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Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy
The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients' quality of life and medical expenses. Furthermore, there are limited drugs for treating diabetic nephropathy patients. Impaired lipid signaling, especially abnormal protein kinase C (PKC) activation by de novo-synthesized diacylglycerol (DG) under high blood glucose, is one of the causes of diabetic nephropathy. DG kinase (DGK) is an enzyme that phosphorylates DG and generates phosphatidic acid, i.e., DGK can inhibit PKC activation under diabetic conditions. Indeed, it has been proven that DGK activation ameliorates diabetic nephropathy.
diabetic nephropathy;protein kinase C;diacylglycerol kinase;67 kDa laminin receptor
1. Diabetes and Diabetic Nephropathy
Diabetes is a chronic metabolic disease that causes high blood glucose levels, resulting in serious health problems and death. In 2021, the number of people living with diabetes globally was estimated to be 536.6 million (prevalence: 10.5%), and this number is expected to reach 783.2 million (prevalence: 12.2%) by 2045 [1]. Diabetes significantly increases the risk of various health issues such as heart attacks, strokes, and infections compared to healthy individuals [2,3][2][3]. Diabetes also causes serious vascular complications. Diabetic retinopathy, neuropathy, and nephropathy are major microvascular complications of diabetes caused by microangiopathy. These complications lead to blindness, gangrene, and end-stage renal disease, respectively. Diabetic nephropathy (DN) is the leading cause of chronic kidney disease (CKD) in the world, leading to the need for dialysis, reducing patients' quality of life, and increasing medical care expenses.
DN causes glomerular filtration failure that leads to uremia in one in three diabetic patients after several years of latency [4]. Since a high blood glucose level is the fundamental cause of the complications, delaying the onset of DN by controlling the blood glucose level is the primary treatment strategy [5]. Recently, many drugs to control blood glucose levels, such as insulin, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists, have become available. It is also well recognized that the renin-angiotensin-aldosterone system (RAAS), which controls arterial pressure, plays a pivotal role in the pathogenesis of DN. So far, drugs targeting the RAAS, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), have been the first choice for preventing and delaying the onset of DN. However, there are limits to the drugs available for DN, and there are no specific therapeutics for ameliorating DN once hyperglycemia and high blood pressure become uncontrolled. Although controlling blood glucose levels is the most simple and effective approach to delaying the onset of microvascular complications, and inhibiting RAAS is effective for DN, finding a novel target with a renoprotective effect was necessary. Therefore, to develop a novel drug for DN, it was vital to understand the mechanisms of the development and progression of DN and find an effective therapeutic target.
2. Hyperglycemia Impairs Lipid Signaling
Among the causes of DN, impaired lipid signaling, especially diacylglycerol (DG) signaling, is well known. Generally, DG is produced from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and phosphatidylcholine (PC) by the action of phosphoinositide-specific phospholipase C (PI-PLC) and PC-specific PLC (PC-PLC) upon various growth factors and T-cell receptors (TCR) (Figure 1) [6,7,8][6][7][8]. In addition, DG is generated from the dephosphorylation of phosphatidic acid (PA) by phosphatidate phosphohydrolases (PAPs), including lipins [9,10][9][10]. PA is generated by hydrolyzing PC by phospholipase D (PLD) [11] and de novo synthesis from glycerol [12]. Glyceraldehyde 3-phosphate, an intermediate of glycolysis, is reversibly isomerized into dihydroxyacetone-phosphate and produces glycerol 3-phosphate. The glycerol 3-phosphate undergoes acylation and generates phosphatidic acid (PA), and dephosphorylates PA into DG (Figure 1). Under hyperglycemic conditions, excess blood glucose is uptaken intracellularly by the glucose transporter (GLUT) [13[13][14],14], and excess intracellular glucose results in DG production by de novo synthesis [12]. Both DG and PA are important intermediates for membrane lipids and are bioactive lipids involved in various signal transductions. For example, DG regulates conventional and novel protein kinase C (cPKC and nPKC) [15[15][16],16], Ras guanyl nucleotide-releasing protein (RasGRP) [17], and transient receptor potential channel (TRPC) [18]. PA regulates atypical PKC (aPKC) [19], phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) [20], Raf-1 kinase [21], and mammalian target of rapamycin (mTOR) [22]. Therefore, abnormal DG production causes severe changes in their signaling pathways. The abnormal activation of cPKC and nPKC has been reported as a cause of DN.
Generation pathways of DG and pathways leading to diabetic nephropathy.
P: phosphate.
3. Diabetic Nephropathy and PKC
PKC is a family of serine/threonine kinases, and nine mammalian isozymes are categorized into three groups based on their domain structure and characteristics [23]. cPKC (PKCα, β, γ) possesses diacylglycerol (DG) binding C1 domains (C1A and C1B) and a Ca2+ binding C2 domain, and their activity depends on DG and Ca2+ [24,25][24][25]. nPKC (PKCδ, ε, η, θ) has a slightly different domain composition than cPKC and lost Ca2+ dependency [26]. The DG-responsive characteristics of cPKC and nPKC are crucial to the pathogenesis of DN. The final subfamily requires neither Ca2+ nor DG for its activity and was cloned and classified as aPKC (PKCι, ζ). It is activated by PA [27,28][27][28]. These PKCs phosphorylate many proteins, including receptors, transporters, kinases, and phosphatases; thus, PKCs play a central role in cell signaling [23]. To date, the increase in DG mass and the abnormal activation of cPKC and nPKC under hyperglycemic conditions have been observed in vivo and in vitro [29[29][30][31],30,31], and evidence supports the idea that the abnormal activation of cPKC and nPKC is one of the causes of the development and progression of diabetic nephropathy [32,33,34,35][32][33][34][35].
Abnormally activated PKC causes various biological changes, such as growth factor upregulation, extracellular matrix production, and oxidative stress increase (Figure 1). Among PKC isozymes, activation of PKCα, β (cPKC) and PKCε, δ (nPKC) have been observed in DN [28,34,35,36,37,38][28][34][35][36][37][38]. One of the mechanisms underlying how PKC activation causes DN is related to various growth factors [39]. The upregulation of transforming growth factor-β (TGF-β) signaling, a profibrotic cytokine, is considered a critical pathogenic and progression factor of DN by activating various signal transductions, expression of the extracellular matrix, and reactive oxygen species production [40,41][40][41]. It has been reported that diabetes-induced activation of PKCβ and PKCδ upregulates TGF-β expression and the sensitivity of the cell against TGF-β, promoting the production of the extracellular matrix [42,43][42][43]. In addition to TGF-β, connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) are also recognized as key factors in DN progression [37]. CTGF is known to promote extracellular matrix production, leading to fibrosis [44]. VEGF is known as an angiogenic factor promoting vascular endothelial cell proliferation and pathological angiogenesis [45]. Several studies have reported that activation of PKCα, β, and ε upregulates VEGF expression [46[46][47],47], and PKCβ upregulates CTGF expression [34]. Therefore, PKC inhibition can normalize these growth factor expressions and signaling and ameliorate DN. Moreover, PKCα and β are associated with reactive oxygen species (ROS) production by activation of NADPH oxidase, causing renal injury [34,48][34][48].
To develop drugs targeting abnormal PKC activation, a PKCβ-specific inhibitor, ruboxistaurin, was developed and showed a renoprotective effect in several animal studies [49,50][49][50]. However, in human clinical trials, although ruboxistaurin showed some renoprotective effect in diabetes patients, statistical significance was not observed compared to placebo patients [35]. Furthermore, since DG–PKC pathway activation is a common event in other diabetic microvascular complications, ruboxistaurin underwent phase 3 clinical trials for diabetic retinopathy. Nevertheless, the trial failed due to the insignificance of its effect on retinopathy compared to the placebo group [51]. Taken together, the upregulation of the DG–PKC pathway in diabetes is one of the key events in the pathogenesis and progression of DN. However, since several independent PKC isoforms are involved in complex and multifactorial pathways, developing a drug targeting PKC is not simple. For example, PKCα deficiency prevents albuminuria by reducing VEGF. However, glomerular hypertrophy is not inhibited due to no change in TGF-β expression [33]. In contrast, PKCβ deficiency prevents glomerular hypertrophy by reducing TGF-β but not albuminuria in mice [34,52][34][52]. Therefore, inhibiting a single PKC might be insufficient to prevent DN. One can overcome this by developing a pan-inhibitor for cPKC and nPKC, or a combination of several specific inhibitors, though issues with side effects may emerge.
4. Diabetic Nephropathy and DGK
DG kinase (DGK) is a family of enzymes that converts DG into PA by phosphorylation [53]. As illustrated in Figure 1, DGK is a central regulator in various signaling pathways related to DG and PA [54]. Since DGKs consume DG, DGK is recognized as an indirect inhibitor of cPKC and nPKC. So far, 10 subtypes of mammalian DGKs have been discovered and divided into Type I~V based on their structural characteristics [54,55,56,57][54][55][56][57]. All mammalian DGKs have several C1 domains homologous to the one of PKCs at the nitrogen ends of catalytic domains (CD). Type I DGKs (DGKα, β, γ) have a recoverin homology (RVH) domain and two EF-hand motifs, which bind to Ca2+ at the nitrogen end of the two C1 domains [58]. Type II DGKs (DGKδ, η, κ) are characterized by a split CD, with a pleckstrin homology domain (PH domain) at the N terminus. Among Type II DGKs, DGKδ and η have a sterile α motif domain (SAM domain) at the C terminus [59,60,61][59][60][61]. DGKε has a simple structural feature composed of two C1 domains and a CD and is the only Type III DGK subtype [62]. Type IV DGKs (DGKζ, ι) possess ankyrin repeats at the C terminus, and residue between the C1 domains and the CD have homologs to the myristoylated alanine-rich C-kinase substrate phosphorylation site [63,64,65][63][64][65]. Type V DGKs (DGKθ) is the only subtype that has three C1 domains, and a PH domain overlapping the Ras-associating domain (RA domain) is localized between the C1 domains and the CD [66]. In addition, splicing variants to alter their domain composition has been reported in several subtypes.
Vitamin E is a hydrophobic antioxidant agent, and α-tocopherol is the most active vitamin E compound that humans preferentially absorb [67]. The main function of α-tocopherol is its antioxidant effect, preventing lipid peroxidation in the cell membrane [68]. In 1997, it was reported that α-tocopherol ameliorates the symptoms of DN by activating DGK and inhibiting glomerulus PKC in diabetic rats, suggesting the possibility of DGK as a therapeutic target for DN [69,70][69][70]. However, the subtype of DGK involved in the amelioration was unclear. In 2005, it was revealed that a Type I DGK, DGKα, is sensitive to α-tocopherol among the DGKs expressed in the murine glomeruli (DGKα, γ, δ, ε, and ζ) [71], i.e., in the cultured cell, α-tocopherol induced translocation of GFP tagged DGKα to the plasma membrane, which is the hallmark of DGK activation, while the other DGKs did not [72,73][72][73]. Although the primary function of α-tocopherol as a vitamin is its antioxidant effect, several studies have reported that the antioxidant effect of α-tocopherol is not related to PKC inhibition [74,75][74][75]. Indeed, it was revealed that the antioxidant effect of α-tocopherol is not necessary to activate DGKα [73]. There is a report showing that the antioxidant effect of α-tocopherol plays a protective role against the loss of activity of DGKα under the high glucose condition [76]. The detailed mechanisms of DGKα activation by α-tocopherol are discussed in a later section.
Sun, H.; Saeedi, P.; Karuranga, S.; Pinkepank, M.; Ogurtsova, K.; Duncan, B.B.; Stein, C.; Basit, A.; Chan, J.C.N.; Mbanya, J.C.; et al. IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045. Diabetes Res. Clin. Pract. 2022, 183, 109119.
Sarwar, N.; Gao, P.; Kondapally Seshasai, S.R.; Gobin, R.; Kaptoge, S.; Di Angelantonio, E.; Ingelsson, E.; Lawlor, D.A.; Selvin, E.; Stampfer, M.; et al. Diabetes Mellitus, Fasting Blood Glucose Concentration, and Risk of Vascular Disease: A Collaborative Meta-Analysis of 102 Prospective Studies. Lancet 2010, 375, 2215–2222.
Carey, I.M.; Critchley, J.A.; Dewilde, S.; Harris, T.; Hosking, F.J.; Cook, D.G. Risk of Infection in Type 1 and Type 2 Diabetes Compared with the General Population: A Matched Cohort Study. Diabetes Care 2018, 41, 513–521.
Hovind, P.; Tarnow, L.; Rossing, P.; Jensen, B.R.; Graae, M.; Torp, I.; Binder, C.; Parving, H.H. Predictors for the Development of Microalbuminuria and Macroalbuminuria in Patients with Type 1 Diabetes: Inception Cohort Study. Br. Med. J. 2004, 328, 1105–1108.
Samsu, N. Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed. Res. Int. 2021, 2021, 1497449.
Secrist, J.P.; Karnitz, L.; Abraham, R.T. T-Cell Antigen Receptor Ligation Induces Tyrosine Phosphorylation of Phospholipase C-Γ1. J. Biol. Chem. 1991, 266, 12135–12139.
Rhee, S.G.; Bae, Y.S. Regulation of Phosphoinositide-Specific Phospholipase C Isozymes. J. Biol. Chem. 1997, 272, 15045–15048.
Monick, M.M.; Carter, A.B.; Gudmundsson, G.; Mallampalli, R.; Powers, L.S.; Hunninghake, G.W. A Phosphatidylcholine-Specific Phospholipase C Regulates Activation of P42/44 Mitogen-Activated Protein Kinases in Lipopolysaccharide-Stimulated Human Alveolar Macrophages. J. Immunol. 1999, 162, 3005–3012.
Carman, G.M.; Han, G.S. Phosphatidic Acid Phosphatase, a Key Enzyme in the Regulation of Lipid Synthesis. J. Biol. Chem. 2009, 284, 2593–2597.
Carman, G.M.; Han, G.-S. Roles of Phosphatidate Phosphatase Enzymes in Lipid Metabolism. Trends Biochem. Sci. 2006, 31, 694–699.
Exton, J.H. Phospholipase D: Enzymology, Mechanisms of Regulation, and Function. Physiol. Rev. 1997, 77, 303–320.
Craven, P.A.; Davidson, C.M.; DeRubertis, F.R. Increase in Diacylglycerol Mass in Isolated Glomeruli by Glucose from de Novo Synthesis of Glycerolipids. Diabetes 1990, 39, 667–674.
Thorens, B.; Mueckler, M. Glucose Transporters in the 21st Century. Am. J. Physiol. Endocrinol. Metab. 2010, 298, 141–145.
Jiang, X.; Yang, F.; Brailoiu, E.; Jakubowski, H.; Dun, N.J.; Schafer, A.I.; Yang, X.; Durante, W.; Wang, H. Differential Regulation of Homocysteine Transport in Vascular Endothelial and Smooth Muscle Cells. Diabetes 1993, 42, 80–89.
Nishizuka, Y. Intracellular Signaling by Hydrolysis of Phospholipids and Activation of Protein Kinase, C. Science 1992, 258, 607–614.
Newton, A.C. Regulation of Protein Kinase, C. Curr. Opin. Cell Biol. 1997, 9, 161–167.
Ebinu, J.O.; Bottorff, D.A.; Chan, E.Y.W.; Stang, S.L.; Dunn, R.J.; Stone, J.C. RasGRP, a Ras Guanyl Nucleotide- Releasing Protein with Calcium- and Diacylglycerol-Binding Motifs. Science 1998, 280, 1082–1086.
Lucas, P.; Ukhanov, K.; Leinders-Zufall, T.; Zufall, F. A Diacylglycerol-Gated Cation Channel in Vomeronasal Neuron Dendrites Is Impaired in TRPC2 Mutant Mice: Mechanism of Pheromone Transduction. Neuron 2003, 40, 551–561.
Limatola, C.; Schaap, D.; Moolenaar, W.H.; van Blitterswijk, W.J. Phosphatidic Acid Activation of Protein Kinase C-Zeta Overexpressed in COS Cells: Comparison with Other Protein Kinase C Isotypes and Other Acidic Lipids. Biochem. J. 1994, 304, 1001–1008.
Jones, D.R.; Sanjuan, M.A.; Mérida, I. Type Iα Phosphatidylinositol 4-Phosphate 5-Kinase Is a Putative Target for Increased Intracellular Phosphatidic Acid. FEBS Lett. 2000, 476, 160–165.
Ghosh, S.; Strum, J.C.; Sciorra, V.A.; Daniel, L.; Bell, R.M. Raf-1 Kinase Possesses Distinct Binding Domains for Phosphatidylserine and Phosphatidic Acid: Phosphatidic Acid Regulates the Translocation of Raf-1 in 12-O-Tetradecanoylphorbol-13-Acetate-Stimulated Madin-Darby Canine Kidney Cells. J. Biol. Chem. 1996, 271, 8472–8480.
Fang, Y.; Vilella-Bach, M.; Bachmann, R.; Flanigan, A.; Chen, J. Phosphatidic Acid-Mediated Mitogenic Activation of MTOR Signaling. Science 2001, 294, 1942–1945.
Newton, A.C. Protein Kinase C: Perfectly Balanced. Crit. Rev. Biochem. Mol. Biol. 2018, 53, 208–230.
Parker, P.J.; Coussens, L.; Totty, N.; Rhee, L.; Young, S.; Chen, E.; Stabel, S.; Waterfield, M.D.; Ullrich, A. The Complete Primary Structure of Protein Kinase C—The Major Phorbol Ester Receptor. Science 1986, 233, 853–859.
Knopf, J.L.; Lee, M.H.; Sultzman, L.A.; Kriz, R.W.; Loomis, C.R.; Hewick, R.M.; Bell, R.M. Cloning and Expression of Multiple Protein Kinase C CDNAs. Cell 1986, 46, 491–502.
Ohno, S.; Akita, Y.; Konno, Y.; Imajoh, S.; Suzuki, K. A Novel Phorbol Ester Receptor/Protein Kinase, NPKC, Distantly Related to the Protein Kinase C Family. Cell 1988, 53, 731–741.
Ono, Y.; Fujii, T.; Ogita, K.; Kikkawa, U.; Igarashi, K.; Nishizuka, Y. The Structure, Expression, and Properties of Additional Members of the Protein Kinase C Family. J. Biol. Chem. 1988, 263, 6927–6932.
Nakanishi, H.; Exton, J.H. Purification and Characterization of the ζ Isoform of Protein Kinase C from Bovine Kidney. J. Biol. Chem. 1992, 267, 16347–16354.
Craven, P.A.; DeRubertis, F. Protein Kinase C Is Activated in Glomeruli from Streptozotocin Diabetic Rats. Possible Mediation by Glucose. J. Clin. Investig. 1989, 83, 1667–1675.
Inoguchi, T.; Battan, R.; Handler, E.; Sportsman, J.R.; Heath, W.; King, G.L. Preferential Elevation of Protein Kinase C Isoform Beta II and Diacylglycerol Levels in the Aorta and Heart of Diabetic Rats: Differential Reversibility to Glycemic Control by Islet Cell Transplantation. Proc. Natl. Acad. Sci. USA 1992, 89, 11059–11063.
Ayo, S.H.; Radnik, R.; Garoni, J.A.; Troyer, D.A.; Kreisberg, J.I. High Glucose Increases Diacylglycerol Mass and Activates Protein Kinase C in Mesangial Cell Cultures. Am. J. Physiol. Physiol. 1991, 261, F571–F577.
Koya, D.; King, G.L. Protein Kinase C Activation and the Development of Diabetic Complications. Diabetes 1998, 47, 859–866.
Menne, J.; Park, J.K.; Boehne, M.; Elger, M.; Lindschau, C.; Kirsch, T.; Meier, M.; Gueler, F.; Fiebeler, A.; Bahlmann, F.H.; et al. Diminished Loss of Proteoglycans and Lack of Albuminuria in Protein Kinase C-α-Deficient Diabetic Mice. Diabetes 2004, 53, 2101–2109.
Ohshiro, Y.; Ma, R.C.; Yasuda, Y.; Hiraoka-Yamamoto, J.; Clermont, A.C.; Isshiki, K.; Yagi, K.; Arikawa, E.; Kern, T.S.; King, G.L. Reduction of Diabetes-Induced Oxidative Stress, Fibrotic Cytokine Expression, and Renal Dysfunction in Protein Kinase Cβ-Null Mice. Diabetes 2006, 55, 3112–3120.
Tuttle, K.R.; Bakris, G.L.; Toto, R.D.; McGill, J.B.; Hu, K.; Anderson, P.W. The Effect of Ruboxistaurin on Nephropathy in Type 2 Diabetes. Diabetes Care 2005, 28, 2686–2690.
Shiba, T.; Inoguchi, T.; Sportsman, J.R.; Heath, W.F.; Bursell, S.; King, G.L. Correlation of Diacylglycerol Level and Protein Kinase C Activity in Rat Retina to Retinal Circulation. Am. J. Physiol. 1993, 265, E783–E793.
Derubertis, F.R.; Craven, P.A. Activation of Protein Kinase C in Glomerular Cells in Diabetes: Mechanisms and Potential Links to the Pathogenesis of Diabetic Glomerulopathy. Diabetes 1994, 43, 1–8.
Babazono, T.; Kapor-Drezgic, J.; Dlugosz, J.A.; Whiteside, C. Altered Expression and Subcellular Localization of Diacylglycerol- Sensitive Protein Kinase C Isoforms in Diabetic Rat Glomerular Cells. Diabetes 1998, 47, 668–676.
Chiarelli, F.; Gaspari, S.; Marcovecchio, M.L. Role of Growth Factors in Diabetic Kidney Disease. Horm. Metab. Res. 2009, 41, 585–593.
Reeves, W.B.; Andreoli, T.E. Transforming Growth Factor β Contributes to Progressive Diabetic Nephropathy. Proc. Natl. Acad. Sci. USA 2000, 97, 7667–7669.
Arora, M.K.; Singh, U.K. Molecular Mechanisms in the Pathogenesis of Diabetic Nephropathy: An Update. Vascul. Pharmacol. 2013, 58, 259–271.
Koya, D.; Jirousek, M.R.; Lin, Y.W.; Ishii, H.; Kuboki, K.; King, G.L. Characterization of Protein Kinase C β Isoform Activation on the Gene Expression of Transforming Growth Factor-β, Extracellular Matrix Components, and Prostanoids in the Glomeruli of Diabetic Rats. J. Clin. Investig. 1997, 100, 115–126.
Hayashida, T.; Schnaper, H.W. High Ambient Glucose Enhances Sensitivity to TGF-Β1 via Extracellular Signal-Regulated Kinase and Protein Kinase Cδ Activities in Human Mesangial Cells. J. Am. Soc. Nephrol. 2004, 15, 2032–2041.
Riser, B.L.; Denichilo, M.; Cortes, P.; Baker, C.; Grondin, J.M.; Yee, J.; Narins, R.G. Regulation of Connective Tissue Growth Factor Activity in Cultured Rat Mesangial Cells and Its Expression in Experimental Diabetic Glomerulosclerosis. J. Am. Soc. Nephrol. 2000, 11, 25–38.
Khamaisi, M.; Schrijvers, B.F.; De Vriese, A.S.; Raz, I.; Flyvbjerg, A. The Emerging Role of VEGF in Diabetic Kidney Disease. Nephrol. Dial. Transplant. 2003, 18, 1427–1430.
Hoshi, S.; Tomari, S.; Hoshi, S.; Nomoto, K.I.; Kuromitsu, J.; Nagata, M. High Glucose Induced VEGF Expression via PKC and ERK in Glomerular Podocytes. Biochem. Biophys. Res. Commun. 2002, 290, 177–184.
Xia, L.; Wang, H.; Munk, S.; Frecker, H.; Goldberg, H.J.; Fantus, I.G.; Whiteside, C.I. Reactive Oxygen Species, PKC-A1, and PKC-ζ Mediate High-Glucose-Induced Vascular Endothelial Growth Factor Expression in Mesangial Cells. Am. J. Physiol. Endocrinol. Metab. 2007, 293, 1280–1288.
Thallas-Bonke, V.; Thorpe, S.R.; Coughlan, M.T.; Fukami, K.; Yap, F.Y.T.; Sourris, K.C.; Penfold, S.A.; Bach, L.A.; Cooper, M.E.; Forbes, J.M. Inhibition of NADPH Oxidase Prevents Advanced Glycation End Product-Mediated Damage in Diabetic Nephropathy through a Protein Kinase C-α-Dependent Pathway. Diabetes 2008, 57, 460–469.
Ishii, H.; Jirousek, M.R.; Koya, D.; Takagi, C.; Xia, P.; Clermont, A.; Bursell, S.E.; Kern, T.S.; Ballas, L.M.; Heath, W.F.; et al. Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC β Inhibitor. Science 1996, 272, 728–731.
Koya, D.; Haneda, M.; Nakagawa, H.; Isshiki, K.; Sato, H.; Maeda, S.; Sugimoto, T.; Yasuda, H.; Kashiwagi, A.; Ways, D.K.; et al. Amelioration of Accelerated Diabetic Mesangial Expansion by Treatment with a PKC β Inhibitor in Diabetic Db/Db Mice, a Rodent Model for Type 2 Diabetes. FASEB J. 2000, 14, 439–447.
Sheetz, M.J.; Aiello, L.P.; Davis, M.D.; Danis, R.; Bek, T.; Cunha-Vaz, J.; Shahri, N.; Berg, P.H. The Effect of the Oral PKC β Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies. Investig. Ophthalmol. Vis. Sci. 2013, 54, 1750–1757.
Meier, M.; Park, J.K.; Overheu, D.; Kirsch, T.; Lindschau, C.; Gueler, F.; Leitges, M.; Menne, J.; Haller, H. Deletion of Protein Kinase C-β Isoform in Vivo Reduces Renal Hypertrophy but Not Albuminuria in the Streptozotocin-Induced Diabetic Mouse Model. Diabetes 2007, 56, 346–354.
Kanoh, H.; Yamada, K.; Sakane, F. Diacylglycerol Kinase: A Key Modulator of Signal Transduction? Trends Biochem. Sci. 1990, 15, 47–50.
Sakane, F.; Imai, S.I.; Kai, M.; Yasuda, S.; Kanoh, H. Diacylglycerol Kinases: Why so Many of Them? Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2007, 1771, 793–806.
Topham, M.K.; Prescott, S.M. Mammalian diacylglycerol kinases, a Family of Lipid Kinases with Signaling Functions. J. Biol. Chem. 1999, 274, 11447–11450.
Van Blitterswijk, W.J.; Houssa, B. Properties and Functions of Diacylglycerol Kinases. Cell. Signal. 2000, 12, 595–605.
Kanoh, H.; Yamada, K.; Sakane, F. Diacylglycerol Kinases: Emerging Downstream Regulators in Cell Signaling Systems. J. Biochem. 2002, 131, 629–633.
Sakane, F.; Yamada, K.; Kanoh, H.; Yokoyama, C.; Tanabe, T. Porcine Diacylglycerol Kinase Sequence Has Zinc Finger and E-F Hand Motifs. Nature 1990, 344, 345–348.
Klauck, T.M.; Xu, X.; Mousseau, B.; Jaken, S. Cloning and Characterization of a Glucocorticoid-Induced Diacylglycerol Kinase. J. Biol. Chem. 1996, 271, 19781–19788.
Letwin, K.; Yee, S.P.; Pawson, T. Novel Protein-Tyrosine Kinase CDNAs Related to Fps/Fes and Eph Cloned Using Anti-Phosphotyrosine Antibody. Oncogene 1988, 3, 621–627.
Imai, S.; Kai, M.; Yasuda, S.; Kanoh, H.; Sakane, F. Identification and Characterization of a Novel Human Type II Diacylglycerol Kinase, DGK Kappa. J. Biol. Chem. 2005, 280, 39870–39881.
Tang, W.; Bunting, M.; Zimmerman, G.A.; McIntyre, T.M.; Prescott, S.M. Molecular Cloning of a Novel Human Diacylglycerol Kinase Highly Selective for Arachidonate-Containing Substrates. J. Biol. Chem. 1996, 271, 10237–10241.
Bunting, M.; Tang, W.; Zimmerman, G.A.; McIntyre, T.M.; Prescott, S.M. Molecular Cloning and Characterization of a Novel Human Diacylglycerol Kinase Zeta. J. Biol. Chem. 1996, 271, 10230–10236.
Goto, K.; Kondo, H. A 104-KDa Diacylglycerol Kinase Containing Ankyrin-like Repeats Localizes in the Cell Nucleus. Proc. Natl. Acad. Sci. USA 1996, 93, 11196–11201.
Ding, L.; Traer, E.; McIntyre, T.M.; Zimmerman, G.A.; Prescott, S.M. The Cloning and Characterization of a Novel Human Diacylglycerol Kinase, DGKiota. J. Biol. Chem. 1998, 273, 32746–32752.
Houssa, B.; Schaap, D.; Van Der Wal, J.; Goto, K.; Kondo, H.; Yamakawa, A.; Shibata, M.; Takenawa, T.; Van Blitterswijk, W.J. Cloning of a Novel Human Diacylglycerol Kinase (DGKθ) Containing Three Cysteine-Rich Domains, a Proline-Rich Region, and a Pleckstrin Homology Domain with an Overlapping Ras-Associating Domain. J. Biol. Chem. 1997, 272, 10422–10428.
Rigotti, A. Absorption, Transport, and Tissue Delivery of Vitamin E. Mol. Asp. Med. 2007, 28, 423–436.
Traber, M.G.; Atkinson, J. Vitamin E, Antioxidant and Nothing More. Free Radic. Biol. Med. 2007, 43, 4–15.
Koya, D.; Lee, I.K.; Ishii, H.; Kanoh, H.; King, G.L. Prevention of Glomerular Dysfunction in Diabetic Rats by Treatment with D-Alpha-Tocopherol. J. Am. Soc. Nephrol. 1997, 8, 426–435.
Tada, H.; Ishii, H.; Isogai, S. Protective Effect of D-α-Tocopherol on the Function of Human Mesangial Cells Exposed to High Glucose Concentrations. Metabolism 1997, 46, 779–784.
Kakehi, T.; Yagi, K.; Saito, N.; Shirai, Y. Effects of Vitamin E and Its Derivatives on Diabetic Nephropathy in Rats and Identification of Diacylglycerol Kinase Subtype Involved in the Improvement of Diabetic Nephropathy. Funct. Foods Health Dis. 2017, 7, 816–832.
Shirai, Y.; Segawa, S.; Kuriyama, M.; Goto, K.; Sakai, N.; Naoaki, S. Subtype-Specific Translocation of Diacylglycerol Kinase α and γ and Its Correlation with Protein Kinase C. J. Biol. Chem. 2000, 275, 24760–24766.
Fukunaga-Takenaka, R.; Shirai, Y.; Yagi, K.; Adachi, N.; Sakai, N.; Merino, E.; Merida, I.; Saito, N. Importance of Chroman Ring and Tyrosine Phosphorylation in the Subtype-Specific Translocation and Activation of Diacylglycerol Kinase α by D-α-Tocopherol. Genes Cells 2005, 10, 311–319.
Tasinato, A.; Boscoboinik, D.; Bartoli, G.M.; Maroni, P.; Azzi, A. D-α-Tocopherol Inhibition of Vascular Smooth Muscle Cell Proliferation Occurs at Physiological Concentrations, Correlates with Protein Kinase C Inhibition, and Is Independent of Its Antioxidant Properties. Proc. Natl. Acad. Sci. USA 1995, 92, 12190–12194.
Pryor, W.A.; Cornicelli, J.A.; Devall, L.J.; Tait, B.; Trivedi, B.K.; Witiak, D.T.; Wu, M. A Rapid Screening Test To Determine the Antioxidant Potencies of Natural and Synthetic Antioxidants. J. Org. Chem. 1993, 58, 3521–3532.
Atsumi, H.; Kitada, M.; Kanasaki, K.; Koya, D. Reversal of Redox-Dependent Inhibition of Diacylglycerol Kinase by Antioxidants in Mesangial Cells Exposed to High Glucose. Mol. Med. Rep. 2011, 4, 923–927.
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)


