Interferon (IFN)-like the well-known antitumor biotherapeutic IFN-is a robust antiproliferative and defense modulatory cytokine, but mixed outcomes from clinical tests, together with problems of systemic toxicity, have dampened excitement for its make use of in the treating tumor. necrosis (or necroptosis) in in any other case resistant cells. Second, we suggest that fusing IFN- to tumor-specific antibodies will stabilize IFN- in serum and focus on this cytokine to tumor cells. We anticipate that such IFN-Cantibody chimeras (known as immunocytokines), when Th 50298-90-3 manufacture coupled with providers that neutralize tumor-intrinsic success signals such as for example NF-B, will exert powerful tumoricidal activity 50298-90-3 manufacture with reduced systemic unwanted effects. Although this review will concentrate on exploiting IFN–induced necrosis for treatment of renal cell carcinoma, these methods are also straight applicable to many human cancers where IFNs show restorative potential. Intro The interferons (IFNs) certainly are a category of cytokines categorized into type I (mainly /), type II (), and type III (), centered primarily within the cell surface area receptors they make use of, the stimuli that result in their production, as well 50298-90-3 manufacture as the cells that create them. All sorts of IFNs, nevertheless, activate virtually identical Jak-/STAT-dependent signaling cascades downstream of their structurally unique receptors. Originally found out as antiviral cytokines over 50 years back, the IFNs also have potent development suppressive and immunomodulatory properties. The antitumor potential of the properties was identified early in the annals of IFN study, leading to recombinant IFN- getting the 1st ever natural agent authorized for the treating cancer (Borden while others 2007). As IFN-the lone type II IFNexerts lots of the same natural results as IFN-, many clinical tests with recombinant IFN- (primarily IFN-1b; Actimmune) had been completed in the middle-1980s to determine its potential against a number of 50298-90-3 manufacture cancers and additional diseases. Because of these tests, Actimmune was authorized by the meals and Medication Administration in 1991 for reducing the regularity and intensity of repeated microbial attacks in chronic granulomatous disease, and (in 2000) for delaying development of disease in sufferers with malignant osteopetrosis, an inherited disorder seen as a osteoclast flaws and reduced phagocyte oxidative capability. In both situations, the power of IFN- to cause superoxide era via induction of the respiratory burst in phagocytes is certainly considered to underlie its healing effects [analyzed in (Miller among others 2009)]. The outcomes from the usage of IFN- in cancers studies were mixed. In lots of of these studies, IFN- demonstrated significant clinical advantage, either being a monotherapy, or when coupled with various other agencies. Other studies, however, demonstrated no benefit to using IFN-, or needed to be terminated prematurely due to toxicity due to the combined usage of IFN- with chemotherapeutic medications [for examples, find (Foon among others 1985; Kurzrock among others 1985; Bennett among others 1986; Muss among others 1986; Vadhan-Raj among others 1986; D'Acquisto among others 1988; Street among others 1989; Abbruzzese among others 1990; Yoshida among others 1990; Jett among others 1994); analyzed in (Miller among others 2009)]. The final results of clinical studies using IFN- as an experimental therapy for advanced renal cell carcinoma (RCC) highlight the huge benefits and limitations of the cytokine as an anticancer agent, that cause we will concentrate this review on IFN- and RCC. We will put together developments from our groupings and from various other laboratories that lend brand-new insight in to the system of IFN- cytotoxic actions and offer powerful next-generation opportunities for the revival of IFN- being a healing strategy for RCC and various other cancers. Specifically, we will explain (1) the id of a book necrotic cell loss of life system induced by IFN-; (2) a nuclear factor-kappa B (NF-B)-reliant survival plan that protects cells from IFN-; and (3) our ongoing initiatives to induce tumor-selective necrosis by focusing on IFN- to tumors. IFN- and RCC Kidney malignancy is probably the top 10 most-frequent malignancies in Traditional western countries, as well as the 13th most-common malignancy world-wide. Globally, about 270,000 instances of kidney malignancy are diagnosed each year, with 116,000 annual fatalities. Approximately 90% of most kidney malignancies are RCCs (Ljungberg while others 2011). Although early-stage RCC could be efficiently controlled by medical and additional interventions, RCC is basically asymptomatic, and 20%C30% of individuals possess metastatic disease during demonstration. Unlike early-stage disease, metastatic RCC is definitely a chemotherapy-resistant malignancy that is generally lethal (Chen and Uzzo 2011; Ljungberg while others 2011). RCC comprises many distinct histological types, which clear-cell (cc) RCC represents the dominating subtype and makes up about up to 85% of most RCC instances (Kovacs while others 1997; Storkel while others 1997). The best-recognized hereditary hallmark of ccRCC is definitely inactivation from the von Hippel Lindau (gene mutations happen in 20%C70% of instances of sporadic ccRCC, with promoter hypermethylation from the gene.
Background Chronic intermittent hypoxia-hypercapnia (CIHH) exposure leads to learnning and memory deficits in rats. Today's research intends to explore the aftereffect of lovastatin on CIHH-induced cognitive deficits as well as the NR2B-ERK signaling pathway. Strategies and Results Eighty man Sprague Dawley rats had been randomly split into five groupings. Aside from those in the control group, the rats had been subjected to chronic intermittent hypoxia-hypercapnia (CIHH) (911%O2, 5.56.5%CO2) for four weeks. After lovastatin administration, the rats performed better in the Morris drinking water maze check. Electron microscopy demonstrated alleviated hippocampal neuronal synaptic harm. Further observation recommended that either lovastatin or ifenprodil (a selective NR2B antagonist) administration likewise downregulated NR2B subunit appearance resulting in a suppression of CaMKII/SAP102/SynGAP signaling cascade, which improved the phosphorylation of ERK1/2. The phosphorylated ERK1/2 induced signaling cascade regarding cAMP-response element-binding proteins (CREB) phosphorylation and brain-derived neurotrophic aspect (BDNF) activation, which is in charge of neuroprotection. Conclusions These results claim that the ameliorative cognitive deficits due to lovastatin are because of the downregulation of extreme NR2B expression followed by increased appearance of ERK signaling cascade. The result of NR2B in upregulating pERK1/2 probably credited, at least partly, to inactivation of CaMKII/SAP102/SynGAP signaling cascade. Launch Chronic obstructive pulmonary disease (COPD) is normally a major reason behind chronic morbidity and mortality . Many studies reveal its dangerous influence on learning and storage function, which can't be explained simply by coincidence or by melancholy . Autopsy reviews and pet experiments concur that this cognitive disorder relates to pathological adjustments in the central anxious system (CNS), especially in the hippocampus , . Chronic intermittent hypoxia hypercapnia (CIHH) can be an pet model just like pathophysiological procedure in individuals with COPD . Inside our earlier study, we verified that the publicity of CIHH deteriorated the training and memory space ability from the experimental rats as the publicity time was long term after fourteen days , . Glutamate is among the most significant excitatory neurotransmitters in CNS, playing an essential part in mediating synaptic plasticity and receptor function in the rules of learning and memory space . NMDARs are cation stations that are gated from the neurotransmitter AG-1478 glutamate. Normally, NMDARs are crucial regulators of synaptic plasticity, neuronal advancement and synaptic transmitting AG-1478 , . Nevertheless, in neurodegeneration and hypoxic tension, extreme launch of glutamate qualified prospects to suffered activation of NMDA-type glutamate receptors and downstream effectors, leading to neuronal harm and cell loss of life. This process is recognized as synaptic excitotoxicity . Synaptosome excitotoxicity is known as a pivotal element causing CNS harm Rabbit Polyclonal to Paxillin (phospho-Ser178) , . NMDARs are tetrameric proteins complexes made up of NR1 subunits with least one kind of NR2 subunit(NR2A-D, also called GluN2A-D). NR2A and NR2B will be the predominant NR2 subunits in the neurons from the hippocampus and prefrontal cortex. Nevertheless, the NR2A and NR2B display difference in synaptic localization and practical properties. The activation of AG-1478 synaptic NR2A can be involved with neuroprotection as the excitement of extrasynaptic NMDARs, that are predominantly made up of NR2B subunits , perform an important part in learning and memory space. Nevertheless, in pathophysiological circumstances, such as for example ischaemia and/or hypoxia, or neurodegeneration,NR2B subunits result in cell harmful pathways as well as the continual activation of extrasynaptic NR2B is in charge of excitotoxicity , . The mitogen-activated proteins kinase phosphatase (MAPK) sign transduction program, the eventual common pathway in eukaryotic cells for the transmitting of various info, transduces extracellular info towards the nucleus and regulates cell development and differentiation , . Among the best-characterized MAPK pathways requires the 44-and 42-kDa isoforms, that are named extracellular signal-regulated kinase 1 and 2 (ERK1/2). Research have proven ERK signalling cascade can be an essential pathway in mediating NMDAR-dependent neuronal plasticity and success , . Regular indicated NMDAR-dependent signalling activates the ERK1/2 cascade with pro-survival outcomes including CREB and BDNF activation , pro-apoptotic elements inactivation, and antagonizing GSK3-induced apoptosis . Additional researches discovered that the ERK cascade can be closely from the NMDAR once they observed the immediate discussion of ERK with NR2B subunit and calcium-calmodulin-regulated guanine-nucleotide exchange element RasGRF1 . Nevertheless, how NR2B regulates the ERK activity continues to be obscure. NMDARs are localized.
Granulin-epithelin precursor (GEP) is a pluripotent secretory development element which promotes tumor progression in several human malignancies. Suppression from the HS polymerase exostosin-1 decreased the rGEP binding and rGEP-mediated signaling transduction. Suppression of a particular HS proteoglycan, glypican-3, also demonstrated a partial reduced amount of rGEP binding and an inhibition on rGEP-mediated activation of AKT. Furthermore, glypican-3 was proven to correlate using the expressions of GEP in 182760-06-1 IC50 medical examples (Spearmans = 0.363, = 0.001). This research identified HS, partially through glypican-3, like a book binding partner of GEP on the top of liver tumor cells. Intro Hepatocellular carcinoma (HCC) can be a malignant neoplasm of hepatocytes and it makes up about 80% of major liver malignancies (1). This disease rates as the 5th most common tumor worldwide and may be the third leading tumor killer. Because liver organ cancer is generally diagnosed at a sophisticated stage, just ~30C40% of individuals meet the criteria for curative 182760-06-1 IC50 treatment, which include medical resection, transplantation or percutaneous ablation (2). Additional patients need to receive systemic chemotherapies however the response prices are 20% p150 (3). Furthermore, even after operative resection, the speed of recurrence is normally fairly high at ~60% (4). Therefore, the 5 calendar year survival prices of HCC sufferers are 15% generally in most countries (5). As a significant global medical condition, the current technology in early medical diagnosis and prognosis of HCC are unsatisfactory. An improved knowledge of the molecular systems of the condition is vital for developing diagnostic technique and for searching for choice or supportive remedies to manage liver organ malignancy. Granulin-epithelin precursor (GEP, also called progranulin, acrogranin or PC-derived development factor) is normally a secretory development aspect that constitutes of seven and half cysteine wealthy granulin subunits. While granulin subunits get excited about regulating irritation (6), its precursor, GEP, has an array of natural roles. It had been demonstrated to control cancer development (7), fetal advancement (8) and tissues fix (9). Besides, mutation on the gene of GEP impacts neuron success and causes frontotemporal dementia (10,11). We previously demonstrated that GEP overexpression was within 70% of individual HCC (12). Besides, GEP was showed being a hepatic oncofetal proteins which governed embryonic stem cell-related signaling substances (13). Functional research demonstrated that GEP managed cell proliferation, invasion, tumorigenicity and chemoresistance of HCC (12,14). In pet model, anti-GEP monoclonal antibody (mAb) was proven to inhibit the development of set up HCC, offering evidences that GEP is normally a potential healing focus on for HCC (15). As a result, it really is urgently had a need to clarify the function of GEP in HCC by characterizing the downstream systems of GEP overexpression. However the signaling transduction mediated by extracellular recombinant GEP (rGEP) is not characterized in liver organ cancer cells, research of other cancer tumor cell types recommended its paracrine impact at triggering many signaling pathways. They are the ERK pathway (16C19), the PI3K cascade (16,18,19) as well as the focal adhesion signaling cascade (16,17). These rGEP-triggered activations are anticipated to be governed by cell surface area receptors. Cell 182760-06-1 IC50 surface-binding companions of GEP never have yet been discovered from cancers cells but from neuronal cell and chondrocyte as sortilin-1 (20) and tumor necrosis aspect (TNF) receptors (21), respectively. Connections between these substances and GEP weren't proven to regulate cell signaling pathways, although sortilin-1 was proven to mediate endocytosis of extracellular GEP (20). Alternatively, in the current presence of CpG-ONDs, proteolytic fragments of GEP connect to toll-like receptor 9 in the endolysosomal compartments of toll-like receptor 9-expressing Organic macrophages (22). Within this research, purified rGEP was assayed 182760-06-1 IC50 because of its paracrine impact and physical connection in liver cancers cells. The signaling pathways turned on by exogenous rGEP had been determined in liver organ cancers cell lines. The binding of rGEP for the cell surface area of liver cancers cells was proven in movement cytometry and seen as a competitive assays. Using heparinase digestive function, we figured the discussion between GEP and cell surface area can be mediated by heparan sulfate (HS). The heparin-binding site of GEP was mapped such as the C-terminal area of the proteins, mainly contributed with the RRH(555-557) residues. A HS polymerase, exostosin-1 (EXT1), and among the HS proteoglycans (HSPGs), glypican-3 (GPC3), had been suppressed to validate the function of HS in GEP.
Berberine is a place alkaloid with multiple pharmacological activities, including antidiarrhoeal activity and offers been proven to inhibit Cl? secretion in distal digestive tract. inhibitor of PKC also to a smaller sized degree by inhibition of p38 MAPK with SB202190 (15%). Berberine treatment induced a rise in association between PKC and PKA with KCNQ1 and created phosphorylation from the route. We conclude that berberine exerts its inhibitory influence on colonic Cl? secretion through inhibition of basolateral KCNQ1 stations in charge of K+ recycling with a PKC-dependent pathway. and in rabbit and rat intestine (Guandalini et al., 1987; 1135695-98-5 Taylor and Baird, 1995). Diarrheal illnesses continue being a major reason behind morbidity and mortality in kids and seniors across the world. Dental rehydration therapy continues to be the mainstay of treatment for diarrhea (Taylor and Greenough, 1989). Nevertheless, lately significant effort continues to be manufactured in the seek out antisecretory drugs that may straight inhibit secretory procedures inside the enterocytes (Ma et al., 2002; Farthing, 2006). Activated Cl? secretion in the intestinal crypt is normally considered to play a significant function in secretory diarrhea of many aetiologies (Field, 2003). The era from the electrochemical generating force necessary for Cl? secretion by crypt epithelial cells depends upon their capability to accumulate intracellular Cl? ions to concentrations higher than their electrochemical equilibrium (Barrett and Keely, 2000; Kunzelmann and Shopping mall, 2002). Cl? enters the cell over the basolateral membrane through the experience of Na+CK+-2Cl? cotransporters. The cotransporter is normally, in turn, powered by a solid inwardly directed electrochemical Na+ gradient set up with the basolaterally located Na+CK+-ATPase. To be able to keep up with the membrane potential at rest and during Cl? secretion, both Na+ and K+ should be recycled from the cell through the basolateral membrane. The Na+CK+-ATPase acts to recycle Na+, while basolateral potassium stations recycle K+ (Schultheiss and Diener, 1998). The basolateral K+ conductance in intestinal epithelial cells is normally produced by at least two 1135695-98-5 various kinds of K+ stations, one turned on by Ca2+-mobilizing secretagogues as well as the various other by cAMP-dependent agonists (Heitzmann and Warth, 1135695-98-5 2008). Electrophysiological research have uncovered the latter to become KCNQ1, a minimal conductance (1C3?pS) basolateral K+ route, which is activated during cAMP-stimulated Cl? secretion and inhibited by chromanol 293B and HMR-1556 (Schroeder et al., 2000; Robbins, 2001). As in every secretory epithelia, the stations and transporters from the crypt epithelial cell must operate in concert to attain vectorial ion transportation. As a result, blockade of particular basolateral K+ conductance will be likely to inhibit the Cl? secretory procedure. The T84 cell series is normally a well-differentiated intestinal individual carcinoma cell series became a sturdy model for the analysis of molecular systems of intestinal secretion in near 1,200 magazines because the early 1980s (Dharmsathaphorn et al., 1984). Prior research using T84 cells, harvested to 1135695-98-5 confluence and installed in Ussing chambers, show that berberine reduced Cl? secretion within a dose-dependent way (Taylor and Baird, 1995). Moreover, berberine attenuated the top Cl? secretory current made by realtors that boost intracellular cAMP. Nevertheless, the specific transportation pathways in charge of the inhibitory aftereffect of berberine on Cl? secretion never have been discovered. Herein we survey on some experiments made to clarify which epithelial transportation processes are influenced by berberine. Using the short-circuit current technique, we examined the power of berberine to inhibit Cl? secretion induced by cAMP in T84 cells. Using the pore-forming antibiotics nystatin and amphotericin B to permeabilized the basolateral and apical membranes respectively, we could actually isolate membrane currents and measure the ramifications of berberine on (1) the apical membrane Cl? conductance, (2) the basolateral membrane Na+CK+-ATPase activity, and (3) the basolateral membrane K+ conductance. Also, we 1135695-98-5 explored the signaling mixed up in antisecretory actions of berberine specifically the function of proteins kinases such as for example PKC, PKA, mitogen-activated proteins kinase (MAPK), and membrane goals such as for example ion stations and transporters. Our outcomes indicate that berberine inhibits Cl? secretion by lowering the basolateral membrane K+ conductance and for that reason K+ recycling essential for the era of the good electrochemical gradient necessary for Cl? secretion. Components and Strategies Cell lifestyle T84 cells (American Type Lifestyle Collection, Manassas, VA, USA) had been cultured within a 1:1 combination of DMEM and Hams F-12 supplemented with 10% fetal bovine serum, 1% nonessential proteins, 50?Uml?1 Rabbit Polyclonal to ARHGEF11 penicillin, 0.05?mgml?1 streptomycin, and grown onto Costar Snapwell lifestyle inserts (Corning, Dublin, Ireland) with a location of just one 1?cm2.
Background UV irradiation may be the main reason behind epidermis photo-damage; causing modulation of matrix metalloproteinases (MMPs) network marketing leads to collagen degradation. hairless mice). Outcomes Our research in HDFs showed that both a Syk inhibitor and Syk siRNA could actually inhibit MMP-1 appearance in HDFs subjected to UV which overexpression of Syk elevated MMP-1 appearance and the experience of JNK kinase, however, not p38 or Erk1/2 MAP kinase. UV publicity enhanced both appearance and activity of Syk in HDFs. Tests with hairless mice recommended that Syk appearance is an previously signal of UV publicity than MMP-13 appearance. Conclusion Our outcomes demonstrate that Syk appearance correlates well with boost of MMPs (MMP-1 in human beings and MMP-13 in mice) in response to UV publicity. The findings claim that Syk could be a novel focus on for the avoidance and treatment of epidermis photodamage by modulating MMPs. Launch Syk (spleen tyrosine kinase) is normally a 72 kD proteins cloned from porcine spleen.1 Originally regarded as exclusively a hematopoietic cell-specific signaling molecule,2C5 latest research have demonstrated that Syk can be expressed by many non-hematopoietic cells,6C8 and may be considered a marker of tumor formation and development.6,9C12 Furthermore, it's been determined that Syk is activated following tension stimulations such as for example H2O2 treatment,13,14 and it is very important to c-Jun NH2-terminal kinase (JNK) activation following oxidative tension.13 Although zero published data indicate that Syk is involved with UV induced skin surface damage, the critical function of Syk in activating mitogen-activated proteins kinases (MAPKs) continues to be established.15C20 MAPKs have already been recognized to play a substantial part in mediating UV induced natural results.21 MAPKs certainly are a family of protein such as the extracellular sign controlled kinases (ERKs), p38 kinase, and JNKs.22 Under tension conditions, such as for example UV excitement, MAPK signaling is very important to protecting the skin and resisting UV induced skin surface damage and carcinogenesis by activating cell routine arrest, apoptosis, and swelling in the damaged cells.23,24 JNK and p38 are believed to stop cell proliferation or promote cell apoptosis via modulation of p53, that may prevent tumor development.25C27 UV irradiation (UVR) is regarded as the root cause of pores and skin photo-damage by inducing break down of collagen, and inhibiting procollagen biosynthesis leading to 2645-32-1 IC50 lack of collagen content material. Because the ozone coating blocks UVC (180C280 nm), UVB (280C320 nm) and UVA (320C400 nm) are usually in charge of sunlight-induced skin surface damage.28,29 Matrix metalloproteinases (MMPs) are believed to play a significant role in collagen degradation, and both UVA and UVB can induce MMP overexpression.30,31 At least 21 MMPs have already been identified in human being pores and skin.32 Among these, MMP-1, 3, and 9 are believed as the utmost very important to UV-induced skin surface damage. MMP-1 may be the just enzyme in a position to catalyze cleavage from the collagen triple helix in type I and III collagens. MMP-3 and 9 can cleave dermal collagens (type I, III and V) just after initiation of cleavage by MMP-1.33 MMP-1 in human being cells and MMP-13 in mice 2645-32-1 IC50 had been selected because of this research because of the pivotal part as known markers of UV harm.33,34 With this research, we investigated the result of Syk on MMP-1 and MMP-13 expressions and the result of UVR on Syk expression and activation. Our results reveal that Syk is actually a fresh previously focus on for the avoidance and treatment of pores and skin photodamage. Components and strategies Antibodies The next antibodies had been found in this research: MMP-1 and MMP-13 antibodies (Calbiochem, UK), Syk and -actin (Santa Cruz Biotechnology Inc., Santa Cruz, CA), TLN1 phospho-JNK, phsopho-p38, phospho-Erk1/2 and JNK (Cell Signaling Technology, Danvers, MA), phosphotyrosine (Millipore, Billerica, MA). Cell tradition, transfection and UVR treatment Human being dermal fibroblasts AG04058 (Coriell Institute for Medical Study, Camden, NJ) had been cultured and taken care of in MEM including blood sugar 2645-32-1 IC50 (4.5 mg/ml), glutamine (2 mM), streptomycin (100 U/ml), penicillin (100 g/ml), and 10% heat-inactivated fetal bovine serum. For cell transfection, Fugene 6 transfection package (Roche, Germany) was utilized to provide Syk cDNA as well as the Saint-Red siRNA delivery program (Synvolux Therapeutics B.V., HOLLAND) was selected to transfect Syk siRNA and control siRNA (Santa Cruz Biotechnology Inc., Santa Cruz, CA) in to the cells. Cells had been subjected to UVB (312 nm) (60 mJ/cm2) with a Stratalinker UV Crosslinker (Stratagene, La Jolla, CA). Cell supernatants had been gathered 24 hrs after UV publicity, and ready for MMP-1 manifestation assay. Animal Tests and UVR treatment The SKH1 hairless mouse can be a more developed animal model to review UV-induced harm in pores and skin.35 SKH1 female albino hairless.
Purpose Maximum tolerated dosage, basic safety, pharmacokinetics, and pharmacodynamics were assessed within this stage 1 research of PNT2258, a BCL-2-targeted liposomal formulation of the 24-bottom DNA oligonucleotide called PNT100. to PNT2258 above the publicity level necessary for anti-tumor activity in preclinical xenograft examining of 22,377?ng?h/ml (PK evaluation 2012). Exhaustion was the mostly reported undesirable event. Dose-limiting toxicity, manifesting being a transient upsurge in aspartate aminotransferase, happened at 150?mg/m2, the best dosage tested. Four topics, two each with medical diagnosis of non-small-cell lung cancers and sarcoma, treated at dosages of 64?mg/m2 or more, remained on research for 5C8 cycles. Conclusions PNT2258 was secure and well tolerated on the dosages examined up to 150?mg/m2. Contact with PNT2258 led to clinically manageable reduces in lymphocyte and platelet concentrations. (%)?Man12 (55)?Female10 (45)Origin?Caucasian18 (82)?African2 (9)?Hispanic2 (9)ECOG performance range, (%)?03 (14)?116 (72)?23 (14)Disease stage at entry, (%)?Stage IV22 (100)Pathologic medical diagnosis?Pancreatic cancer5?Digestive tract adenocarcinoma5?Sarcoma3?Prostate, adenocarcinoma2?Lung, non-small-cell carcinoma2?Breasts, adenocarcinoma1?Endometrial1?Mind and throat carcinoma1?Hepatocellular carcinoma1?Neuroendocrine tumor1Preceding treatment?Systemic therapy22 (100)?Medical procedures17 (77)?Radiotherapy8 (36) Open up in another home window Eastern Cooperative Oncology Group Treatment Patients received PNT2258 at dosages which range from 1 to 150?mg/m2, constituting over 300 dosages and sixty 21-time cycles. Over-all dosage levels, sufferers received a median of 2 finished cycles, with a variety of 0C8 cycles. The most frequent reasons for research discontinuation were intensifying disease or symptomatic deterioration (19 sufferers, 86?%). Two sufferers (9?%) discontinued therapy because of adverse event, and 1 individual (4?%) withdrew up to date consent. From the 335 prepared dosages of PNT2258, 314 had been administered as planned. No patients had been dosage decreased for toxicity. PNT2258 was well tolerated at dosage amounts 1 through 64?mg/m2. An individual individual manifested a quality 3 DLT of back again/flank discomfort while getting the infusion on the 85?mg/m2 dosage level, triggering expansion from the cohort to six content. After the incident from the DLT with the discretion from the dealing with physician, subsequent sufferers could receive premedication ahead of infusion with dexamethasone 10?mg, diphenhydramine 50?mg, and ranitidine 50?mg IV, either alone or in 1243583-85-8 supplier mixture, on time 1 of every cycle seeing that prophylaxis for back again/flank discomfort. This involvement limited extra occurrences of flank/back again pain. No extra DLTs happened on the 85?mg/m2 dosage level or at 113?mg/m2. One DLT happened at 150?mg/m2 manifesting being a quality 1243583-85-8 supplier 3 upsurge in AST that led to expansion from the cohort. No extra routine 1 DLTs had been noted on the 150?mg/m2 dosage level. However, an individual developed a quality 4 thrombocytopenia within 30?times of research participation on the 150?mg/m2 dosage level. Desk?2 summarizes the drug-related toxicities in any way dosage amounts. Across all dosage levels and irrespective of attribution, a complete of 79 adverse occasions and 6 critical adverse occasions (find section below) had been reported. The most frequent AEs were exhaustion (8 occasions in 7 topics; 8/79, 10.1?%; quality range 1C2) and infusion response manifesting as Rabbit Polyclonal to ZNF682 back again or flank discomfort (6 occasions in 4 topics; 6/79; 7.6?%; quality range 2C3). The upsurge in aspartate aminotransferase on the 150?mg/m2 dosage level was seen in an individual with metastatic disease towards the liver organ and elevated amounts resolved spontaneously within 48?h. One affected individual died, due to disease development, within 30?times of research participation. Desk?2 Treated sufferers ((%)(%)(%)(%)(%)(%)(%)(%)(%)grade, patients, amount, milligrams, meter aListed adverse events are those assessed with the investigators as is possible, probably or definitely linked to research drug collected in the first 1243583-85-8 supplier dosage of research medication until 30?times after discontinuation from the analysis. Sufferers are counted only one time per event, with the best experienced quality observed. No drug-related toxicity was reported in 2 or even more patients 1243583-85-8 supplier on the 8 and 32?mg/m2 dosage 1243583-85-8 supplier levels. Just toxicities reported in 2 or even more patients over-all cycles are reported with.
Therapies targeting vascular endothelial development element (VEGF) are revolutionizing the treating diabetic retinopathy (DR) and diabetic macular edema (DME). with the purpose of improving the achievement of clinical medication advancement. This model shows that to supply a validated preclinical focus on, researchers should demonstrate the next: the part of the prospective in regular physiology, a causal connect to disease pathogenesis, relationship to human being disease, and the capability to elicit medically relevant improvements of disease phenotypes in pet versions with multiple, chemically varied interventions. This model provides a platform to validate the existing preclinical focuses on and identify book focuses on to improve medication advancement achievement for DR. Going back twenty years, managing the metabolic deregulation induced by diabetes continues to be the primary & most effective method to slow the advancement and development of microvascular problems including diabetic retinopathy (DR) (1,2). Following the appearance of medically significant vascular lesions and macular edema, laser beam photocoagulation remains a highly effective approach to sluggish the increased loss of visible acuity (3,4). These 104632-25-9 manufacture founded approaches have been recently extensively examined (rev. in 5). Regrettably, ~20% of individuals with type 1 diabetes develop proliferative DR actually under extreme metabolic control by exogenous insulin (6), while some have inherent 104632-25-9 manufacture problems with keeping proper euglycemia. Consequently, understanding the causative root systems of DR continues to be very important in the treating this insidious disease. Fundamental and clinical study in to the inflammatory cytokines and proangiogenic indicators that get DR has supplied new therapeutic strategies for the treating diabetic eyes disease. Significantly, antiCvascular endothelial development aspect (VEGF) 104632-25-9 manufacture therapy provides revolutionized the treating diabetic macular edema (DME). The Diabetic Retinopathy Clinical Analysis Network recommended that ranibizumab increases visible acuity final results in sufferers with DME. Subsequently, in the RISE scientific trial, 44.8% of sufferers treated with 0.3 mg ranibizumab for two years gained 15 words improvement in visible acuity vs. 18% of sham-treated sufferers. In the Trip research, 45.7% of sufferers treated with 0.5 mg ranibizumab obtained 15 words vs. 12.3% of sham-treated sufferers. Furthermore to boosts in visible acuity, improvements had been seen in retinal width as assessed by optical coherence tomography and decreased risk of additional vision reduction (7). This achievement has supplied much-needed therapeutic choices and a blueprint to find novel remedies for diabetic ocular problems. VEGF: dual function in physiology and pathology Clinical achievement of anti-VEGF therapy is dependant on basic scientific analysis into the systems of angiogenesis, neovascularization, and vascular permeability resulting in a wide consensus in the technological community on the importance and dependence on this growth aspect to these described procedures. Exploration in tumor biology resulted in the hypothesis that diffusible elements supplied angiogenic and permeabilizing indicators towards the tumor vasculature. This resulted in the seminal hypothesis by Dr. Judah Folkman that inhibition of angiogenesis could be a strategy to prevent tumor development (8). Proteins purification and molecular cloning allowed two groupings Sermorelin Aceta to find the powerful angiogenic and permeabilizing aspect: one coining the word vascular permeability aspect and the various other VEGF (9,10). An assessment from the biology of VEGF and its own receptors on angiogenesis, proliferation, migration, and vascular permeability was performed by Chung and Ferrara (11). Right here, we offer a retrospective evaluation of the importance from the seminal results in the introduction of anti-VEGF therapies and propose a model to apply straight to the newest group of preclinical focuses on for DR. Crystal clear and compelling hereditary studies exposed that VEGF contributes a crucial and essential part in vascular biology (rev. in 11). Hereditary loss-of-function experiments shown that developmental manifestation of VEGF is necessary for vasculogenesis and angiogenesis, as solitary allele inactivation led to embryonic lethality with lacking vascularization of many organs (12,13). Furthermore, gene focusing on via the Cre-loxP program and administration of the soluble VEGF receptor chimeric proteins resulted in significant raises in mortality and impaired body organ advancement; however, this essential requirement of VEGF waned by four weeks of pet maturation (14). This is the first proof that VEGF function could be modified in the adult with no detrimental effects seen in advancement. VEGF clearly 104632-25-9 manufacture plays a part in vascular homeostasis, and additional research verified that excessive VEGF and aberrant VEGF signaling induces pathological angiogenesis and permeability. Pharmacological 104632-25-9 manufacture focusing on of VEGF started in the tumor field ahead of its software to ocular disease. The 1st preclinical proof anti-VEGF therapy was performed using targeted monoclonal antibody (mAb) technology that effectively prevented the development of tumors in pet versions (15). The outcomes were confirmed by targeted deletion from the.
