Present and Future of EGFR Inhibitors for Head and Neck Squamous Cell Cancer

Although EGFR is expressed at high levels in head and neck squamous cell carcinomas (HNSCCs) and mutations are extremely rare, monotherapy with EGFR inhibitors has shown limited success. The PI3kinase/Akt pathway is responsible for cellular survival, and inhibition of phosphatidylinositol (PI) synthesis has antiproliferative, anti-invasive, and antiangiogenesis effects on HNSCC. Molecular crosstalk has been observed between EGFR and IGF1R signaling through the PI3kinase/Akt pathway in HNSCC, as has molecular crosstalk between the NFκB and STAT3 signaling pathways. Therefore, the combination of an EGFR antagonist with an agent that inhibits the activation of both Akt and NFκB may overcome resistance to EGFR antagonists in HNSCC

Challenges toward achieving a successful hydrogen economy in the US: Potential end-use and infrastructure analysis to the year 2100

Fossil fuels continue to exacerbate climate change due to large carbon emissions resulting from their use across a number of sectors. An energy transition away from fossil fuels seems inevitable, and energy sources such as renewables and hydrogen may provide a low carbon alternative for the future energy system, particularly in large emitting nations such as the United States. This research quantifies and maps potential hydrogen fuel distribution pathways for the continental US, reflecting technological changes, barriers to deployment, and end-use-cases from 2020 to 2100, clarifying the potential role of hydrogen in the US energy transition. The methodology consists of two parts, a linear optimization of the global energy system constrained by carbon reduction targets and system cost, followed by a projection of hydrogen infrastructure development. Key findings include the emergence of trade pattern diversification, with a greater variety of end-uses associated with imported fuels and greater annual hydrogen consumption over time. Further, sensitivity analysis identified the influence of complementary technologies including nuclear power and carbon capture and storage technologies. We conclude that hydrogen penetration into the US energy system is economically viable and can contribute toward achieving Paris Agreement and more aggressive carbon reduction targets in the future

The Rice Annotation Project Database (RAP-DB): hub for Oryza sativa ssp. japonica genome information

With the completion of the rice genome sequencing, a standardized annotation is necessary so that the information from the genome sequence can be fully utilized in understanding the biology of rice and other cereal crops. An annotation jamboree was held in Japan with the aim of annotating and manually curating all the genes in the rice genome. Here we present the Rice Annotation Project Database (RAP-DB), which has been developed to provide access to the annotation data. The RAP-DB has two different types of annotation viewers, BLAST and BLAT search, and other useful features. By connecting the annotations to other rice genomics data, such as full-length cDNAs and Tos17 mutant lines, the RAP-DB serves as a hub for rice genomics. All of the resources can be accessed through

GJETC report 2020 : German-Japanese cooperation in energy research ; supporting the closure of implementation gaps ; key results and policy recommendations

The German-Japanese Energy Transition Council (GJETC) was established in 2016 by experts from research institutions, energy policy think tanks, and practitioners in Germany and Japan. The objectives and main activities of the Council and the supporting secretariats are to identify and analyze current and future issues regarding policy frameworks, markets, infrastructure, and technological developments in the energy transition, and to hold Council meetings to exchange ideas and propose better policies and strategies. In its second project phase (2018-2020), the GJETC had six members from academia on the Japanese side, and eight members on the German side, with one Co-Chair from each country. From October 2018 to March 2020, the GJETC worked on and debated six topics: 1) Digitalization and the energy transition. 2) Hydrogen society. 3) Review of German and Japanese long-term energy scenarios and their evaluation mechanism. 4) Buildings, energy efficiency, heating/cooling. 5) Integration costs of renewable energies. 6) Transport and sector coupling. The outputs and the recommendations of the second phase of the GJETC are summarized in this report

GJETC report 2018 : intensified German-Japanese cooperation in energy research ; key results and policy recommendations

The challenges and also potentials of the energy transition are tremendous in Germany, as well as in Japan. Sometimes, structures of the old energy world need "creative destruction" to clear the way for innovations for a decarbonized, low-risk energy system. In these times of disruptive changes, a constructive and sometimes controversial dialog within leading industrial nation as Japan and Germany over the energy transition is even more important. The German-Japanese Energy Transition Council (GJETC) released a summarizing report for the first project phase 2016-2018. It includes jointly formulated recommendations for politics as well as a controversial dialogue part. The Council jointly states and recommends that: Ambitious long-term targets and strategies for a low-carbon energy system must be defined and ambitiously implemented; Germany and Japan as high technology countries need to take the leadership. Both countries will have to restructure their energy systems substantially until 2050 while maintaining their competitiveness and securing energy supply. Highest priority is given to the forced implementation of efficiency technologies and renewable energies, despite different views on nuclear energy. In both countries all relevant stakeholders - but above all the decision-makers on all levels of energy policy - need to increase their efforts for a successful implementation of the energy transition. Design of the electricity market needs more incentives for flexibility options and for the extensive expansion of variable power generation, alongside with strategies for cost reduction for electricity from photovoltaic and wind energy. The implementation gap of the energy efficiency needs to be closed by an innovative energy policy package to promote the principle of "Energy Efficiency First". Synergies and co-benefits of an enhanced energy and resource efficiency policy need to be realized. Co-existence of central infrastructure and the growing diversity of the activities for decentralization (citizens funding, energy cooperatives, establishment of public utility companies) should be supported. Scientific cooperation can be intensified by a joint working group for scenarios and by the establishment of an academic exchange program

Sex differences in the safety of S‐1 plus oxaliplatin and S‐1 plus cisplatin for patients with metastatic gastric cancer

Previous studies have shown sex‐related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex‐related differences in the safety of S‐1 plus oxaliplatin (SOX) and S‐1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S‐1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex‐related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference

Oxygen-evolving photosystem II structures during S1–S2–S3 transitions

Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1,2,3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4,5,6,7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation