Indians need to get less hyper-sensitive about our national symbols.
A screengrab of CCTV footage of the Bengaluru molestation case.
There are two extreme and opposing positions when it comes to national symbols. Some make a case for a European approach where flag-waving nationalism is frowned upon (with exceptions made for football matches) while others link extreme piety for every national symbol to patriotism.
In the West, it's common for celebrities and sportstars to pose for photographs wearing undergarments in the colours of the national flag. Religious icons figure in popular songs laden with sexual innuendo. For a long time, it has been fashionable to ape the West. Could we copy them in this regard as well? I feel it is quite impossible. India has worshipped trees, rivers, the sun, and the earth we live on since the ancient times. The elders in my village would admonish children for urinating on tree trunks. Trees are deemed divine. The Indian tradition treats the earth as mother. To try and use Western frameworks to understand Indian life would be futile.
There is bound to be a difference in how the West influences our minds and Indian minds' attitude towards national symbols. Can Indians think of wearing flip-flops with the Indian flag printed on it?
In the Mahabharata, Hanuman graced Arjuna's chariot flag. It was Hanuman's promise to the Pandavas that he'd be with them throughout war and help them.
For a people whose tradition teaches them the value of symbols such as flags, it would be inconceivable to denigrate them by sporting them on shoes or undergarments.
But in the name of guarding our traditions, the thought process of Indians is slowly but surely being directed towards fascism.
At the recent Chennai Film Festival, I happened to watch five films in a day and had to stand up for the national anthem each time a film began. The screening at one of the theatres had to be stopped because some tried to rough up a group of women who hadn't bothered to stand up for the anthem.
This heady cocktail of Hindutva and ultra-nationalism seeks to chip away at our great diversity. Unlike China, and other modern Western nation states, there is no cultural, racial, or linguistic homogeneity in India. India has countless languages, dialects, ethnicities and cultural traditions. In our diversity lies our greatness. The forces of Hindutva-hypernationalism seek to flatten out this diverse landscape. They realise that mere slogans won't help them achieve their objective. They need everyday rituals to constantly reinforce their message. The forcible worship of national symbols are those rituals.
Incidents such as the molestation of a Bengaluru woman on New Year's Eve, and the attack on women in theatres for not standing up for the national anthem are closely connected. In the worldview of those who unleash such violence, the Indian woman is meant to demurely stay within the household. That is Indian culture for them. How dare they go out at midnight to party like men? If they do that, they are meant to be criticised. This is the view of our custodians of culture. These are the same people who now pretend to be the protectors of our national symbols in the "New India". I fear we are moving towards a very dangerous brand of fascism.
There has been oft-repeated controversies regarding respect for flags, national anthem, national songs and other symbols of national importance. Most of the controversies are unnecessary because those behind such incidents have no logic or justification for their negative approach to the national anthem or the national flag. A few years ago, a parliamentarian cited religion as a reason for not singing the national song, Vande Mataram, and more recently Amazon Canada used the tricolour for making doormats.
In Kerala, some radicals refused to sing the national anthem in cinema halls. A pertinent question arises: why Indians are sensitive to national symbols? And why we do not treat them liberally as some of the advanced democracies do? To understand this problem one has to reexamine the growth of our national sentiments.
The first and foremost thing, which India is privileged with, is the concept of holiness. We have inherited a legacy of cultural and civilisational tradition, which adds spiritual values to even material things of larger importance. Our civilisation has never been materialistic; material fortunes have always been superseded by intellectual and spiritual prosperity. Therefore, unlike other countries, Indian nationalism distinctly gives a sense of spiritualism too and we celebrate our territorial boundary not merely as a piece of land or a sign of mere sovereignty, but as a spiritual entity (which should not be confused with religious entity). We consider India as our motherland, Bharat Mata. This trait is present in each and every Indian, and even in those who oppose it due to political reasons or ideological indoctrination. But a close scrutiny of the behavioural pattern shows that Indians too have cultural nationalism.
This is one of the reason we consider our symbols of sovereignty and freedom holy and do not treat them as material things. This argument may be unpalatable to many who see life from the materialistic prism and the nation form the Western materialistic indoctrination. There is another rationale behind our ultimate respect for these symbols. The tricolour, Vande Matram and the national anthem have not been in the aftermath of intellectual discussion or political decisions. They have evolved along the process of development of modern nationalism, along with anti-imperialist struggles. The best political and intellectual minds contributed to their adoption and they inspired millions to sacrifice their lives for the motherland. Seven teenagers in Patna sacrificed their lives for the honour of the national flag on August 11, 1942. Four of them — Umakant Prasad Sinha, Ramanand Singh, Devipada Choudhry and Ramgovind Singh — were Class 9 students.
Similarly, Vande Mataram was a war cry during the freedom movement. RSS founder K.B. Hedgewar was thrown out from the school in Nagpur for shouting Vande Mataram. The imperialist government issued a circular known as Risley Circular against shouting Vande Mataram. The context of their evolution made them inalienable ingredients of our nationalist tradition.
There is sentiment of millions attached with them, they symbolised our brave struggle against imperialism and sacrifices of our martyrs and also inspire us to protect our freedom. They are not the things of the past, but present and future possession of our posterity. A few radicals can't defy millions under the pretext of freedom of expression.


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cgallina Conquest Era March 26, 2020 2 Minutes
Reuben, Gad, and half of Manasseh inherited the land east of the Jordan. "Nevertheless the children of Israel did not drive out the Geshurites or the Maachathites, but the Geshurites and the Maachathites dwell among the Israelites until this day." Remember the Lord instructed the Israelites over and over again to drive the people out of the land and do not commingle with those walking outside the presence of the Lord. As with any other disobedience, there will be consequences to their failure to drive the people out of the land.
The remaining nine and half tribes will inherit the land west of the Jordan. "For Moses had given the inheritance of the two tribes and the half-tribe on the other side of the Jordan; but to the Levites he had given no inheritance among them. For the children of Joseph were two tribes: Manasseh and Ephraim. And they gave no part to the Levites in the land, except cities to dwell in, with their common-lands for their livestock and their property." The Levites will be scattered amongst the tribes of Israel in order to minister to and serve the people.
First up to receive the land inheritance west of the Jordan is the faithful spy Caleb from the tribe of Judah. Caleb steps forward and requests to be given the land in Hebron where the descendants of Anak live. Remember when the twelve spies initially went to scout out the land they came back and ten of the twelve spies said, "There we saw the giants (the descendants of Anak came from giants); and we were like grasshoppers in our own sight, and so we were in their sight" (Numbers 13:33). Well Caleb, at the age of eight-five, is as strong as he was at the age of forty when he first scouted out the land and he is just as faithful. Caleb is basically saying that this grasshopper is going to take down the Anakims because he trusts the Lord – "Now therefore, give me this mountain of which the Lord spoke in that day; for you heard in that day how the Anakim were there, and that the cities were great and fortified. It may be that the Lord will be with me, and I shall be able to drive them out as the Lord said." And that he did! 💪
Then Caleb says, "He who attacks Kirjath Sepher and takes it, to him I will give Achsah my daughter as wife." Othniel, Caleb's nephew, conquers Kirjath Sepher and as a reward he is given Caleb's daughter in marriage. Othniel will show up again later in the Story in the Judges Era as Israel's first judge. But first, the remaining tribes have to settle into the land. Keep reading.
(Joshua 12:7-15:19)
#bibleliteracymovement #chronologicalbibleteaching
Previous Post From today's reading in Tyndale's One Year Chronological Bible dated 3/25:

