Shipowners\u27 Limitation of Liability in International seafaring Disasters

Adherence to the principle of strict limitation of liability in any area of the law has been out of vogue since the time of Winterbottom v. Wright. This is true whether it be in the area of products liability, master-servant relations, or international air travel. The trend is to remove all limitation on recoveries available under our law for death or injury. An exception is the limitation of liability in maritime disasters. Here, in this watery domain, the narrowness that formerly dominated the field of products liability continues to exist. Some critics condemn such strict limitation as an anachronism in our modern society, while others continue to cling to its principles steadfastly. For example, it is argued that the American airline industry, which is held to a higher standard of liability than that of the Warsaw Convention, cannot be compared to the shipping industry. That [the airline industry enjoys an ever increasing volume of business and commensurate profit while the shipping industry is on a descending plane, existing on marginal profits, is but one expression of this opinion made by John F. Gerity, Chairman of the Association of Average Adjusters of the United States. Although this paper deals with some of the more technical points of this complex admiralty controversy, it should also be of interest to all those -remotely concerned with international law, or the concepts of equity and jurisprudence. This is because of the maze of international regulation in the area and the self-contradiction that exists in American law on the subject - principally, where damages are highest, the degree of fault more culpable, and the injured party\u27s need for recovery greater, the liability is least or non-existent

Physiological strength electric fields modulate human T cell activation and polarisation

Acknowledgements: This work was supported by grants from an NHS Grampian Endowment Fund (Grant number 10/19). C.E.A was supported by an Institution of Medical Science University studentship. The authors acknowledge and are grateful to all volunteers for donating blood for T cell isolation. The authors also thank the University of Aberdeen Iain Fraser Cytometry Centre for their assistance.Peer reviewedPublisher PD

Modulational Instability in Equations of KdV Type

It is a matter of experience that nonlinear waves in dispersive media, propagating primarily in one direction, may appear periodic in small space and time scales, but their characteristics --- amplitude, phase, wave number, etc. --- slowly vary in large space and time scales. In the 1970's, Whitham developed an asymptotic (WKB) method to study the effects of small "modulations" on nonlinear periodic wave trains. Since then, there has been a great deal of work aiming at rigorously justifying the predictions from Whitham's formal theory. We discuss recent advances in the mathematical understanding of the dynamics, in particular, the instability of slowly modulated wave trains for nonlinear dispersive equations of KdV type.Comment: 40 pages. To appear in upcoming title in Lecture Notes in Physic

Friends or foes? migrants and sub-state nationalists in Europe

How do sub-state nationalists respond to the growing presence of cultural diversity in their ‘homelands’ resulting from migration? Sub-state nationalists in Europe, in ‘nations without states’ such as Catalonia and Scotland, have been challenging the traditional nation-state model for many decades. While the arguments in favour of autonomy or independence levelled by these movements have become more complex, sub-state nationalist movements remain grounded by their perceived national community that is distinct from the majority nation. Migration to the ‘homeland’ of a sub-state nation, then, presents a conundrum for sub-state elites that we label the ‘legitimation paradox’: too much internal diversity may undermine the claim to cultural distinctiveness. We engage with three common intervening variables thought to influence how sub-state nationalists confront the ‘legitimation paradox’: civic/ethnic nationalism, degree of political autonomy, and party competition. Our overarching argument is that none of these factors have a unidirectional or determinate effect on the sub-state nationalism-immigration nexus, which is why the nuanced case studies that comprise this Special Issue are worthwhile endeavours

Airborne quantification of net methane and carbon dioxide fluxes from European Arctic wetlands in Summer 2019

From The Royal Society via Jisc Publications RouterHistory: received 2021-05-27, accepted 2021-08-03, pub-electronic 2021-12-06, pub-print 2022-01-24Article version: VoRPublication status: PublishedFunder: UK Research and Innovation; Id: http://dx.doi.org/10.13039/100014013; Grant(s): NE/L002469/1, NE/N015835/1, NE/N016211/1Arctic wetlands and surrounding ecosystems are both a significant source of methane (CH4) and a sink of carbon dioxide (CO2) during summer months. However, precise quantification of this regional CH4 source and CO2 sink remains poorly characterized. A research flight using the UK Facility for Airborne Atmospheric Measurement was conducted in July 2019 over an area (approx. 78 000 km2) of mixed peatland and forest in northern Sweden and Finland. Area-averaged fluxes of CH4 and carbon dioxide were calculated using an aircraft mass balance approach. Net CH4 fluxes normalized to wetland area ranged between 5.93 ± 1.87 mg m−2 h−1 and 4.44 ± 0.64 mg m−2 h−1 (largest to smallest) over the region with a meridional gradient across three discrete areas enclosed by the flight survey. From largest to smallest, net CO2 sinks ranged between −513 ± 74 mg m−2 h−1 and −284 ± 89 mg m−2 h−1 and result from net uptake of CO2 by vegetation and soils in the biosphere. A clear gradient of decreasing bulk and area-averaged CH4 flux was identified from north to south across the study region, correlated with decreasing peat bog land area from north to south identified from CORINE land cover classifications. While N2O mole fraction was measured, no discernible gradient was measured over the flight track, but a minimum flux threshold using this mass balance method was calculated. Bulk (total area) CH4 fluxes determined via mass balance were compared with area-weighted upscaled chamber fluxes from the same study area and were found to agree well within measurement uncertainty. The mass balance CH4 fluxes were found to be significantly higher than the CH4 fluxes reported by many land-surface process models compiled as part of the Global Carbon Project. There was high variability in both flux distribution and magnitude between the individual models. This further supports previous studies that suggest that land-surface models are currently ill-equipped to accurately capture carbon fluxes inthe region. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'

Genetic analysis of Mendelian mutations in a large UK population-based Parkinson's disease study

Our objective was to define the prevalence and clinical features of genetic Parkinson's disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson's study, 424 had young-onset Parkinson's disease (age at onset ≤ 50) and 1799 had late onset Parkinson's disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 'Kompetitive' allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ≤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson's disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson's disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors

Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent

The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and corniWed layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, diVerentiation, and cell death. To determine genes responsible for initiating and maintaining a corniWed epidermis, organotypic cultures comprised entirely of stratiWed KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array proWle of submerged cultures containing KCs predominantly in a proliferative (relatively undiVerentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct proWle of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, diVerentiation, and cell death. Next, diVerentially expressed microRNAs (miRNAs) and long noncoding (lncRNA) RNAs were identiWed in EEs. Several diVerentially expressed miRNAs were validated by qRT-PCR and Northern blots. miRNAs 203, 205 and Let-7b were up-regulated at early time points (6, 18 and 24 h) but downregulated by 120 h. To study the lncRNA regulation in EEs, we proWled lncRNA expression by microarray and validated the results by qRT-PCR. Although the diVerential expression of several lncRNAs is suggestive of a role in epidermal diVerentiation, their biological functions remain to be elucidated. The current studies lay the foundation for relevant model systems to address such fundamentally important biological aspects of epidermal structure and function in normal and diseased human skin

Spatial pattern of accumulation at Taylor Dome during Marine Isotope Stage 4: stratigraphic constraints from Taylor Glacier

New ice cores retrieved from the Taylor Glacier (Antarctica) blue ice area contain ice and air spanning the Marine Isotope Stage (MIS) 5–4 transition, a period of global cooling and ice sheet expansion. We determine chronologies for the ice and air bubbles in the new ice cores by visually matching variations in gas- and ice-phase tracers to preexisting ice core records. The chronologies reveal an ice age–gas age difference (Δage) approaching 10 ka during MIS 4, implying very low snow accumulation in the Taylor Glacier accumulation zone. A revised chronology for the analogous section of the Taylor Dome ice core (84 to 55 ka), located to the south of the Taylor Glacier accumulation zone, shows that Δage did not exceed 3 ka. The difference in Δage between the two records during MIS 4 is similar in magnitude but opposite in direction to what is observed at the Last Glacial Maximum. This relationship implies that a spatial gradient in snow accumulation existed across the Taylor Dome region during MIS 4 that was oriented in the opposite direction of the accumulation gradient during the Last Glacial Maximum

A Resource for Discovering Specific and Universal Biomarkers for Distributed Stem Cells

Specific and universal biomarkers for distributed stem cells (DSCs) have been elusive. A major barrier to discovery of such ideal DSC biomarkers is difficulty in obtaining DSCs in sufficient quantity and purity. To solve this problem, we used cell lines genetically engineered for conditional asymmetric self-renewal, the defining DSC property. In gene microarray analyses, we identified 85 genes whose expression is tightly asymmetric self-renewal associated (ASRA). The ASRA gene signature prescribed DSCs to undergo asymmetric self-renewal to a greater extent than committed progenitor cells, embryonic stem cells, or induced pluripotent stem cells. This delineation has several significant implications. These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs. Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification

Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals