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Major histocompatibility complex
|Major histocompatibility complex
The major histocompatibility complex (MHC) is a set of cell surface proteins essential for the acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility. The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.[1] MHC molecules mediate interactions of leukocytes, also called white blood cells (WBCs), which are immune cells, with other leukocytes or with body cells. The MHC determines compatibility of donors for organ transplant, as well as one's susceptibility to an autoimmune disease via crossreacting immunization. The human MHC is also called the HLA (human leukocyte antigen) complex (often just the HLA). The MHC in mice is called the H-2 complex or H-2.
In a cell, protein molecules of the host's own phenotype or of other biologic entities are continually synthesized and degraded. Each MHC molecule on the cell surface displays a molecular fraction of a protein, called an epitope.[2] The presented antigen can be either self or non-self, thus preventing an organism's immune system targeting its own cells. In its entirety, the MHC population is like a meter indicating the balance of proteins within the cell.
The MHC gene family is divided into three subgroups: class I, class II, and class III. Class I MHC molecules have β2 subunits so can only be recognised by CD8 co-receptors. Class II MHC molecules have β1 and β2 subunits and can be recognised by CD4 co-receptors. In this way MHC molecules chaperone which type of lymphocytes may bind to the given antigen with high affinity, since different lymphocytes express different T-Cell Receptor (TCR) co-receptors.
Diversity of antigen presentation, mediated by MHC classes I and II, is attained in at least three ways: (1) an organism's MHC repertoire is polygenic (via multiple, interacting genes); (2) MHC expression is codominant (from both sets of inherited alleles); (3) MHC gene variants are highly polymorphic (diversely varying from organism to organism within a species).[3] Major histocompatibility complex and sexual selection has been observed in male mice making mate choices of females with different MHCs and thus demonstrating sexual selection.[4] Also, at least for MHC I presentation, there has been evidence of antigenic peptide splicing which can combine peptides from different proteins, vastly increasing antigen diversity.[5]
The first descriptions of the MHC were made by British immunologist Peter Gorer in 1936.[6] MHC genes were first identified in inbred mice strains. Clarence Little transplanted tumors across differing strains and found rejection of transplanted tumors according to strains of host versus donor.[7] George Snell selectively bred two mouse strains, attained a new strain nearly identical to one of the progenitor strains, but differing crucially in histocompatibility—that is, tissue compatibility upon transplantation—and thereupon identified an MHC locus.[8] For this work, Snell was awarded the 1980 Nobel Prize in Physiology or Medicine, together with Baruj Benacerraf and Jean Dausset.
In Immunity
Of the three MHC classes identified, attention commonly focuses on classes I and II. By interacting with CD4 molecules on surfaces of helper T cells, MHC class II mediates establishment of specific immunity (also called acquired immunity or adaptive immunity). By interacting with CD8 molecules on surfaces of cytotoxic T cells, MHC class I mediates destruction of infected or malignant host cells, the aspect of specific immunity termed cellular immunity. (The other arm of specific immunity is humoral immunity, whose relation to MHC is more indirect.)
MHC is the tissue-antigen that allows the immune system (more specifically T cells) to bind to, recognize, and tolerate itself (autorecognition). MHC is also the chaperone for intracellular peptides that are complexed with MHCs and presented to T cell receptors (TCRs) as potential foreign antigens. MHC interacts with TCR and its co-receptors to optimize binding conditions for the TCR-antigen interaction, in terms of antigen binding affinity and specificity, and signal transduction effectiveness.
Essentially, the MHC-peptide complex is a complex of autoantigen/alloantigen. Upon binding, T cells should in principle tolerate the auto-antigen, but activate when exposed to the allo-antigen. Disease states occur when this principle is disrupted.
Antigen presentation: MHC molecules bind to both T cell receptor and CD4/CD8 co-receptors on T lymphocytes, and the antigen epitope held in the peptide-binding groove of the MHC molecule interacts with the variable Ig-Like domain of the TCR to trigger T-cell activation[9]
Autoimmune reaction: Having some MHC molecules increases the risk of autoimmune diseases more than having others. HLA-B27 is an example. It is unclear how exactly having the HLA-B27 tissue type increases the risk of ankylosing spondylitis and other associated inflammatory diseases, but mechanisms involving aberrant antigen presentation or T cell activation have been hypothesized.
Tissue allorecognition: MHC molecules in complex with peptide epitopes are essentially ligands for TCR. T cells become activated by binding to the peptide-binding grooves of any MHC molecule that T cells were not trained to recognize during thymus positive selection.
As a lineage of leukocytes, lymphocytes reside in peripheral lymphoid tissues, including lymphoid follicles and lymph nodes, and include B cells, T cells, and natural killer cells (NK cells). B cells, which act specifically, secrete antibody molecules, but do not bind MHC. T cells, which act specifically, as well as NK cells, which act innately, interact with MHC. NK cells express Killer Ig-like receptors (KIRs) that bind to MHC I molecules and signal through ITIM (immunoreceptor tyrosine inhibition motif) recruitment and activation of protein tyrosine phosphatases. This means in contrast to CD8/TCR interaction that activates Tc lymphocytes, NK cells becomes deactivated when bound to MHC I. When MHC class I expression is low, as is typically the case with abnormal cell function during viral infection or tumourigenesis, NK cells lose the inhibitory KIR signal and trigger programmed cell death of the abnormal cell. NK cells thus help prevent progress of cancerous cells by contributing to tumor surveillance.
MHC class II
MHC class II can be conditionally expressed by all cell types, but normally occurs only on professional antigen-presenting cells (APCs): macrophages, B cells, and especially dendritic cells (DCs). An APC takes up an antigenic protein, performs antigen processing, and returns a molecular fraction of it—a fraction termed the epitope—and displays it on the APC's surface coupled within an MHC class II molecule (antigen presentation). On the cell's surface, the epitope can be recognized by immunologic structures like T cell receptors (TCRs). The molecular region which binds to the epitope is the paratope.
On surfaces of helper T cells are CD4 receptors, as well as TCRs. When a naive helper T cell's CD4 molecule docks to an APC's MHC class II molecule, its TCR can meet and be imprinted by the epitope coupled within the MHC class II. This event primes the naive helper T cell. According to the local milieu, that is, the balance of cytokines secreted by APCs in the microenvironment, the naive helper T cell (Th0) polarizes into either a memory Th cell or an effector Th cell of phenotype either type 1 (Th1), type 2 (Th2), type 17 (Th17), or regulatory/suppressor (Treg), as so far identified, the Th cell's terminal differentiation.
MHC class II thus mediates immunization to—or, if APCs polarize Th0 cells principally to Treg cells, immune tolerance of—an antigen. The polarization during primary exposure to an antigen is key in determining a number chronic diseases, such as inflammatory bowel diseases and asthma, by skewing the immune response that memory Th cells coordinate when their memory recall is triggered upon secondary exposure to similar antigens. (B cells express MHC class II to present antigen to Th0, but when their B cell receptors bind matching epitopes, interactions which are not mediated by MHC, these activated B cells secrete soluble immunoglobulins: antibody molecules mediating humoral immunity.)
MHC class I
MHC class I occurs on all nucleated cells and also in platelets—in essence all cells but red blood cells. It presents epitopes to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition to TCRs. When a CTL's CD8 receptor docks to a MHC class I molecule, if the CTL's TCR fits the epitope within the MHC class I molecule, the CTL triggers the cell to undergo programmed cell death by apoptosis. Thus, MHC class I helps mediate cellular immunity, a primary means to address intracellular pathogens, such as viruses and some bacteria, including bacterial L forms, bacterial genus Mycoplasma, and bacterial genus Rickettsia. In humans, MHC class I comprises HLA-A, HLA-B, and HLA-C molecules.
MHC gene families are found in all vertebrates, though they vary widely. In humans, the MHC region occurs on chromosome 6, between the flanking genetic markers MOG and COL11A2 (from 6p22.1 to 6p21.3 about 29Mb to 33Mb on the hg38 assembly), and contains 224 genes spanning 3.6 megabase pairs (3 600 000 bases).[10] About half have known immune functions.
The same markers in the gray short-tailed opossum (Monodelphis domestica), a marsupial, span 3.95 Mb, yielding 114 genes, 87 shared with humans.[11] Marsupial MHC genotypic variation lies between eutherian mammals and birds, taken as minimal MHC encoding, but is closer in organization to that of nonmammals, and MHC class I genes of marsupials have amplified within the class II region, yielding a unique class I/II region.[11]
Class III functions very differently from class I and class II, but its locus occurs between the other two classes, on chromosome 6 in humans, and are frequently discussed together.
|(1) peptide-binding proteins, which select short sequences of amino acids for antigen presentation, as well as (2) molecules aiding antigen-processing (such as TAP and tapasin).
|One chain, called α, whose ligands are the CD8 receptor—borne notably by cytotoxic T cells—and inhibitory receptors borne by NK cells
|(1) peptide-binding proteins and (2) proteins assisting antigen loading onto MHC class II's peptide-binding proteins (such as MHC II DM, MHC II DQ, MHC II DR, and MHC II DP).
|Two chains, called α & β, whose ligands are the CD4 receptors borne by helper T cells.
|Other immune proteins, outside antigen processing and presentation, such as components of the complement cascade (e.g., C2, C4, factor B), the cytokines of immune signaling (e.g., TNF-α), and heat shock proteins buffering cells from stresses
MHC proteins have immunoglobulin-like structure.
Class I
