vs the Prius’s 60, but its impact on the road is probably much more than 10x that of the Prius. A Tesla weighs as much as more than a Chevy Malibu, and thus wears the road just as much, so why should it get a free ride?
Climate change activists, fossil fuel foes, and other social engineering types will argue that government encourages high mileage vehicles by making it relatively more expensive to own gas guzzlers, but activist government is anathema to libertarian ideals. In other words, it’s not the government’s place to tell us what to buy or how to live. Taxation as social policy is incompatible with liberty.
I’ve written in the past that there are two types of taxes: fee-for-service and redistributive. There is no principle of liberty under which the government can take from A merely to give to B. On the other hand, citizens of a city, state or nation receive some basic services from government, services that even exist in libertarian versions of how the world would work, and they do need to be paid for. While coercive taxation is at odds with the philosophy, as I noted, we are very, very far away from that, and so making a distinction between types of taxes should not incite screams of “you’re not a real libertarian!” After all, it is proper that one pays for a good or service. Yes, taxation is coercive, and yes, there are non-coercive ways to pay for building and maintaining public roads, but lets be honest – our system of paying for roads and highways is not about to be radically reformed into any of those.
So, lets work on making things more just and fair within the present reality.
One problem with gasoline taxes is that the push towards more fuel-efficient vehicles harms revenues. Yes, government wants us in more fuel-efficient cars, and has for decades. In the past, it was about reducing dependence on foreign oil. But, now, with the fracking revolution, we’ve got oodles of the stuff, and so now it’s supposedly about reducing carbon emissions. So, mileage mandates continue to climb upwards. And, so, gas tax revenues have decreased even as Americans drive more (and thus put more wear and tear on the roads).
A per-mile tax, weighted for vehicle weight in a manner that best reflects a car’s impact on the road, would establish a proper fee-for-service connection between user and asset. Properly as well, there should be an exclusion for off-road use, but that’s just a detail of implementation. This is how taxation should work: people pay for the public goods they consume. The principle can be conveyed to other basic functions of government, i.e. national defense, courts and other federal-level functions, police and other municipal services at the local level, and so forth. Taxation in this manner would reset people’s thinking about taxes, government, fairness and justice, away from the “soak some to benefit others” to “we pay for what we use and for what government should be doing.”
Of course, the odds of a mileage tax replacing a gas tax, instead of supplementing it, are low. This sad reality – that taxes are applied in “death by a thousand cuts” form – is why I stand leery of the Fair Tax, which is supposed to replace income taxation with consumption taxation. Certainly, the latter would be a welcome change, and alter the entire dynamic of our country and its revenue generation. But, barring a repeal of the 16th Amendment, it’s a given that the next time a tax-loving administration and Congress took the reins of power, there’d be a reinstatement of income taxation, and we’d be getting it from both ends, the way the Europeans do. And, the devil is very much in the details. How to secure privacy, how to avoid charging for private road mileage, how to make this work at the state and local level – all real questions worthy of real debate. Questions about implementation, however, do not obviate the soundness or validity of the principle.
The reality that gas taxation is an increasingly unbalanced way of paying for roads is going to force legislators’ hands at some point. As the debate of how to pay for roads that are seeing increased use even as fuel efficiency decreases revenues comes to the fore, we should involve ourselves rather than stonewall-dismiss the idea of a mileage tax. We should demand it replace the gas tax, not supplement it. As we should do with other taxes. Taxes should be user fees, not rob-Peter-to-give-to-Paul. In the name of fairness. Fairness is, after all, a warm-and-fuzzy word to politicians, but since it’s indeed fuzzy, we need to manage what they mean when they say it.
How we tax is as important as how much we tax, or what we tax, and we should seize every opportunity to help shape that debate.
I am twice-retired, a former rocket engineer and a former small business owner. At the very least, it makes for interesting party conversation. I'm also a life-long libertarian, I engage in an expanse of entertainments, and I squabble for sport.
Nowadays, I spend a good bit of my time arguing politics and editing this website.
By clicking this flag, you will send an anonymous report to the website admins alerting them that this comment should be looked at for violating the commenting terms for this site. The admins may or may not, at their discretion, decide to remove the comment and/or block the commenter. | 2023-12-30T01:26:29.851802 | https://example.com/article/3333 |
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