History & Aims Transforming growth issue beta 1 (TGF1) role in cholangiocarcinoma (CCA) initiation and growth needs additional definition. Conclusions This research shows that TGF1 is definitely involved with CCA tumor development and participates through miR-34a mediated downstream cascades, and it is a focus on to inhibit CCA advancement and development. utilizing a rat intrahepatic model. Overexpression of TGF1 considerably improved the CCA tumor quantity and quantity of metastatic foci (Fig. 6A and B). To determine whether TGF1 also promotes CCA development through miR-34a connected cascades, manifestation degrees of miR-34a focus on genes, CCND1, CDK6, and c-Met had been also evaluated. Consistent with discovering that shTGF1 inhibits miR-34a focus on gene manifestation, we noticed that mRNA manifestation degrees of CCND1, CDK6 and c-Met had been also considerably improved in tumor cells upon overexpression of TGF1 (Fig. 6C and D). The proteins manifestation degrees buy 65-86-1 of cyclin D1, CDK6, and c-Met had been improved by overexpressing TGF1 aswell. Finally, TGF1 considerably promotes the manifestation from the EMT marker, (-catenin) with this rat intrahepatic model program (Fig. 6E and F). Open up in another window Number 6 Overexpression of TGF1 promotes CCA development(A) Macroscopic pictures of intrahepatic CCA and metastatic tumors inside a rat model inoculated with BDE-Neu cells transfected with lentivirus comprising bare vector (EV) or TGF1 expressing cDNAs. Best panel displays tumor quantity as indicated. (B) Metastatic foci had been identified as indicated with this rat intrahepatic CCA model. The mRNA manifestation degrees of (C) CCND1, CDK6, and (D) c-Met had been assessed in tumor cells as indicated. (E) Immunoblotting outcomes of CCND1, CDK6, -catenin, and c-Met manifestation are demonstrated. Coomassie blue offered as launching control. (F) Proteins manifestation degrees of cyclin D1, CDK6, -catenin and c-Met in accordance with control are demonstrated. *, p 0.05; **, p 0.01. 4. Conversation Parasitic attacks and biliary-tract inflammatory disorders have already been founded as risk elements for CCA advancement. Recent meta-analysis shows that cirrhosis is definitely a significant risk factor because of this disease aswell . With this framework, manifestation of TGF1 is definitely highly from the advancement of intensifying fibrosis resulting in cirrhosis , Nevertheless, it's been controversial concerning the part of buy 65-86-1 TGF1 manifestation in tumor advancement and development. One hypothesis offered is definitely that TGF1 inhibits cell routine development and proliferation at first buy 65-86-1 stages of tumor development and promotes metastasis through EMT development at later phases of the condition . Recently, many novel findings possess recommended that TGF1 manifestation promotes malignancy stem cell development and level of resistance to chemotherapy. Therefore, focusing on TGF1 was expected to enhance the potency of chemotherapy in breasts cancer, for instance . To get this idea, TGF1-FOXO signaling could be required for keeping leukemia initiating cells in chronic myeloid leukaemia . Many targeting approaches aimed against TGF1 possess shown some anti-tumor activity. A particular inhibitor from the TGF1 receptor, SB-431542 shown restorative potential against many human being tumors . Another TGF1 receptor inhibitor, LY-2157299 offers completed stage II and offers entered stage III clinical tests for a number of buy 65-86-1 types of tumors  and claim that TGF1 could be a practical oncogenic focus on. From previous research, cirrhosis continues to be proven a significant risk element for CCA advancement and since TGF1 is definitely highly linked to pathogenesis of the disease procedure, we raised the chance that TGF1 could be very important to CCA advancement and development and a potential restorative focus on because of this disease. Nevertheless, there is certainly controversy concerning the part of TGF1 on CCA TRK development and development [36, 37]. Many research on TGF1 signaling in CCA are linked to short-term publicity with recombinant TGF1 proteins which is not really obvious if these results continue being energetic under long-term circumstances connected with tumor development. With this study, focusing on TGF1 both with particular shRNA and pharmacological substances considerably inhibited CCA development; the underlying systems for TGF1 results had been explored. Previous results show that TGF1.
Gentle tissue sarcomas certainly are a heterogeneous band of tumors numerous different subtypes. tumors. Seafood amplification and duplicate number gain had been within 4% from the tumors (15/413). Two examples, both undifferentiated pleomorphic sarcomas, satisfied the requirements for higher level amplification of hybridization and immunohistochemistry. Intro Soft cells sarcomas represent a heterogeneous tumor group which includes over 50 different histologic subtypes . Used together approximated 12,020 fresh cases will become diagnosed and 4,740 smooth cells sarcomas related fatalities should be expected in america in 2014 . Soft cells sarcomas tend to be 497-76-7 diagnosed at advanced stage, because symptoms could be absent for a long period. At period of analysis, 10C25% of individuals present hematogenous metastases, mainly to lung, bone tissue and liver organ . Regular treatment for localized tumors is definitely surgery treatment. High-grade tumors are using clinical configurations treated with 497-76-7 rays therapy, and in addition conventional chemotherapy is effective in some individuals. In advanced stage, chemotherapy happens to be used as regular treatment . Nevertheless, these treatments frequently have undesireable effects or are inadequate, e.g., for retroperitoneal sarcomas the 5-yr local control price is 40C71% as well as the 5-yr survival rate is definitely low with 51C60% . 497-76-7 Sarcomas from the extremities possess a high regional recurrence price of 30C50% and half the individuals die using their disease . For a few sarcoma subtypes tumor particular molecular aberrations such as for example gene translocations, amplifications or mutations MAP2 have already been identified, nevertheless, their exploitation as restorative targets continues to be limited. The very best example for molecular targeted therapy in mesenchymal tumors is definitely treatment with tyrosine kinase inhibitors in gastrointestinal stromal tumors (GIST) which bring activating or mutations in around 90%. For individuals with other smooth cells sarcoma entities, nevertheless, fresh effective and dependable molecular based remedies are desirable. Focusing on tyrosine kinases offers given promising outcomes in lots of malignancies, but extensive research on soft cells sarcomas remain lacking. One particular therapeutically tractable tyrosine kinases is definitely MET which happens to be at the mercy of many clinical tests with promising outcomes. MET is definitely a transmembrane tyrosine kinase receptor and can be referred to as hepatocyte development aspect receptor (HGFR) . It really is generally located at the top of epithelial cells  and continues to be within fibroblasts , endothelial cells , pericytes and even muscles 497-76-7 cells . It really is activated within a paracrine way by its just known ligand HGF/SF (hepatocyte development aspect or scatter aspect) which is normally secreted by mesenchymal cells . The HGF/MET pathway promotes cell proliferation, motility and angiogenesis. Physiologically it really is turned on during embryogenesis, morphogenesis, tissues regeneration and fix. Improper activation can lead to tumorigenesis, tumor angiogenesis, invasion and metastasis. Aberrant activation could be ligand powered by paracrine and autocrine systems or predicated on ligand unbiased mechanisms such as for example receptor overexpression, activating gene mutations, gene amplification or changed transcription [12, 13]. MET appears to are likely involved in the pathogenesis of a number of tumors such as for example lung, liver organ, renal and gastric cancers [14C20]. Some gentle tissue sarcomas are also reported to overexpress MET, included in this synovial sarcomas, leiomyosarcomas, rhabdomyosarcomas, fibrosarcomas and other styles [21C27]. An overexpression from the MET ligand HGF could possibly be foundamong othersin malignant pleural mesotheliomas, gastric carcinomas, gliomas aswell as in a few soft tissues sarcomas [22, 24]. The HGF/MET pathway can therapeutically end up being targeted in many ways, e.g., blockade from the ligand-receptor connections using HGF antagonists, HGF neutralizing antibodies or MET antibodies, inhibition of receptor dimerization and inhibition of kinase activity with interruption of downstream signaling using little molecule inhibitors . There are several HGF/MET inhibiting medications in clinical studies. Most sufferers contained in those research are treated for carcinomas in support of seldom for sarcomas. Among all scientific trials shown at clinicaltrials.gov  for MET and HGF inhibitors four research are open up explicitly for sufferers with sarcomas and a couple of multiple research open to sufferers with not further specified great tumors, that could include also soft tissues sarcomas (June 2014). Few sarcoma subgroups.
We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve development factor (NGF) manifestation in post-infarcted normoglycemic rats, concentrating on adenosine and reactive air species creation. traditional western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic ratings in the sitagliptin-treated infarcted rats had been significantly less than those in automobile. studies showed an identical aftereffect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated degrees of superoxide and NGF. Furthermore, the helpful ramifications of sitagliptin on superoxide anion creation and NGF amounts could be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated development of superoxide in the nondiabetic infarcted rats. local types of myocardial necrosis 6. On the other hand, others demonstrated a considerably attenuated infarct size after administering ADA blockers 7. The discrepancy may derive from the variations in regional interstitial adenosine focus during ischemia, which may buy Isoliensinine be acquired using the microdialysis technique. Extremely recently, we shown that oxidative tension is improved and plays a crucial part in ventricular remodelling after MI 8,9. During chronic stage of MI, local upsurge in sympathetic innervation was frequently observed in the remote control zone 10. Improved sympathetic nerve denseness has been proven to lead to the event of lethal arrhythmias and unexpected cardiac loss of life in human beings 11. Nerve development factor (NGF) is definitely a prototypic person in the neurotrophin family members, members which are crucial for the differentiation, success and synaptic activity of the peripheral sympathetic and buy Isoliensinine sensory anxious systems 12. The NGF promoter consists of activator proteins-1 13, which is definitely put through redox rules through its conserved cysteine residue 14. We've shown that superoxide was in charge of sympathetic innervation in infarcted rats 9. A significant way to obtain superoxide anion may be the sequential rate of metabolism of adenosine DPP-4 and xanthine oxidase to the crystals 3. Accumulating data possess indicated that DPP-4 inhibitors offer cardioprotection within an insulin-independent way ancillary pathways 1. Earlier studies show the DPP-4 inhibitor sitagliptin can decrease myocardial damage and improve cardiac function in the severe configurations of ischemia/reperfusion model 15,16. DPP-4 knockout mice demonstrated a smaller sized infarct and improved success after remaining anterior descending coronary artery ligation compared to the control mice 17. Nevertheless, sitagliptin attenuated many, however, not all, areas of undesirable remodelling in the post-MI establishing 18. For instance, Yin released by the united states Country wide Institutes of Wellness (NIH Publication No. 85-23, modified 1996). Test 1 (substrate development in sitagliptin-related superoxide and NGF amounts, we utilized the ADA inhibitor, the A1R inhibitor and hypoxanthine, respectively, within buy Isoliensinine an model. A month after induction of MI by coronary ligation, infarcted rat hearts had been isolated and put through no treatment (automobile), sitagliptin (5?M), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 250?M, ADA inhibitor), sitagliptin + 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX, 100?nM, A1R antagonist), or sitagliptin + hypoxanthine buy Isoliensinine (1?mM). The dosages of sitagliptin, EHNA, DPCPX and hypoxanthine have already been been shown to be effective in modulating natural actions 5,17,24,25. The center was perfused using a noncirculating improved Tyrode's solution filled with (in mM): blood sugar 5.5, NaCl 117.0, NaHCO3 23.0, KCl 4.6, NaH2PO4 0.8, MgCl2 1.0 and CaCl2 2.0, equilibrated in 37C and oxygenated using a 95% O2 to 5% CO2 gas mixture 26. The medications had been infused for 60?min. By the end of the analysis, all hearts (test. A month after induction of MI by coronary ligation, infarcted rat hearts had been isolated and put through no treatment (automobile), sitagliptin (10?M), or a combined mix of sitagliptin and 3-morpholinosydnonimine (37?M, SIN-1, a peroxynitrite generator). Each center was perfused using the same process as test 2. The dosage of SIN-1 was utilized as previously defined 27. To preclude nonspecific activities to SIN-1, the fairly low focus of SIN-1 was utilized. By the end of the analysis, hearts (electrophysiological research In order to avoid the confounding aftereffect of central sympathetic actions on pacing-induced ventricular arrhythmias, we utilized the Langendorff center. As the residual neural integrity in the infarct site is among the determinants from the response to electric induction of ventricular arrhythmias 30, just rats with transmural scar tissue had been included. Programmed electric excitement was performed with electrodes sewn towards the epicardial surface area of the proper ventricular out-flow system. Pacing pulses had been generated from a Bloom stimulator Rabbit polyclonal to ANAPC2 (Fischer Imaging Company, Denver, CO, USA). To stimulate ventricular arrhythmias,.


text:
Q: Font Awesome 6 (beta) and dynamic icon name in Next JS I am developing a website with Next JS. This is the first time I use this language and I still have a lot to learn.
Now, I have a Pro subscription to Font Awesome and I am looking to use their component directly in my project, as described in their guides.
https://fontawesome.com/v6.0/docs/web/use-with/react/
https://fontawesome.com/v6.0/docs/web/use-with/react/add-icons
Basically, just using a component like this:
<FontAwesomeIcon icon={brands("google")} />

It works.
The problem, which I can't solve, is how to set the "google" value dynamically, in a previously initialized variable. I need that because this values are coming dynamically from a database.
If I try:
var example = "google";
<FontAwesomeIcon icon={brands(example)} />

Then I receive this error: "Only string literals are supported when referencing icons (use a string here instead)".
Anyone have any ideas?

A: The way you import your icons uses a babel macro. It means that the referenced icon must be known at build time. It just won't work, because Babel can't figure out what icon should be imported, it can only be done during runtime. That's why it tells you that only string literals are supported.
So you need to use the second method, explained in the docs. You have to have some kind of mapping between icon and the value from DB and then grab the relevant icon. Something like this:
// not sure about exact import
import { faGoogle } from '@fortawesome/free-brand-svg-icons';

// you'd put all valid values that can come from the backend here
const myIcons = {
  google: faGoogle
}

// ...

const example = 'google';
<FontAwesomeIcon icon={myIcons[example]} />

The other option is to use library.add, explained here and then do the same as above but instead of imported icon use a string, e.g. google: 'fa-brands fa-google' (again, not sure about exact value here).

A: Would the following work?
var example = ['fab', 'google'];

<FontAwesomeIcon icon={example} />

P.S. It is recommended to use the let or const keywords with ES6.

A: // Utils
const UpperFirst = (sentence) => {
    if (!sentence || (typeof sentence !== 'string')) return null
    return `${sentence.charAt(0).toUpperCase()}${sentence.slice(1)}`
}

// React Generic Component
import React from 'react'
import { FontAwesomeIcon } from '@fortawesome/react-fontawesome'
import * as solid from '@fortawesome/free-solid-svg-icons'
import * as regular from '@fortawesome/free-regular-svg-icons'
import { UpperFirst } from '@utils'

const GenFontAwe = ({ isReg, customClass, nameIco }) => {
    if (!nameIco) return null
    const finalName = nameIco.split('-').map((cv, ind) => ind === 0 ? cv : UpperFirst(cv)).join('')
    const finalIcon = isReg ? regular[finalName] : solid[finalName]
    if(!finalIcon) return null
    return <FontAwesomeIcon icon={finalIcon} className={customClass || ''} />
}

export default GenFontAwe

// Consume that way:
<GenFontAwe nameIco='fa-folder-open' isReg customClass="h1 p-5" />

redpajama_set_name: RedPajamaStackExchange


text:
Це стаття про британську телеком компанію, якщо Ви шукаєте про оператора мобільного зв'язку в Україні, який працює під брендом цієї компанії, див. статтю Vodafone Україна.

Водафон () — британська міжнародна телекомунікаційна компанія з штаб-квартирою у Лондоні (юридично компанія зареєстрована в м. Ньюбері, що в графстві Беркшир). Є другим за величиною мобільним оператором у світі (після China Mobile) — як за кількістю абонентів так і за рівнем доходу станом на 2013. Понад 449 млн абонентів в Європі, на Близькому Сході, в Африці та Південно-Східній Азії користуються послугами Vodafone.

Компанії належать мережі в 21 країнах світу (з них 4G — у 18 країнах), також вона має партнерські мережі в понад 40 інших країнах. Його структурний підрозділ Vodafone Global Enterprise веде діяльність у сфері телекомунікацій та обслуговування в IT у понад 65 країнах.

Акції компанії котуються на Лондонській фондовій біржі та є складовою частиною індексу FTSE 100 Index.

Назва
Назва «Vodafone» — це скорочення від англомовних слів «voice data phone» (голос, інформація, телефон).

Історія
Заснована в 1983 під назвою Racal Strategic Radio Ltd як дочірня компанія Racal Electronics.

1 січня 1985 здійснено перший дзвінок в аналоговій мережі.

У 1991 компанія виділилася зі складу Racal Electronics та перейменовується в Vodafone Group.

У липні 1992 запущена перша GSM-мережа Vodafone у Великій Британії.

Vodafone в Європі

Vodafone діє в таких країнах Європи (дані про кількість абонентів на грудень 2005 року):

У жовтні 2007 року стало відомо, що компанія Tele2 продала свої підрозділи в Іспанії та Італії компанії Vodafone за 775 млн євро.

В Україні

16 жовтня 2015 року другий за величиною абонентської бази мобільний оператор в Україні «МТС Україна» оголосила про договір з Vodafone щодо спільного запуску в Україні цілих спектрів сервісів, включаючи послугу мобільного інтернет-доступу на основі 3G-технології. «МТС Україна» поступово перейшла на бренд Vodafone, спочатку два бренди існували паралельно.

Примітки

Посилання

 Vodafone Україна
 Офіційний інтернет-магазин Vodafone Shop Україна

Оператори стільникового зв'язку
Підприємства, засновані 1983
Підприємства Нью-Йоркської фондової біржі
Телекомунікаційні підприємства Великої Британії
Виробники мобільних телефонів

redpajama_set_name: RedPajamaWikipedia


Domestic workers face low pay, rampant sexual harassment, and a lack of benefits. The National Domestic Workers Alliance works tirelessly to help improve the lives of women and workers to get them the respect they deserve.
Support this work and the National Domestic Workers Alliance with a tax-deductible gift today.