redpajama_set_name: RedPajamaCommonCrawl


Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived from it to show that this inhibition is mediated by CD36, a transmembrane glycoprotein found on microvascular endothelial cells. Both IgG antibodies against CD36 and glutathione-S-transferase–CD36 fusion proteins that contain the TSP-1 binding site blocked the ability of intact TSP-1 and its active peptides to inhibit the migration of cultured microvascular endothelial cells. In addition, antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 to solid phase CD36 and its fusion proteins, as well as to CD36-expressing cells. Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SM∅, oxidized (but not unoxidized) low density lipoprotein, and human collagen 1, mimicked TSP-1 by inhibiting the migration of human microvascular endothelial cells. Transfection of CD36-deficient human umbilical vein endothelial cells with a CD36 expression plasmid caused them to become sensitive to TSP-1 inhibition of their migration and tube formation. This work demonstrates that endothelial CD36, previously thought to be involved only in adhesion and scavenging activities, may be essential for the inhibition of angiogenesis by thrombospondin-1.
Thrombospondin-1 (TSP-1)1 is one of a small number of molecules found naturally in vertebrates that can inhibit angiogenesis, the sprouting of new blood vessels from preexisting ones (Bouck et al., 1996). It is secreted at high levels by a variety of normal cells (Frazier, 1991; Lahav, 1993; Bornstein, 1995) and can decrease the density of the vasculature that forms during embryonic development (Stellmach et al., 1997) and wound healing in granulation tissue (Polverini, P.J., L.A. DiPietro, V.M. Dixit, R.O. Hynes, and J. Lawler. 1995. FASEB [Fed. Am. Soc. Exp. Biol.] J. 9:272a). In addition, TSP-1 can be an antiangiogenic barrier to the development of malignant tumors (Dameron et al., 1994; Weinstat-Saslow et al., 1994; Hsu et al., 1996; Volpert et al., 1997), which must induce a vigorous angiogenic response to grow and progress (Folkman, 1995b).
TSP-1 is an extremely potent inhibitor of angiogenesis. It is effective at subnanomolar concentrations in vitro and able to prevent neovascularization in vivo in the rodent cornea and polyvinyl sponge assays (Good et al., 1990; Tolsma et al., 1993). The 50-kD central stalk region of the 180-kD subunit of homotrimeric TSP-1 is sufficient for its full antiangiogenic activity. Molecules that retain either the procollagen homology region or the properdin type 1 repeat region from this stalk also retain antiangiogenic activity (Tolsma et al., 1993; Volpert et al., 1995), and small peptides derived from each of these domains are independently able to block endothelial cell migration in vitro and neovascularization in vivo (Tolsma et al., 1993).
Soluble TSP-1 inhibits angiogenesis by interacting directly with endothelial cells. At concentrations below 20 nM, which is about forty times that seen in normal plasma (Saglio and Slayter, 1982; Dawes et al., 1983; Harker et al., 1983; Browne et al., 1996), it inhibits endothelial cells in vitro, blocking their proliferation (Bagavandoss and Wilkes, 1990; Good et al., 1990; Taraboletti et al., 1992; Vogel et al., 1993; Raychaudhury et al., 1994) and migration (Rastinejad et al., 1989; Good et al., 1990; Taraboletti et al., 1990, 1992; Tolsma et al., 1993, 1997; Volpert et al., 1995) and their ability to form lumens (Tolsma et al., 1997) and tubes (Iruela-Arispe et al., 1991; DiPietro et al., 1994; Canfield and Schor, 1995), although at higher concentrations it can be stimulatory for endothelial cell migration (Taraboletti et al., 1990; Tolsma et al., 1993; Gao et al., 1996).
TSP-1 can render endothelial cells refractory to a wide variety of inducers from prostaglandins to VEGF (Volpert et al., 1995), all of which stimulate cells through different receptors. To address the mechanism by which TSP-1 induces this unresponsiveness in the endothelial cell, we have sought a receptor through which it might act. The intact TSP-1 molecule binds to at least 12 different receptors (Bornstein, 1995), many of which are present on the surface of the endothelial cell. Some, including integrin αvβ3 (Lawler, 1993), integrin-associated protein (also referred to as CD47 [Gao et al., 1996]), and possibly low-density lipoprotein related receptor protein (Godyna et al., 1995; Mikhailenko et al., 1995), interact with TSP-1 motifs that lie outside the 50-kD stalk and thus seem unlikely to be involved in mediating the antiangiogenic activity of TSP-1. Although there are uncharacterized receptors present on endothelial cells that can bind to TSP-1 (Chen et al., 1996) and TSP-1–interacting molecules identified on other cell types that could also be present on endothelial cells (Yabkowitz and Dixit, 1991; Tuzinsky et al., 1993), CD36 currently appears to be the most likely candidate to mediate the angioinhibitory activity of TSP-1.
CD36, also called glycoprotein IV, is an 88-kD transmembrane glycoprotein with a large extracellular domain (Greenwalt et al., 1992). Originally found on platelets and monocytes, it is also expressed on the microvascular cells that give rise to neovascularization in vivo (Swerlick et al., 1992; Peltzbauer et al., 1993). CD36 is well known as an adhesion receptor for TSP-1 (Asch et al., 1987, 1993; Li et al., 1993; Pearce et al., 1995) and Plasmodium falciparum parasitized erythrocytes (Oquendo et al., 1989; Baruch et al., 1996), facilitates the binding of platelets to collagen, monocytes, and the subendothelium, and contributes to the activation of monocytes and platelets (Greenwalt et al., 1992). CD36 also serves as a scavenger receptor. It mediates the uptake of anionic phospholipids (Rigotti et al., 1995) and oxidized low-density lipoprotein (OxLDL) (Endemann et al., 1993; Nicholson et al., 1995; Nozaki et al., 1995), an activity that may contribute to the formation of foam cells involved in the genesis of artherosclerotic plaques, and plays a key role in the phagocytosis of apoptotic cells (Savill et al., 1992; Ren et al., 1995; Stern et al., 1996) and rod outer segments in the retina (Ryeom et al., 1996a,b). Although not usually considered to be a signaling receptor, it coprecipitates from platelets and endothelial cells with several src-related kinases (Huang et al., 1991; Bull et al., 1994). Here we demonstrate that CD36 is an essential mediator of the antiangiogenic action of TSP-1 on endothelial cells in vitro. This is the first indication that engagement of CD36 can produce a biological response in endothelial cells and the first identification of a receptor able to mediate the effects of a broad spectrum inhibitor of angiogenesis like thrombospondin-1.
FA6-152 monoclonal antibody against CD36 was purchased from Immunotech (Westbrook, ME), and SM∅ monoclonal antibody against CD36 and IgG1 and IgM control monoclonal antibodies, MOPC-21 and MOPC-104E, were from Sigma Chemical Co. (St. Louis, MO). OKM-5 monoclonal antibody against CD36 was kindly provided by Dr. Mary Makowski (Ortho Diagnostic Systems, Raritan, NJ). Before use, all monoclonal antibodies were extensively dialyzed against DME using a 30-kD Centricon® concentrator (Amicon Corp., Beverly, MA).
Purified human platelet TSP-1 was kindly provided by Jack Lawler (Harvard University, Cambridge, MA). TSP-1 peptides were synthesized, purified, and dialyzed as previously described (Tolsma et al., 1993) and included Col overlap, NGVQYRN representing TSP-1 amino acid residues 303–309; Mal III, SPWDIASVTAGGGVQKRSK representing TSP-1 amino acid residues 481–499 with the cysteines present in the native molecule replaced with alanines; and Mal III variant, SPWDIASTSAGGGVQRSK, containing Mal III residues with an altered VTCG sequence. The position of these peptides in the intact TSP-1 molecule is shown in Fig. 1. Angiostatin was kindly provided by Michael O'Reilly and Judah Folkman (Harvard University). Recombinant human basic fibroblast growth factor (bFGF) was purchased from R & D Systems Inc. (Minneapolis, MN), human type I collagen was from Collaborative Biomedical Products (Bedford, MA), and human LDL was from Sigma Chemical Co. LDL was oxidized by dialyzing 200 μg/ml LDL against 5 μM CuSO4 in PBS for 24 h at 37°C (Nicholson et al., 1995).
The relationship of small TSP-1 peptides to the 180-kD monomer of TSP-1 and of GST–CD36 fusion proteins to the whole CD36 receptor protein. Numbers indicate amino acid residues present in the peptide or fusion protein. Shading on the whole CD36 molecule defines the minimal region of CD36 required for binding to TSP-1 (Pearce et al., 1995). Actual peptide sequences and detailed description of the fusion proteins are included in Materials and Methods.
CD36–glutathione-S-transferase (GST) recombinant fusion proteins spanning ∼98% of the human CD36 sequence were previously generated in a bacterial expression system (Pearce et al., 1995). In this study, we used fusion proteins containing the TSP-1 binding region and spanning amino acids 67–157, 93–120, and 93–298. As a control, we used a fusion protein unable to bind TSP-1 spanning CD36 amino acids 298–439. For the relative positions of these peptides on CD36, see Fig. 1. As described previously (Pearce et al., 1995), all plasmid constructs were mapped and insertion sites sequenced to confirm that the fusion protein sequences were correct and in frame. Generated fusion proteins were examined by SDS-PAGE, Western blot, gel filtration chromatography, and ELISA to confirm size and document CD36 immunoreactivity. All molecular weights as determined by gel filtration chromatography under nondenaturing conditions varied no more than 5% from calculated values (Pearce et al., 1995). These assays also showed that the fusion proteins did not form dimers or large multimers.
