text:
Title: Osteopontin
Subject: CD44, Angiogenesis inhibitor, OPN, Osteoblast, Osteocalcin
Secreted phosphoprotein 1
Rendering based on PDB .
Available structures
Ortholog search: PDBe, RCSB
List of PDB id codes
; BNSP; BSPI; ETA-1; OPN
ChEMBL: GeneCards:
Sources: Amigo / QuickGO
Location (UCSC)
PubMed search
PROSITE
PDOC00689
Available protein structures:
RCSB PDB; PDBe; PDBj
PDBsum
Not to be confused with Osteocalcin, Osteonectin or Osteoprotegerin (OPG).
Osteopontin (OPN), also known as bone sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric),[1] is a protein that in humans is encoded by the SPP1 gene (secreted phosphoprotein 1). The murine ortholog is Spp1. Osteopontin is a SIBLING (glycoprotein) that was first identified in 1986 in osteoblasts.
The prefix osteo- indicates that the protein is expressed in bone. Synonyms for this protein include sialoprotein I and 44K BPP (bone phosphoprotein).
The gene has 7 exons, spans 5 kilobases in length and in humans it is located on the long arm of chromosome 4 region 22 (4q1322.1). The protein is composed of ~300 amino acids residues and has ~30 carbohydrate residues attached including 10 sialic acid residues, which are attached to the protein during post-translational modification in the Golgi apparatus. The protein is rich in acidic residues: 30-36% are either aspartic or glutamic acid.
Structure 1
General structure 1.1
Isoforms 1.2
Biosynthesis 2
Regulation 2.1
Biological function 3
Role in biomineralization 3.1
Role in bone remodeling 3.2
Role in immune functions 3.3
Role in Heart 3.3.1
Chemotaxis 3.3.2
Cell activation 3.3.3
Apoptosis 3.3.4
Potential clinical application 4
Role in autoimmune diseases 4.1
Role in cancers and inflammatory diseases 4.2
Role in colitis 4.3
Role in allergy and asthma 4.4
Role in muscle disease and injury 4.5
Additional images 6
Further reading 7
OPN is a highly negatively charged, extracellular matrix protein that lacks an extensive secondary structure.[2] It is composed of about 300 amino acids (297 in mouse; 314 in human) and is expressed as a 33-kDa nascent protein; there are also functionally important cleavage sites. OPN can go through posttranslational modifications, which increase its apparent molecular weight to about 44 kDa.[3] The OPN gene is composed of 7 exons, 6 of which containing coding sequence.[4][5] The first two exons contain the 5' untranslated region (5' UTR).[6] Exons 2, 3, 4, 5, 6, and 7 code for 17, 13, 27, 14, 108 and 134 amino acids, respectively.[6] All intron-exon boundaries are of the phase 0 type, thus alternative exon splicing maintains the reading frame of the OPN gene.
Figure 1. Proteolytic cleavage sites for full length osteopontin (OPN-FL). Thrombin exposes the cleaved epitope SVVYGLR (OPN-R), and then CPB removes the c-terminal arginine from OPN-R. The cleaved epitope has a non-RGD domain, which binds to integrin receptors (α4β1, α9β1, and α9β4). Next to the cleaved epitope, there is a RGD domain that interacts with other integrin receptors (αvβ1,3,5, and α5β1).
Isoforms
Full-length OPN (OPN-FL) can be modified by thrombin cleavage, which exposes a cryptic sequence, SVVYGLR on the cleaved form of the protein known as OPN-R (Fig. 1). This thrombin-cleaved OPN (OPN-R) exposes an epitope for integrin receptors of α4β1, α9β1, and α9β4.[7][8] These integrin receptors are present on a number of immune cells such as mast cells,[9] neutrophils,[10] and T cells. It is also expressed by monocytes and macrophages.[11] Upon binding these receptors, cells use several signal transduction pathways to elicit immune responses in these cells (See Section 3 for more detail). OPN-R can be further cleaved by Carboxypeptidase B (CPB) by removal of C-terminal arginine and become OPN-L (Fig. 2). The function of OPN-L is largely unknown.
It appears an intracellular variant of OPN (iOPN) is involved in a number of cellular processes including migration, fusion and motility.[12][13][14][15] Intracellular OPN is generated using an alternative translation start site on the same mRNA species used to generate the extracellular isoform.[16] This alternative translation start site is downstream of the N-terminal endoplasmic reticulum-targeting signal sequence, thus allowing cytoplasmic translation of OPN.
Various human cancers, including breast cancer, have been observed to express splice variants of OPN.[17][18] The cancer-specific splice variants are osteopontin-a, osteopontin-b, and osteopontin-c. Exon 5 is lacking from osteopontin-b, whereas osteopontin-c lacks exon 4.[17] Osteopontin-c has been suggested to facilitate the anchorage-independent phenotype of some human breast cancer cells due to its inability to associate with the extracellular matrix.[17]
Biosynthesis
Osteopontin seen in a lung tissue sample from a patient with ideopathic pulmonary fibrosis.
Osteopontin is biosynthesized by a variety of tissue types including fibroblasts[19] preosteoblasts, osteoblasts, osteocytes, odontoblasts, some bone marrow cells, hypertrophic chondrocytes, dendritic cells, macrophages,[20] smooth muscle,[21] skeletal muscle myoblasts,[22] endothelial cells, and extraosseous (non-bone) cells in the inner ear, brain, kidney, deciduum, and placenta. Synthesis of osteopontin is stimulated by calcitriol (1,25-dihydroxy-vitamin D3).
Regulation of the osteopontin gene is incompletely understood. Different cell types may differ in their regulatory mechanisms of the OPN gene. OPN expression in bone predominantly occurs by osteoblasts and osteocyctes (bone-forming cells) as well as osteoclasts (bone-resorbing cells).[23] Runx2 (aka Cbfa1) and osterix (Osx) transcription factors are required for the expression of OPN [24] Runx2 and Osx bind promoters of osteoblast-specific genes such as Col1α1, Bsp, and Opn and upregulate transcription.[25]
Hypocalcemia and hypophosphatemia (instances that stimulate kidney proximal tubule cells to produce calcitriol (1α,25-dihydroxyvitamin D3)) lead to increases in OPN transcription, translation and secretion.[26] This is due to the presence of a high-specificity vitamin D response element (VDRE) in the OPN gene promoter.[27][28][29]
Extracellular inorganic phosphate (ePi) has also been identified as a modulator of OPN expression.[30]
Stimulation of OPN expression also occurs upon exposure of cells to pro-inflammatory cytokines,[31] classical mediators of acute inflammation (e.g. tumour necrosis factor α [TNFα], infterleukin-1β [IL-1β]), angiotensin II, transforming growth factor β (TGFβ) and parathyroid hormone (PTH),[32][33] although a detailed mechanistic understanding of these regulatory pathways are not yet known. Hyperglycemia and hypoxia are also known to increase OPN expression.[32][34][35]
Biological function
Role in biomineralization
OPN belongs to a family of secreted acidic proteins whose members have an abundance of negatively charged amino acids such as Asp and Glu.[36] OPN also has a large number of consensus sequence sites for post-translational phosphorylation of Ser residues to form phosphoserine, providing additional negative charge.[37] Contiguous stretches of high negative charge in OPN have been identified and named the polyAsp motif (poly-aspartic acid) and the ASARM motif (acidic serine- and asparate-rich motif), with the latter sequence having multiple phosphorylation sites.[38][39][40][41] This overall negative charge of OPN, along with its specific acidic motifs and the fact that OPN is an intrinsically disordered protein[42][43] allowing for open and flexible structures, permit OPN to bind strongly to calcium atoms available at crystal surfaces in various biominerals.[41][44][45] Such binding of OPN to various types of calcium-based biominerals ‒ such as calcium-phosphate mineral in bones and teeth,[46] calcium-carbonate mineral in inner ear otoconia[47] and avian eggshells,[48] and calcium-oxalate mineral in kidney stones[49][50][51] – acts as a mineralization inhibitor to regulate crystal growth.[52]
OPN is a substrate protein for a number of enzymes whose actions may modulate the mineralization-inhibiting function of OPN, a prominent one being PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome), which can extensively degrade OPN and whose inactivating gene mutations lead to altered processing of OPN and osteomalacia (soft hypomineralized bones) in X-linked hypophosphatemia (XLH).[53]
Along with its role in the regulation of normal mineralization within the extracellular matrices of bones and teeth,[54] OPN is also upregulated at sites of pathologic, ectopic calcification[55][56] – such as for example, in urolithiasis and vascular calcification ‒ presumably at least in part to inhibit debilitating mineralization in these soft tissues.
Role in bone remodeling
Osteopontin has been implicated as an important factor in hydroxyapatite, Ca10(PO4)6(OH)2. Loss of this mineral may lead to osteoporosis, as the bone is depleted for calcium if this is not supplied in the diet.
OPN serves to initiate the process by which osteoclasts develop their ruffled borders to begin bone resorption. It is also found in urine, where it inhibits kidney stone formation.
Role in immune functions
As discussed, OPN binds to several integrin receptors including α4β1, α9β1, and α9β4 expressed by leukocytes. These receptors have been well-established to function in cell adhesion, migration, and survival in these cells. Therefore, recent research efforts have focused on the role of OPN in mediating such responses.
Osteopontin (OPN) is expressed in a range of immune cells, including macrophages, neutrophils, dendritic cells, and T and B cells, with varying kinetics. OPN is reported to act as an immune modulator in a variety of manners.[2] Firstly, it has chemotactic properties, which promote cell recruitment to inflammatory sites. It also functions as an adhesion protein, involved in cell attachment and wound healing. In addition, OPN mediates cell activation and cytokine production, as well as promoting cell survival by regulating apoptosis.[2] The following examples are found.[2]
Role in Heart
OPN expression increases under a variety of conditions of the heart, and is associated with increased myocyte apoptosis and myocardial dysfunction.[58]
Chemotaxis
OPN plays an important role in neutrophil recruitment in alcoholic liver disease.[10][59] OPN is important for the migration of neutrophil in vitro.[60] In addition, OPN recruits inflammatory cells to arthritis joints in the collagen-induced arthritis model of rheumatoid arthritis.[61][62] A recent in vitro study in 2008 has found that OPN plays a role in mast cell migration.[63] Here OPN knock-out mast cells were cultured and they observed a decreased level of chemotaxis in these cells compared to wildtype mast cells. OPN was also found to act as a macrophage chemotactic factor.[64] In this study, researchers looked at the accumulation of macrophages in the brain of rhesus monkeys and found that OPN prevented macrophages from leaving the accumulation site, indicating an increased level of chemotaxis.
Cell activation
Activated T cells are promoted by IL-12 to differentiate towards the Th1 type, producing cytokines including IL-12 and IFNγ. OPN inhibits production of the Th2 cytokine IL-10, which leads to enhanced Th1 response. OPN influences cell-mediated immunity and has Th1 cytokine functions. It enhances B cell immunoglobulin production and proliferation.[2] Recent studies in 2008 suggest that OPN also induces mast cell degranulation.[63] The researchers here observed that IgE-mediated anaphylaxis was significantly reduced in OPN knock-out mice compared to wild-type mice. The role of OPN in activation of macrophages has also been implicated in a cancer study, when researchers discovered that OPN-producing tumors were able to induce macrophage activation compared to OPN-deficient tumors.[65]
Fig 2. Known immunologic functions of OPN. OPN binds to several integrin receptors including α4β1, α9β1, and α9β4 expressed by leukocytes and are known to induce cell adhesion, migration, and survival in immune cells including neutrophils, macrophages, T cells, mast cells, and osteoclasts.
OPN is an important anti-apoptotic factor in many circumstances. OPN blocks the activation-induced cell death of macrophages and T cells as well as fibroblasts and endothelial cells exposed to harmful stimuli.[66][67] OPN prevents non-programmed cell death in inflammatory colitis.[68]
Potential clinical application