MHC I occurs as an α chain composed of three domains—α1, α2, and α3. The α1 rests upon a unit of the non-MHC molecule β2 microglobulin (encoded on human chromosome 15). The α3 domain is transmembrane, anchoring the MHC class I molecule to the cell membrane. The peptide being presented is held by the floor of the peptide-binding groove, in the central region of the α1/α2 heterodimer (a molecule composed of two nonidentical subunits). The genetically encoded and expressed sequence of amino acids, the sequence of residues, of the peptide-binding groove's floor determines which particular peptide residues it binds.[12]
Classical MHC molecules present epitopes to the TCRs of CD8+ T lymphocytes. Nonclassical molecules (MHC class IB) exhibit limited polymorphism, expression patterns, and presented antigens; this group is subdivided into a group encoded within MHC loci (e.g., HLA-E, -F, -G), as well as those not (e.g., stress ligands such as ULBPs, Rae1, and H60); the antigen/ligand for many of these molecules remain unknown, but they can interact with each of CD8+ T cells, NKT cells, and NK cells.
Class II
MHC class II is formed of two chains, α and β, each having two domains—α1 and α2 and β1 and β2—each chain having a transmembrane domain, α2 and β2, respectively, anchoring the MHC class II molecule to the cell membrane.[13] The peptide-binding groove is formed of the heterodimer of α1 and β1.
MHC class II molecules in humans have five to six isotypes. Classic molecules present peptides to CD4+ lymphocytes. Nonclassic molecules, accessories, with intracellular functions, are not exposed on cell membranes, but in internal membranes in lysosomes, normally loading the antigenic peptides onto classic MHC class II molecules.
Class III
Class III molecules have physiologic roles unlike classes I and II, but are encoded between them in the short arm of human chromosome 6. Class III molecules include several secreted proteins with immune functions: components of the complement system (such as C2, C4, and B factor), cytokines (such as TNF-α, LTA, and LTB), and heat shock proteins.
Antigen processing and presentation
Peptides are processed and presented by two classical pathways:
- In MHC class II, phagocytes such as macrophages and immature dendritic cells take up entities by phagocytosis into phagosomes—though B cells exhibit the more general endocytosis into endosomes—which fuse with lysosomes whose acidic enzymes cleave the uptaken protein into many different peptides. Via physicochemical dynamics in molecular interaction with the particular MHC class II variants borne by the host, encoded in the host's genome, a particular peptide exhibits immunodominance and loads onto MHC class II molecules. These are trafficked to and externalized on the cell surface.[14]
- In MHC class I, any nucleated cell normally presents cytosolic peptides, mostly self peptides derived from protein turnover and defective ribosomal products. During viral infection, intracellular microorganism infection, or cancerous transformation, such proteins degraded in the proteosome are as well loaded onto MHC class I molecules and displayed on the cell surface. T lymphocytes can detect a peptide displayed at 0.1%-1% of the MHC molecules.
|MHC-I pathway
|MHC-II pathway
|Composition of the stable peptide-MHC complex
|Polymorphic chain α and β2 microglobulin, peptide bound to α chain
|Polymorphic chains α and β, peptide binds to both
|Types of antigen presenting cells (APC)
|All nucleated cells
|Dendritic cells, mononuclear phagocytes, B lymphocytes, some endothelial cells, epithelium of thymus
|T lymphocytes able to respond
|Cytotoxic T lymphocytes (CD8+)
|Helper T lymphocytes (CD4+)
|Origin of antigenic proteins
|cytosolic proteins (mostly synthetized by the cell; may also enter from the extracellular medium via phagosomes)
|Proteins present in endosomes or lysosomes (mostly internalized from extracellular medium)
|Enzymes responsible for peptide generation
|Cytosolic proteasome
|Proteases from endosomes and lysosomes (for instance, cathepsin)
|Location of loading the peptide on the MHC molecule
|Endoplasmic reticulum
|Specialized vesicular compartment
|Molecules implicated in transporting the peptides and loading them on the MHC molecules
|TAP (transporter associated with antigen processing)
|DM, invariant chain
T lymphocyte recognition restrictions
In their development in the thymus, T lymphocytes are selected to recognize MHC molecules of the host, but not recognize other self antigens. Following selection, each T lymphocyte shows dual specificity: The TCR recognizes self MHC, but only non-self antigens.
MHC restriction occurs during lymphocyte development in the thymus through a process known as positive selection. T cells that do not receive a positive survival signal — mediated mainly by thymic epithelial cells presenting self peptides bound to MHC molecules — to their TCR undergo apoptosis. Positive selection ensures that mature T cells can functionally recognize MHC molecules in the periphery (i.e. elsewhere in the body).
The TCRs of T lymphocytes recognise only sequential epitopes, also called linear epitopes, of only peptides and only if coupled within an MHC molecule. (Antibody molecules secreted by activated B cells, though, ligate diverse epitopes—peptide, lipid, carbohydrate, and nucleic acid—and recognize conformational epitopes, which have three-dimensional structure.)
In sexual mate selection
MHC molecules enable immune system surveillance of the population of protein molecules in a host cell, and greater MHC diversity permits greater diversity of antigen presentation. In 1976, Yamazaki et al demonstrated a sexual selection mate choice by male mice for females of a different MHC. Similar results have been obtained with fish.[16] Some data find lower rates of early pregnancy loss in human couples of dissimilar MHC genes.[17]
MHC may be related to mate choice in some human populations, a theory that found support by studies by Ober and colleagues in 1997,[18] as well as by Chaix and colleagues in 2008.[19] However, the latter findings have been controversial.[20] If it exists, the phenomenon might be mediated by olfaction, as MHC phenotype appears strongly involved in the strength and pleasantness of perceived odour of compounds from sweat. Fatty acid esters—such as methyl undecanoate, methyl decanoate, methyl nonanoate, methyl octanoate, and methyl hexanoate—show strong connection to MHC.[21]
In 1995, Claus Wedekind found that in a group of female college students who smelled T-shirts worn by male students for two nights (without deodorant, cologne, or scented soaps), by far most women chose shirts worn by men of dissimilar MHCs, a preference reversed if the women were on oral contraceptives.[22] Results of a 2002 experiment likewise suggest HLA-associated odors influence odor preference and may mediate social cues.[23] In 2005 in a group of 58 subjects, women were more indecisive when presented with MHCs like their own,[24] although with oral contraceptives, the women showed no particular preference.[25] No studies show the extent to which odor preference determines mate selection (or vice versa).
Evolutionary diversity
Most mammals have MHC variants similar to those of humans, who bear great allelic diversity, especially among the nine classical genes—seemingly due largely to gene duplication—though human MHC regions have many pseudogenes. The most diverse loci, namely HLA-A, HLA-B, and HLA-DRB1, have roughly 1000, 1600, and 870 known alleles, respectively .[26] Many HLA alleles are ancient, sometimes of greater homology to a chimpanzee MHC alleles than to some other human alleles of the same gene.
MHC allelic diversity has challenged evolutionary biologists for explanation. Most posit balancing selection (see polymorphism (biology)), which is any natural selection process whereby no single allele is absolutely most fit, such as frequency-dependent selection and heterozygote advantage. Recent models suggest a high number of alleles is implausible via heterozygote advantage alone.
Pathogenic coevolution, a counterhypothesis, posits that common alleles are under greatest pathogenic pressure, driving positive selection of uncommon alleles—moving targets, so to say, for pathogens. As pathogenic pressure on the previously common alleles decreases, their frequency in the population stabilizes, and remain circulating in a large population. Despite great MHC polymorphism at the population level, an individual bears at most 18 MHC I or II alleles.
Relatively low MHC diversity has been observed in the cheetah (Acinonyx jubatus),[27] Eurasian beaver (Castor fiber),[28] and giant panda (Ailuropoda melanoleuca).[29] In 2007 low MHC diversity was attributed a role in disease susceptibility in the Tasmanian devil (Sarcophilus harrisii), native to the isolated island of Tasmania, such that an antigen of a transmissible tumor, involved in devil facial tumour disease, appears to be recognized as a self antigen.[30] To offset inbreeding, efforts to sustain genetic diversity in populations of endangered species and of captive animals have been suggested.
In transplant rejection
In a transplant procedure, as of an organ or stem cells, MHC molecules act themselves as antigens and can provoke immune response in the recipient, thus causing transplant rejection. MHC molecules were identified and named after their role in transplant rejection between mice of different strains, though it took over 20 years to clarify MHC's role in presenting peptide antigens to cytotoxic T lymphocytes (CTLs).[31]
Each human cell expresses six MHC class I alleles (one HLA-A, -B, and -C allele from each parent) and six to eight MHC class II alleles (one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations of these). The MHC variation in the human population is high, at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR, and 90 alleles for DQ. Any two individuals who are not identical twins will express differing MHC molecules. All MHC molecules can mediate transplant rejection, but HLA-C and HLA-DP, showing low polymorphism, seem least important.
When maturing in the thymus, T lymphocytes are selected for their TCR incapacity to recognize self antigens, yet T lymphocytes can react against the donor MHC's peptide-binding groove, the variable region of MHC holding the presented antigen's epitope for recognition by TCR, the matching paratope. T lymphocytes of the recipient take the incompatible peptide-binding groove as nonself antigen. The T lymphocytes' recognition of the foreign MHC as self is allorecognition.
Transplant rejection has various types known to be mediated by MHC (HLA):
- Hyperacute rejection occurs when, before the transplantation, the recipient has preformed anti-HLA antibodies, perhaps by previous blood transfusions (donor tissue that includes lymphocytes expressing HLA molecules), by anti-HLA generated during pregnancy (directed at the father's HLA displayed by the fetus), or by previous transplantation;
- Acute cellular rejection occurs when the recipient's T lymphocytes are activated by the donor tissue, causing damage via mechanisms such as direct cytotoxicity from CD8 cells.
- Acute humoral rejection and chronic disfunction occurs when the recipient's anti-HLA antibodies form directed at HLA molecules present on endothelial cells of the transplanted tissue.
In all of the above situations, immunity is directed at the transplanted organ, sustaining lesions. A cross-reaction test between potential donor cells and recipient serum seeks to detect presence of preformed anti-HLA antibodies in the potential recipient that recognize donor HLA molecules, so as to prevent hyperacute rejection. In normal circumstances, compatibility between HLA-A, -B, and -DR molecules is assessed. The higher the number of incompatibilities, the lower the five-year survival rate. Global databases of donor information enhance the search for compatible donors.
HLA biology
Human MHC class I and II are also called human leukocyte antigen (HLA). To clarify the usage, some of the biomedical literature uses HLA to refer specifically to the HLA protein molecules and reserves MHC for the region of the genome that encodes for this molecule, but this is not a consistent convention.
The most studied HLA genes are the nine classical MHC genes: HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1. In humans, the MHC gene cluster is divided into three regions: classes I, II, and III. The A, B and C genes belong to MHC class I, whereas the six D genes belong to class II.
MHC alleles are expressed in codominant fashion.[13] This means the alleles (variants) inherited from both parents are expressed equally:
- Each person carries 2 alleles of each of the 3 class-I genes, (HLA-A, HLA-B and HLA-C), and so can express six different types of MHC-I (see figure).
- In the class-II locus, each person inherits a pair of HLA-DP genes (DPA1 and DPB1, which encode α and β chains), a couple of genes HLA-DQ (DQA1 and DQB1, for α and β chains), one gene HLA-DRα (DRA1), and one or more genes HLA-DRβ (DRB1 and DRB3, -4 or -5). That means that one heterozygous individual can inherit six or eight functioning class-II alleles, three or more from each parent. The role of DQA2 or DQB2 is not verified. The DRB2, DRB6, DRB7, DRB8 and DRB9 are pseudogenes.
The set of alleles that is present in each chromosome is called the MHC haplotype. In humans, each HLA allele is named with a number. For instance, for a given individual, his haplotype might be HLA-A2, HLA-B5, HLA-DR3, etc... Each heterozygous individual will have two MHC haplotypes, one each from the paternal and maternal chromosomes.
The MHC genes are highly polymorphic; many different alleles exist in the different individuals inside a population. The polymorphism is so high, in a mixed population (nonendogamic), no two individuals have exactly the same set of MHC molecules, with the exception of identical twins.
The polymorphic regions in each allele are located in the region for peptide contact. Of all the peptides that could be displayed by MHC, only a subset will bind strongly enough to any given HLA allele, so by carrying two alleles for each gene, a much larger set of peptides can be presented.
On the other hand, inside a population, the presence of many different alleles ensures there will always be an individual with a specific MHC molecule able to load the correct peptide to recognize a specific microbe. The evolution of the MHC polymorphism ensures that a population will not succumb to a new pathogen or a mutated one, because at least some individuals will be able to develop an adequate immune response to win over the pathogen. The variations in the MHC molecules (responsible for the polymorphism) are the result of the inheritance of different MHC molecules, and they are not induced by recombination, as it is the case for the antigen receptors.
Because of the high levels of allelic diversity found within its genes, MHC has also attracted the attention of many evolutionary biologists.[32]
See also
Notes and references
- ↑ Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001 The Major Histocompatibility Complex and Its Functions
- ↑ Kimball's Biology Histocompatibility Molecules
- ↑ Janeway CA Jr, Travers P, Walport M, et al, Immunobiology: The Immune System in Health and Disease, 5th edn (New York: Garland Science, 2001), "The major histocompatibility complex and its functions".
- ↑ Yamazaki, K.; Boyse, E. A.; Miké, V.; Thaler, H. T.; Mathieson, B. J.; Abbott, J.; Boyse, J.; Zayas, Z. A.; Thomas, L. (1976-11-02). "Control of mating preferences in mice by genes in the major histocompatibility complex". Journal of Experimental Medicine. 144 (5): 1324–1335. doi:10.1084/jem.144.5.1324. ISSN 0022-1007. PMC 2190468
- ↑ Vigneron, Nathalie; Stroobant, Vincent; Chapiro, Jacques; Ooms, Annie; Degiovanni, Gérard; Morel, Sandra; Bruggen, Pierre van der; Boon, Thierry; Eynde, Benoît J. Van den (2004-04-23). "An Antigenic Peptide Produced by Peptide Splicing in the Proteasome". Science. 304 (5670): 587–590. doi:10.1126/science.1095522. ISSN 0036-8075. PMID 15001714.
- ↑ Klein J (1986). "Seeds of time: Fifty years ago Peter A. Gorer discovered the H-2 complex". Immunogenetics. 24: 331–338. doi:10.1007/bf00377947.
- ↑ Little CC 1941, "The genetics of tumor transplantation", pp 279–309, in Biology of the Laboratory Mouse, ed by Snell GD, New York: Dover.
- ↑ Snell GD, Higgins GF (1951). "Alleles at the histocompatibility-2 locus in the mouse as determined by tumor transplantation". Genetics. 36: 306–310.
- ↑ Thomas J. Kindt; Richard A. Goldsby; Barbara Anne Osborne; Janis Kuby (2007). Kuby immunology. Macmillan. ISBN 978-1-4292-0211-4. Retrieved 28 November 2010.
- ↑ MHC Sequencing Consortium (1999). "Complete sequence and gene map of a human major histocompatibility complex". Nature. 401 (6756): 921–923. doi:10.1038/44853. PMID 10553908.
- 1 2 Belov K, Deakin JE, Papenfuss AT, Baker ML, Melman SD, Siddle HV, Gouin N, Goode DL, Sargeant TJ, Robinson MD, Wakefield MJ, Mahony S, Cross JG, Benos PV, Samollow PB, Speed TP, Graves JA, Miller RD (March 2006). "Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex". PLoS Biol. 4 (3): e46. doi:10.1371/journal.pbio.0040046. PMC 1351924
- ↑ Toh H, Savoie CJ, Kamikawaji N, Muta S, Sasazuki T, Kuhara S (October 2000). "Changes at the floor of the peptide-binding groove induce a strong preference for proline at position 3 of the bound peptide: molecular dynamics simulations of HLA-A*0217". Biopolymers. 54 (5): 318–27. doi:10.1002/1097-0282(20001015)54:5<318::AID-BIP30>3.0.CO;2-T. PMID 10935972.
- 1 2 Abbas; Lichtman A.H. (2009). "Ch.3 Antigen capture and presentation to lymphocytes". Basic Immunology. Functions and disorders of the immune system (3rd ed.). p. A.B. ISBN 978-1-4160-4688-2.
- ↑ Aderem A, Underhill DM (1999). "Mechanisms of phagocytosis in macrophages". Annu. Rev. Immunol. 17: 593–623. doi:10.1146/annurev.immunol.17.1.593. PMID 10358769.
- ↑ K. Murphy, "Antigen recognition by T cells," in Janeway's Immunobiology, 8th, Ed., Garland Science, 2012, pp. 138-153.
- ↑ Boehm T; Zufall F (2006). "MHC peptides and the sensory evaluation of genotype". Trends Neurosci. 29 (2): 100–107. doi:10.1016/j.tins.2005.11.006. PMID 16337283.
- ↑ Haig D (November 1997). "Maternal-fetal interactions and MHC polymorphism". J. Reprod. Immunol. 35 (2): 101–9. doi:10.1016/s0165-0378(97)00056-9. PMID 9421795.
- ↑ Ober C, Weitkamp LR, Cox N, Dytch H, Kostyu D, Elias S (September 1997). "HLA and mate choice in humans". Am. J. Hum. Genet. 61 (3): 497–504. doi:10.1086/515511. PMC 1715964
- ↑ Chaix R, Chen C, Donnelly P (September 2008). "Is Mate Choice in Humans MHC-Dependent?". PLoS Genetics. 4 (9): e1000184. doi:10.1371/journal.pgen.1000184. PMC 2519788
- ↑ Derti A, Cenik C, Kraft P, Roth FP (April 2010). "Absence of evidence for MHC-dependent mate selection within HapMap populations". PLoS Genetics. 6 (4): e1000925. doi:10.1371/journal.pgen.1000925. PMC 2861700
- ↑ Janeš D, Klun I, Vidan-Jeras B, Jeras M, Kreft S (2010). "Influence of MHC on odour perception of 43 chemicals and body odor". Central European Journal of Biology. 5 (3): 324–330. doi:10.2478/s11535-010-0020-6.
- ↑ Wedekind C, Seebeck T, Bettens F, Paepke AJ (June 1995). "MHC-dependent mate preferences in humans". Proc. Biol. Sci. 260 (1359): 245–9. doi:10.1098/rspb.1995.0087. PMID 7630893.
- ↑ Jacob S, McClintock MK, Zelano B, Ober C (February 2002). "Paternally inherited HLA alleles are associated with women's choice of male odor". Nat. Genet. 30 (2): 175–9. doi:10.1038/ng830. PMID 11799397.
- ↑ Santos, P S; Schinemann JA; Gabardo J; Bicalho MG (April 2005). "New evidence that the MHC influences odor perception in humans: A study with 58 southern Brazilian students". Horm Behav. 47 (4): 384–388. doi:10.1016/j.yhbeh.2004.11.005. PMID 15777804.
- ↑ "The pill makes women pick bad mates"
- ↑ HLA Alleles Numbers
- ↑ Castro-Prieto A, Wachter B, Sommer S (April 2011). "Cheetah paradigm revisited: MHC diversity in the world's largest free-ranging population". Mol. Biol. Evol. 28 (4): 1455–68. doi:10.1093/molbev/msq330. PMID 21183613.
- ↑ Babik W, Durka W, Radwan J (December 2005). "Sequence diversity of the MHC DRB gene in the Eurasian beaver (Castor fiber)". Mol. Ecol. 14 (14): 4249–57. doi:10.1111/j.1365-294X.2005.02751.x. PMID 16313590.
- ↑ Zhu L, Ruan XD, Ge YF, Wan QH, Fang SG (2007). "Low major histocompatibility complex class II DQA diversity in the Giant Panda (Ailuropoda melanoleuca)". BMC Genet. 8: 29. doi:10.1186/1471-2156-8-29. PMC 1904234
- ↑ Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ, Pyecroft S, Woods GM, Belov K (October 2007). "Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial". Proc. Natl. Acad. Sci. U.S.A. 104 (41): 16221–6. doi:10.1073/pnas.0704580104. PMC 1999395
- ↑ Abbas; Lichtman A.H. (2009). "Ch.10 Immune responses against tumors and transplant". Basic Immunology. Functions and disorders of the immune system (3rd ed.). p. A.B. ISBN 978-1-4160-4688-2.
- ↑ Spurgin, Lewis G.; Richardson, David S. (2010-04-07). "How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings". Proceedings of the Royal Society of London B: Biological Sciences. 277 (1684): 979–988. doi:10.1098/rspb.2009.2084. ISSN 0962-8452. PMC 2842774
- Daniel M. Davis, The Compatibility Gene, London, Penguin Books, 2014 (ISBN 978-0-241-95675-5).
External links
- Major+Histocompatibility+Complex at the US National Library of Medicine Medical Subject Headings (MeSH)
- Molecular individuality (German online-book 2012)
- NetMHC 3.0 server — predicts binding of peptides to a number of different MHC (HLA) alleles
- T-cell Group - Cardiff University
- The story of 2YF6: A Chicken MHC
- RCSB Protein Data Bank: Molecule of the Month - Major Histocompatibility Complex
- dbMHC Home, NCBI's database of the Major Histocompatibility Complex


text:
Eva Stubbs
Canadian (born in Hungary), b. 1925
Multiples, 1995
clay, oxides, stains
Collection of the Winnipeg Art Gallery; Gift of the artist
2001-67 a-n
Sculpture, Canadian Contemporary (1980-present)
Consisting of 14 fired clay components arranged as an installation, Multiples speaks to the similarities and differences that characterize contemporary Canadian society. Stubbs' work often expresses the continuity of human life and her desire for understanding among people of different cultural histories. The sturdy, mushroom-like forms of Multiples are in contrast to the inherent fragility of clay, paralleling the strength and vulnerability of the human condition. Each pod was made by pounding clay into a plaster mold and then manipulating each to create different, individual forms. Recognized for her bronze and ceramic sculpture of the human figure, this substantial and abstract work also retains references to the body. Collectively the pods take on the shape of an ancient formation of disembodied heads.
Gallery Hours
- Tuesday 11am-5pm
- Wednesday 11am-5pm
- Thursday 11am-5pm
- Friday 11am-9pm
- Saturday 11am-5pm
- Sunday 11am-5pm
- Closed Monday

subset: commoncrawl


text:
What's New in Creative Cloud: Edge Reflow Preview and New Dreamweaver Features
Today, we're very excited to share two big updates to Creative Cloud for web designers and developers.
Edge Reflow – We first sneaked a look at Adobe Edge Reflow during our Create the Web event last September, and are eager to share that we've just released the first public preview of it today. Edge Reflow – a part of the Edge Tools & Services offering in Creative Cloud – is a new responsive design tool for web designers and developers creating websites and content for screens of virtually all sizes. It features an intuitive resizable design surface that shows how layouts and visuals will adapt to different screen sizes and enables users to create high fidelity web designs on the application's native web surface leveraging the power of CSS. Get all the details from the Edge Reflow Team blog. Looking to get started right away? Here's an intro to Reflow video from evangelist Paul Trani.
Also new to the Edge Tools & Services offering are new feature releases to Edge Animate and the introduction of Edge Code preview.
Edge Animate now supports CSS gradients and filters (so you can, for example, easily add blur effects) and makes it simpler to add rich typography with the free Edge Web Fonts service
Edge Code is our code editor for HTML, CSS and JavaScript that is completely written in HTML5. We're released a preview of it today that allows developers to:
- See changes in the browser as they make them, and code hinting for more CSS properties and HTML tags
- Edit code in context instead of having to switch between files with the addition of a Quick Edit feature.
Adobe Dreamweaver – We've introduced a second Dreamweaver update for Creative Cloud members. Here's a brief overview of what new in this release:
- Improvements to Fluid Grids
- Bring print-quality typography to the web with Edge Web Fonts
- Custom settings retained after upgrade
- Expanded table view is back
- HTML5 support
- Critical bug fixes
For the full scoop, check out the Dreamweaver Team Blog.
Not a Creative Cloud member yet? Upgrade today and save 40%.


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Hi everyone, I have been completing a couple of unfinished objects this week, the first one is this little cross stitch gift set, I only had the little oblong pillow to finish, it has been sitting in my unfinished pile for quite a while now.
I have made this set a few times for friends but I wanted one for myself as I love the design, the first was this set here where you can also see a matching gift box that I designed. If you check out my finishing tutorials blog you can see the biscornu tutorial showing how to stitch it together.
The pattern is from this blog here I could not find the pattern on this Biscornu page but if you email the blog owner I am sure she will send it to you. She has lots of patterns in the freebie section, if you don't know how to translate the page just look for Grilles Gratuite in the sidebar listings to locate the free patterns section.
I painted two coats of acrylic paint on the little wooden basket, you can buy these at any good craft store.
Here is the basket before I painted it
I am off to finish some more stitching in my unfinished objects stash!
Until next time - Happy Stitching....................


text:
I have run across Trader Joe's Rye-Less Rye more times than I can count at Trader Joe's. This is because I buy the Trader Joe's French Rolls on a regular basis. I had always been scared (LOL) to buy the Rye-less Rye, but took the plunge a week or so ago. It was $3.49/loaf and Trader Joe's is really good about taking back stuff (and giving a store credit) for things that you don't like or aren't up to your expectations. I have to say that I was pleasantly surprised by this bread. Yes, you have to toast it. Also, I put my loaf directly into the freezer so that it would keep, as I would never eat it all before the date stamped on the package. Now I enjoy in various ways, a piece or 2 at a time. The bread toasts up wonderfully and has that "rye" taste that I remember from my pre-gluten-free days. The texture is amazing. The only thing negative I have to say about this bread is that the pieces aren't bigger. I am not talking thickness of slice here, but size of the slice. These are relatively small, way too small for a lunch-sized sandwich, in my opinion. Of course, I am a big eater, so maybe for someone with a smaller appetite, this bread would work perfectly for sandwiches. Being the creative person that I am…LOL…I have found many other uses for this bread. Here is my "after dinner rye-less rye", complete with strawberry fruit spread & some chocolate chips (BTW, those are regular size chocolate chips, so you can get an idea of the size of the bread):
Some other uses are with peanut butter or almond butter as a snack, with butter with a meal, with cream cheese as a snack or with a meal. You could use these for appetizers, too. Maybe cut each slice in make Crostini.
I would absolutely buy this product again and again. Highly recommend.
Filed under: Family, Gluten-Free, Gluten-free Products | 20 Comments »


text: Hey, i found plant map for gothic 3 on internet and there is supposed to be dragon root north of montera/west of gotha precisely. i know its kinda stupid to make a new thread just because of one plant but im an insane completionist and this freaking root is driving me crazy. can anyone help me please ?


text:
Dr. McIntosh offers patients an array of surgical procedures, including: Breast Augmentation, Breast Reconstruction, Tummy Tuck, Eyelid Surgery, Rhinoplasty, and more. He is also skilled in all types of non-surgical cosmetic procedures and injections such as: Botox Cosmetic, Juvéderm, Latisse, Vivité, and more. Our goal is to create and restore health, beauty, function, and self confidence for our patients by providing quality care, compassion, and unparalleled medical expertise. Schedule a no-obligation consultation with Dr. McIntosh to discuss the changes you would like to see in your body, and explore all of your options so you can make an informed decision that's best for you.
Certified by the American Board of Plastic Surgery
Member of the American Society of Plastic Surgeons
Voted #1 Plastic Surgeon in Washington State for 2013 (HealthTap)
Best in Show, Northwest Women's Show, 2013 and 2014


text:
Sugarloaf Crafts Festival Discount Tickets
Holiday Chantilly / VA / DC Area
December 6, 7, 8, 2019 • Fri 10-6, Sat 10-6, Sun 10-5
If you need more than 3 tickets, buy a 4-pack…
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text:
On December 19, 2002, Washington University in St. Louis' Faculty Senate approved a Policy on Discriminatory Harassment, applicable to all members of the university community.
In addition, a special task force appointed by the chancellor determined that supplemental informal procedures are appropriate generally in instances where an undergraduate student seeks to pursue a grievance against a faculty member and that supplemental formal procedures are appropriate where the grievance alleges discrimination by a faculty member.
Accordingly this policy, supplemental to the Policy on Discriminatory Harassment adopted by the Faculty Senate, applies to claims made by an undergraduate student against a faculty member.
Policy Statement
Washington University is committed to assuring that appropriate options are available to students with grievances against faculty members, including grievances involving discrimination and/or discriminatory harassment. University policy prohibits discrimination on the basis of race, color, age, religion, sex, sexual orientation, gender identity or expression, national origin, veteran status, disability or genetic information. Discrimination or discriminatory harassment based on any of these classifications violates university policy and will not be tolerated. In some circumstances, such harassment may also violate federal, state or local law.
This statement describes the informal procedures available to undergraduate students who have any type of grievance against faculty members and the more formal procedures available to students who believe that they have been subjected to discrimination or discriminatory harassment by faculty members.
What Is Discriminatory Harassment?
Discriminatory harassment is a subset of discrimination and consists of unwelcome and objectively offensive conduct by a faculty member against a student that (a) has the purpose or effect of unreasonably interfering with that student's work or educational environment, (b) is directed at a particular student or group of students because of the student's/students' race, color, age, religion, gender, sexual orientation, national origin, veteran status or disability, and (c) is abusive or severely humiliating. A faculty member alleged to be routinely abusive to all students might be the subject of a complaint of "harassment," but it would not be "discriminatory harassment" because it is not targeted at a particular group.
What is Sexual Harassment?
Sexual harassment is a subset of discriminatory harassment. The definition of sexual harassment adopted by the university can be found in Section II of the Washington University Discrimination and Harassment Policy Statement. If you believe that you have been the victim of sexual harassment, the policy describes options for resolution and university action as well as where you can get help. Complaints of sexual harassment are handled according to the Discrimination and Harassment Policy.
Seeking Assistance for Claims Against Faculty Members
If your claim against a faculty member is for discrimination or discriminatory harassment, you have options, both informal and formal, for dealing with your concerns. You may pursue informal means instead of or before making a formal complaint. If an informal procedure is ineffective, the formal procedures remain open to you. If your claim is not for discrimination or discriminatory harassment, you may pursue the informal procedures outlined below.
Informal Procedures: Faculty-Student Mediator
If you would like to proceed informally with the assistance of a third person, you should contact the faculty-student mediator for your school.
Each mediator is a full-time faculty member or administrator of his/her school designated to consider student grievances from a neutral perspective. The mediator will attempt to help you resolve your concern. If your grievance involves a faculty member from another school, your mediator will advise the mediator for that school of the complaint.
In the process of addressing a grievance, the mediator will make a brief written record of your grievance, including the names of the parties, the nature of the accusation, the responsive explanation of the faculty member and the resolution of the case. In processing any type of grievance, the mediator will strive to protect, to the greatest extent possible, the confidentiality of your complaint, but complete confidentiality cannot be guaranteed in every instance.
Other Confidential Resources
If you want to discuss your situation in a more confidential setting or clarify your feelings about whether and how you wish to proceed, you may want to consult with a social worker, therapist, or member of the clergy, many of whom are permitted, by law, to assure greater confidentiality. Clergy and counseling resources are listed in Bearings and Security on the Danforth Campus. In addition, you may contact Student Counseling Services at 314-935-6666 for a confidential discussion and, if desired, referral to off-campus resources.
Formal Procedures for Grievances Alleging Discrimination or Discriminatory Harassment
If your claim involves discrimination or discriminatory harassment and you are not satisfied with the results of an informal procedure, or elect not to participate in an informal procedure, you may file a formal grievance with the Discrimination and Title IX Grievance Committee, formerly known as the "Title IX Committee" ("Committee"). This process may lead to a formal hearing at which evidence will be considered and witnesses heard. The specifics of this process are set forth below:
The Complaint
1. The undergraduate student complaining of discrimination or discriminatory harassment by a faculty member ("Complainant") shall submit a brief written statement to the chairperson of the committee in care of Legail Poole Chandler at Campus Box 8002.
2. The chairperson shall promptly review the complaint and may meet informally with the complainant. The chairperson may seek to obtain additional relevant information and may informally interview the charged party or parties.
3. If the chairperson determines that there is no reasonable basis to believe that an act of discrimination has occurred, the complaint shall be dismissed and the complainant, all charged parties, and all committee members shall be informed, in writing, of the action.
4. If the chairperson determines that there is at least some basis to believe that a discriminatory act has occurred, the chairperson shall refer the complaint to the committee for hearing.
- The chairperson shall prepare a summary of the complaint that includes a description of the alleged discriminatory conduct, and have it served by mail or hand delivery to the charged party or parties, and the dean(s) of the school(s) in which the parties are enrolled or employed. The chairperson shall also furnish a copy to the complainant.
- The charged party or parties shall have the opportunity to submit a brief written response to the chairperson, with copies to the d eans who received the summary of the complaint and to the charged party(ies).
The Hearing
5. Hearings shall be conducted informally in the sense that legal rules of evidence shall not govern the testimony received. However, the procedures outlined herein shall be followed in the interest of fairness to all parties involved.
6. The chairperson shall promptly convene a panel from among the committee members to hear the complaint. The panel shall consist of the chairperson, plus six (6) other members from the committee, of which three (3) shall be students and three (3) shall be members of the faculty, administration, or staff. A quorum consists of four (4) members, plus the chairperson. All decisions of the panel shall be resolved in favor of the majority of those voting on a particular issue. The panel may also seek assistance from members of the office of the executive vice chancellor and general counsel, who shall not vote.
7. The chairperson shall provide reasonable advance written notice to all parties and panel members of the set time and place for the hearing. Five (5) working days prior to the hearing, each party shall submit to the chairperson and to all other parties a list of witnesses and copies of any documents each party expects to present in support or defense of the complaint.
8. Each party may have one adviser (for example, a friend, family member, colleague, or attorney), of his or her choice and at his or her expense, present during the evidentiary hearing. Such adviser shall have no right to participate in the proceedings except at the specific request or permission of the panel, and must agree to abide by the confidentiality restrictions set forth in these procedures. If a party's adviser is an attorney, the party shall provide the attorney's name and telephone number to the chairperson at least five (5) working days prior to the start of the hearing.
9. The chairperson shall preside at the hearing. The panel members may question the parties and all witnesses who appear at the hearing. All questions and comments by the parties shall be directed to the Panel; adverse parties and witnesses will not generally be permitted to cross-examine or confront each other directly.
10. All parties shall be provided the full and fair opportunity to present evidence relevant (in the panel's judgment) to the issues raised. All parties may make opening and closing statements. Each party may call witnesses that it previously identified to the panel. The panel may also invite witnesses on its own initiative.
11. The hearing proceedings are closed to the public. Only the parties, the parties' advisers, representatives from the office of the executive vice chancellor and general counsel, and witnesses (but only during their own testimony) may be present when evidence is being presented or arguments are being heard; no one else may attend the hearings or deliberations without the express invitation of the panel. The panel shall limit its inquiry exclusively to matters determined to be relevant to the particular issues in dispute. All proceedings are confidential and the results shall be disclosed only to the parties, to university officials with a "need to know," and where required by law.
12. The evidentiary hearing, but not the panel deliberations, may be sound recorded at the panel's election, and copies made available to the parties upon their request and at their expense.
The Decision
13. Within ten (10) working days of the last day of the evidentiary hearing, the panel shall submit to all parties and appropriate university administrators a written decision explaining the reasons for the panel's decision and setting forth findings of fact, conclusions, and recommendations. Findings of fact, conclusions, and recommendations shall be limited to the issues in dispute before the panel. Any panel member may include a written dissent from the written report.
14. Panel decisions are recommendations to the university administration and the Faculty Senate, which will make the final determination on grievances. Both the administration and the Faculty Senate Council retain their general jurisdiction over the allegations of faculty misconduct.
Updated August 2012 to be consistent with the Discriminatory Harassment Policy and reference to the Discrimination and Title IX Grievance Committee


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International Rugby
Fuimaono-Sapolu waits on appeal
ESPNscrum Staff
November 20, 2011
Eliota Fuimaono-Sapolu represented himself at his appeal against a suspended six-month ban © Getty Images
Gloucester centre Eliota Fuimaono-Sapolu must wait before discovering whether or not he has won his appeal against a suspended six-month ban.
The Samoa international appealed the punishment, which was meted out during the Rugby World Cup in New Zealand by tournament disciplinary chiefs. Judicial officer Judge Jeff Blackett upheld a misconduct charge against Fuimaono-Sapolu for comments made about Welsh referee Nigel Owens during the competition via Twitter.
Fuimaono-Sapolu, who is currently serving a three-week suspension imposed by the Rugby Football Union relating to separate Twitter comments, represented himself at Sunday's appeal hearing in London. The three-man independent appeal committee, comprising Professor Lorne Crerar (Scotland), Graeme Mew (Canada) and Nicholas Davidson QC (New Zealand) heard submissions from the player. No new evidence was presented or new witnesses called.
The committee reserved its judgement to consider all the evidence, and expects to reach a decision within the next seven days.
At the initial hearing in Auckland, Fuimaono-Sapolu was given a six-month suspension, suspended for two years, subject to three conditions. These were that he gives a full and unconditional apology to Owens and unconditional retraction of any criticism of him; carry out a minimum of 100 hours' rugby community work in Samoa in support of the IRB high performance programme within the next 12 months; and that the player attends and passes a recognised referee course within three months.
© ESPN Sports Media Ltd.
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text:
Harlem Book Fair
Harlem Book Fair is happening Saturday, July 21st on West 135th Street between Lenox and Adam Clayton Powell, Jr. Boulevard in NYC. Walter Mosely, Dominic Carter ("No Momma's Boy"), Amiri Baraka, Clifford the Big Red Dog, Omar Tyree, Zane . . .
There will be appearances by Walter Mosely, Dominic Carter ("No Momma's Boy"), Amiri Baraka, Clifford the Big Red Dog, Omar Tyree, Zane and more.
QBR The Black Book Review will present the 9th annual Harlem Book Fair on Saturday, July 21st on West 135th Street between Lenox and Adam Clayton Powell, Jr. Boulevard in New York City from 11:00 a.m. to 6:00 p.m.
The largest African American book event nationally, the Harlem Book Fair is designed to bring African American authors, poets, and performers together with the community they serve. Highlights of the Harlem Book Fair weekend will begin with the opening night Wheatley Book Awards program on Friday evening, July 20th, at the renowned Schomburg Center for Research in Black Culture, honoring noted author, Walter Mosley, poet/activist, Amiri Baraka and children's author Eloise Greenfield.
Saturday's festivities include a host of authors displaying their talents along 135th Street such as NY1 News veteran newsman, Dominic Carter showcasing his new book "No Momma's Boy" as well as a BBQ Jazz and Author Brunch with authors Zane and Omar Tyree, the State of African American Literacy address by former Congressman J. C. Watts, and the many performances and readings by authors, spoken word artists, musicians, storytellers, fiction and non-fiction writers, and children's book authors.
The HBF Panel Discussions, televised annually on C-SPAN's Book TV, again promise to be provocative and engaging and the HBF Gospel Stage will feature exciting performance profiling a diverse selection of gospel tunes from gospel hip hop to gospel jazz all in support of the best in Christian fiction and nonfiction books. The book fair provides books and reading for all ages. The HBF Children's' Pavilion will feature authors, storytellers with special guest panelists Roscoe Orman better known as Gordon the dad from Sesame Street. Sheron Umi Smith, mother of rapper/actor Mos Def will participate in a panel which focuses on the encouragement of reading among our youth. Some beloved children's characters like Bea the Reader and Clifford the Dog will also make an appearance.
The Harlem Book Fair will present best-selling authors, emerging writers, spoken word artists, and performers to an enthusiastic public community. A full-day program introducing diverse ideas and innovative forms of expression, the Harlem Book Fair is important for Harlem and the New York community. Awareness in reading, literacy, education and positive role modeling are just a few of the benefits of the Harlem Book Fair.
For further information on the 9th Annual Harlem Book Fair, please visit www.qbr.com.
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I think you have "Filtered HTML" turned on here. If you switch to "Full HTML," it will probably...
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Facebook posts made recently by a Conservation Commission member were the center of a long discussion at Monday evening's selectmen meeting.
EASTON — One by one, the five selectmen decried the recent posts by a town official that were perceived by some to be racist and bigoted.
Then, residents spoke — a majority against the anti-Muslim and anti-Islamic memes, but some showing support for a man they know to be a "nice" guy with a "huge heart."
Michael Goodman was at the center of an hour-plus discussion Monday night regarding Facebook images he posted in the past weeks. Goodman was appointed in June to the Conservation Commission by a 3-2 vote of the selectmen.
Selectmen Chairman Kevin McIntyre made it clear from the beginning Monday evening that the board couldn't take immediate action against Goodman because the agenda only stated a discussion would take place.
But, by the end of the discussion, despite pleas from residents to take action in the future, McIntyre wouldn't commit to putting the issue on another meeting agenda.
"It was a difficult week for Easton," Vice Chair Carol Nestler said. "I think the post was more than unpleasant. I think it was offensive. Rightfully, people in the community were outraged."
Selectman Dan Murphy said he has nothing against Goodman, but that the posts showed poor judgment.
"It was really stupid and showed poor judgment and showed a real lack of ability to make distinctions between things that should be fairly obvious," he said. "I like him, personally, but he caused a lot of harm. It was a really sad week."
McIntyre, who said he knows Goodman well, also called it a difficult week for the town.
"The initial posting and the subsequent posting were extremely unfortunate, certainly not something I would have posted or anyone else on this board hopefully would have posted," he said. "It was an extremely poor lack of judgment on his part. I wish that the fallout from that had been a little more articulate and forceful."
The initial meme posted by Goodman was an image of a nuclear explosion, which said the way to deal with Muslims was to kill the enemy. The second photo suggested the United States should make "peace with Islam," the same way the country did with Japan in 1945, when a formal surrender agreement was signed after the atomic bombings.
"How do we think he's going to have good judgment when it comes down to doing something that involves laws and bylaws and things you have to research and spend time on? I think everyone's looking at how the Board of Selectmen is going to handle this," Selectman Dottie Fulginiti said.
Selectman David Mills, who has always known Goodman for a long time, said he hopes the board will work toward creating a policy to prevent such comments through education.
"It was unfortunate. It was a foolish move on his part," he said. "I think he learned a good lesson. Hopefully we don't see anything like this again."
Goodman was not present at the meeting, but was in the building for a Conservation Commission meeting.
Residents asked the selectmen to take action in the future and put the issue on another meeting agenda, but McIntyre wouldn't commit either way.
This story will be updated.


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Street Address:
« Back | Forward »
« Back
I had a fender bender late last year. So, I sentenced myself to attend one of the six-hour defensive driving classes that I make teenagers go to as part of first-offender probation. I'm a traffic judge, you know.
I saunter into the classroom on a cold January morning. I wait in line with my hat pulled over my forehead. The guy at the desk takes my check and asks, "What court sentenced you?"
"I'm not court-ordered," I mutter.
He doesn't like that. That'll mess up a line item on the completion certificate. Or maybe I'm projecting. He gets past it. So do I. I take a seat in the back and look around. There are only a few teens, but I'm the senior member of the class by a quarter-century.
A video montage of people texting and driving and crashing plays on the screen, catchy music in the background. Taglines pop up from various businesses and celebrities. "Make your car a no-phone zone. … Take the pledge … Click it or ticket."
"OK, folks," the instructor begins. "If you fall asleep once, I'll wake you."
Why does he look at me when he says that? It's the people beside me whose heads are on the table.
"If I wake you a second time, you'll be asked to leave the class."
Then, looking away – thank goodness, because I'm about to pinch my lips to keep from laughing – he says, "I want you to pretend the judge is in the room with us."
He does not smirk, smile or glance in my direction. Nor does anyone else. On the strength of that, I'm convinced that I am incognito!
I relax and enjoy the ride.
I learn that you're no longer supposed to position your hands at 10 and 2 on the wheel. The new rule, 9 and 3, is due to air bags, which deploy at such a force that forearms over the steering wheel may snap back and cause you to punch yourself in the nose.
When someone in the back seat isn't buckled up, there's more to worry about than her being thrown through the windshield. Her head becomes the loose marble, or pool ball, that may easily collide with those belonging to people who are strapped in.
Graphic video from the U.K. drives home the point.
I'm successfully maintaining my silence when the instructor asks a question that he's decided each person will answer, as he circles the room: "How many more years do you want to live?"
As others begin responding – "60 …70 … forever" – I'm tempted to bolt for the restroom. But I don't.
I think of a smart-aleck answer I'd have given as a kid ("You call this living?!"). But I suppress it. When he stops in front of me, I deadpan, "55." What's he gonna do, cross-examine me?
He's making a point: If you want a shot at living to a ripe old age, you might want to avoid eating, drinking, texting, sexting, fixing your hair and talking on cell phones while, uh, driving?
And while you're at it, avoid speeding, tailgating, napping and going after anyone who's crazy with road rage.
Time flies. Three o'clock is nearing when someone asks, "If four drivers stop simultaneously at a four-way stop, who has the right of way?"
The instructor doesn't miss a beat.
"The law doesn't address this. Who goes first? The answer is … 'Not me.'" He sees me lip-syncing the answer. And smiles.
Treat yourself to drivers' school this year. It's worth every buck I shelled out.
Vic Fleming is a district court judge in Little Rock, Ark., where he also teaches at the William H. Bowen School of Law. Contact him at firstname.lastname@example.com.
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ManageEngine Desktop Central has become more enviable now. System Administrators can now manage a heterogeneous network using Desktop Central. Even the most complex tasks like patching various applications from time to time has now become a cake walk. System administrators can schedule the patch management process and automate it. Patching computers(Windows & Mac) which are located across the world is no more a daunting task.
"A sound mind in a sound body" is a saying, so does the health of computers. Systems health and vulnerability plays a vital role to determine employees productivity and business continuity. Thereby the success of every business heavily depends on the healthy network which means all the computers need to be patched with the latest updates periodically. So every enterprise needs a Patch Management Software, to ensure that all applications, to run their business are maintained updated. . For instance, Apple and other third parties release an array of patches of various applications from time to time. It becomes extremely important for enterprises to keep abreast with the latest patch updates. Every system Administrators dream and hunt has ended with Desktop Central.
The mac patch management architecture remains the same as windows. To know more about patch management architecture, refer to this: Patch Management Architecture
Desktop Central supports Patch Management for computers using the following versions of Mac operating system .
To know more about the supported applications refer to this: Patch Management Supported Applications.
To listen to our customers talk , refer here.


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PWR PrimeTime Wrestling Talk TV
May 26
Official Free Replay
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- Pro Wrestling Report -
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Catch the next episode of PWR PrimeTime Wrestling Talk TV on FITE!
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text:
shravan necesitaba un nuevo diseño de banner publicitario y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 40 diseños de 14 diseñadores freelance.
Seeking innovative enhancement of rough mock of upscale event promotional ad...
http://www.insidermg.com is an upscale social calendar site seeking to create our its own party "brand" - so a promo ad for the parties is needed - this ad will be used over and over for repeating events (but the dates/times/venue only will change)...
The EVOLUTION concept of these being sophisticated cocktail parties (no loud music, DJs, etc.) needs to come through... The REVOLVER concept that these parties COMBINE 3 Professional Groups each party - so that the people who attend the parties "revolve" through a diversity of new exposure to people is important. 1) Be consistent with the http://www.insidermg.com look and feel (this is an upscale site) 2) Please see the following mock image at http://www.insidermg.com/user/revolver.htm for detailed instructions - though PLEASE USE freedom to deviate if you have other ideas as we believe that if something works in a different way, then we will go with that - though we may redirect you if it doesn't.
1) Low end / generic party ad - this is an upscale site so we need a sophisticated modern feel to all the font/images/finish, etc.


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Heidi Montag is treating hubby and manager Spencer Pratt like her old boobs, trading him in for a newer, shinier career guide.
The top-heavy blonde is remaining married to her vapid Svengali, but she's turning over the managing of her career to a Malibu-based psychic.
"No longer is my husband the face of my business or managing my career," Montag told People magazine. "I am going to have Aiden Chase help manage my new life and career in a very different and positive way with light and love. The time for change is now. Never mix business and pleasure. We are no longer Speidi but Spencer and Heidi."
Pratt has managed the reality TV starring couple since the day they met nearly five years ago, when Montag was just 19 and only resembled her current self. Although her husband was the brains behind landing her a Playboy pictorial, Montag seems to believe Chase can take her career to another level.
"After the incredible experiences I have had healing my life and truly connecting to my dreams with healer intuitive Aiden Chase, I have officially asked him to become my manager," Montag told the mag. "Having an intuitive psychic leading my team gives me an edge no one else has."
Montag made news last year when she had 10 plastic surgeries in one day. She said she has now "cleared all the negative energy in my life" and has signed on for a Ron Howard-related show business project and a feature film comedy. She's also booked for an appearance with Jay Leno on "The Tonight Show" next week.
"I am so excited for my future and the bright successes coming my way," said Montag.


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WACO, Texas - An AWOL soldier remained defiant Friday as a judge sentenced him to life in federal prison for collecting bomb-making materials to carry out what he told authorities would be a massive attack on a Texas restaurant full of Fort Hood troops.
Army Pfc. Naser Jason Abdo, a Muslim, was planning a religious mission seeking justice for the people of Iraq and Afghanistan, according to a recorded jail conservation with his mother played for jurors at trial.
U.S. District Judge Walter Smith allowed Abdo to represent himself at Friday's sentencing after the 22-year-old told the judge last month that he and his attorneys weren't communicating effectively.
Abdo, who was sentenced to two life terms plus additional time, sat in court with a white cloth bound over his mouth and a black mesh covering his hair and face. He has previously been accused of spitting what he thought was HIV-infected blood on agents escorting him.
Referring to Maj. Nidal Hasan, the Army psychiatrist accused in the fatal shooting of 13 people at the Fort Hood military post, Abdo said that he lived in Hasan's shadow despite "efforts to outdo him."
Abdo said he would continue his jihad - an Arabic term for holy war - "until the day the dead are called to account for their deeds."
He spoke in Arabic several times during his allocution, and then translated it for the court.
"I do not ask the court to give me mercy, for Allah is the one that gives me mercy," he said while reading from notes.
A federal jury convicted Abdo in May on six charges, including attempting to use a weapon of mass destruction. He was AWOL from Fort Campbell, Ky., when arrested with bomb-making materials last summer at a Fort Hood-area motel.
He also was found guilty of attempted murder of U.S. officers or employees and four counts of possessing a weapon in furtherance of a federal crime of violence.
There is no parole in the federal prison system.
After the sentencing, U.S. Attorney Robert Pitman compared Abdo's plot to recent mass shootings at a movie theatre near Denver and a Sikh temple in suburban Milwaukee.
"In the wake of the tragic events in Colorado and Wisconsin, this is yet another reminder that there are those among us who would use or plan to use violence to advance their twisted agenda," Pitman said.
In a recorded police interview, Abdo said he wanted to carry out the attack "because I don't appreciate what my unit did in Afghanistan." His plan, according to what he told authorities, was to place a bomb in a busy restaurant filled with soldiers, wait outside and shoot anyone who survived - and become a martyr after police killed him.
According to testimony, Abdo told an investigator he didn't plan an attack inside Fort Hood because he didn't believe he would be able to get past security at the gates.
Abdo grew up in the Dallas suburb of Garland and at age 17 decided to follow Islam. He enlisted in the military in 2009, thinking that the service wouldn't conflict with his religious beliefs.
But in an essay that was part of his conscientious objector status application filed in June 2010, Abdo wrote that he reconsidered as he explored Islam further.
Abdo said in his discharge request that other soldiers harassed him about his religion during basic and advanced training. As he neared deployment, he said he studied Islam more closely to learn "whether going to war was the right thing to do Islamically."
Abdo's unit was deployed to Afghanistan without him. He said he would refuse to go even if it resulted in a military charge against him.
His conscientious objector status was put on hold after he was charged with possessing child pornography in May 2011. Two months later, during the Fourth of July weekend, Abdo went AWOL from the Kentucky Army post.
In the essay included in the conscientious objector status application, Abdo described the 2009 Fort Hood shooting rampage that left 13 dead and more than two dozen wounded as "an act of aggression by a man and not by Islam."
Hasan faces the death penalty if convicted in the Army post shootings. His court-martial is set for later this month at Fort Hood.


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How I Discovered Bliss…From Bumper Stickers
I was headed home from a weekend yoga retreat, and my brain must have been unusually uncluttered because I found myself noticing things I'd never noticed before—the way the road seemed to rise to meet the wheels of the bus I was on, how the turn signal clicked in time to the music on the radio. And the bumper stickers on the cars we passed on the highway.…Was it only me, or were some, like, incredibly profound?
Did I mention I'd just done quite a bit of yoga?
Seriously, apart from the occasional eye roller ("I had a handle on life, but it broke") and snarky worldview ("Just when you think life's a bitch, it has puppies"), I spotted quite a few that seemed to convey a universal truth or, at least, made good sense. It got me wondering: Was it possible to espouse a wise life philosophy on a sticker slapped on the back of a Prius?
To find out, I contacted experts in various fields to see if I should yield to these pithy sayings or let them recede in the rearview mirror. What I discovered: Happiness may be all around you. You simply have to slow down and notice it.
Not all who wander are lost.
I doubt that this quote, adapted from J.R.R. Tolkien's The Lord of the Rings, is much comfort to parents whose grown children work in Starbucks while taking pottery classes, then move to China to teach English and ultimately return home to become Zumba instructors. Fortunately, I'm not one of those parents (yet). To me, this homily means that even when someone seems to lack a long-term plan, that doesn't mean she's flailing. She may simply be an in-the-moment planner. "People who rely on intuition to decide their path may come off as aimless, but they might simply prefer a nonlinear approach to life," says Richard Bolles, author of the best-selling career-seeker's bible What Color Is Your Parachute?
Of course, some folks who wander, do, in fact, need a Saint Bernard to track them down, give them a shot of brandy and shepherd them inside before they die of exposure. How to tell if you're in need of some guidance? You might want to consult a friend (preferably a nonjudgmental one) who appreciates your way of thinking but who can also remind you that, although your new ambition to be a trapeze artist might make you happy, it could delay your long-held plan of getting pregnant. "It also helps to jot down answers to questions like 'When did I enjoy myself today?' and 'What did I learn?'" Bolles says. What's crucial is tuning in to your feelings, then paying attention to them as you find your way to your passion.
Those who discourage your dreams have likely abandoned their own.
Back in college, I had a cynical friend who, when I'd told him how jazzed I was by the positive feedback I'd gotten from my first-ever published article, said, "Great writers write what must be written. They're not looking for praise." He then suggested that my personality was better suited to a more quotidian profession with a steady paycheck than to a potentially unstable writing career. At first, I felt like a squashed insect. Then I thought, What a jerk.
"Many people do say things to hold others back, whether consciously or unconsciously," says Nina Brown, Ed.D., a counselor and author of Uptight and In Your Face. "It's possible that they have a dream that has not been realized, then project their failure onto others." But that's not always the case. Certain dream discouragers might be pessimists—or hard-nosed realists. "Studies suggest that compared with optimists, pessimistic types can be more in touch with reality, though often painfully so," she points out. In other words, just because Debbie Downer is trying to deflate your balloon doesn't mean what she's saying is wrong.
"It's vital to look at that person's history," Brown told me. If someone has a habit of being envious or underestimating everyone, take what she says with a grain of salt. "But don't automatically dismiss a naysayer," Brown advises. "Listen to what she has to say, absorb it, then make up your own mind."
Don't believe everything you think.
This idea is the basis for a branch of psychology known as cognitive-behavioral therapy. CBT works by helping you challenge false thoughts and beliefs (e.g., I'm worthless) that can sap confidence and prevent you from going after what you want. "It can be helpful to take another look at certain assumptions that might be making you feel bad unnecessarily—such as 'I must have everyone's approval,'" explains Aldo Pucci, Psy.D., president of the National Association of Cognitive-Behavioral Therapists in Pittsburgh. That reminded me of how I beat myself up one weekend after I lay down for a nap rather than spend time with my young daughters. My last thought before dropping off should have been, "This feels wonderful." Instead, it was, "I'm a bad mom."
"You're operating on the belief that a good mom must spend every available moment with her children," Pucci told me. It sounded so silly, but on some level, I did believe that. He suggested I replace my self-criticism with more rational self-talk and practice repeating it to myself. I came up with "I love my kids and spend time with them when I can. Needing a nap has nothing to do with the quality of my mothering." The next time I was tempted to criticize myself for doing something for me alone, I repeated my mantra and felt so energized I didn't even need to lie down.
Honk if you love Jesus.
I choose to translate this bumper sticker more broadly as "Honk if you love God, in whatever form you believe in Him or Her." I figure, why exclude Jews or Muslims or Hindus or any other believer from honking their horn if they are so moved? The fact is, whatever a person's spiritual views, participating in any kind of religion seems to confer multiple happiness benefits. "People who have religious beliefs and partake in spiritual activities regularly report greater feelings of happiness and feel a deeper sense of meaning and purpose in life, possibly because they're better equipped to deal with stress," says Harold G. Koenig, M.D., director of the Center for Spirituality, Theology and Health at Duke University.
Of course, organized religion is not for everyone. And research suggests that spiritual practices such as meditating or volunteering for a good cause offer a similar positive benefit. But although those spiritually oriented activities are associated with greater happiness, "there really does seem to be something key about feeling connected to a creator who is in control of everything, extending to the next life," Dr. Koenig says.
That's a toughie for people who have lapsed, who don't believe in God or who are Bill Maher. And then there are folks like me who feel that there may well be something divine in how the universe operates but who are basically nonreligious. To my credit, I do strive to be honest and forgiving, doing unto others and all that, which in itself gives me a warm and fuzzy feeling. "The question is, Is there more to life than that?" Dr. Koenig asks. "You've got to keep an open mind." I'm all for open minds, but faith isn't something I can flick on and off like a light switch. And I've never been much of a joiner, even for a higher cause. So for now, I'll have to let my own moral code be my guide and take pleasure in that.
A woman needs a man like a fish needs a bicycle.
You've probably seen this bumper sticker on a 40-year-old VW bus. Feminist Gloria Steinem popularized the slogan, but it was coined by Australian writer and politician Irina Dunn in 1970. Steinem herself ditched the motto in 2000, when she found a "bicycle" worth taking for a spin and walked down the aisle. Later, she clarified her view: "To be against unequal marriage is not the same thing as being against marriage," she said.
True enough, but is it ever OK to need a man, if not for financial support then for emotional sustenance, or perhaps to move the odd refrigerator when you need to sweep underneath? "Technically, nobody needs anybody—no adult is going to die without another human being," says Terry Real, author of The New Rules of Marriage. "But on a broader level, everybody needs everybody. Having the attitude that you don't need anyone isn't independent; it's antidependent. It isn't healthy, nor is it conducive to being in a loving relationship." I'd heartily agree with that sentiment, but after a gnarly breakup or two in my 20s, I can remember drunkenly declaring my independence from men and feeling pretty good about it, at least for a while. Maybe that's because back then, I had a bad habit of dating guys with whom I felt needy, probably because they never gave me much. It took me a number of years to realize that I wasn't abnormally needy; I simply picked boyfriends who bridled at my having any expectations of them whatsoever. "There's a big difference between saying 'I'd love a hug' and 'I will fall apart without a hug,'" Real points out. "A healthy dependency is when you can let yourself lean on someone to do for you what you can't do for yourself. That's not weak. That's human."
If at first you don't succeed, redefine success.
You're probably familiar with this saying's first cousin: "Winners never quit. Quitters never win." I like the idea of redefining success much better. If you see your sole options as winning, losing or quitting, that leaves you with only one happy outcome of the three. But if you give yourself the choice of reconfiguring your goals as you go along, the odds of coming out feeling good about yourself and your efforts rise exponentially.
Let's say your aim is to lose 10 pounds in a month and instead you lose 5 (or even 2). You can say, "I didn't lose 10 pounds and so I failed. Pass the M&Ms." You might also say, "I lost 5 pounds, but I'm still on track and I feel happy with what I've achieved." (Success redefined.) Healthier yet: "I lost weight—good for me! But I haven't reached my final goal, so it looks as if I might have to give myself some more time to lose those 5 pounds." (Success still pending; original goal slightly altered.)
Rather than focusing on how you've fallen short, "you're taking into account the wisdom you've gleaned from your attempts at achieving the goal," says Kate Ebner, founder of The Nebo Company, a coaching consultancy in Washington, D.C. "That's empowering and will spur you on."
I'm not perfect, but parts of me are fantastic.
A woman I know who modeled nude for an art class gave me some good advice: "When posing, drape something over one breast, because a breast on its own often looks better than a pair." It's only when you see breasts together and notice that they don't match—one is perkier or has a more symmetrical nipple—that you start to think other women's breasts match better and that maybe you need implants and…you see where I'm going with this.
The idea that it's possible to always be better looking, that we can get that much closer to perfection, is pervasive in our society, says Alice Domar, Ph.D, author of Be Happy Without Being Perfect. "Sometimes, it seems to me as if the only women who aren't wrapped up in the whole self-improvement thing are those who've had a serious illness," she says. "After coping with something like cancer, you tend to think, Well, I'm alive and I'm happy. But you shouldn't have to get sick to learn to appreciate what you have."
Hear, hear! Instead of focusing on an "imperfect" part, Domar suggests, ask yourself, What beauty do I see today? Maybe it's a great haircut or glowing skin. Don't stop looking until you find something kind to say about yourself. "If you keep at it," Domar says, "the exercise can really change your perspective."
The truth shall set you free, but first it will piss you off.
We all know that some truths are easier to digest than others. ("You're an incredibly generous person!" versus "I don't know who told you you'd look good with bangs.") "The problem is, truth is often a euphemism for flaw," says Karen Reivich, Ph.D., coauthor of The Resilience Factor.
That's been my experience. When someone feels that I must know the "truth" about myself, it's usually something that I'd prefer not to hear. ("As a matter of fact, you do look fat in that.") So of course that kind of truth-telling is going to piss me off! I'm well acquainted with my many shortcomings, thank you very much. And I'm not ashamed to admit that I don't mind being lied to in certain instances. ("You look exactly the same as the day I met you 15 years ago" comes to mind.)
Yet even I have to concede that, occasionally, getting another viewpoint, even a critical one, can feel like a relief, especially if it confirms something I've already suspected about myself. It all depends on the timing and delivery. "Hurt feelings arise when we point out things in anger rather than to help someone reach her potential," Reivich says. "Making a person feel judged, ashamed or embarrassed doesn't lead to openness." The lesson is that the truth combined with compassion (rather than hurled like a Molotov cocktail) can help all of us address issues in a healthier way.
I don't want buns of steel. I want buns of cinnamon.
I can really, really relate to this. Faced with a choice of doing squats and lunges or losing myself in a Cinnabon as big as my head, I know which option I'd prefer. I also know which would help my butt look better. Yet, sometimes, despite being all too aware that a cinnamon bun is no friend to my derriere, my thighs or any other part of my body, I might decide against what's healthy in exchange for a hit of pleasure.
There's no reason for me to beat myself up for that, according to Reivich. It's easy to get so caught up in the angel-devil paradigm that you forget to ask, Why do I have to choose one or the other? "That's all-or-nothing thinking, which is linked to depression," she says. When you give yourself rigid choices at opposite ends of the spectrum—yes or no, feast or famine—you probably won't be happy with whichever one you choose. You're also apt to swing back to the other extreme.
Here's another option: Go for buns of, well, not Jell-O perhaps, but not of steel either. Maybe buns of the kind of firm, smooth foam that fills the inside of a couch. And treat yourself to the occasional cinnamon bun. One at a time. And maybe not an 800-calorie whopper like the behemoths they sell at the mall. It's about becoming comfortable with the concept of enough, and about moderation and contentment. That doesn't make for a deep or witty bumper sticker, but it's definitely a healthier, happier way to live.
Photo Credit: Riccardo Tinelli/Trunk Archives


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Accuracy Checking Technician - Redditch
- Recruiter
- PHOENIX Medical Supplies Ltd
- Location
- 7 Church Green West, Redditch, Worcestershire, B97 4DU
- Salary
- Competitive
- Posted
- 06 Sep 2018
- Closes
- 06 Oct 2018
- Ref
- lb/1502
- Contract
- Full-time
- Pharmacy sector
- Community
- Job Type
- Pharmacy technician
- Sector
- Pharmacy
- Specialist area
- Public health
We are currently looking for a Accuracy Checking Technician in our Church Green branch, working 40 hours per week. Reporting to the Pharmacist Manager, your overall responsibility will be to participate in the whole dispensing process.
Proposed working pattern will be:
Monday: 09:00 - 18:30 (1 hour break)
Tuesday: 09:00 - 18:00 (30 minute break)
Wednesday: 09:00 - 17:30 (30 minute break)
Thursday: 09:00 - 17:30 (30 minute break)
Friday: 08:30 - 16:00 (30 minute break)
The role will also involve establishing and developing long term relationships with customers and healthcare professionals, ensuring to always deliver courteous and effective customer service. You will be required to assist in the delivery of all commercial pharmacy services where appropriate, including blood pressure measuring and weight management.
In this role you will be required to complete administrative records, and ensure that these records are adequately maintained. You will effectively manage pharmaceutical stock and equipment, including the administration of receiving, storing, maintaining and issuing. You may be required to deliver healthcare advice and signpost where necessary. You will be expected to assist in the sale of medicines and other merchandise when required.
In order to be successful, you must be registered with the GPhC and be able to provide a membership number upon request. Also must have an NVQ3 in Pharmacy Services or Accredited equivalent qualification and experience of working in a customer focused environment.
We reserve the right to close this vacancy when sufficient applications are received.
Previous applicants need not apply.
Please note if you are progressed to interview stage you will be invited to a Competency interview accompanied by a 30 minute working interview.
The closing date for all applications is {Expiry Date}
The PHOENIX Group will not be processing applications of applicants who are family members, or have any personal relationship with a current employee working in the same department as the position being advertised.
Direct Applications only- Strictly no Recruitment Agencies.


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I've been managing injury since Sept 2010. Basically, it's a pelvic/hip problem which has been causing a series of related injuries in my left quad, hip and knee. It has been an immensely frustrating period but lately progress has been good and we are all optimistic that full recovery is not far away. I have been looked after very well by the VIS team of specialists, without whom I would have cracked. The injury meant that I had to miss nationals and am only just returning to racing now. It is a slow and frustrating process.
I chose not to pursue a team contract overseas for this year. Racing in Europe is great but so is my career, my life and relationships in Australia and the best combination for my general happiness is to do a bit of racing o/s without spending the whole year away. My plan had been to train up a storm over Summer, and get results at nationals, Tour of NZ and Oceanias that were good enough to go overseas with the national team for some cool races in 2011 - like what I did last year. Unfortunately, getting injured put paid to my master plan.
Rehab has been pretty intense - at one stage I counted up 9 rehab-related appointments each week - and I was getting sick of not making progress. So I've taken some time out from my career as a lawyer to focus on getting back to full fitness and back overseas. The paycheck isn't quite the same but I can be a lawyer for a lot longer than I can be a cyclist, and taking some time out to re-evaluate my career direction will be good for my mental health. I've got a few projects I'd like to give some time to (including rebuilding Ride Happy into something bigger and better) and this is the perfect time to explore them. I'm doing some more writing and am just about to start working with Scody. I've also just been granted a scholarship to study post graduate Law and business strategy, thanks to a partnership between VIS and Open Universities.
So that's about it. Injury is part and parcel of being an elite athlete, and some of us have to deal with it more than we'd like to. I'm immensely lucky to have the support of the VIS and some awesome sponsors (they're listed on the right, but a special shout out to John Hill @ High5, Mel Lambourn @ St Mel and Marcus Speed @ Perfect Pilates - you guys rock). My coach, Donna Rae-Szalinski, is The Original Supercoach, and if anyone can get me back into form it's her. The lovely Andy continues to be lovely. All in all, I am very lucky.
My race calendar for the next little while looks to be the national road series in Australia, and if I can show some lightning form, maybe some races overseas. At the end of the day, if I ride fast, I'll get overseas. If I don't, I won't. Pretty simple really.
Whew! That's enough factoids for today. Don't worry kids, the Ride Happy you know and love will be back to normal tomorrow!


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Rose Parade hosts 1st gay marriage on wedding cake float
PASADENA, Calif. (AP) — Standing atop a giant wedding cake float, Aubrey Loots and Danny Leclair exchanged vows New Year's Day in the first same-sex marriage during the Tournament of Roses Parade.
Throngs of spectators cheered as the men, dressed in dark suits, faced each other and held hands before the Rev. Alfreda Lanoix, who officiated the ceremony aboard the AIDS Healthcare Foundation float.
Days earlier, a San Diego woman launched a Facebook page urging people to boycott the 125th Rose Parade after learning of the couple's plans. But some, like Jennifer Adair, who cheered along with her girlfriend, lined the streets just for this moment.
"We're a modern-day society, so accept it. Don't worry about what other people do," Adair told the Los Angeles Times.
The Pasadena Tournament of Roses, which puts on the parade, had said the float represents this year's parade theme, "Dreams Come True."
Kevin Ferguson, who watched the couple pass by, said he supported their move despite opposition by some.
"You can't put a timetable on another person's freedom," Ferguson told the Times.
Loots and Leclair, who met across a crowded dance floor 12 years ago, own a small chain of hair salons. Their wedding came toward the end of the two-hour parade festivities.
Los Angeles Dodgers longtime broadcaster Vin Scully, the parade's grand marshal, kicked off the show after six F-16s from the Air Force's Thunderbirds roared overhead.
"Instead of me throwing out the first pitch, let's start the parade," said Scully, who will toss the kickoff coin at the Rose Bowl match between Stanford and Michigan State.
One by one, flowered floats, exotic equestrians and brass bands marched along the 5 ½-mile route.
A heavy police presence ringed this year's revelry in the aftermath of the Boston Marathon bombings. More than 1,100 officers patrolled the crowd. Bomb-sniffing dogs and a wide range of video surveillance also were used to detect suspicious behavior.
At the start of the parade route, police arrested 19 people who tried to stop the SeaWorld float featuring orcas. The demonstrators were booked on suspicion of interfering with a special event, Pasadena police Lt. Terysa Rojas said.
The parade went on as scheduled with officers and sheriff's deputies guarding the SeaWorld float as it passed by onlookers.
Overnight, 17 people were arrested along the parade route on suspicion of various offenses including public intoxication, vandalism and battery.
Despite the arrests, Rojas said parade-goers were mostly well-behaved.
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