It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods. During the accretion ...stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer decreases in the later evolutionary stages, these binaries host a radio millisecond pulsar whose emission is powered by the neutron star's rotating magnetic field. This evolutionary model is supported by the detection of millisecond X-ray pulsations from several accreting neutron stars and also by the evidence for a past accretion disc in a rotation-powered millisecond pulsar. It has been proposed that a rotation-powered pulsar may temporarily switch on during periods of low mass inflow in some such systems. Only indirect evidence for this transition has hitherto been observed. Here we report observations of accretion-powered, millisecond X-ray pulsations from a neutron star previously seen as a rotation-powered radio pulsar. Within a few days after a month-long X-ray outburst, radio pulses were again detected. This not only shows the evolutionary link between accretion and rotation-powered millisecond pulsars, but also that some systems can swing between the two states on very short timescales.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic ...potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24‐dependent and Yap/Taz‐dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease.
Synopsis
The molecular characterization of tumor‐propagating cells in mouse models of lung cancer reveals CD24+/Sca1+ and increased Yap/Taz activity as predictive for tumor metastasis.
Murine lung TPCs with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays.
In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature.
Knockdown of the Hippo mediators Yap1 or Taz decreased migration and metastatic potential of lung cancer cells.
Yap activation was sufficient for driving tumor progression in the Kras mouse model of lung cancer.
The molecular characterization of tumor‐propagating cells in mouse models of lung cancer reveals CD24+/Sca1+ and increased Yap/Taz activity as predictive for tumor metastasis.
Accelerating imaging speed in optical microscopy is often realized at the expense of image contrast, image resolution, and detection sensitivity--a common predicament for advancing high-speed and ...high-throughput cellular imaging. We here demonstrate a new imaging approach, called asymmetric-detection time-stretch optical microscopy (ATOM), which can deliver ultrafast label-free high-contrast flow imaging with well delineated cellular morphological resolution and in-line optical image amplification to overcome the compromised imaging sensitivity at high speed. We show that ATOM can separately reveal the enhanced phase-gradient and absorption contrast in microfluidic live-cell imaging at a flow speed as high as ~10 m/s, corresponding to an imaging throughput of ~100,000 cells/sec. ATOM could thus be the enabling platform to meet the pressing need for intercalating optical microscopy in cellular assay, e.g. imaging flow cytometry--permitting high-throughput access to the morphological information of the individual cells simultaneously with a multitude of parameters obtained in the standard assay.
Structure, gaseous phase hydrogen storage, and electrochemical properties of a series of Laves phase-related BCC solid solution metal hydride alloys with BCC/C14 ratios ranging from 0.09 to 8.52 were ...studied. Some properties are correlated to the phase abundance and V-content in the alloy with monotonic evolutions, for example, lattice constant, phase abundance, and hydrogen storage pressure. Other properties such as gaseous phase capacities, PCT hysteresis, high-rate dischargeability, and bulk hydrogen diffusion correlate better with the C14 phase crystallite size, which are considered to be more related to the synergetic effect between main and secondary phases. In contrast with conventional metal hydride alloys used in NiMH batteries, the electrochemical discharge capacities of these alloys are not between the maximum and the reversible hydrogen storage measured in the gaseous phase. The current study's alloys have electrochemical capacities that are insensitive to composition but have much room for improvement, with high-rate dischargeabilities that are superior compared to other commercially available alloys. With further research, these alloys show potential for high-rate battery applications.
Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these ...patients.
HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death.
Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7-90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death.
Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in individuals without dementia.
(11)CPiB images were obtained ...to measure fibrillar Abeta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure (11)CPiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations.
(11)CPiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions.
Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early Abeta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging.
Objectives
Human age‐dependent telomere attrition and telomere shortening are associated with several age‐associated diseases and poorer overall survival. The aim of this study was to determine ...longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length.
Design and Methods
Leucocyte telomere length was measured by quantitative polymerase chain reaction in 8074 participants from the Prevention of Renal and Vascular End‐stage Disease (PREVEND) study, an ongoing community‐based prospective cohort study initiated in 1997. Follow‐up data were available at two time‐points up to 2007. Leucocyte telomere length was measured, on between one and three separate occasions, in a total of 16 783 DNA samples. Multilevel growth models were created to identify the factors that influence leucocyte telomere dynamics.