Cell binding assays were performed with Bowes melanoma cells stably transfected with human CD36 cDNA, or with a control plasmid, prepared and maintained as previously described (Silverstein et al., 1992). Cells were allowed to attach to 12-well plates. Radiolabeled TSP-1 was prepared as previously described (Pearce et al., 1995) with specific activity ranging from 0.5–1 mCi/mg. Inhibition studies were carried out by combining 125I–TSP-1 (20 μg/ml) with increasing concentrations of peptide (0.1–1000 μM). After incubation for 2 h at 37°C, the cells were washed five times with cold PBS and lysed with 0.1 N NaOH. The amount of bound radioactivity was determined by gamma counting. The peptide LYPQHKT, obtained from a domain of CD36 that does not bind TSP, was used as a control. IC50's were calculated using the curve fitting software program Enzfitter (Elsevier Biosoft, Cambridge, UK).
Solid phase binding assays were used to measure TSP-1 interactions with CD36 or CD36–GST fusion proteins in the presence of TSP-1 peptides. CD36 or CD36–GST fusion protein was immobilized on wells in a detachable 96-microwell plate by overnight incubation at 4°C. CD36 was adsorbed at 4 μg/ml in PBS, while fusion proteins were adsorbed at 10 μg/ ml in carbonate buffer (100 mM NaHCO3, 1 mM Mg Cl2, 0.02% NaN3, pH 9.8). Total protein coating the wells ranged from 200–280 ng. Wells were washed three times with 20 mM Tris, 150 mM NaCl, pH 7.4, containing 0.05% Tween-20 (TBS-T) and then blocked with TBS-T containing 0.5% BSA. Radiolabeled TSP-1 (20 μg/ml) along with two concentrations of peptide (at the Kd and five times the Kd as predicted by the cell binding studies) were added in TBS-T, and the mixture was incubated for 2 h at 22°C. Wells were then washed thoroughly three to four times with TBS-T and dried, and bound radioactivity was measured by gamma counting. The addition of 5 mM EDTA was used to determine nonspecific binding.
Bovine adrenal capillary endothelial cells (BCECs), kindly provided by Judah Folkman, were grown in DME with 10% donor calf serum (Flow Laboratories, McLean, VA) and 1% endothelial cell mitogen (Biomedical Technologies, Inc., Stoughton, MA) and used at passage 15. Human dermal microvascular endothelial cells (HMVECs) were purchased from Clonetics (San Diego, CA), grown in Clonetics' endothelial cell growth media, and used between passages 6 and 9. Human umbilical vein endothelial cells (HUVECs), generously provided by Dr. L. Cornelius (Washington University, St. Louis, MO), were grown in 199 Earles medium with 20% FCS and 10 μg/ml endothelial cell mitogen and used between passages 6–11.
Migrations were performed as previously described (Polverini et al., 1991). Briefly, confluent flasks of endothelial cells were starved overnight in control medium (DME containing 0.1% BSA). Cells were harvested, resuspended in control medium, and plated at 3 × 104 cells/well on the bottom side of a gelatinized 5 μM (for BCECs) or 8 μM (for HMVECs and HUVECs) porous membrane (Nucleopore Corp., Pleasanton, CA) in an inverted modified Boyden chamber. Cells were allowed to attach to the membrane for 2 h at 37°C, after which the chamber was reinverted, test samples were added to the top wells, and cells were allowed to migrate towards the top well for 4 h at 37°C. Membranes were removed, fixed, and stained, and the number of cells migrating to the top side of the membrane per 10 high-power fields was counted. Test samples containing GST fusion proteins were first preincubated for 2 h at 4°C and then warmed to room temperature before addition to the chamber. With the exception of SM∅, monoclonal antibodies, when used, were added to both the upper and lower wells. Because OKM-5 is unable to recognize bovine CD36 (Ockenhouse et al., 1989), human HMVECs were used instead of bovine BCECs for migrations with anti-CD36 monoclonal antibodies. Control medium alone was used as a negative control to measure background resulting from random cell movement. Samples in each experiment were tested in quadruplicate, and experiments were repeated at least twice. Data presented in figures have been normalized to maximum migration, where 100% was calculated as the migration towards bFGF minus the background migration towards control medium alone. Background was consistently less than 60% of migration towards bFGF. Negative percentages appear when test samples suppressed random cell movement. Where indicated, statistical significance between sample means was determined using a two-tailed t test on initial raw data within a single experiment, before background subtraction and normalization.
The plasmid pCDM8-CD36 was a kind gift of Dr. B. Seed (Massachusetts General Hospital, Boston, MA). The HindIII-NotI fragment of CD36 was ligated to the vector pcDNAneo (Invitrogen, San Diego, CA) predigested with HindIII and NotI to produce a CD36 mammalian expression vector containing an enhancer/promoter sequence of the immediate early gene of the human cytomegalovirus and a SV-40 polyadenylation signal. HUVECs at passage 2 were transfected with this pcDNAneo-CD36 using lipofectin reagent (GIBCO BRL, Gaithersburg, MD). 30 μg of plasmid DNA was preincubated in 100 μl lipofectin for 15 min at room temperature. Cells grown to 30–50% confluency were washed with serum-free media and refed with 4 ml of Opti-MEM medium (GIBCO BRL) plus the plasmid/lipofectin mix. The cells were then incubated for 5 h in 5% CO2 at 37°C, subsequently rinsed twice with growth medium, allowed to recover in normal growth medium for 2 d, and finally split into selection medium with 100 μg/ml G418. Single colonies were picked with cloning rings (Bellco Glass, Inc., Vineland, NJ), expanded, and screened.
CD36-positive clones were characterized and analyzed by flow cytometric analysis. Cells were washed twice with cold PBS, incubated with anti-CD36 monoclonal antibody SM∅ or with an IgM control at 5 μg/ml for 45 min on ice, washed, incubated with FITC-conjugated goat anti–mouse IgM (5 μg/ml) for an additional 45 min on ice, washed again, and finally analyzed on a Becton-Dickinson FACScan® flow cytometer (Mountain View, CA).
Matrigel was purchased from Biomedical Technologies, Inc. 150 μl of Matrigel matrix was added to each well of a 48-well plate and incubated at 37°C for 30 min to allow for gel formation. HUVECs at 80–90% confluency were trypsinized, washed twice with PBS, plated on the Matrigel at 3.5 × 104 cells/well, incubated in 5% CO2 at 37°C for 24 h, and then photographed.
To determine if an interaction between CD36 and TSP-1 could block the antiangiogenic activity of TSP-1, soluble GST–CD36 fusion proteins were tested for their ability to block the inhibition of bovine capillary endothelial cell migration by TSP-1. This assay measures the migration of cultured endothelial cells toward a known angiogenic factor (bFGF) and consistently parallels angiogenic activity seen in vivo (Folkman and Klagsbrun, 1987; Klagsbrun and D'Amore, 1991; Bouck et al., 1996). TSP-1 was previously shown to interact in a specific, saturable, and reversible manner with a minimal region of CD36 encompassing amino acids 93–120 (Pearce et al., 1995). As shown in Fig. 2 A, GST–CD36 fusion proteins FP93-120 and FP93-298, both of which contained the TSP-1 binding domain, were able to block TSP-1 inhibition of bFGF-induced migration in a dose-dependent fashion, whereas GST alone (data not shown) and fusion protein FP298-439, which lacked the TSP-1 binding domain (Fig. 2 A), were ineffective.
Interference with the activity of TSP-1 and its antiangiogenic peptides by soluble GST–CD36 fusion proteins. Increasing concentrations of CD36 fusion proteins that contain a TSP-1 binding site, FP93-120 (circles) or FP93-298 (triangles), or a CD36 fusion protein that lacks a TSP-1 binding site, FP298-439 (squares), were preincubated for 2 h at 4°C with (A) 2 nM TSP-1, (B) 10 μM Mal III peptide, (C) 30 μM Col overlap peptide, or (D) control media. Each mixture was then tested for the ability to block bovine capillary endothelial cell migration towards bFGF (solid symbols) or influence background migration in the absence of bFGF (D, open symbols). Data, accumulated from nine experiments, are reported as a percentage of maximum migration, where 100% represents the number of cells migrating towards the inducer bFGF alone, and 0% corresponds to the number of cells migrating randomly in the absence of inducer (Bkgd). 100% varied between experiments from 32 to 81 cells migrated/10 high-power fields. Bars indicate standard errors.
To more stringently link the TSP-1–CD36 interaction with inhibition of angiogenesis, blocking studies with the GST–CD36 fusion proteins were repeated with small TSP-1 peptides known to inhibit endothelial cell migration and neovascularization in vivo (Tolsma et al., 1993). Concentrations of inhibiting TSP-1 peptides were deliberately chosen to be less than 100% effective so that both positive and negative effects on migration could be observed. CD36 fusion proteins containing TSP-1 binding sites interfered with the antiangiogenic activity of Mal III, a 19-mer containing a homologue of the CSVTCG sequence previously reported to interact with CD36 (Asch et al., 1992; Leung et al., 1992; Li et al., 1993), and of Col overlap, a 7-mer lacking the CSVTCG sequence (Figs. 2, B and C). Loss of inhibition could not be attributed to induction of migration by the fusion proteins themselves as each was neutral when tested alone in this assay (Fig. 2 D). The inhibitory activities of the peptides were quenched only by CD36 fusion proteins that also bound TSP-1 (Figs. 2, B and C).
