Areal Foliation and AVTD Behavior in T^2 Symmetric Spacetimes with Positive Cosmological Constant

We prove a global foliation result, using areal time, for T^2 symmetric spacetimes with a positive cosmological constant. We then find a class of solutions that exhibit AVTD behavior near the singularity.Comment: 15 pages, 0 figures, 2 references adde

Running Footwear In-Situ Exploration For A Carbon Neutral Tomorrow

89 page

What are the current challenges of managing cancer pain and could digital technologies help?

OBJECTIVES: Pain remains a problem for people with cancer despite effective treatments being available. We aimed to explore current pain management strategies used by patients, caregivers and professionals and to investigate opportunities for digital technologies to enhance cancer pain management. METHODS: A qualitative study comprising semistructured interviews and focus groups. Patients with cancer pain, their caregivers and health professionals from Northeast Scotland were recruited from a purposive sample of general practices. Professionals were recruited from regional networks. RESULTS: Fifty one participants took part in 33 interviews (eight patients alone, six patient/caregiver dyads and 19 professionals) and two focus groups (12 professionals). Living with cancer was hard work for patients and caregivers and comparable to a 'full-time job'. Patients had personal goals which involved controlling pain intensity and balancing this with analgesic use, side effects, overall symptom burden and social/physical activities.Digital technologies were embraced by most patients, and made living life with advanced cancer easier and richer (eg, video calls with family). Technology was underutilised for pain and symptom management. There were suggestions that technology could support self-monitoring and communicating problems to professionals, but patients and professionals were concerned about technological monitoring adding to the work of managing illness. CONCLUSIONS: Cancer pain management takes place in the context of multiple, sometimes competing personal goals. It is possible that technology could be used to help patients share individual symptom experiences and goals, thus enhancing tailored care. The challenge is for digital solutions to add value without adding undue burden

Selective truncations of an optical state using projection synthesis

Selective truncation of Fock-state expansion of an optical field can be achieved using projection synthesis. The process removes predetermined Fock states from the input field by conditional measurement and teleportation. We present a scheme based on multiport interferometry to perform projection synthesis. This scheme can be used both as a generalized quantum scissors device, which filters out Fock states with photon numbers higher than a predetermined value, and also as a quantum punching device, which selectively removes specific Fock states making holes in the Fock-state expansion of the input field.Comment: 4 pages, 2 figure

Near-Constant Mean Curvature Solutions of the Einstein Constraint Equations with Non-Negative Yamabe Metrics

We show that sets of conformal data on closed manifolds with the metric in the positive or zero Yamabe class, and with the gradient of the mean curvature function sufficiently small, are mapped to solutions of the Einstein constraint equations. This result extends previous work which required the conformal metric to be in the negative Yamabe class, and required the mean curvature function to be nonzero.Comment: 15 page

Tracking replication enzymology in vivo by genome-wide mapping of ribonucleotide incorporation

Ribonucleotides are frequently incorporated into DNA during eukaryotic replication. Here we map the genome-wide distribution of these ribonucleotides as markers of replication enzymology in budding yeast, using a new 5′-DNA end-mapping method, Hydrolytic End Sequencing. HydEn-Seq of DNA from ribonucleotide excision repair-deficient strains reveals replicase- and strand-specific patterns of ribonucleotides in the nuclear genome. These patterns support the role of DNA polymerases α and δ in lagging strand replication and of DNA polymerase ε in leading strand replication. They identify replication origins, termination zones and variations in ribonucleotide incorporation frequency across the genome that exceed three orders of magnitude. HydEn-Seq also reveals strand-specific 5′-DNA ends at mitochondrial replication origins, suggesting unidirectional replication of a circular genome. Given the conservation of enzymes that incorporate and process ribonucleotides in DNA, HydEn-Seq can be used to track replication enzymology in other organisms

HER2 cancer vaccine optimization by combining Drosophila S2 insect cell manufacturing with a novel VLP-display technology

Breast cancer is a widespread oncology indication affecting more than 1.3 million people worldwide annually, 20%-30% of which are HER2 positive. HER2 is a tyrosine kinase receptor that is frequently overexpressed in several solid-tumor cancers (incl. breast, prostate, gastric, esophageal and osteosarcoma) where it denotes an aggressive phenotype, high metastatic rate, and poor prognosis. In a human context, passive HER2-targeted immunotherapy using monoclonal antibodies (mAb, e.g. Trastuzumab and Pertuzumab) has proven to be an effective treatment modality, which has dramatically improved clinical outcomes. Unfortunately, mAb therapy is very expensive and the repeated injections of high doses can be associated with severe side-effects that reduce efficacy. Vaccines are highly cost-effective, but overall progress in development of anti-cancer vaccines based on cancer-associated antigens (e.g. HER2) has been hampered by inherent immune-tolerogenic mechanisms rendering the immune system incapable of reacting against the body’s own cells/proteins (i.e. self-antigens). Consequently, many attempts to develop anti-cancer vaccines have failed in clinical trials due to insufficient immunogenicity. To circumvent this central issue, we have developed a proprietary virus-like particle (VLP)-based vaccine delivery platform. Notably, the VLP-platform is currently the only available technology to effectively facilitate multivalent “virus-like” display of large/complex vaccine antigens. This is key to overcome immune-tolerance and enable induction of therapeutically potent antibody responses directed against cancer-associated self-antigens. In this talk I will discuss the non-viral Drosophila S2 insect cell production system and how it was applied to the production of hHer2/neu antigen, including using advanced production methods such as perfusion for clinical material manufacture. Furthermore, I will present our data from a transgenic mouse model for spontaneous breast cancer development, where high-density display of the HER2 extracellular domain on the surface of virus-like particles (VLPs) enables induction of therapeutically potent anti-HER2 responses. Split-protein tag/catcher conjugation was used to facilitate directional covalent attachment of HER2 to the surface of icosahedral bacteriophage-derived VLPs, thereby harnessing the VLP platform to effectively overcome B-cell tolerance. Vaccine efficacy was demonstrated both in prevention and therapy of mammary carcinomas in HER2 transgenic mice. Thus, the HER2-VLP vaccine shows promise as a new strategy for treatment of HER2-positive cancer. The modular VLP system may also represent an effective tool for development of self-antigen based vaccines against other non-communicable diseases

Chemical identification of point defects and adsorbates on a metal oxide surface by atomic force microscopy

Lauritsen JV, Foster AS, Olesen GH, et al. Chemical identification of point defects and adsorbates on a metal oxide surface by atomic force microscopy. Nanotechnology. 2006;17(14):3436-3441.Atomic force microscopy in the non-contact mode (nc-AFM) can provide atom-resolved images of the surface of, in principle, any material independent of its conductivity. Due to the complex mechanisms involved in the contrast formation in nc-AFM imaging, it is, however, far from trivial to identify individual surface atoms or adsorbates from AFM images. In this work, we successfully demonstrate how to extract detailed information about defects and the chemical identity of adsorbates on a metal oxide surface from nc-AFM images. We make use of the observation that the apex of the AFM tip can be altered to expose either a positive or negative tip termination. The complementary set of images recorded with the two tip terminations unambiguously define the ionic sub-lattices and reveal the exact positions of oxygen vacancies and hydroxyl (OH) defects on a TiO2 surface. Chemical specificity is extracted by comparing the characteristic contrast patterns of the defects with results from comprehensive AFM simulations. Our methodology of analysis is generally applicable and may be pivotal for uncovering surface defects and adsorbates on other transition metal oxides designed for heterogeneous catalysis, photo-electrolysis or biocompatibility

A call for action: Improve reporting of research studies to increase the scientific basis for regulatory decision-making

Publisher's version (útgefin grein)This is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer‐reviewed research studies in regulatory decision‐making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.Nordic Council of Minister

Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition

Mutational heterogeneity must be taken into account when reconstructing evolutionary histories, calibrating molecular clocks, and predicting links between genes and disease. Selective pressures and various DNA transactions have been invoked to explain the heterogeneous distribution of genetic variation between species, within populations, and in tissue-specific tumors. To examine relationships between such heterogeneity and variations in leading- and lagging-strand replication fidelity and mismatch repair, we accumulated 40,000 spontaneous mutations in eight diploid yeast strains in the absence of selective pressure. We found that replicase error rates vary by fork direction, coding state, nucleosome proximity, and sequence context. Further, error rates and DNA mismatch repair efficiency both vary by mismatch type, responsible polymerase, replication time, and replication origin proximity. Mutation patterns implicate replication infidelity as one driver of variation in somatic and germline evolution, suggest mechanisms of mutual modulation of genome stability and composition, and predict future observations in specific cancers