1,935 research outputs found
Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity
During macroautophagy, conjugation of ATG12 to ATG5 is essential for LC3 lipidation and autophagosome formation. Additionally, ATG12 has ATG5-independent functions in diverse processes including mitochondrial fusion and mitochondrial-dependent apoptosis. In this study, we investigated the regulation of free ATG12. In stark contrast to the stable ATG12–ATG5 conjugate, we find that free ATG12 is highly unstable and rapidly degraded in a proteasome-dependent manner. Surprisingly, ATG12, itself a ubiquitin-like protein, is directly ubiquitinated and this promotes its proteasomal degradation. As a functional consequence of its turnover, accumulation of free ATG12 contributes to proteasome inhibitor-mediated apoptosis, a finding that may be clinically important given the use of proteasome inhibitors as anticancer agents. Collectively, our results reveal a novel interconnection between autophagy, proteasome activity, and cell death mediated by the ubiquitin-like properties of ATG12
High energy Coulomb-scattered electrons for relativistic particle beam diagnostics
A new system used for monitoring energetic Coulomb-scattered electrons as the
main diagnostic for accurately aligning the electron and ion beams in the new
Relativistic Heavy Ion Collider (RHIC) electron lenses is described in detail.
The theory of electron scattering from relativistic ions is developed and
applied to the design and implementation of the system used to achieve and
maintain the alignment. Commissioning with gold and 3He beams is then described
as well as the successful utilization of the new system during the 2015 RHIC
polarized proton run. Systematic errors of the new method are then estimated.
Finally, some possible future applications of Coulomb-scattered electrons for
beam diagnostics are briefly discussed.Comment: 16 pages, 23 figure
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Life in the Atacama — Year 2: Geologic reconnaissance through long-range roving and implications on the search for life
The Life in the Atacama-2004 project, which included geological, morphological, and mineralogical mapping through combined satellite, field-based, and microscopic perspectives and long-range roving, led to the localization of potential habitats
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Early maternal depressive symptoms and child growth trajectories: a longitudinal analysis of a nationally representative US birth cohort
Background: Maternal depressive symptoms are negatively associated with early child growth in developing countries; however, few studies have examined this relation in developed countries or used a longitudinal design with data past the second year of the child’s life. We investigated if and when early maternal depressive symptoms affect average growth in young children up to age 6 in a nationally representative sample of US children. Methods: Using data from 6,550 singleton births from the Early Childhood Longitudinal Study -- Birth Cohort (ECLS-B), we fit growth trajectory models with random effects to examine the relation between maternal depressive symptoms at 9 months based on the twelve-item version of the Center for Epidemiologic Studies Depression Scale (CES-D) and child height and body mass index (BMI) to age 6 years. Results: Mothers with moderate/severe depressive symptoms at 9 months postpartum had children with shorter stature at this same point in time [average 0.26 cm shorter; 95% CI: 5 cm, 48 cm] than mothers without depressive symptoms; children whose mothers reported postpartum depressive symptoms remained significantly shorter throughout the child’s first 6 years. Conclusions: Results suggest that the first year postpartum is a critical window for addressing maternal depressive symptoms in order to optimize child growth. Future studies should investigate the role of caregiving and feeding practices as potential mechanisms linking maternal depressive symptoms and child growth trajectories
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Spectroscopic results from the Life in the Atacama (LITA) project 2004 field season
Analysis of spectroscopy datasets from rover field tests in the Atacama Desert (Chile), focusing on the composition of the surface and identification of potential habitats for life
Effects of palm oil mill effluent (POME) anaerobic sludge from 500 m3 of closed anaerobic methane digested tank on pressed-shredded empty fruit bunch (EFB) composting process
In this study, co-composting of pressed-shredded empty fruit bunches (EFB) and palm oil mill effluent (POME) anaerobic sludge from 500 m3 closed anaerobic methane digested tank was carried out. High nitrogen and nutrients content were observed in the POME anaerobic sludge. The sludge was subjected to the pressed-shredded EFB to accelerate the co-composting treatment. In the present study, changes in the physicochemical characteristics of co-composting process were recorded and evaluated. The cocomposting treatment was completed in a short time within 40 days with a final C/N ratio of 12.4. The co-composting process exhibited a higher temperature (60 - 67°C) in the thermophilic phase followed by curing phase after four weeks of treatment. Meanwhile, pH of the composting pile (8.1 - 8.6) was almost constant during the process and moisture content was reduced from 64.5% (initial treatment) to52.0% (final matured compost). The use of pressed-shredded EFB as a main carbon source and bulking agent contributed to the optimum oxygen level in the composting piles (10 - 15%). The biodegradation of composting materials is shown by the reduction of cellulose (34.0%) and hemicellulose (27.0%) content towards the end of treatment. In addition, considerable amount of nutrients and low level of heavy metals were detected in the final matured compost. It can be concluded that the addition of POME anaerobic sludge into the pressed-shredded EFB composting process could produce acceptable and consistent quality of compost product in a short time
Implementing an inpatient social early warning system for child maltreatment
Objectives: The current article describes the process evaluation of a social early warning system (SEWS) for the prevention of
child maltreatment in the federal state of Hamburg. This prevention initiative targets expectant mothers and their partners
including an initial screening of risk factors for child maltreatment, a subsequent structured clearing interview further exploring risks
and identifying protective factors and an optional referral to the regional health and social care system. Method: The process
evaluation was conducted by examining the flow of participants through the different stages of the SEWS as well as asking social
education workers, parents, and regional institutions about their satisfaction with the process of the SEWS. Results: The participation
rate throughout the SEWS as well as the satisfaction rates were high. Conclusions: The SEWS is a secondary prevention
initiative with a substantial difference to other early prevention initiatives, as it aims to facilitate intervention rather than providing it
Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine.
The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine
Accelerator system for the PRISM based muon to electron conversion experiment
The next generation of lepton flavor violation experiments need high
intensity and high quality muon beams. Production of such beams requires
sending a short, high intensity proton pulse to the pion production target,
capturing pions and collecting the resulting muons in the large acceptance
transport system. The substantial increase of beam quality can be obtained by
applying the RF phase rotation on the muon beam in the dedicated FFAG ring,
which was proposed for the PRISM project.This allows to reduce the momentum
spread of the beam and to purify from the unwanted components like pions or
secondary protons. A PRISM Task Force is addressing the accelerator and
detector issues that need to be solved in order to realize the PRISM
experiment. The parameters of the required proton beam, the principles of the
PRISM experiment and the baseline FFAG design are introduced. The spectrum of
alternative designs for the PRISM FFAG ring are shown. Progress on ring main
systems like injection and RF are presented. The current status of the study
and its future directions are discussed.Comment: Studies performed within the PRISM Task Force initiativ
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