The Mal III and Col overlap peptides physically interacted with CD36 because both were able to competitively displace 125I –TSP-1 from CD36 expressed in its natural context on the surface of CD36 cDNA-transfected Bowes melanoma cells. TSP-1 peptides Mal III and Col overlap, as well as the Mal III variant that lacks the VTCG motif but still inhibits endothelial cell migration (Tolsma, S., and N. Bouck, personal communication), were all able to inhibit binding of TSP-1 to CD36 (Fig. 3 A). Inhibition constants (IC50's) were 8.60 ± 1.12 μM for Mal III, 30.08 ± 8.88 μM for Col overlap, and 15.78 ± 2.08 μM for Mal III variant. A control peptide did not inhibit binding demonstrating specificity. Melanoma cells not transfected with CD36 do not bind TSP-1 (Silverstein et al., 1992). The calculated IC50 of each peptide closely approximated its previously reported ED50 for inhibition of endothelial cell migration (Tolsma et al., 1993).
Inhibition of TSP-1 binding to CD36 and its fusion proteins by antiangiogenic TSP-1 peptides. (A) Binding of 125I–TSP-1 (20 μg/ ml) to a confluent monolayer of Bowes melanoma cells expressing CD36 was determined in the presence of increasing concentrations of antiangiogenic TSP-1 peptides Mal III (circles, lowest curve), Mal III variant (triangles, second lowest curve), and Col overlap (squares, third lowest curve) or of control peptide LYPQHKT (diamonds, top curve). Data were normalized as a percentage of TSP-1 bound under control conditions. (B) The effects of TSP-1 peptides Mal III and Col overlap on the binding of 125I–TSP-1 (20 μg/ml) to solid phase CD36 and CD36 fusion proteins FP67-157 and FP93-120, which contain a TSP-1 binding site, and to FP298-439, which does not, are shown. Nonspecific binding was determined in the presence of 5 mM EDTA. Bars indicate standard error (n = 3 for A and n = 5 for B).
To demonstrate that TSP-1 peptides interacted only with CD36 fusion proteins containing the TSP-1 binding domain (Pearce et al., 1995), their ability to block 125I–TSP-1 binding to immobilized CD36 and CD36–GST fusion proteins was tested (Fig. 3 B). Mal III at 10 μM reduced the specific binding of TSP-1 to CD36 and to two CD36–GST fusion proteins by 53–65%. Col overlap was similarly effective at inhibiting the binding of TSP-1 to intact CD36 and to the longer fusion protein FP67-157. The CD36 fusion protein FP298-439, which lacks the TSP binding site, showed only background binding equal to that seen in the presence of 5 mM EDTA. The clear dose response relationship seen for peptide binding to CD36 expressed on cells in Fig. 3 A was much less evident in the cell-free binding experiments (Fig. 3 B), likely caused in part by immobilization of CD36 and its fusion proteins on plastic and in part by the use of high peptide concentrations where a significant dose response effect might not be expected. There is an interesting discrepancy in that the Col overlap peptide failed to block TSP-1 binding to the CD36–GST fusion protein containing the minimal TSP-1 binding domain (FP93-120; Fig. 3 B), although this same fusion protein blocked the inhibitory effects of Col overlap on endothelial cell migration (Fig. 2 C). This discrepancy suggests that Col overlap has a much lower affinity for solid phase FP93-120 than soluble FP93-120, perhaps because of constraints imposed on this short fusion protein when bound to plastic.
To demonstrate more directly that TSP-1 inhibits angiogenesis via an interaction with CD36, two anti-CD36 monoclonal antibodies, OKM-5 and FA6-152, known to map to an immunodominant epitope on the extracellular region of CD36 (Daviet et al., 1995) as well as to physically displace TSP-1 from CD36 (Asch et al., 1987; Kieffer et al., 1989), were tested. Both antibodies blocked the inhibition of bFGF-induced migration of HMVECs by TSP-1 (Fig. 4 A) and by TSP-1 peptides (Fig. 4 B). This block was specific to TSP-1 as neither antibody affected the inhibition of endothelial cell migration by angiostatin (Fig. 4 A), another well-established inhibitor of endothelial cell migration in vitro (Gately et al., 1996) and of angiogenesis in vivo (O'Reilly et al., 1994). An isotype-matched control monoclonal antibody was without effect in the assay (Fig. 4 A). The two anti-CD36 antibodies were also able to block TSP-1 inhibition of migration induced by angiogenic molecules other than bFGF. For example, antibody FA6-152 blocked TSP-1 inhibition of endothelial cell migration induced by either scatter factor (Lamszus et al., 1996) or vascular endothelial growth factor (Koch et al., 1994) (data not shown).
Interference with the activity of TSP-1 and its antiangiogenic peptides by monoclonal IgG antibodies against CD36. Monoclonal IgG antibodies against CD36, FA6-152, and OKM-5 or an isotype-matched control were tested at 10 μg/ml for ability to block the inhibition of human microvascular endothelial cell migration towards bFGF by (A) TSP-1 (2 nM) or (B) TSP-1 peptides Mal III (30 μM) or Col overlap (50 μM). Angiostatin (2 μg/ml) served as a control inhibitor. Data from three separate experiments were normalized and reported as in Fig. 1. 100% varied between experiments from 32 to 53 cells migrated/10 high-power fields. *Samples significantly different from parallel condition using control media, P < 0.02.
SM∅, an anti-CD36 monoclonal antibody of the IgM class, mimicked the activity of TSP-1 and inhibited bFGF-induced HMVEC migration, while an isotype-control monoclonal antibody had no significant effect (Fig. 5 A). The high valency of this pentameric IgM presumably allowed for oligomerization of receptors that did not occur when divalent anti-CD36 antibodies of the IgG class were used (Fig. 4). Similar differential antibody effects of IgGs and IgMs are also seen with FAS and TNF receptors (Nagata, 1997). Two other known ligands of CD36, human collagen I and OxLDL, also inhibited bFGF-induced HMVEC migration (Fig. 5 B) and showed maximal inhibitory activity at concentrations similar to those at which they saturably bind CD36 (Tandon et al., 1989; Endemann et al., 1993). These effects were mediated via CD36, for they were blocked by anti-CD36 monoclonal antibodies OKM-5 or FA6-152 (Fig. 5 B). Inhibition was concentration dependent, as both collagen I and OxLDL were ineffective at inhibiting migration at concentrations below 0.1 nM (data not shown). Unoxidized LDL, which is unable to bind CD36 (Endemann et al., 1993), failed to influence HMVEC migration (Fig. 5 B).
Inhibition of endothelial cell migration by additional CD36 ligands. (A) A murine anti-CD36 IgM monoclonal antibody SM∅ and an isotype-matched control monoclonal antibody were tested at 1 μg/ml for ability to inhibit human microvascular endothelial cell migration towards bFGF. Data were normalized and reported as in Fig. 1. *Significant inhibition compared with bFGF tested alone, P < 0.001. (B) Human collagen I, LDL, and OxLDL were tested at 2 μg/ml in the presence or absence of 10 μg/ml of monoclonal antibodies against CD36 for ability to inhibit migration of human microvascular cells. Data from two experiments were normalized and reported as in Fig 1. When tested alone, collagen I, OxLDL, and LDL had no significant effect on migration. 100% varied between experiments from 29 to 42 cells migrated/10 high-power fields. *Samples significantly different from bFGF tested with control media, P < 0.001.
CD36 is typically expressed on human microvascular endothelial cells such as HMVECs, but it is absent from large vessel endothelial cells such as HUVECs (Swerlick et al., 1992; Peltzbauer et al., 1993), thus providing a useful way to assess CD36 function. HUVECs negative for CD36 as determined by FACS® (Fig. 6), by immunoprecipitation followed by Western blot, and by Northern blot (data not shown) were transfected with a CD36 expression vector, and a series of clones expressing increasing levels of CD36 as judged by FACS® and by Western blots were selected (Fig. 6). It was noted that clones expressing any appreciable level of CD36 had slower growth rates than parental HUVECs. For example, the relative increases in cell number after 8 d of culture for each clone were HUVEC, 6.2; clone 35, 5.5; clone 31, 2.1; and clone 36, 1.4. The transfectants also exhibited a progressively aberrant, very highly spread morphology as seen in the middle panels of Fig. 6 (photographed at confluency). When plated in Matrigel, the degree of inhibition of tube formation was correlated with level of CD36 expression (Fig. 6). In total, 30 clones expressing various levels of CD36 were characterized and found to have growth impairment and morphological changes proportional to their CD36 levels. An additional five clones were analyzed for tube formation, and they fit the pattern seen in Fig. 6. All of the CD36-positive clones maintained high levels of TSP-1 expression as determined by Western blotting of serum-free culture media collected over 24 h. Relative amounts of TSP-1 as determined by densitometry were HUVEC, 6.8; clone 35, 8.1; clone 31, 6.3; and clone 36, 6.0.
