Pooling Step Research Articles

Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation

Graft-versus-host disease (GVHD) is the main complication after hematopoietic stem cell transplantation (HSCT). Evidence for non-HLA gene polymorphisms as a cause of GVHD lacks consistency, which is, in part, due to methodological issues of previous candidate gene association studies and small effect size of their results, demanding for larger scale and more robust approaches. Here, non-HLA gene polymorphisms were studied on a large population (922 HSCT pairs) from a homogeneous ethnic background with selection/correction for important clinical confounders. A methodology was applied exploiting the strength of confirmatory typing in an independent study cohort. Targeting an immunogenome of 2,909 genes, an approach of pooled DNA typing of 4,321 microsatellite (MS) markers in two independent screening steps and confirmation of associated markers by further individual genotyping on combined screening cohorts was used to identify genetic susceptibility loci for moderate to severe GVHD (grades 2-4). Ten MS loci (D5S424, D6S0035i, D1S0818i, DXS0151i, D17S0219i, DXS0629i, DXS0324i, D17S0271i, D6S0330i, and D1S1335i) passed the two pooled DNA typing steps and confirmation by individual sample genotyping; two of these (D1S0818i-ELTD1 and D6S0035i-MAPK14) remain associated following application of Bonferroni's correction and multivariate analysis. The MAPK14 locus was exemplarily explored by typing of haplotype single nucleotide polymorphisms (SNP) confirming this association. This study identified several new MS susceptibility loci for GVHD that warrant further investigation. Immunogenome scanning using MS markers is a useful method for the identification of non-HLA gene loci associating with HSCT outcomes.

Modeling and analysis of pooled stepped chutes

We consider a mathematical model describing pooled stepped chutes where the transport in each pooled step is described by the shallow-water equations. Such systems can be found for example at large dams in order to release overflowing water. We analyze the mathematical conditions coupling the flows between different chutes taken from the engineering literature. For the case of two canals divided by a weir, we present the solution to the Riemann problem for any initial data in the subcritical region, moreover we give a well-posedness result. We finally report on some numerical experiments.

The Mirasol Pathogen Reduction Technology system and quality of platelets stored in platelet additive solution.

The Mirasol Pathogen Reduction Technology system for platelets and plasma uses riboflavin and UV light to introduce irreparable lesions into nucleic acids thereby inhibiting pathogen and white blood cell replication and reducing the load of infectious pathogens. The aim of the present study was to evaluate low plasma buffy coat platelet concentrates obtained from the OrbiSac System and to examine the effects on the development of platelet storage lesion during storage in platelet additive solution. Twenty buffy coat platelet concentrates were generated by pooling five individual units using the OrbiSac System. Riboflavin was added during the final pooling step, and the units were exposed to UV light. The bag was removed after the target energy of 6.24 J/mL had been delivered and 150 mL of platelet additive solution were added prior to storage. Platelet quality was assessed by pH, swirl, CD62P expression, lactate dehydrogenase, lactate production and glucose consumption rates over 7 days of storage. Buffy coat platelet concentrates generated on the OrbiSac contained an average 3.5 +/- 0.6 x 10(11) platelets at a concentration of 2976+/- 406 x 10(6)/mL. After addition of 150 mL platelet additive solution the storage concentration was 1043 +/- 148x 10(6)/mL. Values obtained for pH, lactate production and glucose consumption rates were all within the limits of previously established correlations between in vitro cell quality and in vivo performance of Pathogen Reduction Technology-treated platelets in plasma. In vitro studies show that OrbiSac-derived platelets treated with the Mirasol Pathogen Reduction Technology system preserve adequate function, which would indicate acceptable in vitro viability.

Indirect Cation Pool Method. Rapid Generation of Alkoxycarbenium Ion Pools from Thioacetals.

