The implications of fossil fuel supply constraints on climate change projections: a supply-side analysis

Climate projections are based on emission scenarios. The emission scenarios used by the IPCC and by mainstream climate scientists are largely derived from the predicted demand for fossil fuels, and in our view take insufficient consideration of the constrained emissions that are likely due to the depletion of these fuels. This paper, by contrast, takes a supply-side view of CO emission, and generates two supply-driven emission scenarios based on a comprehensive investigation of likely long-term pathways of fossil fuel production drawn from peer-reviewed literature published since 2000. The potential rapid increases in the supply of the non-conventional fossil fuels are also investigated. Climate projections calculated in this paper indicate that the future atmospheric CO concentration will not exceed 610ppm in this century; and that the increase in global surface temperature will be lower than 2.6°C compared to pre-industrial level even if there is a significant increase in the production of non-conventional fossil fuels. Our results indicate therefore that the IPCC's climate projections overestimate the upper-bound of climate change. Furthermore, this paper shows that different production pathways of fossil fuels use, and different climate models, are the two main reasons for the significant differences in current literature on the topic

EGFR and COX-2 protein expression in non-small cell lung cancer and the correlation with clinical features

<p>Abstract</p> <p>Background</p> <p>To evaluate the expression of EGFR and COX-2 and their correlation with prognosis in NSCLC</p> <p>Methods</p> <p>The paraffin embedded tumor samples of 50 NSCLC patients receiving radical resection were analyzed immunohistochemically for EGFR and COX-2 expression and their prognostic values were explored.</p> <p>Results</p> <p>The positive rate of EGFR protein in NSCLC tumor cells was 46%, which was significantly higher than its expression in normal lung (p = 0.0234) and paracancerous tissues (p = 0.020). EGFR expression was significantly higher in nodal positive than in nodal negative patients (p = 0.04). The mean survival time for EGFR positive patients (31 months) was significantly lower than that for patients with EGFR negative expression (48 months) (p = 0.008,). In patients receiving post-operation thoracic irradiation, the mean survival time for EGFR positive patients was significantly lower than that for patients without EGFR positive expression (25 vs. 48 months, P = 0.004). The positive rate of COX-2 protein expression in NSCLC tumor cells was 90%, which was significantly higher than that in normal tissue(p = 0.00) and paracancerous tissue (p = 0.00). There was no correlation between COX-2 expression and patient survival, and no correlation between COX-2 and EGFR protein expression (P = 0.555).</p> <p>Conclusions</p> <p>COX-2 and EGFR are over-expressed in NSCLC. EGFR is an independent prognostic factor and a predictive factor for radiotherapy response in NSCLC.</p

Water use for shale gas extraction in the Sichuan Basin, China

This study investigates the use of water for extracting shale gas in the Sichuan Basin of China. Both net water use and water intensity (i.e., water use per unit of gas produced) of shale wells are estimated by applying a process-based life cycle inventory (LCI) model. The results show that the net water use and water intensity are around 24500 m3/well and 1.9 m3 water/104m3 gas respectively, and that the fracturing and completion stage of shale gas extraction accounts for the largest share in net water use. A comparison shows that China's water use for shale gas extraction is generally higher than that of other countries. By considering the predicted annual drilling activities in the Sichuan Basin, we find that the annual water demand for shale gas development is likely to be negligible compared to total regional water supply. However, considering the water demand for shale gas extraction and the water demand from other sectors may make water availability a significant concern for China's shale gas development in the future

Effect of 4-nonylphenol on the sperm dynamic parameters, morphology and fertilization rate of Bufo raddei

4-Nonylphenol (NP) is a compound that causes endocrine disruption and affects sperm quality of mammals and fish. However, the effects of NP on the sperm and fertilization rate of amphibians remain unknown. This study investigates the in vivo and in vitro effects of NP on the sperm dynamic parameters and fertilization rate of Bufo raddei during the period of amplexus and fertilization, and proposes the induction of these effects. In in vivo assay, male B. raddei were exposed to 3 concentrations of NP (50, 200, or 400 μg/l) or alcohol (0.04‰, control) for 1-3 days. The results suggested that effects on NP on the sperm dynamic parameters, sperm integrity and fertilization rate were not significant (p&gt;0.05). In in vitro assay, the sperm of B. raddei was directly exposed to NP. Based on the results, NP significantly affected the sperm dynamic parameters and integrity (p&lt;0.05). Meanwhile, the sperm reactive oxygen species (ROS) level in the sperm increased significantly (p&lt;0.05), and a negative correlation was recorded between sperm motility and its corresponding ROS level (R=−0.90). Besides, fertilization rate was significantly reduced compared with that of control (p&lt;0.01). The sperm membrane was impaired as well. However, a risk that NP can disrupt the reproduction behavior of B. raddei exists, and the ROS induced by NP and NP itself would be associated with the reduction of fertilization.Keywords: 4-Nonylphenol, Bufo raddei, sperm, morphology, fertilizatio

Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis.

