Структурно-грамматическое оформление лингвистических терминов в крымскотатарском языке

В статье предпринята попытка исследования структурных и частеречных особенностей лингвистических терминов крымскотатарского языка. Подробно анализируется соотношение однословных и многокомпонентных терминологических единиц. Рассматриваются типология структурных моделей двухсловных терминов-словосочетаний.У статті здійснена спроба дослідження структурних особливостей лінгвістичних термінів кримськотатарської мови та їх належність до частин мови. Докладно аналізується співвідношення однослівних і багатокомпонентних терінологічних одиниць. Розглядається типологія структурних моделей двослівних термінів-словосполучень.The author of the article makes an effort to research into structural and parts-of-speech peculiarities of Crimean Tatar linguistic terminology. The correlation of one-word and multi-componential terminological units is analyzed in detail. The article also deals with the structural types of the two-word term combinations

Grazing away the resilience of patterned ecosystems

Ecosystems’ responses to changing environmental conditions can be modulated by spatial self-organization. A prominent example of this can be found in drylands, where formation of vegetation patterns attenuates the magnitude of degradation events in response to decreasing rainfall. In model studies, the pattern wavelength responds to changing conditions, which is reflected by a rather gradual decline in biomass in response to decreasing rainfall. Although these models are spatially explicit, they have adopted a mean-field approach to grazing. By taking into account spatial variability when modeling grazing, we find that (over)grazing can lead to a dramatic shift in biomass, so that degradation occurs at rainfall rates that would otherwise still maintain a relatively productive ecosystem. Moreover, grazing increases the resilience of degraded ecosystem states. Consequently, restoration of degraded ecosystems could benefit from the introduction of temporary small-scale exclosures to escape from the basin of attraction of degraded states.</p

Ezh2 inhibition in Kras-driven lung cancer amplifies inflammation and associated vulnerabilities

Kras-driven non–small-cell lung cancers (NSCLCs) are a leading cause of death with limited therapeutic options. Many NSCLCs exhibit high levels of Ezh2, the enzymatic subunit of polycomb repressive complex 2 (PRC2). We tested Ezh2 inhibitors as single agents or before chemotherapy in mice with orthotopic Kras-driven NSCLC grafts, which homogeneously express Ezh2. These tumors display sensitivity to EZH2 inhibition by GSK126 but also amplify an inflammatory program involving signaling through NF-κB and genes residing in PRC2-regulated chromatin. During this process, tumor cells overcome GSK126 antiproliferative effects. We identified oncogenes that may mediate progression through an in vivo RNAi screen aimed at targets of PRC2/NF-κB. An in vitro compound screening linked GSK126-driven inflammation and therapeutic vulnerability in human cells to regulation of RNA synthesis and proteostasis. Interestingly, GSK126-treated NSCLCs in vivo also showed an enhanced response to a combination of nimesulide and bortezomib. Thus, Ezh2 inhibition may restrict cell proliferation and promote defined adaptive responses. Targeting these responses potentially improves outcomes in Kras-driven NSCLCs

Long-term transients help explain regime shifts in consumer-renewable resource systems

As planetary boundaries loom, there is an urgent need to develop sustainable equilibriums between societies and the resources they consume, thereby avoiding regime shifts to undesired states. Transient system trajectories to a stable state may differ substantially, posing significant challenges to distinguishing sustainable from unsustainable trajectories. We use stylized models to show how feedbacks between anthropogenic harvest regimes and resource availability drive transient dynamics. We show how substantial time lags may occur between interventions and social-ecological outcomes, and that sudden system collapses need not be linked to recent environmental changes. Historical reconstructions of island state populations show a variety of transient dynamics that closely corresponds to model expectations based on island differences in productivity and harvesting regime. We conclude that vulnerable social-ecological systems may persist when the population:resource ratio remains within a viable range of intermediate (rather than small) values, which implies that averting environmental crises may require counter-intuitive measures

Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer

Background: The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype and a basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options are limited, highlighting the need for the development of novel targeted therapies for this tumor subtype. Methods: Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient breast tumors and blocking EZH2 enzymatic activity could be a potent treatment strategy. To validate the role of EZH2 as a therapeutic target and to identify new synergistic drug combinations, we performed a high-throughput drug combination screen in various cell lines derived from BRCA1-deficient and -proficient mouse mammary tumors. Results: We identified the combined inhibition of EZH2 and the proximal DNA damage response kinase ATM as a novel synthetic lethality-based therapy for the treatment of BRCA1-deficient breast tumors. We show that the combined treatment with the EZH2 inhibitor GSK126 and the ATM inhibitor AZD1390 led to reduced colony formation, increased genotoxic stress, and apoptosis-mediated cell death in BRCA1-deficient mammary tumor cells in vitro. These findings were corroborated by in vivo experiments showing that simultaneous inhibition of EZH2 and ATM significantly increased anti-tumor activity in mice bearing BRCA1-deficient mammary tumors. Conclusion: Taken together, we identified a synthetic lethal interaction between EZH2 and ATM and propose this synergistic interaction as a novel molecular combination for the treatment of BRCA1-mutant breast cancer.Toxicolog

Cognitive function and drivers of cognitive impairment in a European and a Korean cohort of people living with HIV

Although cognitive impairments are still prevalent in the current antiretroviral therapy era, limited investigations have compared the prevalence of cognitive disorder in people living with HIV (PLWH) and its determinants in different regions and ethnicities. We compared cognitive performance across six domains using comparable batteries in 134 PLWH aged ≥45 years from the COBRA study (Netherlands, UK), and 194 PLWH aged ≥18 years from the NeuroAIDS Project (South Korea). Cognitive scores were standardized and averaged to obtain domain and global T-scores. Associations with global T-scores were evaluated using multivariable regression and the ability of individual tests to detect cognitive impairment (global T-score ≤45) was assessed using the area-under-the-receiver-operating-characteristic curve (AUROC). The median (interquartile range) age of participants was 56 (51, 62) years in COBRA (88% white ethnicity, 93% male) and 45 (37, 52) years in NeuroAIDS (100% Korean ethnicity, 94% male). The rate of cognitive impairment was 18.8% and 18.0%, respectively (p = 0.86). In COBRA, Black-African ethnicity was the factor most strongly associated with cognitive function (11.1 [7.7, 14.5] lower scores vs. white ethnicity, p < 0.01), whereas in NeuroAIDS, age (0.6 [0.1, 1.3] per 10-year, p<0.01) and education (0.7 [0.5, 0.9] per year, p<0.01) were significantly associated with cognitive function with anemia showing only a weak association (−1.2 [−2.6, 0.3], p=0.12). Cognitive domains most associated with cognitive impairment were attention (AUROC = 0.86) and executive function (AUROC = 0.87) in COBRA and processing speed (AUROC = 0.80), motor function (AUROC = 0.78) and language (AUROC = 0.78) in NeuroAIDS. Two cohorts of PLWH from different geographical regions report similar rates of cognitive impairment but different risk factors and cognitive profiles of impairment

Do people living with HIV experience greater age advancement than their HIV-negative counterparts?

Objectives: Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement. Design: Cross-sectional analysis of 134 PLWH on suppressive antiretroviral therapy, 79 lifestyle-comparable HIV-negative controls aged 45 years or older from the Co-mor- Bidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors. Methods: Biological age was estimated using a validated algorithm based on 10 biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression. Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6–14.9) years] and HIV-negative [5.5 (3.8–7.2) years] COBRA participants compared with blood donors [7.0 (4.1 to 9.9) years, both P’s<0.001)], but also in HIV-positive compared with HIV-negative participants (P<0.001). Chronic HBV, higher anti-CMV IgG titer and CD8þ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1–6.8) years among those with nadir CD4þ T-cell count less than 200 cells/ml and by 0.1 (0.06–0.2) years for each additional month of exposure to saquinavir

Ecosystems off track : rate-induced critical transitions in ecological models

Theory suggests that gradual environmental change may erode the resilience of ecosystems and increase their susceptibility to critical transitions. This notion has received a lot of attention in ecology in recent decades. An important question receiving far less attention is whether ecosystems can cope with the rapid environmental changes currently imposed. The importance of this question was recently highlighted by model studies showing that elevated rates of change may trigger critical transitions, whereas slow environmental change would not. This paper aims to provide a mechanistic understanding of these rate-induced critical transitions to facilitate identification of rate sensitive ecosystems. Analysis of rate sensitive ecological models is challenging, but we demonstrate how rate-induced transitions in an elementary model can still be understood. Our analyses reveal that rate-induced transitions 1) occur if the rate of environmental change is high compared to the response rate of ecosystems, 2) are driven by rates, rather than magnitudes, of change and 3) occur once a critical rate of change is exceeded. Disentangling rate-induced transitions from classical transitions in observations would be challenging. However, common features of rate-sensitive models suggest that ecosystems with coupled fast–slow dynamics, exhibiting repetitive catastrophic shifts or displaying periodic spatial patterns are more likely to be rate sensitive. Our findings are supported by experimental studies showing rate-dependent outcomes. Rate sensitivity of models suggests that the common definition of ecological resilience is not suitable for a subset of real ecosystems and that formulating limits to magnitudes of change may not always safeguard against ecosystem degradation. Synthesis Understanding and predicting ecosystem response to environmental change is one of the key challenges in ecology. Model studies have suggested that slow, gradual environmental change beyond some critical threshold can trigger so-called critical transitions and abrupt ecosystem degradation. An important question remains however whether ecosystems can cope with the ongoing rapid anthropogenic environmental changes to which they are currently imposed. In this study we demonstrate that in some ecological models elevated rates of change can trigger critical transitions even if slow environmental change of the same magnitude would not. Such rateinduced critical transitions in models suggest that concepts like resilience and planetary boundaries may not always be sufficient to explain and prevent ecosystem degradation

Ecosystems off track: rate-induced critical transitions in ecological models

Theory suggests that gradual environmental change may erode the resilience of ecosystems and increase their susceptibility to critical transitions. This notion has received a lot of attention in ecology in recent decades. An important question receiving far less attention is whether ecosystems can cope with the rapid environmental changes currently imposed. The importance of this question was recently highlighted by model studies showing that elevated rates of change may trigger critical transitions, whereas slow environmental change would not. This paper aims to provide a mechanistic understanding of these rate-induced critical transitions to facilitate identification of rate sensitive ecosystems. Analysis of rate sensitive ecological models is challenging, but we demonstrate how rate-induced transitions in an elementary model can still be understood. Our analyses reveal that rate-induced transitions 1) occur if the rate of environmental change is high compared to the response rate of ecosystems, 2) are driven by rates, rather than magnitudes, of change and 3) occur once a critical rate of change is exceeded. Disentangling rate-induced transitions from classical transitions in observations would be challenging. However, common features of rate-sensitive models suggest that ecosystems with coupled fast–slow dynamics, exhibiting repetitive catastrophic shifts or displaying periodic spatial patterns are more likely to be rate sensitive. Our findings are supported by experimental studies showing rate-dependent outcomes. Rate sensitivity of models suggests that the common definition of ecological resilience is not suitable for a subset of real ecosystems and that formulating limits to magnitudes of change may not always safeguard against ecosystem degradation. Synthesis Understanding and predicting ecosystem response to environmental change is one of the key challenges in ecology. Model studies have suggested that slow, gradual environmental change beyond some critical threshold can trigger so-called critical transitions and abrupt ecosystem degradation. An important question remains however whether ecosystems can cope with the ongoing rapid anthropogenic environmental changes to which they are currently imposed. In this study we demonstrate that in some ecological models elevated rates of change can trigger critical transitions even if slow environmental change of the same magnitude would not. Such rateinduced critical transitions in models suggest that concepts like resilience and planetary boundaries may not always be sufficient to explain and prevent ecosystem degradation