The fact that OPN interacts with multiple cell surface receptors that are ubiquitously expressed makes it an active player in many physiological and pathological processes including wound healing, bone turnover, tumorigenesis, inflammation, ischemia, and immune responses1. Therefore, manipulation of plasma (or local) OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, bone (and tooth) mineralization diseases, osteoporosis, and some forms of stress.[2]
Role in autoimmune diseases
OPN has been implicated in pathogenesis of rheumatoid arthritis. For instance, researchers found that OPN-R, the thrombin-cleaved form of OPN, was elevated in the rheumatoid arthritis joint. However, the role of OPN in rheumatoid arthritis is still unclear. One group found that OPN knock-out mice were protected against arthritis.[69] while others were not able to reproduce this observation.[70] OPN has been found to play a role in other autoimmune diseases including autoimmune hepatitis, allergic airway disease, and multiple sclerosis.[71]
Role in cancers and inflammatory diseases
It has been shown that OPN drives IL-17 production;[72] OPN is overexpressed in a variety of cancers, including lung cancer, breast cancer, colorectal cancer, stomach cancer, ovarian cancer, papillary thyroid carcinoma, melanoma and pleural mesothelioma; OPN contributes both glomerulonephritis and tubulointerstitial nephritis; and OPN is found in atheromatous plaques within arteries. Thus, manipulation of plasma OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, osteoporosis and some forms of stress.[2]
Research has implicated osteopontin in excessive scar-forming and a gel has been developed to inhibit its effect.[73]
Role in colitis
Opn is up-regulated in inflammatory bowel disease (IBD).[74] Opn expression is highly up-regulated in intestinal immune and non-immune cells and in the plasma of patients with Crohn's disease (CD) and Ulcerative colitis (UC), as well as in the colon and plasma of mice with experimental colitis.[74][75][76] Increased plasma Opn levels are related to the severity of CD inflammation, and certain Opn gene (Spp1) haplotypes are modifiers of CD susceptibility. Opn has also a proinflammatory role in TNBS- and dextran sulfate sodium (DSS)-induced colitis, which are mouse models for IBD. Opn was found highly expressed by a specific dendritic cell (DC) subset derived from murine mesenteric lymph nodes (MLNs)and is highly proinflammatory for colitis.[77] Dendritic cells are important for the development of intestinal inflammation in humans with IBD and in mice with experimental colitis. Opn expression by this inflammatory MLN DC subset is crucial for their pathogenic action during colitis.[77]
Role in allergy and asthma
Osteopontin has recently been associated with allergic inflammation and asthma. Expression of Opn is significantly increased in lung epithelial and subepithelial cells of asthmatic patients in comparison to healthy subjects.[78] Opn expression is also upregulated in lungs of mice with allergic airway inflammation.[78] The secreted form of Opn (Opn-s) plays a proinflammatory role during allergen sensitization (OVA/Alum), as neutralization of Opn-s during that phase results in significantly milder allergic airway inflammation.[78] In contrast, neutralization of Opn-s during antigenic challenge exacerbates allergic airway disease.[78] These effects of Opn-s are mainly mediated by the regulation of Th2-suppressing plasmacytoid dendritic cells (DCs) during primary sensitization and Th2-promoting conventional DCs during secondary antigenic challenge.[78] OPN deficiency was also reported to protect against remodeling and bronchial hyperresponsiveness (BHR), again using a chronic allergen-challenge model of airway remodeling.[79] Furthermore, it was recently demonstrated that OPN expression is upregulated in human asthma, is associated with remodeling changes and its subepithelial expression correlates to disease severity.[80] OPN has also been reported to be increased in the sputum supernatant of smoking asthmatics,[81] as well as the BALF and bronchial tissue of smoking controls and asthmatics.[82]
Role in muscle disease and injury
Evidence is accumulating that suggests that osteopontin plays a number of roles in diseases of skeletal muscle, such as Duchenne muscular dystrophy. Osteopontin has been described as a component of the inflammatory environment of dystrophic and injured muscles,[22][83][84][85] and has also been shown to increase scarring of diaphragm muscles of aged dystrophic mice.[86] A recent study has identified osteopontin as a determinant of disease severity in patients with Duchenne muscular dystrophy.[87] This study found that a mutation in the osteopontin gene promoter, known to cause low levels of osteopontin expression, is associated with a decrease in age to loss of ambulation and muscle strength in patients with Duchenne muscular dystrophy.
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^ Burdo TH, Wood MR, Fox HS (June 2007). "Osteopontin prevents monocyte recirculation and apoptosis". J. Leukoc. Biol. 81 (6): 1504–11.
^ Crawford HC, Matrisian LM, Liaw L (November 1998). "Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo". Cancer Res. 58 (22): 5206–15.
^ Denhardt DT, Noda M, O'Regan AW, Pavlin D, Berman JS (May 2001). "Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival". J. Clin. Invest. 107 (9): 1055–61.
^ Standal T, Borset M, Sundan A (September 2004). "Role of osteopontin in adhesion, migration, cell survival and bone remodeling". Exp. Oncol. 26 (3): 179–84.
^ Da Silva AP, Pollett A, Rittling SR, Denhardt DT, Sodek J, Zohar R (September 2006). "Exacerbated tissue destruction in DSS-induced acute colitis of OPN-null mice is associated with downregulation of TNF-alpha expression and non-programmed cell death". J. Cell. Physiol. 208 (3): 629–39.
^ Yumoto K, Ishijima M, Rittling SR, Tsuji K, Tsuchiya Y, Kon S, Nifuji A, Uede T, Denhardt DT, Noda M (April 2002). "Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice". Proc. Natl. Acad. Sci. U.S.A. 99 (7): 4556–61.
^ Jacobs JP, Pettit AR, Shinohara ML, Jansson M, Cantor H, Gravallese EM, Mathis D, Benoist C (August 2004). "Lack of requirement of osteopontin for inflammation, bone erosion, and cartilage damage in the K/BxN model of autoantibody-mediated arthritis". Arthritis Rheum. 50 (8): 2685–94.
^ Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, Sobel RA, Lock C, Karpuj M, Pedotti R, Heller R, Oksenberg JR, Steinman L (November 2001). "The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease". Science 294 (5547): 1731–5.
^ Steinman L (February 2007). "A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage". Nat. Med. 13 (2): 139–45.
^ "'"Gel 'to speed up wound healing. Health. BBC NEWS. 2008-01-22. Retrieved 2009-01-26.
^ a b Gassler N, Autschbach F, Gauer S, Bohn J, Sido B, Otto HF, Geiger H, Obermüller N (November 2002). "Expression of osteopontin (Eta-1) in Crohn disease of the terminal ileum". Scand J Gastroenterol 37 (11): 1286–95.
^ Sato T, Nakai T, Tamura N, Okamoto S, Matsuoka K, Sakuraba A, Fukushima T, Uede T, Hibi T (September 2005). "Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response". Gut 54 (9): 1254–62.
^ Mishima R, Takeshima F, Sawai T, Ohba K, Ohnita K, Isomoto H, Omagari K, Mizuta Y, Ozono Y, Kohno S (February 2007). "High plasma osteopontin levels in patients with inflammatory bowel disease". J Clin Gastroenterol 41 (2): 167–72.
^ a b Kourepini E, Aggelakopoulou M, Alissafi T, Paschalidis N, Simoes DC, Panoutsakopoulou V (March 2014). "Osteopontin expression by CD103- dendritic cells drives intestinal inflammation". Proc Natl Acad Sci U S A 111 (9): E856–E865.
^ a b c d e Xanthou G, Alissafi T, Semitekolou M, Simoes DC, Economidou E, Gaga M, Lambrecht BN, Lloyd CM, Panoutsakopoulou V (May 2007). "Osteopontin has a crucial role in allergic airway disease through regulation of
^ Simoes DC, Xanthou G, Petrochilou K, Panoutsakopoulou V, Roussos C, Gratziou C (May 2009). "Osteopontin
^ Samitas K, Zervas E, Vittorakis S, Semitekolou M, Alissafi T, Bossios A, Gogos H, Economidou E, Lötvall J, Xanthou G, Panoutsakopoulou V, Gaga M (2010). "Osteopontin expression and relation to disease severity in human asthma.". Eur. Respir. J. 37 (2): 331–41.
^ Hillas G, Loukides S, Kostikas K, Simoes D, Petta V, Konstantellou E, Emmanouil P, Papiris S, Koulouris N, Bakakos P (Jan 2013). "Increased levels of osteopontin in sputum supernatant of smoking asthmatics.". Cytokine. 61 (1): 251–5.
^ Samitas K, Zervas E, Xanthou G, Panoutsakopoulou V, Gaga M (Feb 2013). "Osteopontin is increased in the bronchoalveolar lavage fluid and bronchial tissue of smoking asthmatics.". Cytokine 61 (3): 713–5.
^ Porter JD, Khanna S, Kaminski HJ, Rao JS, Merriam AP, Richmonds CR, Leahy P, Li J, Guo W, Andrade FH (May 2002). "A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice". Hum Mol Genet 11 (3): 263–72.
^ Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM (2002). "Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle". Proc Natl Acad Sci U S A 99 (23): 15000–15005.
^ Hirata A, Masuda S, Tamura T, Kai K, Ojima K, Fukase A, Motoyoshi K, Kamakura K, Miyagoe-Suzuki Y, Takeda S (2003). "Expression profiling of cytokines and related genes in regenerating skeletal muscle after cardiotoxin injection: a role for osteopontin". Am J Pathol 163 (1): 203–215.
^ Vetrone SA, Montecino-Rodriguez E, Kudryashova E, Kramerova I, Hoffman EP, Liu SD, Miceli MC, Spencer MJ (2009). "Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-beta". J Clin Invest 119 (6): 1583–1594.
^ Pegoraro E, Hoffman EP, Piva L, Gavassini BF, Cagnin S, Ermani M, Bello L, Soraru G, Pacchioni B, Bonifati MD, Lanfranchi G, Angelini C, Kesari A, Lee I, Gordish-Dressman H, Devaney JM, McDonald CM (2011). "SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy". Neurology 76 (3): 219–226.
Osteoclast
Fujisawa R (2002). "[Recent advances in research on bone matrix proteins]". Nippon Rinsho. 60. Suppl 3: 72–8.
Denhardt DT, Mistretta D, Chambers AF, Krishna S, Porter JF, Raghuram S, Rittling SR (2003). "Transcriptional regulation of osteopontin and the metastatic phenotype: evidence for a Ras-activated enhancer in the human OPN promoter". Clin. Exp. Metastasis 20 (1): 77–84.
Yeatman TJ, Chambers AF (2003). "Osteopontin and colon cancer progression". Clin. Exp. Metastasis 20 (1): 85–90.
O'Regan A (2004). "The role of osteopontin in lung disease". Cytokine Growth Factor Rev. 14 (6): 479–88.
Wai PY, Kuo PC (2004). "The role of Osteopontin in tumor metastasis". J. Surg. Res. 121 (2): 228–41.
Konno S, Hizawa N, Nishimura M, Huang SK (2007). "Osteopontin: a potential biomarker for successful bee venom immunotherapy and a potential molecule for inhibiting IgE-mediated allergic responses". Allergology international : official journal of the Japanese Society of Allergology 55 (4): 355–9.
Rodrigues LR, Teixeira JA, Schmitt FL, Paulsson M, Lindmark-Mänsson H (2007). "The role of osteopontin in tumor progression and metastasis in breast cancer". Cancer Epidemiol. Biomarkers Prev. 16 (6): 1087–97.
Ramaiah SK, Rittling S (2007). "Role of osteopontin in regulating hepatic inflammatory responses and toxic liver injury". Expert opinion on drug metabolism & toxicology 3 (4): 519–26.
Osteopontin at the US National Library of Medicine Medical Subject Headings (MeSH)
Cell signaling: cytokines
Chemokine
CCL2/MCP1
CCL3/MIP1α
CCL4/MIP1β
CCL5/RANTES
CCL18/PARC/DCCK1/AMAC1/MIP4
CXCL
CXCL1/KC
CXCL8/IL8
CXCL10
CX3CL
CX3CL1
XCL
XCL1
TNFA
Lymphotoxin
TNFB/LTA
TNFC/LTB
TNFSF4
TNFSF5/CD40LG
TNFSF13B
(grouped by
subunit)
γ chain
IL2/IL15
β chain
GMCSF
IL6 like/gp130
+non IL OSM
CNTF
IL12 family/IL12RB1
IL10 family
IL10/IL22
Interferon type III
IL28/IFNL2+3
IL29/IFNL1
IFNA1
IFNA10
IFNK
IFNW1
IFNG
Ig superfamily
IL1 family: IL1A/IL1F1
IL1B/IL1F2
1Ra/IL1F3
IL1F5
IL1F10
33/IL1F11
18/IL1G
IL17/IL25 (IL17A)
KITLG
Colony-stimulating factor
By function/
proinflammatory cytokine
Monokine
Lymphokine
IFNγ
TNFβ
Index of
Human proteins
Protein pages needing a picture
Wellcome Trust, Merops, Research center, European Bioinformatics Institute, Multiple sequence alignment
Metabolism, X-ray crystallography, Protein folding, Biochemistry, Glycolysis
Lung cancer, Breast cancer, Colorectal cancer, Medical imaging, Prostate cancer
Protein Data Bank
Protein structure, X-ray crystallography, Nuclear magnetic resonance spectroscopy of proteins, Bioinformatics, Protein Data Bank (file format)
Species, Mitosis, Centromere, Chromatin, DNA replication
Gene, Protein, Cd18, Mucin, Glycoprotein
Angiogenesis inhibitor
Thrombospondin, Cancer, Angiostatin, Endostatin, Platelet factor-4
Osteopontin, Object Process Network, Meta-language, Optics & Photonics News, Oneohtrix Point Never
Digital object identifier, Bone marrow, Cartilage, Chondrocyte, Bone
Gene, Pancreas, Testosterone, Cytoskeleton, Calcium


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Home News New contribution from Cristiano's in the fight against the coronavirus
New contribution from Cristiano's in the fight against the coronavirus
New contribution from Cristiano's in the fight against the coronavirus. Jorge Mendes, on behalf of his representatives, including Cristiano Ronaldo, donated 1,500 masks to a hospital in Portugal to fight COVID-19.
The coronavirus crisis, which has already left almost 40,000 deaths worldwide, generates all kinds of signs of solidarity.
One of the most recent, born from soccer, is that of Jorge Mendes, in front of his represented. Cristiano Ronaldo's agent, among other players, made a new donation for hospitals in his native Portugal.
MENDES AND CRISTIANO, HELPING WITH EVERYTHING
Mendes and his representatives, according to the Portuguese media, donated 150,000 masks to the Santo Antonio Hospital, in Porto.
Previously, the same health center helped him with 1,000 inhalation chambers and 200,000 gowns a week ago. Both Mendes and his most famous client, Cristiano Ronaldo, also helped finance 35 places at the Lisbon North University Hospital Center.
The Lisbon North University Hospital Center is made up of the Santa María and Pulido Valente hospitals. They also funded beds in the Intensive Care Unit for the Santo Antonio Hospital.
THE BALANCE OF THE CORONAVIRUS
As of Monday night, with updated data, Portugal had suffered 140 deaths from the coronavirus. Italy leads the sad world classification of deceased by COVID-19, with 11,591 deaths, followed by Spain, with 7,716.
Around the world there are almost 40 thousand deaths, which has forced governments to order quarantine. The measure serves to curb the spread of the disease, as scientists search for vaccines for cure.
Twitter CEO Elon Musk Says the Checked Ticks are Coming Back Again
Europe's largest battery storage system will start working four months earlier
An unforgettable scene with a glass bow, which Rian Johnson almost cut out until he watched the film with a test audience
Insecure Server Reveals US Government's "No-Fly List"
Forgotten Manchester United Player Returns to Training to Help Erik Ten Hag Expand Opportunities
Erik Ten Hag Dismisses Concerns About The Team's Defensive Prowess
Tiffany Haddish Stood Her Ground at The Sundance Festival After One of The Audience Was Outraged by Her New Film
Two Major German Festivals Are Excluding Pantera From The Lineup Due to Protests Against Alleged Racism in The Past.
Ticketmaster Blamed a Cyberattack For Problems With The Sale of Taylor Swift's Tour
Last Summer, Manchester United Talked to Antoine Griezmann, But Eventually Stayed at Atletico Madrid.
Jonathan Majors Shared His Workout Schedule For Magazine Dreams.
Noctua Releases Low-Profile Coolers For New AMD Ryzen Processors
Review of "Boundless Pool": Immerse Yourself in This Dirty World of Death and Debauchery
Enjin, spoken by Samsung and Microsoft partnership, opens to 1.4 billion...
The second season of "The Witcher" is already filming

redpajama_set_name: RedPajamaCommonCrawl


Japan Festival CANADA was held on August 26th and 27th 2017. This 2nd Annual event since Japan Festival Mississauga 2016 which was held 1st time in July 2016 in Mississauga city, Ontario. Japan Festival Mississauga 2016 attracted over 40,000 attendees in one day on July 10th despite of short hours from 12 (noon) to 19:00 and it had become one of the largest Japanese Cultural events in Canada. Since the success of 1st time event the expectation and encoura gement f rom J apa n and Canada Government sectors, municipal level sectors and sponsors were paramount led to organizing this year's event renamed as Japan Festival CANADA 2017 involving not only Province of Ontario but also Canada Nationwide to signify and celebrate Diplomatic relationship between Canada and Japan and to contribute in promoting Japanese Culture.
Since the first event in 2016 was a success the event has become larger scale in 2017 as 2 days End of the Summer event in the last weekend of August. The concept of the event was to introduce and promote Japanese food, culture and technologies to Canada and the World. Variety of entertainment program such as Traditional, J-Pop, Anime and etc. were some of the major attractions to the event as well as the cuisines from popular and trendy Japanese Restaurants in Ontario, Japanese Corporation booths with state of the art technologies, products and service and etc. Japan Festival CANADA 2017 was for families and friends in all ages to experience and enjoy Japan.
Japan Festival CANADA 2017 attracted over 70,000 attendees in 2 days event which surpassing the 40,000 attendees recorded in 2016 event. More variety and improved stage performance program and increased number of event booths as 60 from 50 in 2016 was also contributed to the positive factor of high turnout of attendees. Especially the highlight of the 1st day was night program after dusk until 11:00 pm of J-pop and DJ Live performance attracting not only young generations but also the older generations among different ethnic backgrounds. Japan Festival CANADA 2017 was an opportunity for everyone to experience Japan.
Japan Festival Mississauga 2016 was held at Celebration Square on July 10 and the inaugural festival will boast booths run by popular Japanese restaurants, Japanese beverage booths, traditional Japanese music, entertainment, live performances and more. The event was held to celebrate the 35th anniversary of Mississauga's relationship with its Japanese sister city, Kariya. It was a great success with more than 40,000 attendees recorded.


of a SAN is to enhance pre-existing storage networks.
This is often made possible by reorganising the resources that are already on the network in order for the storage to be locally attached. This allows several servers to all access shared storage.
One of the main benefits of SAN in businesses is easier storage administration. With the files being shared locally, people within the business can access their files from different locations. This means that there is less storage needed on the network server, so more powerful applications can be run.


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Home Letter of Credit Basics What are the Consequences of not Allowing Partial Shipments?
Although the letter of credit rules allow partial shipments, importers may prohibit them by giving clear instructions to the issuing bank to this effect when opening the letter of credit. On this post I will analyse the consequences of not allowing partial shipments.
Normally the letter of credit rules allow partial shipments.
UCP 600 Article 31 states that partial drawings or shipments are allowed.
If an applicant does not want to permit partial shipments, he must give clear instructions to the issuing bank to this effect, when opening the letter of credit.
Why Would Applicants Prohibit Partial Shipments?
Technical Reasons to Disallow Partial Shipments: Shipping of goods in partial may not be meaningful.
For example, if an exporter should be dispatching one piece of Offset Printing Machine under a letter of credit, shipping the machine dismantled via partial shipments would be meaningless.
As a result, an importer needs to disallow partial shipment under such a scenario.
Commercial Reasons to Disallow Partial Shipments: Under some circumstances, commercial conditions may make partial shipments unsuitable for the importers.
Generally, importers are not the end buyers in international trade transactions. They are big wholesalers.
They import the goods in to their countries and then they will distribute them to smaller distributors or end customers.
If importers need specific amount of goods within a specific periods of time, they may forced to prohibit partial shipments under the letter of credit transactions.
What are the Consequences of Prohibiting Partial Shipments?
If partial shipments are not allowed under a letter of credit, issuing bank, confirming bank and nominated bank should check the presented documents very carefully in order to make sure that documents do not evidence a partial shipment.
Exporters could not make short shipments, except allowed tolerance limits, if any, under letters of credit where partial shipments are prohibited.
Exporters could not make partial drawings and could not get partial payments from the banks.
Exporters who act on the contrary may face discrepancies and non-payment risks.
Next articlePartial Drawings and Partial Shipments: What is the Difference?


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ZoneOptions Broker Review 2019
Trade with ZoneOptions
ZoneOptions stands as one of the top selected trading brokers for traders across Latin America and Spain. One of the top reasons why ZoneOptions has become so popular for many of these traders is because it's available in Spanish. ZoneOptions review discovered this broker is being a regulated broker and also one of the most streamlined binary options brokers currently available. With a wealth of options as well as a maximum payout of 87%, this is an extremely competitive broker that's available for a minimum deposit of just $250.
ZoneOptions Account Features
ZoneOptions is a quite respected broker as the trading interface is quite sophisticated and the customer support is excellent. With its license, the broker is also a very secure and well-featured trading platform governed under all of the appropriate licenses required for use in Cyprus. It doesn't take a lot of effort to master the features on ZoneOptions and through the intuitive Spot Option based software, you can see considerable profits with excellent customer support.
Several account option types are available on ZoneOptions. Each with their own unique enhancements for the system. Multiple accounts from this broker will ensure that almost every type of user can get access to the level of features that will be most interesting to them. Here are some of the top account features that you can receive with each account level:
Due to CySEC's decision, StockPair no longer provides binary options bonuses!
ZoneOptions Beginner account: beginners receive a demo account with up to $1000 from a $250 deposit. ZoneOptions review found there is also access to several of the training support items, access to the IOS and android app, 1 weekly trading session, 120% welcome bonus and a payout up to 82%. Beginner accounts even get access to a personal account manager to assist with troubleshooting.
ZoneOptions Advanced account: advanced users need to deposit at least US$1000 and he will get access to all of the same features the beginner users get plus an additional $4000 in their demo account. Welcome bonuses for danced users can go up to 60% and they will get access to three weekly trading sessions with a professional. Advanced users are the first to get access to the colored trend signals, express 24-hour withdrawal, trading on all demo accounts and more.
ZoneOptions Professional account: for $5000 a professional user can get access to $10,000 in a demo account, all of the features from the previous accounts including a payout of up to 84%, welcome bonuses of up to 75%, five weekly trading sessions, improved training on speculation and graphical analysis and more.
ZoneOptions VIP users: the VIP users require a $10,000 deposit and they can receive unlimited money in their demo account for trading strategies. VIP users can also receive payouts of up to 86%, a 100% welcome bonus, 10 weekly trading sessions, custom signals and filters for a customized trading platform experience, custom alerts and automation, customize risk management strategies and extra educational resources.
ZoneOptions Trading Software
The trading platform in itself comes with some fantastic features for traditional High Low options, Touch no cash options, Turbo and 60-second options, asset type expiry time filters and more. It extremely intuitive to use and with a wide range of assets available for trade, you can enjoy seeing some excellent options.
ZoneOptions may not have the massive amounts of assets available for trade as some other trading platforms but you can currently trade up to 30 currency pairs, three commodities, 27 stocks and 13 indices. ZoneOptions review found that the trading environment is competitive and with this number of assets the program remains a healthy contender in the market, especially for international users.
Signals can be taken with a one-hour expiry, 30 min. expiry, 15 min. expiry as well as a wealth of very quick expiry or turbo options. The risk level in signals also displays at a power level which can be a huge asset to traders on this platform. Not many other brokers offer up signals for free and ZoneOptions has trading signal displays with risk levels to help both beginners and advanced users.
ZoneOptions review found that broker also has an extensive interactive e-book, a PDF guide, trading guide and ongoing Ecorse is available in several different languages to help users to adapt to the profile as well is make smarter trading decisions. This type of educational resource ensures the traders can do more with their money.
The ZoneOptions platform itself as a full-screen solution and an interface that can be customized with a wealth of filters. The improvements available on this platform for reading charts and more can be quite helpful for generating a custom trading environment for every user. You can customize the desktop to a fair degree to make sure that you can track any of the assets that are most important to you. The trading graph is quite intuitive and easy to follow a narrow wealth of various educational tools in multiple languages on the platform too.
ZoneOptions Support Information
Customer support from ZoneOptions is available in Spanish and English and most of the staff on the support team is multilingual available to help people in both language backgrounds. Support can be easily contacted through live chat, a WhatsApp line, through the phone as well as through e-mail.
ZoneOptions review found out this broker features fantastic live chat support as well as a platform that remains easy to use. The regulated broker inspires real confidence under its government regulatory agency license and the multilanguage support ensures that ZoneOptions is a well adopted binary options platform across many parts of the world.
The about section of the website is also home to a wide range of literature that can help you through a number of troubleshooting issues and present you with FAQ information on the basics of the trading platform. The educational resources and FAQs are a great way to learn more about signals, using the platform, upgrading your membership and dealing with common support problems.
Overall the multilanguage support with this company is fantastic and amongst the best from a trading platform in its market.
With a wealth of options as well as a maximum payout of 87%, this is an extremely competitive broker that's available for a minimum deposit of just $250.
ZoneOptions Company Information
Banking with ZoneOptions can be quite simple and it does require some degree of verification including a proof of address, ID and a payment option for withdrawal and deposit. ZoneOptions review found traders can use credit cards like Visa, MasterCard, Discover, Maestro international, Carte Bleue, Dankort and more. There's also the option to use bank traders and net wallets like OKPay, Paypal, Neteller, Skrill, and others. The minimum deposit for any banking is $250 and most wire transfers will require at least $500 for deposit.
Minimum withdrawals for any ZoneOptions customers are at least $50 and some small fees could be incurred on wire transfers from the system. The good news is that ZoneOptions review found you can enjoy unlimited withdrawals from the system without the need to pay extra fees for multiple withdrawals. The fees will be the same every time.
ZoneOptions Review Conclusion:
In ZoneOptions review we have acknowledged this broker is a great place to get started with binary options trading especially if you would like to take advantage of an account that's going to have ongoing signals. Although the deposit limit can be quite steep for many users, the multilanguage support and the custom interfaces available for some of the users is a huge asset in trading. When coupled with excellent customer service and some healthy bonuses this remains one of the best binary options accounts you can open.
Not too many platforms feature the same robust demo accounts. The only real drawback with this broker is the higher rating on bank transfers and the current lack of tradable assets when compared to other brokers.
ZoneOptions - Review Conclusion
Demo account available
Fee for bank wire transactions


This couple is currently galavanting around Thailand and I was just thinking that I never shared much of the amazing goodness that was their engagement session. I met up with these two last winter, in their home and we celebrated their engagement by hanging around the house, and it was seriously so much fun! You don't have to do typical engagement photos. I think they mean the most when they are something that reflects you as a couple. Just you two, exactly as you are.


text:
AUXLANG Archives
AUXLANG@LISTSERV.BROWN.EDU
AUXLANG Home
AUXLANG November 2007, Week 1
Re: Novial Lexike online
"Donald J. HARLOW" <[log in to unmask]>
International Auxiliary Languages <[log in to unmask]>
Je 07:10 atm 10/30/2007, Bruce GILSON skribis:
>The expanded version will also have some words added which Jespersen
>could not have put in in 1930 (things like "televisione" which are
>obviously easy to construct, but which refer to things that didn't
>exist in 1930!)
Actually, the first television was demonstrated in 1884
(electromechanical rather than strictly electronic), and the word
itself dates from 28 years before Novial (1900). I remember reading
somewhere that the first American government official to appear in a
TV transmission (not broadcast) was Secretary of Commerce ... Herbert
Hoover. The world's first color TV transmission was more or less
simultaneous with the publication of Novial (1928).
>or didn't think to put in (like some of the chemical elements; he
>put in some, but not all).
On the other hand, there are a number of chemical elements extant
today -- I presume you will include them -- which were unknown, or at
least had different names, in Jespersen's time, including a couple
that are not transuranics (e.g. promethium).
-- Don HARLOW
http://www.webcom.com/~donh/don/don.html
Opinions (in English): http://www.harlows.org/don/opinions/
Esperanto (in English): http://www.harlows.org/don/esperanto/
Literaturo (Esperante): http://donh.best.vwh.net/Esperanto/Literaturo


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President returns to Dhaka after medical check-up in UK
Photo: PID
UNB, Dhaka :
President Abdul Hamid on Thursday returned home from the United Kingdom after a health check-up.
A VVIP flight of Biman Bangladesh Airlines carrying the president landed at Hazrat Shahjalal International Airport at 11:05 am today.
Minister for Liberation War Affairs AKM Mozammel Haque, British High Commissioner to Bangladesh, Cabinet Secretary, Chief of Three Forces, Chief Coordinator of SDG Affairs of Prime Minister's Office, Foreign Secretary, Home Secretary, IGP and other military and civilian officials were present at the airport to welcome the president.
For Advertisement, [email protected]gla.net


text:
From the hospital to Xi Jinping, a turbulent day for the Argentine president at the G20
embed note
The Argentine president, Alberto Fernández, experienced a turbulent first day at the G20 summit in Bali, victim of "gastritis" which, however, did not prevent his meeting with the Chinese leader Xi Jinping.
The Argentine president had placed hopes in the second meeting this year with Xi, from which came a commitment to extend its "swap" currency exchange agreements with the Bank of China by 5,000 million dollars.
"President Xi informed us that he had authorized the Chinese government to allow Argentina to freely dispose of 35,000 million yuan, which means 5,000 million dollars," Fernández said in a subsequent appearance.
The "swap" is an exchange of currencies between two countries, which has no cost while the currencies are not used but remains accounted for in the reserves, in this case of Argentina.
Until now, the amount of the exchange mechanism agreed with China amounted to 130,000 million yuanabout 18,500 million dollars, but Buenos Aires had been asking for an extension for months.
The Chinese state media did not record this pact in their reports on the meeting between the two leaders.
This agreement supposes "to have 5,000 million dollars more in the reserves at the time of arranging the action of the Central Bank for the strengthening of our currency", affirmed in the same round the Minister of Economy, Sergio Massa.
At the last meeting of presidents in February, on the occasion of the Beijing Winter Olympics, Argentina joined the Chinese macro-project of the Belt and Road Initiative, which, according to Casa Rosada, will involve financing for investments of more than 23.7 billion dollars.
But the high-level meeting in Bali was on the air for much of the morning, in which the Argentine president "suffered an episode of hypotension and dizziness" that forced him to absent himself from the debates between the G20 leaders and go to the hospital for a review.
There, he was diagnosed with "erosive gastritis with signs of bleeding," indicated the Argentine presidency. "He received the appropriate medical treatment, being in good health and resuming his activities with medical supervision," she added.
"I thank you all for your concern. I'm fine, I'm working well," Fernández later said.
Nevertheless, The drop in tension made the Argentine the only Latin American leader present in Bali due to the absence of the Brazilian Jair Bolsonaro and the Mexican Andrés Manuel López Obrador, will be absent from the debate sessions scheduled for the first day of the summit.
Due to a medical recommendation, he also did not attend the gala dinner organized by the Indonesian president and on Wednesday he will only have a meeting with the managing director of the International Monetary Fund (IMF), Kristalina Georgieva, and an act with the head of the Spanish government. Pedro Sanchez.
In the first meeting of the day, focused on food security and nutrition, the Minister of Foreign Relations, Santiago Cafiero, was in charge of delivering the speech prepared by Fernández.
The foreign minister asked the leaders to "restore peace and contribute to world recovery" and stressed "the effects of war" around the world.
"In the northern hemisphere the merchants of death trade lethal weapons, but in the southern hemisphere food becomes more expensive or lacking and what ends up killing is not bullets or missiles, but poverty and hunger," he said.
The foreign minister highlighted the especially negative impact of the war in Latin Americawhich has already been deeply hit by the pandemic and registered a 27-year setback in poverty levels, according to the UN Economic Commission for Latin America and the Caribbean (ECLAC).
"Latin America and the Caribbean became the region in the world that lost the most years in life expectancy. Now we must face the effects of the war," he said.
Afro Brasil Museum honors artist Emanoel Araujo
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CPLT supports the CDE for the lawsuit against Raúl Torrealba: "If proven, we are talking about a tremendous embezzlement"
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Karol G gave a tremendous surprise to children in a hospital at Christmas
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Alert for the increase in "substance use" in girls, boys and adolescents
Due to judicial vacation, the Court of Justice of La Paz suspended the execution of warrants until December 30
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Check out some of the best goals Pelé scored!
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Manchester City win 3-1 at Leeds and move back to second place
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text:
My Family Tree
Climbing the branches of my family tree
Person Page 3574
Main Page - Master Index - Surname Index - Master Place Index - Home - Family Tree DNA
Thelma Loughmiller (F)
Thelma Loughmiller was the daughter of James Wiley Loughmiller Jr.. She married L. Tackett.
Immigrant=N
Related_By=C
Theressa Jane Loughmiller1 (F)
b. 9 May 1855, d. 20 November 1862
Theressa was born at Indiana on 9 May 1855. She was the daughter of Alexander Rogers Loughmiller and Nancy Elizabeth Gregg. Theressa died on 20 November 1862 at Indiana at age 7. She was buried in November 1862 at Bethlehem Cemetery, Jackson Twp., Washington Co., Indiana.
[S129] GEDCOM file # 3, Patti Nilssen.
Thomas C. Loughmiller (M)
b. 1879, d. 1952
Thomas C. Loughmiller was born in 1879. He was the son of James Anderson Loughmiller and Frances Leeper. Thomas C. Loughmiller married Patricia Elnora Merrit. Thomas C. Loughmiller died in 1952.
Children of Thomas C. Loughmiller and Patricia Elnora Merrit
Lavera Ione Loughmiller
Ralph Francis Loughmiller
Wilma H. Loughmiller
Thomas J. Loughmiller
Fred Raymond Loughmiller+ b. 1915, d. 1991
Thomas J. Loughmiller (M)
Thomas J. Loughmiller was the son of Thomas C. Loughmiller and Patricia Elnora Merrit.
Thomas Kelly Loughmiller1,2 (M)
b. 28 March 1838
Thomas was born at Hawkins Co., Tennessee, on 28 March 1838. He was the son of Philip Loughmiller and Sarah Jane Kelley. He married Miriam C. Sutton at Indiana on 2 May 1850. Thomas Kelly Loughmiller was census 1870 in 1870 at Morgan Twp., Harrison Co., Indiana; In the 1870 census for Morgan Twp., Harrison Co., Indiana the following family is found at household # 98:
Thomas K. Loughmiller, age 32, born in Tennessee;
M.C. Loughmiller, born in Indiana;
Charles Loughmiller, age 7, born in Indiana;
Lydia A. Loughmiller, age 5, born in Indiana;
John D. Loughmiller, age 2, born in Indiana;
Stephen Loughmiller, age 9, born in Indiana. He was census 1880 in 1880 at Morgan Twp., Harrison Co., Indiana; In the 1880 census for Morgan Twp., Harrison Co., Indiana the following family is found:
Thomas K. Loughmiller, born in Tennessee;
Charles Loughmiller, age 17, born in Indiana;
Lydia Loughmiller, age 14, born in Indiana;
John D. Loughmiller, age 11, born in Indiana;
Wilber Loughmiller, age 8, born in Indiana;
Jessie Loughmiller, age 6, born in Indiana;
Benjamin Loughmiller, age 3, born in Indiana;
Arthur Loughmiller, under 1 year old, born in Indiana. He was census 1900 in 1900 at Logan Twp., Pike Co., Indiana; Thomas was living with his son Jesse at the time of the 1900 census. He was buried at Old Cemetery, Linton, Greene Co., Indiana.
Children of Thomas Kelly Loughmiller and Miriam C. Sutton
(?) Loughmiller
Stephen H. Loughmiller b. 1861
Charles K. Loughmiller+ b. Dec 1862, d. 1933
Lydia A. Loughmiller b. c 1866
John D. Loughmiller b. c 1869
George Wilbur Loughmiller+ b. Nov 1872
Jesse Theodore Loughmiller b. Feb 1874
Benjamin F. Loughmiller b. Nov 1878
Arthur Loughmiller b. 1880
[S171] Sue Pearson Carpenter, "Descendants of Jurig Lochmiller".
Thomas Rogers Loughmiller1 (M)
b. 15 May 1850, d. 23 April 1900
Thomas was born at Greenville, Floyd Co., Indiana, on 15 May 1850. He was the son of Alexander Rogers Loughmiller and Nancy Elizabeth Gregg. He married Emma Bell Mosier at New Albany, Floyd Co., Indiana, on 23 June 1880. Thomas died on 23 April 1900 at Clark Co., Indiana, at age 49. He was buried in April 1900 at Greenville, Floyd Co., Indiana.
Children of Thomas Rogers Loughmiller and Emma Bell Mosier
Mary Esther Loughmiller b. 10 Oct 1881
Florence Rosalie Loughmiller b. 10 Mar 1883, d. 20 Feb 1886
Charles Alexander Loughmiller b. 1 Feb 1885
Joseph Lawrence Loughmiller b. 31 Dec 1886, d. 1932
John Christian Loughmiller b. 4 Mar 1889, d. 26 May 1889
Ruth Elizabeth Loughmiller b. 20 Feb 1892, d. 28 Dec 1914
Tilman Howard Loughmiller1 (M)
Tilman Howard Loughmiller was the son of Jacob Loughmiller and Aurelia Overton.
Victoria Loughmiller1 (F)
Victoria Loughmiller was the daughter of Jacob Loughmiller and Aurelia Overton. She married Jessie Browniee.
Viola Loughmiller1 (F)
b. 17 May 1894
Viola Loughmiller was born on 17 May 1894 at Indiana. She was the daughter of Lafayette Loughmiller and Elizabeth Baker.
Violet Rosalene Loughmiller1 (F)
b. 30 September 1899, d. 24 July 1962
Violet Rosalene Loughmiller was born on 30 September 1899 at Brazil, Clay Co., Indiana. She was the daughter of John Loughmiller and Anna Laura Hoback. Violet Rosalene Loughmiller married (?) Woods. Violet Rosalene Loughmiller died on 24 July 1962 at age 62.
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Monday, 1st of September 2014 I went to visit GaudiLabs in Lucerne to try and find a DIY solution to produce precise microfluidics, We wanted to try and reproduce the design of the Mother Machine ("Robust Growth of Escherichia Coli, P.Wang, L. Robert) or the compact portable biosensor from the microsystems laboratory of EPFL and HES-SO Wallis. Therefore our aim was to try and test the precision of DIY microfluidics. What was the minimal size of the channel that could easily be made.
We started first by listing the different methods that are possible to do DIY microfluidics.
Use scotch again, but this time we can laser cut it.
It is possible to use a metal mold to print the circuit in the plastic of an old DVD, a technique similar to lithography.
As we are looking for a precise, cheap and simple method, we chose to experiment with the nail studio microfluidics. We spent the afternoon testing the right combination of UV exposure, cleaning of the glass slate, heating of the slate etc.. We tried two different UV methods for the curing of the gel. The first was a basic UV lamp that you find in nail studios where you could adjust the number of UV lamps and the exposure time. The other method was a device that Urs built that used a UV lamp and a lens where the strength of the light and the exposure time where kept constant (3W Led at 1.5 W during 22 seconds)..Our best results were made using the homemade device.
After a few tests we concluded that we were missing an element because the nail polish would not stick enough to the glass slates. To try and adjust this we went to a nail salon and bought some nail primer. The sticking became much better but sadly the primer clouded the slate and it was harder to see through the glass slate.
We are not done yet working with microfluidics, we will try producing the chips in the lab at EPFL and in our DIY lab and compare precisely the precision of the DIY device!
good job! Have you refined your technology and compared it with the EPFL "product"?
Have you tried to seal the gel chip with o2 plasma/corona? What is the smallest feature you achieved?


Product Productions has been in business, as a prominent member of Chicago's production community, for over thirty years. And, over those 30 years we've grown and evolved Product Productions to meet the ever changing requirements of our clients.
Today, Product Productions offers equipment and services that are unique and all encompassing... equipment and services that includes lighting and grip packages, mobile production vehicles, generators, crewing, video and audio packages, dollies and jibs, production consultation, production management, studio facilities and more. "More" means that even if you don't see it on our site, if you need it we will do everything we can to get it for you. The other thing you receive when you use Product Productions is real, definable customer service. All of the staff at Product Productions takes great pride in our ability to make our clients feel that their project, no matter the size, is the most important project we have in house.


text:
2 Esdras1 RSV
1The second book of the prophet Ezra the son of Serai'ah, son of Azari'ah, son of Hilki'ah, son of Shallum, son of Zadok, son of Ahi'tub, 2son of Ahi'jah, son of Phin'ehas, son of Eli, son of Amari'ah, son of Azari'ah, son of Mera'ioth, son of Arna, son of Uzzi, son of Borith, son of Abishu'a, son of Phin'ehas, son of Elea'zar, 3son of Aaron, of the tribe of Levi, who was a captive in the country of the Medes in the reign of Ar-ta-xerx'es, king of the Persians.
4The word of the Lord came to me, saying, 5"Go and declare to my people their evil deeds, and to their children the iniquities which they have committed against me, so that they may tell their children's children 6that the sins of their parents have increased in them, for they have forgotten me and have offered sacrifices to strange gods. 7Was it not I who brought them out of the land of Egypt, out of the house of bondage? But they have angered me and despised my counsels. 8Pull out the hair of your head and hurl all evils upon them, for they have not obeyed my law — they are a rebellious people. 9How long shall I endure them, on whom I have bestowed such great benefits? 10For their sake I have overthrown many kings; I struck down Pharaoh with his servants, and all his army. 11I have destroyed all nations before them, and scattered in the east the people of two provinces, Tyre and Sidon; I have slain all their enemies.
12"But speak to them and say, Thus says the Lord: 13Surely it was I who brought you through the sea, and made safe highways for you where there was no road; I gave you Moses as leader and Aaron as priest; 14I provided light for you from a pillar of fire, and did great wonders among you. Yet you have forgotten me, says the Lord.
15"Thus says the Lord Almighty: The quails were a sign to you; I gave you camps for your protection, and in them you complained. 16You have not exulted in my name at the destruction of your enemies, but to this day you still complain. 17Where are the benefits which I bestowed on you? When you were hungry and thirsty in the wilderness, did you not cry out to me, 18saying, 'Why hast thou led us into this wilderness to kill us? It would have been better for us to serve the Egyptians than to die in this wilderness.' 19I pitied your groaning and gave you manna for food; you ate the bread of angels. 20When you were thirsty, did I not cleave the rock so that waters flowed in abundance? Because of the heat I covered you with the leaves of trees. 21I divided fertile lands among you: I drove out the Canaanites, the Per'izzites, and the Philistines before you. What more can I do for you? says the Lord. 22Thus says the Lord Almighty: When you were in the wilderness, at the bitter stream, thirsty and blaspheming my name, 23I did not send fire upon you for your blasphemies, but threw a tree into the water and made the stream sweet.
24"What shall I do to you, O Jacob? You would not obey me, O Judah. I will turn to other nations and will give them my name, that they may keep my statutes. 25Because you have forsaken me, I also will forsake you. When you beg mercy of me, I will show you no mercy. 26When you call upon me, I will not listen to you; for you have defiled your hands with blood, and your feet are swift to commit murder. 27It is not as though you had forsaken me; you have forsaken yourselves, says the Lord.
28"Thus says the Lord Almighty: Have I not entreated you as a father entreats his sons or a mother her daughters or a nurse her children, 29that you should be my people and I should be your God, and that you should be my sons and I should be your father? 30I gathered you as a hen gathers her brood under her wings. But now, what shall I do to you? I will cast you out from my presence. 31When you offer oblations to me, I will turn my face from you; for I have rejected your feast days, and new moons, and circumcisions of the flesh. 32I sent to you my servants the prophets, but you have taken and slain them and torn their bodies in pieces; their blood I will require of you, says the Lord.
33"Thus says the Lord Almighty: Your house is desolate; I will drive you out as the wind drives straw; 34and your sons will have no children, because with you they have neglected my commandment and have done what is evil in my sight. 35I will give your houses to a people that will come, who without having heard me will believe. Those to whom I have shown no signs will do what I have commanded. 36They have seen no prophets, yet will recall their former state.1.36 Other authorities read their iniquities37I call to witness the gratitude of the people that is to come, whose children rejoice with gladness; though they do not see me with bodily eyes, yet with the spirit they will believe the things I have said.
38"And now, father, look with pride and see the people coming from the east; 39to them I will give as leaders Abraham, Isaac, and Jacob and Hose'a and Amos and Micah and Jo'el and Obadi'ah and Jonah 40and Nahum and Habak'kuk, Zephani'ah, Haggai, Zechari'ah and Mal'achi, who is also called the messenger of the Lord.
Good News Bible (GNB)New Revised Standard Version (NRSV)Beibl Cymraeg Newydd (BCN)An Testament Nowydh ha'n Salmow 2014 (ABK)


text:
Il Pattaya Women's Open 2001 è stato un torneo di tennis giocato sul cemento. È stata l'11ª edizione del Pattaya Women's Open, che fa parte della categoria Tier V nell'ambito del WTA Tour 2001. Si è giocato a Pattaya in Thailandia, dal 5 all'11 novembre 2001.

Campioni

Singolare

 Patty Schnyder ha battuto in finale  Henrieta Nagyová 6–0, 6–4

Doppio

 Åsa Svensson /  Iroda Tulyaganova hanno battuto in finale  Liezel Huber /  Wynne Prakusya 4–6, 6–3, 6–3

Collegamenti esterni

redpajama_set_name: RedPajamaWikipedia


text:
How does certificate-based authentication work?
TCP/IP stack vulnerabilities threaten IoT devices
VMware, Dell split to form independent firms
AT&T picked as top managed-SD-WAN provider for the third year
Cisco DevNet certs: 10k awarded in first year
How to shop for a colocation provider
Major League Baseball makes a run at network visibility
New York gets smarter, one tech trial at a time
Review: 5 prepaid mobile hotspots fire up business travel
Wi-Fi hotspot blocking persists despite FCC crackdown
Good riddance payphones: NYC's free gigabit Wi-Fi kiosks go live
LinkNYC kiosks boast 100 times faster connectivity than typical Wi-Fi networks
Network World |
NYC Mayor's Office
New York City on Thursday officially launched its payphone booth replacements: shiny new 9-foot-plus-high kiosks dubbed Links that offer free Gigabit-speed Wi-Fi as well as free domestic VoIP calls via a tablet app.
Mayor Bill de Blasio, joined by vendor partners such as Qualcomm and NYC Department of IT and Telecommunications reps, showed off the first operating LinkNYC kiosks, just over a dozen of which are spread across 3rd Avenue for starters (see map). The spacing of the hotspots will enable users to stay connected as they walk down the street.
MORE: Coolest & Most Unusual NYC Toy Fair 2016 Techie Playthings
More than 500 Links are slated to be operational by mid-year, across all five boroughs, including neighborhoods such as St. George on Staten Island, Jamaica in Queens and Flatbush Avenue in Brooklyn. More than 4,500 kiosks are scheduled to be installed over the next four years. Overall, at least 7,500 Links are planned for installation, supported by a $200 million high-speed fiber network funded t by NYC's CityBridge partners.
"LinkNYC is a true, five-borough project that touches communities citywide, builds capacity and stands as one the largest investments in public broadband infrastructure in City history," said DoITT Commissioner Anne Roest, in a statement. "This transformational project is an important step towards Mayor de Blasio's goal of providing every resident and business access to affordable, reliable, high-speed broadband service by 2025."
The kiosks, in addition to supporting encrypted Wi-Fi connectivity for hundreds of HotSpot 2.0-enabled devices within 150 feet of them, will each include two USB charging ports, a red 911 button to contact emergency services and a weather- and vandalism-proof Android tablet that can be used to access information about the city and allow for free phone calls via Vonage. Opt-in Bluetooth-based location services will also be offered, as will apps for web browsing, maps, etc.
(A hands-on test by an Engadget reporter found Wi-Fi speeds significantly slower than 1G -- more like 70Mbps down and 150Mbps up -- but still way faster than most public or home Wi-Fi.)
Network services are free to users, as the system is supported via advertising that is projected by the organization to generate hundreds of millions of dollars for the city. In fact, that advertising play has some observers keeping a close eye on whether users' privacy will be compromised, even though the city insists that no personally identifiable information will be shared outside of CityBridge. LinkNYC also has shared tips for connecting to its network securely.
Join the Network World communities on Facebook and LinkedIn to comment on topics that are top of mind.
Bob Brown is the former news editor for Network World.
SD-WAN buyers guide: Key questions to ask vendors (and yourself)
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I'm Eric Wiese, and this is my favorite site on the Citadel.
I am Eric Wiese: a Web Application developer with extensive experience in both responsive HTML5 frontend and PHP / Magento engineering.
I'm currently working as a Lead Software Engineer and Front End Developer for the Magento Gold Partner Classy Llama in Springfield, MO.
I have a double degree in Computer Science and Mathematics from College of the Ozarks, also know as "Hard Work U".
I have worked as a member of a team as well as managed fellow developers on a variety of projects for clients of all sizes, from small start-up businesses to Fortune 500 companies. Below you will find samples of my previous work.
In addition to large projects, some of which are described in my portfolio, I often work on smaller, more targeted projects. Many of these features are open sourced on github.