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Mechanisms of Allergic Immunity firstname.lastname@example.com
Normal larynxLaryngeal oedema
Cellular culprits of allergy: Mast cells Most informative early analysis conducted in patients with asthma Early studies (pre-1980) implicated mast cells and histamine as part of an archetypal immediate type I hypersensitivity Provoked by allergenic and non allergenic substances Explained atopic and non-atopic asthma Explained why mast cell stabilising drugs worked
Cellular culprits of allergy: Mast cells?? Corticosteroid treatment worked, but had no effect on histamine release Anti-histamine treatment had little effect on asthma Could not explain 'organ specificity' of asthma Could not explain the hyperresponsive airway in asymptomatic asthmatics Fibreoptic bronchoscopy - immunohistology, biopsy and analysis of bronchoalveolar lavage (BAL) cells (1980's - present)
The early evidence: Eosinophil & mononuclear cells infiltrate the bronchi of asthmatics Activated T cells elevated in the peripheral blood of severe acute asthmatics Activated T cells in peripheral blood correlated with airway narrowing Bronchial CD4 lymphocyte numbers correlated with eosinophil numbers Elevated IL-5 expressing T cells in asthmatic bronchial mucosa and BAL T cells that release IL-5 co-localise with eosinophils Eosinophils cause airway hyperresponsiveness, inflammationdesquamative bronchitis, mucous hypersecretion and smooth muscle contraction IL-5 promotes differentiation and regulates the survival of eosinophils Steroid treatment associated with a decrease in IL-5 producing cells Cellular culprits of allergy: T cells
Wider analysis of cytokines in atopy showed that BAL T cells that expressed elevated levels of IL-5, also expressed IL-4 - a profile typical of Th2 cells in mice Th2 IL-3 Growth of progenitor haemopoeitic cells GM-CSF Myelopoiesis. IL-4 B cell activation and growth IgE isotype switch. Induction of MHC class II. Macrophage inhibition IL-5 Eosinophil growth IL-6 B cell growth Acute phase protein release IL-10 Inhibits macrophage activation Inhibits Th1 cells TGF- Inhibits macrophage activation
Lebman & Coffman 1988 J Exp Med 168, 853-862
Th2 'Textbook' scheme of allergic immunity is centred around polarised Th cells Mast cell Eosinophil Differentiation and development Ig isotype switch B IgE Th1 -ve MM Where do Th2 cells come from? Why are they so dominant in allergic individuals? What are they really for?
Journal of Immunology 136, 2348-2357 1986 The discovery of Th1 and Th2 subsets
IL-4 IFN- T cell clones that make IFN- , but not IL-4 T cell clones that make IL-4, but not IFN- Enhances IgE & IgG1 Do not provide help to IgE and IgG1 secreting B cells Provide help to IgE and IgG1 secreting B cells In vitro - Th1 and Th2 subsets
Relevance in vivo - Infection Non-healing BALB/cResistant C57BL/6 Draining LN T cells express IL-4 mRNA Draining LN T cells express IFN- mRNA T Leishmania - specific T cells Irradiated BALB/c recipient Resistance Reiner & Locksley Annu. Rev. Immunol. 13, 151-177, 1995
IFN- / IL-12 or anti-IL-4 Pro-Th1 treatments or anti-Th2 treatments protect against infection Relevance in vivo - Infection
Inflammatory Th1 T cell Th1 Macrophage and Leishmania Macrophage infected with Leishmania kills pathogen when activated Macrophage activation is dependent upon Th1 cells Leishmania resistance - mechanism IFN-
Tuberculoid leprosy Low infectivity Localised infection Normal serum Ig Normal T cell response Poor growth of mycobacteria in macrophages Th2 Th1 Lepromatous leprosy High infectivity Disseminated infection Hypergammaglobulinaemia Unresponsive Florid growth of mycobacteria in macrophages Relevance of Th subsets in humans Lepromatous and tuberculoid leprosy Infection with Mycobacterium leprae shows two main clinical forms associated with Th1 and Th2 responses
Tuberculoid leprosy
Lepromatous Leprosy
'Textbook' scheme of allergic immunity is centred around polarised Th cells Immunological fashions 1960's & 1970's Immunoglobulin E 1970's & 1980's Mast cells & Eosinophils 1980's & 1990's Environment – ante-natal & adult, allergens, Th2 cells 1990's & 2000's Microbial experience, Epithelium, Tregs Although undoubtedly a useful model, the textbook 'skew to Th2' model is too simplistic to explain allergy Allergy is a disease of impaired immune regulation Where is the regulatory lesion?
Barrier: Skin, gut, lung, eye, nose etc Non self protein from allergen or pathogen Allergic immune responses are much like any other immune response and involves the same regulators Inflammation inc. MIP-1 , MCP-1 MIP-1 Activation and migration of dendritic cells to site of inflammation
Tracheal Dendritic Cells Langerhan's cells In-vitro differentiated monocyte-derived Dendritic Cell
[Ca 2+ ] i Time (s) [Ca 2+ ] i Time (s) Immature DC migrate into inflamed tissue in response to MIP-1 , MCP-1 MIP1- which bind to, and trigger CCR1, CCR2 and CCR5 respectively. Migration of immature DC to sites of inflammation Sallusto et al., Eur. J. Immunol. 1998 28 2760-2769 Immature DC do not respond to the lymph node derived CCR7 ligand MIP-3 Time (s) [Ca 2+ ] i
Mature DC stop migrating into inflamed tissue and make no response to MIP-1 , MCP-1 MIP1- Mature DC respond to the lymph node derived CCR7 ligand MIP-3 Time (s) [Ca 2+ ] i Migration of mature DC to 2º lymphoid tissue Sallusto et al., Eur. J. Immunol. 1998 28 2760-2769 Time (s) [Ca 2+ ] i Time (s) [Ca 2+ ] i
Mempel, T.R et al Nature 427: 154-159, 2004. Splenic DC Pulsed with Ag OVA 323-329 Not pulsed with Ag T cells labelled GREEN Anti OVA 323-329 TcR transgenic mouse DC labelled RED DC – T cell interactions in the lymph node -18hr 0hr 2hr Anti-L selectin Ab Imaging at various timepoints
2. Distribution of Ag-loaded DCs and T cells is ordered 4-5hr after T cells are injectedDistribution of Ag-loaded DCs and T cells is ordered 4-5hr after T cells are injected 1. DCs strategically cluster around HEV 18hr after entering the LNDCs strategically cluster around HEV 18hr after entering the LN Early entry of DC to the lymph node Mempel, T.R et al Nature 427: 154-159, 2004.
3. DC become highly migratory & change shape (20hr)DC become highly migratory & change shape (20hr)
4. T cells cover large territories in LNT cells cover large territories in LN
6. Short, serial T cell-DC contacts of ~ 5 minutes (2-4hrs after injection of T cells)Short, serial T cell-DC contacts of ~ 5 minutes (2-4hrs after injection of T cells) 7. Stable T cell-DC conjugates of 30-180 minutes (8-12hr after injection of T cells)Stable T cell-DC conjugates of 30-180 minutes (8-12hr after injection of T cells) 8. Simultaneous stable and dynamic interactions between DC and T cellsSimultaneous stable and dynamic interactions between DC and T cells
5. 44hr after injection of T cells, DCs decrease motility and become anchored to reticular fibres, T cells rapidly migrate again44hr after injection of T cells, DCs decrease motility and become anchored to reticular fibres, T cells rapidly migrate again T cells start to proliferate and produce cytokines 44hr after transfer
More information than is provided by the antigen is exchanged between the DC and T cell DC have a profound influence on the properties of the T cell that develops
Signals 1, 2 DC Th Signal 1 antigen & antigen receptor Signal 2 B7 - CD28 Costimulation and 3 Signals 1 & 2 activate T cells to proliferation and effector function But what 'tunes' the response to Th1 or Th2? Signal 3 - pathogen polarised DC
Polarised DC subsets DC Th The properties of the allergen, or allergen carrier influences the DC to drive the development of appropriate Th cells Signal 3 Th polarising signal Integration of signals from pathogen/allergen and the extracellular milieu polarise the DC to produce qualitatively different signals 3 Signal 1 Signal 2
Microbial Patterns Janeway & Medzhitov 2002 Ann Rev Immunol 20 197-216 Pathogen-associated molecular patterns (PAMPS) Conserved microbial molecules shared by many pathogens Include: Bacterial lipopolysaccharides Peptidoglycan Zymosan Flagellin Unmethylated CpG DNA Pattern Recognition Receptors (PRR) Include: Toll like receptors Receptors for apoptotic cells Receptors for opsonins Receptors for coagulation and complement proteins Pathogen-associated molecular patterns (PAMPS) Conserved microbial molecules shared by many pathogens Include: Bacterial lipopolysaccharides Peptidoglycan Zymosan Flagellin Unmethylated CpG DNA
CD40 + CD80/CD86 Type 1 and 2 DC Polarising PAMPS Type 1 PAMPS bind to PRR Class II Type 2 PAMPS bind to PRR Th1 polarising factor IL-12 Th2 polarising factor CCL2 (MCP-1) T + +
CD14 TLR 4 MD-2 TLR 3TLR 9TLR 2 TLR 1 TLR 6 TLR 2 Type 1 PAMPS and their PRR Peptidoglycan (Gram + bacteria) Lipoproteins Lipoarabinomannan (Mycobacteria) LPS (Leptospira) LPS (Porphyromonas) Glycophosphatylinositol - (T. Cruzi) Zymosan (Yeast) LPS Lipotechoic acid - (Gram + bacteria) RSV F protein dsDNA Unmethylated CpG DNA Low level IL-12p70 Some ligands induce IL-10 or IL-12p35 High IL-12p70 IFN- High IL-12p70 High IL-12p70 IFN-
Type 2 PAMPS and their PRR ??
Endogenous molecular patterns Include: Heat shock proteins (HSP60 HSP70 GP96) Extracellular matrix proteins (hyaluronan, fibronectin, fibrinogen) Immune complexes Surfactant protein A Necrotic cell components Pattern Recognition Receptors (PRR) Include: Toll like receptors Receptors for apoptotic cells Receptors for opsonins Receptors for coagulation and complement proteins Receptors for apoptotic cells Receptors for opsonins Receptors for coagulation and complement proteins
Indirect activation of DC by 'modulatory tissue factors' Direct activation by PAMP-PRR interactions Necrotic/apoptotic cell death - neo expression of PRR ligands Heat shock proteins Extracellular matrix components Necrotic cell lipids Cytokines Chemokines Eicosanoids Coagulation components Complement components Allergen Activates the expression of costimulatory molecules on DC
Could be argued that the development of Th2 cells is the default pathway DC polarisation by modulatory tissue factors DC polarising factors IFN- IFN- IFN- Th0 to Th1 polarising cytokines IL-12p70 IL-27 TNF- IL-18 DC polarising factors CCL7 (MCP-3), CCL13 (MCP-4), PGE 2, Histamine Th0 to Th2 polarising cytokines CCL2 (MCP-1), ?IL-4 Lack of high level IL-12p70 IL-27 TNF- IL-18
NK Epithelium Mast Fibroblast PGE 2 CCR2L Histamine IFN- IFN- IL-18 Viruses Fungi Parasites Bacteria Viruses Fungi Parasites Viruses Sources of modulatory tissue factors Th2 Th1
The hygiene hypothesis (Strachan, 1989) Based upon the epidemiology of hay fever "Declining family size, improved household amenities, and higher standards of personal cleanliness have reduced the opportunities for cross-infection in young families. This may have resulted in more widespread clinical expression of atopic disease"..can be interpreted in terms of a failure to microbially modulate default Th2 responses in childhood young families Explains how Th2 arise, but… …does not explains why some individuals are allergic and others are not and why the incidence of allergy is increasing. Reduced numbers of IL-12 producing cells? Reduced ability to produce or respond to IL-12? Reduced stimulation of IL-12 by microbial substances?
Th2 Th1 Th2 Balanced Th1/Th2 at ~2yr Neonatal & infant immune systems The intrauterine environment is powerfully Th2 – this imprints Th2 dominance upon the neonate Serial infections Age Immune response
Th1 Th2 Unbalanced Th1/Th2 Th2 dominance at ~2yr Delayed maturation of Th1 capacity Few serial infections – hygiene, small family size etc Age Immune response Longer period of time in which to make and establish Th2 responses to environmental antigens (i.e. allergens)
Do infections only reduce Th2 dominance by inducing Th1 responses? Aerosolised ovalbumin (OVA) OVA – allergic mice with asthma-like symptoms Eosinophils in airway, dominance of OVA-specific Th2 cells, OVA-specific IgE W h e e z e Vaccinate with mycobacteria No asthma-like symptoms W h e e z e Have the Th1 cells induced by the mycobacteria downregulated the activity of the Th2 responsible for the symptoms?
Vaccinate with mycobacteria W h e e z e No asthma-like symptoms Do infections only reduce Th2 dominance by inducing Th1 responses? Th CD4+ cells specific for OVA that produce high levels of the immunosuppressive cytokines TGF and IL-10 Mycobacteria induced REGULATORY T cells
Th cell polarisation DC mediated – decision influenced by infection Extracellular milieu - mediated
0 110 Factor increase over control 0 110 Factor increase over control Journal of Immunology 1994 152 4755-4782 Priming conditions IFN U/ml IL-4 pg/ml Control Ab5892 256 Anti-IFN Ab1534 624 IL-4 + control Ab1740 839 IL-4 + anti-IFN Ab 3481245
Resting Mast cellDegranulated mast cell Mediators released include: Leukotriene C 4 & D 4, Prostaglandin D 2 Platelet Activating Factor, Chymase, Tryptase, Heparin, Histamine IL-4, IL-5, IL-6, IL-8, TNF- IL-4, IL-5 IL-4 is not only a product of Th2 cells IL-4 from the innate immune system
Journal of Experimental Medicine, 1992 176 1381-1386 Sequential 2 m sections from a mucosal biopsy of a patient with asthma Tryptase IL-4
What properties and characteristics make a substance an allergen? How do these properties disregulate the processes described?
L. destructor G. domesticus D. pteronyssinus A. siro T. putrescentiae
Allergens of Dermatophagoides pteronyssinus Proteinase allergens are common and widespread: Fungi, insects, plants, parasites, drugs (but…most allergens are not proteases) Der p 1Cysteine protease Der p 2? Der p 3Trypsin (serine protease) Der p 4Amylase Der p 5? Der p 6Chymotrypsin (serine protease) Der p 7? Der p 8Glutathione transferase Der p 9Collagenase (serine protease) Der p 10Tropomyosin Der p 14Apolipophorin like protein
Protease allergens can breach epithelial barriers Wan et al., Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions J Clin Invest, 1999, 104, 123-133 Leads to immune sensitisation without the 'deliberate' invasion and infection mechanisms of a pathogen
Proteases as activators of cells Protease Activated Receptors PARActivatorsInactivators PAR1Thrombin, Trypsin Granzyme ACathepsin G, Elastase, Plasmin Proteinase 3 PAR2Trypsin, Tryptase, Factor Xa, Proconvertin Cathepsin G,, Plasmin, Proteinase 3 PAR3ThrombinCathepsin G, Elastatase PAR4Thrombin, Trypsin, Cathepsin G? Inactivators
Journal of Immunology 2001 167 1014-1021 PAR are also involved in: Induction of of epithelial cell & fibroblast proliferation Induction of cytokines & chemokine expression Induction of pharmacological mediator release Induction of metalloproteases Regulation of smooth muscle tone
Resting Mast cellDegranulated mast cell Mediators released include: Leukotriene C 4 & D 4, Prostaglandin D 2 Platelet Activating Factor, Chymase, Tryptase, Heparin, Histamine IL-4, IL-5, IL-6, IL-8, TNF- IL-4, Do protease allergens induce IL-4 release by Mast cells
Journal of Leukocyte Biology 2003, 73 165-171
Constitutive & Induced Cytokine Expression by KU812 Basophils -actin IL-3IL-4IL-5IL-6IL-8IL-13 IFN- 516bp Constitutive PMA/Ionomycin Induced
-actin 516bp IL-4 IL-5 IL-13 IFN- Der p1 Inhibited Der p1 Inhibitors 0 +ve -ve Der p1 Induces Cytokine Type-2 Cytokine mRNA Expression in KU812
516bp PMA/Ionomycin Inhibitors -- ++ + + -- -actin IL-13 Protease Inhibitors Do Not Prevent Cytokine mRNA Expression by KU812
516bp -actin IL-13 - - - + PMA/Ionomycin Tetanus toxoid - - - + - + -ve 516bp Time (hr)11444 Non-Proteolytic Antigens Do Not Induce Cytokine mRNA Expression by KU812
Der p1 induces IL-4 and IL-13 protein expression in Freshly isolated Basophils
516bp -actin IL-4 IL-5 IL-13 IFN- - Inhibitors + Inhibitors -ve +ve 0 ES 100ng/ml ES200ng/ml ES 1000ng/ml ES 0 ES 100ng/ml ES200ng/ml ES 1000ng/ml ES Necator Americanus Proteases Induce Type-2 Cytokine Expression by KU812
Der p1 and hookworm excretory/secretory products induce IL-4 and IL-13 protein expression in KU812 Basophils
The switch to IgE
Lebman & Coffman 1988 J Exp Med 168, 853-862
C2C2CC C4C4C2C2C1C1C1C1C3C3CC CC Switch regions The S consists of 150 repeats of [(GAGCT)n(GGGGGT)] where n is between 3 and 7. Switching is mechanistically similar to V(D)J recombination. S3S3S1S1S1S1S2S2S4S4SS S2S2 SS Switch regions - repetitive regions of DNA that physically recombine Upstream of C regions CC CC C3C3 VDJ C3C3 IgG3 produced. Switch from IgM
Switch recombination to IgE A three signal process: 1.Antigen – controls entire process 2.Soluble help via IL-4 or IL-13 from T helper cells 3.Cognate help via CD40 L from T helper cells
Y Y Y T cell help to B cells B Antigen Th IL-4 and IL-13 CD40 Ligand CD40
Switch recombination to IgE A three signal process: 1.Antigen 2.Soluble help via IL-4 or IL-13 from T helper cells 3.Cognate help via CD40 L from T helper cells
Stat-6 P P Soluble help via IL-4 or IL-13 from T helper cells IL-4R CCIL-13R 1/2 IL-13 IL-4IL-13IL-4 IL-4RIL-13R JAK1 JAK3 TYK1 JAK1 TYK2 PP Stat-6 P P P P P P P P P P P Dimerised Stat-6 translocates to nucleus
Switch recombination to IgE A three signal process: 1.Antigen 2.Soluble help via IL-4 or IL-13 from T helper cells 3.Cognate help via CD40 L from T helper cells
Ligation promotes aggregation in lipid rafts Cognate help via CD40 L from T helper cells CD40 2 3 5 6 TNF receptor associated factors IBIB NF BB IBIB BB Uninhibited NFkB translocates to the nucleus
Stat6 II C1C1C2C2C3C3C4C4SS II NF B C/EBP PU.1 BSAP AP-1 BSAP – B cell specific activator protein. C/EBP CCAAT/enhancer binding protein. PU.1 – Spi1 equivalent in humans, ets transcription factor Induced by IL-4/IL-13 and CD40 ligation Activation of the I promoter Activation/cytokine responsive promoter
C1C1C2C2C3C3C4C4SS II Stat6 NF B C/EBP PU.1 Germline IgE transcripts Transcription Why has this mechanism evolved to transcribe just the C region? V H D H J H is needed to make a functional IgE Why is the epsilon switch region spliced out? DNA C1C1C2C2C3C3C4C4SS II RNA CC II Spliced RNA Germline transcripts
What do germline transcripts do? CC II C1C1C2C2C3C3C4C4SS II RNA Spliced RNA SS C1C1C2C2C3C3C4C4SS II Stat6 NF B C/EBP PU.1 S region RNA hybridises with template DNA
Single stranded DNA II C1C1 SS SS 5' 3' SS SS R loop 1. S region in the genomic DNA 'melts' 2.S region RNA spliced from germline RNA transcript hybridises to single-stranded DNA 3. ssDNA R loop formed – a substrate for AID - ACTIVATION- INDUCED CYTIDINE DEAMINASE Mechanism of class switch recombination
NF B Stat6 Activation-induced cytidine deaminase gene Activation-induced cytidine deaminase Soluble help via Th cell IL-4 or IL-13 Induces Stat 6 Cognate help via Th cell CD40 L from T helper Releases NFkB from IkB B cell activation by antigen leads to: AID gene is expressed under the same conditions as B cells induced to switch Ig isotype
Expressed only in B cells Involved in isotype class switching & somatic hypermutation AID knockout mice do not class switch Ig isotype Ectopic expression in non B cells causes class switch Mutation in the AID gene can cause hyper IgM syndrome Deaminates cytidine on ssDNA, i.e. substitutes U for C Activation-induced cytidine deaminase
