Sendingsarbeid onder Natalse Indiërs*

“What is it like to labour among the Indians,” I am often asked by my friends in the Transvaal. “ Is it easy?” “Do they accept the gospel gladly?” “ In which language do you preach to them?

Discovering the roots: Uniform closure results for algebraic classes under factoring

Newton iteration (NI) is an almost 350 years old recursive formula that approximates a simple root of a polynomial quite rapidly. We generalize it to a matrix recurrence (allRootsNI) that approximates all the roots simultaneously. In this form, the process yields a better circuit complexity in the case when the number of roots $r$ is small but the multiplicities are exponentially large. Our method sets up a linear system in $r$ unknowns and iteratively builds the roots as formal power series. For an algebraic circuit $f(x_1,\ldots,x_n)$ of size $s$ we prove that each factor has size at most a polynomial in: $s$ and the degree of the squarefree part of $f$. Consequently, if $f_1$ is a $2^{\Omega(n)}$-hard polynomial then any nonzero multiple $\prod_{i} f_i^{e_i}$ is equally hard for arbitrary positive $e_i$'s, assuming that $\sum_i \text{deg}(f_i)$ is at most $2^{O(n)}$. It is an old open question whether the class of poly($n$)-sized formulas (resp. algebraic branching programs) is closed under factoring. We show that given a polynomial $f$ of degree $n^{O(1)}$ and formula (resp. ABP) size $n^{O(\log n)}$ we can find a similar size formula (resp. ABP) factor in randomized poly($n^{\log n}$)-time. Consequently, if determinant requires $n^{\Omega(\log n)}$ size formula, then the same can be said about any of its nonzero multiples. As part of our proofs, we identify a new property of multivariate polynomial factorization. We show that under a random linear transformation $\tau$, $f(\tau\overline{x})$ completely factors via power series roots. Moreover, the factorization adapts well to circuit complexity analysis. This with allRootsNI are the techniques that help us make progress towards the old open problems, supplementing the large body of classical results and concepts in algebraic circuit factorization (eg. Zassenhaus, J.NT 1969, Kaltofen, STOC 1985-7 \& Burgisser, FOCS 2001).Comment: 33 Pages, No figure

Effects of freshwater crayfish on influenza A virus persistence in water

Several investigations have recently assessed the ability of some aquatic invertebrates to act as tools for avian influenza A virus (IAV) surveillance as well as their potential role(s) in IAV ecology. Because of this, as well as the high IAV seroprevalence rates noted in select mesocarnivores that commonly inhabit aquatic and semi-aquatic habitats, we evaluated the effects that freshwater crayfish have on IAV in water at three dose levels and monitored for the presence of IAV in crayfish tissues (gill and green gland) and haemolymph at multiple time points. At relatively high, medium 432 and low (approximately 10 , 10 and 10 EID50/ml, respectively) doses, mesocosms containing crayfish (Orconectes sp.) had less detectable IAV RNA present when final water samples were assayed (9 days post-contact [DPC]). In general, containers without crayfish present had nearly three-fold greater quantities of viral RNA at 9 DPC. A varying number of RNA positive samples were detected for the three crayfish sample types collected. Gill tissue produced the largest number of positive non-water samples (n = 26), with the highest quantities detected from crayfish sampled on 1 and 4 DPC (103.5 EID50 equivalent/ml). On a few occasions, gill (n = 8) and haemolymph samples (n = 1) produced higher quantities of viral RNA than their respective water samples or water samples collected 1–2 DPC earlier, but these differences were typically minor. Based upon water samples, statistical models indicated that the interaction of dose and crayfish exposure days explained most of the variation in these data. Future efforts should address if crayfish exposed to IAV-laden water have the capacity to successfully transmit IAVs to mammals and birds which frequently prey upon them

Evaluating multisite multiprofessional simulation training for a hyperacute stroke service using the behaviour change wheel

Background Stroke is a clinical priority requiring early specialist assessment and treatment. A London (UK) stroke strategy was introduced in 2010, with Hyper Acute Stroke Units (HASUs) providing specialist and high dependency care. To support increased numbers of specialist staff, innovative multisite multiprofessional simulation training under a standard protocol-based curriculum took place across London. This paper reports on an independent evaluation of the HASU training programme. The main aim was to evaluate mechanisms for behaviour change within the training design and delivery, and impact upon learners including potential transferability to the clinical environment. Methods The evaluation utilised the Behaviour Change Wheel framework. Procedures included: mapping training via the framework; examination of course material; direct and video-recorded observations of courses; pre-post course survey sheet; and follow up in-depth interviews with candidates and faculty. Results Patient management skills and trainee confidence were reportedly increased post-course (post-course median 6 [IQ range 5–6.33]; pre-course median 5 [IQ range 4.67–5.83]; z = 6.42, P <.001). Thematic analysis showed that facilitated ‘debrief’ was the key agent in supporting both clinical and non-clinical skills. Follow up interviews in practice showed some sustained effects such as enthusiasm for role, and a focus on situational awareness, prioritization and verbalising thoughts. Challenges in standardising a multi-centre course included provision for local context/identity. Conclusions Pan-London simulation training under the London Stroke Model had positive outcomes in terms of self-reported skills and motivation. These effects persisted to an extent in practice, where staff could recount applications of learning. The evaluation demonstrated that a multiple centre simulation programme congruent with clinical practice can provide valuable standard training opportunities that support patient care

Early Neoproterozoic Basin Formation in Yukon, Canada: Implications for the make-up and break-up of Rodinia

SUMMARY: Geological mapping and stratigraphic anaylsis of the early Neoproterozoic Fifteenmile Group in the western Ogilvie Mountains of Yukon, Canada, has revealed large lateral facies changes in both carbonate and siliciclastic strata.  Syn-sedimentary NNW-side-down normal faulting during deposition of the lower Fifteenmile Group generated local topographic relief and wedge-shaped stratal geometries. These strata were eventually capped by platformal carbonate after the establishment of a NNW-facing stromatolitic reef complex that formed adjacent to the coeval Little Dal Group of the Mackenzie Mountains, Northwest Territories.  Correlations between specific formations within these groups are tested with carbon isotope chemostratigraphy.  As there are no known 830-780 Ma stratigraphic successions south of 62°N, the basin-forming event that accommodated the Fifteenmile and Little Dal Groups of the Ogilvie and Mackenzie Mountains and equivalent strata in the Shaler Supergroup of Victoria Island was restricted to the northwest margin of Laurentia. Therefore, this event does not represent widespread rifting of the entire western margin of Laurentia and instead we propose that these strata were accommodated in a failed rift generated by localized subsidence associated with the emplacement of the coeval Guibei (China) and Gairdner (Australia) large igneous provinces.  The northern margin of Laurentia was reactivated by renewed extension at ca. 720 Ma associated with the emplacement of the Franklin large igneous province.  Significant crustal thinning and generation of a thermally subsiding passive margin on the western margin of Laurentia may not have occurred until the late Ediacaran.RÉSUMÉLe cartographiage géologique et l’analyse stratigraphique du groupe néoprotézoïque Fifteenmile situé à l’ouest des montagnes Ogilvie du Yukon, Canada, ont révélé de grands changements latéraux de faciès à la fois pour les strates carbonatées et silicoclastiques. La mise en place des failles normales syn-sédimentaires inclinées vers le NNW au cours du dépôt du groupe Fifteenmile inférieur, a entrainé la formation locale d’un relief topographique et une prisme des strates. Ces dernières ont finalement été recouvertes de carbonates de plate-forme issus de la mise en place d’un complexe récifal stromatolitique exposé NNW contigu à la formation de même âge du groupe Little Dal des montagnes Ogilvie, en Territoires du Nord-Ouest. Les corrélations existant entre des formations spécifiques de chacun de ces groupes, sont testées grâce à la chimiostratigraphie des isotopes du carbone. Aucunes successions stratigraphiques agées de 830-780 Ma n’étant connues au sud de 62° N, la formation du bassin où sont accumulés les groupes Fifteenmile et Little Dal des massifs Ogilvie et Mackenzie, ainsi que les strates analogues du supergroupe Shaler de l’île Victoria, était restreinte à la bordure nord-ouest de la Laurentie. De ce fait, cet événement ne correspond pas au large rifting s’étendant sur l’entière bordure ouest de la Laurentie et nous proposons à la place, que ces strates ont été localisées au cours d’un rift avorté généré par la mise en place simultanée des larges provinces ignées Guibei (Chine) et Gairdner (Australie). La bordure nord de la Laurentie a été réactivée par une nouvelle phase d’extension à ca. 720 Ma associée à l’emplacement de la province ignée Franklin. L’amincissement crustal et la formation d’une marge passive thermiquement subsidente le long de la bordure ouest de la Laurentie ne se sont certainement pas produits avant l’Édiacarien supérieur

Role of Kozak sequence polymorphism of platelet glycoprotein Ibα as a risk factor for coronary artery disease and catheter interventions

AbstractOBJECTIVESWe sought to determine the role of the −5T/C polymorphism of the platelet glycoprotein (GP) Ibα as a potential risk factor for coronary artery disease (CAD) and adverse events complicating a coronary catheter intervention.BACKGROUNDThe platelet GP Ib-IX-V receptor complex plays a crucial role in arterial thrombus formation. The −5T/C polymorphism of GP Ibα is associated with increased receptor density.METHODSWe genotyped 1,000 patients with angiographically confirmed CAD, as well as 1,000 age- and gender-matched control subjects, for this polymorphism by polymerase chain reaction/restriction fragment length polymorphism. Among the patients with CAD, 269 underwent percutaneous transluminal coronary angioplasty (PTCA), 103 underwent directional coronary atherectomy and 278 underwent stenting. This intervention group was followed for a 30-day composite end point of target vessel revascularization, myocardial infarction or death.RESULTSCarriers of the −5C allele were significantly over-represented in the group of patients developing acute coronary syndromes (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, p = 0.02). The −5C allele furthermore predicted an increased risk for developing complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, p = 0.029).CONCLUSIONSThe −5C allele of the GP Ibα Kozak polymorphism may represent a risk factor in clinical conditions in which thrombosis plays an important role, such as in acute coronary syndromes and in complications after PTCA

Earthworm activity and availability for meadow birds is restricted in intensively managed grasslands

Earthworms are an important prey for the endangered meadow birds of northwest Europe. Although intensive grassland management with high manure inputs generally promotes earthworm abundance, it may reduce the effective food availability for meadow birds through desiccation of the topsoil, which causes earthworms to remain deeper in the soil. We studied the response of Red Worm Lumbricus rubellus, a detritivore, and Grey Worm Aporrectodea caliginosa, a geophage, to soil moisture profiles in the field and under experimental conditions. Surfacing earthworms were counted weekly in eight intensively managed grasslands (treated with high inputs of slurry by slit injection) with variable groundwater tables in the Netherlands. At each count, soil penetration resistance, soil moisture tension and groundwater level were measured, while air temperature and humidity were obtained from a nearby weather station. The response to variation in the vertical distribution of soil moisture was also experimentally studied in the two earthworm species. In the field, earthworms’ surfacing activity at night was negatively associated with soil moisture tension and positively by relative air humidity. Surprisingly, there was no effect of groundwater level; an important management variable in meadow bird conservation. Under experimental conditions, both L. rubellus and A. caliginosa moved to deeper soil layers (&gt;20 cm) in drier soil moisture treatments, avoiding the upper layer when moisture levels dropped below 30%. Synthesis and applications. We propose that in intensively managed grasslands with slurry application, topsoil desiccation reduces earthworm availability for meadow birds. This can be counteracted by keeping soil moisture tensions of the top soil above −15 kPa. We suggest that the late raising of groundwater tables in spring and the disturbance of the soil by slit injection of slurry increase topsoil desiccation. This decreases earthworm availability when it matters most for breeding meadow birds. Meadow bird conservation will benefit from revised manure application strategies that promote earthworm activity near or at the soil surface.</p

Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations

Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.The High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This study was supported by Wellcome Trust Strategic Award 082030 (CCG), Wellcome Trust Studentship 094446/Z/10/Z (KRB), the Oxford NIHR Biomedical Research Centre, and the MRC Human Immunology Unit (RJC). AJR and GL were supported by Wellcome Trust grant 090532/Z/ 09/Z, CCG and AE by a Major initiative Award from the Clive and Vera Ramaciotti Foundation, and AE by an NHMRC Career Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8-dendritic cells require the intramembrane endopeptidase SPPL2A

Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase-like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature B cell subsets, mirroring deficiency of the cytokine B cell-activating factor (BAFF). Accumulation of Sppl2a-deficient B cells was rescued by overexpression of the BAFF-induced survival protein B cell lymphoma 2 (BCL2) but not BAFF and was distinguished by low surface BAFF receptor and IgM and IgD B cell receptors. CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 endosomal retention and processing. The findings illuminate an important role for the final step in the CD74-MHC II pathway and a new target for protease inhibitor treatment of B cell diseases.R01 AI052127/AI/NIAID NIH HHS/United States U19 AI100627/AI/NIAID NIH HHS/United States Medical Research Council/United Kingdom Wellcome Trust/United Kingdo