Human VPS34 is required for internal vesicle formation within multivesicular endosomes

After internalization from the plasma membrane, activated EGF receptors (EGFRs) are delivered to multivesicular bodies (MVBs). Within MVBs, EGFRs are removed from the perimeter membrane to internal vesicles, thereby being sorted from transferrin receptors, which recycle back to the plasma membrane. The phosphatidylinositol (PI) 3′-kinase inhibitor, wortmannin, inhibits internal vesicle formation within MVBs and causes EGFRs to remain in clusters on the perimeter membrane. Microinjection of isotype-specific inhibitory antibodies demonstrates that the PI 3′-kinase required for internal vesicle formation is hVPS34. In the presence of wortmannin, EGFRs continue to be delivered to lysosomes, showing that their removal from the recycling pathway and their delivery to lysosomes does not depend on inward vesiculation. We showed previously that tyrosine kinase-negative EGFRs fail to accumulate on internal vesicles of MVBs but are recycled rather than delivered to lysosomes. Therefore, we conclude that selection of EGFRs for inclusion on internal vesicles requires tyrosine kinase but not PI 3′-kinase activity, whereas vesicle formation requires PI 3′-kinase activity. Finally, in wortmannin-treated cells there is increased EGF-stimulated tyrosine phosphorylation when EGFRs are retained on the perimeter membrane of MVBs. Therefore, we suggest that inward vesiculation is involved directly with attenuating signal transduction

Assessment of the applicability of failure frequency models for dense phase carbon dioxide pipelines

In Carbon Capture, Usage and Storage (CCUS) schemes, Carbon Dioxide (CO2) is captured from large scale industrial emitters and transported to geological sites for storage. The most efficient method for the transportation of CO2 is via pipeline in the dense phase. CO2 is a hazardous substance which, in the unlikely event of an accidental release, could cause people harm. To correspond with United Kingdom (UK) safety legislation, the design and construction of proposed CO2 pipelines requires compliance with recognised pipeline codes. The UK code PD-8010-1 defines the separation distance between a hazardous pipeline and a nearby population as the minimum distance to occupied buildings using a substance factor. The value of the substance factor should be supported by the results of a Quantitative Risk Assessment (QRA) approach to ensure the safe design, construction and operation of a dense phase CO2 pipeline. Failure frequency models are a major part of this QRA approach and the focus of this paper is a review of existing oil and gas pipeline third-party external interference failure frequency models to assess whether they could be applied to dense phase CO2 pipelines. It was found that the high design pressure requirement for a dense phase CO2 pipeline typically necessitates the use of high wall thickness linepipe in pipeline construction; and that the wall thickness of typical dense phase CO2 pipelines is beyond the known range of applicability for the pipeline failure equations used within existing failure frequency models. Furthermore, even though third party external interference failure frequency is not sensitive to the product that a pipeline transports, there is however a limitation to the application of existing UK fault databases with to onshore CO2 pipelines as there are currently no dense phase CO2 pipelines operating in the UK. Further work needs to be conducted to confirm the most appropriate approach for calculating failure frequency for dense phase CO2 pipelines, and it is recommended that a new failure frequency model suitable for dense phase CO2 pipelines is developed that can be readily updated to the latest version of the fault database

Semiconductor disk lasers: the future's bright; the colour's flexible

Presentation describing semiconductor disk lasers, their use and how they work

Blue-enriched Lighting for Older People Living in Care Homes: Effect on Activity, Actigraphic Sleep, Mood and Alertness