AID RPA AID RPA AID RPA AID RPA AID RPA AID RPA AID RPA AID RPA GGGCTGGGCTGAGCTGRGCTGAGCTGRGCTGAGCTRARNT CCCGACCCGACTCGACYCGACTCGACYCGACTCGAYTYNA IgE S region Non-template strand is G-Rich and contains RGYW (A/G G T/C A/T) motifs Preferred S region target sequence for AID GGGCTGGGCTGAGCTGRGCTGAGCTGRGCTGAGCTRARNT AID RPA AID RPA Replication protein A (RPA) targets AID to ssDNA in R loops by binding to RGYW motifs
GGGCTGGGCTGAGCTGRGCTGAGCTGRGCTGAGCTRARNT CCCGACCCGACTCGACYCGACTCGACYCGACTCGAYTYNA Non-template ssDNA RNA/template DNA hybrid GGGCTGGGCTGAGCTGRGCTGAGCTGRGCTGAGCTRARNT CCCGACCCGACTCGACYCGACTCGACYCGACTCGAYTYNA Activation induced cytidine deaminase NH 2 N N O Cytidine O N HN O Uridine AID AID mediated deamination of cytidine to Uridine Activation induced cytidine deaminase AID may also deaminate C on the template strand ?RNAase?
GGGUTGA CCCGACT GGGUTGA CCCGACT S region DNA now contains mismatched G – U pairs that must be repaired e.g. by the base excision repair mechanism GGGUTGGGUTGAGUTGRGUTGAGUTGRGUTGAGUTRARNT CCCGACCCGACTCGACYCGACTCGACYCGAUTCGAYTYNA G - U mismatch repair GGGUTGGGUTGAGUTGRGUTGAGUTGRGUTGAGUTRARNT CCCGACCCGACTCGACYCGACTCGACYCGAUTCGAYTYNA PPPPPP PPPPPP GGGUTGGGUTGAGUTGRGUTGAGUTGRGUTGAGUTRARNT CCCGACCCGACTCGACYCGACTCGACYCGAUTCGAYTYNA Uracil-DNA glycolase (UNG) removes uracil to leave abasic sites in S region UNG Base is removed, but backbone remains intact
GGGUTGA CCCGACT PPPPPP PPPPPP G - U mismatch repair APE1 Abasic site is processed by the apurinic/apyrimidimic endonuclease 1 (APE1) GGGUTGA CCCGACT PP P PPP PPPPPP OH DNA is now nicked to produce a single strand break GGGUTGGGUTGAGUTGRGUTGAGUTGRGUTGAGUTRARNT CCCGACCCGACTCGACYCGACTCGACYCGAUTCGAYTYNA APE1 GGGCTGGGU TGAGCTGRGCTGAGCTGRGCTGAGCTRARNT CCCGACCCGACTCGACYCGACTCGACYCGAU TCGAYTYNA Similar mechanism on the template strand creates a staggered double strand break
Processing of staggered ends GGGCTGGG CCCGACCCGACTCGACYCGACTCGACYCGA TGAGCTGRGCTGAGCTGRGCTGAGCTRARNT TCGAYTYNA GGGCTGGG TGAGCTGRGCTGAGCTGRGCTGAGCTRARNT CCCGACCCGACTCGACYCGACTCGACYCGA TCGAYTYNA End fill-in reactions ACTCGACYCGACTCGACYCGAC Exonuclease activity C2C2CC C4C4C2C2C1C1C1C1C3C3CC CC S3S3S1S1S1S1S2S2S4S4SS S2S2 SS
C2C2CC C4C4C2C2C1C1C1C1C3C3CC CC S3S3S1S1S1S1S2S2S4S4SS S2S2 SS CC CC C3C3 VDJ C1C1C1C1 C2C2 C4C4 CC C2C2 CC C2C2 CC CC C3C3 C1C1C1C1 C2C2 C4C4 Excised episomal circle of intervening DNA Activation of I & I promoter by Ag, IL-4/13 and CD40L Production of germline transcripts and splicing of S and S Deamination of ssDNA in S and S by AID Base excision and mismatch repair Blunt-ended ds breaks and synapsis of S to S by non-homologous end joining Process occurs in two S regions simultaneously
After N and P nucleotides have been inserted, several other proteins, (Ku70:Ku80, XRCC4 and DNA dependent protein kinases,ARTEMIS exonuclease, DNA ligase IV) bind to the hairpins and the heptamer ends. Ig gene recombination 723 9 712 9 Non-homologous end joining in class switch V D J Closely resembles another B cell Ig gene mechanism Defects in NHEJ proteins impair class switch
Stat6 NF B C/EBP PU.1 BSAP BCL-6 BCL-6 binds to the Stat-6 binding site and represses switching Stat6 is involved in Th2 cell differentiation, the expression of CD23 (the low affinity IgE receptor) and VCAM expression BCL-6 may exert it's anti/pro-allergic activities via these genes Stat6 Transcription blocked BCL-6 -/- mice have enhanced IgE isotype switching BCL-6 -/- Stat6 -/- mice have no IgE An RFLP has been mapped to the first intron of the BCL-6 gene that is significantly associated with atopy - but not IgE levels
Additional areas to think about Can't get over a 2.2 mark without showing evidence of outside reading in answers
Relationship between isotype switch, somatic hypermutation and proliferation of B cells in the germinal centre What is the relationship between the deliberately mutagenic mechanisms of isotype switch and somatic hypermutation in B cells and the propensity of B cells to form tumours Where are the holes in the 'skew to Th2' model of allergy? What are allergic responses really for?
What are allergic immune responses really for? Trichuris Trypanosoma Toxoplasma Enterobious Ascaris Leishmania Schistosome Hookworm Plasmodium Wuchereria Onchocerca Taenia
Text book view Helminth infections induce IgE, mastocytosis and eosinophilia A classic Th2-driven response Eosinophils killing a schistosome egg in vitro
Susceptible mice However…….. Heavily parasitised individuals exist - despite Th2 responses and eosinophilia. Scarce in vivo evidence of eosinophil and IgE control of helminth infection Yet IL-4 may be involved - Trichuris muris model Resistant mice Else et al., 1994 J. Exp Med 179 347-351
Nippostrongylus infection Th2 cells themselves may not be needed IL-4 from any source is sufficient to induce worm expulsion IL-4 Urban et al., 1995 J. Immunol. 154, 4675-4684
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25 Jul 2011
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User talk:Connall
Hey connall, I need confirmation on an edit on the A Full Kettle page. One of the recipes in crafting isn't related to the entry, so is it alright if I remove it or should I leave it? Drewfus (talk)
Connall, Agree with your assessment of the Occupations page and links. Go ahead and consolidate away. Pianoman 22:46, 12 November 2013 (UTC)
Could you undo the last change of Template:RecipeLookup ? I somehow cant submit anything... is there some kind of submit limit ? And, well this is also a test whether i can submit or not.
ZombieLawnGnome I added the Ham entry but I couldn't find a good template. I just copied some formatting from the Salmon entry and modified it. The article is rough and could use some review.
- 1 28_мая_2011_года
- 2 UnPacker
- 3 Page delete request
- 4 Code Sections
- 5 Farm Guide Alterations
- 6 Page move request
- 7 Item Crafting Template
- 8 Skirt/Shoes deletion
- 9 redirects (items related)
- 10 Russian pages with russian letter in name.
- 11 What about english pages titles
- 12 remove this please
- 13 About images resizing and duplicates
- 14 Happy to help out
- 15 RE: Main Page Changes
- 16 Main Page rough draft final draft
- 17 Main Page
- 18 I'm so sorry about my OCD
- 19 Main Page
- 20 Image update request
- 21 Question Rescinded.
- 22 Spam filter blocks force sorting type on tables
- 23 Template update request
- 24 Formal replacement of Boilerplate Templates requested (either unlock protection or replace)
- 25 Template Boilerplates and Category/Template Protections
- 26 New Main Page Design
Will try deleting this later. I am getting a database error that may be related to the update of the wiki software to the latest greatest version. I already killed the link from the main page. Pianoman (talk) 19:47, 18 November 2013 (UTC)
Sharing is enabled now. Is my first time using mediafire ^^. Please tell me if there are any bugs.
Page delete request
There is a duplicate article for beef jerky.
One has a capital J and one doesn't. Recommend deleting the one with the lower-case 'j' as the capital 'J' is the one linked to from the items page.
Code Sections
I saw one of your edits to the wooden chair page. Since there's no stylesheets for the wiki (yet) I have to ask... Why are we adding code snippets to the pages. Seems like we're creating more work and much more overhead keeping the information up to date for no benefit I can ascertain...
Modders the only ones I can even remotely see getting any sort of useful benefit from the the code section, but then they should be referring to the actual code itself, rather than a possibly dated version of the code listed on the wiki.
I can't see any other use case besides idle curiosity, and for that (in my rather worthless opinion) the time would be better spent updating parts of they wiki that everyone will use rather than a small subset of people that shouldn't even be using it anyway.
If you insist on having a code section, my fallback position would be to create a template, using a collapsible table format, that contains the version information the code was taken from, so people would at least know how old the code was.
Farm Guide Alterations
Hey Connall, im also trying to make a table of seeds gained from farming, but have only harvested my cabbage yet, as soon as I have more info i will either send them to you or put them in the farming guide, what do you want me to? --Mullelars (talk) 12:11, 11 December 2013 (UTC)
Page move request
Could you please move File:Large Table.gif to File:Large Table anim.gif, and File:Small Table.gif to File:Small Table anim.gif ? I think there should be Itemname.png. But I didn't notice that the same pagename of png and gif can't exist at the same time. Thank you. --Itok (talk) 01:54, 15 December 2013 (UTC)
Item Crafting Template
Taking you up on your offer, could you guide me or, tell me how you alter a table on crafting, it would make updating quicker and simpler Zachariah Zuan (talk) 23:54, 25 December 2013 (UTC)
- Still not sure, I'm trying to change the table on the Rain Collector craft box, but don't see how I can edit it, there are no given fields for me to add data into, and the recipe is very wrong , thank you for any help you can offer. Zachariah Zuan (talk) 23:32, 2 January 2014 (UTC)
- that's perfect thank you! Zachariah Zuan (talk) 16:06, 8 January 2014 (UTC)
- sorry to keep bothering you, I just haven't been on and spent a bit trying what you said, I just get "RecipeLookup|1012" on both pages, both on edit at the top, and edit on the documentation Zachariah Zuan (talk) 01:05, 15 January 2014 (UTC)
- that's perfect thank you! Zachariah Zuan (talk) 16:06, 8 January 2014 (UTC)
Skirt/Shoes deletion
Hi there! Just wanted to know why those where deleted since they do have a use (warmth&bandages,sheetrope). --Susmab (talk) 01:11, 22 January 2014 (UTC)
fair enough, i m the one who added skirt in the recipelist too (for bandages/sheetrope). just checked out the items list page and saw that the information is in fact already available there. my points was just to have a fully blue navbox for clothing items (meaning no red link) but i understand your point. --Susmab (talk) 17:36, 22 January 2014 (UTC)
Just want to do it the right way.
I just modified 9mm bullets so that instead of redirecting to [[9mm Rounds]] it redirects to the Ammo section in the Items page (Items#Ammo).
I dont know if it s the right way to do it.
Just to be clear, I think it s better to put redirects because if not we will have plenty of pages to modify (compared to 3 redirects).
And finally, we can do the same thing for every other item who was qualified as a stub and deleted.
It will really help in cleaning the Special:WantedPages
Please let me know what do you think about this. --Susmab (talk) 20:03, 23 January 2014 (UTC)
Hi again, I ve made the same thing for shoes and all bags except the garbage bag which is nominated for deletion, it should just be changed to a redirection like the other bags (which points to [[Items#Baggage]]) since there will be links to it when the rain barrel collector article gets an improvement for example. --Susmab (talk) 23:57, 23 January 2014 (UTC)
- np np, first time contributing on a wiki just so you know. (I love this game soooo much ;)) --Susmab (talk) 00:07, 24 January 2014 (UTC)
I don't know what you mean by "I need to ask is evidence to back up that the kitchen knife it used to make bread". I don't remember changing anything that relates to kitchen knives recently. Can you clarify this please? Thanks! --Rorschach (talk) 17:27, 3 February 2014 (UTC)
I know that there is already a Fixing page, but it's pretty thin on useful info. I started to make this one to see if I could improve on what was already available - maybe one could be folded into the other at some point. I was wondering, do you think I should keep working on this, or is it a waste of time and should be deleted? Ta. --Rorschach (talk) 17:39, 3 February 2014 (UTC)
- Edit: the Fixing page just got deleted! It wasn't me...
Hi Connall! Just an FYI, since you probably saw this already but the user Michaelrandolf created an account and then started putting online gambling links into a few pages. I didn't know if you had to remove them, or if I should/could. --Rorschach (talk) 15:50, 11 February 2014 (UTC)
Russian pages with russian letter in name.
OK, I understand. I will continue make new pages without russian letters. I found some links: Бейсбольная бита, Баррикада, Бейсбольная бита с шипами, Боб Смит, Аптечка. -- Hamsteri (talk) 14:42, 27 February 2014 (UTC)
What about english pages titles
I've got a problem with the names of the articles : sometimes they look "Like This", with an uppercase character at the beginning of each title, and some other times they look "Like this".
I am translating the pages for the french wiki, and I've got the tentation to give the english articles the right name. But what should I choose ? It seems that older articles are "Like This" and newer ones are "Like this", and a lot of translated pages are "Like This/lang", so it's a big temptation to put the article into the "Like This" case and keep a redirection more because I am not allowed to delete pages than because it is really useful to keep them.
Last but not least : french maintainers used the both too... I'm changing it all to "Like this" for french titles. It does not change anything for links with the matching english articles.
So my questions :
- Do you prefer "Spiked Baseball Bat" or "Spiked baseball bat" as a title for your article ?
- Could I have the right to delete pages, for maintenance purpose ? A lot of "Like this" pages redirecting to "Like This", and the reverse, exist. I'm ready to take a little time to clean it up properly, if I was allowed too.
Thanks, have fun with PZ ;)
remove this please
im still inexperienced and uploaded two obsolete files. please remove: File:9mmBox.png and File:Pistol new.png
About images resizing and duplicates
Hello Connal,
I've uploaded a lot of updates of main images these days. ie
To explain why I did this : the idea is to improve quality and maintainability, in the long run :
- some images have not the official game name. It would be preferable to get this one. So I've uploaded some duplicates, I'm sorry, but I think we should finally keep only the officially named image.
- I think that the file with the official name should get the official image resolution : 1 pixel for 1 pixel. I know some browsers don't zoom this kind of images cleanly, and it's why 120x120 images are useful. But thoses images are not the official one, so we should decide a naming standard for 120x120 images, ie like Official_Name_120.png or Official_Name_big.png (I prefer this one). So we could this in naming of the item template image and get the zoomed image clean in all browsers.
- Most of items are expected to be 32x32, so I've choosen to keep this format when it's possible, even if the image is a little bit smaller, in order to have a normalize size of images and have a maximum of them with the same size.
- My "item source template generator" and the "recipes source generator" I worked on calculates the images following these rules, and it will make easier to add items and recipes into the wiki with a clean-normalized-automatically-generated model.
- My wiki source generator for item
- My wiki source generator for recipes (use ?lang=FR for french language, or others)
So that's why I begun to upload duplicates and re-zoomed images. I hope this is ok for you. If so I will work on the use of the normalized images names on pages.
Happy to help out
I'm glad to help out with the wiki, Con. Btw, what's your steam name?--LaDestitute (talk) 19:41, 2 July 2014 (BST)
Thanks Connall! I've been working to learn mediawiki, so it's been quite the learning process. Bowlympicshero has been a great help with formatting and getting a ton of files uploaded too. Hemilash (talk) 03:10, 23 August 2014 (BST)
RE: Main Page Changes
Yeah, that's my bad actually. Didn't even realize there was a code of conduct for that and all until just recently. I'll be switching to a draft THEN implement procedure more like whatHemilash used for the Recipe Ingredients page. The layout of this wiki and the main page can be quite confusing to newcomers and is in desperate need of some tweaking. I'm currently taking a hiatus from working on anything right now because I believed I burnt myself out. So in a day or so I should be back with some ideas that I'll drop on the discussion page and see what you guys think about it. I'm also working on compiling a list of all items that I need to finish adding to the Items page. With Project Zomboid creeping closer to a full release, I believe there is a greater need to focus on getting it's wiki page current and presentable.
Looking forward to working with everyone and hope to make this the best damned post apocalyptic wiki ever. --Bowlympicshero (talk) 16:10, 24 August 2014 (BST)
Main Page
rough draft final draft
I'm nearing the end of my drafting process. Looking for any final suggestions. I would like to get this live ASAP so that more people can enjoy better ease of access to the majority of the content. NOTE: The 3 main sections have temp links under them for the time being. My next project will be the corresponding sub-portal pages Basics and the new Survival Guide. Once the sub-portals go live, section explanation/description will replace the temp links.
--Bowlympicshero (talk) 20:46, 30 August 2014 (BST)
New draft of main page is up. --Bowlympicshero (talk) 21:04, 3 September 2014 (BST)
Main Page
Project Zomboid is a zombie survival RPG for Windows, Mac and Linux. The game is currently in alpha, and is being developed by The Indie Stone, which consists of Will Porter, Andy Hodgetts, Marina Siu-Chong, Chris Simpson, Romain Dron, Paul Ring and Spiffo, the community raccoon. It is available to buy on Desura and Steam The game will be updated in a modular style similar to the development of Minecraft, Towns, or Kenshi. A purchase at any time guarantees updates throughout its development lifetime, and Steam keys will be issued to anyone who owns the game through an alternate service up to and possibly after its Steam release. The official forums can be found here.
Stable Release Version:
Latest Steam Beta Version:
May 12 2014
Survival Guide
Frequently Asked Questions
Game Modes
Map of Knox County
Selected Screenshot
We currently have 1,354 articles!
To propose changes to the main page, please see the main page sandbox.
Project Zomboid is a zombie survival RPG for Windows, Mac and Linux. The game is currently in alpha, and is being developed by The Indie Stone, which consists of Will Porter, Andy Hodgetts, Marina Siu-Chong, Chris Simpson, Romain Dron, Paul Ring and Spiffo, the community raccoon. It is available to buy on Desura and Steam
Stable Release Version:
Latest Steam Beta Version:
Useful Pages
Selected Screenshot
We currently have 1,354 articles!
To propose changes to the main page, please see the main page sandbox.


text:
Over time, the majority of us are bound to put on some extra weight or, if you are still young, to simply grow. But that is no reason to throw away your favourite pair of trousers. Making trousers larger, otherwise known as "letting out," is a simple process if you have the right tools.
- Skill level:
- Moderately Challenging
Other People Are Reading
Things you need
- Sewing machine
- Straight pins
- Dressmaker's chalk
- Small scissors or stitch cutters
- Colour-matching thread
- Iron
Show MoreHide
- 1
Remove the belt loop, if there is one, with your scissors or stitch cutters by cutting the stitching and not the belt loop.
- 2
Cut out the stitching over the centre seam, releasing the waist line as far as it will go.
- 3
Put your trousers on and take in the waist line to the right fit. Have someone pin the fabric in place and mark it with the dress makers chalk.
- 4
Rejoin the fabric with a sewing machine along the marked line, taking out the pins as you go.
- 5
Try on the trousers again. If they still fit, resew the marked line several more times to strengthen the seam and protect from embarrassing blowouts. If it is not a good fit, repeat steps 2-4.
- 6
Press the new seam flat with a hot iron.
- 7
Reattach the belt loop by sewing it in place.
How to Increase the Waist Line
- 1
Remove the stitching at the bottom of your pant legs by using scissors or stitch cutters.
- 2
Try on your trousers with a pair of dress shoes. Have someone fold up the excess fabric to the desired length. Hold in place with pins and mark with the dress makers chalk.
- 3
Sew along the marked line with a sewing machine, removing the pins as you go.
- 4
Put the trousers on again. If it is still a good fit, resew the marked line several more time to make the stitch strong. If it is not a good fit, repeat steps 1-3.
- 5
Iron the seam flat to finish off your alteration.
How to Lengthen Pants
Tips and warnings
- Ironing the seams which you will modify before beginning work on them will make the process easier and create a more professional look.
- Always cut the stitching and never the fabric. Only a true professional should be making any alterations to the fabric.
- Dress trousers are made with extra fabric so that they can be let out. If trousers have already been let out, and the fabric used up, you may not be able to make them any larger.
Don't Miss
- 20 of the funniest online reviews ever
- 14 Biggest lies people tell in online dating sites
- Hilarious things Google thinks you're trying to search for


text:
Arched windows can add interest to a room. Typically, the windows have rich wood mouldings that do not require window treatment coverings. However, this can also leave the room feeling harsh. If you want a softer look to your window, consider sewing a window treatment for arched windows. This treatment will fit inside the window casing, leaving the moulding exposed while providing soft texture and colour. A sheer or lightweight fabric will hang along the curve of your arch in a more uniform way than a heavier fabric.
- Skill level:
- Moderately Challenging
Other People Are Reading
Things you need
- Arched curtain rod and kit
- Measuring tape
- Fabric
- Scissors
- Sewing machine
- Thread
Show MoreHide
- 1
Install the arch curtain rod inside the window casing. Follow the packaging directions for placement of the clips that will secure the rod in place.
- 2
Measure the length of the arched curtains. Begin at the tallest section of the rod and measure downward to the length you want the curtains to hang. Add three-and-a-half inches for the top and bottom hems. If you want your curtains to puddle on the floor, measure to the floor and add 12 inches in addition to the hems.
- 3
Cut the fabric according to your panel measurements. Stitch the fabric together with half-inch seam allowances until the panel is the width you need. Stitch a half-inch seam along the top of the curtain. This forms a narrow rod casing.
- 4
Fold the bottom edge to form a double one and one-half-inch hem. Sew with a basting stitch. Do not press. The panel will hang longer on the ends than in the middle due to the arch of the window. This helps the curtains hang better when pulled back on the sides. If your curtain will hang straight down, hang the curtains and mark a horizontal hem line straight across the length you want them to hang. Remove from the rod. Cut the curtain one and one-half inches below the line, then baste.
- 5
Insert the rod and place the rod in the clips. Hang three days, to allow the fabric to stretch or shrink. Remove the basting and adjust the hem if needed. Machine stitch the hem, press and rehang.
Tips and warnings
- Many panels of fabric can be hung in one curved window. Multiple panels will create a fuller look and make the covering less transparent. Consider hanging two colours of sheer fabric in the arched windows. Arch curtain kits can be purchased at larger home improvement stores.
- Narrow arched windows will not accommodate heavyweight drapery.
Don't Miss
- 20 of the funniest online reviews ever
- 14 Biggest lies people tell in online dating sites
- Hilarious things Google thinks you're trying to search for