Sensitivity to TSP-1 inhibition of tube formation induced by CD36 expression in CD36-deficient HUVECs. The first column shows FACS® analysis for CD36 expression performed on untransfected HUVECs, a transfectant expressing very low levels of CD36 (clone 35), and two transfectants expressing higher levels of CD36 (clones 31 and 36). Fluorescence is plotted vs. cell number. The dotted line in the clones reproduces the HUVEC CD36 null pattern. The morphology of each of the transfectants grown in two-dimensional cell culture is shown in the second column. In the third column, tube formation in a three-dimensional culture of Matrigel is pictured for each line.
When tested in a migration assay, clones 31 and 36 were sensitive to TSP-1 inhibition, and this inhibition was abrogated by a CD36-blocking antibody (Fig. 7). Clone 35, which expressed only very low levels of CD36 (FACS® analysis in Fig. 6 and Western blotting with anti-CD36 mAb Mo-91, not shown), was refractory to TSP-1 inhibition (Figs. 6 and 7). Thus, introduction of CD36 into HUVECs rendered them susceptible to inhibition of chemotaxis by TSP-1 and induced, either directly or indirectly, changes in growth rate, morphology, and ability to organize into tubular structures in Matrigel.
Sensitivity to TSP-1 inhibition of migration after transfection of HUVECs with CD36. Clones described in Fig. 5 were tested for sensitivity to inhibition of migration by 2 nM TSP-1 in the presence and absence of 10 μg/ml anti-CD36 monoclonal antibody OKM-5. Data from four separate experiments were normalized and reported as in Fig 1. 100% varied between experiments from 37 to 82 cells migrated/10 high-power fields. *Samples that differ significantly from bFGF tested alone, P < 0.02.
CD36 is necessary for the inhibition of endothelial cell migration and tube formation by TSP-1. Soluble GST–CD36 proteins blocked the inhibition of migration by either intact TSP-1 or small TSP-1 peptides only when they contained the TSP-1 binding site. Blocking antibodies against CD36 prevented TSP-1 from inhibiting migration, while an IgM monoclonal antibody against CD36 mimicked TSP-1 and directly inhibited migration. Large vessel endothelial cells that lacked CD36 became sensitive to TSP-1 inhibition of both migration and tube formation after CD36 transfection. The inhibition mediated by CD36 in vitro likely reflects the in vivo situation because inhibition of migration is a consistent predictor of inhibition of neovascularization in vivo (Folkman and Klagsbrun, 1987; Klagsbrun and D'Amore, 1991; Bouck et al., 1996). Furthermore, experiments to be reported elsewhere show that inhibition of corneal neovascularization by TSP-1 but not by angiostatin is defective in CD36 null animals (Febbraio, M., O.V. Volpert, N.P. Bouck, and R.L. Silverstein, unpublished data).
These results indicate that the antiangiogenic activity of TSP-1 is receptor mediated. They are not consistent with TSP-1 inhibiting angiogenesis by sequestering inducers, as has been suggested by the finding that TSP-1 can bind directly to inducers of angiogenesis, such as scatter factor (Lamszus et al., 1996). In fact, in this study TSP-1 inhibition of scatter factor–induced migration could be completely blocked by an antibody to CD36. Our results are also not consistent with models suggesting that TSP-1 inhibits bFGF-induced angiogenesis by competing with it for binding proteoglycans on endothelial cells, as suggested by experiments with heparin-binding TSP-1 peptides (Vogel et al., 1993), because migration induced by bFGF was effectively blocked in the absence of TSP-1 by agents that directly activated CD36, and inhibition by TSP-1 was antagonized by antibodies that blocked CD36 engagement.
While CD36 has often been implicated in adhesion and scavenging (Greenwalt et al., 1992), data presented here show that CD36 expressed on endothelial cells is also a signaling receptor able to trigger a biological response. The response in this case is one that generates an inhibitory signal that blocks a positive response to inducers of angiogenesis. It is reminiscent of receptor-mediated negative signals to which immune cells are particularly sensitive (Scharenberg and Kinet, 1996). Such signals often require a coreceptor and are mediated by src family kinases. It is not known if CD36 acts alone or in concert with an unidentified coreceptor or other surface molecule, but it does coprecipitate from endothelial cells in association with the src family kinase p59fyn, and possibly other src family kinases (Bull et al., 1994). It is also not yet clear how a signal emanating from CD36 might block the variety of stimulatory signaling cascades initiated by many different inducers of angiogenesis. However, the cytoplasmic domain of CD36 has been seen to associate with focal adhesion kinase (Sheibani, N., R. Zhong, and W.A. Frazier, manuscript in preparation), a kinase that can be essential for the stimulation of cell movement (Cary et al., 1996; Gilmore and Romer, 1996). If activation of CD36 were to disable focal adhesion kinase and thereby prevent the adhesion-associated tyrosine phosphorylation that may be essential for endothelial cell motility (Williams et al., 1996), the effectiveness of a wide variety of inducers of angiogenesis would be severely compromised.
Although the CSVTCG motif on TSP-1 has previously been thought to mediate its interactions with CD36 (Asch et al., 1992; Catimel et al., 1992; Li et al., 1993), data presented here show that an additional TSP-1 motif can interact with CD36. The Col overlap peptide lacking CSVTCG was antiangiogenic, was able to displace TSP-1 from CD36-transfected melanoma cells, and was rendered inactive by CD36 fusion proteins. A Mal III variant also lacking CSVTCG was antiangiogenic and able to displace TSP-1 from CD36-expressing cells. These peptides share a central GVQXR sequence that could represent a second CD36 binding motif. Two-step binding of TSP-1 to CD36 has been postulated by others (Leung et al., 1992). Perhaps CSVTCG facilitates an initial interaction between TSP-1 and CD36 and GVQXR mediates a signaling response. Such a role would fit well with our observation that the Mal III peptide, which contains both motifs, had a higher affinity for CD36 and is a more potent inhibitor of migration (Tolsma et al., 1993) than Col overlap, which lacks CSVTCG.
The identification of CD36 as a mediator of the inhibitory effects of TSP-1 helps to explain the unusual biphasic dose response curve generated when TSP-1 effects on endothelial cell migration are measured. TSP-1 inhibits endothelial cell migration at low concentrations less than 20 nM, yet stimulates migration at higher concentrations (Taraboletti et al., 1990; Tolsma et al., 1993; Gao et al., 1996), a fact that has led to much confusion about its ultimate activity. Recent work has shown that a blocking antibody against the integrin-associated protein (IAP) prevents higher concentrations of TSP-1 from inducing endothelial cell migration (Gao et al., 1996). Thus, the biphasic dose response curve for TSP-1 can be explained as resulting from the sum of activities of two distinct receptors, inhibitory CD36 and stimulatory IAP. CD36 mediates the inhibitory effects of TSP-1 at lower concentrations. The ability of CD36 to mediate phagocytosis (Ryeom et al., 1996a,b) and the rapid degradation of lipids (Nozaki et al., 1995) suggest that it may be rapidly cleared from the cell surface upon engagement with TSP-1. Thus, at high concentrations of TSP-1, CD36 may be sufficiently depleted to allow IAP to act unopposed, resulting in the stimulation of endothelial cell migration.
The binding activity of CD36 expressed on platelets has been shown to be regulated by the extracellular phosphorylation state of its ectodomain, with increasing phosphorylation decreasing its binding to TSP-1 and increasing its affinity for collagen and vice versa (Asch et al., 1993). The in vitro sensitivity of CD36 to both ligands suggests that cultured endothelial cells have both phosphorylated and unphosphorylated CD36 molecules on their surface. In vivo it is possible that changes in CD36 phosphorylation by extracellular phosphatases and kinases could regulate the effect of both TSP-1 and other CD36 ligands on endothelial cells. This may be of particular importance at sites of platelet secretion and inflammation.
A variety of antiangiogenic compounds are now entering clinical trials as anticancer agents (Folkman, 1995a; Gradishar, 1997). The identification of CD36 as an inhibitory signaling receptor for TSP-1 could be useful in the design and discovery of additional pharmacologic agents that can inhibit pathologic neovascularization.
This work was supported in part by grants from the National Institutes of Health/National Cancer Institute (NIH/NCI) CA52750 and CA64239 (to N.P. Bouck) and CA65872 (to W.A. Frazier); NIH/NCI Institutional Training Grant 5T32CA09569 and Chicago Baseball Charities (to D.W. Dawson); NIH HL46403 and EY10967 and the Charles Fogarty Trust (to R.L. Silverstein); and a grant-in-aid from the American Heart Association, New York City Affiliate, and the Dorothy Rodbell Cohen Foundation (to S.F.A. Pearce).
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text:
Sidolo es una fracción de 6,92 kilómetros que forma parte del municipio de Bardi en la provincia de Parma, región de Emilia-Romaña en Italia. Se eleva a 706 metros sobre el nivel del mar.
Está cercano al río Toncina, uno de los principales afluentes del río Ceno. Se accede por la carretera de Compiano hacia Bardi. Sidolo está rodeado por montes y a una distancia de 9 nueve kilómetros de Bardi.
La mayoría de sus viviendas fueron construidas con mampostería y hasta el año 2005 contaba con 34 edificaciones.

