Cell biology:Collagen secretion explained

Cells package proteins into vesicles for secretion to the extracellular milieu. A study shows that an enzyme modifies the packaging machinery to encapsulate unusually large proteins such as collagen

Identification and classification of host cell proteins during biopharmaceutical process development

As significant improvements in volumetric antibody productivity have been achieved by advances in upstream processing over the last decade, and harvest material has become progressively more difficult to recover with these intensified upstream operations, the segregation of upstream and downstream processing has remained largely unchanged. By integrating upstream and downstream process development, product purification issues are given consideration during the optimization of upstream operating conditions, which mitigates the need for extensive and expensive clearance strategies downstream. To investigate the impact of cell culture duration on critical quality attributes, CHO-expressed IgG1 was cultivated in two 2 L bioreactors with samples taken on days 8, 10, 13, 15, and 17. The material was centrifuged, filtered and protein A purified on a 1 ml HiTrap column. Host cell protein (HCP) identification by mass spectrometry (MS) was applied to this system to provide insights into cellular behavior and HCP carryover during protein A purification. It was shown that as cultivation progressed from day 8 to 17 and antibody titer increased, product quality declined due to an increase in post-protein A HCPs (from 72 to 475 peptides detected by MS) and a decrease in product monomer percentage (from 98% to 95.5%). Additionally, the MS data revealed an increase in the abundance of several classes of post-protein A HCPs (e.g., stress response proteins and indicators of cell age), particularly on days 15 and 17 of culture, which were associated with significant increases in total overall HCP levels. This provides new insight into the specific types of HCPs that are retained during mAb purification and may be used to aid process development strategies

Differentiating patterns of violence in the family

The feasibility and prevalence of Reciprocal, Hierarchical and Paternal patterns of family aggression hypothesised by Dixon and Browne (2003) were explored within a sample of maltreating families. The psychological reports of 67 families referred to services for alleged child maltreatment that evidenced concurrent physical intimate partner violence and child maltreatment were investigated. Of these, 29 (43.3%) cases were characterised by hierarchical; 28 (41.8%) Reciprocal and 10 (14.9%) Paternal patterns. Significant differences in the form of child maltreatment perpetrated by mothers and fathers and parent dyads living in different patterns were found. In Hierarchical sub-patterns, fathers were significantly more likely to have been convicted for a violent and/or sexual offence than mothers and were significantly less likely to be biologically related to the child. The findings demonstrate the existence of the different patterns in a sample of families involved in the Child Care Protection process in England and Wales, supporting the utility of a holistic approach to understanding aggression in the family

Molecular physics of a polymer engineering instability: Experiments and computation

Entangled polymer melts exhibit a variety of flow instabilities that limit production rates in industrial applications. We present both experimental and computational findings, using flow of monodisperse linear polystyrenes in a contraction-expansion geometry, which illustrate the formation and development of one such flow instability. This viscoelastic disturbance is observed at the slit outlet and subsequently produces large-scale fluid motions upstream. A numerical linear stability study using the molecular structure based Rolie-Poly model confirms the instability and identifies important parameters within the model, which gives physical insight into the underlying mechanism. Chain stretch was found to play a critical role in the instability mechanism, which partially explains the effectiveness of introducing a low-molecular weight tail into a polymer blend to increase its processability

The Vacuum in Light-Cone Field Theory

This is an overview of the problem of the vacuum in light-cone field theory, stressing its close connection to other puzzles regarding light-cone quantization. I explain the sense in which the light-cone vacuum is ``trivial,'' and describe a way of setting up a quantum field theory on null planes so that it is equivalent to the usual equal-time formulation. This construction is quite helpful in resolving the puzzling aspects of the light-cone formalism. It furthermore allows the extraction of effective Hamiltonians that incorporate vacuum physics, but that act in a Hilbert space in which the vacuum state is simple. The discussion is fairly informal, and focuses mainly on the conceptual issues. [Talk presented at {\sc Orbis Scientiae 1996}, Miami Beach, FL, January 25--28, 1996. To appear in the proceedings.]Comment: 20 pages, RevTeX, 4 Postscript figures. Minor typos correcte

Similarity solutions for unsteady shear-stress-driven flow of Newtonian and power-law fluids : slender rivulets and dry patches

Unsteady flow of a thin film of a Newtonian fluid or a non-Newtonian power-law fluid with power-law index N driven by a constant shear stress applied at the free surface, on a plane inclined at an angle α to the horizontal, is considered. Unsteady similarity solutions representing flow of slender rivulets and flow around slender dry patches are obtained. Specifically, solutions are obtained for converging sessile rivulets (0 < α < π/2) and converging dry patches in a pendent film (π/2 < α < π), as well as for diverging pendent rivulets and diverging dry patches in a sessile film. These solutions predict that at any time t, the rivulet and dry patch widen or narrow according to |x|3/2, and the film thickens or thins according to |x|, where x denotes distance down the plane, and that at any station x, the rivulet and dry patch widen or narrow like |t|−1, and the film thickens or thins like |t|−1, independent of N

Effectiveness of a simple lymphoedema treatment regimen in podoconiosis management in southern Ethiopia: one year follow-up

Background: Podoconiosis is a non-filarial elephantiasis caused by long-term barefoot exposure to volcanic soils in endemic areas. Irritant silicate particles penetrate the skin, causing a progressive, debilitating lymphoedema of the lower leg, often starting in the second decade of life. A simple patient-led treatment approach appropriate for resource poor settings has been developed, comprising (1) education on aetiology and prevention of podoconiosis, (2) foot hygiene (daily washing with soap, water and an antiseptic), (3) the regular use of emollient, (4) elevation of the limb at night, and (5) emphasis on the consistent use of shoes and socks. Methodology/Principal Findings: We did a 12-month, non-comparative, longitudinal evaluation of 33 patients newly presenting to one clinic site of a non-government organization (the Mossy Foot Treatment & Prevention Association, MFTPA) in southern Ethiopia. Outcome measures used for the monitoring of disease progress were (1) the clinical staging system for podoconiosis, and (2) the Amharic Dermatology Life Quality Index (DLQI), both of which have been recently validated for use in this setting. Digital photographs were also taken at each visit. Twenty-seven patients completed follow up. Characteristics of patients completing follow-up were not significantly different to those not. Mean clinical stage and lower leg circumference decreased significantly (mean difference -0.67 (95% CI -0.38 to -0.96) and -2.00 (95% CI -1.26 to -2.74), respectively, p<0.001 for both changes). Mean DLQI diminished from 21 (out of a maximum of 30) to 6 (p<0.001). There was a non-significant change in proportion of patients with mossy lesions (p = 0.375). Conclusions/Significance: This simple, resource-appropriate regimen has a considerable impact both on clinical progression and self-reported quality of life of affected individuals. The regimen appears ideal for scaling up to other endemic regions in Ethiopia and internationally. We recommend that further research in the area include analysis of cost-effectiveness of the regimen

Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species

Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range

Inattentive Consumers in Markets for Services

In an experiment on markets for services, we find that consumers are likely to stick to default tariffs and achieve suboptimal outcomes. We find that inattention to the task of choosing a better tariff is likely to be a substantial problem in addition to any task and tariff complexity effect. The institutional setup on which we primarily model our experiment is the UK electricity and gas markets, and our conclusion is that the new measures by the UK regulator Ofgem to improve consumer outcomes are likely to be of limited impact