From modeling to medicinal chemistry: automatic generation of two-dimensional complex diagrams

As a result of the increasing application of structure-based drug design, the visualization of protein-ligand complexes has become an important feature in medicinal chemistry. The large number of experimentally resolved complex structures and the further development of computer-aided methods like docking or de novo design establishes new possibilities in this field. During lead finding and optimization, a manual investigation of many complexes and their interaction patterns is typically performed. We present an algorithm that automatically generates 2D-protein-ligand diagrams as a possible solution for a transparent visualization of the contact partners in a complex and as a support for scientists in the evaluation of structure-based design results. Running the software on representative test data sets, it generates collision free layouts for approximately 76% of the cases in the range of tenths of a second per complex. The success rate for complexes with ligands which have a molecular weight <500 Da is 87%.     

Multi-scale product property model of polypropylene produced in a FBR: From chemical process engineering to product engineering

A multi-scale product model has been built to characterize the polypropylene (PP) formation dynamics in a catalytic FBR. For the first time, the gas–solid flow field, the morphological and molecular properties of particles, as well as their dynamics can be simultaneously obtained by solving the unique model that couples a CFD model, a population balance model (PBM) and moment equations. The quantitative relationships between the operating conditions and the multi-scale particle properties have been further established. The results demonstrate that the product model can be used to guide a multi-scale generalization of the polymer product from chemical process to product engineering.     

Progress of polymer reaction engineering: From process engineering to product engineering

Polymer reaction engineering studies the design, operation, and optimization of reactors for industrial scale polymerization, based on the theory of polymerization kinetics and transfer processes (e.g., flow, heat and mass transfer). Although the foundation and development of this discipline are less than 80 years, the global production of polymers has exceeded 400 million tons per annum. It demonstrates that polymer reaction engineering is of vital importance to the polymer industry. Along with the maturity of production processes and market saturation for bulk polymers, emerging industries such as information technology, modern transportation, biomedicine, and new energy have continued to develop. As a result, the research objective for polymer reaction engineering has gradually shifted from maximizing the efficiency of the polymerization process to the precise regulation of high-end product-oriented macromolecules and their aggregation structures, i.e., from polymer process engineering to polymer product engineering. In this review, the frontiers of polymer reaction engineering are introduced, including the precise regulation of polymer chain structure, the control of primary aggregation structure, and the rational design of polymer products. We narrow down the topic to the polymerization reaction engineering of vinyl monomers. Moreover, the future prospects are provided for the field of polymer reaction engineering.     

Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives

Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.     

Structural modeling and analysis of FRP composite product subsystems—A systems approach

This study derives a new mathematical model aimed to consider virtual design and manufacturing procedures for developing highly competitive, complex geometry composite products for various engineering applications. The fiber‐reinforced polymer (FRP) composite industry faces several critical issues right from selection (of product, process, equipment, tooling, materials) to manufacturing the final products by meeting several design criteria and customer requirements. An attempt has been made in this article to identify different subsystems and other constituents of five main systems–resin system, reinforcement system, process equipment, tooling system, and product design of total composite product system. Intermediate processes, alternative designs, process sequence, technological changes, chemical reactions, and other performance affecting parameters have been discussed. Graph theoretical models, variable permanent adjacency matrix models, and permanent functions of these systems based on graph theory–matrix algebra–permanent function methodology are developed. Analytical tests for structural analysis of composite product system are derived to select optimum constituents in each of these five systems of composite product. Coefficient of similarity and dissimilarity are useful aid to take right decision between alternative solutions. Permanent function is a unique representation and to be used by composite industry for coding, evaluation, comparison, ranking, and optimum selection. Structural models are useful for basic understanding of complete composite product system, leading to right decisions for manufacturing and business strategies. Step‐by‐step procedure is developed to assist composite industry to implement the proposed method in a right way. Usefulness of the proposed methodology to composite industry is also presented. POLYM. COMPOS., 27:681–699, 2006. © 2006 Society of Plastics Engineers     

Cannabinoids Drugs and Oral Health—From Recreational Side-Effects to Medicinal Purposes: A Systematic Review

Background: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. Methods: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. Results: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. Conclusions: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases.     

Versatility of photoalignment techniques: From nematics to a wide range of functional materials

Alignment methods of nematic liquid crystals (LCs) by surface photoreactions on substrate surfaces were initially proposed around 1990, and the photoalignment technology of nematic LCs has recently been integrated into the LC device fabrication industry due to its profitable features. Accumulated efforts in this field have revealed that applications of photoalignment processes are not limited to conventional nematic LCs but that a variety of functional materials can also be manipulated according to this principle. Target materials have now been extended to thermotropic smectic LCs, discotic LCs, LC polymers, block copolymers, gel networks, conjugated polymers, and organic semiconductors and lyotropic systems including chromonic LCs and inorganic–organic mesostructured hybrids. Through these photochemical approaches, many types of photopatterning for both topographical and orientational modulations have become feasible. This article reviews photoalignment processes applied to a wide range of materials, surveying relatively recent work. Some important related alignment and patterning processes are also introduced to clarify the significance of these photoalignment techniques.     