Central Bedfordshire Council is supporting the Bedfordshire based charity, The Road Victims Trust through its new car parking contract with JustPark.
The Road Victims Trust (RVT) provide free emotional and practical support to all persons affected by a road death across Bedfordshire, Cambridgeshire and Hertfordshire. Each year the Trust supports in excess of 550 people who have been affected by the 80-85 deaths that occur on the roads of the 3 counties.
RVT Ambassador, Kate Goldsmith, whose 11 years old daughter Aimee was killed in a road collision alongside her step-brothers Ethan, Josh and their mother Tracey Houghton, is pictured with Cllr Budge Wells, Deputy Executive Member for Community Services at Central Bedfordshire Council.
The 8 carparks involved in the scheme include Grove Park, Matthew Street, Priory Gardens, Regent Street, and St Marys Gate in Dunstable and Duncombe Drive and Hockliffe Street in Leighton Buzzard.


This week, Ness is back!
And we are talking about what it's really like to run 100km. We talk about how she felt going into it after her last (very) long run, how she felt going into such an epic run, support crew shenanigans and would she do it again?
You can follow Ness on facebook and instagram. And you can check out her interview on Sparta Chicks Radio too!
And I had a bit of surprise news this week too!
It's been a huge week! And I talk a bit about some of the exciting things that have been happening in Operation Move land. But if you want to skip to the juicy bit you can do that here.
It was pretty incredible to be honoured by some of the women that I admire the most and to be put forward for that honour by the most amazing women I know.


text:
No mask requirement planned in Wood County after state Supreme Court strikes down governor's order
Alan Hovorka
Wisconsin Rapids Daily Tribune
WISCONSIN RAPIDS - Officials in the Wood County area have no immediate plans to impose a local mask mandate.
Wood County Health Director Sue Kunferman said her office does not plan to issue a local emergency order requiring face coverings after the Wisconsin Supreme Court ended Gov. Tony Evers's statewide mask mandate on Wednesday. The court's conservative majority ruled 4-3 to block the governor from issuing further emergency orders on masks amid the COVID-19 pandemic. The ruling requires Evers to seek approval from state Legislature on future mandates.
The court's action does not prevent local governments from pursuing their own local health emergency orders.
Kunferman said in an email that the county's goal continues to be seeking voluntary compliance through public education.
"We do not have plans to institute a mask order in Wood County. We hope to continue to educate the public on the value of wearing face coverings and continuing to take precautions," she wrote. "The pandemic is not over."
The ruling came a day after the governor announced anyone 16 years or older will be eligible for the COVID-19 vaccine next week.
RELATED:Local mask mandates possible in Portage County, Stevens Point as state court throws out Evers order
RELATED:Wisconsin Supreme Court overturns statewide mask mandate, blocks Evers from declaring multiple emergency orders
Wisconsin Rapids Mayor Shane Blaser said neither he nor the City Council have talked about enacting a local mask order.
"My opinion as of right now sitting in my office just because there's not a mask order for wearing a mask doesn't preclude people who want to wear mask from wearing a mask," he said.
Blaser said he's not sure how a local order would be enforceable, as the city has no city health department. Wood County handles health inspections and other work for the city. He said he planned to speak with the city attorney about the matter but said a local order was unlikely with the end of the pandemic in sight.
Questions on what the city of Marshfield might do in response to the state Supreme Court's ruling were not returned Wednesday. Elsewhere in central Wisconsin, Stevens Point and Portage County are considering imposing their own mask requirements while Wausau will consider extending its existing mask advisory.
Blaser said a local order would be unlikely to change anyone's minds on wearing a mask a year into the pandemic. People have already decided how they're going to respond to the virus.
"They choose to wear a mask more so because of their personal beliefs and because that's what they're comfortable doing," he said. "Out of respect for others, I'm going to keep wearing it."
Allison Garfield contributed to this report.
Contact reporter Alan Hovorka at 715-345-2252 or ahovorka@gannett.com. Follow him on Twitter at @ajhovorka.

redpajama_set_name: RedPajamaCommonCrawl


For this 3 Months forecast the algorithm had successfully predicted 8 out of 10 movements. The highest trade return came from GNCMA, at 76.66%. The suggested trades for IMGN and ATRS also had notable 3 Months yields of 26.56% and 26.51%, respectively. The overall average return in this Insiders Stocks package was 18.46%, providing investors with a 15.18% premium over the S&P 500's return of 3.28% during the same period.


text:
Thursday April 15th, 2021 Friday November 5th, 2021 chenxiang
We seek to understand and explore the emerging energy storage. We are interested into both the fundamental science and the large-scale engineering applications. We aim to build better energy storage towards a green and wireless world. Our current research interests focus on non-aqueous electrolyte and interfacial chemistry, lithium-sulfur batteries, solid-state batteries, fast-charge Li-ion batteries, electrocatalysis, theoretical simulations, and machine-learning assisted material design.
Prof. Qiang Zhang is now a tenured professor in Tsinghua University, China. He held the Newton Advanced Fellowship from Royal Society, UK and the National Science Fund for Distinguished Young Scholars. He is a highly cited researcher (2017-2019, Clarivate) with more than 30,000 citations. He is an invited/adjudicative referee for Nat. Energy, Nat. Nanotechnol., Nat. Catal., Sci. Adv., JACS, Adv. Mater. Angew. Chem. Int. Ed., and so on. He is editor of Journal of Energy Chemistry.
To learn more information about Prof. Qiang Zhang, please refer to the websites below:
https://scholar.google.com/citations?user=qkcc0OYAAAAJ&hl=en
https://publons.com/researcher/1308120/qiang-zhang/
We are now seeking applications for postdoctoral positions from around the world. Research themes include: non-aqueous electrolyte and interfacial chemistry, lithium-sulfur batteries, solid-state batteries, fast-charge Li-ion batteries, electrocatalysis, and theoretical modelling and simulations. We welcome junior scholars who are committed to academic research and who are brave for innovation to join the group.
Applicants must fulfill the following requirements:
1) Applicants must have a PhD degree.
2) Under 35 years old; PhD degree is obtained within the last 3 years; fresh graduates are given priority in consideration.
3) Must work full time at Tsinghua University after entering Tsinghua University.
4) Strong sense of cooperation, good organization and coordination ability.
5) Good English writing and communication skills.
1) Salary is commensurate with qualifications and experience, compliant with policies for postdoctoral recruitment. The basic policies and application process of the postdoctoral in Tsinghua University can be found in the following website: http://postdoctor.tsinghua.edu.cn/bsh/index.jsp. We also provide opportunities for overseas conference/cooperation. The treatment of outstanding people and work arrangements after leaving the station can be discussed in person.
2) The outstanding applicants will be supported to apply the Shuimu Tsinghua Scholar Program. To attract excellent junior scholars to do research in Tsinghua University, support their academic career, and educate leading researchers in various fields, Tsinghua University has set up the "Shuimu Tsinghua Scholar Program". The annual salary is 300,000 RMB before tax for two years. Shuimu Scholars will be provided with transitional housing on the campus or provided with housing subsidies of 42,000 RMB per year, state-funded housing subsidies of 1,2000 RMB per year, as well as subsidies for property management and heating. For more details: http://postdoctor.tsinghua.edu.cn/info/zxtz/1777
Candidates will be interviewed in terms of their academic ability, their research plan, and the potential effect on the subject field, etc. Please send the application materials to the email of Prof. Qiang Zhang.
1) Curriculum vitae, including the education and research experience to date.
2) Research plan during the postdoctoral.
3) Academic and scientific research materials (a scanned original in PDF format). Articles, monographs, patents or awards representing the applicant's highest academic level and scientific research achievements. Among them: full text is provided for articles (Accept letters should be provided for unpublished papers); cover, catalogue and abstract are provided for monographs; copies of certificates are provided for patents or awards.
4) 2-3 letters of recommendation (including PhD advisor's recommendation letter) should be sent by recommenders directly to the department's mail address. If the recommendation letter is sent as an attachment, it must be signed by the recommender (sender).
Prof. Dr. Qiang ZHANG
Department of Chemical Engineering, Tsinghua University
Tsinghua Road, Beijing 100084, P.R. China
E-mail: zhang-qiang@mails.tsinghua.edu.cn
Here,
You will find a brand-new start to your independent academic career,
And you will be nourished by the culture of this top-tiered university in the world.
Welcome to the family of Prof. Qiang Zhang group. Building better energy storage for world! *This recruitment is valid for a long time.
Next Next post: Recruitment for Research Staff


The One Month Enterprise Architecture - Realising the Impossible through Enterprise Anatomy In this Keynote, Krish will take us through a week by week approach to solving Business Problems using Enterprise Anatomy - a new concept. Key Takeaways are - Better understanding of what is Enterprise Architecture and how to apply it in your organisations to improve Business Agility.
Effective Strategies to Improve Utilization of EA?
After much deliberations, EA team is set up and they start the work with taking stock of IT inventories. Sometimes it's portfolio rationalization or IT-driven transformation. How to realize the true value of Enterprise Architecture beyond one or two projects?
Economical Insurance, one of Canada's leading property and casualty insurance companies, is making it easier than ever for brokers to match customers with the right insurance coverage with the launch of Vyne. Rolling out beginning June 2018 through to the end of the year, Vyne was built on an industry-leading architecture, leveraging existing Guidewire platforms and analytics. Vyne strengthens Economical's commitment to the broker channel by providing faster service, streamlined workflows, and customer-centric products and pricing.
The IA Baseline was created for the benefit of all ministries within CAC, to serve as a guide for future application integration and business intelligence solution opportunities.The business solution opportunities aid businesses of a common nature (i.e. Government Decision Making, Budgeting & Finances, Taxation, Benefits, and Procurement) by providing enterprise-wide reusable common components.
SFO's strategic objective is to transform its current operational model towards a service driven digital enterprise with a target operating model that empowers a digital workforce with information-driven tools and capabilities for supporting operational functions throughout the enterprise. The power of digital convergence delivered through AIIS provides the path to achieve this strategic objective by bringing real-time decision making insights into the hands of SFO's staff, business partners and ultimately to passengers through brokered information services.
The architecture will allow our enterprise to build the Family of Robots with optimized architecture for cost-effectiveness. RaDa is running in Vistara lounge (Delhi airport) from 5th July is arguably most cost-effective and first of its kind robot which is deployed commercially. The number of such Robots will carry out repetitive functions at airport mainly check-In, boarding pass scanning, entertainment, baggage carrier, customer assistance.
Leveraging the "One National Airport APP" built on digital platform all the ecosystems involved with Airports are connected, including the passengers, airports, airlines and other sub-systems. Thus, brings in hassle free travel closer to reality with optimized operations, increased operational efficiency, improved passenger experience and increased non – aeronautical revenue.
How to identify the key stakeholders, what questions to ask, how to define the business goals and the technology goals, tools, and technology selection, Team members and the differentiators, timeline and change plan?


Situated within Hanoi's new Center Business District (CBD), Mulberry Lane can be conveniently accessed via the main road To Huu (extended Le Van Luong road). Besides, the project is located on the main route to Noi Bai Airport. New modern infrastructure scheduled to complete in the near future such as the sky train to be launched in 2017 will create a convenient link between old and new CBD of Hanoi.
Mulberry Lane is also surrounded by a variety of public amenities such as hospitals, supermarkets, secondary schools, high schools and many reputable universities in Hanoi.


Some of these materials are metals, foam, wood, plastic and vinyl. Choosing the correct material and style for your project is very important Metal dimensional letters can often times convey a sense of integrity and permanence to customers. Plastic and foam letters are easily customized and do an excellent job of identification.
You can rest assured that our experts at SIGNARAMA will tailor what lettering you need to your needs.


text:
An Internet Humanist community
About iHumanism
© 2020 iHumanism
The 10 Points of Humanism: A Definition
How can someone find out if they may be a Humanist? That question is one that is asked frequently. I offer a selection from Corliss Lamont's book 'The Philosophy of Humanism'. I think he sets out some good principles as to what Humanism is about. It isn't just about being a humanitarian.
Post categories In Intro to Humanism
Cover to the 8th Edition of The Philosophy of Humanism
How can someone find out if they may be a Humanist? That question is one that is asked frequently. I gave a simple definition on the introduction to this section but for those who wish to have a more detailed explanation of what makes up the Humanist philosophy, I offer a selection from Corliss Lamont's book The Philosophy of Humanism. I think he sets out good points as to what Humanism is about.
First, Humanism believes in a naturalistic metaphysics or attitude toward the universe that considers all forms of the supernatural as myth; and that regards Nature as the totality of being and as a constantly changing system of matter and energy which exists independently of any mind or consciousness.
Second, Humanism, drawing especially upon the laws and facts of science, believes that we human beings are an evolutionary product of the Nature of which we are a part; that the mind is indivisibly conjoined with the functioning of the brain; and that as an inseparable unity of body and personality we can have no conscious survival after death.
Third, Humanism, having its ultimate faith in humankind, believes that human beings possess the power or potentiality of solving their own problems, through reliance primarily upon reason and scientific method applied with courage and vision.
Fourth, Humanism, in opposition to all theories of universal determinism, fatalism, or predestination, believes that human beings, while conditioned by the past, possess genuine freedom of creative choice and action, and are, within certain objective limits, the shapers of their own destiny.
Fifth, Humanism believes in an ethics or morality that grounds all human values in this-earthly experiences and relationships and that holds as its highest goal the this-worldly happiness, freedom, and progress?economic, cultural, and ethical of all humankind, irrespective of nation, race, or religion.
Sixth, Humanism believes that the individual attains the good life by harmoniously combining personal satisfactions and continuous self-development with significant work and other activities that contribute to the welfare of the community.
Seventh, Humanism believes in the widest possible development of art and the awareness of beauty, including the appreciation of Nature?s loveliness and splendor, so that the aesthetic experience may become a pervasive reality in the lives of all people.
Eighth, Humanism believes in a far-reaching social program that stands for the establishment throughout the world of democracy, peace, and a high standard of living on the foundations of a flourishing economic order, both national and international.
Ninth, Humanism believes in the complete social implementation of reason and scientific method; and thereby in democratic procedures, and parliamentary government, with full freedom of expression and civil liberties, throughout all areas of economic, political, and cultural life.
Tenth, Humanism, in accordance with the scientific method, believes in the unending questioning of basic assumptions and convictions, including its own. Humanism is not a new dogma, but is a developing philosophy ever open to experimental testing, newly discovered facts, and more rigorous reasoning.
*From "The Philosophy of Humanism" – 8th edition by Corliss Lamont pps 13-15
Humanism Can Be A Vehicle For Change
Crowdsourced Commandments Fit Humanism
Humanism Has A Broad Purpose
Tags Corliss Lamont, non-theism, philosophy, principles
←Previous post:Animal Rights, Anthropomorphism, and Traumatized Fish
→Next post:The Roots of Humanism
secularleft says:
RT @ihumanism: The 10 Points of Humanism: A Definition http://t.co/W9mhi4eCxb #p2 #tcot #nontheism
cadfile says:
religious humanism honesty religious freedom religious bigotry racism social justice principles civil rights American Humanist Association religious discrimination church and state 1st amendment secular humanism freethought debate group politics groups atheism civil liberties blasphemy


Composed between 1984 and 2016, this selection of poems is loosely based on the theme ofvoyaging. Part 1 deals with the inward journey: part 2 was inspired by the poet's journeys through Asia and North Africa. The journey of human life is itself a pilgrimage; a journey beginning at birth and proceeding through to our final breath. Rumi Weeds takes the reader on an insightful journey from the inner to the outer, from birth to death..
He remains a visiting professor in the Centre for the Study of Islam in Britain based at the University of Cardiff. In 1994 he published the biography of Abdullah Quilliam, the iconic British convert to Islam who founded the first mosque and Islamic centre in Liverpool in 1893.


Hi and thanks for the forum. I desperately trying to find a replacement NS driveshaft for my old 2006 Corsa. The sellers I've contacted thus far say the SXI has a different shaft and they don't do it.
I spoke with AUTODOC - online car parts store with over 1 million auto parts for two hours (yer really) in a webchat and I wasn't convinced that they provided me with any useful info. I suspect I might need to measure the shaft but that isn't really practical. Any suggestions on how I might establish what is fitter to this car ? Thanks in advance.
I use J&R Driveshafts in the Midlands. You could give them a ring .
Thanks - I tried them and they couldn't help I'm afraid. Thank you though.
Can you post you vin number? I've had a quick look on vauxhll epc and there seems to some variants, depends on vin number.
It looks like they should have id stamps on the shaft and going by the vin allocation I'd say yours should be the later GKN.
I've had a look on gsf and eurocarparts, they only do the later GKN. You could always use these and if it is wrong you can take it back. If you do use these, order online using the discount codes.
Thank you so much ! So you think it's likely the OEM is 24427062 ?
I reckon so, shame gsf and ecp don't do both versions, you could have got the two then took the wrong one back (I've done that a few times).
Thank you ! I've searched for 24427062 on ECP website and it doesn't come up ?
I've just googled GM24427062 .Not many hits . Found a german site, that appeared to order from opel, but the price was about 750 euro!
Some were listing the part as 24427062 but others listed it as GKN 304400 or SPIDAN 24052 (an aftermarket maker?) You could try searching under those numbers.
But they also listed various bearings and parts for rebuilding half shafts. That might be the way to go. See if a specialist can rebuild it. Or you might be able to get the bearings,shells and bits and do it yourself. You might be able to get them from GKN .
Or investigate what the differences are. You might be able fit a cheaper more readily available shaft by changing bits on the car, or by fitting bits from the old shaft onto a different spec shaft. There are, or were, specialists who could lengthen and shorten prop shafts ,then weld and balance them. They may be able to do it with dive shafts and make you a hybrid.
Last edited by Bugman; 09-02-2019, 07:54 AM.
Try the second number 374442 for that part. Parts catalogues often have two different part numbers, the actual manufacturer of the part's number and the car manufacturers own allocated number for that part.
When it comes to the likes of eurocarparts or gsf they don't use either of these numbers, they go by your registration number and if there are variants they will use VIN numbers 'to' and 'from' and also engine code numbers.
Both ecp and gsf are £52 ish after the dscount codes.
Thanks. I'm still a bit confused. As you say both shafts epc list are chasis numbers from.
The last 8 of my chasis no. starts with 6 and on your pictures and epc it starts with 2.
By this logic it's obviously over 2 but I'm concerned that no other big shaft sellers do this shaft and epc do.
I guess I'll just have to take a punt and hope for the best. Many thanks once again.
Thank you. I may have to go down the route of rebuilding the shaft.
Just so happens I was changing a valve cover gasket and an 02 sensor on a Corsa C this morning, I checked the drveshafts to see if there were any stamps but found a sticky label (drivers side) hanging on by a thread, it has a 'PG' on it plus a bar code. Have you checked yours? This was a 2003 car so wth a little luck you might still have them on there.
Thank you - I'll have a look and see if the label is still there !