Historia

Las primeras noticias datan del año 890, cuando se  menciona a la Iglesia San Ambrosio de Sidolo en un decreto del rey y emperador Carlos III el Gordo.
En 1180, el extinto Castillo de Sidolo perteneciente a la Familia Platoni, es cedido a la comuna de Piacenza por el conde de Bardi Armanno Platoni.

En 1943, el ejército de la Alemania nazi asesina a 8 civiles y religiosos. Son fusilados el arcipreste Giuseppe Beotti, de 32 años;  Francesco Del Nevo, párroco de Porcigatone de la comuna de Borgo Val di Taro; Italo Subacchi, seminarista de 23 años; Bruno Benci, de 42 años; Francesco Bozzia, de 44 años; Giovanni Brugnoli, de 40 años; Girolamo Brugnoli, de 48 años y Giuseppe Ruggeri, de 42 años.

Personalidades
Solestella Platoni, Condesa de Bardi.

Luigi Marchini nace en Sidolo 22/12/1921 al 19/09/1980
Estudió medicina y cirugía, formó parte de la lucha clandestina contra el régimen nazi, fue concejal de Bardi, muere en 1980 y es enterrado en el cementerio de Sidolo.

Referencias

Bibliografía

Enlaces externos
 Territorio de Sidolo Comuna de Bardi

Casa de Platoni
Localidades de la provincia de Parma

redpajama_set_name: RedPajamaWikipedia


text:
Milan, KFC chimneys and Chinatown residents protest: "Because of the smell we can't open the windows" Netflix unveils first measures to prevent password sharing | television space, 20 years after the disaster of the space shuttle "Columbia" UISP National Tournament – 11 Player Soccer, 3 Days Back January 26-30, 2023 • [Castel Bolognese news] 6.5″ FHD display and lightning-fast speed: POCO M3 Pro 5G at an amazing price
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The Academy of Motion Picture Arts and Sciences, the association that awards the Academy Awards, has decided that Controversial promotional...
reading time: 3 Session minutesSo many emotions at the opening of the exhibition "Synchronicity in art and science. A unified...


Is it strange to love a bathroom this much? I've wondered. This loo was the very first room in the house to be designed with fixtures and tile (you can see the design here, from nearly nine months ago!) and I had a clear vision of what I wanted it to feel like: a restful retreat, spa-like; mid-century modern in a timeless way. When we renovated our master bathroom in LA, our biggest splurge was on the Fireclay hex tile, and I never regretted it. Once you get the tile samples in the mail, there's kind of no going back. They're like pieces of art, paint on clay, and they're totally addicting. Here's the thing that I will likely say like a broken record with every room reveal: Since we went the route of building new, and not renovating, I think that it is extra important that we find ways to add warmth and character and one of the easiest ways to do that is in selecting handmade finishes like handmade tile. There is so much tile in this space! We went with 2 x 8 tile throughout the bathroom and all stack bond for a more modern look. The green shade is flagstone and the white is sugar. The grout color is snow white. (PS. The day I get tired of stack bond tile we will be in big trouble because it's all over the house!) The paint color that we used in here is the same paint color that we used throughout most of the downstairs and it's Behr Gallery White in the matte finish for the walls and satin finish for the doors and trim. We tried out so many different whites and love the one we landed on. This is from the Behr Marquee line and we actually got feedback from one of the painters who came back after the job was done about how much he liked painting with it and how well it covered.
With the color palette picked out, it was time to choose fixtures. I really feel like the Purist Collection from Kohler perfectly epitomizes this idea of mid-century modern in a timeless way. The pieces are simple and architectural feeling, not at all busy and they're really heavy and well-made. We went with two wall mounted faucets for the sink and a floor mount for the tub filler. The shower faucet is Purist, too, and the finish throughout is brushed nickel. Honestly, if it had been up to me a year ago, I would have chosen the brushed gold. Aaron wasn't into it, though, so we both agreed on brushed nickel. I had dreams about that brushed gold. Was it a missed opportunity?! Could I ever love another finish as much as I would that brushed gold? Fast forward a year later and I WOULD NOT CHANGE A THING. I love the way the brushed nickel complements the cool color palette and it feels like it will be more enduring than the brushed gold. Brushed gold was a teenage romance. Brushed nickel is the marrying type.
The floating vanity is the Kohler Jute vanity in the 72″ size. It's perfect. This is absolutely the next best thing to custom. I can say with absolute certainty that there is nothing else ready-made that I like even a fraction as much as I love this vanity.
Once the color palette was set, tile ordered, and fixtures chosen, one of the last big decisions to make was lighting and mirrors. If ever there was a shop that encompassed all of my favorite things in mirrors and lighting in one place, it's Rejuvenation. I feel like they also do timeless modern really, really well. (Our lighting and mirrors in our master bathroom in LA were from them as well.) I liked these sconces a lot when I chose them. I love them now that they're installed and we're moved in. There are can lights in the ceiling that we almost never use because the lighting that the sconces give off is so nice. It's the perfect glow, especially at night. You might have also noticed that we mixed metals here, opting for matte black mirrors and light fixtures. Again, I'm so happy with the way it turned out. Is this a major faux pas? Probably. But I wouldn't change a thing. To me it makes the room feel less matchy-matchy, and more unique and definitely more modern than if we had done brushed nickel lighting and mirrors. This space makes me so crazy happy and that's the whole point, right?
Your bathroom looks heavenly and the perfect place to unwind. I love how y'all did the shower/bathroom/tile area. Gorgeous. Congrats, on the new home and being closer to family.
And thank you for the towel rec, I'm in need of new ones and I'm looking for quality. Thanks so much!
Thanks so much, Katie! Yes, I really like the towels, but Aaron says he wishes they were thicker, so there's that! They are really soft and absorbent though!
Your bathroom is gorgeous! I love the tile and that tub looks wonderful!
I'm so excited the reveal has begun! your choices are perfect, including the mixed metals – it's a very gorgeous bathroom – enjoy!
Thank you so much, Sue! That makes two of us, re: the excitement!!
Love the mixed metals and the colors your choose, particularly how you can see the green tiles in the mirrors on the wall of white. It's beautiful!
Stunning space! Grabing tons of ideas and implementing in my upcoming master bath project. Do you recall which pulls you used For the kohler cabinet? Thanks!


text:
Q: gcloud datastore emulator: [Errno 8] nodename nor servname provided, or not known I just installed the Google cloud datastore emulator locally for testing my applications. I'm getting a weird error when starting it up. Google search didn't return any results.
I installed it with the following command:
gcloud components install cloud-datastore-emulator

Installation seemed successful.
Here's the output of starting it with debug verbosity:
❯ gcloud beta emulators datastore start --verbosity debug
DEBUG: Running [gcloud.beta.emulators.datastore.start] with arguments: [--verbosity: "debug"]
DEBUG: (gcloud.beta.emulators.datastore.start) [Errno 8] nodename nor servname provided, or not known
This may be due to network connectivity issues. Please check your network settings, and the status of the service you are trying to reach.
Traceback (most recent call last):
  File "/usr/local/google-cloud-sdk/lib/googlecloudsdk/calliope/cli.py", line 787, in Execute
    resources = calliope_command.Run(cli=self, args=args)
  File "/usr/local/google-cloud-sdk/lib/googlecloudsdk/calliope/backend.py", line 759, in Run
    resources = command_instance.Run(args)
  File "/usr/local/google-cloud-sdk/lib/surface/emulators/datastore/start.py", line 69, in Run
    datastore_util.GetHostPort(), ipv6_enabled=socket.has_ipv6)
  File "/usr/local/google-cloud-sdk/lib/googlecloudsdk/command_lib/emulators/datastore_util.py", line 162, in GetHostPort
    return util.GetHostPort(DATASTORE)
  File "/usr/local/google-cloud-sdk/lib/googlecloudsdk/command_lib/emulators/util.py", line 222, in GetHostPort
    if sock.connect_ex((host, port)) != 0:
  File "/usr/local/Cellar/python/2.7.11/Frameworks/Python.framework/Versions/2.7/lib/python2.7/socket.py", line 228, in meth
    return getattr(self._sock,name)(*args)
gaierror: [Errno 8] nodename nor servname provided, or not known
ERROR: (gcloud.beta.emulators.datastore.start) [Errno 8] nodename nor servname provided, or not known
This may be due to network connectivity issues. Please check your network settings, and the status of the service you are trying to reach.

Any ideas of what is going on are welcome.

A: I just made a quick test and installed Cloud Datastore with $ gcloud components install cloud-datastore-emulator and run $ gcloud beta emulators datastore start --verbosity debug without a problem.
What's the output if you run $ gcloud beta emulators datastore start with no flags?
Looks to be a connectivity issue. Have you tried forcing the host and port? Try running $ gcloud beta emulators datastore start --verbosity debug --host-port 127.0.0.1:8080

redpajama_set_name: RedPajamaStackExchange


The SDI contribution has nearly doubled since 2007 and is forecast to remain 1.1% in 2011. Self-insuring SDI can represent savings for employees as well as the employer. This podcast provides an overview of SDI, the advantages of self-insuring, the requirements involved to do so, and why now is an excellent time to self-insure.
For more information on this and other insurance topics, please contact your Woodruff-Sawyer account representative, or call Jim McCabe at 415.402.6502.


She was a 220 ft long steel freighter that sunk in 1941 in collision with the shoal between American and Canadian Channels. The navigator did not see the shoal in a deep fog and Daryaw run into the shoal bow first with significant speed. She sunk soon thereafter. During sinking, she flipped upside down and landed right next to the wall with the deepest part at 90ft.
The current on this wreck ranges from strong to ripping, but the wall provides a little bit of protection once you get down to the wreck. The descent line is tied near the props and then another line leads to the block on the bottom. There is also a line running alongside the wreck that could be used for pulling when the current is just too strong.
Highlights include twin props on the stern that are now rising to the sky and spacious cargo holds. If you make it all the way to the bow, you can then drift (or rocket, depending on how strong the current is) back to the stern and the props.
Dangers include very tight and very silty engine room (second hand info as I never been in the engine room) and ripping current as evidenced by the first picture below.


text:
Racial Binds: Trapping Asians in Australia's Education Wars
By: Gilbert Caluya, Filed under: AADC,Politics | Published: July 22, 2015
Library Photography Competition 2011 entry, Rich Grundy, Creative Commons attribution
Few things so potently demonstrate oppression than a well-constructed double bind. And though not all double binds are oppressive; all oppressions employ double binds. They keep us scrambling to prove ourselves, keep us hoping that if only we did this one thing we would be left alone, become normal, or even accepted.
I recall the difficulties of searching for work as an Asian Australian teenager just after the Pauline Hanson era in the 1990s. Back then Aussie newspapers and TV programs regularly complained about unemployed Asians as 'dole bludgers', immigrants living off the taxes of hardworking (read: white) Australians. If you were a young Asian male you were often presumed to be part of a triad gang. Finding work took on a fevered tone. I was desperate to not be perceived as living off other Australians' work, I wanted to be 'self-reliant', 'independent'.
But when I got my first job I soon found myself the epitome of a new stereotype. TV programs like Today Tonight swapped panning shots of Asians lined up outside of Centrelink with shots of Asian faces in factories as the voiceover warned of a new wave of Asian 'job stealers' who were undercutting 'ordinary Australians' with our 'cheap labour'. Apparently I had 'stolen' my job from some other (presumably white) worker, who now was forced to live off the pitiful dole.
So if I was unemployed then I was living off the sweat of white Australian workers, but if I got work then I had stolen a job that consigned some working-class white person to a life of poverty (even as the racial discrepancy in wages was naturalized as a result of my being Asian).
Yet even then, at 19 years old, I still didn't see the double bind. I still believed that fundamentally it was my fault and that if I did the right thing Australians would finally accept me. I worked hard at my studies, determined to move into a career that didn't force me to compete with my 'average' Australians. After almost a decade of studying and working, I finally became a university lecturer, no longer stealing jobs from the working-class or living off their hard work; I thought I had finally made it.
That's when the shock jocks started complaining about 'Asian elites' whose wealth or status suddenly placed them in positions above 'average Australians'. Their wealth or job did not reflect their hard work but was taken as evidence of how multiculturalism was racially unjust (despite the lack of affirmative action in Australian education or employment). Asian employers or managers were proof that Australia was not only not racist anymore but that we were actively 'taking over' by 'hoarding top jobs' (despite evidence a 'bamboo ceiling' exists).
It was only then, after almost a decade of trying to fit in, that I suddenly realised that there was no use attempting to please racists.
So you can understand why, when I heard about Asians threatening not 'our' jobs this time but 'our' education, I couldn't help but take it with a grain of salt.
On one side, you have complaints about the racial segregation of schools where Asians are getting better grades and dominating entrance exams into selective private and public schooling. There is even talk of 'white flight' from schools. Here Asian 'tiger mums' stand accused of unfairly cheating the system by using extra-curricular tutoring and coaching to artificially enhance their kids' performance in schools. These harsh 'tiger mums' are portrayed as cold, calculating, scheming slave drivers heartlessly destroying their own kids' childhoods in some twisted sense of achievement that barely masks their own selfish desires and hubris.
Consequently, Asian students' academic achievements are recast as artificial. Here, tutoring and coaching are analogous to performance enhancement drugs while studying becomes an illegitimate, nefarious Asian activity designed to undermine the natural order of pedagogical things. Asians are blamed for artificially increasing the standards of entry into good schools, universities and programs, and thus excluding 'naturally talented' students who do not need tutoring or coaching. As a result, we are told Asians are now undermining our long-held tradition of a meritocratic education system.
If Asians in primary and high schools are accused of artificially raising the standards of our education system, simultaneously Asians are also accused of artificially lowering the standards of our higher education. In the Four Corners special report 'Degrees of Deception', international students from Asia who 'pay their way' through full-fee university enrolments are accused of subverting the meritocracy of our higher education admissions systems. Accused of uniformly lying and forging documents in order to access these programs, they are portrayed as compensating for their lack of talent through the use ghost writers from Chinese-run essay writing companies. These 'undeserving' international students (reduced to Asians in media representations when in fact we have students from all over the world), lying and cheating their way through university (as if Asian students have singularly invented plagiarism), are thus held to be incapable of actually completing a degree fairly.
This is coupled by university lecturers who portray them on national television as 'problem students' who unfairly place pressure on them. Here Asian students are portrayed as 'protected customers' of a university administration addicted to Asian money or as 'administrative headaches' in a time-poor university. Students begging and pleading with lecturers not to fail them, a normal response by many students, are recast as rich bullies, unfairly pressuring vulnerable academics to undermine their academic standards in the face of an insecure employment future.
To be clear, as a lecturer I certainly sympathise with these pressures and am concerned about changing pedagogical landscapes and drops in academic standards. But it requires a certain mindset to blame Asian international students for these problems as opposed to the shape of higher education funding and the influence of its stakeholders, the poor use of specific models of teacher assessment, the lack of infrastructural support for teachers and international students alike, and the overreliance on neoliberal management techniques in universities.
The fact that Asian student performances in primary and secondary schools are helping us raise the standards of our education system overall to be more competitive in a global economy, not to mention the benefits we gain from transnational networks, is completely ignored in this discussion. Further, the fact that international university students are currently the only thing that keeps our higher education system afloat, which allows us to maintain the remaining academic quality we still have left is also not examined.
Frankly, I'm disappointed in my colleagues who should know better than to individualise structural problems onto minority students. Then again, there's no use trying to please racism.
The Asian Australian Democracy Caucus (AADC) is a non-partisan organisation. One of our ongoing commitments is to contribute a monthly blog in collaboration with Peril magazine. To find out more about this collaboration read here. If you want more information or would like to write for us, get in touch with us, Jen Tsen Kwok or Shinen Wong at aadc@peril.com.au
Author: Gilbert Caluya
Dr Gilbert Caluya is a Research Fellow at the University of South Australia. His research focuses on the intersections of race, gender and sexuality, specialising in the relationship between race and intimacy. He has published widely in international academic journals. You can follow his work here --> https://unisa-au.academia.edu/GilbertCaluya	View all posts by Gilbert Caluya
A Natural Education The significance of the first anti-Chinese legislation in Australia Thirty one Victorian Multicultural, Faith and Community organisations oppose amendments to the Racial Discrimination Act


