Small dense B cells are stimulated to proliferate by membranes prepared from activated helper T (Th) cell clones. In combination with Th2 lymphokines, Th membranes stimulate B cells to differentiate ...to secrete predominantly immunoglobulin (Ig)M, IgG1 and IgE. The activity in Th membrane requires the expression of CD40 ligand by the T cells, and initiation of the B cell response occurs through the ligation of CD40 on the B cell surface. We have further characterized the properties of the B cell response and found that Th membranes stimulated B cell proliferation and Ig secretion in a cell density independent manner and the majority of the stimulated B cells underwent a limited number of division rounds between day 2 and 5 of culture. IgM-secreting cells appeared in culture by day 3 and increased to reach a maximum, comprised of 30% of the viable cells, on day 5. IgG1-secreting cells appeared 12-24 h after IgM-secreting cells, and IgE-secreting cells did not appear until day 5. These data are consistent with a sequential model of isotype switching related to cell division. As lymphokines were absolutely required for antibody production we were able to determine when during culture they were essential. Lymphokines needed to be present prior to and during B cell proliferation for differentiation to Ig-secreting cells to proceed. This period corresponded closely to the time of maximum DNA synthesis. Consistent with sequential switching of Ig isotypes, differentiation to IgM secretion required the shortest exposure to lymphokines and IgE the longest. These experiments strongly suggest that the lymphokine-induced commitment to differentiate is made before DNA synthesis begins, although the lymphokine-delivered signals are necessary during DNA synthesis to support Ig class switching.
Oral-facial-digital type I (OFDI) syndrome is a male-lethal X-linked dominant developmental disorder belonging to the heterogeneous group of oral-facial-digital syndromes (OFDS). OFDI is ...characterized by malformations of the face, oral cavity, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This rare genetic disorder is due to mutations in the OFD1 gene that encodes a centrosome/basal body protein necessary for primary cilium assembly and for left-right axis determination, thus ascribing OFDI to the growing number of disorders associated to ciliary dysfunction. We now report a mutation analysis study in a cohort of 100 unrelated affected individuals collected worldwide. Putative disease-causing mutations were identified in 81 patients (81%). We describe 67 different mutations, 64 of which represent novel mutations, including 36 frameshift, nine missense, 11 splice-site, and 11 nonsense mutations. Most of them concentrate in exons 3, 8, 9, 12, 13, and 16, suggesting that these exons may represent mutational hotspots. Phenotypic characterization of the patients provided a better definition of the clinical features of OFDI syndrome. Our results indicate that renal cystic disease is present in 60% of cases >18 years of age. Genotype-phenotype correlation did not reveal significant associations apart for the high-arched/cleft palate most frequently associated to missense and splice-site mutations. Our results contribute to further expand our knowledge on the molecular basis of OFDI syndrome. Hum Mutat 0, 1-10, 2008.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To study elementary school principals' understandings and enactments of instructional leadership, we collected data through individual interviews, focusgroup discussions, and in-school observations. ...Three categories captured principals' conceptualizations of instructional leadership: curriculum expertise, formal delivery of professional development, and informal culture building. Their enactment of instructional leadership was influenced by three dimensions: their personal style, degree of coherence in agendas and initiatives, and availability of enabling structures. We anticipated the influence of personal style, but not the impact of coherence and structure, which introduces a new dimension to the literature on contextual influences impinging on individual practice /// Pour étudier la conception et la mise en œuvre du leadership pédagogique chez des directeurs et directrices d'école, les auteures ont colligé des données au moyen d'entrevues individuelles, de discussions en groupe et d'observations sur place. La conception du leadership pédagogique des directeurs et directrices d'école a été analysée à l'aide de trois catégories : expertise en matière de programmes scolaires, prestation de services de perfectionnement professionnel et édification d'une culture informelle. La mise en œuvre du leadership pédagogique a été étudiée pour sa part à l'aide de trois volets : style personnel, degré de cohérence dans les calendriers et les initiatives et mise en place de structures d'incitation. Les auteures avaient prévu l'influence du style personnel, mais non l'impact de la cohérence et des structures, ce qui introduit une nouvelle dimension dans la littérature au sujet des influences contextuelles sur la pratique de chacun.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The SoLid experiment aims to measure neutrino oscillation at a baseline of 6.4 m from the BR2 nuclear reactor in Belgium. Anti-neutrinos interact via inverse beta decay (IBD), resulting in a positron ...and neutron signal that are correlated in time and space. The detector operates in a surface building, with modest shielding, and relies on extremely efficient online rejection of backgrounds in order to identify these interactions. A novel detector design has been developed using 12800 5 cm cubes for high segmentation. Each cube is formed of a sandwich of two scintillators, PVT and 6LiF:ZnS(Ag), allowing the detection and identification of positrons and neutrons respectively. The active volume of the detector is an array of cubes measuring 80x80x250 cm (corresponding to a fiducial mass of 1.6 T), which is read out in layers using two dimensional arrays of wavelength shifting fibres and silicon photomultipliers, for a total of 3200 readout channels. Signals are recorded with 14 bit resolution, and at 40 MHz sampling frequency, for a total raw data rate of over 2 Tbit/s. In this paper, we describe a novel readout and trigger system built for the experiment, that satisfies requirements on: compactness, low power, high performance, and very low cost per channel. The system uses a combination of high price-performance FPGAs with a gigabit Ethernet based readout system, and its total power consumption is under 1 kW. The use of zero suppression techniques, combined with pulse shape discrimination trigger algorithms to detect neutrons, results in an online data reduction factor of around 10000. The neutron trigger is combined with a large per-channel history time buffer, allowing for unbiased positron detection. The system was commissioned in late 2017, with successful physics data taking established in early 2018.
Interviews with 12 teacher educators at a Canadian university explored the characteristics and roles of educational leaders in general and what constituted educational leadership at the school level. ...These faculty generally held traditional views of educational leadership. Implications for teacher education and faculty development are discussed. (Contains 37 references.) (SV)
The SoLid experiment has been designed to search for an oscillation pattern induced by a light sterile neutrino state, utilising the BR2 reactor of SCK\(\bullet\)CEN, in Belgium. The detector ...leverages a new hybrid technology, utilising two distinct scintillators in a cubic array, creating a highly segmented detector volume. A combination of 5 cm cubic polyvinyltoluene cells, with \(^6\)LiF:ZnS(Ag) sheets on two faces of each cube, facilitate reconstruction of the neutrino signals. % The polyvinyltoluene scintillator is used as an \(\overline{\nu}_e\) target for the inverse beta decay of (\(\overline{\nu}_e + p \rightarrow e^{+}+n\)), with the \(^6\)LiF:ZnS(Ag) sheets used for associated neutron detection. Scintillation signals are read out by a network of wavelength shifting fibres connected to multipixel photon counters. Whilst the high granularity provides a powerful toolset to discriminate backgrounds; by itself the segmentation also represents a challenge in terms of homogeneity and calibration, for a consistent detector response. The search for this light sterile neutrino implies a sensitivity to distortions of around \(\mathcal{O}\)(10)\% in the energy spectrum of reactor \(\overline{\nu}_e\). Hence, a very good neutron detection efficiency, light yield and homogeneous detector response are critical for data validation. The minimal requirements for the SoLid physics program are a light yield and a neutron detection efficiency larger than 40 PA/MeV/cube and 50 \% respectively. In order to guarantee these minimal requirements, the collaboration developed a rigorous quality assurance process for all 12800 cubic cells of the detector. To carry out the quality assurance process, an automated calibration system called CALIPSO was designed and constructed.
This paper presents a comprehensive optimisation study to maximise the light collection efficiency of scintillating cube elements used in the SoLid detector. Very short baseline reactor experiments, ...like SoLid, look for active to sterile neutrino oscillation signatures in the anti-neutrino energy spectrum as a function of the distance to the core and energy. Performing a precise search requires high light yield of the scintillating elements and uniformity of the response in the detector volume. The SoLid experiment uses an innovative hybrid technology with two different scintillators: polyvinyltoluene scintillator cubes and \(^6\)LiF:ZnS(Ag) screens. A precision test bench based on a \(^{207}\)Bi calibration source has been developed to study improvements on the energy resolution and uniformity of the prompt scintillation signal of antineutrino interactions. A trigger system selecting the 1~MeV conversion electrons provides a Gaussian energy peak and allows for precise comparisons of the different detector configurations that were considered to improve the SoLid detector light collection. The light collection efficiency is influenced by the choice of wrapping material, the position of the \(^6\)LiF:ZnS(Ag) screen, the type of fibre, the number of optical fibres and the type of mirror at the end of the fibre. This study shows that large gains in light collection efficiency are possible compared to the SoLid SM1 prototype. The light yield for the SoLid detector is expected to be at least 52\(\pm\)2 photo-avalanches per MeV per cube, with a relative non-uniformity of 6 %, demonstrating that the required energy resolution of at least 14 % at 1 MeV can be achieved.
'The life of a patient is the only life the patient has - can we really make a judgment call on who to treat or not?' J Puchula (from his address at the 2008 congress of the European Club for ...Paediatric Burns, Gdansk). The matter of triaging severe burns so that expensive and potentially futile treatment should not be initiated was discussed in a priority setting process by the Western Cape Health Department, and led us to question the validity of such an approach.
Activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM), class switch recombination (CSR), and immunoglobulin gene conversion in B-lymphocytes. Here we report for the first ...time the expression of AID in healthy human B-lymphocytes and in B-cell non-Hodgkin lymphomas (B-NHL). AID mRNA expression in humans is restricted to the CD19+CD38+IgD−germinal center cells, namely the CD19+CD38+CD44− centroblasts. After in vitro stimulation of naive human B cells by CD40-L and IL-4, AID mRNA is strongly induced for only 48 hours. In a survey of human B-NHL AID was found to be constitutively expressed in follicular lymphoma and in diffuse large B-cell lymphoma but to be absent in B-precursor lymphoblastic leukemia, in mantle cell lymphoma, and in plasma cell myeloma. In B-cell chronic lymphatic leukemia, in immunocytoma, and in extranodal marginal zone B-cell lymphoma of MALT, AID mRNA was expressed only in some samples. In follicular lymphoma and diffuse large B-cell lymphoma, the expression of AID mRNA was coincident with the presence of SHM in the variable region exons of the immunoglobulin heavy-chain gene. In human B-NHL, the AID mRNA is spliced into 4 different variants but does not contain point mutations. Thus AID, which is highly regulated during healthy B-cell development, is constitutively expressed in human germinal center B-NHL and in subsets of nongerminal center B-NHL. This constitutive expression of AID may promote illegitimate DNA recombinations and somatic mutations in B-NHL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The SoLid collaboration has developed a new detector technology to detect electron anti-neutrinos at close proximity to the Belgian BR2 reactor at surface level. A 288\(\,\)kg prototype detector was ...deployed in 2015 and collected data during the operational period of the reactor and during reactor shut-down. Dedicated calibration campaigns were also performed with gamma and neutron sources. This paper describes the construction of the prototype detector with a high control on its proton content and the stability of its operation over a period of several months after deployment at the BR2 reactor site. All detector cells provide sufficient light yields to achieve a target energy resolution of better than 20%/\(\sqrt{E(MeV)}\). The capability of the detector to track muons is exploited to equalize the light response of a large number of channels to a precision of 3% and to demonstrate the stability of the energy scale over time. Particle identification based on pulse-shape discrimination is demonstrated with calibration sources. Despite a lower neutron detection efficiency due to triggering constraints, the main backgrounds at the reactor site were determined and taken into account in the shielding strategy for the main experiment. The results obtained with this prototype proved essential in the design optimization of the final detector. This paper is dedicated to our SCK\(\cdot\)CEN colleague, Edgar Koonen, who passed away unexpectedly in 2017. Edgar was part of the SoLid collaboration since its inception and his efforts were vital to get the experiment started. He will be duly missed.
