2,275 research outputs found
Solar influenced late Holocene temperature changes on the northern Tibetan Plateau
Considerable efforts have been made to extend temperature records beyond the instrumental period through proxy reconstructions, in order to further understand the mechanisms of past climate variability. Yet, the global coverage of existing temperature records is still limited, especially for some key regions like the Tibetan Plateau and for earlier times including the Medieval Warm Period (MWP). Here we present decadally-resolved, alkenone-based, temperature records from two lakes on the northern Tibetan Plateau. Characterized by marked temperature variability, our records provide evidence that temperatures during the MWP were slightly higher than the modern period in this region. Further, our temperature reconstructions, within age uncertainty, can be well correlated with solar irradiance changes, suggesting a possible link between solar forcing and natural climate variability, at least on the northern Tibetan Plateau. © 2013 The Author(s).published_or_final_versio
Prostate transglutaminase (TGase-4) antagonizes the anti-tumour action of MDA-7/IL-24 in prostate cancer
Background
Transglutamiase-4 (TGase-4), also known as prostate transglutaminase, belongs to the TGase family and is uniquely expressed in the prostate gland. The functions of this interesting protein are not clearly defined. In the present study, we have investigated an unexpected link between TGase-4 and the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24), a cytokine known to regulate the growth and apoptosis of certain cancer and immune cells.
Methods
Frozen sections of normal and malignant human prostate tissues and human prostate cancer (PCa) cell lines PC-3 and CA-HPV-10, cell lines expressing low and high levels of TGase-4, and recombinant MDA-7/IL-24 (rhMDA-7/IL-24) were used. Expression construct for human TGase-4 was generated using a mammalian expression vector with full length human TGase-4 isolated from normal human prostate tissues. PC-3 cells were transfected with expression construct or control plasmid. Stably transfected cells for control transfection and TGase-4 over expression were created. Similarly, expression of TGase-4 in CA-HPV-10 cells were knocked down by way of ribozyme transgenes. Single and double immunofluorescence microscopy was used for localization and co-localization of TGase-4 and MDA-7/IL-24 in PCa tissues and cells with antibodies to TGase-4; MDA-7/IL-24; IL-20alpha; IL-20beta and IL-22R. Cell-matrix adhesion, attachment and migration were by electric cell substrate impedance sensing and growth by in vitro cell growth assay. A panel of small molecule inhibitors, including Akt, was used to determine signal pathways involving TGase-4 and MDA-7/IL-24.
Results
We initially noted that MDA-7 resulted in inhibition of cell adhesion, growth and migration of human PCa PC-3 cells which did not express TGase-4. However, after the cells over-expressed TGase-4 by way of transfection, the TGase-4 expressing cells lost their adhesion, growth and migratory inhibitory response to MDA-7. On the other hand, CA-HPV-10 cells, a cell type naturally expressing high levels of TGase-4, had a contrasting response to MDA-7 when compared with PC-3 cells. Inhibitor to Akt reversed the inhibitory effect of MDA-7, only in PC-3 control cells, but not the TGase-4 expressing PC-3 cells. In human prostate tissues, TGase-4 was found to have a good degree of co-localization with one of the MDA-7 receptor complexes, IL-20Ra.
Conclusion
The presence of TGase-4 has a biological impact on a prostate cancer cell's response to MDA-7. TGase-4, via mechanism(s) yet to be identified, blocked the action of MDA-7 in prostate cancer cells. This has an important implication when considering the use of MDA-7 as a potential anticancer cytokine in prostate cancer therapies
Building robust prediction models for defective sensor data using Artificial Neural Networks
Predicting the health of components in complex dynamic systems such as an
automobile poses numerous challenges. The primary aim of such predictive
systems is to use the high-dimensional data acquired from different sensors and
predict the state-of-health of a particular component, e.g., brake pad. The
classical approach involves selecting a smaller set of relevant sensor signals
using feature selection and using them to train a machine learning algorithm.
However, this fails to address two prominent problems: (1) sensors are
susceptible to failure when exposed to extreme conditions over a long periods
of time; (2) sensors are electrical devices that can be affected by noise or
electrical interference. Using the failed and noisy sensor signals as inputs
largely reduce the prediction accuracy. To tackle this problem, it is
advantageous to use the information from all sensor signals, so that the
failure of one sensor can be compensated by another. In this work, we propose
an Artificial Neural Network (ANN) based framework to exploit the information
from a large number of signals. Secondly, our framework introduces a data
augmentation approach to perform accurate predictions in spite of noisy
signals. The plausibility of our framework is validated on real life industrial
application from Robert Bosch GmbH.Comment: 16 pages, 7 figures. Currently under review. This research has
obtained funding from the Electronic Components and Systems for European
Leadership (ECSEL) Joint Undertaking, the framework programme for research
and innovation Horizon 2020 (2014-2020) under grant agreement number
662189-MANTIS-2014-
Surprising dissimilarities in a newly formed pair of 'identical twin' stars
The mass and chemical composition of a star are the primary determinants of
its basic physical properties--radius, temperature, luminosity--and how those
properties evolve with time. Thus, two stars born at the same time, from the
same natal material, and with the same mass are 'identical twins,' and as such
might be expected to possess identical physical attributes. We have discovered
in the Orion Nebula a pair of stellar twins in a newborn binary star system.
Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to
within 2 percent. Here we report that these twin stars have surface
temperatures that differ by ~300K (~10%), and luminosities that differ by ~50%,
both at high confidence level. Preliminary results indicate that the stars'
radii also differ, by 5-10%. These surprising dissimilarities suggest that one
of the twins may have been delayed by several hundred thousand years in its
formation relative to its sibling. Such a delay could only have been detected
in a very young, definitively equal-mass binary system3 such as that reported
here. Our findings reveal cosmic limits on the age synchronisation of young
binary stars, often used as tests for the age calibrations of star-formation
models.Comment: Published in Nature, 19 June 200
The Kondo effect in ferromagnetic atomic contacts
Iron, cobalt and nickel are archetypal ferromagnetic metals. In bulk,
electronic conduction in these materials takes place mainly through the and
electrons, whereas the magnetic moments are mostly in the narrow
-electron bands, where they tend to align. This general picture may change
at the nanoscale because electrons at the surfaces of materials experience
interactions that differ from those in the bulk. Here we show direct evidence
for such changes: electronic transport in atomic-scale contacts of pure
ferromagnets (iron, cobalt and nickel), despite their strong bulk
ferromagnetism, unexpectedly reveal Kondo physics, that is, the screening of
local magnetic moments by the conduction electrons below a characteristic
temperature. The Kondo effect creates a sharp resonance at the Fermi energy,
affecting the electrical properties of the system;this appears as a Fano-Kondo
resonance in the conductance characteristics as observed in other artificial
nanostructures. The study of hundreds of contacts shows material-dependent
lognormal distributions of the resonance width that arise naturally from Kondo
theory. These resonances broaden and disappear with increasing temperature,
also as in standard Kondo systems. Our observations, supported by calculations,
imply that coordination changes can significantly modify magnetism at the
nanoscale. Therefore, in addition to standard micromagnetic physics, strong
electronic correlations along with atomic-scale geometry need to be considered
when investigating the magnetic properties of magnetic nanostructures.Comment: 7 pages, 5 figure
Revisiting special relativity: A natural algebraic alternative to Minkowski spacetime
Minkowski famously introduced the concept of a space-time continuum in 1908,
merging the three dimensions of space with an imaginary time dimension , with the unit imaginary producing the correct spacetime distance , and the results of Einstein's then recently developed theory of special
relativity, thus providing an explanation for Einstein's theory in terms of the
structure of space and time. As an alternative to a planar Minkowski space-time
of two space dimensions and one time dimension, we replace the unit imaginary , with the Clifford bivector for the plane
that also squares to minus one, but which can be included without the addition
of an extra dimension, as it is an integral part of the real Cartesian plane
with the orthonormal basis and . We find that with this model of
planar spacetime, using a two-dimensional Clifford multivector, the spacetime
metric and the Lorentz transformations follow immediately as properties of the
algebra. This also leads to momentum and energy being represented as components
of a multivector and we give a new efficient derivation of Compton's scattering
formula, and a simple formulation of Dirac's and Maxwell's equations. Based on
the mathematical structure of the multivector, we produce a semi-classical
model of massive particles, which can then be viewed as the origin of the
Minkowski spacetime structure and thus a deeper explanation for relativistic
effects. We also find a new perspective on the nature of time, which is now
given a precise mathematical definition as the bivector of the plane.Comment: 29 pages, 2 figure
Magnetic effects at the interface between nonmagnetic oxides
The electronic reconstruction at the interface between two insulating oxides
can give rise to a highly-conductive interface. In analogy to this remarkable
interface-induced conductivity we show how, additionally, magnetism can be
induced at the interface between the otherwise nonmagnetic insulating
perovskites SrTiO3 and LaAlO3. A large negative magnetoresistance of the
interface is found, together with a logarithmic temperature dependence of the
sheet resistance. At low temperatures, the sheet resistance reveals magnetic
hysteresis. Magnetic ordering is a key issue in solid-state science and its
underlying mechanisms are still the subject of intense research. In particular,
the interplay between localized magnetic moments and the spin of itinerant
conduction electrons in a solid gives rise to intriguing many-body effects such
as Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions, the Kondo effect, and
carrier-induced ferromagnetism in diluted magnetic semiconductors. The
conducting oxide interface now provides a versatile system to induce and
manipulate magnetic moments in otherwise nonmagnetic materials.Comment: Nature Materials, July issu
Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.
IMPORTANCE: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed. OBJECTIVE: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs. DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed. EXPOSURES: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. MAIN OUTCOMES AND MEASURES: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated. RESULTS: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-123/QALY), and £2381/QALY (1328/QALY), £771/QALY (3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs. CONCLUSIONS AND RELEVANCE: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management
Overexpression of transglutaminase 4 and prostate cancer progression: a potential predictor of less favourable outcomes
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