Brands in international and multi‐platform expansion strategies: economic and management issues

Powerful media branding has historically facilitated successful international expansion on the part of magazine and other content forms including film and TV formats. Multi-platform expansion is now increasingly central to the strategies of media companies and, as this chapter argues, effective use of branding in order to engage audiences effectively and to secure a prominent presence across digital platforms forms a core part of this. Drawing on original research into the experience of UK media companies, this chapter highlights some of the key economic, management and socio-cultural issues raised by the ever-increasing role of brands and branding in the strategies of international and multi-platform expansion that are increasingly common- place across media

Extraction of cocoa proanthocyanidins and their fractionation by sequential centrifugal partition chromatography and gel permeation chromatography

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)Cocoa beans contain secondary metabolites ranging from simple alkaloids to complex polyphenols with most of them believed to possess significant health benefits. The increasing interest in these health effects has prompted the need to develop techniques for their extraction, fractionation, separation, and analysis. This work provides an update on analytical procedures with a focus on establishing a gentle extraction technique. Cocoa beans were finely ground to an average particle size of <100 μm, defatted at 20°C using n-hexane, and extracted three times with 50 % aqueous acetone at 50°C. Determination of the total phenolic content was done using the Folin-Ciocalteu assay, the concentration of individual polyphenols was analyzed by electrospray ionization high performance liquid chromatography-mass spectrometry (ESI-HPLC/MS). Fractions of bioactive compounds were separated by combining sequential centrifugal partition chromatography (SCPC) and gel permeation column chromatography using Sephadex LH-20. For SCPC, a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4:1:5, v/v/v) was successfully applied for the separation of theobromine, caffeine, and representatives of the two main phenolic compound classes flavan-3-ols and flavonols. Gel permeation chromatography on Sephadex LH-20 using a stepwise elution sequence with aqueous acetone has been shown for effectively separating individual flavan-3-ols. Separation was obtained for (-)-epicatechin, proanthocyanidin dimer B2, trimer C1, and tetramer cinnamtannin A2. The purity of alkaloids and phenolic compounds was determined by HPLC analysis and their chemical identity was confirmed by mass spectrometry

Fundamental properties of the pre-main sequence eclipsing stars of MML 53 and the mass of the tertiary

We present the most comprehensive analysis to date of the Upper Centaurus Lupus eclipsing binary MML 53 (with PEB = 2.097892 d), and for the first time, confirm the bound-nature of the third star (in a P3 ∼ 9 yr orbit) by constraining its mass dynamically. Our analysis is based on new and archival spectra and time-series photometry, spanning 80% of one orbit of the outer component. From the spectroscopic analysis, we determined the temperature of the primary star to be 4880 ± 100 K. The study of the close binary incorporated treatment of spots and dilution by the tertiary in the light curves, allowing for the robust measurement of the masses of the eclipsing components within 1% (M1 = 1.0400 ± 0.0067 M⊙ and M2 = 0.8907 ± 0.0058 M⊙), their radii within 4.5% (R1 = 1.283 ± 0.043 R⊙ and R2 = 1.107 ± 0.049 R⊙), and the temperature of the secondary star (Teff, 2 = 4379 ± 100 K). From the analysis of the eclipse timings, and the change in systemic velocity of the eclipsing binary and the radial velocities of the third star, we measured the mass of the outer companion to be 0.7 M⊙ (with a 20% uncertainty). The age we derived from the evolution of the temperature ratio between the eclipsing components is fully consistent with previous, independent estimates of the age of Upper Centaurus Lupus (16 ± 2 Myr). At this age, the tightening of the MML 53 eclipsing binary has already occurred, thus supporting close-binary formation mechanisms that act early in the stars’ evolution. The eclipsing components of MML 53 roughly follow the same theoretical isochrone, but appear to be inflated in radius (by 20% for the primary and 10% for the secondary) with respect to recent evolutionary models. However, our radius measurement of the 1.04 M⊙ primary star of MML 53 is in full agreement with the independent measurement of the secondary of NP Per which has the same mass and a similar age. The eclipsing stars of MML 53 are found to be larger but not cooler than predicted by non-magnetic models, it is not clear what is the mechanism that is causing the radius inflation given that activity, spots and/or magnetic fields slowing their contraction, require the inflated stars to be cooler to remain in thermal equilibrium

Human Gyrovirus Apoptin shows a similar subcellular distribution pattern and apoptosis induction as the chicken anaemia virus derived VP3/Apoptin

The chicken anaemia virus-derived protein Apoptin/VP3 (CAV-Apoptin) has the important ability to induce tumour-selective apoptosis in a variety of human cancer cells. Recently the first human Gyrovirus (HGyV) was isolated from a human skin swab. It shows significant structural and organisational resemblance to CAV and encodes a homologue of CAV-Apoptin/VP3. Using overlapping primers we constructed a synthetic human Gyrovirus Apoptin (HGyV-Apoptin) fused to green fluorescent protein in order to compare its apoptotic function in various human cancer cell lines to CAV-Apoptin. HGyV-Apoptin displayed a similar subcellular expression pattern as observed for CAV-Apoptin, marked by translocation to the nucleus of cancer cells, although it is predominantly located in the cytosol of normal human cells. Furthermore, expression of either HGyV-Apoptin or CAV-Apoptin in several cancer cell lines triggered apoptosis at comparable levels. These findings indicate a potential anti-cancer role for HGyV-Apoptin

A cohort study of 30 day mortality after NON-EMERGENCY surgery in a COVID-19 cold site

BACKGROUND: Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. METHODS: During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. RESULTS: 500 patients underwent surgery with median age 62.5 (IQR 51-71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. CONCLUSION: It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration

Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy

Monoclonal antibodies are widely used to treat non-infectious conditions but are costly. Vaccines could offer a cost-effective alternative but have been limited by sub-optimal T-cell stimulation and/or weak vaccine responses in recipients, for example, in elderly patients. We have previously shown that the repetitive structure of virus-like-particles (VLPs) can effectively bypass self-tolerance in therapeutic vaccines. Their efficacy could be increased even further by the incorporation of an epitope stimulating T cell help. However, the self-assembly and stability of VLPs from envelope monomer proteins is sensitive to geometry, rendering the incorporation of foreign epitopes difficult. We here show that it is possible to engineer VLPs derived from a non human-pathogenic plant virus to incorporate a powerful T-cell-stimulatory epitope derived from Tetanus toxoid. These VLPs (termed CMVTT) retain self-assembly as well as long-term stability. Since Th cell memory to Tetanus is near universal in humans, CMVTT-based vaccines can deliver robust antibody-responses even under limiting conditions. By way of proof of concept, we tested a range of such vaccines against chronic inflammatory conditions (model: psoriasis, antigen: interleukin-17), neurodegenerative (Alzheimer’s, β-amyloid), and allergic disease (cat allergy, Fel-d1), respectively. Vaccine responses were uniformly strong, selective, efficient in vivo, observed even in old mice, and employing low vaccine doses. In addition, randomly ascertained human blood cells were reactive to CMVTT-VLPs, confirming recognition of the incorporated Tetanus epitope. The CMVTT-VLP platform is adaptable to almost any antigen and its features and performance are ideally suited for the design of vaccines delivering enhanced responsiveness in aging populations

LNCS

Reachability analysis is difficult for hybrid automata with affine differential equations, because the reach set needs to be approximated. Promising abstraction techniques usually employ interval methods or template polyhedra. Interval methods account for dense time and guarantee soundness, and there are interval-based tools that overapproximate affine flowpipes. But interval methods impose bounded and rigid shapes, which make refinement expensive and fixpoint detection difficult. Template polyhedra, on the other hand, can be adapted flexibly and can be unbounded, but sound template refinement for unbounded reachability analysis has been implemented only for systems with piecewise constant dynamics. We capitalize on the advantages of both techniques, combining interval arithmetic and template polyhedra, using the former to abstract time and the latter to abstract space. During a CEGAR loop, whenever a spurious error trajectory is found, we compute additional space constraints and split time intervals, and use these space-time interpolants to eliminate the counterexample. Space-time interpolation offers a lazy, flexible framework for increasing precision while guaranteeing soundness, both for error avoidance and fixpoint detection. To the best of out knowledge, this is the first abstraction refinement scheme for the reachability analysis over unbounded and dense time of affine hybrid systems, which is both sound and automatic. We demonstrate the effectiveness of our algorithm with several benchmark examples, which cannot be handled by other tools

Progress and Challenges in the Diagnosis of Dementia: A Critical Review

Longer life expectancies have led to an increased number of neurodegenerative disease cases globally. Accurate diagnosis of this devastating disorder is of crucial importance but is still feasible only by a brain biopsy after death. An enormous amount of attention and research has been in place over the years toward the better understanding of the mechanisms, as well as the early diagnosis, of neurodegeneration. However, numerous studies have been contradictory from time to time, while new diagnostic methods are constantly developed in a tireless effort to tackle the disease. Nonetheless, there is not yet a conclusive report covering a broader range of techniques for the diagnosis of different types of dementia. In this paper, we critically review current knowledge on the different hypotheses about the pathogenesis of distinct types of dementia, as well as risk factors and current diagnostic approaches in a clinical setting, including neuroimaging, cerebrospinal (CSF), and blood tests. Encouraging research results for the diagnosis and investigation of neurodegenerative disorders are also reported. Particular attention is given to the field of spectroscopy as an emerging tool to detect dementias, follow-up patients, and potentially monitor the patients’ response to a therapeutic approach. Spectroscopic techniques, such as infrared and Raman spectroscopy, have facilitated numerous disease-related studies, including neurodegenerative disorders, and are currently undergoing trials for clinical implementation. This review constitutes a comprehensive report with an in-depth focus on promising imaging, molecular biomarker and spectroscopic tests in the field of dementive diseases

Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757