Clathrin-mediated endocytosis (CME) involves the recruitment of numerous proteins to sites on the plasma membrane with prescribed timing to mediate specific stages of the process. However, how choreographed recruitment and function of specific proteins during CME is achieved remains unclear. Using genome editing to express fluorescent fusion proteins at native levels and live-cell imaging with single-molecule sensitivity, we explored dynamin2 stoichiometry, dynamics, and functional interdependency with actin. Our quantitative analyses revealed heterogeneity in the timing of the early phase of CME, with transient recruitment of 2-4 molecules of dynamin2. In contrast, considerable regularity characterized the final 20 s of CME, during which ∼26 molecules of dynamin2, sufficient to make one ring around the vesicle neck, were typically recruited. Actin assembly generally preceded dynamin2 recruitment during the late phases of CME, and promoted dynamin recruitment. Collectively, our results demonstrate precise temporal and quantitative regulation of the dynamin2 recruitment influenced by actin polymerization

Siah2 control of T-regulatory cells limits anti-tumor immunity.

Understanding the mechanisms underlying anti-tumor immunity is pivotal for improving immune-based cancer therapies. Here, we report that growth of BRAF-mutant melanoma cells is inhibited, up to complete rejection, in Siah2-/- mice. Growth-inhibited tumors exhibit increased numbers of intra-tumoral activated T cells and decreased expression of Ccl17, Ccl22, and Foxp3. Marked reduction in Treg proliferation and tumor infiltration coincide with G1 arrest in tumor infiltrated Siah2-/- Tregs in vivo or following T cell stimulation in culture, attributed to elevated expression of the cyclin-dependent kinase inhibitor p27, a Siah2 substrate. Growth of anti-PD-1 therapy resistant melanoma is effectively inhibited in Siah2-/- mice subjected to PD-1 blockade, indicating synergy between PD-1 blockade and Siah2 loss. Low SIAH2 and FOXP3 expression is identified in immune responsive human melanoma tumors. Overall, Siah2 regulation of Treg recruitment and cell cycle progression effectively controls melanoma development and Siah2 loss in the host sensitizes melanoma to anti-PD-1 therapy

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background: Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects. Methodology/Principal Findings: aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%). Conclusions/Significance: It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects

Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

Abstract Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC. Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more CNAs and marked for worse prognosis compared with subtype2. Moreover, database annotation suggested that two significantly differential CNA genes (PIK3CA and FBXW7) between subtype3 and subtype2 may serve as therapeutic drug targets. This study has extended our knowledge of the genetic basis of ESCC and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients

Associations between composite dietary antioxidant index and estimated 10-year atherosclerotic cardiovascular disease risk among U.S. adults

BackgroundAtherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death and disability both in U.S. and worldwide. Antioxidants have been proved critical in mitigating the development of atherosclerosis. This study aimed to investigate the associations between composite dietary antioxidant index (CDAI) and estimated 10-year ASCVD risk among U.S. adults.MethodsData extracted from the National Health and Nutrition Examination Survey were analyzed. A total of 10,984 adults aged 18 years and above were included in this study. CDAI was calculated based on the dietary intake reported in their 24-h recall interviews. The estimated 10-year ASCVD risk was calculated via Pooled Cohort Equations (PCE).ResultsAfter adjusting potential confounders, it was indicated that CDAI score was negatively correlated with 10-year ASCVD risk (OR 0.97, 95% CI 0.95–0.99). Stratify CDAI score by quartile, results showed that participants in the second, third, and fourth quartiles had lower ASCVD odds ratio (Q2: OR 0.87, 95% CI 0.69–1.09; Q3: OR 0.78, 95% CI 0.62–0.98; Q4: OR 0.74, 95% CI 0.59–0.94) than those in the first quartile (Q1, lowest CDAI score group), which was confirmed by the trend test as well (p &lt; 0.05). Subgroup analyses stratified by sex, age, race/ethnicity, and smoking status did not show significant effect modification.ConclusionHigher dietary antioxidants intake is associated with lower ASCVD risk among U.S. adults, for which policymakers and healthcare professionals may consider increasing the consumption of antioxidant-rich foods as a preventive strategy for ASCVD