Kevin is a 30 year veteran of the creative experience – a composer, songwriter, lyricist, director, as well as an advisor to artists, a creative consultant, and a producer. Kevin creates, manages and directs creatives of all kinds with the explicit goal of delivering a one-of-a-kind, original experience that leaves a lasting impression.
As the creator of 5by4 Productions, Kevin has conceived, written and produced all of 5by4's award-winning immersive theatrical experiences. 5by4 has built its unique brand of live entertainment into a commercially successful franchise, with five different productions that have toured extensively throughout the U.S., Canada, Mexico, and Europe. 5by4's productions have been heavily featured in the media, with a PBS Television Special amongst other dedicated programs, and to date, the Company has performed over 300 shows in six countries to over one million adoring fans. 5by4's newest production, Fate Still Rests, is currently being developed for the company's first New York City production.
As a composer, Kevin has composed the score to more than 45 feature films, including two Academy Award® nominated documentaries and is the recipient of two 21st Century Filmmaker Awards for Excellence.
In addition Kevin has composed, recorded, performed and produced music for a variety of television, animation and advertising clients including; NBC, ABC, CBS, Turner, The Cartoon Network, Syfy, National Geographic, A&E, Animal Planet. AT&T, Volvo, Mercedes Benz, Ford, Dodge, Six Flags, Discover Card, Toyota, and Kellogg's.
As a songwriter, Kevin has created, record and produced the title tracks to 12 feature films, as well as the book, music and lyrics for 15 stage musicals.
When not working, Kevin dreams of radically different new ways to immerse audiences in extraordinary, life-changing story-telling experiences.


Are you still thinking where to take your toddlers within Delhi/NCR to have a fun time? I had already covered National Rail Museum and Old Fort Show in my earlier blog (https://www.mysecondinnings.in/2018/11/Day-Trips-Delhi-Museum-Oldfort.html). Below are some more places I found which I am sure your kiddos will enjoy as my daughter did.
My daughter absolutely enjoys jumping on the bed and when I told her about a place where she can keep on jumping continuously, her excitement was at its peak. Opened in 2017, Skyjumper Trampoline Park became India's largest indoor trampoline arena. The arena is huge with about 100 interconnected trampoline to jump on and the whole premises is meticulously designed giving safety a lot of priority. Such is the atmosphere of the park that adults too feel to enter the arena and give it a shot, maybe trying to reminisce their younger days.
We went on a weekend and took a Mother Child combo ticket which cost Rs 650 for 30 minutes. There is an indoor cafe serving snacks and beverages outside the arena where my husband decided to stay. The park has a separate section for toddlers as they are too young to balance themselves sometimes and here they can jump at their own pace. My daughter first found difficulty in balancing and was constantly holding my hands. But as she gained confidence she started jumping independently and enjoyed more. As was expected, my daughter resisted coming out of the park once 30 minutes passed and it took a while to convince her to do so.
Besides normal jumping, the park offers Tarzan Rope, Volleyball, Dodgeball, Basketball Walk the Wall and slides falling into foam of foam cubes, so that every age group is engaged. My only advise is to not eat for an hour before you go there. The park offers packages for special events, such as birthday parties, corporate events and school trips, and also offers coaching on gymnastics for kids 6 and above. You can even purchase a trampoline for your personal use.
When to Visit: On weekdays the timings are 11:30 AM to 9 PM, while on Sat and Sun the park opens at 10 AM.
In December 2018, South Delhi Municipal Corporation opened Nandan Van in GK-1, a park fully focused on children aged 12 years or below. A one of its kind in South Delhi, the park has been creatively designed offering ample playing opportunities to kids and at the same time promoting outdoor playing activities culture rather than being confined to mobiles and tablets. With respect to safety, the play area has specialized rubber surface to prevent any fatal injury to the children. Also, the fibre made multi-purpose play stations are safer than orthodox iron made play equipment.
The park has a separate toddlers section which I really liked. The park also includes a number of activities to keep the children engaged physically and mentally. One can find swings, board games, musical instruments, rope bridges, animal statues and much more in this park. My daughter enjoyed the Stapu game arena and slides the most. She also had a fun time with the animated statues of Shrek, Goofy and Minions. Besides children, there are facilities for adults accompanying these children such as proper benches, gazebos and walkways have been developed for their usage.
Another unique feature of this park is it has installed a sensory wall for visually disabled children and I am not able to recall any other park doing so. The artistic entry gates with sculptures is a good strategy to attract a large number of kids. There is also a small canteen from where you can grab a quick bite or quench your thirst. The park has been designed with modern equipment and innovative swings which makes it a perfect place to go with your kids.
Every city requires its escape valves where people can feel they are away from the noise of a commercial city. As a mother, I always look for outdoor places which are kids friendly and my daughter can just run around and play freely. There are certain areas in Delhi which are lush green and apt for a family excursion. Deer Park, located in South Delhi's Hauz Khas area, is one such park where people usually go with their families for picnic and at the same time taking a break from their hectic schedule.
The park is a home to a number of species, primarily deer, from where it derived its name. Other species include peacocks, rabbits, ducks, guinea pigs and a wide range of bird life, all living in harmony with each other. With large number of shady trees, lush grasses and a water body, the park offers a peaceful ambience which is a delight for any nature lover. This serene surrounding also attracts a lot of morning walkers to this place. Despite being close to busy markets of Hauz Khas and Green Park, the park manages to sustain an illusion of remoteness. There is a Rose Garden and a district park adjacent to Deer Park and this whole belt is one of the biggest green spaces of Delhi. One should visit this place during winters or early spring and utilize the time to recharge their physical and emotional batteries.
When to Visit: The park is opened all days of the week. The timings are 5 AM to 7:30 PM during summer and 5:30 AM to 6:30 PM in winters.
I hope you found the above list useful and I recommend you should definitely take your children to all these places and I am sure you will not be disappointed. If you know any other place where I can take my daughter, do mention in the comments section.


If It's Too Loud...: The Beths - "Great No One"
If you've been reading this blog for any length of time, you know that we have a soft spot for the current crop of 90's influenced indie rockers, especially ones hailing from Australia or New Zealand. This is why we've been adoring the singles being released by The Beths, and "Great No One," their latest, is more of the same. It's incredibly upbeat, catchy as can be with just enough dirty fuzz to keep it interesting. Plus, we love sad songs that sound happy, and The Beths are proving themselves to be masters of that. This new album can not come quickly enough.
You can watch the lyric video for "Great No One" below. (I know, lyric videos are completely boring 95% of the time, but this one is totally worth it and a ton of fun.) Future Me Hates Me, the new album from The Beths, will be out August 10 on Carpark Records. You can pre-order a copy here. For more on The Beths, be sure to follow them on Facebook and Twitter.


You could win two tickets to the LIVE finale of American Idol!
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Discover how to use the Three Dimensional building block approach to training so your players develop a deeper understanding of their roles and how to play the way you want.
Now this is comprehensive! Three Dimensional Soccer Training is a book born from analyzing how the world's most popular formations are played and what training systems are needed to play them effectively. Rather than focus on technique or formations independently, this book shows you how to combine elements like building blocks to create complete 'three dimensional training'.
Do you want to make your coaching sessions more specific and focused? Would you like to know how to build sessions together that give your players a deeper understanding of how to combine technique with tactics on game day? Well, Three Dimensional Soccer Training is a book that has all the answers.
Born from its author's passion for studying how formations are played around the world, Three Dimensional Soccer Training explains how to coach players so they gain an enriched technical and tactical understanding of their position.
Instead of coaching technique, formations and roles individually, Three Dimensional Soccer Training explains step-by-step how to progressively train players in all these areas in each coaching session. It tells you what to teach, when and why. The outcome is that your players will develop a three dimensional understanding of how everything fits together. Rather than simply be able to pass smoothly or know where they need to place the ball, they will know which foot to pass to and why.
Whether you want to play the 4-3-3 or 4-4-2, 4-2-3-1, zonal or man marketing, Three Dimensional Soccer Training gives you a complete model for progressively training players to develop a deeper, more rounded view of how technique and tactics fit in your system.


In the spring of 1945, Dave Williams (Denny's father) began making the now famous "Williams French fries" in his garage, selling them to customers in the Lykens area. They quickly became a favorite at carnivals, fairs and football games, and they sold for 15 cents per cup. Denny started working in his father's business at 4 years old making change. Denny quickly learned the secrets of making Williams French fries taste so GREAT! After the passing of Denny's father, in 1975, Denny purchased the business with one small food truck. In May 1977, Denny leased a parcel of ground on the square in Millersburg and opened a sandwich shop with a small menu to include: hamburgers in sauce, hot dogs and of course "Williams French Fries". In 1992 Denny purchased Lennie's Restaurant located at 3828 Peters Mountain Road, Halifax, PA. It's open daily and offers an expanded menu and many PA Dutch favorites.
We specialize in on-site cooking for corporate functions: including employee appreciation parties, picnics, safety award meals, grand openings or any other special event. We also cater holiday meals, banquets and weddings. Choose from one of our many menus or design your own. WE CATER TO PLEASE!
Interested in employment opportunities with Williams Enterprises?