Objective: Environmental (little outdoor light; low indoor lighting) and age-related physiological factors (reduced light transmission through the ocular lens, reduced mobility) contribute to a light-deprived environment for older people living in care homes. Methods: This study investigates the effect of increasing indoor light levels with blue-enriched white lighting on objective (rest-activity rhythms, performance) and self-reported (mood, sleep, alertness) measures in older people. Eighty residents (69 female), aged 86 ± 8 yrs (mean ± SD), participated (MMSE 19 ± 6). Overhead fluorescent lighting was installed in communal rooms (n=20) of seven care homes. Four weeks of blue-enriched white lighting (17000 K ≅ 900 lux) were compared with four weeks of control white lighting (4000 K ≅ 200 lux), separated by three weeks wash-out. Participants completed validated mood and sleep questionnaires, psychomotor vigilance task (PVT) and wore activity and light monitors (AWL). Rest-activity rhythms were assessed by cosinor, non-parametric circadian rhythm (NPCRA) and actigraphic sleep analysis. Blue-enriched (17000 K) light increased wake time and activity during sleep decreasing actual sleep time, sleep percentage and sleep efficiency (p < 0.05) (actigraphic sleep). Compared to 4000 K lighting, blue-enriched 17000 K lighting significantly (p < 0.05) advanced the timing of participants’ rest-activity rhythm (cosinor), increased daytime and night-time activity (NPCRA), reduced subjective anxiety (HADA) and sleep quality (PSQI). There was no difference between the two light conditions in daytime alertness and performance (PVT). Conclusion: Blue-enriched lighting produced some positive (increased daytime activity, reduced anxiety) and negative (increased night-time activity, reduced sleep efficiency and quality) effects in older people

The effect of lamb carcase weight and GR depth on the production of value-added cuts – A short communication

Times for the progressive breakdown of 95 lamb carcases were recorded to determine the impact of carcase weight and GR tissue depth on the time and therefore cost to produce value added retail cuts. Further analysis also assessed the potential to use these carcase traits as predictors of fabrication times. Regression modeling demonstrated there was a limited ability to predict the difference in time to fabricate mid value-added (R2 = 0.18) and extreme value-added (R2 = 0.12) cuts compared to traditional cuts, suggesting that other factors need to be considered. However, this study highlighted the significant increases in time required to fabricate more value-added cuts and to breakdown heavier carcases. Furthermore, this study demonstrated the changes to the saleable meat yield as the degree of fabrication increased, such that the average product prices increased ($20.64/kg for mid value added and$28.72/kg for extreme value added) compared to traditional retail cuts ($15/kg) to offset the increased labour of fabricating value-added cuts

The differential analytic index in Simons-Sullivan differential K-theory

We define the Simons-Sullivan differential analytic index by translating the Freed-Lott differential analytic index via explicit ring isomorphisms between Freed-Lott differential K-theory and Simons-Sullivan differential K-theory. We prove the differential Grothendieck-Riemann-Roch theorem in Simons-Sullivan differential K-theory using a theorem of Bismut.Comment: 14 pages. Comments are welcome. Final version. To appear in Annals of Global Analysis and Geometr

Feedback control of spin systems

The feedback stabilization problem for ensembles of coupled spin 1/2 systems is discussed from a control theoretic perspective. The noninvasive nature of the bulk measurement allows for a fully unitary and deterministic closed loop. The Lyapunov-based feedback design presented does not require spins that are selectively addressable. With this method, it is possible to obtain control inputs also for difficult tasks, like suppressing undesired couplings in identical spin systems.Comment: 16 pages, 15 figure

Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation

Although defects in intestinal barrier function are discussed as a key pathogenic factor in patients with inflammatory bowel diseases (IBD), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we performed a novel approach to characterize the transcriptome of IECs from IBD patients using a genome wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBD where Rho-A activation was suppressed due to reduced expression of the Rho-A prenylation enzyme GGTase-I. The functional relevance of this pathway was highlighted by studies in mice with conditional gene targeting in which deletion of RhoA or GGTase-I in IECs caused spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4+ T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBD. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-I deficient IECs, our findings open new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients

Some Relations between Twisted K-theory and E8 Gauge Theory

Recently, Diaconescu, Moore and Witten provided a nontrivial link between K-theory and M-theory, by deriving the partition function of the Ramond-Ramond fields of Type IIA string theory from an E8 gauge theory in eleven dimensions. We give some relations between twisted K-theory and M-theory by adapting the method of Diaconescu-Moore-Witten and Moore-Saulina. In particular, we construct the twisted K-theory torus which defines the partition function, and also discuss the problem from the E8 loop group picture, in which the Dixmier-Douady class is the Neveu-Schwarz field. In the process of doing this, we encounter some mathematics that is new to the physics literature. In particular, the eta differential form, which is the generalization of the eta invariant, arises naturally in this context. We conclude with several open problems in mathematics and string theory.Comment: 23 pages, latex2e, corrected minor errors and typos in published versio