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Indirect Cation Pool Method. Rapid Generation of Alkoxycarbenium Ion Pools from Thioacetals

A sequential one-pot indirect cation pool method has been developed. The method involves the electrochemical generation and accumulation of ArS(ArSSAr)+ at low temperature (step 1) and the follow-up reaction with a thioacetal to generate an alkoxycarbenium ion pool (step 2), which reacts with various carbon nucleophiles (step 3). Steps 2 and 3 are extremely fast. The electrogenerated ArS(ArSSAr)+ was well-characterized by 1H NMR and CSI-MS. The alkoxycarbenium ion pool generated by the present indirect method exhibited 1H and 13C NMR spectra and thermal stability similar to those of the alkoxycarbenium ion pool generated by the direct electrochemical method.

A modelling study of hyporheic exchange pattern and the sequence, size, and spacing of stream bedforms in mountain stream networks, Oregon, USA

Studies of hyporheic exchange flows have identified physical features of channels that control exchange flow at the channel unit scale, namely slope breaks in the longitudinal profile of streams that generate subsurface head distributions. We recently completed a field study that suggested channel unit spacing in stream longitudinal profiles can be used to predict the spacing between zones of upwelling (flux of hyporheic water into the stream) and downwelling (flux of stream water into the hyporheic zone) in the beds of mountain streams. Here, we use two-dimensional groundwater flow and particle tracking models to simulate vertical and longitudinal hyporheic exchange along the longitudinal axis of stream flow in second-, third-, and fourth-order mountain stream reaches. Modelling allowed us to (1) represent visually the effect that the shape of the longitudinal profile has on the flow net beneath streambeds; (2) isolate channel unit sequence and spacing as individual factors controlling the depth that stream water penetrates the hyporheic zone and the length of upwelling and downwelling zones; (3) evaluate the degree to which the effects of regular patterns in bedform size and sequence are masked by irregularities in real streams. We simulated hyporheic exchange in two sets of idealized stream reaches and one set of observed stream reaches. Idealized profiles were constructed using regression equations relating channel form to basin area. The size and length of channel units (step size, pool length, etc.) increased with increasing stream order. Simulations of hyporheic exchange flows in these reaches suggested that upwelling lengths increased (from 2·7 m to 7·6 m), and downwelling lengths increased (from 2·9 m to 6·0 m) with increase in stream order from second to fourth order. Step spacing in the idealized reaches increased from 5·3 m to 13·7 m as stream size increased from second to fourth order. Simulated downwelling lengths increased from 4·3 m in second-order streams to 9·7 m in fourth-order streams with a POOL–RIFFLE–STEP channel unit sequence, and increased from 2·5 m to 6·1 m from second- to fourth-order streams with a POOL–STEP–RIFFLE channel unit sequence. Upwelling lengths also increased with stream order in these idealized channels. Our results suggest that channel unit spacing, size, and sequence are all important in determining hyporheic exchange patterns of upwelling and downwelling. Though irregularities in the size and spacing of bedforms caused flow nets to be much more complex in surveyed stream reaches than in idealized stream reaches, similar trends emerged relating the average geomorphic wavelength to the average hyporheic wavelength in both surveyed and idealized reaches. This article replaces a previously published version (Hydrological Processes, 19(17), 2915–2929 (2005) [DOI:10.1002/hyp.5790]. See also retraction notice DOI:10.1002/hyp.6350 Copyright © 2006 John Wiley & Sons, Ltd.

Morphological effects of local scouring in step–pool streams

AbstractStep–pool morphology characterizes many high‐gradient streams in a variety of natural settings, but formative processes and evolutionary dynamics are still poorly understood. In this paper, natural step–pool geometry is compared with steep alluvial channels where grade‐control structures such as check‐dams and bed sills make the stream profile resemble a natural stepped stream. Along these channels, local scouring due to falling jets forms plunge pools under each structure, analogous to natural steps determining the formation of pools. In order to test the hypothesis that natural pools are analogous to pools formed below grade‐control works with respect to their dimensions, shape and formative dynamics, 37 natural pools and 73 artificial pools were surveyed in 10 mountain streams of the eastern Italian Alps. Pools below grade‐control works featured a transitional zone between the scour hole and the downstream sloping bed, marked by a depositional berm. When geometric parameters such as maximum pool depth, length and step–berm distances are normalized to the jet virtual energy, no statistically significant differences were detected between natural and artificial systems. These results lend support to an upstream‐forced cascade model for step–pool formation, where the energy of falling jets controls the geometry of the pools, and is therefore regarded as the most important scaling‐independent variable. Copyright © 2005 John Wiley & Sons, Ltd.

Retracted and replaced: A modelling study of hyporheic exchange pattern and the sequence, size, and spacing of stream bedforms in mountain stream networks, Oregon, USA

AbstractThis article has been retracted and replaced. See Retraction and Replacement Notice DOI: 10.1002/hyp.6350Studies of hyporheic exchange flows have identified physical features of channels that control exchange flow at the channel unit scale, namely slope breaks in the longitudinal profile of streams that generate subsurface head distributions. We recently completed a field study that suggested channel unit spacing in stream longitudinal profiles can be used to predict the spacing between zones of upwelling (flux of hyporheic water into the stream) and downwelling (flux of stream water into the hyporheic zone) in the beds of mountain streams. Here, we use two‐dimensional groundwater flow and particle tracking models to simulate vertical and longitudinal hyporheic exchange along the longitudinal axis of stream flow in second‐, third‐, and fourth‐order mountain stream reaches. Modelling allowed us to (1) represent visually the effect that the shape of the longitudinal profile has on the flow net beneath streambeds; (2) isolate channel unit sequence and spacing as individual factors controlling the depth that stream water penetrates the hyporheic zone and the length of upwelling and downwelling zones; (3) evaluate the degree to which the effects of regular patterns in bedform size and sequence are masked by irregularities in real streams. We simulated hyporheic exchange in two sets of idealized stream reaches and one set of observed stream reaches. Idealized profiles were constructed using regression equations relating channel form to basin area. The size and length of channel units (step size, pool length, etc.) increased with increasing stream order. Simulations of hyporheic exchange flows in these reaches suggested that upwelling lengths increased (from 2·7 m to 7·6 m), and downwelling lengths increased (from 2·9 m to 6·0 m) with increase in stream order from second to fourth order. Step spacing in the idealized reaches increased from 5·3 m to 13·7 m as stream size increased from second to fourth order. Simulated upwelling lengths increased from 4·3 m in second‐order streams to 9·7 m in fourth‐order streams with a POOL–RIFFLE–STEP channel unit sequence, and increased from 2·5 m to 6·1 m from second‐ to fourth‐order streams with a POOL–STEP–RIFFLE channel unit sequence. Downwelling lengths also increased with stream order in these idealized channels. Our results suggest that channel unit spacing, size, and sequence are all important in determining hyporheic exchange patterns of upwelling and downwelling. Though irregularities in the size and spacing of bedforms caused flow nets to be much more complex in surveyed stream reaches than in idealized stream reaches, similar trends emerged relating the average geomorphic wavelength to the average hyporheic wavelength in both surveyed and idealized reaches. Copyright © 2005 John Wiley & Sons, Ltd.

Accuracy of Service Cost Allocations

Abstract Within most multiple cost pool allocation systems, the direct and step methods are commonly used to allocate service activity costs to production activities. But because they ignore service activity interactions, these methods can produce significant allocation errors, inaccurate product costs, and poor operating decisions. This paper provides data on allocation errors for 54,000 computer generated firms across a variety of service environments. The results show that allocation errors can vary a great deal, can be quite large, and are dependent on specific measurable service activity characteristics. The data can assist individual managers in determining if a switch to the theoretically correct reciprocal allocation method is justified, thus helping to further improve existing cost allocation systems.

Combinatorial modification of natural products: Preparation of unencoded and encoded libraries of Rauwolfia alkaloids

We report the preparation of combinatorial libraries which consist of derivatives of the stereoisomeric alkaloids yohimbine and rauwolscine—members of the Rauwolfia genus. The chemistry was performed on solid support using the divide-and-pool method, and involved the derivatization of the E-ring carboxylates and hydroxyls of these alkaloids with 36 amino acids and 22 carboxylic acids, respectively, to afford 792 bifunctionalized derivatives. The rauwolscine library was prepared using an encoding strategy in which the identity of each incorporated amino acid was recorded by cosynthesizing chemically inert tags prior to the pooling step. The general strategy for library synthesis exploits existing functionality present on the natural products, and should be applicable to other families of secondary metabolites.