Book #2 in the new MEDAL OF HONOR series by Michael P. Spradlin focuses on the war in Afghanistan.
Ryan Pitts was born in Massachusetts and raised in New Hampshire. During his senior year in high school, he decided to enlist. It was 2003. Ryan knew he wanted to go to college, but he wasn't sure what he wanted to study so he joined the army.
He trained at the U.S. Army Field Artillery School. His training specialized in close-combat aviation. After completing training as a paratrooper, he was assigned to the 173rd Airborne Brigade in Italy. The 173rd was famous for combat in multiple wars.
The battle that earned Pitts his Medal of Honor involved the Battle of Wanat just outside of Kabul, Afghanistan. His unit was to defend Observation Post Topside to protect the Vehicle Patrol Base Kahler. The surprise attack took place at 4:00 am and lasted several hours. Pitts was badly wounded during the attack that killed the rest of his fellow soldiers. Despite severe blood loss, Pitt held back the insurgents with gunfire and grenades until supporting troops could arrive.
While reading Ryan Pitts' story, I learned about other achievements of the 173rd Airborne Brigade in Vietnam, about the difficult conditions of fighting in Afghanistan, about the role of paratroopers and the weapons they use, and also about aircraft used in battle like the Apache attack helicopters and more. Author Michael P. Spradlin's ability to research and share facts in an informative and entertaining way is sure to attract readers as his MEDAL OF HONOR series continues.
As a total fan of Wendelin Van Draanen's books, I had to get my hands on a copy of WILD BIRD. Readers who enjoyed THE RUNNING DREAM will definitely want to read it.
Wren Clemmens is fourteen. She is the perfect example of a rebellious middle child. She never seems to measure up to her older sister Anabella, and she no longer possesses the innocence of her little brother Mo. If she can't measure up to everyone's expectations, why not act however she wants.
Wren meets Meadow in a school restroom. Meadow is into drinking and drugs which fascinates Wren. It doesn't take long for Wren to join in, and soon she is stealing money from her parents, shoplifting, and even delivering drugs for a cool, older guy named Nico. Her new life is filled with thrills and excitement, but that ends up sending Wren on an unexpected journey.
It is barely 4:00 am when several large men enter Wren's bedroom. They man-handle her out to a waiting vehicle and shove her in. Her family watches tearfully, explaining they love her and this is for the best. Wren is taken to the airport where she joins another teen just as confused as she is. Hours later she is given a backpack and supplies and marched to a camp in the desert.
Wren begins eight weeks in a wilderness therapy camp. Sleeping under a tarp, using a latrine pit, building her own fire, and cooking her own meals takes Wren to a mental place where she can contemplate what has become of her life. She is forced to face her anger and fear as she comes to terms with her actions and the pain and suffering she has brought to a family who she realizes does love and care about her.
WILD BIRD is a hard hitting, tough love story of what it sometimes takes to put someone back on the straight and narrow. Consider it a good addition to any middle/high school collection.
NEW KID by Jerry Craft is a graphic novel that deftly conveys the feelings of being the new kid in a world quite different than your own.
More than anything, Jordan Banks wants to go to art school. Unfortunately, his parents, especially his mother, have different ideas about what's best for Jordan. He is about to start seventh grade at Riverdale Academy Day School. Completely different from his urban, city school, it promises a great educational opportunity, but a lack of diversity means Jordon will be one of only a few brown kids.
The moment his "guide's" father picks him up in a fancy car, Jordan knows he's out of his element. A kid named Liam has been assigned to take Jordan around on the first day and be there for him should he have any questions. Liam quickly abandons Jordan. Using a map to find his classrooms proves nearly impossible, and no one seems to be interested in getting his name right.
Author Jerry Craft takes readers along as Jordan meets his new classmates and figures out both the written and unwritten rules of the unfamiliar society of Riverdale Academy. Each day when he gets home, his mother is excited to hear about his day, his dad seems oddly uninterested, and his neighborhood friends aren't as welcoming as usual. Will he ever make new friends? Will he survive the year? Will Riverdale ever seem like the best place to be?
Author Michael P. Spradlin has released a new series titled MEDAL OF HONOR. The first book in the series is JACK MONTGOMERY: WORLD WAR II-GALLANTRY AT ANZIO. Thank you to the author and publisher for a copy and the chance to review it.
First Lieutenant Jack Montgomery was born in Oklahoma in 1917. He joined the National Guard and become part of a unit comprised of most Native American soldiers. After attending college and earning a Bachelor's degree in physical education, he went back to his National Guard unit. He was discharged after the required year of service in 1941.
With the attack on Pearl Harbor and the involvement of the United States in the European war, Montgomery ended up serving his country on the front lines in Sicily and Italy. His platoon saw action as the Allied troops worked their way up the Italian peninsula.
It was in the attack on Anzio that Montgomery earned his Medal of Honor. He single-handedly took out three machine gun nests, killing German soldiers while taking others captive. The remaining 20 or so soldiers in his platoon had him to thank for their lives. Montgomery was severely injured but went on to recover and accept his medal from President Franklin Roosevelt in January 1945.
The MEDAL OF HONOR series will feature some of the 3,500 soldiers who have received the honor since its creation during the Civil War. Author Michael P. Spradlin tells the story of Jack Montgomery's experiences and heroism on the battlefield and also sprinkles in photographs and colorful details of World War II throughout the text. History buffs are sure to enjoy this new series. It is perfect for middle grade and even high school readers and could be used to supplement history lessons about the time periods. Stay tuned for a review of Book #2 about Ryan Pitts, a soldier in Afghanistan.
This reviewer eagerly awaits all new books by April Henry. THE LONELY DEAD did not disappoint.
Adele can't believe she has become the main suspect in the death of her ex-best friend Tori. True, Adele was caught kissing Tori's boy friend during a drunken game of hide and seek, but that was an accident. It was on the way home from the party that Adele came face to face with the dead Tori.
Thanks to an inherited ability from her mother and grandmother, Adele sees the images of the dead tethered to their remains. Diagnosed with schizophrenia, Adele doesn't see the images if she takes her medication, but recently she stopped, claiming to feel more like herself without the drug. The result - Tori appears to Adele tethered to her dead body buried in a shallow grave in the woods.
Tori begs Adele to help find her killer. A call from a nearby payphone sends the police to the woods where Tori's body is recovered and funeral proceedings follow. Adele continues to communicate with Tori's ghost attempting to find out the truth.
Adele's decision to report Tori's death backfires as police repeatedly question her about her presence in the woods after her confrontation with Tori at the party. Not able to explain her visions of the dead, Adele begins to doubt her own innocence and believes it might be easier to simply confess.
THE LONELY DEAD is classic April Henry with page-turning suspense and spot-on details. This may be my favorite yet.
Spencer's parents won't lay off. They are constantly bugging him to do better in school and to try harder in hockey. Even his sister is nagging him about writing application letters and applying to colleges. He just isn't sure that whole scene is for him. That's why he decides to be a rebel and climb the library.
It would have been cool, too, if he hadn't accidentally put his knee through that $4000 dollar window on his way to the roof. Now he is doing community service at the library where he's shelving books, straightening chairs, and helping people log on to computers. It is also where he meets a green eyed girl named Mallory.
Mallory's mother has changed. She used to be independent and confident, but after she met Charlie, she seemed to lose herself. Mallory is trying to convince her mother, pregnant with Charlie's child, to leave him and start over before the baby is born.
She was sure she had convinced her, but when the time came to leave, her mother refused. But, Mallory wasn't staying a day longer. Now she's homeless and hiding out in the library after closing time, hoping it will provide a warm place for the night. That's how she met Spencer.
When Spencer realizes Mallory has nowhere to go, he tries to step in with a solution. The more he interacts with her during his library shifts, the more he begins to like her. Her life is so different than his, he can't stop thinking about her even when they aren't together.
The discovery of a dead body in the library throws a kink in Mallory's plans to continue hiding out there. Spencer not only wants to help Mallory, but also help solve the mystery of the dead woman and the strange signs left behind in the library. Mystery and intrigue mount as Mallory tries to stay hidden from Charlie's threats and Spencer hides from responsibilities he isn't ready to face.
Natalie D. Richards is also the author of SIX MONTHS LATER, ONE WAS LOST, and WE ALL FALL DOWN. Suspense and mystery are her trademarks and WHAT YOU HIDE will not disappoint.


The USAID Macro-Economic Stabilization and Reform (MESR) project will address Egypt's macroeconomic challenges, assist with implementing critical public financial management reforms, and set the stage for broad-based economic growth and achievement of the Sustainable Development Strategy 2030.
The Tax Policy/Administration Specialist will be responsible for providing technical assistance on tax policy reform, regulations, revenue impact analysis, tax administration, audit, and collections, as part of the Public Investment Objective.
Lead the preparation of the Objective 2 work plan, carry out technical and training assignments related to tax policy and administration.
Provide MOF with tax policy advice to prepare potential amendments to tax legislation and assist with subsequent regulatory and administrative changes.
Advise in the development of the capacity, policy, and procedures of the Macro-Fiscal Policy Unit.
Assist in the design and development of input-output analysis for VAT, trend analysis for excises and customs duties, and computable general equilibrium (CGE) modeling for estimating the economic impact of major tax changes.
Institute train-the trainers and online training system for tax revenue analysis and forecasting.
Lead administrative enhancements to include new systems and procedures for tax administration, focusing on opportunities for automation, such as expanded e-filing, case management, risked-based audit selection, automated collection notifications, and enhanced data analytics and visualization.
Prepare technical studies, incorporating best practices and lessons learned, related to tax policy, tax revenue analysis, and tax administration.
Assist GOE MOF counterparts in strategic planning for institutional change, designing and implementing training and capacity building for government staff.
Conducts gap analyses and implements plans for tax administration modernization efforts in conjunction with the crosscutting IT team.
in economics, finance, audit, tax or related field.
At least 8 years of experience assisting government or corporate clients in tax regulations, policy, collections, and audits.
Knowledge of Egypt's Ministry of Finance, previous work with ministry preferred.
The Tax Administration/Policy Specialist will be based in Cairo, Egypt and will report to the Public Financial Management Team Lead.
To apply, please send your CV to Apply to send email to the employer with the subject line "Tax Admin/Policy Specialist" by September 17, 2018.


