568 research outputs found
Samenwerking in de detailhandel: Theorie en praktijk
In dit artikel staat de vraag "Waarom zijn ondernemers lid van een inkoopcombinatie?" centraal. Uitgaande van de 'strategic behaviour'-benadering en de transactiekostentheorie wordt beschreven of de redenen van samenwerking van toepassing zijn op een zevental geinterviewde leden. De resultaten moeten vanwege het geringe aantal waarnemingen met een zekere voorzichtigheid genterpreteerd worden. Uit de interviews kwam naar voren dat vrijwel alle voordelen en slechts een van de nadelen zoals onderscheiden in de 'strategic behaviour'- benadering daadwerkelijk ervaren werden door de ondernemers. Bij de transactiekostentheorie is een onderscheid gemaakt naar directe en indirecte transactiekosten. Het bleek dat samenwerking via de inkoopcombinatie alleen maar voordelen en geen nadelen op het gebied van de produktiekosten en directe transactiekosten oplevert. Er was geen uitspraak mogelijk of en in hoeverre er indirecte transactiekostenvoordelen of - nadelen werden ervaren.Op basis van de waarnemingen zou geconcludeerd kunnen worden dat samenwerken via een inkoopcombinatie een efficint alternatief is voor ondernemers, aangezien de voordelen ervan groter zijn dan de nadelen. Tevens geldt dat de voordelen minus de nadelen van de inkoopcombinatie duidelijk opwegen tegen andere alternatieven. Tenslotte kwam uit de interviews naar voren dat de aantrekkelijkheid van de inkoopcombinatie in de loop van de tijd reeds is toegenomen en dat de verwachting bestaat dat deze trend zich zal voortzetten in de toekomst.Retailing;Cooperation;Small Business;small and medium sized business
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Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System.
Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy
Identification of a target antigen in human anti-tubular basement membrane nephritis
Identification of a target antigen in human anti-tubular basement membrane nephritis. Sera from two patients with primary anti-tubular–basement–membrane–mediated tubulointerstitial nephritis, one a renal allograft recipient and the other with spontaneous anti-tubular–basement–membrane disease, were analyzed for the specificity of their autoantibodies. Both sera had circulating antibodies that reacted by ELISA with extracts of tubular basement membrane from several species, but failed to react significantly with extracts of glomerular basement membrane. Reactive antigen was solubilized with 6 M guanidine-HCl, 6 M urea, with reduction and alkylation, and with sodium dodecylsulfate. Digestion of the basement membrane with collagenase released relatively small quantities of antigen from the membrane, and trypsin and pepsin destroyed its antigenicity. The antigenic activity was characterized with respect to its size distribution by gel filtration and by immuno-overlay analysis of protein blots. Collectively, the results indicate that the major reactivity of both sera is directed towards a Mr 58,000 component that is unique to the tubular basement membrane. Minor reactivities toward high molecular weight components common to both glomerular and tubular basement membranes were detected by immuno-overlay analysis. This study identifies an antigen that is involved in human anti-tubular–basement–membrane–mediated tubulointerstitial nephritis, and demonstrates an advantage of the use of denaturing extraction over proteolytic methods to prepare the antigen
In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.
Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients' acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter
Detection Thresholds and Bias Correction in Polarized Intensity
Detection thresholds in polarized intensity and polarization bias correction
are investigated for surveys where the polarization information is obtained
from RM synthesis. Considering unresolved sources with a single rotation
measure, a detection threshold of applied to the Faraday
spectrum will retrieve the RM with a false detection rate less than ,
but polarized intensity is more strongly biased than Ricean statistics suggest.
For a detection threshold of , the false detection rate
increases to ~4%, depending also on coverage and the extent of the
Faraday spectrum. Non-Gaussian noise in Stokes Q and U due to imperfect imaging
and calibration can be represented by a distribution that is the sum of a
Gaussian and an exponential. The non-Gaussian wings of the noise distribution
increase the false detection rate in polarized intensity by orders of
magnitude. Monte-Carlo simulations assuming non-Gaussian noise in Q and U, give
false detection rates at similar to Ricean false detection
rates at .Comment: 8 pages, 8 figures, accepted for publication in Publications of the
Astronomical Society of Australi
Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells
AbstractDuring recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML) that developed fourteen years after allogeneic stem cell transplantation for treatment induced AML for his primary malignancy Immunoblastic lymphoma. This case allows us to postulate a possible mechanism of the origin of donor leukemia. The de novo AML clone contained a distinct cytogenetic abnormality, trisomy 11, which was simultaneously detected in preserved peripheral blood obtained at the time of transplantation as well as in the current bone marrow from an otherwise clinically and phenotypically normal donor. The findings from this unique case, provides insight into the process of leukemogenesis, and suggests that the sequence of events leading to leukemogenesis in this patient involved the senescence/apoptosis of normal donor hematopoietic cells due to telomere shortening resulting in the selective proliferation and transformation of this clone with MLL (mixed-lineage leukemia) gene amplification
Distribution of basement membrane antigens in glomeruli of mice with autoimmune glomerulonephritis.
peer reviewedGlomerulonephritis was induced in mice by the repeated injection of human glomeruli or purified glomerular basement membrane. The glomerular basement membranes of nephritic animals were observed to develop subepithelial extensions, "spikes." Although normally Type IV collagen is found throughout the full thickness of basement membranes, the "spikes" reacted with antibodies to laminin but not with antibodies to Type IV collagen. It is proposed that in murine autoimmune glomerulonephritis, the visceral epithelial cells produce an excess of laminin
The discovery of diffuse steep spectrum sources in Abell 2256
Context: Hierarchical galaxy formation models indicate that during their
lifetime galaxy clusters undergo several mergers. Here we report on the
discovery of three diffuse radio sources in the periphery of Abell 2256, using
the GMRT.
Aims: The aim of the observations was to search for diffuse ultra-steep
spectrum radio sources within the galaxy cluster Abell 2256.
Methods: We have carried out GMRT 325 MHz radio continuum observations of
Abell 2256. V, R and I band images of the cluster were taken with the 4.2m WHT.
Results: We have discovered three diffuse elongated radio sources located
about 1 Mpc from the cluster center. Two are located to the west of the cluster
center, and one to the southeast. The sources have a measured physical extent
of 170, 140 and 240 kpc, respectively. The two western sources are also visible
in deep low-resolution 115-165 MHz WSRT images, although they are blended into
a single source. For the combined emission of the blended source we find an
extreme spectral index of -2.05\pm 0.14 between 140 and 351 MHz. The extremely
steep spectral index suggests these two sources are most likely the result of
adiabatic compression of fossil radio plasma due to merger shocks.
Conclusions: The discovery of the steep spectrum sources implies the
existence of a population of faint diffuse radio sources in (merging) clusters
with such steep spectra that they have gone unnoticed in higher frequency
(\gtrsim 1 GHz) observations. An exciting possibility therefore is that such
sources will determine the general appearance of clusters in low-frequency high
resolution radio maps as will be produced by for example LOFAR or LWA.Comment: 5 pages, 2 figures, accepted for publication in A&A on October 16,
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