The transcriptional co‐activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and ...liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD‐family co‐activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP‐TEAD cooperates with the RAS‐induced AP‐1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF‐SRF to promote activation of cancer‐associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2‐LATS1/2) pathway and the key upstream activators are mechanically induced Integrin‐SRC and E‐cadherin‐AJUBA/TRIP6/LIMD1, growth factor induced PI3K‐AKT, and inflammation‐induced G‐protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy.
YAP and TAZ are key mediators of wound healing and tissue regeneration responses as well as important drivers of solid tumor growth, metastasis, and resistance to therapy, making them attractive therapeutic targets for cancer.
Engineering controllable, strongly interacting many-body quantum systems is at the frontier of quantum simulation and quantum information processing. Arrays of laser-cooled neutral atoms in optical ...tweezers have emerged as a promising platform because of their flexibility and the potential for strong interactions via Rydberg states. Existing neutral atom array experiments utilize alkali atoms, but alkaline-earth atoms offer many advantages in terms of coherence and control, and also open the door to new applications in precision measurement and time keeping. In this Letter, we present a technique to trap individual alkaline-earth-like ytterbium (Yb) atoms in optical tweezer arrays. The narrow ^{1}S_{0}-^{3}P_{1} intercombination line is used for both cooling and imaging in a magic-wavelength optical tweezer at 532 nm. The low Doppler temperature allows for imaging near the saturation intensity, resulting in a very high atom detection fidelity. We demonstrate the imaging fidelity concretely by observing rare (<1 in 10^{4} images) spontaneous quantum jumps into and out of a metastable state. We also demonstrate stochastic loading of atoms into a two-dimensional, 144-site tweezer array. This platform will enable advances in quantum information processing, quantum simulation, and precision measurement. The demonstrated narrow-line Doppler imaging may also be applied in tweezer arrays or quantum gas microscopes using other atoms with similar transitions, such as erbium and dysprosium.
Our objective was to compare the effects on mental and physical wellbeing, health related quality of life and long-term adherence to physical activity, of participation in physical activity in ...natural environments compared with physical activity indoors. We conducted a systematic review using the following data sources: Medline, Embase, Psychinfo, GreenFILE, SportDISCUS, The Cochrane Library, Science Citation Index Expanded, Social Sciences Citation Index, Arts and Humanities Citation Index, Conference Proceedings Citation Index − Science and BIOSIS from inception to June 2010. Internet searches of relevant Web sites, hand searches of relevant journals, and the reference lists of included papers and other review papers identified in the search were also searched for relevant information. Controlled trials (randomized and nonrandomized) were included. To be eligible trials had to compare the effects of outdoor exercise initiatives with those conducted indoors and report on at least one physical or mental wellbeing outcome in adults or children. Screening of articles for inclusion, data extraction, and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Due to the heterogeneity of identified studies a narrative synthesis was performed. Eleven trials (833 adults) were included. Most participants (6 trials; 523 adults) were young students. Study entry criteria and methods were sparsely reported. All interventions consisted of a single episode of walking or running indoors with the same activity at a similar level conducted outdoors on a separate occasion. A total of 13 different outcome measures were used to evaluate the effects of exercise on mental wellbeing, and 4 outcome measures were used to assess attitude to exercise. Most trials (n = 9) showed some improvement in mental wellbeing on one or other of the outcome measures. Compared with exercising indoors, exercising in natural environments was associated with greater feelings of revitalization and positive engagement, decreases in tension, confusion, anger, and depression, and increased energy. However, the results suggested that feelings of calmness may be decreased following outdoor exercise. Participants reported greater enjoyment and satisfaction with outdoor activity and declared a greater intent to repeat the activity at a later date. None of the identified studies measured the effects of physical activity on physical wellbeing or the effect of natural environments on exercise adherence. The hypothesis that there are added beneficial effects to be gained from performing physical activity outdoors in natural environments is very appealing and has generated considerable interest. This review has shown some promising effects on self-reported mental wellbeing immediately following exercise in nature which are not seen following the same exercise indoors. However, the interpretation and extrapolation of these findings is hampered by the poor methodological quality of the available evidence and the heterogeneity of outcome measures employed. The review demonstrates the paucity of high quality evidence on which to base recommendations and reveals an undoubted need for further research in this area. Large, well designed, longer term trials in populations who might benefit most from the potential advantages of outdoor exercise are needed to fully elucidate the effects on mental and physical wellbeing. The influence of these effects on the sustainability of physical activity initiatives also awaits investigation.
Single atoms and atomlike defects in solids are ideal quantum light sources and memories for quantum networks. However, most atomic transitions are in the ultraviolet-visible portion of the ...electromagnetic spectrum, where propagation losses in optical fibers are prohibitively large. Here, we observe for the first time the emission of single photons from a single Er^{3+} ion in a solid-state host, whose optical transition at 1.5 μm is in the telecom band, allowing for low-loss propagation in optical fiber. This is enabled by integrating Er^{3+} ions with silicon nanophotonic structures, which results in an enhancement of the photon emission rate by a factor of more than 650. Dozens of distinct ions can be addressed in a single device, and the splitting of the lines in a magnetic field confirms that the optical transitions are coupled to the electronic spin of the Er^{3+} ions. These results are a significant step towards long-distance quantum networks and deterministic quantum logic for photons based on a scalable silicon nanophotonics architecture.
Alkylation reactions represent an important organic transformation to form C–C bonds. In addition to conventional approaches with alkyl halides or sulfonates as alkylating agents, the use of ...unactivated olefins for alkylations has become attractive from both cost and sustainability viewpoints. This Review summarizes transition-metal-catalyzed alkylations of various carbon–hydrogen bonds (addition of C–H bonds across olefins) using regular olefins or 1,3-dienes up to May 2016. According to the mode of activation, the Review is divided into two sections: alkylation via C–H activation and alkylation via olefin activation.
Neutral atom qubits with Rydberg-mediated interactions are a leading platform for developing large-scale coherent quantum systems. In the majority of experiments to date, the Rydberg states are not ...trapped by the same potential that confines ground state atoms, resulting in atom loss and constraints on the achievable interaction time. In this Letter, we demonstrate that the Rydberg states of an alkaline earth atom, ytterbium, can be stably trapped by the same red-detuned optical tweezer that also confines the ground state, by leveraging the polarizability of the Yb^{+} ion core. Using the previously unobserved ^{3}S_{1} series, we demonstrate trapped Rydberg atom lifetimes exceeding 100 μs, and observe no evidence of auto- or photoionization from the trap light for these states. We measure a coherence time of T_{2}=59 μs between two Rydberg levels, exceeding the 28 μs lifetime of untrapped Rydberg atoms under the same conditions. These results are promising for extending the interaction time of Rydberg atom arrays for quantum simulation and computing, and are vital to capitalize on the extended Rydberg lifetimes in circular states or cryogenic environments.
Fatigue-related impairments in the nursing workforce contribute to a multitude of health, safety, and economic consequences at the individual, organizational and societal levels. Long and compressed ...work schedules are commonly worked in the healthcare industry, but more research is needed to understand the cumulative effects of multiple work shifts on physiology-based performance outcomes in nurses. The purpose of this study was to compare the effects of a single nursing work shift versus three compressed (one every 24 hours) 12 hour shifts on performance-based fatigue in nurses and aides. Twenty-six fulltime hospital working nurses and aides (age = 36.1 ± 13.3 years) reported to the lab for testing before, immediately after working a single 12 hour shift, and after working three 12 hour shifts in a 72 hour period. Outcome measures included vigilance-based reaction time, lapses of attention, and muscle function assessments (lower and upper body muscle strength, explosive strength and vertical jump performance). All variables except hand grip strength showed a significant decline following the three work shifts. The psychomotor vigilance reaction time and lapses of attention variables also generally showed a significant decline from the end of shift one to the end of shift three, indicting an accumulation of fatigue in these metrics with increasing number of shifts worked. Muscle function variables responded early in the duty cycle, showing a significant decline after a single work shift, but did no further decline by the end of the third shift. These findings use objective measures to substantiate that fatigue impairments occur from working a single 12 hour shift, and in several instances, increase further with more successive work shifts. Caution should be employed by personnel and administrators with work schedules involving multiple compressed 12 hour shifts. Fatigue management strategies may be used to improve risks and consequences from fatigue-related mishaps, and this study reports several variables that appear sensitive to identifying and tracking fatigue in this population.
ABSTRACT
Objective
“Pro‐ana” or Thinspiration websites are internet sites that support weight loss and eating disorders. Fitspiration websites are a newer type of site that supposedly advocates a fit ...and healthy lifestyle.
Method
The first 10 images from a sample of 50 Fitspiration and 50 Thinspiration websites, chosen using a standard internet search protocol, were rated on a variety of weight, eating, and appearance characteristics. χ2 analyses were conducted to compare website content.
Results
Thinspiration sites featured more content related to losing weight or fat, praising thinness, showng a thin pose, and providing food guilt messages than Fitspiration sites. However, sites did not differ on guilt‐inducing messages regarding weight or the body, fat/weight stigmatization, the presence of objectifying phrases, and dieting/restraint messages. Overall, 88% of Thinspiration sites and 80% of Fitspiration sites contained one or more of the coded variables.
Discussion
Prior research has examined Thinspiration websites and noted the potentially hazardous messages contained on these sites. This content analysis indicates that sites supposedly devoted to healthy pursuits (fitness) may also contain thematically similar content. (Int J Eat Disord 2016; 49:98–101)
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