Particle physics experiments at JLC

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Process time and cost savings achieved through automation and islands of integration in existing facilities.

For most biopharmaceutical manufacturers the cost, time and quality improvements offered by adopting continuous manufacturing operations is, as with any new technology, inhibited by the research and validation costs associated with early adoption. Additional effort is needed to validate the novel technology in-house. There are simple changes that can be made in disposable biomanufacturing , which are necessary for the eventual adoption of full continuous operations, and yet have benefits now. These step changes are shown by economic & scheduling models to offer direct cost savings and improved facility throughput. A road map of these step-wise improvements is provided that leads to fully continuous processing, but minimises the technological risk. The first step change is a wider adoption of process automation. Automation eliminates operator error, reduces contamination risk and improves batch-batch quality. The higher direct cost of the operating system is offset by improved utilisation of facilities and fewer batch failures. The next step is to automate the operation of a combination of relatively simple units, such as dead-end filtration, flow-through adsorption, virus filtration, in-line concentration. The aim is to minimise hold steps, QC testing, processing time and maximise the use of disposable manifolds. Incorporating automated integrity testing into the operation further enhances the processing. Examples of such operating systems will be described, either as standard items that require configuration or as customised options, to illustrate the economic risk/benefit analysis. Additionally, the islands of continuous operation can be extended - for example, perfusion bioreactor operation, capture chromatography integrated with low pH virus inactivation, or flowthrough polishing chromatography integrated with virus filtration and diafiltration. Integrated chromatography and virus inactivation will be reported with the main advantages seen from contracting the process from two working shifts to one and yield increase when producing biotherapeutics sensitive to low pH or sensitive to changes in pH through the isoelectric point. How each step change compares to envisioned full continuous processing depends on the operating requirements of the facility, with the key variables being the number of biopharmaceutical products manufactured, number of batches per product, titre, bioreactor volume, changeover time and QA release time. As with all facility and operational changes, the value of the benefits discussed depends on the demand being placed on the facilities by products in clinical phases or commercial manufacturin

Cell-based therapies for stroke : promising solution or dead end?

The introduction of recanalization procedures has revolutionized acute stroke management, although the narrow time window, strict eligibility criteria and logistical limitations still exclude the majority of patients from treatment. In addition, residual deficits are present in many patients who undergo therapy, preventing their return to premorbid status. Hence, there is a strong need for novel, and ideally complementary, approaches to stroke management. In preclinical experiments, cell-based treatments have demonstrated beneficial effects in the subacute and chronic stages following stroke [1; 2; 3] and therefore are considered a promising option to supplement current clinical practice. At the same time, great progress has been made in developing clinically feasible delivery and monitoring protocols [4]. However, efficacy results initially reported in clinical studies fell short of expectations [5] raising concerns that cell treatment might eventually share the ‘dead end fate’ of many previous experimental stroke therapies. This Research Topic reviews some of the latest and most innovative studies to summarize the state of the art in translational cell treatments for stroke

Detection and molecular characterisation of Cryptosporidium parvum in British European hedgehogs (Erinaceus europaeus)

Surveillance was conducted for the occurrence of protozoan parasites of the genus Cryptosporidium in European hedgehogs (Erinaceus europaeus) in Great Britain. In total, 108 voided faecal samples were collected from hedgehogs newly admitted to eight wildlife casualty treatment and rehabilitation centres. Terminal large intestinal (LI) contents from three hedgehog carcasses were also analysed. Information on host and location variables, including faecal appearance, body weight, and apparent health status, was compiled. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, revealed an 8% (9/111) occurrence of Cryptosporidium parvum in faeces or LI contents, with no significant association between the host or location variables and infection. Archived small intestinal (SI) tissue from a hedgehog with histological evidence of cryptosporidiosis was also positive for C. parvum by PCR and sequence analysis of the 18S rRNA gene. No other Cryptosporidium species were detected. PCR and sequencing of the glycoprotein 60 gene identified three known zoonotic C. parvum subtypes not previously found in hedgehogs: IIdA17G1 (n=4), IIdA19G1 (n=1) and IIdA24G1 (n=1). These subtypes are also known to infect livestock. Another faecal sample contained C. parvum IIcA5G3j which has been found previously in hedgehogs, and for which there is one published report in a human, but is not known to affect livestock. The presence of zoonotic subtypes of C. parvum in British hedgehogs highlights a potential public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in hedgehogs