text:
Bus Myslenice Myślenice • Lesser Poland Voivodeship » Sahagun Sahagún
Myslenice to Sahagun buses and coaches • Eurolines Switzerland offer • Cheap online tickets
Choose your best offer from Myslenice to Sahagun.
When you go to tickets offer you can verify your fare in booking system, to which you will be redirected after clicking BUY button. Fill the forms as if you would book your ticket. Set the number and type of tickets, look for available discounts and deals. Cancel your booking without consequences whenever you want, as well just before the payment.
Myslenice to Sahagun coach and bus online tickets
Tickets from Myslenice to Sahagun are provided by Eurolines Switzerland company.
Verify other possible journeys from Myslenice to cities in Spain at Myslenice - Spain page. Check rebrutto.com offer for return tickets at Sahagun to Myslenice or Sahagun to other cities in Poland bus services.
You will find more information on your journey in the FAQ section.
Use rebrutto.com to find your cheapest fare.


text:
Langri Tangpa Centre Inc ABN 49 770 532 185
535 Old Cleveland Rd., Camp Hill QLD 4152 Australia
tel: (07) 3398 3310
fax: (07) 3398 3314
Unless otherwise stated all pages © Langri Tangpa Centre Inc. 2007 Important - Disclaimer
Site Designed by Sin-Iqual
Calendars & News
View Online
Program Booklet
Month at a Glance
Click here for weekly email reminders!
Click here for the NEW LTC library catalogue!
Our Programs
Learn to Meditate
Members Login
Learn to Meditate
Buddhist meditation is about training the mind in positive habit patterns, and removing the agitation that normally disturbs our thoughts and emotions. Our courses are about learning what to meditate on, and the guided meditations are where we can put it all into practice. Meditating in a group is more powerful; it is easier to concentrate, and it can re-charge your own practice at home. Our meditations are relaxed and informal. The weekday classes include a couple of short meditations and time for questions. Weekend courses include both morning and full-day retreats. We have both cushions and chairs to sit on.
Raising content, happy children
Learn simple ways to increase connection with your family for happier kids and more peaceful parents. Topics to be discussed include: What is mindfulness? What is mindful parenting? What are its benefits for children and parents/caregivers? Strategies to live a more mindful life. Simple ways to help children practice mindfulness.
NEW Buddhist DVD's and NEW meditations on cleansing body, speech and mind! Join us for a relaxed, informal meeting every Sunday. Beginning with a 45 minute guided meditation on the Shakyamuni Buddha purification and blessing, then have an informal discussion and DVD on a Buddhist topic, and end with delicious chai tea and biscuits.
Tag Cloud - Click & Discover!
Featured Events
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2017 Open Day
SATURDAY 20 May (10 am - 3 pm) Bring your friends and family and discover your local Buddhist community. Highlights of the day include: public talk with the Tibetan Lama...Read more
Learn to Meditate
A 4-week experiential course on the basics of meditation. Discover the benefits of meditation and practice a correct and comfortable posture. Investigate the different types of meditation and which methods...Read more
Mindful Parenting
Raising content, happy children Learn simple ways to increase connection with your family for happier kids and more peaceful parents. Topics to be discussed include: What is mindfulness? What is mindful parenting?...Read more
Saka Dawa - Buddha's Birthday!
Join us for SAKA DAWA - celebrating the Buddha's birth, enlightenment and paranirvana. We will offer the Shakyamuni Buddha Puja (in English) that celebrates the life of the Buddha. View...Read more
Everyday Dharma for Daily Life
Whether we are religious or not—we all want to make the most of our life and not be caught in wasting time on distractions! Discover how to make every moment...Read more
Introduction to Tantra
Learn the definition of tantra, how tantra works and why it is a powerful form of practice. Get a broad overview of the four classes of tantra and learn how...Read more
The Spiritual Teacher
Investigate the role of the teacher on the spiritual path: the need for a teacher and the qualities to look for, the responsiblities of a student, and how to relate...Read more
Opening Hours
Opening for Class
Reception and Meditation Hall opens half an hour before class and half an hour after class. The reception closes whilst class is on.
Shop Hours
Tue 9 am - 1 pm
Wed 5 pm - 9 pm
Sat 9 am - 5 pm
Sun 9 am - 1 pm
Front Hall Yoga Times
Mon 9.30 am
6.30 pm
Wed 9.30 am
6.30 pm
Fri 9.30 am
(opens 15 minutes early)


text: La Fourmi Ailée by Flyingants published on 2012-12-30T22:31:44Z ..to all the people who live far from useless words... Flyingants is composed of Lele Fontana, Francesco Ballerini, Donald Renda. Graphic concept by Daniele Madio - www.socialdesign.eu Photos by Silvia Amodio - www.silviaamodio.com Published and Copyright control by Cavernjatt Records. Available for: radio station, television, compilation, film, mastertone licensing. email@example.com,firstname.lastname@example.com,www.facebook.com/Flyingants3 Genre Ambient


text:
10 Oct 2016
In a Montana Bear Attack, Lessons on Hope, Survival and First Aid
A 50-year-old man was attacked by a bear in the wilderness of southwest Montana. Alone and injured, he walked — then drove — for miles to save himself. How did he do it? The man, Todd Orr, said he was scouting for elk in a mountainous valley on Sept. 30


text:
Unfortunately this item is unavailable
We're sorry about that, but please don't despair! We want to help you find whatever you're looking for.
- Call our Customer Services Team
on 01432 377089
- Search for another product
- Or browse similar items below:
Joules Dorrit Double Oven Glove
(V_DORRIT) PM ref: 940018
You might be interested in:
Joules Cuppa Porcelain Mug
Joules Cuppa Mug Floral 4 Pack


text:
Latest Updated (20th December 2016): KGMU Recruitment Notification 2016-17 Apply Online 58 Teaching Posts at www.kgmu.org
KGMU Lucknow Recruitment 2016
In this article, we are going to describe the KGMU Recruitment 2016-17 details. Candidates who are finding the teaching jobs then they should need to read the below section details. Candidates first take all details and then apply online at www.kgmu.org. We described the each and every detail in the following sections regarding the recruitment.
KGMU Job Notification 2016-17
The KGMU Lucknow Recruitment 2016 notification has been revealed by the King George's Medical University for the posts of 58 Teaching Faculty Positions. Candidates who want to get appointed on the Professor, Assistant Professor, and Associate Professor posts then must apply for the KGMU Teaching Recruitment 2016 before the 20th December 2016.
UPPSC Medical Officer Vacancy 2016
www.kgmu.org Recruitment
|Name of Conducting Authority
|KGMU (King George's Medical University), Lucknow
|Name of The Available Post
|Professor, Assistant Professor, and Associate Professor
|Total Numbers of Posts
|58 Vacancies
|Employment Type
|Uttar Pradesh Govt Jobs
|Job Location
|Uttar Pradesh State
|Application Method
|Online Mode Only
|Official Website
KGMU Teaching Recruitment 2016
The online application forms are incited from the suitable and skilled aspirants by the KGMU (King George's Medical University), Lucknow regarding the 58 Professor, Assistant Professor, and Associate Professor posts. Candidates can apply for the KGMU Lucknow Recruitment 2016 by sending the online application before the closing date.
Only those candidates can apply for the KGMU Teaching Vacancy 2016 those have the eligibility criteria. Below you can take the eligibility criteria details. Candidates should need to submit their application form before the last date which is 20th December 2016 otherwise King George's Medical University officials will not receive your application form.
Educational Qualification:
- Candidate educational qualification will be measured for the KGMU Teaching Recruitment 2016 MCI/ DCI norms and KGMU Act 2002.
- For more information, you can download the advertisement from the King George's Medical University official website.
Age Limitations:
- The age limits of the candidate should be lies between the age criteria set up by the King George's Medical University.
- The upper age relaxation will be provided to the candidates as per government norms.
Selection Process: On the basis of Interview performance applicants will be appointed on the available posts.
Application Fee:
The application charges will be applicable as per the below details:-
|Category Name
|Application Charges
|Open category candidates
|SC (Schedule Class)/OBC (Other Backward Class)
|Submission Process
|through Online mode while filling Online Application
Uttar Pradesh TET Admit Card 2016
KGMU Teaching Recruitment Dates
|Online Application From Commencement Date
|Available Now
|The last date to submit the Online Application Form
|20th December 2016
How to Apply Online for KGMU Recruitment 2016-17?
Willing candidates can apply online for the vacant posts by submitting the application form. Candidates can easily apply online with the help of below instructions.
- First of all, candidates need to log on to the KGMU (King George's Medical University), Lucknow official website.
- Then check out the latest notification section and search the KGMU Teaching Recruitment 2016.
- Open the notification on next web page and click on apply online button if you are eligible.
- Enter the all required details on the application form and enclosed the scanned copies of the related documents.
- Submit the application fee and collect the hard copy of the duly filled application form.
- At last, check out the complete form details and press on the submit button.
Here we discuss KGMU Lucknow teaching Recruitment 2016 details. Those candidates want to get more details regarding the latest release admit card, recruitment, answer key and admit card then must bookmark our website. A team of professionals updates this site day by day according to the official notification. You can also share all details with their friends and colleagues on social networking sites.


text:
I'm looking forward to the possibility that spring is just around the corner. One of the most versatile and season transitioning items that we can embrace is the vest. Making a Longer Vest Work #PlusSize #Fashion For what may seem to be forever, we have seen the vest as … [Read more...]
The 3 Hot Trends in #PlusSize Fitness Looks
It's new year and we are heading to the gym! The 3 Hot Trends in #PlusSize Fitness Looks What are girls with curves rocking this season? Here is what is hot in PlusSize Fitness Looks 1. Colorblock Jackets We know that coloblock is slimming. We also know that a long … [Read more...]
#PlusSize Wedding Dress Preview
Now that we have passed the holiday season, we can focus on wedding season. Wedding season is just around the corner, if you ask any bride- to- be. #PlusSize Wedding Dress Preview Because finding the perfect dress in the perfect size, can be a challenge From Kiyonna … [Read more...]
Looking Slim in an Off-Shoulder Look #PlusSize
Showing off your shoulder can actually slim your look. Luckily, there are a lot of great looking off-shoulder styles for curvy gals. Looking Slim in an Off-Shoulder Look #PlusSize An 'off the shoulder' look can really mean: A Cold Shoulder- when the shoulders are exposed … [Read more...]
100 Plus Size Sweaters Each Under $20 #plussize #Deals
We have officially entered into sweater season. It is a good thing that there are plenty of great deals out there! 100 Plus Size Sweaters Each Under $20 #plussize #Deals Many of these sweaters will have additional discounts on the site. Sweaters under $20 … [Read more...]
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text:
What is a brand? Does everyone know about the meaning of brand?
I guess that there are many people know about this information.
But somehow some people if they not study in this category.
They're not know about it.
Here some of the meaning of branding
Ancient and modern
The Oxford American Dictionary (1980) contains the following definition:
Brand: a trade mark, goods of a particular make: a mark of identification made with a hot iron, the iron used for this: a piece of burning or charred wood, (verb): to mark with a hot iron, or to label with a trade mark.
Brands are more than telling name and symbols. Brands represent consumer's perceptions and feeling about a product and performance. High brand equity provides a company with many competitive advantages.
A powerful brand enjoys a high level of consumer brand awareness and loyalty. Because consumers expect stores to carry the brand, the company had more leverage in bargaining with resellers, the brand name carries high credibility, and the company can more easily launch line. Above all, a powerful brand offers the company some defense against fierce price competition.


text:
Few neighborhoods are as lovely as Gramercy, arguably the most charming area of New York City.
Situated between Murray Hill and the East Village, Gramercy has a relaxed, old-money type of feel. It's no wonder, as in pre-civil war New York the brownstones and mansions facing the park were the poshest places to live in the city. Former New York governors and presidential candidates have lived in Gramercy, as did young Theodore Roosevelt.learn more about this neighborhood
#9Neighborhood popularity:based on Naked Apartments searches
Building Mix
- 27% Elevator/Laundry Building
- 22% Luxury Highrise
- 21% Pre War
- 9% Post War
- 8% Walk-Up
Legal Disclosure: Neighborhood descriptions and data are created exclusively by Naked Apartments without contributions or approval from the agents listed on this page.
From the west gate by Beyond_My_Ken is licensed under GFDL
Don't miss this large one bedroom, one bath with outdoor patio! This apartment features brand new windows and sliding glass door, and great natural light with southern exposure. 210 East 22nd Street boasts laundry on every floor, part time doorman, live in super, elevator, full time maintenance crew, and is located on a tree lined block in the heart of Gramercy Park. Pets OK. Call to make an appointment with the leasing office to see your new home today!
Apartment Details
$3,000, One Bedroom, 1.0 Bathroom
Last Updated ~ 4 Years
Listed For ~ 4 Years
Available Immediately
Pets: Pets Allowed
- Elevator/Laundry Building
- 600 sq. ft.
- Web ID: 210GLM
Doorman, Elevator, Laundry Room, On-site super, Outdoor Space, Storage Room
Nearby Subway Stations
123rd St (0.07 mi)
C E23rd St (0.15 mi)
118th St (0.18 mi)
F M23rd St (0.23 mi)
128th St (0.27 mi)
A C E L14th St-8th Av (0.4 mi)
F M L 1 2 314th St (0.42 mi)
F M L 1 2 36th Av (0.43 mi)


text:
Hey I was watching Phantom Planet again and well I had an idea what if after PP Danny's parents didn't accecpt him they rejected him and did experiments on him they tortured him snd thretened to kill Jazz and Danny if they told anybody
This is Danny's thoughts as he is telling the story
Most people think that after I saved the world life was great.
That people accepted me
That my parents accepted me
That I wasn't hunted
That I got everything I ever wanted.
They were wrong...dead wrong
If you heard about this from a textbook of how after I saved the world life was perfect after that
They lied
They saved you from my terrible life story
They saved you from having nightmares about this story
This isn't the story of how my parents loved me, isn't a story of me and Sam, or me beating up bad guys (Well in the end) So if you want that story stop listening now. This isn't that story. This isn't a happy story where everything turns out perfect in the end. Don't say I didn't warn you.
This is the story of how I was broken then taped back together.
This is the story of how I was saved from my destiny by someone who went through the same thing
This is the story of how part of my heart died
Of how my obsession was replaced how I got a new family and friends
This is the story of how I was tortured.
How do you guys like it! I thought of this while also reading fanfictions but the prolouge came to me while watching PP
Hope you guys review!
~ D-Bug


text:
Rival Bach editions will no doubt dominate the coming CD year (they've already started), but Teldec's budget-price enterprise has a missionary zeal that sets it apart. Who can resist Nikolaus Harnoncourt's blazing Christmas Oratorio, or Ton Koopman's improvisatory - and, in many cases, newly released - accounts of the organ works, or Il Giardino Armonico's provocative set of the Brandenburg Concertos? True, the Harnoncourt-Leonhardt sacred cantatas are sounding a little tired nowadays, hi-fi-wise, but I still wouldn't trade them for their successors.
Teldec's Bach is available virtually anywhere, but if you want the New York Philharmonic's limited-edition 10-CD American Celebration (New York Philharmonic NYP9904) you'll need either to go to your nearest Tower Records or e-mail the Philharmonic at: www.newyorkphilharmonic.org
It'll be well worth the trouble, with previously-unissued Bernstein recordings of key Copland, MacDowell, Schuman, Rorem and Varese vying with Barbirolli's Loeffler, Monteux's Creston, and Boulez's Carter for top billing. Just a tad esoteric, perhaps? Not in the least. Twentieth-century musical Americans have bags to say and their best interpreters help them say it with style. Artur Rubinstein's piano-playing was, in a sense, the very epitome of sophisticated interpretative style.
Listening to the 94 CDs of RCA's Rubinstein Edition (RCA Red Seal 09026- 63000-2) recalls a brand of post-Romantic excitement (in the early recordings) and a degree of urbanity (in the later ones) that are fairly characteristic of this great artist. RCA's sumptuous presentation borders on kitsch and there are countless repertory duplications (most of them illuminating), but the actual playing, of Chopin and Brahms in particular, is indelibly memorable. Still, if pressed to choose a recording of Chopin's two piano concertos, I would personally opt for Krytsian Zimerman's newest, with the Polish Festival Orchestra (DG 459 684-2, two discs).
True, the performances are pretty slow, and Zimerman's very individual way of bending the musical line will not be to all tastes (even I can imagine tiring of it on occasion). But with every note of both scores presented intact, and a fastidiously attentive approach to Chopin's orchestral writing, I doubt that these loveable war-horses will ever sound more musically interesting.
Hearing "standard rep" brought newly to life is a major justification for listening to fresh recordings of old favourites, which is why the late Sergiu Celibidache's conducting has made such a strong impact among collectors. Celibidache's well-known refusal to make records is hardly an issue now that EMI and DG have provided us with generous "official" CD "editions" of live or broadcast material.
DG's Brahms symphony cycle (459 635-2, three discs plus a free rehearsal disc) with the Stuttgart Radio Symphony offers a luminous slant on music that others tend to smother with excessively rich textures. Subsequent DG/"Celi" collections of Strauss, Debussy, Ravel and mixed Russian repertoire have proved equally stimulating.
Nikolaus Harnoncourt is similarly attentive to Dvorak's Eighth Symphony, inspiring his woodwinds to virtual birdsong and treating the dance element as a central musical priority. Harnoncourt's live Concertgebouw recording is brimful of musical points worth making, with the grizzly tone-poem The Noon Witch as a modern-sounding extra (Teldec 3984-24487-2).
Dvorak's last orchestral works are rich in shock-value, but there are other ways of arresting musical attention. Pianist Thomas Larcher alternates Schubert's late piano pieces (or Klavierstucke) with piano pieces by Schoenberg (ECM 1667), allowing one voice to pose the questions while the other responds with relevant answers. It's a strange but effective idea, much aided by Larcher's intensity.
The ever-provocative Hagen Quartet adopt a similar interpretative manner in Beethoven's "Serioso" and Schubert's late G major Quartets, maximising contrasts between charm and chill while keeping the near-surreal element of both scores in clear focus (DG 457 615-2).
The Leopold String Trio are rather less innervating in Beethoven's three delightful Op 9 Trios (Hyperion CDA67254), though always genial, warmly blended and appreciative of musical argument. Sergio Fiorentino's more concentrated playing style suits Schumann's turbulent Fantasie in C major, which clocks up a very broad total timing of 35'07" (the finale runs to 13'40"). Appian's continuing efforts on behalf of this underrated musician - who died suddenly on 22 August 1998 - have never borne richer fruit and the remaining items (more Schumann, including the G minor Sonata) are virtually as distinctive (APR5560).
Indeed, pianists have been enjoying a bumper year on CD, what with a healthy deluge of new issues and the much-lauded climax of Philips's exhaustive "Great Pianists of Twentieth Century" series. There's also Frederic Rzewski's 36 piano variations on the Chilean song "The People United Will Never Be Defeated", pleasing to the ear but very difficult to play. Marc-Andre Hamelin takes it all in his stride, adds an amazing cadenza and rounds off with Rzewski's minimalist-style "North American Ballads" (Hyperion CDA67077). Rzewski's musical agenda has jazz hovering somewhere in the background, but when it comes to the "real thing", no one in my book compares with Duke Ellington.
RCA's handsome limited edition Duke Ellington Centennial Edition: the Complete RCA Victor Recordings 1927-1973 (RCA 09026-63386-2, 24 discs) takes us from Cotton Club to Church, toying with harmonies that even nowadays sound new, and proving beyond doubt that the Duke was one of the century's greatest composers.
Edgar Varese is another unsung musical innovator, and while Riccardo Chailly's spectacular Gramophone-award-winning Decca "Complete Varese" wins justified plaudits, I'd like to recall a rather earlier and even more vividly spot-lit-account of Varese's "Arcana".
Jean Martinon conducts the Chicago Symphony (RCA 09026 63315 2) in an aural star-burst, while the couplings are Bartok's Miraculous Mandarin Suite and the finest-ever recording of Hindemith's Suite "Nobilissima visione". It would seem that Thomas Ades has earned himself the unofficial title of crown prince among younger British composers. But while Ades's opera Powder Her Face will likely provoke the strongest reaction among a wider public (you can see it for yourself on Channel 4 on Christmas Day), his purely orchestral "Asyla" is surely the more enduring work.
Sir Simon Rattle's fine-tipped CBSO reportage of "Asyla" (EMI CDC5 56818 2) creates an appropriate illusion of space. Mysterious half-lights predominate, much as they do in Simon Bainbridge's disquieting "Ad Ora Incerta". Bainbridge takes Primo Levi's Holocaust poetry as his starting point, and his music swirls off the page like a sickly ill wind.
Martyn Brabbins conducts the BBC Symphony in a fine performance (NMC D059), whereas composer Frank Bridge enjoys an extra dash of interpretative perception under his one-time star-pupil Benjamin Britten. "Enter Spring" is a glorious paean to nature which, towards the end of its ecstatic course, delivers a sure premonition of Britten's own Spring Symphony.
It's the star attraction on a memorable BBC Legends CD (BBC BBCB 8007- 2) that also features Bridge's evocative suite "The Sea".
Antonio Pappano, like Britten, is a deeply intuitive interpreter. Pappano's new Werther for EMI was among the year's happiest operatic releases and is only marginally surpassed by his Il Trittico (EMI CDS 56587-2, three discs) with Roberto Alagna and Angela Gheorghiu tackling some of the pivotal roles. Pappano's handling of Il Tabarro - "one-part Tosca, two of Turandot and one of Richard Strauss", as I wrote at the time - is consistently satisfying.
Alagna and Gheorghiu crop up again in Riccardo Chailly's La Scala La boheme (Decca 466 070-2, two discs), a vivacious reading with a warmly lyrical core that occasionally recalls Toscanini's legendary 50th- anniversary broadcast (RCA). Chailly keeps to the musical text without resorting to dry literalism and his refusal to wallow (always a temptation with Puccini) somehow lends extra pathos to the drama.
Another brand of pathos visited the 1951 post-war opening of Wagner's Bayreuth Festival when Hans Knappertsbusch conducted Parsifal and a complete Ring cycle. Legal wrangles had long deprived us of the Ring's crowning Gotterdammerung, that was until Testament fought the battle head-on and won. Soprano Astrid Varnay is a resplendent Brunnhilde, but the real hero is Knappertsbusch himself who, though hardly the most disciplinarian of maestros, inspires a reading of unrivalled cumulative power (SBT 4175, four discs).
And while Gotterdammerung marks the end of one world, Jean- Luc Godard's Histoire(s) du Cinema (ECM New Series 465 151-2 five discs, plus four hard-bound books) symbolises the coming of another. Only Godard and Manfred Eicher could have celebrated cinema without recourse to the visual image, and the resulting aural montage (snippets of soundtrack, concert music, recitations, etc) is breathtaking.
It was the most nourishing musical surprise of my year, but before taking my leave, I simply have to recall an historical release that will have you dancing deliriously round the living-room.
Grigoras Dinicu was a resourceful - and highly creative - Romanian gypsy fiddler who inspired both Menuhin and Heifetz. Listening to his records is like sampling ceilidh music spiced with garlic. The sound-frame might be scuffed, the musical material occasionally strong meat (loads of darkening minor-key stuff), but Dinicu's playing is aflame with dash and bravura. It is called Zigeunerweisen (Symposium 1218), so be sure to add it to your trans-millennial play list.Reuse content


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Mortgage Loan Loss Mitigation Application – Financial Ratios – Be Careful: In this video, attorney Jason McGrath, who handles many mortgage dispute and foreclosure matters, discusses an important loss mitigation issue. Persons filling out their mortgage loan loss mitigation applications need to be very aware that the financials they are listing may make or break… Read more »
Home Affordable Modification Program
Mortgage Loan Servicers – Illegal Delays and Denials of Modification and Loss Mitigation
Mortgage Loan Servicers – Illegal Delays & Denials of Modification & Loss Mitigation Large mortgage loan servicers often illegally delay & deny modification & other loss mitigation / mortgage relief attempts. In this video, attorney Jason McGrath discusses some of these issues. We hope that you find this video helpful. While we do assist clients… Read more »
Mortgage Relief – Hope Loan Port Hands Jail Keys to Inmates
Mortgage Relief – Hope Loan Port Hands Jail Keys to Inmates McGrath & Spielberger works with borrowers to save their homes. Certain mortgage loan servicers, like Bank of America, force us to use a "neutral" online platform to submit mortgage loan relief and loss mitigation applications. This platform is known as Hope LoanPort (although it… Read more »
Does Your Mortgage Loan Servicer Participate in Loss Mitigation?
Does your mortgage loan servicer participate in the Home Affordable Modification Program? Here is a list of the mortgage loan servicers (not mortgage lenders) who participate in the Federal Government's Home Affordable Modification Program (HAMP), according to the Federal Governement itself (as of April 30, 2013). Please note this list does not include lenders and/or… Read more »
HAMP: Fewer Borrowers Offered Loan Modification Relief in 2013 (monthly average)
HAMP: Fewer Borrowers Offered Loan Modification Relief in 2013, Compared to Average Month in 2012 The Home Affordable Modification Program (HAMP) is part of the Federal Government's Making Home Affordable (MHA) program. (No, I don't know why HAMP includes "Program" as part of it's title and the "Making Home Affordable" program does not.) The way… Read more »
FHA Loan Mortgage Relief – Many More Borrowers Now Eligible
Changes in FHA Mortgage Relief / Loss Mitigation Policies Should Allow Many More Borrowers to Save Their Homes My law firm represents borrowers who are in need of assistance with their mortgage loans, and we do so in multiple states (FL, GA, NC, OH, SC, TN). Some of those homeowners have Federal Housing Administration (FHA)… Read more »
How BOA Tainted the Allegedly Independent Foreclosure Review
How BOA Tainted the Allegedly Independent Foreclosure Review The "Independent Foreclosure Review" (may it now rest in peace) was established as a result of a settlement of federal lawsuits against numerous mortgage loan lenders and servicers. The intent was to provide compensation to borrowers who were improperly foreclosed upon. Borrowers were supposed to be able… Read more »
BOA mortgage loan modification offers – errors & mistakes abound
BOA Mortgage Loan Modification Offers – Errors & Mistakes Abound As an attorney who represents mortgage loan borrowers and homeowners, I see more than my share of mistake-filled Bank of America mortgage loan modification offers. I just reviewed another modification offer from BOA, made to new clients of mine. Almost every modification offer I've ever reviewed… Read more »
BOA Responds to my Blog on Supposed Modification Denials
BOA Responds to my Blog on Supposed Modification Denials (UPDATE: I have been contacted by numerous homeowners who describe being told the exact same thing I was about how BOA handled this.) On May 16, 2012 I published this blog post (click title to read it): DOJ Settlement Results in BOA "Denying" Thousands of Mortgage… Read more »
DOJ Settlement Results in BOA "Denying" Mortgage Modifications? (huh?)
DOJ Settlement Results in BOA "Denying" Thousands of Mortgage Modifications? (huh?) (UPDATE: see the bottom of this page for a link which explains BOA's direct response to this blog article) A few days ago, I was on the phone with a supervisor at Bank of America, discussing the unexpected mortgage loan modification denial letter… Read more »


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Which would you all recommend? My wife and I are headed to Charleston at the end of May for our anniversary.
DoubleTree is $169/nt and Embassy is $199/nt. I have read on here that DoubleTree has an excellent location, but I have never been disappointed staying at an Embassy Suites.
Help! Thanks!
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Charleston: DoubleTree or Embassy Suites?
Which would you all recommend? My wife and I are headed to Charleston at the end of May for our anniversary.
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We stayed at the embassy suites a couple of years ago. It was pretty (former military academy) but the location is not perfect. it is quite near the museum and visitor center, but a decent walk in to the town center. I don't know anything about the Doubletree, but I felt that another time we would choose a location more in the center of Charleston. However, do not it was a walk, not a drive to the restaurants and beautiful homes.
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We stayed at the Doubletree in February. The hotel was conveniently located - near the corner of Church and Market - and close to Bay, Broad, Queen, King and Meeting Streets. The hotel was very nice. We had a room (all suites in this hotel except for annex building) on the fifth floor facing the front of the hotel with a harbor (several blocks away) view. The hotel has a pleasant courtyard with water fountain, potted plants, tables and chairs, benches. It was very pleasant to sit out there.There are some 2 level rooms which open onto the courtyard. There is also an annex at the opposite end of the courtyard from the main building. Our suite in the main building had a spacious livingroom(couch, tv, tables, dining table and chairs)/kitchen area (small fridge, microwave, coffee pot, sink) and bedroom (king bed, another tv). Breakfast was very good - fruit, yogurt, cereal, scrambled eggs or sometimes French toast, pastries, grits, biscuits, gravy, bacon, sausages, coffee, tea, juice.
If I recall correctly, the Embassy Suites is quite a long walk to the center of town. If we go again, we would stay at the Doubletree.
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The Doubletree is in a much better location and it is a much nicer hotel.
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I agree that DoubleTree is a better choice. I walked into the Embassy Suites while in Charleston last month, as I too usually like Embassy Suites, and was not impressed. It is in the old Citadel, and while the outside architecture is quite interesting, the inside seemed rather austere and old to me. Not your usual bright-tiered lobby. Also it is on the far side of town. DoubleTree is right beside Market Street, across the block from the carriage tours and just a couple of blocks from the water. It was a great location.
I was not sure where to stay and everyone at this forum was so kind to stear me in the direction of DoubleTree. We were very pleased with their recommendations. Have fun. We really enjoyed our visit there.
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Whichever you choose, ask for a room on one of the upper floors. I love Charleston, but its historic district is one of the loudest, late night places I've visited. We stayed at the Vendue Inn which was beautiful but our first room was so loud we went looking for a place in one of the high rises and none were available. They moved us to a "quieter" room. Unfortunately the main parking garage was close enough that we woke up at 2 a.m. when the bars closed and everyone was going back to their cars!
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Choose neither. stay in a historic inn or carriage house. I suggest old village post house inn, historic charleston b and b rentals on broad street, and charminginns.com. go to the charlestoncvb.com and find the best way to stay. you can stay at a doubletree anywhere. not to mention the inns are a whole lot less!
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I disagree about the Inns being a whole lot less. We are going to Charleston in July (as we do every summer) and we decided to stay at The Doubletree this time. We usually stay at a Inn. The Doubletree is costing us less per night than any of the Inns we have stayed at and we have booked the largest suite they have.
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The Doubletree in Charleston is so unusual and so nice, it is more like an inn than a chain hotel. The lobby is beautiful! It is one of the only hotels I've ever stayed in with two story rooms.
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Gift GuidePrevious Next
How to Get Promotion Worthy Gift Ideas for Your Boss
Bosses: Whether you love 'em or leave 'em, they're in charge - which means that sometimes, you're in charge of getting them a gift. Think positively and shop for gifts that truly rule (and will maybe score you a raise?).
Stick with humor
A sense of humor is great quality - especially if you work in a serious office. Your boss is bound to crack a smile when you gift her with a silly mug, a funny "name plate," or a hilarious desk accessory. Plus, it'll make her more relatable to everyone who steps foot inside her office.
Deck out his desk
A set of high-quality pens, a leather portfolio, a docking station, or a fancy letter opener will upgrade the desk where he likely spends most of his day.
Cater to the traveling boss
A framed map, a portable alarm clock, a toiletry case, or a travel mug are all great gift ideas for a boss who's always on the go. Think also about her actual travel time - a portable neck pillow, a travel blanket, or a weekend bag are thoughtful presents, too.
Consider his family
He's not always the boss. Sometimes he's a husband, a dad, a friend - you know, a person. A picture frame for family photos, a golf set for outings with friends, or a game he can play with his kids show you think of him as an equal as well as a superior.
Encourage her health
Odds are, your boss works a lot. She's the boss, after all! So if you know she likes to keep fit, consider athletic gifts like a yoga mat, a water bottle, or a subscription to fruit-of-the-month club.
Keep him alert
Being the boss requires major brain power. A coffee maker for his office, crossword puzzles to keep his mind sharp, or vitamins to help him function on a high level are all great gift ideas for a boss.
Give her the day off
Reservations at a raved-about restaurant or tickets to a sporting event or concert will help your boss make the most of her weekend.
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Journalist Report
Tereza Pultarova
It's time to expand the base
The first crew on Mars would have the most difficult task - confined
into a tiny habitable structure
with minimal personal space and only the most necessary facilities,
they will live and work
similarly to analogue crews at the Mars Desert Research Station.
However, they won't remain in these
ascetic conditions for ever. They will expand the base - to prepare it
for those coming next and
also to get more personal comfort.
Crew 135 commander and extreme environments architect Ondrej Doule has
come up with a proposal to
upgrade the aging Mars Desert Research Station structure not only to
make it more cosy and crew-
friendly, but also to enter the next stage of Mars colonization.
"First, we had to understand how the base is constructed and what are
the structures," explains
Ondrej. "That took the biggest part of the design inclusive mapping
all the layers of the metal
structures which are quite complex. Based on this information I am
proposing several upgrades."
First of all, he believes, comes personal space of the crew members.
It's understandable - they will
spend months, perhaps years living at close quarters. Chances are they
would eventually start
getting on each other's nerves - hence the need of sufficient private space.
Instead of the existing parallel chambers with alternate lower and
upper bunks (where one risks
crashing his or her head with every not-well-thought-through
movement), Ondrej proposes a concentric
layout with the bedroom doors opening toward a small newly created
circular hall in the middle of
the upper deck leading into the slightly expanded work area.
"These rooms wouldn't be larger than the existing ones but they
wouldn't be so thin and long, there
would be more open space inside and you wouldn't be afraid that you
bang your head somewhere. It's
really only the simplicity of the geometry," says Ondrej. "Also those
rooms are equal in size, there
are no bigger rooms and smaller rooms, which is the case now and the
now smaller rooms would be
bigger with the new concept."
However, the optimal solution, according to Ondrej, would be a bit
more ambitious. Instead of six
rooms squeezed one next to each other, he proposes placing only four
astronauts' bedrooms into the
main station building and connecting this area through a bridge with
another cell outside.
"This structure is elevated so you can have an ATV parking below and a
water tank above so you are
utilizing basically the water gradient," says Ondrej. "Another very
important structure would be the
emergency escape vehicle that would probably have the same size as the
MDRS, only that it would be
accommodating lots of fuel and escape pods, space suit pods for the
entire crew and a MDRS control
center that is currently missing."
In the case of emergency - such as a sudden collapse of the station's
life-support systems or a
biological contamination, the astronauts could run from the main
station into the escape vehicle
through an emergency bridge, taking off from Mars, leaving the station behind.
With a bit of luck, such a scenario would never happen, however, it is
better to be safe than sorry.
Ondrej's proposal includes also a greenhouse ten-times the size of the
current green hab, providing
space to grow enough plants to cover most of the astronauts' nutritional needs.
Using natural terrain geomorphology in the vicinity of the station,
Ondrej proposes building a space
port behind a nearby hill connected to the base with an underground tunnel.


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Make an Appointment
At the Seattle Foot and Ankle Clinic, our doctors and staff are committed to providing high quality care for all of your foot and ankle needs. If you are looking to schedule an appointment, please contact us now:
Foot & Ankle Problems
Here are some common foot and ankle problems that our trained specialists will help correct:
- Bunions
- Heel Pain
- Foot Pain
- Fractures
- Ankle Sprains
- Nail Problems
Dr. Erik C. Lilja FACFAS
Dr Lilja, after 13 years at SFAC, is joining UW/NWH Fremont Specialty Clinic. His first appointment week will be April 3rd, 2017. The last clinic appointment in Northgate will be March 17th. Contact information is available through our current clinic phone, 206 527-4177. Billing inquiries may be made to Tonya at 206 527-9160.
Dr. Newell is going to take a sabbatical effective March 15th, 2017. Continuing care for his patients will be available through Dr Lilja in his Fremont location.
Dr. Hale will continue in practice in his downtown location at 600 Broadway across from the Swedish First Hill campus. His forwarding phone number is 206 344-3808. He can also be reached at www.footankle.com.


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How Do Plants Pollinate? (To the tune of: "This Land Is Your Land")
What does a plant need
To make a new seed?
Three things give flowers reproductive powers—
The sticky pollen,
The slender stamen,
And pistils make the flower whole.
What gets the pollen going
To keep new plants growing?
Different kinds of birds do,
Or the wind that's blowing.
Butterflies and bees,
Carry pollen they need.
That's what makes pollination work.
If a flower's not scented,
Or brightly colored,
And the flowers are smaller,
In clusters tighter.
With stamens longer,
the signs are stronger,
This plant spreads pollen on the wind.
When bright colored flowers,
Have a sweet perfume,
And a sugary nectar,
Then chances are good,
That birds and insects active,
Find the plants attractive,
Find the plants attractive,
And they'll spread the pollen as they go.
To hear this song click on " Sing The Pollination Song" here. Visit Pollen Study for more pollen learning!


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Valtorta conferences are important events for the discussion, sharing, and promotion of Maria Valtorta's writings throughout the world. Conferences are an opportunity for scholars and experts to give talks about their research into Maria Valtorta's writings, her history, and the impact her writings have, are having, and will have on the hundreds of thousands of readers in dozens of countries around the world. It is also an opportunity for Valtorta readers to gather together and share their mutual love of Valtorta and her writings, as well as their insights and experiences.
There have been numerous Valtorta conferences in Italy and Australia over the years. Most of the Italian conference materials have not yet been translated into English, but you can watch a video clip and find out more information about the 2011 Italian Valtorta Conference here. This web page includes an English translation of an excerpt from Archbishop Nuncio Apostolic Pier Giacomo De Nicolò's's homily about Valtorta that he preached in the Basilica of the Most Holy Annunciation in Florence on the occasion of the 50th anniversary of Maria Valtorta's entrance into Heaven.
On this page, we will give information about the Italian, French, and Australian Valtorta conferences.
The first International Italian Valtorta Conference took place in Pisa, Italy, on October 22-23, 2016. Six professors, two other doctors, an engineer, a geologist, a professional astronomer, a professional artist, a professional musician, a publisher, and a devout father gave presentations about Maria Valtorta and her writings. Each talk focused on a different topic. I will list each of the speakers further below.
Stephen Austin of the Maria Valtorta Readers' Group represented the Maria Valtorta Readers' Group as a speaker at the conference. You can read Stephen's comments about the conference in our December 2016 newsletter. You can view his talk by clicking the video below:
at the First International Italian Valtorta Conference in Pisa, Italy, on October 22, 2016
Zenit, a popular international news agency, published two articles about this conference:
Discovering the "Gospel" of Maria Valtorta
Maria Valtorta: Science and Faith Converge
Stephen's talk is mentioned in the second article. An excerpt from the second article is below:
[...] In the same vein as Lavère, ranks the work of another engineer, Stephen Austin, from the United States, a young thirty-year old man. He originally ran up against this mystic's work for the sole purpose of repudiating it, but he then ended up subdued by the completeness and beauty of her The Poem of the Man-God (now known as The Gospel as Revealed to Me) to such extent that he dedicated four years of research to compile his e-book in English A Summa & Encyclopedia to Maria Valtorta's Extraordinary Work and present it to the public, at this first International meeting. Constantly updated, Stephen's work has 13 chapters and 49 sub-chapters, in which he introduces The Gospel as Revealed to Me to readers. The theological objections of the Church against private revelations are eviscerated in this e-book by a careful investigation of the approval that Valtorta's work has received from saints and prelates: Saint Padre Pio and Saint Teresa of Calcutta; Pope Pius XII; cardinals, archbishops and bishops; 23 doctors of theology, divinity, or canon law; 16 university professors; etc. Stephen Austin then compares Valtorta's visions with those of the other mystics, Blessed Anne Catherine Emmerich and Venerable Mary of Agreda, both of which are less detailed and less accurate. He also emphasizes the almost absolute correlation between the Gospel and the text of Viareggio's mystic, with the difference that, compared with the 141 days of Jesus' ministry in the Sacred Scriptures, there are in The Gospel as Revealed to Me about 500 days, presented in much greater detail, historically valid, on account of the valuable and unique information on botany, geography, ethnology, and astronomy. Austin's e-book is known as far as Oceania and Australia, thanks to his promotional work, which included participating in an interview on the Australian TV program of a religious nature Spirit of Life.To view the informational video for this international Valtorta conference which gives details and showcases the speakers, see: Video Convegno Valtortiano Internazionale Ottobre 2016 (versione ridotta).
You can also download the poster for the International Italian Valtorta Conference (showcasing all the conference speakers) here: 2016 International Italian Valtorta Conference Poster (PDF).
The official page for the first International Italian Valtorta Conference is: Primo Convegno Valtortiano Internazionale. The videos of the other speakers are available on that page.
I will list each of the speakers below. Next to their name will be the title of their talk in Italian or French (with an English translation of the talk title). Click on the title of their talk to watch it.
Don Ernesto Zucchini is president of the Maria Valtorta Foundation (distinct from the Maria Valtorta Foundation CEV Onlus) and is a Professor of Theology since 2009 at the School of Theological Formation (Scuola di Formazione Teologica) of the diocese of Massa Carrara. He is the main speaker in a Radio Maria broadcast on the mystic and a parish priest at Pontremoli, in the province of Massa Carrara and in four other, neighboring localities. He hosted the first International Italian Valtorta Conference took place in Pisa, Italy, on October 22-23, 2016. Zenit, a popular international news agency, published two articles about the conference (mentioned earlier):
Discovering the "Gospel" of Maria Valtorta
Maria Valtorta: Science and Faith Converge
The first article is an interview with Don Zucchini and the second article discusses the conference. You can find out more information about the conference and listen to Don Zucchini's talk here: Maria Valtorta, un Miracolo Storico (Maria Valtorta, a Historical Miracle).
Professor Fernando La Greca: Ci sono anacronismi storici nell'Opera di Maria Valtorta? (Are There Historical Anachronisms in the Work of Maria Valtorta?)
Professor Maria Grazia Sovrano: Gesù e i gentili (Jesus and the Gentiles)
Professor Emilio Biagini: La Sacra Sindone e Maria Valtorta (The Holy Shroud and Maria Valtorta)
Dr. Liberato De Caro: L'opera valtortiana al vaglio dell'astronomia (Valtorta's Work from an Astronomical Viewpoint)
Geologist Thomas Dubé: Chronology, History, and Astronomy in the Writings of Maria Valtorta
Professor Francesco Rizzi: L'Assunta in Maria Valtorta, Dante e San Tommaso (The Assumption in Maria Valtorta, Dante, and St. Thomas)
Professor Anna Maria Costa: Maria Ss. Corredentrice nella vita quotidiana (Most Holy Mary as Redemptrix in Everyday Life)
Professor Ruben Pineda Esteban: L'Immolazione nelle opere di Maria Valtorta (Immolation in the Works of Maria Valtorta)
Professor Giuseppe Fioravanti: Considerazioni sul laicato al tempo di Maria Valtorta (A Reflection on the Laity in Maria Valtorta's Time)
Monsieur Bruno Perrinet: L'historique et les différentes activités de l'Association Maria Valtorta (The History and the Various Activities of the Maria Valtorta Association)
Engineer Stephen Austin: Promoting Maria Valtorta's Extraordinary Writings Around the World
Maestro Giovanni Mezzasalma: Riflessioni sull'arte sacra alla luce dell'Opera valtortiana (Reflections on Sacred Art in the Light of the Work of Valtorta)
Ivano Conti: concerto su Maria, testi e canzoni sulla vita della Madre di Gesù (Concert of Maria, Texts and Songs About the Life of the Mother of Jesus)
Signore Michael Mellner: Maria Valtorta e la Chiesa Cattolica (Maria Valtorta and the Catholic Church)
The first French Valtorta Conference took place in Paris on May 28, 2016. You can view videos (in French) of some of conference talks here and here. Titles of some of the talks include "Maria Valtorta: Le don extraordinaire pour notre temps" [Valtorta: The Extraordinary Gift for Our Time], "Maria Valtorta, un don de Dieu validé par la science" [Maria Valtorta, a Gift from God Validated by Science], "Que lire de Maria Valtorta?" [Why Read Valtorta?], and "Maria Valtorta: La meilleure formation pour un prêtre à la pastorale" [Valtorta: The Best Training for a Priest in Pastoral Care].
Details about two of the speakers are given below:
Fr. Yannik Bonnet, D.Sc., is a Doctor of Science from Polytechnique School, which is the most famous school in France for engineers as well as for chairmen in many domains. In France, Polytechnique may be compared to Yale, MIT, or Harvard. In France, D.Sc. is considered a higher doctorate than a Ph.D. Fr. Bonnet was not only a professor, but was for eleven years the director of Ecole Supérieure de Chimie de Lyon (a university for engineers). After being widowed in 1995, he was ordained a priest in 1999, and is now writing in many religious newspapers. Fr. Yannik Bonnet, D.Sc., spoke at the French Maria Valtorta Conference on May 28, 2016, where he gave his testimony about how the work of Maria Valtorta entered into his life and discussed various aspects of her work. He discusses the characters in her work in his talk here: Maria Valtorta / Quelques personnages dans l'oeuvre / Père Yannik Bonnet - 28 mai 2016. He gives his talk "Maria Valtorta: The best training for a pastoral priest" here: Maria Valtorta: La meilleure formation pour un prêtre à la pastorale.
Peter Bannister is an exceptionally talented musician who holds graduate degrees in music from King's College Cambridge and systematic/philosophical theology from the University of Wales. He has been the recipient of numerous awards and has been invited to give concert performances in many countries. His bio is here. He gave his testimony at the 2016 French Valtorta Conference and wrote an article in favor of Maria Valtorta on the Sciences & Religion website. His article is available here: Les écrits de Maria Valtorta (1897-1961) - imagination surchauffée ou percée pour l'exégèse biblique?
The Australian Valtorta Conference took place on October 22-23, 2016, headed up by Catherine Loft of the Maria Valtorta Readers' Group. You can read about the events of the conference and testimonials from attendees in our December 2016 newsletter. You can also download the conference flyer here: 2016 Australian Valtorta Conference Flyer (PDF).