Apoptosis is a cellular suicide program that plays a critical role in development and human diseases, including cancer. Cancer cells evade apoptosis, thereby enabling excessive proliferation, ...survival under hypoxic conditions, and acquired resistance to therapeutic agents. Among various mechanisms that contribute to the evasion of apoptosis in cancer, metabolism is emerging as one of the key factors. Cellular metabolites can regulate functions of pro- and antiapoptotic proteins. In turn, p53, a regulator of apoptosis, also controls metabolism by limiting glycolysis and facilitating mitochondrial respiration. Consequently, with dysregulated metabolism and p53 inactivation, cancer cells are well-equipped to disable the apoptotic machinery. In this article, we review how cellular apoptosis is regulated and how metabolism can influence the signaling pathways leading to apoptosis, especially focusing on how glucose and lipid metabolism are altered in cancer cells and how these alterations can impact the apoptotic pathways.
Summary
Aims
This systematic review and meta‐analysis evaluated the associations between shift work patterns and risks of specific types of obesity.
Methods
PubMed was searched until March 2017 for ...observational studies that examined the relationships between shift work patterns and obesity. Odds ratio for obesity was extracted using a fixed‐effects or random‐effects model. Subgroup meta‐analyses were carried out for study design, specific obesity types and characteristics of shift work pattern.
Results
A total of 28 studies were included in this meta‐analysis. The overall odds ratio of night shift work was 1.23 (95% confidence interval = 1.17–1.29) for risk of obesity/overweight. Cross‐sectional studies showed a higher risk of 1.26 than those with the cohort design (risk ratio = 1.10). Shift workers had a higher frequency of developing abdominal obesity (odds ratio = 1.35) than other obesity types. Permanent night workers demonstrated a 29% higher risk than rotating shift workers (odds ratio 1.43 vs. 1.14).
Conclusion
This meta‐analysis confirmed the risks of night shift work for the development of overweight and obesity with a potential gradient association suggested, especially for abdominal obesity. Modification of working schedules is recommended, particularly for prolonged permanent night work. More accurate and detailed measurements on shift work patterns should be conducted in future research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The interbeds in marble have significant influence on deformation, failure and energy conversion responses.•The interbed structure affects the damage accumulation at the fatigue cyclic stage that ...controls the final failure behaviors.•The energy dissipation and release characteristics are in good agreement with the crack pattern visualization.•Anisotropic failure modes of marble were identified by failure morphology description and X-ray CT scanning.
To exam the anisotropic deformation and energy evolution characteristics of interbedded marble, cylindrical marble samples cored along angles of 0°, 30°, 60°, and 90° with respect to interbeds were subjected to a triaxial compression experiencing disturbance of the fatigue cyclic-confining pressure unloading (FC-CPU) condition. The triaxial stress disturbance process is divided into three stages: a primary static loading stage, a secondary fatigue cyclic loading stage with the same stress amplitude of 120 MPa, and a confining pressure unloading stage. The deformation, crack pattern and energy conversion were studied using the GCTS RTR 2000 rock mechanical system, post-test X-ray computed tomography (CT) scanning technique, and energy mechanism analysis. Results showthat the interbed orientation has an obvious effect on the deformation and crack pattern of marble. Four kinds of crack patterns are revealed from the CT images, and the crack morphology is the simplest for a sample with a 30° orientation. The interbed structure affects the damage accumulation at the fatigue cyclic stage that controls the final failure behavior. The dissipated energy used to drive the crack propagation is relatively large for marble samples undergoing the stress disturbance test compared to those under conventional triaxial tests. The energy dissipation result is in good agreement with the crack pattern, and it is found that the formation of a curved crack consumes much more energy than straight cracks. Through a series of triaxial compression tests under stress disturbance paths, the mechanism of the effect of interbed orientation on fracture behavior and energy evolution of marble are documented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mechanochemistry of glycine under compression and shear at room temperature is predicted using quantum-based molecular dynamics (QMD) and a simulation design based on rotational diamond anvil cell ...(RDAC) experiments. Ensembles of high throughput semiempirical density functional tight binding (DFTB) simulations are used to identify chemical trends and bounds for glycine chemistry during rapid shear under compressive loads of up to 15.6 GPa. Significant chemistry is found to occur during compressive shear above 10 GPa. Recovered products consist of small molecules such as water, structural analogs to glycine, heterocyclic molecules, large oligomers, and polypeptides including the simplest polypeptide glycylglycine at up to 4% mass fraction. The population and size of oligomers generally increases with pressure. A number of oligomeric polypeptide precursors and intermediates are also identified that consist of two or three glycine monomers linked together through C-C, C-N, and/or C-O bridges. Even larger oligomers also form that contain peptide C-N bonds and exhibit branched structures. Many of the product molecules exhibit one or more chiral centers. Our simulations demonstrate that athermal mechanical compressive shearing of glycine is a plausible prebiotic route to forming polypeptides.
Compressive shearing forces can induce mechanochemical oligomerization reactions in glycine.
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IJS, KILJ, NUK, UL, UM, UPUK
ABSTRACT Extended time series of Solar Activity Indices (ESAI) extended the Greenwich series of sunspot area from the year 1874 back to 1821. The ESAI's yearly sunspot area in the northern and ...southern hemispheres from 1821 to 2013 is utilized to investigate characteristics of the north-south hemispherical asymmetry of sunspot activity. Periodical behavior of about 12 solar cycles is also confirmed from the ESAI data set to exist in dominant hemispheres, linear regression lines of yearly asymmetry values, and cumulative counts of yearly sunspot areas in the hemispheres for solar cycles. The period is also inferred to appear in both the cumulative difference in the yearly sunspot areas in the hemispheres over the entire time interval and in its statistical Student's t-test. The hemispherical bias of sunspot activity should be regarded as an impossible stochastic phenomenon over a long time period.
Abstract
Amorphous carbon (a-C) has attracted considerable interest due to its desirable properties, which are strongly dependent on its structure, density and impurities. Using ab initio molecular ...dynamics simulations we show that the sp
2
/sp
3
content and underlying structural order of a-C produced via liquid quenching evolve at high temperatures and pressures on sub-nanosecond timescales. Graphite-like densities (
$$\lesssim$$
≲
2.7 g/cc) favor the formation of layered arrangements characterized by sp
2
disordered bonding resembling recently synthesized monolayer amorphous carbon (MAC), while at diamond-like densities (
$$\gtrsim$$
≳
3.3 g/cc) the resulting structures are dominated by disordered tetrahedral sp
3
hybridization typical of diamond-like amorphous carbon (DLC). At intermediate densities the system is a highly compressible mixture of coexisting sp
2
and sp
3
regions that continue to segregate over 10’s of picoseconds. The addition of nitrogen (20.3%) (a-CN) generates major system features similar with those of a-C, but has the unexpected effect of reinforcing the thermodynamically disfavored carbon structural motifs at low and high densities, while inhibiting phase separation in the intermediate region. At the same time, no nitrogen elimination from the carbon framework is observed above
$$\simeq$$
≃
2.8 g/cc, suggesting that nitrogen impurities are likely to remain embedded in the carbon structures during fast temperature quenches at high pressures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
2,6-Diamino-3,5-dinitropyrazine-1-oxide (LLM-105) is a relatively new and promising insensitive high-explosive (IHE) material that remains only partially characterized. IHEs are of interest for a ...range of applications and from a fundamental science standpoint, as the root causes behind insensitivity are poorly understood. We adopt a multitheory approach based on reactive molecular dynamic simulations performed with density functional theory, density functional tight-binding, and reactive force fields to characterize the reaction pathways, product speciation, reaction kinetics, and detonation performance of LLM-105. We compare and contrast these predictions to 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), a prototypical IHE, and 1,3,5,7-tetranitro-1,3,5,7-tetrazoctane (HMX), a more sensitive and higher performance material. The combination of different predictive models allows access to processes operative on progressively longer timescales while providing benchmarks for assessing uncertainties in the predictions. We find that the early reaction pathways of LLM-105 decomposition are extremely similar to TATB; they involve intra- and intermolecular hydrogen transfer. Additionally, the detonation performance of LLM-105 falls between that of TATB and HMX. We find agreement between predictive models for first-step reaction pathways but significant differences in final product formations. Predictions of detonation performance result in a wide range of values, and one-step kinetic parameters show the similar reaction rates at high temperatures for three out of four models considered.
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IJS, KILJ, NUK, PNG, UL, UM
Background
The objective of this study was to describe the first US‐based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis ...(CRS) in a general‐population sample.
Methods
A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups.
Results
We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms.
Conclusions
CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This work aims at investigating the fracture evolution and energy characteristics of marble subjected to fatigue cyclic loading and confining pressure unloading (FC-CPU) conditions. Although rocks ...under separated fatigue cyclic loading and triaxial unloading conditions have been well studied, little is known about the dependence of the fatigue damage accumulation on the subsequent confining pressure unloading condition that influences the rock fracture behaviors. In this work, the servo-controlled GCTS 2000 rock mechanical system combined with the post-test X-ray computed tomography (CT) scanning technique were used to reveal the fracture behaviors of the marble samples. The samples were tested at three stages: the static loading stage, the fatigue cyclic loading stage, and the confining pressure unloading stage. Results show that the damage index-cycle number curve shows a different pattern—the damage increasing rate is different for the samples experiencing different fatigue damage. The damage accumulation at the fatigue cyclic stage influences the final failure mode and energy conversion. In addition, post-test CT scanning further reveals the effects of fatigue cycles on the crack pattern, as well as the stimulated crack scale and density after FC-CPU testing depending on the fatigue cycle. Furthermore, the stored elastic energy decreases and the dissipated energy increases with increasing fatigue cycle at the fatigue loading stage, and the energy conversion is consistent with the crack pattern analysis. By investigating the failure mechanism of marble under FC-CPU conditions, a theoretical basis for rock dynamic disaster prediction can be created.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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