Io'S Atmospheric Freeze-Out Dynamics In The Presence Of A Non-Condensable Species

One dimensional direct simulation Monte Carlo (DSMC) simulations are used to examine the effect of a trace non-condensable species on the freeze-out dynamics of Io's sulfur dioxide sublimation atmosphere during eclipse and egress. Due to finite ballistic times, essentially no collapse occurs during the first 10 minutes of eclipse at altitudes above similar to 100 km, and hence immediately after ingress auroral emission morphology above 100 km should resemble that of the immediate pre-eclipse state. In the absence of a non-condensable species the sublimation SO2 atmosphere will freeze-out (collapse) during eclipse as the surface temperature drops. However, rapid collapse is prevented by the presence of even a small amount of a perfect non-condensable species due to the formation of a static diffusion layer several mean free paths thick near the surface. The higher the non-condensable mole fraction, the longer the collapse time. The effect of a weakly condensable gas species (non-zero sticking/reaction coefficient) was examined since real gas species may not be perfectly non-condensable at realistic surface temperatures. It is found that even a small sticking coefficient dramatically reduces the effect of the diffusion layer on the dynamics. If the sticking coefficient of the non-condensable exceeds similar to 0.25 the collapse dynamics are effectively the same as if there was no non-condensable present. This sensitivity results because the loss of non-condensable to the surface reduces the effective diffusion layer size and the formation of an effective diffusion layer requires that the layer be stationary which does not occur if the surface is a sink. As the surface temperature increases during egress from eclipse the sublimating SO2 gas pushes the non-condensable diffusion layer up to higher altitudes once it becomes dense enough to be collisional. This vertical species stratification should alter the auroral emissions after egress.Aerospace Engineerin

Consistent Factorization of Jet Observables in Exclusive Multijet Cross-Sections

We demonstrate the consistency at the next-to-leading-logarithmic (NLL) level of a factorization theorem based on Soft-Collinear Effective Theory (SCET) for jet shapes in e+e- collisions. We consider measuring jet observables in exclusive multijet final states defined with cone and k_T-type jet algorithms. Consistency of the factorization theorem requires that the renormalization group evolution of hard, jet, and soft functions is such that the physical cross-section is independent of the factorization scale mu. The anomalous dimensions of the various factorized pieces, however, depend on the color representation of jets, choice of jet observable, the number of jets whose shapes are measured, and the jet algorithm, making it highly nontrivial to satisfy the consistency condition. We demonstrate the intricate cancellations between anomalous dimensions that occur at the NLL level, so that, up to power corrections that we identify, our factorization of the jet shape distributions is consistent for any number of quark and gluon jets, for any number of jets whose shapes are measured or unmeasured, for any angular size R of the jets, and for any of the algorithms we consider. Corrections to these results are suppressed by the SCET expansion parameter lambda (the ratio of soft to collinear or collinear to hard scales) and in the jet separation measure 1/t^2 = tan^2(R/2)/tan^2(psi/2), where psi is the angular separation between jets. Our results can be used to calculate a wide variety of jet observables in multijet final states to NLL accuracy.Comment: 8 pages, 1 figure, uses elsarticle.cls; v2: minor edits, added reference

Jet Substructure Without Trees

We present an alternative approach to identifying and characterizing jet substructure. An angular correlation function is introduced that can be used to extract angular and mass scales within a jet without reference to a clustering algorithm. This procedure gives rise to a number of useful jet observables. As an application, we construct a top quark tagging algorithm that is competitive with existing methods.Comment: 22 pages, 16 figures, version accepted by JHE

Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects

Purpose: To investigate macular ganglion cell–inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs. Methods: 112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs. Result: 47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect. Conclusion: The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect