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Supplementary Figure 2. The EGFR-GC1118 interaction is not disrupted by excess amounts of high- or low-affinity EGFR ligands. The indicated colorectal cancer cell lines were pre-incubated with 0.1 ug/ml of cetuximab or GC1118 for 2 h prior to the addition of EGFR ligands for 10 min (EGF, HB-EGF, BTC, and TGF-�, 20~500 ng/ml; AREG and EREG, 40~1000 ng/ml). The blue and red lines indicate the relative % of cetuximab and GC1118, respectively, bound to EGFR in the presence of competing ligands compared with bound antibodies in the absence of blocking ligands. Antibody binding to EGFR was assessed by measuring the fluorescence intensity using flow cytometry. The results are expressed as the average{plus minus}SE of % maximal binding of the antibody of triplicate experiments.

Supplementary Figure 1. Kinetic binding interactions between GC1118 and EGFR as analyzed by SPR. SPR sensorgrams were obtained from injections of (A) GC1118 or (B) cetuximab over an EGFR-immobilized surface at a flow rate of 30 µl/min. The results of a quantitative evaluation of the experimental data are shown in Supplementary Table 2.

Supplementary Table 1. X-ray data collection and refinement statistics.

Surface plasmon resonance (SPR)

Folates are essential nutrients with important roles as cofactors in one-carbon transfer reactions, being heavily utilized in the synthesis of nucleic acids and the metabolism of amino acids during cell division(1,2). Mammals lack de novo folate synthesis pathways and thus rely on folate uptake from the extracellular milieu(3). The human reduced folate carrier (hRFC, also known as SLC19A1) is the major importer of folates into the cell(1,3), as well as chemotherapeutic agents such as methotrexate(4–6). As an anion exchanger, RFC couples the import of folates and antifolates to anion export across the cell membrane and it is a major determinant in methotrexate (antifolate) sensitivity as genetic variants and its depletion exhibit drug resistance(4–8). Despite its importance, the molecular basis of substrate specificity by hRFC remains unclear. Here we present cryo-electron microscopy structures of hRFC, in the apo state and captured in complex with methotrexate. Combined with molecular dynamics simulations and functional experiments, our study uncovers key determinants of hRFC transport selectivity amongst folates and antifolate drugs while shedding light on important features of anion recognition by hRFC.

CO2 utilization technologies can not only provide a pathway to reduce greenhouse gas emissions but may also enable renewable energy to be incorporated into important materials used in the society such as fuel and chemicals. Power to gas (PtG) technologies, especially Power to methane has been deemed as one of the promising pathways for the conversion of CO2 into valuable gaseous fuel. Many reports have reviewed the academic literature related to CO2 methanation. While the benefits of high temperature methanation for overall process efficiency are well understood, the potential for low-temperature methanation is less understood. In particular the opportunities that arise from coupling a low-temperature methanation process with low temperature hydrogen production technologies, such as PEM electrolysis, have received little attention. It is therefore considered valuable to provide a critical review of the state of the art of this technology at low temperature conditions for the interests of broader research community. In this paper we focus on the recent work around low temperature CO2 methanation including reaction thermodynamics and kinetics, catalyst materials including supports and promoters, and suitable reactor technologies. We discuss each of these critical aspects of the technology and identify key challenges and opportunities for low temperature CO2 methanation (methanation conducted at temperatures less than 300 °C). As part of this paper, we also present the results of an ASPEN Plus simulation study based on data available from the literature to highlight the potential energy efficiency gains of a low temperature methanation process.

With the advancements in deep learning, deep generative models combined with graph neural networks have been successfully employed for data-driven molecular graph generation. Early methods based on the non-autoregressive approach have been effective in generating molecular graphs quickly and efficiently but have suffered from low performance. In this paper, we present an improved learning method involving a graph variational autoencoder for efficient molecular graph generation in a non-autoregressive manner. We introduce three additional learning objectives and incorporate them into the training of the model: approximate graph matching, reinforcement learning, and auxiliary property prediction. We demonstrate the effectiveness of the proposed method by evaluating it for molecular graph generation tasks using QM9 and ZINC datasets. The model generates molecular graphs with high chemical validity and diversity compared with existing non-autoregressive methods. It can also conditionally generate molecular graphs satisfying various target conditions.

The discovery of high-performance functional materials is crucial for overcoming technical issues in modern industries. Extensive efforts have been devoted toward accelerating and facilitating this process, not only experimentally but also from the viewpoint of materials design. Recently, machine learning has attracted considerable attention, as it can provide rational guidelines for efficient material exploration without time-consuming iterations or prior human knowledge. In this regard, here we develop an inverse design model based on a deep encoder-decoder architecture for targeted molecular design. Inspired by neural machine language translation, the deep neural network encoder extracts hidden features between molecular structures and their material properties, while the recurrent neural network decoder reconstructs the extracted features into new molecular structures having the target properties. In material design tasks, the proposed fully data-driven methodology successfully learned design rules from the given databases and generated promising light-absorbing molecules and host materials for a phosphorescent organic light-emitting diode by creating new ligands and combinatorial rules. Tell your computer the materials properties you need, and it will design the molecule you are looking for. Kyungdoc Kim and colleagues from Samsung and Sungkyunkwan University, Republic of Korea, have developed two computer algorithms that work together for this purpose. The first algorithm looks at a database of known organic molecules and their properties, and finds abstract rules to describe the structure/property relationships; the second one uses these rules to design new molecular structures expected to have the same targeted properties. Using this approach, the researchers have already proposed molecules able to absorb light of a desired color, and materials for the realization of stable and efficient organic displays emitting in the blue. The technique might be applied to discover novel molecules and design rules relevant to a broader range of applications.

As renewable energy source integration increases, P2G technology that can store surplus renewable power as methane is expected to expand. The development of a CO2 methanation catalyst, one of the core processes of the P2G concept, is being actively conducted. In this work, low-rank coal (LRC) was used as a catalyst support for CO2 methanation, as it can potentially enhance the diffusion and adsorption behavior by easily controlling the pore structure and composition. It can also improve the process efficiency owing to its simplicity (no pre-reduction step) and high thermal conductivity, compared to conventional metal oxide-supported catalysts. A screening of single metals (Ni, Co, Ru, Rh, and Pd) on LRC was performed, which showed that Ni was the most active. When Ni on the LRC catalyst was doped with a promoter (Ce and Mg), the CO2 conversion percentage increased by >10% compared to that of the single Ni catalyst. When the CO2 methanation activity was compared at 250–500 °C, the Ce-doped Ni/Eco and Mg-doped Ni/Eco catalysts showed similar or better activity than the commercial metal oxide-supported catalyst. In addition, the catalytic performance remained stable even after the test for an extended time (~200 h). The results of XRD, TEM, and TPR showed that highly efficient LRC-based CO2 methanation catalysts can be made when the metal dispersion and composition are modified.

The wood processing industry produces a significant amount of wood waste. Biomass valorization through pyrolysis has the potential to increase the added value of wood wastes. Pyrolysis is an important thermochemical process that can produce solid, liquid, and gas products. This paper aims to review the pyrolysis of wood wastes from Indonesia, including teak wood (Tectona grandis), meranti (Shorea sp.), sengon (Paraserianthes falcataria (L) Nielsen), and rubberwood (Hevea brasiliensis). The review is based on an in-depth study of reliable literatures, statistical data from government agencies, and direct field observations. The results showed that pyrolysis could be a suitable process to increase the added value of wood waste. Currently, slow pyrolysis is the most feasible for Indonesia, with the main product of charcoal. The efficiency of the slow pyrolysis process can be increased by harvesting also liquid and gaseous products. The use of the main product of pyrolysis in the form of charcoal needs to be developed and diversified. Charcoal is not only used for fuel purposes but also as a potential soil improvement agent.

Bamboo is a potential energy crop for the future and an attractive option to replace wood due to its fast growth, high productivity, and essential fuel characteristics such as low ash content, alkali index, and high heating value. This study aimed to evaluate the effects of torrefaction on the physical properties of andong (Gigantochloa pseudoarundinacea) and betung (Dendrocalamus asper) bamboo pellets. Torrefaction of bamboo pellets was conducted in an oxidative atmosphere using an electric furnace at 280°C with a residence time of 40 min. The results showed that oxidative torrefaction caused a decrease in the equilibrium moisture content of bamboo pellets. Water resistance and water adsorption test showed that the torrefied pellets are more resistant to water and relative humidity than the non-torrefied pellet, which is beneficial when the pellet is stored for a long time and in humid conditions. The results also showed that the density of bamboo pellets decreased after torrefaction.

The purpose of this study was to determine the effect of biochar application in growing media on the development ofthe roots of Falcataria moluccanna seedlings. Biochar from the waste of meranti wood (Shorea sp.) was produced bya slow pyrolysis process using a traditional kiln at a temperature of 600°C. The study was arranged in a completelyrandomized design with three treatments and 15 replications. The treatments were 100% topsoil (control), 5% biocharand 10% biochar addition to the planting media. F. moluccana was grown from seeds germinated in sand media. Afterone month, F. moluccana was transferred to polybags filled with planting media according to the treatment. Theobservations were conducted for four months. The parameters observed were root length, root volume, and root biomass. The results showed that the addition of biochar indicated a very significant difference in root length, root volume, and root biomass compared to the control. However, the two dosages showed no significantly different effect on root growth. This study concluded that the addition of 5% biochar meranti in the planting media could increase theroot growth of F. moluccana. Keywords: Biochar, Falcataria moluccanna, root growth.

Oil palm (Elaeis guineensis) empty fruit bunches (EFB) have not been utilized optimally. Currently, it is considered as a resource with low economic value. This biomass can be converted into bioenergy through a torrefaction process. Torrefaction is a mild pyrolysis at temperatures ranging between 200 and 300 °C, and it is generally performed under an inert atmosphere. The objective of this study was to evaluate the effects of torrefaction using Counter-Flow Multi Baffle (COMB) on the properties of oil palm EFB pellets. Torrefaction was conducted at 280 °C temperature with a residence time of 4 minutes. The results showed a decrease in the equilibrium moisture content and an increase in hydrophobicity after torrefaction using the COMB reactor. The change in the hygroscopic property could make the oil palm EFB pellet more stable against chemical oxidation and microbial degradation, hence self-heating and auto-ignition during storage could be prevented. The heating value of biomass increased after torrefaction. Torrefaction with the COMB reactor resulted in a heating value of 17.90 MJ/kg, which is comparable with the results of oxidative torrefaction (with longer residence time) of 18.28 MJ/kg. The results suggested that torrefaction using the COMB reactor could provide a great improvement in the quality of the bioenergetic properties of oil palm EFB pellets. However, the high ash content of the EFB pellets implied that the EFB pellets suitable for a small-scale application, but not yet for cofiring in power plants or as a feedstock for gasification . Keywords : Counter-Flow Multi Baffle; oil palm empty fruit bunches; renewable; torrefaction A B S T R A K Tandan kosong kelapa sawit ( Elaeis guineensis ) belum dimanfaatkan secara optimal. Saat ini bahan tersebut masih dianggap sebagai sumber daya bernilai ekonomi rendah. Tandan kosong kelapa sawit (TKKS) dapat dikonversi menjadi bioenergi melalui proses torefaksi. Torefaksi merupakan proses pirolisis ringan pada suhu berkisar antara 200 dan 300 °C dan umumnya dilakukan di bawah kondisi inert. Penelitian ini bertujuan untuk mengetahui pengaruh torefaksi dengan reaktor Counter-Flow Multi Baffle (COMB) terhadap sifat-sifat pelet TKKS. Torefaksi dilakukan pada suhu 280 °C dengan waktu tinggal 4 menit. Hasil penelitian menunjukkan bahwa torefaksi menyebabkan penurunan kadar air kesetimbangan dan menjadi hidrofobik setelah torefaksi dengan reaktor COMB. Perbaikan sifat higroskopis dapat membuat pelet TKKS lebih stabil terhadap oksidasi kimia dan degradasi mikroba, sehingga pemanasan sendiri dan pembakaran spontan selama penyimpanan dapat dicegah. Nilai kalor biomassa meningkat setelah torefaksi. Torefaksi dengan reaktor COMB menghasilkan nilai kalor 17,90 MJ/kg, yang sebanding dengan hasil torefaksi oksidatif dengan waktu tinggal lebih lama, sebesar 18,28 MJ/kg. Hasil penelitian menunjukkan bahwa torefaksi dengan reaktor COMB dapat meningkatkan kualitas energi pelet TKKS. Tetapi pelet TKKS masih memiliki kadar abu yang tinggi sehingga biomassa hasil torefaksi belum sesuai untuk cofiring di pembangkit listrik atau sebagai bahan baku untuk gasifikasi. Kata kunci: Counter-Flow Multi Baffle ; tandan kosong kelapa sawit; terbarukan; torefaksi

A channel for calcium Maintaining the correct balance of calcium concentrations between the cytosol and the mitochondria is essential for cellular physiology. A calcium-selective channel called the mitochondrial calcium uniporter (MCU) mediates calcium entry into mitochondria. Yoo et al. report the high-resolution structure of MCU from Neurospora crassa. The channel is formed by four MCU protomers with differing symmetry between the soluble and membrane domains. The structure, together with mutagenesis, suggests that two acidic rings inside the channel provide the selectivity for calcium. Science , this issue p. 506

Summary N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders. The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase, GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin. Tunicamycin has potent antibacterial activity by inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT. Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information. Here we present crystal structures of human GPT in complex with tunicamycin. Our structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin. We demonstrate that this difference could be exploited for the design of MraY-specific inhibitors as potential antibiotics.

The utilization of low-rank coal is restricted by such factors as high moisture content, low heating value, high propensity to low-temperature oxidation, spontaneous combustion, etc. Some coal upgrading technologies to reduce the moisture content have been developed, one of them is coal upgrading palm oil technology using palm fatty acid distillate as an additive to keep the stability of moisture content in the coal after the process. To study the possibility of the upgrading technology application in Indonesia, some studies have been conducted. The study covered coal characterization such as proximate, ultimate and calorific value, palm fatty acid distillate for stabilization of upgraded low-rank coal and coal upgrading by coal upgrading palm oil technology in laboratory scale. By using 7 Indonesian low-rank coals and 4 palm fatty acid distillates, it is confirmed that the coal upgrading palm oil technology is effective to reduce the moisture content and increase the calorific value of low rank coal.

The objective of the study was to examine the effect of biochar addition on the growth of Paraserianthes falcataria seedlings. Biochar from shorea was produced using a traditional kiln at 400 °C and 600 °C. The scarification of P. falcataria seeds were conducted using hot water with temperature at 80 °C and then soaked for 24 h. The seeds were then spread on to the germination media and after germinated, the seedlings were moved to polybags contain soil and biochar. Two dosages of biochar such as 25 and 50% were applied and compared with control. The research was arranged in a completely randomized design with 15 replicates. The examination of seedlings growth was conducted one week after transplanting, then subsequently monitored every month. The results showed that the addition of biochar improved the survival rate of seedlings, height and diameter increments, root length and root volume. The results showed a potential of using biochar to improve the growth of P. falcataria seedlings in the nursery.

The objective of this study was to determine the properties of biochar from meranti (Shorea sp.) and oil palm (Elaeis guineensis) empty fruit bunches (OPEFB). Biochar was produced using a traditional kiln with a temperature of 400°C and 600°C. The char yield, pH, and proximate analysis were evaluated. The results showed that the maximum char yield was obtained at 400°C, and the increase in temperature resulted in decreased char yield. At the same pyrolysis temperature, char yield was higher in meranti than OPEFB. The results revealed that the pH of meranti and OPEFB changed into basic after pyrolysis, which is essential when biochar is added to soil to neutralize soil acidity and increase the soil cation exchange capacity. The results also showed an increase of fixed carbon in meranti and OPEFB after pyrolysis at 400°C and 600°C. The higher heating values (HHV) in meranti and OPEFB increased after pyrolysis, with a remarkable increase of HHV observed in meranti than OPEFB, showing a higher potential of biochar from meranti to be used for bioenergy application than OPEFB.

본 연구에서는 용매추출 공정 중 최종 건조 과정에서 회수방식을 달리하여 무회분석탄을 제조한 후 물리적 특성과 화학적 구조를 비교하였다. 무회분석탄 제조에는 아역청탄 등급의 Kideco coal과 극성용매인 N-methyl-2-pyrrolidone(NMP)를 사용하였으며, 회수방식으로는 감압건조, 희석침전, 분무건조 방식을 사용하였다. 제조된 무회분석탄의 물성변화를 확인하기 위해 공업분석, 원소분석, 발열량분석을 실시하였고, 화학적 구조를 알아보고자 FT-IR, NMR 분석을 하였다. 공업분석을 통해 무회분석탄의 회분함량이 원탄에 비해 줄어든 것을 확인하였다. FT-IR 분석 결과 감압건조로 회수한 샘플은 추출용매의 피크가 나타나는 반면 희석침전방식으로 제조한 무회분석탄에는 추출용매 피크가 사라지는 것을 확인하였다. 희석침전방식을 사용할 경우 다른 회수방식에 비해 저온공정이 가능하였고, 추출용매로부터 무회분석탄을 보다 확실하게 분리할 수 있었다.

The EGFR-targeted monoclonal antibodies are a valid therapeutic strategy for patients with metastatic colorectal cancer (mCRC). However, only a small subset of mCRC patients has therapeutic benefits and there are high demands for EGFR therapeutics with a broader patient pool and more potent efficacy. In this study, we report GC1118 exhibiting a different character in terms of binding epitope, affinity, mode of action, and efficacy from other anti-EGFR antibodies. Structural analysis of the EGFR–GC1118 crystal complex revealed that GC1118 recognizes linear, discrete N-terminal epitopes of domain III of EGFR, critical for EGF binding but not overlapping with those of other EGFR-targeted antibodies. GC1118 exhibited superior inhibitory activity against high-affinity EGFR ligands in terms of EGFR binding, triggering EGFR signaling, and proliferation compared with cetuximab and panitumumab. EGFR signaling driven by low-affinity ligands, on the contrary, was well inhibited by all the antibodies tested. GC1118 demonstrated robust antitumor activity in tumor xenografts with elevated expression of high-affinity ligands in vivo, whereas cetuximab did not. Considering the significant role of high-affinity EGFR ligands in modulating tumor microenvironment and inducing resistance to various cancer therapeutics, our study suggests a potential therapeutic advantage of GC1118 in terms of efficacy and a range of benefited patient pool. Mol Cancer Ther; 15(2); 251–63. ©2015 AACR.

As part of a study of mixed n-type electronic and ionic conductors, the conductivities of indium doped strontium ruthenium titanates were determined. The SrTi1-x-yRuxInyO3-δ (x ​= ​0.1–0.4, y ​= ​0–0.2) compositions were prepared by conventional solid-state synthesis. Samples were determined to be of a single phase by X-ray powder diffraction and electron probe microanalysis. The temperature and pO2 dependences of the electrical conductivities were investigated by using DC and AC four-probe methods. STRIO820 and STRIO640 have conductivity of 6.4 and 5.4 Scm−1, respectively, at 900 ​°C and pO2 ​= ​1 ​atm. The conductivities of the In-doped samples under the same conditions were lower than that of SrTi1-xRuxO3-δ by around two orders of magnitude. For STRIO622, when pO2 was increased from 10−4 to 1 ​atm, the DC conductivities decreased, indicating n-type conduction. The pO2 dependence of conductivity was analyzed using the relation σT ​= ​ApO21/x ​+ ​σi. STRIO622 shows significant ionic conductivity, with σi ~0.21 Scm−1 at 1000 ​°C. The DC conductivities of STRIO622 in reducing environments (5% H2/N2 saturated with water) show protonic conduction at low temperatures. The thermal expansion coefficients (TECs) were ~8.9–11.2 ​× ​10−6 ​K−1 ​at 200 ​≤ ​T ​≤ ​990 ​°C.

What is the best number of gear steps for parallel type hybrid electric vehicles (HEVs) and what are the pros and cons of the power split type HEV compared to the parallel type have been interesting issues in the development of HEVs. In this study, a comparative analysis was performed to evaluate the fuel economy potential of a parallel HEV and a power split type HEV. First, the fuel economy potential of the parallel HEV was investigated for the number of gear steps. Four-speed, six-speed, and eight-speed automatic transmissions (ATs) and a continuously variable transmission (CVT) were selected, and their drivetrain losses were considered in the dynamic programming (DP). It was found from DP results that the power electronics system (PE) loss decreased because the magnitude of the motor load leveling power decreased as the number of gear steps increased. On the other hand, the drivetrain losses including the electric oil pump (EOP) loss increased with increasing gear step. The improvement rate from the 4-speed to the 6-speed was the greatest, while it decreased for the higher gear step. The fuel economy of the CVT HEV was rather low due to the large EOP loss in spite of the reduced PE loss. In addition, the powertrain characteristics of the parallel HEV were compared with the power split type HEV. In the power split type HEV, the PE loss was almost double compared to that of the parallel HEV because two large capacity motor-generators were used. However, the drivetrain loss and EOP loss of the power split type HEV were found to be much smaller due to its relatively simple architecture. It is expected that the power characteristics of the parallel and power split type HEVs obtained from the DP results can be used in the development of HEV systems.

− The characteristics of binderless briquettes for dried low-rank coal was studied in this work. Two kinds of Indonesian coals were used to briquette after drying them in electric oven. The characteristics of briquettes have been examined by moisture contents, particle size, hydraulic force, and storing period. The optimum moisture contents of briquettes were observed at between 10 wt% and 15 wt%. The strength of coal briquette was stronger as particle size became smaller. The strength of coal briquette was proportional to the hydraulic force under 300 kN, whereas there was little difference among the briquettes made at more than 300 kN of hydraulic force. The strength of briquettes sharply decreased for a week after produced, and then showed the tendency of converging. The results from this work can be a useful guideline of manufacturing and managing upgraded coal briquettes.

Indonesian low rank coal (LRC) was upgraded by the addition of palm acid oil (PAO), and the efficiency of the inhibition of spontaneous combustion, as well as the resistance to moisture readsorption, was compared with raw coal. Fluorescence microscopy images revealed that PAO was well distributed in the coal matrix during the drying process. The PAO coating the surface of coal decreased the pore volume and the surface area of the upgraded coal and improved its stability. The upgraded LRCs had higher heat calorimetry values, greater resistance to moisture readsorption, and a reduced tendency toward spontaneous combustion when compared to raw coal. In upgraded coal briquettes, PAO was present in the form of a network-like structure, which led to an increase in the compressive strength by binding the coal particles. The upgraded LRCs showed less susceptibility to isothermal oxidation due to the PAO coating on the coal particles, which suppressed the reaction of active functional groups with oxygen in the air.

The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na+ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.