Awesome! I love these....particularly that fab necklace and those beautiful vases!
I love the Creole Top! I'm going to look at her stuff right now. lol.
I am so loving that blouse! Etsy is dangerous... and so are bloggers like you that point out these things!
What a sweet collection of pretties this is!
what an awesome quartet. i love all four.
That,s marvelous specially vases that look pretty decent.
thanks marichelle, you always assemble the prettiest posts!
wow. the gilded necklace made from a mix of vintage chains is so clever!!
pretty decent look specially Gilded Era Necklace and Vases is so cool.


Marijuana is a wonderful herb that grows naturally all over the planet. Unfortunately it is still illegal to grow marijuana in many countries. Please check your local laws before growing marijuana. With that said, let's get growing!
Since you have chosen to grow with hydroponics (nice choice) it is important understand nutrients. There are several brands of nutrients to choose from. General Hydroponics is a great economical choice but if you can splurge a little bit pick up a Fox Farm system. Regardless of your nutrient choice, to grow marijuana you need to provide your plants with the right nutrients during the right cycles. Don't feel intimidated, nutrients are easy to measure and add with a PPM meter so you should always be confident in knowing your plants have what they need. If you don't already have a PPM meter hit up your local hydro shop or order one online. They cost around and they measure the parts per million of total nutrients. With one of these meters you can keep your plants well fed and happy.
During the vegetative state your plants are going to be craving a lot of nitrogen. Nitrogen is a basic building block and helps the plant to establish a strong root system and a strong core. The vegetative cycle can vary but typically lasts 6-8 weeks. For the first 5 days of your plants life don't even bother adding nutrients. At any given time, too many nutrients will cause leaves to burn and plants to go into nutrient lock, making it impossible for them to get any nourishment. Add a small amount of your stage 1 nutrients to the hydro tank for the first 2 weeks. Your PPM should stay a steady 50-150. Keep increasing the nutrient intake by 50-100 per week. You can feed your plants until you notice discoloration of leaves, at which point you should dilute your nutrient base. As you approach 6-8 week you will be adding more of the stage 2 nutrients. During the transitional phase plants need more phosphates. This helps them get ready for flowering. When you make the switch from 24 hour lighting to 12 hours on and 12 off, you need to change the flow of nutrients again. By this point your plants are ready for a steady dose of potassium. Your stage 3 nutrients should be administered at around 1000 PPMs to start with. Increase the dose by 50-100 per week and your flowering cycle will conclude in 8-11 weeks. The last two weeks of your flowering cycle change your basin to only purified water. Too many nutrients down the home stretch will give your bud a funky chemical flavor and diminish your smoking experience with harsh hits. The last 3-5 days of flowering your should pull the water out altogether. Since you are about to embark on the curing process, the water that is filling your plant is no longer necessary.
Always track your PPMs on a notepad for record and change your water at least weekly to avoid any algae growth. If your plant's leaves start yellowing or burning, adjust your nutrients accordingly. When properly administered, nutrients will plump up your plants and they will erupt with luscious buds.
Check your room temperature and make sure your light source isn't to close if it is hot. You should also be testing and balancing the pH of you water. Never over-fertilize either. Hope this helps.


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Proposed Legislation on Statute of Repose: Clarifying that the Statute Runs from Completion of Performance
by Christie Bredahl
As Florida's 2016 Legislative Session approaches, two companion bills have been introduced – Senate Bill ("SB") 316 and House Bill ("HB") 297. These bills seek to address the interpretation and application of the statute of repose set forth in § 95.11(3)(c), Florida Statutes. Intended to impose finality on the availability of claims for latent defects, the statute of repose imposes a ten-year expiration date on actions founded upon the design, planning, or construction of improvements to real property. Per the statute, the ten-year expiration date begins to run from the latter of the following events:
Actual possession of the improvement by the owner;
Issuance of a Certificate of Occupancy;
Abandonment of the construction, if not completed; or
Completion or termination of the contract between the professional engineer, registered architect, or licensed contractor and his or her employer.
SB 316 and HB 297 were introduced as a direct response to the Fifth District Court of Appeal's decision in Cypress Fairway Condominium Association, Inc. v. Bergeron Construction Co., Inc., 164 So. 3d 706 (Fla. 5th DCA 2015).
In Cypress Fairway, the Fifth District reviewed a trial court's order granting summary judgment on the basis that the construction defect claims were barred by the statute of repose. In its order, the trial court concluded that, based upon the preamble to § 95.11(3)(c), Florida Statutes, the Legislature intended that the term "completion of the contract" "had to do with the date of completion of the construction that would have been done under the contract, not the date of final payment." Cypress Fairway, 164 So. 3d at 708. Accordingly, the trial court determined that the plaintiff's claims were time-barred by the statute of repose because the claims were filed ten years after the completion of the construction project.
On appeal, however, the Fifth District concluded that the trial court erred by relying on the preamble to interpret the meaning of § 95.11(3)(c), Florida Statutes, because the statutory language was clear and unambiguous. The Fifth District stated that "[h]ad the legislature intended the statute to run from the time the contractor completed performance, it could have simply so stated." (For further information on the Cypress Fairway decision, please see our prior post).
In response to the Cypress Fairway decision, Senator Kelli Stargel (District 15) introduced SB316 and Representatives Keith W. Perry (District 21) and Jay Fant (District 15) introduced HB297. The bills propose an amendment to § 95.11(3)(c), Florida Statutes, that plainly defines when a contract is considered "complete." Specifically, the bills propose the addition of the following language:
The date of completion of the contract between the professional engineer, registered architect, or licensed contractor and his or her employer is the last day during which the professional engineer, registered architect, or licensed contractor furnishes labor, services, or materials, excluding labor, services, or materials relating to the correction of deficiencies in previously performed work or materials supplied.
This proposed language seeks to confirm the interpretation offered by the trial court in Cypress Fairway as to when a contract is deemed complete—i.e., when the work that is the subject of the contract has been fully performed as opposed to the date final payment is tendered under the contract. CSK will continue to monitor SB 316 and HB 297 as they progress through the 2016 Legislative Session. In the meantime, if you have any questions about the bills or how they may impact particular claims, please contact David Harrigan at david.harrigan@csklegal.com or (321) 972-0014, or Christie Bredahl at christie.bredahl@csklegal.com or (321) 972-0025.


Honorary Chair to the International Salute to Dr. Martin Luther King, Jnr.
Young Humanitarian of the Year - Mode Men Magazine.
Patron of Nigeria's National Heritage - In recognition of unrelenting effort and support for various causes through corporate social responsibility in Nigeria.
Award of Excellence - Global Initiative for Peace, Love and Care (GIPLC).
Young Entrepreneur of the Year - Mode Men Magazine.
Male Entrepreneur of the Year - Federal Capital Territory Business Excellence Awards, organized by the Abuja Enterprise Agency (AEA), Department of International Development (DFID) and the Federal Capital Territory Administration.


The UAB Strategic Planning Council includes representatives from all campus stakeholder groups.
Representing: School of Medicine Suzanne Austin, Ph.D.
Representing: Office of the Provost Christopher Brown, Ph.D.
Representing: Athletics Josh Carpenter, Ph.D.
Representing: Office of Diversity, Equity and Inclusion Alecia Gross, Ph.D.
Representing: Staff John Jones, Ph.D.
Representing: Faculty Kathy Nugent, Ph.D.
Representing: College of Arts and Sciences David Randall, Ph.D.


I was recently happy to have good news: last week, the WSU English Department graduate students gave me the "Most Supportive Faculty Member" award (which particularly delights me in that they're amazing people with whom to work). Yesterday I learned that I'd won a teaching grant. And I'll brag about my wife too: Lauralea today received an invitation to give a keynote address at a professional conference. We are apparently doing some good things professionally, and those good things seem to sometimes intersect: we'll both be presenting about quantitative rhetorics and research at Feminisms & Rhetorics in the fall, as well.
I'm kind of amazed, even though I know I shouldn't be, to work with students who have such goodwill and creativity. The projects above reflect some of the best aspects of what I consider to be excellent multimodal collaborative scholarship.
And today, in class, we concluded with the intersections of James Gleick's The Information, Marshall McLuhan, "The Library of Babel," smartphone dating, big data, Robert Burton's Anatomy of Melancholy, and the Skyrim/Valve paid mods user revolt. A good end to a good semester.


The ECMC Network is made up of Centres across the UK - both adult and paediatric - and is dedicated to supporting pioneering, early-stage clinical trials and translation of scientific discoveries into new cancer treatments for patients. Here you can filter by expertise to find out more about the work of each of our ECMCs.
The ECMC Network aims to act as an efficient and effective network that will assist in the delivery of early phase cancer studies between research partners to enable faster and more personalised patient benefit. There are 18 Adult Centres.
The Paediatric Network works in partnership to enable study recruitment, including pharmacokinetic, pharmacodynamics, biomarker and imaging studies, to facilitate to development of targeted therapies and improve the outcome for high risk childhood cancers.
The trials that are presently being carried out throughout the ECMC Network are listed here. The Network is constantly looking for help in speeding up patient recruitment through referrals and/or openings at additional sites.