Bayesian analysis of color preferences: An application for product and product line design

When choosing which colors to offer in their product lines, firms often rely upon consumer preference models that do not account for the heterogeneity of their target market and do not consider the trade‐offs consumers are willing to make for different color options. For this research we used visual conjoint analysis to assess preference for backpack color and then modeled respondent utilities with a Bayesian hierarchal multinomial logit model. This provided counter intuitive results in which product line color options are not additive but each color changes depending on the number of options the firm is willing to offer and that colors which seem to dominate secondary preferences within a target market may not be the best colors to choose for product line expansion. © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 445–456, 2016     

微囊藻毒素降解酶MlrA的结构功能分析

MlrA（亦称microcystinase）是微囊藻毒素（microcystins, MCs）细菌降解途径中负责催化起始反应的关键蛋白酶,其结构特征与底物水解机制尚未明确。使用折叠识别法构建MlrA分子模型,通过分子对接和定点突变分析了酶-底物的结合方式与相互作用,结合蛋白重组表达对酶活性影响机制等进行了探究。结果表明MlrA是定位于细菌细胞质膜的整合膜蛋白,主要由8个跨膜α-螺旋（TM1~8）组成,功能结构域ABI（TM4~7）形成向周质空间开放的底物反应空腔。MlrA催化残基（E172、H205、H260和N264）位于膜内,其侧链投射至反应腔内部。微囊藻毒素LR （MC-LR）采用β-发夹构型与酶结合并将易裂键暴露于水分子附近,其水解机制为E172和H205通过一般碱催化将水分子去质子化激活,对Adda-Arg肽键羰基碳进行亲核攻击;接着H260和N264构成氧阴离子穴以稳定过渡态氧阴离子;最后H205或E172催化胺离去基团发生质子化,使四面体氧阴离子中间体崩解。此外,MlrA不是金属蛋白酶,无法与金属离子（Ⅱ）配位结合,菲咯啉类化合物使酶分子发生非特异性解折叠而失活,EDTA对底物结合位点具有竞争作用。本研究揭示了MlrA的属性与水解机制,为进一步探索MCs微生物降解机理提供一定参考依据。     

制定湿法磷酸净化产品——工业级磷酸和食品级磷酸的企业标准

为了用低能耗的湿法磷酸净化生产工业级和食品级磷酸,以适应我国快速发展的精细磷化工业的需要,急需解决其产品的质量标准及包装标识标注问题。介绍宏福公司于2004年制定的溶剂萃取法净化湿法磷酸生产工业级磷酸及食品级磷酸的企业标准及包装标识标注的有关规定。     

Neutron activation analysis and its application to the analysis of food products

High-flux thermal-neutron activation analysis (NAA) is an extremely sensitive means of quantitatively determining most of the elements of the periodic system. The usual limits of detection, for 75 of the elements, in the absence of appreciable interferences, range from picograms (for some elements) to as high as micrograms (for less sensitive elements). A typical element can be determined down to as low as a nanogram. This high sensitivity enables one to analyze food products, for example, for numerous trace-level elements that may be present: whether natural or added beneficial essential trace elements, or deleterious elements introduced from pesticide residues (such as Br, As and Hg), or from processing (such as Cr, Sn, Sb and Cu). Studies to be reported include the nondestructive determination of Hg in foodstuffs down to levels as low as 0.01 ppm, and of Br in foodstuffs down to about 0.1 ppm. With radiochemical separations, these detection limits can both be extended to 0.001 ppm, if needed. By combination with paper chromatographic or solvent extraction techniques, phosphorus- and halogen-containing pesticides can be sensitively determined. The NAA method can also be used to advantage at element levels much higher than trace levels, and in such cases the very high neutron flux of a nuclear reactor may not be necessary. For example, even with a small 14 Mev neutron generator, the nitrogen content of foodstuffs can be determined nondestructively, rapidly and accurately, down to levels of about 100 ppm. These determinations can also be made on-line, in food processing plants. Presented at the AOCS-AACC Joint Meeting, Washington, D.C., April, 1968.     

Systematic management and analysis of fatty acid data from multiple tissue samples

A systematic approach has been developed for the collection and analysis of gas chromatographic (GC) data from multiple fatty acid profiles. The approach was applied to a series of polar and nonpolar tissue lipids generated in animal feeding studies to allow a comparison of mean fatty acid profiles as a function of either dietary regimen or tissue location. The magnitude of the studies, sufficiently large to minimize error from animal variabilities, mandated the use of computer assistance. Nevertheless, manual input was essential due to the complexity of the GC patterns, and was invoked for peak assignment and report editing. The approach discussed here allowed for the consolidation and statistical analysis of data from over 30,000 GC peaks, and generated results in both tabular and graphic formats. It should be extendable to other chromatographic studies of lipid components. Agricultural Research Service, U.S. Department of Agriculture, 600 E. Mermaid Lane.     

Systematic energetics study of graphene nanoflakes: From armchair and zigzag to rough edges with pronounced protrusions and overcrowded bays

Using the PM3 molecular orbit method, we have determined the cohesive energies of 214 fully relaxed hexagonal graphene nanoflakes with different edge structures. The energies of flakes with deep and ultra-deep bays, and protrusions with trio-carbons (C₃H₃) and quadro-carbons (C₄H₄) were determined. The pristine hexagonal zigzag flakes (C₂₄H₁₂, C₅₄H₁₈, C₉₆H₂₄, C₁₅₀H₃₀, C₂₁₆H₃₆, C₂₉₄H₄₂, and C₃₈₄H₄₈) are found to become more energetically stable with size. Yet, the addition of bays or protrusions reduces their relative stability. Inclusion of shallow armchair bays keeps the planar structure of the flakes intact and leads to small changes in energy. HH fjord overcrowding in deep and ultra-deep bays leads to twisting and bending of the flakes and very strong destabilization. For selected flakes, we also calculated the energies of structural isomers where the relative positions of bays or protrusions are systematically varied. We develop structure–energy relationships (SERs) by comparing tendencies for the energetic variability of the structural isomers.     

Fluid Biomarkers in HPV and Non-HPV Related Oropharyngeal Carcinomas: From Diagnosis and Monitoring to Prognostication—A Systematic Review

Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.     

Polymerization of melamine and formaldehyde in homogeneous continuous-flow stirred-tank reactors using functional group approach: Part A: Conversion of functional groups

A comprehensive kinetic model using the functional group approach has been proposed for the polymerization of melamine and formaldehyde. The kinetic model is consistent with the basic chemistry of polymerization and involves five rate constants which have been estimated using the experimental data of Tomita. Homogeneous continuous-flow stirred-tank reactors (HCSTRs) have been modelled and the mole balance relations for various functional groups have been written. The performance of HCSTRs is governed by algebraic equations and, for any specified residence time, is found by the method of successive substitution using the Brown's algorithm. The computations show that as long as free formaldehyde is present, the reaction mass would consist predominantly of substituted melamine molecules. However, after formaldehyde is completely reacted, larger oligomers are formed in larger concentrations. On comparison of results with batch reactors, it is found that for the same reaction time HCSTRs yield polymer with higher branching.     

Sensitivity analysis of mathematical models for final product properties: Link to DTG curve

Compressive strength and water absorption of fired heavy clay products varies with firing temperatures, but not entirely according to linear function, as it is mostly reported in literature. Also, differential thermo-gravimetric curve shows many turnovers in all the samples tested, within observed temperature range (820–920 °C). The aim of this research was to find a cause for such behaviour. Except derivative weight (DW), compressive strength (CS) and water absorption (WA) are chosen as outputs that represent properties of the fired samples. These parameters can be calculated using second order polynomial models (SOPs), on the basis of content of major oxides and firing temperature, as shown in our previous research. Sensitivity analysis was used as the effective approach in testing changes observed in the SOP outputs, due to the variation of content of major oxides for +1% or −1% of their nominal value. This study reveals in more detail the most significant influence of inputs (SiO₂, Al₂O₃, Fe₂O₃ and CaO content) over the outputs (DW, CS and WA) in every observed firing temperature. Addition or lowering of content of major oxides can both increase and decrease all the observed outputs, as revealed using sensitivity analysis.     

Photoinduced-electron-transfer chemistry: from studies on PET processes to applications in natural product synthesis

The application of photoinduced electron transfer (PET) for the construction of heterocyclic ring systems is an appealing route in synthetic organic photochemistry. Electronically excited carbonyl chromophors in ketones, aldehydes, amides, or imides are strong electron acceptors that oxidize alkenes, amines, thioethers, or carboxylates. In subsequent steps, the radical anions formed thereof either are operating as secondary electron donors and initiate a photon-driven chain reaction or combine with electrophilic species and form products. These reactions are applied in the synthesis of heterocyclic compounds. The basic structures of these target molecules are bicyclic tertiary amines from the pyrrolizidine, benzopyrrolizidine, and indolizidine families, cyclic oligopeptides, macrocyclic ring systems, and many more.     

Dynamic risk analysis using alarm databases to improve process safety and product quality: Part II—Bayesian analysis

Part II presents step (iii) of the dynamic risk analysis methodology; that is, a novel Bayesian analysis method that utilizes near‐misses from distributed control system (DCS) and emergency shutdown (ESD) system databases—to calculate the failure probabilities of safety, quality, and operability systems (SQOSs) and probabilities of occurrence of incidents. It accounts for the interdependences among the SQOSs using copulas, which occur because of the nonlinear relationships between the variables and behavior‐based factors involving human operators. Two types of copula functions, multivariate normal and Cuadras–Augé copula, are used. To perform Bayesian simulation, the random‐walk, multiple‐block, Metropolis–Hastings algorithm is used. The benefits of copulas in sharing information when data are limited, especially in the cases of rare events such as failures of override controllers, and automatic and manual ESD systems, are presented. In addition, product‐quality data complement safety data to enrich near‐miss information and to yield more reliable results. Step (iii) is applied to a fluidized‐catalytic‐cracking unit (FCCU) to show its performance. © 2011 American Institute of Chemical Engineers AIChE J, 2012