Results
We observed an average attrition rate of 0.47 ± 0.16 relative telomere length units (RTLUs) per year in the study population aged 48 (range 39–60) years at baseline. Annual telomere attrition rate increased with age (P < 0.001) and was faster on average in men than in women (P for interaction 0.043). The major independent factors determining telomere attrition rate were active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and multiple traits of the metabolic syndrome (waist–hip ratio, P = 0.007; blood glucose level, P = 0.045, and HDL cholesterol level, P < 0.001).
Conclusions
Smoking and variables linked to the metabolic syndrome are modifiable lifestyle factors that accelerate telomere attrition in humans. The higher rate of cellular ageing may mediate the link between smoking and the metabolic syndrome to an increased risk of several age‐associated diseases.
Since the first release in 2015, OpenTimer v1 has been used in many industrial and academic projects for analyzing the timing of custom designs. After four-year research and developments, we have ...announced OpenTimer v2-a major release that efficiently supports: 1) a new task-based parallel incremental timing analysis engine to break through the performance bottleneck of existing loop-based methods; 2) a new application programming interface (API) concept to exploit high degrees of parallelisms; and 3) an enhanced support for industry-standard design formats to improve user experience. Compared with OpenTimer v1, we rearchitect v2 with a modern C++ programming language and advanced parallel computing techniques to largely improve the tool performance and usability. For a particular example, OpenTimer v2 achieved up to <inline-formula> <tex-math notation="LaTeX">5.33\times </tex-math></inline-formula> speedup over v1 in incremental timing, and scaled higher with increasing cores. Our contributions include both technical innovations and engineering knowledge that are open and accessible to promote timing research in the community.
Creating, manipulating, and detecting coherent electrons is at the heart of future quantum microscopy and spectroscopy technologies. Leveraging and specifically altering the quantum features of an ...electron beam source at low temperatures can enhance its emission properties. Here, we describe electron field emission from a monocrystalline, superconducting niobium nanotip at a temperature of 5.9 K. The emitted electron energy spectrum reveals an ultranarrow distribution down to 16 meV due to tunable resonant tunneling field emission via localized band states at a nanoprotrusion's apex and a cutoff at the sharp low-temperature Fermi edge. This is an order of magnitude lower than for conventional field emission electron sources. The self-focusing geometry of the tip leads to emission in an angle of 3.7°, a reduced brightness of 3.8×10^{8} A/(m^{2} sr V), and a stability of hours at 4.1 nA beam current and 69 meV energy width. This source will decrease the impact of lens aberration and enable new modes in low-energy electron microscopy, electron energy loss spectroscopy, and high-resolution vibrational spectroscopy.
GAMER: GPU-Accelerated Maze Routing Lin, Shiju; Liu, Jinwei; Young, Evangeline F. Y. ...
IEEE transactions on computer-aided design of integrated circuits and systems,
02/2023, Letnik:
42, Številka:
2
Journal Article
Recenzirano
Maze routing is usually the most time-consuming step in global routing and detailed routing. A commonly used maze routing method is to start from one pin and iteratively connect the current route to ...the closest unconnected pin. This method reduces the maze routing problem to multiple multisource-multidestination shortest path problems. The shortest path problem in VLSI routing has: 1) rectilinear routing directions and 2) preferably small via usage. By utilizing these two characteristics, we propose a novel parallel algorithm called GAMER to accelerate the multisource-multidestination shortest path problem for VLSI routing. GAMER decomposes the shortest path search into alternating vertical and horizontal <inline-formula> <tex-math notation="LaTeX">sweep </tex-math></inline-formula> operations, and two parallel algorithms are proposed to accelerate a <inline-formula> <tex-math notation="LaTeX">sweep </tex-math></inline-formula> operation from <inline-formula> <tex-math notation="LaTeX">O(n^{2}) </tex-math></inline-formula> to <inline-formula> <tex-math notation="LaTeX">O(\log _{2}{n}) </tex-math></inline-formula> on a grid graph of <inline-formula> <tex-math notation="LaTeX">n\times n </tex-math></inline-formula>. Several techniques of applying GAMER on irregular routing regions are also introduced. Experiments are conducted by integrating GAMER into the state-of-the-art academic global router CUGR. CUGR adopts a two-level maze routing scheme, including coarse-grained routing and fine-grained routing, and they can be accelerated by <inline-formula> <tex-math notation="LaTeX">19.85\times </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">2.59\times </tex-math></inline-formula>, respectively, with GAMER, achieving an overall speedup of <inline-formula> <tex-math notation="LaTeX">2.7\times </tex-math></inline-formula> without quality degradation.
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