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Last year we presented an exclusive look into the New England studio of printmaker and fine artist Daniel Danger (seen here). With Danger's solo show at Tara McPherson's Cotton Candy Machine Gallery in Brooklyn just around the corner, Hi-Fructose is excited to get a glimpse at a few of the new screen prints and original works that will be debuting this weekend. In addition the works shown after the jump, Danger will also be bringing selected past works including figures, gig posters and records. It all goes down tomorrow Friday, July 8th and the show will be on view until the 31st.


text:
Muriel Bowser poised to net allies on D.C. council in special election
Wards 4 and 8 to vote
Ward 8 Democrats
Brandon Todd
Muriel Bowser
Brandon Todd more >
By Andrea Noble - The Washington Times - Sunday, April 26, 2015
Voters in Wards 4 and 8 will head to the polls Tuesday to choose new lawmakers in special elections that could win the District's mayor crucial allies on the D.C. Council.
Eleven candidates are vying for council seats in each election — the Ward 4 seat was left vacant when D.C. Mayor Muriel Bowser took office in January and the Ward 8 seat when longtime political powerhouse Marion Barry died in November.
Bowser-backed candidates hold significant advantages in both races, making it likely that the new mayor will acquire support among the 13-member D.C. Council as she pursues her first-year agenda.
Ward 4 candidate Brandon Todd, who previously worked as Ms. Bowser's constituent services director, has raised more than $360,000 in his bid, in part by raking in funds from donors who also have contributed to Ms. Bowser. With more than $160,000 on hand as of April 20, Mr. Todd entered the home stretch of the race with the most money to spend.
Ward 8 candidate LaRuby May, who served as Ms. Bowser's Ward 8 coordinator in last year's mayoral campaign, has similarly benefited from donors. Ms. May has outraised all of her competitors, bringing in nearly $270,000. While she had also $40,000 in the bank as of an April 20 campaign finance report, that was still more than double what her closest competitor has on hand to spend.
The Ward 8 race has centered on questions of who can authentically carry on Barry's brand of leadership and whether a council member closely aligned with the mayor would be in residents' best interest.
In the last month, two candidates dropped out of the Ward 8 race to jointly endorse former school board member Trayon White.
Meanwhile, a group of Ward 8 candidates promised a press conference last week to speak out against Ms. Bowser's influence on the D.C. Council race only to cancel it at the last minute.
It has left community activist Eugene Kinlow; Sheila Bunn, former deputy chief of staff for Mayor Vince C. Gray; Natalie Williams, president of Ward 8 Democrats; Marion C. Barry, potential heir to his father's council seat; and five others working frantically in the waning days of the campaign to build a groundswell of opposition to knock Ms. May out of front-runner status.
Civic activist Phil Pannell said voters in Ward 8, the city's poorest, are looking for a candidate who will address their plight and advocate for the disadvantaged.
"Even though no one could ever fill Marion Barry's shoes, they want someone who is at least out there speaking out for the economically disadvantaged," Mr. Pannell said. "That's one of the reasons you saw the candidates saying they are very much part of the Marion Barry legacy."
He said he believes that because Ms. Bowser has been so visible in Ward 8 since her November election that residents will not see a candidate's close ties with the mayor as a bad thing.
"It's very beneficial to the ward to have a council member who is aligned with the mayor," Mr. Pannell said. "It's certainly not helpful to have one who is adversarial."
In Ward 4, Mr. Todd vies with a bevy of Advisory Neighborhood Commission leaders, including Renee Bowser, Ron Austin, Judi Jones, Acqunetta Anderson, and Dwayne Toliver.
Mr. Gray, the former mayor, endorsed Mr. Toliver, a real estate attorney. Renee Bowser, who is not related to the mayor, has been backed by several unions.
As in Ward 8, at least one candidate backed out of the race to endorse another in Ward 4. Leon T. Andrews Jr., who works as a program director at the National League of Cities, received support from ANC member Doug Sloan. Mr. Andrews, who raised $144,000 thanks in part to a $90,000 self loan, is Mr. Todd's closest rival financially.
Turnout is generally light in special elections, so a small number of voters could pick a winner in a tight race.
As of Friday, the D.C. Board of Elections reported that 1,068 voters had cast ballots at the Ward 4 early voting station, 1,092 residents had cast ballots at the Ward 8 station, and 486 people had voted at Judiciary Square, which accepted ballots from both wards.
• Andrea Noble can be reached at anoble@washingtontimes.com.


text:
Cataloging & Classification Quarterly
Empowering Representations: Rethinking Surrogates from the Margins
Lynne Howarth, University of Toronto
Katharine Leigh, Ball State University
The process of describing and categorizing a tangible or intangible object for inclusion in the collection of a cultural heritage institution (CHI) typically involves creating a surrogate. The surrogate represents the acquired item, its provenance, physical, intellectual, and other (e.g., temporal, spatial) origins and characteristics in accordance with established guidelines and standards, further informed by institutional policies and practices. Working within that framework, the "cataloger" selects what aspects of the object to include in the representation. Consistency and uniformity of interpretation and application across the range of physical and digital acquisitions held by a library, archive, museum, or other cultural heritage institution are hallmarks of the process of representation, and the creation of surrogates (an encoded record) that may be shared among similar institutions. There is an authority assumed in the representativeness of the surrogate as determined and applied by information professionals and their institutions as informed by long-established standards and practices, both nationally and internationally.
But what if those representations are themselves open to interpretation, and candidates for the kinds of close scrutiny and substantial rethinking that have emerged with movements, such as Black Lives Matter, Idle No More/Indigenous Lives Matter, and issues relating to LGBTQI communities, persons with dis/abilities, ageism, gender inequality, poverty, people without housing, and others? Cataloging and classification derive largely from 19th century approaches to representation, codified, standardized, applied, and embedded within legacy systems throughout the 20th century. While technologies have allowed for some augmentation of surrogates by those who use the collections, the core, largely Western European values and applications have endured. By providing access to collections and to the items and information associated with them, surrogates have served an important purpose. Nonetheless, approaches to representation deserve a closer look from a contemporary perspective. Informed by the lens of a social justice imperative, what do we preserve, what can we rethink, what does that look like, and how can and should it be done?
We seek submissions on theoretical and applied approaches to representation from scholars and practitioners within North America or internationally, whose work is focused on libraries, archives, museums, or other cultural heritage institutions. We encourage, in particular, papers that address solutions – innovations, novel approaches, a fundamental rethinking of models or frameworks, inclusive engagements with communities and/or collections that have been traditionally marginalized, and reconfigured standards, tools, or technologies that signal transformative change to the process of representation and the surrogates that result. How do or will rethinking theories or practices that have foregrounded certain worldviews to the exclusion or obscuring of others lead to change that is measurably responsive to, and inclusive of those who have been silenced, ignored, underserved, or otherwise diminished?
Lynne Howarth, Faculty of Information, University of Toronto, and Katharine Leigh of Ball State University will be guest editors for this issue, which is scheduled for publication in late 2022. Following a two-step process, authors are invited, first, to submit an extended abstract (1200-1500 words exclusive of references) of their paper to the guest editors for initial review. If accepted, authors will then be asked to submit an anonymized full paper which will be blind reviewed by a minimum of two reviewers. Acceptance of the extended abstract does not guarantee acceptance of the full paper. Those whose full papers are ultimately recommended for publication will revise and finalize the manuscript following the timelines, described below.
Please contact guest editors, [email protected] or [email protected] should you have questions about this call.
Extended Abstract of 1200-1500 words (exclusive of references) due to the guest editors by or before: 31 October 2021
Send the extended abstract as an attachment saved in a .doc, or .docx, or .rtf file format, to both [email protected] and [email protected].
Notification of acceptance of extended abstract and invitation to submit an anonymized full paper for blind peer review: 30 November 2021
Full papers for double blind peer review due by or before: 31 January 2022
Papers must follow CCQ Instructions for Authors and be submitted through ScholarOne Manuscripts.
Peer Review and notification of acceptance of full paper (pending revisions): 15 March 2022
Revisions to full paper due: 15 April 2022
Subsequent review of revisions, as required: 15 May 2022
All manuscript revisions completed by: 15 June 2022
Publication: Fall 2022
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text:
Angelina Jolie right leg pose: Copy of Jennifer Aniston"s red carpet display
Anything Jen can do: How Angelina Jolie (and her unruly right leg) copied love rival Jennifer Aniston's red carpet display
It seems Angelina Jolie and Jennifer Aniston have more in common than the same taste in men.
As this picture from January 2010 shows, it was actually Angelina's love rival Jen who blazed the trail as she flashed a lot of leg at the Golden Globes in a black gown split to the thigh.
The ensemble is very similar to the one worn by Jolie at Sunday's Oscars and begs the question – was Angie trying to outdo Aniston once again
Looks familiar: Angelina Jolie's famous right leg pose from Sunday's Oscars… but it was love rival Jennifer Aniston who got in on the act first, pictured right at the Golden Globes in January 2010
Angelina's unruly right leg has now
made headlines over the world while hilarious spoof images of her limb
have gone viral on the web, with bloggers and artists having fun with photoshop.
Jennifer – who was married to Brad
Pitt for five years before Angelina swooped in – failed to create the same stir when she
strutted onto the red carpet at the Golden Globes two years ago.
While she looked incredible with her
tanned legs on parade, Jennifer breezed into the ceremony in
girl-next-door-style, rather than posing in diva fashion with her leg on show as
deliberately as spotlight-stealing Angelina.
But side by side, the two images certainly make for an interesting comparison.
Seeing double: A mirror-image mock-up was one of
the first parodies to hit the net poking fun at Angelina's leggy pose,
while partner Brad Pitt in Interview with the Vampire was given the
photoshop treatment
The two women have both been
inevitably compared to each other following Jennifer's split from Brad
seven years ago, with intense speculation that he and Angelina became an item on the set of their film Mr & Mrs Smith, while he and Jen
were still together.
In October 2008, Angelina told The New York Times that her children loved Mr & Mrs Smith because: 'Not a
lot of people get to see a movie where their parents fell in love.'
However, the actress has maintained that she and the heartthrob remained nothing more than friends until after Pitt and
Aniston announced they were divorcing in early 2005.
She once said: 'To be intimate with a married man, when
my own father cheated on my mother, is not something I could forgive. I
could not look at myself in the morning if I did that. I wouldn't be
attracted to a man who would cheat on his wife.'
Where they met: Angelina, this time with her left leg on show in a scene still from Mr & Mrs Smith
As they were: Aniston and Pitt were married for five years, splitting in 2005
Angelina also said in a 2006 interview with U.S.
Vogue that when she met the actor, she had not known 'exactly where Brad was in
his personal life.'
She said: 'But it was clear he was with his best friend, someone he loves and respects. And so we were both living, I suppose, very full lives.
'Brad was a huge surprise to me,' she added. 'I think we were the last two
people who were looking for a relationship. I certainly wasn't. I was
quite content to be a single mom.'
The star also said that she and Brad had taken a 'long time' before deciding to embark on a relationship .
'We
spent a lot of time contemplating and thinking and talking about what
we both wanted in life and realised that we wanted very, very similar
things,' she said.
'And then we just continued to take time. We remained very, very good friends – with this realisation – for a long time.
Angelina sought to explain how the film, a romantic comedy action film, had 'brought' she and Brad together.
'Because of the film, we ended up being
brought together to do all these crazy things, and I think we found this
strange friendship and partnership that kind of just suddenly
happened,' she said.
'I think a few months in I realised, "God, I can't wait to get to work."'
However, her comments didn't go down too well with Jennifer who gave her own interview to U.S. Vogue two years later.
When asked about Angelina's comments, she said: 'There was stuff printed there that was definitely from a time when I was unaware that it was happening.
'I felt those details were a little inappropriate to discuss.'
Keeping THAT leg covered: Angelina put THAT very
slim pin into a pair of trousers and a knee-high boot yesterday after it's
attention-seeking turn on the red-carpet at the Oscars on Sunday
According to the interview, Jennifer
shook her head in disbelief as she then added: 'That stuff about how she
couldn't wait to get to work every day That was really uncool.'
And then last year, Brad unintentionally thrust his relationship with Jennifer back into the spotlight during an interview with Parade magazine when he made reference to his first marriage.
'It became very clear to me that I was intent on trying to find a movie about an interesting life, but I wasn't living an interesting life myself,' he said.
'I think that my marriage [to Aniston] had something to do with it. Trying to pretend the marriage was something that it wasn't.'
Mocking: The fun started early, with screenwriter Jim Rash copying the hilarious pose shortly after the actress presented him with an award onstage
He was then forced to clarify his
comments after they made worldwide headlines, releasing a statement
saying: 'It grieves me that this was interpreted this way. Jen is an
incredibly giving, loving, and hilarious woman who remains my friend.
'It is an important relationship I
value greatly. The point I was trying to make is not that Jen was dull,
but that I was becoming dull to myself – and that, I am responsible
for.'
For her part, Jennifer, who is now dating actor Justin Theroux, has revealed she is 'happier than I've ever been,' and told GQ that: 'Oh, my God, my thirties blew. Forties are great,' perhaps referring to her new relationship.
Meanwhile, Angelina, 36, kept her pins covered yesterday as she snapped back to motherly duties shopping with
her twins Vivienne and Knox in Beverly Hills along with Brad's mother Jane.
The original: Angelina's overexposed leg on Oscars night has been the cause of much ridicule
DM.has('rcpv1477674382001','BCVideo');
"Jennifer Aniston threw Brad Pitt out after he confessed his love for Angelina Jolie": New book lifts lid on split of the century
Jennifer Aniston "threw Brad Pitt out after he confessed his love for Angelina Jolie"
Brad Pitt on Jennifer Aniston marriage: "My life is more interesting with Angelina Jolie"
Jennifer Aniston shows Angelina Jolie how to work a little black dress at the Directors Guild Awards in Hollywood
Brad Pitt and Angelina Jolie step out of their Park Lane hotel for Sunday lunch


text:
Home Law Enforcement Brit Paedophile Arrested After 70 Home Security Camera Hack
Brit Paedophile Arrested After 70 Home Security Camera Hack
Aadvik Perry
A Brit paedophile has been arrested in Benidorm. The man had been under suspicion of hacking over 70 families' home security cameras around the world. Spanish Police stated that the unnamed pedophile had worked as a babysitter and private tutor. He had acquired 1,000 images of the naked children.
Apart from this, the Brit paedophile has also been accused of selling child pornography on the dark web utilizing cryptocurrency such as Bitcoin (BTC). He was charged with harassing approximately a dozen minors and filming them naked in the video chats before threatening them, the cops revealed.
The Spanish cops have held him after they received a tip-off from colleagues in Queensland of Australia. The detectives have discovered the actual identity after trespassing the tight security that the Brit paedophile had created. The footage that he had been alleged to have been acquired by hacking the families' indoor home security cameras. The footage consisted of British children as well as children from Canada, Brazil and the United States.
However, the age of the suspect has not been revealed. But the police mentioned that the suspect had been known to the authorities following his arrest as a minor for committing the child porn offences.
A spokesperson for Spain's National Police has confirmed:
"He also allegedly sexually harassed at least 11 minors he filmed naked and sometimes threatened after they accessed video chats. He was very active on the dark web and had organized a system of child porn sales based on bitcoins or the exchange of images filmed by his clients."
The National Police have revealed that the Brit paedophile had utilized various usernames online to post heinous acts and indecent images.
"National Police specialists also discovered he offered his services as a babysitter and, taking advantage of his British nationality, worked as a home tutor teaching English. This work enabled him to have around 10 pupils, which heightened the concern of investigators who decided to proceed to arrest him."
During the search of his residence, a host of sex abuse images had been discovered. Several shreds of evidence pointed to the suspect's use of cryptocurrencies and money transfers to people in Romania involved in child pornography (CP).
The Brit paedophile was also alleged of organizing a bitcoin or image-exchange system of child porn sales. Police mentioned that the accused has also charged commissions for acting as an intermediary between the consumers and the producers.
The police spokesman said: "The home security cameras he hacked are designed to enable parents to monitor their kids when they are not at home and can be accessed over mobiles. If they are not properly configured they are very vulnerable."
"It has also been discovered that on at least one occasion, the suspect obtained images of the underwear of the children he tutored privately and filmed without their knowledge."
"He is now being held on remand in prison following a court appearance as the investigation against him continues."
Source: The U.S. Sun
Brit Paedophile
Child Porn Dealings
Child Porn Media
Child Pornographic Media
Indecent Images
National Police
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Aadvik Perry covers law enforcement and crimes from San Francisco for The New York Times. Before joining The Times he was a reporter at The Los Angeles Times and The Forward. Aadvik is one of the top contributors of Dark Web Links.
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Jagtar Sandhu wanted to keep the doors of Gomora Night Club, based at the Ship and Shovel in Barking, open longer including until 5am on a Friday and Saturday night.
But Mr Sandhu's bid was refused at a public Town Hall meeting of Barking and Dagenham Council's licensing sub-committee last week.
Councillors heard of five occasions after closing time when police were called to the Ripple Road nightspot.
In one case, violence erupted on December 23 with officers finding the clubber with a knife and bat.
In another, six security guards couldn't stop a brawl when four men tried to barge in last November.
The Met was also called to a common assault inside the club at 3.23am last December.
Police licensing officer, Pc Richard Clay, warned the committee drink driving offences could worsen if the hours were extended.
He described an arrest in January after a drunk reveller left the venue, got into their vehicle and smashed it into others in the club's car park.
In a fifth incident, a man was smacked in the face during a fight which saw officers called out at 3.39am on February 19.
Twelve incidents were recorded over the last year, Pc Clay said, with three serious assaults in the last four weeks alone.
"The police feel if the hours are extended, the intoxication of the people attending the club will become a lot higher. Our concern is it will put a drain on police resources having to deal with violence," Pc Clay said.
But Mr Sandhu argued the trouble-makers were coming from other clubs.
"They come in drunk and we don't want them. We do our jobs. We work with the police," he said.
Delivering the decision, Simon Scrowther, the council's legal adviser, said: "The sub-committee was concerned by the criminality arising in and around the premises.


text:
Gang Affiliated is the debut album released by Gospel Gangstaz.  It was released on October 28, 1994 for MYX Records and featured production from DJ Dove and Mr. Solo. The album is widely considered as the first harder-edged Christian hip hop album as the sound and lyrics had a gritty element to them that was virtually unseen in the genre at the time as this album sounded much like the popular West Coast Gangsta G-funk music of the mid-1990s. Gang Affiliated managed to make it to No. 19 on the Top Christian Albums Billboard chart. However, the three singles: "Mobbin' (Gang Affiliated)", "Testimony" and "Y Cain't da Homiez Hear Me?" did not make it to any Billboard charts.

In the July/August 2010 issue of HM Magazine, Gang Affiliated was No. 1 on the list of the "Top 20 Christian Hip Hop Albums of All Time".

Track listing
"Death For Life" - 1:57
"Before Redemption"- 5:24
"O.G.G."- 1:28
"Mobbin' (Gang Affiliated)"- 4:17
"Testimony"- 6:05
"Ain't Nuthin Changed"- :39
"Vengeance is Mine"- 4:47
"Interrogation 1"- 2:32
"Y Cain't da Homiez Hear Me?"- 5:52
"Tha Holy Terra"- 4:52
"Interrogation 2"- 2:59
"One Time"- 3:55
"Trial By Error"- :49
"Tears of a Black Man"- 4:59
"Da Gangsta's Prayer"- :22
"Gospel Gangsta Voyage"- 4:20
"A Gruuv fo Sum Preechin'"- 2:20

1994 debut albums
Gospel Gangstaz albums
G-funk albums

redpajama_set_name: RedPajamaWikipedia


text:
Although there were attorneys-general that served the Colony of Sierra Leone, the Office of the Attorney General and Ministry of Justice that still stands today was first established in 1961. It would not combine with the Ministry of Justice until 1978 when the country's constitution was amended. The office is responsible for prosecuting all offenses in the name of the Republic of Sierra Leone. The Solicitor General and the Director of Public Prosecutions are two sub-units of the Office of Attorney General and Ministry of Justice.

List of attorneys-general and ministers of justice (post-independence from the UK in 1961)

 Victor Bert Grant (c. 1957–1961)
 Berthan Macaulay (1963-1967) []
 Abu Aiah Koroma (1967-1971)
 James Emmanuel Mahoney (1972) [Acting]
 Luseni Brewah (1972-1975)
 Solomon Pratt (1976-1977)
 Abu Kamara (1978-1982)
 Francis Minah (1983-1987)
 Abdulai Conteh (1987-1991)
 J. B. Dauda (1991-1992)
 Arnold Bishop-Gooding (1993-1994)
 Claude Campbell (1995-1996)
 Solomon Berewa (1996-2002)
 Eke Ahmed Halloway (2002-2004)
 Frederick Carew (2004-2006)
 Abdul Serry-Kamal (2007-2010)
 Frank Kargbo (2010-2015)
 Joseph Fitzgerald Kamara (2016-2018)
 Charles Margai (2018)
 Priscilla Schwartz (2018-2020) []
 Anthony Yiehwoe Brewah (2020–present)

See also

 Justice ministry
 Politics of Sierra Leone

References

External links

Attorneys-general of Sierra Leone
Justice ministries