Asked last week about a possible slowdown in construction spending this year, Trade Secretary Ramon M. Lopez said in a mobile message: "Less than quarter of year impact if we consider budget impasse in quarter 1 of this year that affected the BBB (Build, Build, Build) projects, as well as other local infra projects affected by election ban," Mr. Lopez said.
"[C]onsidering almost 16% growth last year, we still can hit double digits, low-teens growth," he added.
According to the Philippine Statistics Authority, construction spending in 2018 totaled P625.23 billion, up 15.9%, accelerating from 5.3% in 2017.
Barry G. Paulino, Philippine Contractors Association executive director, also said that the recently resolved 2019 budget standoff and the election ban on public works will "certainly" affect the sector but he expects a recovery after the May elections.
"We expect the growth to continue," Mr. Paulino told BusinessWorld in an earlier interview, adding the construction projects initiated by the private sector will still drive much of the sector's spending for this year.
Under the recently launched 10-year road map, industry spending is projected to hit P130 trillion by 2030.
The road map, if implemented, also estimates that the construction work force will grow 82.05% to 7.1 million workers from the 3.9 million in 2019.
Among the recommendations of the road map is legislating a long-term infrastructure plan to continue ongoing projects even when governments turn over every six years.
Construction industry stakeholders said they will submit within the year a formal proposal for lawmakers to look into the possibility of legislating a 30-year infrastructure master plan.
The road map proposed that a National Infrastructure Masterplan be allocated a minimum budget equivalent to 5% of GDP and other initiatives to determine appropriate financing modes for public infrastructure projects.
Asked when the proposal will be submitted to Congress, Liberito V. Espiritu, a member of the Domestic Construction Board, one of the implementing bodies of the Trade Department's Construction Industry Authority of the Philippines, said it will be done within the year.
"We are hoping for legislation in which a certain percentage of the projects in the Philippines will be allocated for the industry," Mr. Espiritu told BusinessWorld on the sidelines of the road map's official launching event.
Mr. Lopez said ideally, the 30-year master plan will build on the "Build, Build, Build" program.


The MC&MCA works with the Associated General Contractors of Minnesota (AGC), other industry groups, and the unions in the recruitment and training of our workforce. We are always looking for well-trained workers!
As a sponsor of Construct Tomorrow we work with the unions and others to educate and inform young people and others about job and career opportunities in the Concrete and Masonry Construction Industry. Construct Tomorrow is visiting a number of high schools across Minnesota this year. For a list of schools, dates and for more information, visit their website at www.constructtomorrow.org.
The MC&MCA serves on apprenticeship committees for the bricklayers, cement finishers, and laborers training programs and centers.
The Workforce Development Committee is the newest committee in the MC&MCA structure. Former MC&MCA president Christa Seaberg, then with JE Dunn Construction, was very active with the Construct Tomorrow efforts and after brainstorming with people like Sean Spraungel of All Stacked Up Masonry, John Trout of The Coleman Law Firm, and Barry Blazevic, the committee formed. It became clear that the concrete and masonry construction industry should attempt to reach out to younger people in the schools.
Click here to watch the Workforce Developement Video!
Through discussion with the shop teachers at Maple Grove Middle School and our labor partners, a masonry and concrete construction career event was developed and presented to over 70 grade 7th and 8th grade students on November 7, 2018. The event was held at the BAC Training Center in New Hope with the kids being bussed over. They were treated to a pizza lunch and given some swag for attending. They spent 5 hours working at 10 different concrete and masonry "stations" experiencing the materials and the work situation first hand!
Thanks to our Union Brothers and Sisters that assisted in the effort and covered the 10 "experience stations" for the kids.
Also a special thanks to our sponsors! These events wouldn't be possible without your help!
Mike and the team pop into Portland Oregon to surprise Katie Hughes, a female carpenter who created and runs an incredible skills trade camp for young girls.


The Food and Drug Administration issued a warning today about a heartburn drug, saying it could cause fatal heart problems.
It said the drug, Propulsid, made by Janssen Pharmaceutica, could cause problems for some people who take certain other drugs. The drug, known generically as cisapride, is usually prescribed for nighttime heartburn.
President Clinton has taken Propulsid in the past, and a White House spokesman was checking tonight to see whether Mr. Clinton was still taking it.


Are you looking to return to work from retirement – perhaps you were a Nurse, Social Worker, Youth Worker or a Teacher and miss the rewarding career that you left ? Or have you been bringing up a family and now want a part time flexible role ? Maybe a University Student looking for a sector experience to compliment your career? Or a Teaching Assistant or similar profession with extra hours to spare currently? We are extremely flexible and can work around your availability – this could be Monday – Friday after school, early Evenings or/and Weekends and school holidays? We offer a very competitive rate of pay up to £9.78 per hour + 12.07% holiday pay dependent upon your experience !!!
KIDS provides over 120 different services and works with 80 local authorities throughout England. Last year we supported over 11,000 children.
We are looking for caring, enthusiastic individuals to support disabled children and young people up to the age of 25 Years Old on a 1-1 basis in the London Boroughs of Harrow, Hackney, Hounslow and Waltham Forest.
As a Short Breaks Worker with KIDS you can help disabled children and young people throughout the borough to access and enjoy activities whilst giving their families a much-needed break from their caring role. Previous experience of working with children, preferably disabled children, is desirable. Training (e-learning) will be provided and you will also have the ongoing support of a local supervisor.


Liz Statement Earrings in Rose Gold is rated 4.7 out of 5 by 45.
Rated 5 out of 5 by Marchmoon from Love these earrings I went in for my birthday discount with other items in mind , but when I saw these earrings & tried them on I knew I had to have them. Besides being versatile they brighten my face with the hammered metal and fringe. My first day wearing them I received a compliment.
Rated 5 out of 5 by dgibb from Love earrings These are so cute and light ..have had so many compliments.
Rated 2 out of 5 by Kfischer from Liz Statement Earrings I was disappointed with the size of the earrings, they were smaller than I expected.
Rated 4 out of 5 by TT123 from Small little jingle in my ear Not so wowed in person answer seemed small. Cute earring though - fun to wear.
Rated 5 out of 5 by Michibell from Beautiful Rose Gold They're beautiful and versatile! Love the Rose Gold; can wear with anything!


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Calliope Athletic and Harrier Club
Running Routes (Road)
News/Capers
Northcote Tavern Pub Fun Run/Walk
Beach Haven Fun Run/Walk
Kaipatiki Primary Schools Sports Events
Contact Calliope
Running (Harriers)
Calliope provides a range of activities and events for both runners and walkers of all abilities. We meet every Wednesday night at 6:15, with a run or walk beginning at 6:30. People of all ages are welcome.
The Club Rooms are found at the Osborne Memorial Park (also known as "Birkenhead War Memorial Park") at the bottom of Mahara Ave across from the Birkenhead Leisure Centre. The club rooms are located beneath the grandstand.
** We are currently operating out of the Cricket Club.**
Calliope is also involved with a community 5 km run and walk based at the Northcote tavern in Queen St, Northcote. This takes place on Monday nights during daylight saving, with the walkers starting at 6.15pm and the runners 15 minutes later. Spot prizes are awarded and entry is by way of a gold coin donation, the monies donated to a group for graffiti removal.
Click here for maps of the common Wednesday Road run
Running (Bush)
During the brighter evenings of Day light saving, we run weekly runs through the local bushes, Eskdale, Le Roys, Chelsea Estate Heritage parks to mention just a few. A group of the club members also run on weekends along the coast line from Milford up to and around Northhead and back, along with other fantastic bush/coastal running tracks.
We also encourage and take part in many other organised events held through out the year, such as the Xterra Trail series
Come and join us. We walk all year round in the local area. In the summer we make the most of the bush and reserve tracks. More serious walkers and those training for participation in Half Marathon's and Marathons may go out for longer training walks.
During the summer months walkers may also participate in the Club athletics program, which includes the 3000 meter walk, and the 3000, 5000 and 10000 meters runs, but to which walkers are welcome.
Walkers are also invited on a regular basis to all the club outings, including the Red Stag Relay in the Redwood Forest in Rotorua, the yearly meeting with Hamilton Hawks, and some national events.
If you would like more information, email the club at calliope.birkenhead@gmail.com
During the summer months the Athletics season is held on our track comprising of a mix of track and field events. This culminates in the Club Championship in Feb/March. Road and Bush Runs and Walks are held for non-participants during the summer season.
Calliope Athletic Records
Download file here
Age and gender graded system
Now you might think, it is pretty tough, if you are a 60 year-old competing against a younger athlete.
Well, the good news is that Calliope caters for you.
We have a number of events that are age and gender relative.
You earn a percentage based on your age in years and fractions of years. Also if it is a mixed event, gender is also taken into account.
Read more about the system here
Calliope Life Members are members of the club who are given a full membership for the rest of their time at Calliope as significant gratitude and thanks for their effort and commitment to the Club over time.
Murray Stevens 2015
Rod Barker 2011
John Dwyer 2010
Malcolm Wade 2008
Bruce McLean 2005
Len Lanigan 2005
Trevor Mouldey 2004
Graeme Wells 1996
Steve Lee 1994
John & Gail Harnell 1992
Bill Fell 1990
Peter Forbes 1990
Mrs T Horne 1980
Robert Crowe 1970
James Darrough 1961
A E Clayton 1959
E J Osborne 1958
Frank Taylor 1950
A E H Clow 1946
Mrs B Clow 1941
Famous Calliopians
Like any club, Calliope has had among its members those who have made their mark on the national or international stage. We honor them here.
Mike Parker
The only Calliope athlete who was eventually selected for the Olympics Games. Mike was race walking for the English Club at the time. Unfortunately, it was the Moscow Olympics in 1980 which New Zealand decided to Boycott and Mike was sadly unable to compete. MIke is still walking very successfully after a comeback in 2007.
Norm Ambler
1936- 2nd in the Round the Lake interclass with fastest time. Won Auckland junior cross-country by 21 seconds.
1937- Won Auckland junior Champs. 2 minutes ahead of second place getter.
1938- Captain of Calliope winning team of Auckland Junior Champ.
1939- Won everything he entered or faster time, despite one event where replaced 3rd.
1945- 1st Auckland Cross-country team.
1946- Won Great Eastern Road Race.
1947- Won Onehunga to Auckland race & Auckland Cross-Country Champs
Geoff Shaw
Indisputably Geoff was one of the greatest junior athletes in New Zeland Athletic History. He held a plethora of records including 3:44.1 NZ junior 1500 record.
Geoff's time of 13:48.4 in the 5000m still stands as the best time run by an M20 athlete in New Zealand (he was only 18 at the time). Although Geoff's running career was curtailed by injury he did go on to represent New Zealand in both Track and Cross-country. Geoff is now involved in coaching some of our most promising junior athletes at Calliope. During Geoff's career he was coached by Calliope's Frank Smedley and Jack Ralston.
Ian Studd
Ian Studd's crowning achievement came in 1966 with a bronze medal and a sub four minute mile at the Kingston Commonwealth Games in Jamaica. His time was 3:58.4.
For more in depth history of Calliope, click here.

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