5,841 research outputs found
The early to middle Eocene transition: an integrated calcareous nannofossil and stable isotope record from the Northwest Atlantic Ocean (IODP Site U1410)
The early to middle Eocene is marked by prominent changes in calcareous nannofossil assemblages coinciding both with longāterm climate changes and modification of the North Atlantic deepāocean circulation. In order to assess the impact of Eocene climate change on surfaceāwater environmental conditions of the Northwest Atlantic, we developed calcareous nannoplankton assemblage data and bulk stable isotope records (Ī“18O and Ī“13C) across an early to middle Eocene interval (~52ā43 Ma) at IODP Site U1410 (Southeast Newfoundland Ridge, ~41Ā°N). At this site, early Eocene sediments are pelagic nannofossil chalk, whereas middle Eocene deposits occur as clayārich drift sediments reflecting the progressive influence of northernāsourced deep currents. Between the end of Early Eocene Climatic Optimum and the Ypresian/Lutetian boundary, calcareous nannofossils switched from an assemblage mainly composed of warmāwater and oligotrophic taxa (Zygrhablithus, Discoaster, Sphenolithus, Coccolithus) to one dominated by the more temperate and eutrophic reticulofenestrids. The most prominent period of accelerated assemblage change occurred during a ~2 Myr phase of relatively high bulk Ī“18O values possibly related to the postāEECO cooling. Although the dominance of reticulofenestrids persisted unvaried throughout the middle Eocene interval, early Lutetian (~47.4 to 47 Ma) stable isotope records indicate a reversal in the paleoenvironmetal trends suggesting a potential restoration of warmer conditions. Importantly, our data indicate that the ~2 Myrāinterval immediately following the EECO was crucial in establishing the modern calcareous nannofossil assemblage structure and also reveal that the establishment of Reticulofenestraādominated assemblage occurred prior to the onset of persistent deepācurrent system in the Northwest Atlantic
Ultrafast control of donor-bound electron spins with single detuned optical pulses
The ability to control spins in semiconductors is important in a variety of
fields including spintronics and quantum information processing. Due to the
potentially fast dephasing times of spins in the solid state [1-3], spin
control operating on the picosecond or faster timescale may be necessary. Such
speeds, which are not possible to attain with standard electron spin resonance
(ESR) techniques based on microwave sources, can be attained with broadband
optical pulses. One promising ultrafast technique utilizes single broadband
pulses detuned from resonance in a three-level Lambda system [4]. This
attractive technique is robust against optical pulse imperfections and does not
require a fixed optical reference phase. Here we demonstrate the principle of
coherent manipulation of spins theoretically and experimentally. Using this
technique, donor-bound electron spin rotations with single-pulse areas
exceeding pi/4 and two-pulses areas exceeding pi/2 are demonstrated. We believe
the maximum pulse areas attained do not reflect a fundamental limit of the
technique and larger pulse areas could be achieved in other material systems.
This technique has applications from basic solid-state ESR spectroscopy to
arbitrary single-qubit rotations [4, 5] and bang-bang control[6] for quantum
computation.Comment: 15 pages, 4 figures, submitted 12/2008. Since the submission of this
work we have become aware of related work: J. Berezovsky, M. H. Mikkelsen, N.
G. Stoltz, L. A. Coldren, and D. D. Awschalom, Science 320: 349-352 (2008
Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature
Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components
PET/CT Imaging of c-Myc Transgenic Mice Identifies the Genotoxic N-Nitroso-Diethylamine as Carcinogen in a Short-Term Cancer Bioassay
Background: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. Methodology/Principal Findings: mCT and 18 F-FDG mPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced mCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. Conclusions/Significance: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgeni
Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.
Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives
Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures
Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-Ī± (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKĪ±/Ī² phosphorylation and subsequent NF-ĪŗB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects
Cosmology of a Scalar Field Coupled to Matter and an Isotropy-Violating Maxwell Field
Motivated by the couplings of the dilaton in four-dimensional effective
actions, we investigate the cosmological consequences of a scalar field coupled
both to matter and a Maxwell-type vector field. The vector field has a
background isotropy-violating component. New anisotropic scaling solutions
which can be responsible for the matter and dark energy dominated epochs are
identified and explored. For a large parameter region the universe expands
almost isotropically. Using that the CMB quadrupole is extremely sensitive to
shear, we constrain the ratio of the matter coupling to the vector coupling to
be less than 10^(-5). Moreover, we identify a large parameter region,
corresponding to a strong vector coupling regime, yielding exciting and viable
cosmologies close to the LCDM limit.Comment: Refs. added, some clarifications. Published in JHEP10(2012)06
Characteristics and outcomes of patients with advanced non-small-cell lung cancer who declined to participate in randomised clinical chemotherapy trials
There are inadequate data on the outcomes of patients who declined to participate in randomised clinical trials as compared with those of participants. We retrospectively reviewed the patient characteristics and treatment outcomes of both participants and non-participants in the two randomised trials for chemotherapy-naive advanced non-small-cell lung cancer. Trial 1 compared four platinum-based combination regimens. Trial 2 compared two sequences of carboplatin plus paclitaxel and gefitinib therapies. Nineteen of 119 (16%) and 153 (37%) patients declined to participate in Trials 1 and 2, respectively. Among the background patient characteristics, the only variable associated with trial participation or declining was the patients' attending physicians (P<0.001). Important differences were not observed in the clinical outcomes between participants and non-participants, for whom the response rates were 30.6 vs 34.2% and the median survival times were 489 vs 461 days, respectively. The hazard ratio for overall survival, adjusted for other confounding variables, was 0.965 (95% confidence interval: 0.73ā1.28). In conclusion, there was no evidence to suggest any difference in the characteristics and clinical outcomes between participants and non-participants. Trial designs and the doctorāpatient relationship may have an impact on the patient accrual to randomised trials
TOM40 Mediates Mitochondrial Dysfunction Induced by Ī±-Synuclein Accumulation in Parkinson's Disease.
Alpha-synuclein (Ī±-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype Ī±-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in Ī±-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in Ī±-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in Ī±-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in Ī±-Synucleinopathies
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