103 research outputs found
Response of moist and dry processes in atmospheric blocking to climate change
Weather extremes are often associated with atmospheric blocking, but how the underlying physical processes leading to blocking respond to climate change is not yet fully understood. Here we track blocks as upper-level negative potential vorticity (PV) anomalies and apply a Lagrangian analysis to 100 years of present-day (∼2000) and future (∼2100, under the RCP8.5 scenario) climate simulations restarted from the Community Earth System Model–Large Ensemble Project runs (CESM-LENS) to identify different physical processes and quantify how their relative importance changes in a warmer and more humid climate. The trajectories reveal two contrasting airstreams that both contribute to the formation and maintenance of blocking: latent heating in strongly ascending airstreams (moist processes) and quasi-adiabatic flow near the tropopause with weak radiative cooling (dry processes). Both are reproduced remarkably well when compared against ERA-Interim reanalysis, and their relative importance varies regionally and seasonally. The response of blocks to climate change is complex and differs regionally, with a general increase in the importance of moist processes due to stronger latent heating (+1 K in the median over the Northern Hemisphere) and a larger fraction (+15%) of strongly heated warm conveyor belt air masses, most pronounced over the storm tracks. Future blocks become larger (+7%) and their negative PV anomaly slightly intensifies (+0.8%). Using a Theil–Sen regression model, we propose that the increase in size and intensity is related to the increase in latent heating, resulting in stronger cross-isentropic transport of air with low PV into the blocking anticyclones. Our findings provide evidence that moist processes become more important for the large-scale atmospheric circulation in the midlatitudes, with the potential for larger and more intense blocks
Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration
Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer’s disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (S-depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S-depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S-depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S-depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins
What caused the unseasonal extreme dust storm in Uzbekistan during November 2021?
An unseasonal dust storm hit large parts of Central Asia on 4-5 November 2021, setting records for the column aerosol burden and fine particulate concentration in Tashkent, Uzbekistan. The dust event originated from an agropastoral region in southern Kazakhstan, where the soil erodibility was enhanced by a prolonged agricultural drought resulting from La Niña-related precipitation deficit and persistent high atmospheric evaporative demand. The dust outbreak was triggered by sustained postfrontal northerly winds during an extreme cold air outbreak. The cold air and dust outbreaks were preceded by a chain of processes consisting of recurrent synoptic-scale transient Rossby wave packets over the North Pacific and North Atlantic, upper-level wave breaking and blocking over Greenland, followed by high-latitude blocking over Northern Europe and West Siberia, and the equatorward shift of a tropopause polar vortex and cold pool into southern Kazakhstan. Our study suggests that the historic dust storm in Uzbekistan was a compound weather event driven by cold extreme, high winds, and drought precondition
Photodissociation dynamics of the iodide-uracil (I-U) complex
Photofragment action spectroscopy and femtosecond time-resolved photoelectron imaging are utilized to probe the dissociation channels in iodide-uracil (I− ⋅ U) binary clusters upon photoexcitation. The photofragment action spectra show strong I− and weak [U- H]− ion signal upon photoexcitation. The action spectra show two bands for I− and [U- H]− production peaking around 4.0 and 4.8 eV. Time-resolved experiments measured the rate of I− production resulting from excitation of the two bands. At 4.03 eV and 4.72 eV, the photoelectron signal from I− exhibits rise times of 86 ± 7 ps and 36 ± 3 ps, respectively. Electronic structure calculations indicate that the lower energy band, which encompasses the vertical detachment energy (4.11 eV) of I−U, corresponds to excitation of a dipole-bound state of the complex, while the higher energy band is primarily a π-π∗ excitation on the uracil moiety. Although the nature of the two excited states is very different, the long lifetimes for I− production suggest that this channel results from internal conversion to the I− ⋅ U ground state followed by evaporation of I−. This hypothesis was tested by comparing the dissociation rates to Rice-Ramsperger-Kassel-Marcus calculations
Impact of uPA/PAI-1 and disseminated cytokeratin-positive cells in breast cancer
Background
The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects.
Methods
We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18.
Results
DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1–75) next to T stage.
Conclusions
uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression
State Control and the Effects of Foreign Relations on Bilateral Trade
Do states use trade to reward and punish partners? WTO rules and the pressures of globalization restrict states’ capacity to manipulate trade policies, but we argue that governments can link political goals with economic outcomes using less direct avenues of influence over firm behavior. Where governments intervene in markets, politicization of trade is likely to occur. In this paper, we examine one important form of government control: state ownership of firms. Taking China and India as examples, we use bilateral trade data by firm ownership type, as well as measures of bilateral political relations based on diplomatic events and UN voting to estimate the effect of political relations on import and export flows. Our results support the hypothesis that imports controlled by state-owned enterprises (SOEs) exhibit stronger responsiveness to political relations than imports controlled by private enterprises. A more nuanced picture emerges for exports; while India’s exports through SOEs are more responsive to political tensions than its flows through private entities, the opposite is true for China. This research holds broader implications for how we should think about the relationship
between political and economic relations going forward, especially as a number of countries with partially state-controlled economies gain strength in the global economy
Character pathology and neuropsychological test performance in remitted opiate dependence
<p>Abstract</p> <p>Background</p> <p>Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies.</p> <p>Methods</p> <p>The Millon Multiaxial Clinical Inventory (MCMI) and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM), 27 subjects in protracted abstinence from methadone maintenance treatment (PA), and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis.</p> <p>Results</p> <p>MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use.</p> <p>Conclusion</p> <p>Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects.</p
Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science
It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations
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