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The rate at which states defend their allies in war has dropped from 81% during 1816–1944 to 7% in 1945–2016. I attribute the decline in honored alliances to a dramatic shift in the military capability of alliances. Contrary to the popular belief that alliances have become stronger after 1945, I find that the post-1945 international system also witnessed a significant increase in the number of weaker alliances. This bimodal distribution of alliances produced a pattern where alliances were either violated upon being attacked or never attacked in the first place, leading to a decline in the rate at which alliances were honored. I support my argument using alliance data over two centuries. This research advances our understanding of military alliances by documenting a polarization of alliances in terms of their military capability post-1945 and by providing an explanation for an empirical puzzle—a sharp decline in the rate of honored alliances after 1945. El porcentaje en que los Estados defienden a sus aliados en una guerra ha descendido del 81% durante el periodo de 1816-1944 al 7% durante el periodo de 1945-2016. Atribuimos el deterioro de las alianzas de honor a un cambio drástico en la capacidad militar de las alianzas. En contra de la creencia popular de que las alianzas se han fortalecido después de 1945, observamos que el sistema internacional posterior a 1945 también ha sido testigo de un aumento significativo del número de alianzas más débiles. Esta distribución bimodal de las alianzas produjo un patrón en el que las alianzas fueron vulneradas al ser atacadas o nunca llegaron a ser atacadas, lo que condujo a un descenso en la tasa de cumplimiento de las alianzas. Apoyamos nuestro argumento en los datos sobre las alianzas a lo largo de dos siglos. Esta investigación profundiza nuestra comprensión de las alianzas militares al documentar una polarización de las alianzas en términos de su capacidad militar después de 1945 y al proporcionar una explicación para un rompecabezas empírico: una fuerte disminución en la tasa de alianzas de honor después de 1945. Le taux auquel les États défendent leurs alliés lors de guerres est passé de 81 % durant la période 1816-1944 à 7 % de 1945 à 2016. J'attribue ce déclin du respect des alliances à un changement radical de leurs capacités militaires. Contrairement à la croyance populaire selon laquelle les alliances se sont renforcées depuis 1945, selon moi, le système international a depuis cette date été le témoin d'une augmentation importante des alliances plus fragiles. Cette distribution bimodale des alliances a généré un schéma dans lequel les alliances étaient soit violées lors d'attaques, soit ne subissaient jamais d'attaques, ce qui a conduit à une diminution du taux de respect des alliances. J'étaye mon propos à l'aide de données sur les alliances collectées durant plus de deux siècles. Cet article de recherche vise à affiner notre compréhension des alliances militaires, en documentant une polarisation des alliances relativement à leurs capacités militaires d'après 1945 et en fournissant une explication au puzzle empirique du fort déclin du taux de respect des alliances après 1945. [ABSTRACT FROM AUTHOR]

Fluorescent or LED nail lamps are used in manicure and pedicure salons to cure nail coatings. These are UV sources, but with significant blue light emissions. Most of the literature emphasizes skin damage and cancer risk from UV exposure rather than blue light-induced damage to visual photoreceptors. Nail technicians using the lamps routinely may have potentially greater exposure than customers. However, there are no data on blue light radiance levels combined with time activity patterns for exposure assessment. This research aimed to determine exposures through simulation experiments, informed by observational studies in seven nail salons. Typical and worst-case time activity patterns were established, and spectral radiance doses determined in the occupational visual field for two LED nail curing lamps. The results showed the effective spectral radiance dose were below the current guideline promulgated by the International Commission on Non-Ionising Radiation Protection. Interestingly, radiances at the corners of one LED nail curing lamp was higher than at the center, which shows the amount of exposure can differ depending on the viewing angle. This research is the first to determine spectral radiance doses. A covered design is highly recommended for blocking the emission of blue light from a nail lamp. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex and multifactorial skin disease characterized by skin inflammation and intense pruritus. There are many commercially available treatments such as topical corticosteroids and immunosuppressants to treat of AD, but their effectiveness is limited, and frequent use of these treatments can cause serious side effects. Therefore, the development of new therapeutic agents is necessary for the treatment of AD. Hence, an alternative agent that was derived from natural products that are effective and safe for AD treatment was investigated using experimental models. The biological activity of euscaphic acid has anti-inflammatory, anticoagulant, and antioxidant effects. Despite the various biomedical properties of euscaphic acid, its therapeutic effects on AD have not been well studied. In this study, we investigated the effects of euscaphic acid on skin inflammation and pruritus in AD mouse model. The effects of euscaphic acid were investigated in activated human epidermal keratinocytes and leukemia T lymphoblast cell lines, and Dermatophagoides farina extract and 2,4-dinitrochlorobenzene-induced AD mouse model. Euscaphic acid ameliorated AD properties, such as the expression of inflammatory cytokines and activation of transcription factors. In addition, euscaphic acid reduced critical factors for pruritus such as immunoglobulin E hyperproduction, mast cell invasion, and interleukin-33 expression. Taken together, euscaphic acid could be a potent therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3) (1,2). Although therapy-induced senescence (TIS) improves long-term outcomes (3), potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Eμ-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h[1.sup.-]to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but not TIS-incompetent Suv39h[1.sup.-] lymphomas show increased glucose utilization and much higher ATP production. We demonstrate that this is linked to massive proteotoxic stress, which is a consequence of the senescence-associated secretory phenotype (SASP) described previously (4-6). SASP-producing TIS cells exhibited endoplasmic reticulum stress, an unfolded protein response (UPR), and increased ubiquitination, thereby targeting toxic proteins for autophagy in an acutely energy-consuming fashion. Accordingly, TIS lymphomas, unlike senescence models that lack a strong SASP response, were more sensitive to blocking glucose utilization or autophagy, which led to their selective elimination through caspase-12-and caspase-3-mediated endoplasmic-reticulum-related apoptosis. Consequently, pharmacological targeting of these metabolic demands on TIS induction in vivo prompted tumour regression and improved treatment outcomes further. These findings unveil the hypercatabolic nature of TIS that is therapeutically exploitable by synthetic lethal metabolic targeting., Anticancer agents are known to induce cellular senescence, but diagnostic procedures to non-invasively detect a senescent proliferation arrest of cancer lesions in response to chemotherapy in vivo remain to be [...]