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En 1900, les deux immeubles sont réunis sous un étage à toit plat. C'est en 1901 qu'un étage carré coiffé d'un toit plat vient couvrir les deux édifices voisins. Cette propriété est cédée par les héritiers Renfrew à Holt Renfrew and Co. en 1903. (Source : https://www.ville.quebec.qc.ca/citoyens/patrimoine/bati/fiche.aspx?fiche=6249 ), 1 diapositive : couleur ; 5 x 5 cm, Image réalisée sous la direction de Luc Noppen dans le cadre des travaux du Groupe de recherche en art du Québec (GRAQ) en 1987.

Relief shown by spot heights.; Same map as that in Hayden Atlas of Colorado 1877.; Partly compiled from Clarence King's 40th Parallel Survey.

Many retailers discriminate among their customers based on their value to the firm. Instead of losing a customer due to this discrimination or lack of inventory, a retailer might prefer to place a transshipment request with other retailers to satisfy the customer’s demand. The system as a whole can benefit from this type of transshipments. In this paper, we study a problem of a centrally controlled system with multiple retailers. Each retailer serves two types of customers: high priority and low priority. Each retailer employs a rationing policy with a rationing level k in the context of a continuous-review (r, Q) inventory replenishment model. The overall policy is referred to as an (r, k, Q) policy. Retailers can transship items from either other retailers or a more expensive central depot. We propose an enumeration-based approximation to find the cost-minimizing policy parameters for the individual retailers and an approximation procedure to solve the combined rationing and transshipment problem. The latter relies on adjusting the demand arrival rates and the unit transshipment costs for both types of customers at all retailers. An extensive numerical study highlights the impact of transshipments on the retailers’ rationing policies. Without transshipment opportunities among each other, retailers set their policy parameters so that the resulting service levels are high for both types of customers. Allowing transshipments results in more aggressive rationing policies, and retailers with aggressive rationing policies benefit from the transshipments the most.

Many retailers discriminate among their customers based on their value to the firm. Instead of losing a customer due to this discrimination or lack of inventory, a retailer might prefer to place a transshipment request with other retailers to satisfy the customer’s demand. The system as a whole can benefit from this type of transshipments. In this paper, we study a problem of a centrally controlled system with multiple retailers. Each retailer serves two types of customers: high priority and low priority. Each retailer employs a rationing policy with a rationing level k in the context of a continuous-review (r, Q) inventory replenishment model. The overall policy is referred to as an (r, k, Q) policy. Retailers can transship items from either other retailers or a more expensive central depot. We propose an enumeration-based approximation to find the cost-minimizing policy parameters for the individual retailers and an approximation procedure to solve the combined rationing and transshipment problem. The latter relies on adjusting the demand arrival rates and the unit transshipment costs for both types of customers at all retailers. An extensive numerical study highlights the impact of transshipments on the retailers’ rationing policies. Without transshipment opportunities among each other, retailers set their policy parameters so that the resulting service levels are high for both types of customers. Allowing transshipments results in more aggressive rationing policies, and retailers with aggressive rationing policies benefit from the transshipments the most.

Contains fulltext : 167701.pdf (Publisher’s version ) (Closed access), The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.

The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses c

Item does not contain fulltext, The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.

Contains fulltext : 137990.pdf (publisher's version ) (Open Access)

Contains fulltext : 137990.pdf (publisher's version ) (Open Access)

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ~45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of alpha-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of alpha-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of alpha-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders.Copyright © 2014 The American Society of Human Genetics.

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ~45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of alpha-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of alpha-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of alpha-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders.Copyright © 2014 The American Society of Human Genetics.

Contains fulltext : 137990.pdf (publisher's version ) (Open Access)

IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV) NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response

IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV) NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response

We used Poynting fluxes and densities rho to investigate the stormtime thermosphere on November 10, 2004. Thermospheric energy E(sub th), which is derived from rho, consists of two sources, solar ultraviolet radiation (E(sub rh uv)) and the solar wind (E(sub th sw)). Responses of E(sub th) to interplanetary driving suggest that the thermosphere can be described by the equation dE(sub th sw/dt = alpha epsilon - (E(sub th sw/tau)), where epsilon (sub vs( represents the electric field; alpha and Tau are constants. We show that: (1) E(sub th sw) is three times the ring-current energy; (2) alpha epsilon is comparable with model predictions; (3) signatures of equatorward propagating disturbances were detected in neutral density profiles., Pub. in Journal of Atmospheric and Solar-Terrestrial Physics, v72, p309-318, 2010.

This paper describes six recent attempts to conserve threatened wallabies (Marsupialia: Macropodoidea) by reintroduction. All ended in failure. We place these attempts within the context of nineteen other reintroductions of macropods known to us. Success of reintroduction of macropods appears to depend critically on control or exclusion of exotic terrestrial predators. Islands without exotic predators support a success rate of reintroductions an order of magnitude higher than that of mainland sites and islands with exotic predators (82% cf. 8%). Reintroductions have generally been poorly monitored and poorly documented. Researchers have often failed to appreciate the enormity of the task of controlling introduced predators (foxes and feral cats and dogs) and herbivores (rabbits), and to make adequate use of existing technology (radiotelemetry), and have been unable to overcome the logistical problems of managing reintroductions far from their research bases. Successes in management and reintroduction of other threatened fauna in Australia suggest that effective control of introduced predators and rabbits using the poison 1080, for which many native species have a high tolerance, may provide an effective means of managing mainland reintroductions.