Advancements in the Development of non-BET Bromodomain Chemical Probes

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets.     

A red code triggers an unintended approach motivation toward sweet ultra-processed foods: Possible implications for front-of-pack labels

Front-of-package labels (FOPL) are recommended to reduce consumer intake of ultra-processed food products (UPP). The multiple traffic-light label is one example of FOPL that indicates the content of target nutrients in products by displaying red (high), amber (medium), and/or green (low) color-coding. The red code may implicitly enhance sweetness perception and approach dispositions toward sweet UPP via cross-modal visual-taste interactions. We conducted two experiments to examine the possibility of contradictory influence of explicitly learned and implicit cross-modal associations on the emotional responses evoked by UPP pictures. In both experiments, we first explicitly associated the color codes with health-related meanings. In Experiment I (n = 78), a psychometric tool estimated the emotional responses (pleasantness and arousal ratings) evoked by UPP pictures when preceded by red, amber, or green color-codes. In Experiment II (n = 24), we recorded participants’ electrocortical brain activity to assess the early posterior negativity (EPN) component as an index of the emotional responses to UPP. The reported pleasantness (Experiment I) and the EPN amplitude (Experiment II) were greater for sweet UPP relative to salty UPP when primed with red codes but not when primed with green or amber. A red code increased positive emotions toward sweet UPP despite its explicit association with increased health-risks. Thus, the use of multiple traffic-lights might lead to an unintended implicit approach behavior toward sweet UPP. Designers, researchers, and policy makers may consider color-taste cross-modal associations when designing, testing, and applying FOPL.     

剂油比对煤焦油沥青质加氢过程的影响

以中低温煤焦油沥青质为原料,采用NiMoW/γ-Al_2O_3商业催化剂,在反应温度380℃、反应压力8 MPa和反应时间1.5 h条件下,分别在不同剂油质量比(1∶25、1∶20、1∶15、1∶10)条件下进行加氢实验,通过采用元素分析、FT-IR、XRD、~1H-NMR和XPS等分析表征手段,考察不同剂油质量比对中低温煤焦油沥青质加氢转化过程的影响。结果表明,随着剂油质量比的增加,沥青质转化率提高,加氢产物分布也发生大幅变化,沥青质和芳香分轻质化转化为饱和分。但随着剂油质量比的进一步提高,同时也发生了更多的裂化反应和缩合反应,剂油质量比在合适范围能够很好地起到加氢轻质化且抑制结焦的效果。     

THE effect of Srandom DOPANT fluctuation on threshold voltage and drain current variation in junctionless nanotransistors

We investigate the effect of dopant random fluctuation on threshold voltage and drain current variation in a two-gate nanoscale transistor. We used a quantum-corrected technology computer aided design simulation to run the simulation (10000 randomizations). With this simulation, we could study the effects of varying the dimensions (length and width), and thicknesses of oxide and dopant factors of a transistor on the threshold voltage and drain current in subthreshold region (off) and overthreshold (on). It was found that in the subthreshold region the variability of the drain current and threshold voltage is relatively fixed while in the overthreshold region the variability of the threshold voltage and drain current decreases remarkably, despite the slight reduction of gate voltage diffusion (compared with that of the subthreshold). These results have been interpreted by using previously reported models for threshold current variability, load displacement, and simple analytical calculations. Scaling analysis shows that the variability of the characteristics of this semiconductor increases as the effects of the short channel increases. Therefore, with a slight increase of length and a reduction of width, oxide thickness, and dopant factor, we could correct the effect of the short channel.     

Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

纳米氧化物对水泥基料化学收缩的影响

采用ASTM化学收缩试验方法,研究纳米SiO2、MgO、Al2O3对水泥基材料化学收缩变化的影响,明确纳米材料种类的差异性。结果表明,各实验组水泥基材料化学收缩均经历三阶段:急速变化区、缓慢变化区、平稳区,7d始水泥基材料化学收缩基本稳定。几种纳米材料的最佳掺量对水泥基材料的化学收缩改善作用大小为:SiO2>Al2O3>MgO。研究发现,纳米材料种类和掺量的不同对化学收缩的影响也较大,在选用时,需综合考虑。     

绿色化工技术在精细化工中的应用研究

社会经济快速发展,科学技术不断进步,针对我国现代工业化工行业发展,所产生的新型化工技术应用,促进我国化工生产效率的提升。工业的发展不可避免地会带来污染物的产生,如果不能有效控制化工排放污染物,温室效应问题会更加严重。本文对绿色化工技术在精细化工中的有效应用进行研究,降低工业废气污染物排放量,维护生态环境平衡。     

柠条的纤维特性及其双螺杆CMP制浆性能研究

以柠条为原料，分析了其化学组分和纤维形态，并探讨了柠条双螺杆CMP法的制浆工艺以及浆料的纤维形态和成纸的物理性能。研究结果表明：与针、阔叶木相比，柠条原料中纤维素和综纤维素质量分数较低，苯醇抽出物和热水抽出物质量分数较高，柠条纤维长度总体偏短，木质部和皮部的纤维质量平均长度分别为0.621和0.819 mm，还存在部分杂细胞。采用3.5% Na₂SO₃和1.5% NaOH常温预浸12 h、90℃汽蒸1 h后再用双螺杆挤浆机在质量分数35%下进行搓丝，并结合高浓盘磨机磨浆，所得CMP浆得率可达73%。柠条CMP浆基本保持了纤维原有的长度，质量平均长度达0.650 mm，长宽比为32.7，纤维解离较好，但分丝帚化情况不理想，含有部分纤维束和杂细胞。当加拿大游离度为300 mL时，柠条CMP浆成纸的环压强度指数和松厚度较高，分别为8.67（N·m）/g和2.56 cm³/g，抗张指数为19.6（N·m）/g，本色浆白度较高，达50%（ISO）。柠条CMP浆适合配抄瓦楞原纸等包装用纸，漂白后可配抄新闻纸和白板纸。     

In-situ TEM observation of structural changes in nano-crystalline CoCrCuFeNi multicomponent high-entropy alloy (HEA) under fast electron irradiation by high voltage electron microscopy (HVEM)

The structural changes induced in a CoCrCuFeNi multicomponent nano-crystalline high-entropy alloy (HEA) under fast electron irradiation were investigated by in-situ transmission electron microscopy (TEM) using a high voltage electron microscope (HVEM). A fine-grained face centered cubic (fcc) single phase was obtained in the sputtered specimens. The fcc solid solution showed high phase stability against irradiation over a wide temperature range from 298 to 773 K, and remained as the main constituent phase even when the samples were irradiated up to 40 displacement per atom (dpa). Moreover, the irradiation did not seem to induce grain coarsening. This is the first report on the irradiation damage in 5-component HEA under MeV electron irradiation.