The dryline is an important focal point for convection initiation. Although drylines most commonly occur on the southern Great Plains, dryline passages and subsequent severe weather outbreaks have ...been documented in the Mississippi River valley. This study presents a 15-yr (1999-2013) climatology of these Mississippi River valley drylines and associated severe weather. Additionally, synoptic patterns are identified that may result in drylines moving atypically far eastward into the Mississippi River valley. In total, 39 Mississippi River valley drylines (hereafter referred to as MRV drylines) were identified from the North American Regional Reanalysis (NARR) dataset through the study period. Mean and anomaly synoptic composites were created for these drylines. MRV dryline events typically occur under synoptically active conditions with an amplified upper-air pattern, a 500-hPa shortwave trough to the west or northwest of the dryline, and a strong surface cyclone to the north. These boundaries are often misanalyzed or inconsistently analyzed as cold fronts, stationary fronts, or trough axes on surface maps; of the 33 cases of identified MRV drylines for which the Weather Prediction Center archived analyses were available, only 6 were correctly analyzed as drylines. Drylines moving into the Mississippi River valley often result in severe weather outbreaks in the Mississippi River valley, the Midwest, and the southeastern United States.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Intensive agri-industrial food systems in facing old and new sustainability challenges are now confronted with emergent 'alternatives', particularly local food systems, that pose transformational ...pathways for strong sustainability. But important questions are raised about the role local food will play in the creation of sustainable food futures, including: Are local food systems sustainable? Can they offer a socially just replacement to agriindustrial systems, or will they simply replicate the problems of the past or create new ones? These questions, in turn, are underpinned by the fundamental question: What exactly does 'sustainability' mean in the context of food futures?
Investigates how World Heritage certification, a process which encourages a holistic assessment of the landscape and requires conservation values, cultural values and development needs of local ...people to be addressed, might help with management of the night sky starlight reserve in the Mackenzie Basin. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Intensive agri-industrial food systems in facing old and new sustainability challenges are now confronted with emergent 'alternatives', particularly local food systems, that pose transformational ...pathways for strong sustainability. But important questions are raised about the role local food will play in the creation of sustainable food futures, including: Are local food systems sustainable? Can they offer a socially just replacement to agriindustrial systems, or will they simply replicate the problems of the past or create new ones? These questions, in turn, are underpinned by the fundamental question: What exactly does 'sustainability' mean in the context of food futures?
Prophylactic vaccination of rhesus macaques with rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) elicits immune responses that stringently ...control highly pathogenic SIV infection, with subsequent apparent clearance of the infection, in ~50% of vaccinees. In contrast, here, we show that therapeutic RhCMV/SIV vaccination of rhesus macaques previously infected with SIV and given continuous combination antiretroviral therapy (cART) beginning 4-9 d post-SIV infection does not mediate measurable SIV reservoir clearance during over 600 d of follow-up on cART relative to RhCMV/control vaccination. However, none of the six animals started on cART on day four or five, across both RhCMV/SIV- and RhCMV/control-vaccinated groups, those rhesus macaques with SIV reservoirs most closely resembling those of prophylactically RhCMV/SIV-vaccinated and protected animals early in their course, showed post-cART viral rebound with up to nine months of follow-up. Moreover, at necropsy, these rhesus macaques showed little to no evidence of replication-competent SIV. These results suggest that the early SIV reservoir is limited in durability and that effective blockade of viral replication and spread in this critical time window by either pharmacologic or immunologic suppression may result in reduction, and potentially loss, of rebound-competent virus over a period of ~two years.
Proliferation of latently infected CD4+ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to ...targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4+ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA-treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4+ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.
Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such ...minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.6% of preexisting heterozygous loci in control single blastomere samples appear as homozygous after whole genome amplification indicative of allelic dropouts. To overcome these limitations, we validate on-target modifications seen in gene edited human embryos in embryonic stem cells. We show that, in addition to frequent indel mutations, biallelic double-strand breaks can also produce large deletions at the target site. Moreover, some embryonic stem cells show copy-neutral loss of heterozygosity at the cleavage site which is likely caused by interallelic gene conversion. However, the frequency of loss of heterozygosity in embryonic stem cells is lower than in blastomeres, suggesting that allelic dropouts is a common whole genome amplification outcome limiting genotyping accuracy in human preimplantation embryos.
Widespread concern exists about the impacts of COVID-19 and related public health safety measures (e.g., school closures) on adolescent mental health. Emerging research documents correlates and ...trajectories of adolescent distress, but further work is needed to identify additional vulnerability factors that explain increased psychopathology during the pandemic. The current study examined whether COVID-19-related loneliness and health anxiety (assessed in March 2020) predicted increased depressive symptoms, frequency of non-suicidal self-injury (NSSI), and suicide risk from pre-pandemic (late January/early February 2020) to June 2020.
Participants were 362 middle and high school adolescents in rural Maine (M age = 15.01 years; 63.4% female; 76.4% White). Data were collected during a time in which state-level COVID-19 restrictions were high and case counts were relatively low. Self-reports assessed psychopathology symptoms, and ecological momentary assessment (EMA) was used to capture COVID-19-related distress during the initial days of school closures.
Loneliness predicted higher depressive symptoms for all adolescents, higher NSSI frequency for adolescents with low pre-pandemic frequency (but less frequent NSSI for adolescents with high pre-pandemic frequency), and higher suicide risk for adolescents with higher pre-pandemic risk. Health anxiety predicted higher NSSI frequency for adolescents with high pre-pandemic frequency, and secondary analyses suggested that this pattern may depend on adolescents' gender identity.
Results underscore the impact of COVID-19 on adolescent mental health, with benefits for some but largely negative impacts for most. Implications for caretakers, educators, and clinicians invested in adolescent mental health are discussed.
The rebound competent viral reservoir (RCVR)-virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped-is the primary barrier to ...eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after intravenous challenge with barcoded SIVmac239 as a means to elucidate the dynamics of RCVR establishment in groups of RMs by creating a multi-log range of pre-ART viral loads and then assessed viral time-to-rebound and reactivation rates resulting from the discontinuation of ART after one year. RMs started on ART on days 3, 4, 5, 6, 7, 9 or 12 post-infection showed a nearly 10-fold difference in pre-ART viral measurements for successive ART-initiation timepoints. Only 1 of 8 RMs initiating ART on days 3 and 4 rebounded after ART interruption despite measurable pre-ART plasma viremia. Rebounding plasma from the 1 rebounding RM contained only a single barcode lineage detected at day 50 post-ART. All RMs starting ART on days 5 and 6 rebounded between 14- and 50-days post-ART with 1-2 rebounding variants each. RMs starting ART on days 7, 9, and 12 had similar time-to-measurable plasma rebound kinetics despite multiple log differences in pre-ART plasma viral load (pVL), with all RMs rebounding between 7- and 16-days post-ART with 3-28 rebounding lineages. Calculated reactivation rates per pre-ART pVL were highest for RMs starting ART on days 5, 6, and 7 after which the rate of accumulation of the RCVR markedly decreased for RMs treated on days 9 and 12, consistent with multiphasic establishment and near saturation of the RCVR within 2 weeks post infection. Taken together, these data highlight the heterogeneity of the RCVR between RMs, the stochastic establishment of the very early RCVR, and the saturability of the RCVR prior to peak viral infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely ...inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background. EGFR downstream signaling evaluation further demonstrated that metformin, at its IC50 value, modified apoptosis caused in erlotinib or chemotherapeutic agent-treated cells via AKT activation and the inhibition of caspase 3 and PARP cleavages. These regulations were driven independently from EGFR, LKB1, KRAS, PTEN and p53 status. Metformin triggered autophagy (LC3B expression) was identified to interplay with apoptosis to attenuate the drug effect and postpone cancer cell death. In the retrospective study of 8 NSCLC patients, the administration of metformin did not induce statistically significant changes as assessed by immunohistochemical staining of pERK, pAKT and cleaved PARP. Consequently, the application of metformin for T2D NSCLC patients receiving chemo or EGFR targeted therapy should be considered with caution.
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