text:
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8 Texas CLE hours with .25 ethics
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Disclaimer; The writer, Keshie Muchai, is a Billie Eilish stan. She is obsessed with Billie Eilish and relates to her music on another level. All opinions are hers and hers only. Some opinions may be biased because she loves Billie Eilish more than anything in the world. Enjoy!
The long-awaited debut album "WHEN WE ALL FALL ASLEEP, WHERE DO WE GO?" by Billie Eilish was released on Friday March 29th, 2019. "MY BABY, MY CHILD. this album is the world to me please take care of it ", she went ahead to post on her Instagram when making the big announcement.
With 14 songs, 2 being the intro and outro, we can all agree that this is the perfect length for an album. It's 42 minutes long. Not too long that you get tired of it and not too short to make you ask for more – like this article, just fun and fresh. This is the type of album that gives you closure. Being a Billie Eilish stan, you would expect me to say that I wanted more songs. But no, I felt satisfied. My heart felt full. It was and continues to be a whole experience listening to this work of art.
Produced by Billie's brother Finneas O'Connell who she's been working with since forever, the album starts with '!!!!!!!', yes, 7 exclamation marks which you better get right. In this 13 second intro, she says "…I have taken out my Invisalign and this is the album…" followed by her and Finneas sharing a hearty laugh. A laugh I would probably have if anyone said they don't love this album already.
The main thing that they were trying to achieve with this album is make every song different in its own unique way, which they did. If you put 14 people who like different genres in a room and play this album, everyone will have a favorite song. So, to you who has never listened to Billie Eilish (do you live under a rock or something?), you'll definitely have a favorite song if not two or five.
Every song on the album is something that happens when you are asleep, from night mares to sleep paralysis to lucid dreams. All things that don't have an explanation. Like can you explain where we all go when we fall asleep? No one knows. Also, those things more often times than not we think about but cannot say out loud are said in this album. "I'm that bad type, make your mama sad type, make your girlfriend mad type, might seduce your dad type, I'm the bad guy…", Billie sings on 'bad guy'. She is the type of artist who says all the things you wouldn't think of saying out loud and I love that she was cocky and gave off that provoking vibe in that song with some beats you can dance to.
The last song 'goodbye' is basically her taking lyrics from all the songs (from the last to the first), a perfect ending to an emotional rollercoaster. The track list is well thought out. The first half of the album will make you feel like you can run the world while the other half will make you cry in public because you'll be in your feelings. The titles of the last 3 songs are 'listen before i go', 'i love you' and 'goodbye' which is a sentence making us aware that the album is coming to an end.Whispering vocals is one of the things which makes Billie's songs very unique. In "xanny" she does exactly that over some blown-out bass that would probably break your windows if you played that song out loud. 10/10 would still recommend.
Play this album to your emo kids because Billie Eilish is a role model who will teach you how to deal with your emotions. She wrote '8' from the perspective of someone else. Someone she hurt. The only way she could deal with it was to stop and put herself in that person's place. Sometimes the only way to deal with the pain or something we are going through is look at it from another person's perspective.
Now, if you watch "The Office", a popular American sitcom, you will love 'my strange addiction' because it samples vocal snippets from Season 7 Episode 17 of the show. However, the song was most likely named after My Strange Addiction, a show about people with unusual compulsive behaviors.
Depression and sadness have been a theme for most of her songs and she definitely had to bring that back in 'listen before i go'. " I'm not okay I feel so scattered, don't say I'm all that matters, leave me déjà vu…sorry there's no way out, but down". This song is what happens when you are sad and you just want to leave this cold world. You will cry when listening to this. Sorry not sorry. This is the type of song I would want played at my funeral.
'i love you' is a first for Billie. She confesses that she feels in love. This song is what happens when you fall in love and you don't believe it. When someone says they love you and you wish they were trying to make you laugh because you actually love them but you don't want to because you are not used to these reciprocated feelings.


Creamy avocados are a terrific match with juicy grilled steak. You can marinate the meat ahead (and it's all the better if you do), but don't assemble the salad until just before serving to keep the avocado from turning brown.
1. Reserve a cup of whole cilantro leaves; finely chop the rest. Transfer chopped leaves to a medium bowl.
2. Reserve a cup of whole parsley leaves; finely chop the rest. Transfer chopped parsley to the bowl with the cilantro. Add scallions, jalapeno, garlic, salt, and lemon juice. Stir in oil. Taste and add more salt and/or lemon juice if needed.
3. Scatter the cilantro and parsley leaves over 4 serving plates. Fan the avocados out on top and sprinkle lightly with fine salt to taste.
4. Spoon the herb sauce over the avocado, making sure to include the oil in the bowl. Top with sliced steak and sprinkle with capers. Sprinkle with flaky sea salt and black pepper to taste and serve immediately.


Could someone please explain the function of the bold と that doesn't seem to have a いう or equivalent after it and the bold が that doesn't seem to be functioning as a subject marker or a sentence connecting particle. Part of me suspects that the が is marking the subject of 与える and I would be satisfied with that explanation. I'm very uncertain about the と though.
The subjects are our データ入力ミス and イージーミス. This looks confusing only because they both happen to have fairly substantial qualifying subordinate clauses in front of them.
Not the answer you're looking for? Browse other questions tagged grammar particle-と particle-が or ask your own question.
Particle-が in restaurant's name. Genitive particle?
と particle in this sentence?


Discussion in 'Boxing Discussion' started by Wanderlei4Life, Jun 7, 2014.
Arum said if Canelo gets passed Lara. Him and Oscar want to do a Canelo vs Cotto fight.
Good boxing continue to come to the fans.
Canelo Cotto now?? Sick fight.
Canelo vs Cotto would be a killer fight and would no doubt sell over one million PPVs. While I think Canelo would have the edge, if Cotto somehow pulled off the win, the man would no doubt be greater than Trinidad when it comes to Puerto Rican greats. Cotto would be a fool not to retire with a Canelo win and seal his place in boxing history.
This would be an incredible match up.
Arum can say what he likes - he's not Cotto's promoter. Cotto wouldn't even need him to make this fight, so I'm not sure how it ends the "cold war" - especially as Haymon & Schaefer still won't be working with Arum.
Until Cotto himself announces he wants such a fight, I doubt it happens.
Cotto has an excellent relationship with Todd Debuof which is why Tr pushes Cotto promotions like GB did for Mayweather promotions.
Canelo is exclusively to oscar and GB.
If the fight gets made, first tr and GB event in a long time.
Cotto still doesn't need TR to make this fight, as he's a promotional free agent. The reason Arum wants to be involved is he'd get a cheque; doesn't mean he has any promotional rights to either fighter.
Cotto is a smart businessman. He'll likely wait for a few months and see what offer is best for him - fighting Canelo (Golden Boy) or fighting Floyd (Floyd/Haymon/Schaefer). What fights Bob Arum wants to make won't be a factor.
Canelo vs Cotto would be a more even fight and the Mexican vs Puerto Ricans fans would push the ppv past 1 mil buys.
I love Cotto but he would lose to Floyd again and would get less money and share fighting Floyd where he is the a side against Canelo.
That's a big IF, since I have a feeling Lara gets the better of Canelo.
I'm actually more interested in seeing a fight between GGG and Cotto.
None of that means that the fight is even close to bring made. Nor are you privvy to what Cotto would be offered from either party.
Grrrr Bob Arum is the devil!!!
Nobody even remotely criticised him. I'm sorry that pointing out that he's not Cotto's promoter is somehow seen as being negative in your eyes.
Arum wants to make this fight! Yay! Praise Arum!
Yea I think that's the fight to make IF Canelo gets by my boy which I strongly doubt that will happen.
That's why I said the Canelo vs. Lara is now officially the most important fight of the year.
Cabelo is already technically a mw since now his last two fights have been at 155.
Him and Cotto for the mw crown would sell too well and make too much sense. Rooting for Canelo in his bout against Lara.
Todd duboef and Cotto are discussing a December return.
Is it possible to sell too well?
Regardless of whether his last few fights have been arranged for 155lbs, Canelo is a middleweight; he was far from a small light middleweight.