Outsourcing Strategies – Future Trends?

Outsourcing production of bulk active ingredient manufacture has recently been a growing trend amongst many pharmaceutical companies. To consider how the trend might develop, one needs to consider the factors that have driven outsourcing and the critical role of the custom synthesis industry in delivering expectations

A Basin Analysis of the Wabigoon Area of Lake Agassiz, a Quaternary Clay Basin in Northwerstern Ontario

Information from a wide range of sources is integrated in a basin analysis of the Wabigoon Basin, a Quaternary clay basin located on the Canadian Shield in northwestern Ontario. The basin sediments were deposited between 10.9 ka and 9.5 ka, along the margin of the Rainy Lobe of the Laurentide Ice Sheet, which formed the northern boundary of proglacial Lake Agassiz. The basin architecture is dominated by four major elements: end moraines, eskers, kames and a clay plain, all of which overlie irregular bedrock topography. End moraines, eskers and kames are composed mainly of a fining upward sequence of gravels and sands. The geometry of these sedimentary units, and their sedimentary structures indicates they were deposited mainly by high and low-density turbidity currents, on ice-marginal subaqueous outwash fans. Eskers contain a core of coarse gravel and sand deposited within subglacial meltwater conduits, overlain by subaqueous fan sediments deposited at the conduit mouth. Esker ridges were formed during conduit filling events and flanking deposits were formed when a conduit remained in use during ice-marginal retreat. Where conduits were shortlived, isolated subaqueous fans (kames) were formed. A depositional model is proposed which relates moraine formation to catastrophic releases of subglacial meltwater and sediment simultaneously along the entire margin of the Rainy Lobe. The clay plain forms a broad blanket of fine-grained, rhythmically-bedded sediment which obscures bedrock topography, and often buries esker and kame deposits. Seismic profiles and overburden drilling reveal deep (50-70 m) bedrock lows beneath the clay plain. These lows, oriented sub-parallel to the ice margin, acted as sediment traps, and were infilled by the deposits of underflows generated at the ice margin.Les renseignements tirés d'un grand nombre de sources sont intégrés en vue de l'analyse du bassin de Wabigoon, situé sur le Bouclier canadien. Les sédiments qui le composent ont été déposés entre 10,9 et 9,5 ka, le long de la marge du lobe Rainy de l'Inlandsis laurentidien, qui formait la limite nord du Lac Agassiz. Les quatre formes principales qu'on y trouve sont les moraines frontales, les eskers, les kames et une plaine argileuse; ces formes recouvrent le relief irrégulier du substratum. Les moraines frontales, les eskers et les kames sont surtout composés d'une séquence de graviers et de sables s'affinant vers le haut. La géométrie de ces unités sédimentaires et leur structure montrent qu'elles ont en grande partie été déposées sur des épandages fluvioglaciaires sous-aquatiques de marge glaciaire par des courants de turbidité de haute et de basse densité. Les eskers renferment un noyau de gravier et de sable grossier déposés à l'intérieur des chenaux de fonte sous-glaciaires, recouverts par les sédiments de cône sous-aquatique déposés à l'embouchure des chenaux. Les crêtes d'eskers ont été édifiées en même temps que s'effectuait le remplissage des chenaux et les dépôts latéraux ont été formés alors qu'un chenal demeurait actif pendant le retrait glaciaire. Là où l'activité a été de courte durée, des cônes sous-aquatiques isolés (kames) se sont formés. On propose ici un modèle de mise en place des sédiments qui lie la formation des moraines à des écoulements sous-glaciaires catastrophiques et simultanés d'eau de fonte et de sédiments tout le long de la marge du lobe Rainy. La plaine argileuse forme une couverture étendue de sédiments à grains fins, à stratification rythmique, qui cache le relief du substratum et enfouit souvent les eskers et les kames. Les profils sismiques et les forages dans les dépôts meubles révèlent des dépressions profondes (50-70 m) dans le substratum sous Ia plaine argileuse.Informationen aus einer Vielfalt von Quellen sind fur die Analyse des Wabigoon-Beckens vereinigt, ein Quaternàr-Lehm-Becken, das sich auf dem kanadischen Schild befindet. Die Beckensedimente wurden zwischen 10.9 ka und 9.5 ka abgela-gert, entlang dem Rand der Rainy-Lobe der laurentidischen Eisdecke, welche die nôrdli-che Grenzlinie des proglazialen Agassiz-Sees bildete. Die Becken-Architektur wird von vier Hauptelementen beherrscht: Endmoràne, Eskers, Kames und eine Lehmebene. Die drei ersteren bestehen vor allem aus einer nach oben hin feiner werdenden Sequenz von Kies und Sand. Die Géométrie dieser Sediment-Einheiten und ihre Sediment-Strukturen zeigen, daB sie haupt-àchlich durch Dichtigkeitsstrômungen mit hoher und niedriger Dichte abgelagert wurden auf Unterwasser-Eisrand-Schwemmfàchern. Die Eskers enthalten einen Kern von grobem Kies und Sand, der innerhalb subgla-zialer Schmelzwasserkanàle abgelagert wurde, ùberlagert von Unterwasser-Fàcher-sedimenten, die an der Mùndung der Kanàle abgelagert wurden. Die Esker-Rùcken wurden wàhrend der Fùllung der Kanàle gebildet und seitliche Ablagerungen wurden gebildet, wenn ein Kanal wàhrend des Rùckzugs des Eisrands aktiv blieb. Wo Kanàle kurzlebig waren, bildeten sich isolierte Unterwasser-Fàcher (Kames). Ein Ablagerungsmodell wird vorgeschlagen, das die Bildung der Morâne mit katastrophenartigem gleichzeiti-gem Freiwerden von subglazialem Schmelz-wasser und Sedimenten entlang des ganzen RandsderRainy-Lobeverbindet. DieLehmebene bildet eine breite Decke von feinkôrnigem, rhythmisch gelagertem Sediment, welches die Topographie des anstehenden Gesteins verdeckt und hâufig Esker- und Kame-Ablagerungen ùberlagert. Die seismischen Profile und Bohrungen in den lockeren Ablagerungen lassen tiefe Niederungen (50-70 m) unter der Lehmebene im anstehenden Gestein erkennen

The Beagle 2 environmental sensors: intended measurements and scientific goals

The Beagle 2 lander, due for arrival on Mars in December 2003, carries an Environmental Sensors Suite to monitor the local meteorology and carry out simple dust and oxidant measurements. The suite is described, and the scientific goals are discussed

Origins and Structure of Spike-Type Rotating Stall

In this paper, we describe the structures that produce a spike-type route to rotating stall and explain the physical mechanism for their formation. The descriptions and explanations are based on numerical simulations, complemented and corroborated by experiments. It is found that spikes are caused by a separation at the leading edge due to high incidence. The separation gives rise to shedding of vorticity from the leading edge and the consequent formation of vortices that span between the suction surface and the casing. As seen in the rotor frame of reference, near the casing the vortex convects toward the pressure surface of the adjacent blade. The approach of the vortex to the adjacent blade triggers a separation on that blade so the structure propagates. The above sequence of events constitutes a spike. The computed structure of the spike is shown to be consistent with rotor leading edge pressure measurements from the casing of several compressors: the centre of the vortex is responsible for a pressure drop and the partially blocked passages associated with leading edge separations produce a pressure rise. The simulations show leading edge separation and shed vortices over a range of tip clearances including zero. The implication, in accord with recent experimental findings, is that they are not part of the tip clearance vortex. Although the computations always show high incidence to be the cause of the spike, the conditions that give rise to this incidence (e.g., blockage from a corner separation or the tip leakage jet from the adjacent blade) do depend on the details of the compressor

Identification of the Beagle 2 lander on Mars

The 2003 Beagle 2 Mars lander has been identified in Isidis Planitia at 90.43° E, 11.53° N, close to the predicted target of 90.50° E, 11.53° N. Beagle 2 was an exobiology lander designed to look for isotopic and compositional signs of life on Mars, as part of the European Space Agency Mars Express (MEX) mission. The 2004 recalculation of the original landing ellipse from a 3-sigma major axis from 174 km to 57 km, and the acquisition of Mars Reconnaissance Orbiter High Resolution Imaging Science Experiment (HiRISE) imagery at 30 cm per pixel across the target region, led to the initial identification of the lander in 2014. Following this, more HiRISE images, giving a total of 15, including red and blue-green colours, were obtained over the area of interest and searched, which allowed sub-pixel imaging using super high-resolution techniques. The size (approx. 1.5 m), distinctive multilobed shape, high reflectivity relative to the local terrain, specular reflections, and location close to the centre of the planned landing ellipse led to the identification of the Beagle 2 lander. The shape of the imaged lander, although to some extent masked by the specular reflections in the various images, is consistent with deployment of the lander lid and then some or all solar panels. Failure to fully deploy the panels-which may have been caused by damage during landing-would have prohibited communication between the lander and MEX and commencement of science operations. This implies that the main part of the entry, descent and landing sequence, the ejection from MEX, atmospheric entry and parachute deployment, and landing worked as planned with perhaps only the final full panel deployment failing

Effects of stenting on blood flow in a coronary artery network model

Abstract: The effect of stenting on blood flow is investigated using a model of the coronary artery network. The parameters in a generic non-linear pressure-radius relationship are varied in the stented region to model the increase in stiffness of the vessel due to the presence of the stent. A computationally efficient form of the Navier-Stokes equation is solved using a Lax-Wendroff finite difference method. Pressure, vessel radius and flow velocity are computed along the vessel segments. Results show negative pressure gradients at the ends of the stent and increased velocity through the middle of the stented region. Changes in local flow patterns and vessel wall stresses due to the presence of the stent have been shown to be important in restenosis of vessels. Local and global pressure gradients affect local flow patterns and vessel wall stresses, and therefore may be an important factor associated with restenosis. The model presented in this study can be easily extended to solve flows for stented vessels in a full, anatomically realistic coronary network. The framework to allow for the effects of the deformation of the myocardium on the coronary network is also in place

Malignant Pancreatic Polypeptide Secreting Tumour of Islet Cells: A Case for Aggressive Surgical Palliation

A case of a malignant pancreatic polypeptide secreting tumour is reported. The tumour was metastatic at presentation at which time it was excised. Pancreatic duct obstruction occurred 3 years after excision causing severe pain on eating. Major palliative surgery, in the form of a pancreatico-jejunostomy, cured the severe symptoms. The patient survives, largely symptom free, over six years after original excision. This case illustrates the need for aggressive management of symptoms in tumours in which long term survival is possible despite locally advanced or metastatic disease

Succession of physiological stages hallmarks the transcriptomic response of the fungus Aspergillus niger to lignocellulose.

BackgroundUnderstanding how fungi degrade lignocellulose is a cornerstone of improving renewables-based biotechnology, in particular for the production of hydrolytic enzymes. Considerable progress has been made in investigating fungal degradation during time-points where CAZyme expression peaks. However, a robust understanding of the fungal survival strategies over its life time on lignocellulose is thereby missed. Here we aimed to uncover the physiological responses of the biotechnological workhorse and enzyme producer Aspergillus niger over its life time to six substrates important for biofuel production.ResultsWe analysed the response of A. niger to the feedstock Miscanthus and compared it with our previous study on wheat straw, alone or in combination with hydrothermal or ionic liquid feedstock pretreatments. Conserved (substrate-independent) metabolic responses as well as those affected by pretreatment and feedstock were identified via multivariate analysis of genome-wide transcriptomics combined with targeted transcript and protein analyses and mapping to a metabolic model. Initial exposure to all substrates increased fatty acid beta-oxidation and lipid metabolism transcripts. In a strain carrying a deletion of the ortholog of the Aspergillus nidulans fatty acid beta-oxidation transcriptional regulator farA, there was a reduction in expression of selected lignocellulose degradative CAZyme-encoding genes suggesting that beta-oxidation contributes to adaptation to lignocellulose. Mannan degradation expression was wheat straw feedstock-dependent and pectin degradation was higher on the untreated substrates. In the later life stages, known and novel secondary metabolite gene clusters were activated, which are of high interest due to their potential to synthesize bioactive compounds.ConclusionIn this study, which includes the first transcriptional response of Aspergilli to Miscanthus, we highlighted that life time as well as substrate composition and structure (via variations in pretreatment and feedstock) influence the fungal responses to lignocellulose. We also demonstrated that the fungal response contains physiological stages that are conserved across substrates and are typically found outside of the conditions with high CAZyme expression, as exemplified by the stages that are dominated by lipid and secondary metabolism

Mass deworming programmes in middle childhood and adolescence

Soil-transmitted helminthes (STH) deworming programs remain among the largest public health programs in low- and lower-middle-income countries as measured by coverage. The actual scale of these programs remains unknown but substantial, with more than 1 billion donated doses of medicines effective against STHs delivered by formal programs and supplemented by widespread self-treatment and unprogrammed activities. STH infection declines worldwide likely reflect the influence of improved hygiene and sanitation associated with global declines in poverty, but it also reflects control efforts during the twentieth century that have largely eliminated STHs as a public health problem in previously endemic areas of North America (Mexico and the United States), Japan, Korea, and upper- middle-income countries throughout southern and eastern Asia. Much of the treatment targets delivery through schools and targets school-age children. STH infection associates with clinical and developmental outcomes that prove largely reversible by treatment. Both historical and contemporary trials of targeted treatment of infected individuals have also demonstrated benefit from treatment