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Nine stable structures of complexes formed by interaction of guanine with thymine were located on potential energy surface at B3LYP/6-311++G(2d,2p). The complexes are quite stable with interaction energy from -5,8 to -17,7 kcal.mol-1. Strength of complexes are contributed by hydrogen bonds, in which a pivotal role of N−H×××O/N overcoming C−H×××O/N hydrogen bond, up to to 3.5 times, determines stabilization of complexes investigated. It is found that polarity of N/C−H covalent bond over proton affinity of N/O site governs stability of hydrogen bond in the complexes. The obtained results show that the N/C−H×××O/N red-shifting hydrogen bonds occur in all complexes, and a larger magnitude of an elongation of N−H compared C-H bond length accompanied by a decrease of its stretching frequency is detected in the N/C−H×××O/N hydrogen bond upon complexation. The SAPT2+ analysis indicates the substantial contribution of attractive electrostatic energy versus the induction and dispersion terms in stabilizing the complexes.

Background: Novel coronavirus (2019-nCov) imposed deadly health calamity with unexpected disastrous situation alarming the globe for urgent treatment regimes. World Health Organization (WHO) termed the coronavirus disease as COVID-2019 on February 11, 2020 and announced its outbreak as pandemic on 11 March 2020. The first infection was noticed in Wuhan, Hubei province, China, in December 2019, and it is believed that the corona-virus is transmitted to humans through bats as a reservoir involving human to human transfer. However, the proper intermediary transmission channel is yet to be unestablished. Methods: Elderly populations and patients with concomitant symptoms are more at risk as compared to middle-aged patients as it may progress to pneumonia followed by severe acute respiratory syndrome (SARS) and multi-organ failure. Morbidity rates estimated in patients are less, i.e., 2-3%, but the dearth of a specific treatment strategy to prevent coronavirus infection is a major concern. Results: Currently, anti-viral and anti-malarial drugs are in practice for the management of COVID-19 disease along with plasma therapy in the absence of a potent vaccine. Besides, home isolation and social distancing are the precautionary measures adopted by many countries to minimize the spread of infection. Various studies have been conducted, and numerous are still going on to establish specific treatment for COVID-19. Conclusion: In this review, we summarized information on the structural components of COVID19 virus with special emphasis on the virus genome, life cycle, the importance of protease enzyme, the role of spike proteins in viral replication, validated drug targets, ongoing effective treatments for COVID-19 management and the latest research on drug design to develop anti-CoV drugs.

We propose a nonconvex variational decomposition model which separates a given image into piecewise-constant, smooth, and oscillatory components. This decomposition is motivated not only by image denoising and structure separation, but also by shadow and spot light removal. The proposed model clearly separates the piecewise-constant structure and smoothly varying harmonic part, thanks to having a separated oscillatory component. The piecewise-constant part is captured by TV-like nonconvex regularization, harmonic term via second-order regularization, and oscillatory (noise and texture) term via a H^{-1}-norm penalty. There are interesting interactions between these three regularization terms. We explore the effects of each regularization and the choice of parameters carefully. We propose an efficient alternating direction method of multipliers based minimization for fast numerical computation of the optimization problem. Various experiments are presented to show the robustness against a high level of noise, applications to soft spotlight and shadow removal, and the comparisons with other methods.

A diverse range of linear polysiloxane-based ionic polymers that are hydrophobic and highly flexible can be obtained by substituting the polymers with varying amounts of ionic centers. The materials can be highly crystalline solids, amorphous soft solids, poly(ionic) liquids or viscous polymer liquids. A key to understanding how structural variations can lead to these different materials is the establishment of correlations between the physical (dynamic and static) properties and the structures of the polymers at different distance scales. This short review provides such correlations by examining the influence of structural properties (such as molecular weights, ion pair contents, and ion types) on key bulk properties of the materials.

Background: Pyrazolines are five-membered heterocycles with two adjacent nitrogen atoms present in the ring and they have attracted many researchers all over the world to assess their potential therapeutic significance. Pyrazolines are known for their crucial role in numerous diseases like cancer via various mechanisms. Pyrazoline and its derivatives have been found to have potent anticancer activity by inhibiting EGFR (Epidermal Growth Factor Receptor Tyrosine Kinase) and other types of RTKs. Rapid advances in the understanding of cellular signaling by EGFR in normal and malignant cells have brought to light the EGFR as a selective anticancer target. The review enlists some recently developed pyrazolines as EGFR tyrosine kinase inhibitor along with their structure-activity relationships. Methods: The structure-activity relationship of different pyrazoline derivatives was discussed along with their epidermal growth factor receptor inhibitory activity. Both review and research articles have been considered and cited in the paper. Results: Pyrazolines have assisted medicinal chemistry by their diverse biological activities which make them a beneficial scaffold. The structure-activity relationship studies on pyrazolines revealed that the structural characteristics and different substitutions on pyrazoline ring alter the EGFR inhibitory activity. Conclusion: In the present review, pyrazoline derivatives with EGFR kinase inhibitory activity are described based on their structure-activity relationships based on their structural substitution pattern around the pyrazoline scaffold.

In order to understand the effect of in-situ carbon deposition and permeation process on cobalt-catalyzed heterogeneous reactions, the thermodynamics and kinetics of the carburization process of te...

The T–x (temperature–composition) phase state diagrams of 120 systems RF3–R'F3 (pair combinations of 16 trifluorides of rare-earth elements R and R' without ScF3) represent the interaction of components in terms of phase composition depending on the chemical proximity of RF3 and R'F3, which is defined by the difference ΔZ = Z(R) – Z(R') of the atomic numbers of R and R' (except YF3). The lanthanide contraction of R3+ with increasing Z together with temperature causes polymorphism and morphotropy of RF3 and $${{{\text{R}}}_{{{\text{1}}\,\,-\,\,x}}}{\text{R}}_{x}^{'}{{{\text{F}}}_{{\text{3}}}}.$$ The series of RF3 is divided into structure subgroups (SSs), pair combinations of RF3 of which give 10 types of systems. A classification of RF3–R'F3 systems by ΔZ is proposed, which divides 10 types of systems into four groups of systems (GSs): GS-1 contains 25 systems of RF3 of identical SSs with ΔZ = 2–3; GS-2, 43 systems of RF3 of neighboring SSs with ΔZ = 6–7; GS-3, 32 systems of RF3 separated by one SS with ΔZ = 10; and GS-4, 20 systems of RF3 separated by two SSs with ΔZ = 14.

Chemical modification of proteins is a vintage strategy that is still fashionable due to the information that can be obtained from this approach. An interesting application of chemical modification is linked with membrane transporters. These proteins have peculiar features such as the presence of hydrophobic and hydrophilic domains, which show different degree of accessibility to chemicals. The presence of reactive residues in the membrane transporters is at the basis of the chemical targeting strategy devoted to investigating structure/function relationships; in particular, information on the substrate binding site, regulatory domains, dimerization domains, and the interface between hydrophilic loops and transmembrane domains has been obtained over the years by chemical targeting. Given the difficulty in handling membrane transporters, their study experienced a great delay, particularly concerning structural information. Chemical targeting has been applied with reasonable success to some membrane transporters belonging to the families SLC1, SLC6, SLC7, and SLC22. Furthermore, some data on the potential application of chemical targeting in pharmacology are also discussed.

Steroidal alkaloids contain both steroidal and alkaloid properties in terms of chemical properties and pharmacological activities. Due to outstanding biological activities such as alkaloids and similar pharmacological effects to other steroids, steroidal alkaloids have received special attention in anticancer activity recently. Substituted groups in chemical structure play markedly important roles in biological activities. Therefore, the effective way to obtain lead compounds quickly is structural modification, which is guided by structure–activity relationships (SARs). This review presents the SAR of steroidal alkaloids and anticancer, including pregnane alkaloids, cyclopregnane alkaloids, cholestane alkaloids, C-nor-D-homosteroidal alkaloids, and bis-steroidal pyrazine. A summary of SAR can powerfully help to design and synthesize more lead compounds.

The dramatic increase in the consumption of antidepressants is one indicator, among others, of the contemporary cerebralization of human affliction. This process has been led by expert systems, creating new biosocialities or neurosocialities, and new models of self as well: the neural self. While some research minimizes the neuro-colonization of the self and its impact on lay knowledge systems, here I argue that synergy between neuropolitics and figures characteristic of neoliberal governamentality such as the "entrepreneur of oneself" can give rise to an interiorized, cerebralized, centripetal, inwardly-oriented self. This paper, based on long-term fieldwork among consumers of antidepressants in Catalonia, analyses the emergence of neuronarratives of affliction (NoAs). NoAs privilege neurochemical dysfunction as the source of distress, shortcircuiting an awareness of the social sources of suffering while at the same time obscuring the fact of this concealment. NoAs transform the self into structure and reduce the social world to event.

The expediency of allowance for the links in the georesource-open pit-preparation plant chains as an integral information, technology and management space is considered. The methodical approaches to improvement of useful qualities of coal, in the first turn, its ash content graded as a rank of components are substantiated. In terms of the Elga deposit in South Yakutia, potentiality of increase in completeness and quality of coal extraction based on the studies into structure and contact zones of seams is illustrated. The schemes are proposed for ash content control in coal mining through extraction of dirt and high-ash interbeds of various thickness. The process charts for mining thin coal and dirt interbeds are proposed. The recommendations are provided for development of coal seams composed of bands of different ash content and washability.

Solid-state NMR has emerged as a potent technique in structural biology, suitable for the study of fibrillar, micro-crystalline, and membrane proteins. Recent developments in fast-magic-angle-spinning and proton-detected methods have enabled detailed insights into structure and dynamics, but molecular-weight limitations for the asymmetric part of target proteins have remained at ~30-40 kDa. Here we employ solid-state NMR for atom-specific characterization of the 72 kDa (asymmetric unit) microcrystalline protein tryptophan synthase, an important target in pharmacology and biotechnology, chemical-shift assignments of which we obtain via higher-dimensionality, 4D and 5D solid-state NMR experiments. The assignments for the first time provide comprehensive data for assessment of side chain chemical properties involved in the catalytic turnover, and, in conjunction with first-principles calculations, precise determination of thermodynamic and kinetic parameters is demonstrated for the essential acid-base catalytic residue βK87. The insights provided by this study expand by nearly a factor of two the size limitations widely accepted for NMR today, demonstrating the applicability of solid-state NMR to systems that have been thought to be out of reach due to their complexity.

P-gp-associated multidrug resistance (MDR) is a major impediment to the success of chemotherapy. With the aim of finding non-toxic and effective P-gp inhibitors, we investigated a panel of quinolin-2-one-pyrimidine hybrids. Among the active compounds, two of them significantly increased intracellular doxorubicin and rhodamine 123 accumulation by inhibiting the efflux mediated by P-gp and restored doxorubicin toxicity at nanomolar range. Structure-activity relationships showed that the number of methoxy groups, an optimal length of the molecule in its extended conformation, and at least one flexible methylene group bridging the quinolinone moiety favored the inhibitory potency of P-gp. The best compounds showed a similar binding pattern and interactions to those of doxorubicin and tariquidar, as revealed by MD and hybrid QM/MM simulations performed with the recent experimental structure of P-gp co-crystallized with paclitaxel. Analysis of the molecular interactions stabilizing the different molecular complexes determined by MD and QTAIM showed that binding to key residues from TMH 4–7 and 12 is required for inhibition.

Accuracy of hypocenter location, in particular focal depth, is a precondition for high-resolution seismotectonic analysis of natural and induced seismicity. For instance, linking seismicity with mapped fault segments requires hypocenter accuracy at the sub-kilometer scale. In this study, we demonstrate that inaccurate velocity models and improper phase selection can bias absolute hypocenter locations and location uncertainties, resulting in errors larger than the targeted accuracy. To avoid such bias in densely instrumented seismic networks, we propose a coupled hypocenter-velocity inversion restricted to direct, upper-crustal Pg and Sg phases. The derived three-dimensional velocity models, combined with dynamic phase selection and non-linear location algorithms result in a highly accurate earthquake catalog, including consistent hypocenter uncertainties. We apply this procedure to about 60’000 Pg and 30’000 Sg quality-checked phases of local earthquakes in the Central Alps region. The derived tomographic models image the Vp and Vs velocity structure of the Central Alps’ upper crust at unprecedented resolution, including small-scale anomalies such as those caused by a Permo-Carboniferous trough in the northern foreland, Subalpine Molasse below the Alpine front or crystalline basement units within the Penninic nappes. The external Aar Massif is characterized by low Vp/Vs ratios of about 1.625-1.675 in the depth range of 2-6.5 km, which we relate to a felsic composition of the uplifted crustal block, possibly with increased quartz content. Finally, we discuss along-strike variations imaged by relocated seismicity in the Central Alps and demonstrate how joint interpretation of velocity structure and hypocenters provides additional constraints on lithologies of upper-crustal seismicity.

Arrestins (arr) are multifunctional cytosolic adaptors that bind to active and phosphorylated G protein-coupled receptors (GPCRs) via a highly versatile interface. Arrestins stop G protein signaling and trigger other signaling pathways. Recently, 3D structures of arr-GPCR complexes have been solved, which provide a bulk of structural information for understanding the mechanism of arr recruitment and activation. However, many questions about the functional consequences of structural details and the dynamics of the arr-GPCR interaction remain open. A wealth of information about key determinants for the arr-GPCR interaction and their functional relevance, and dynamic insights into the process of arr binding and the functional outcomes of different binding modes have been provided by a series of biochemical methods which we review here. Importantly, most of these methods provide information from the live cell, which is a necessary validation and complement for structural data. With the main focus on the most recent research, we will highlight major findings about arr structure, function, and dynamics derived from mutagenesis studies, cross-linking studies, conformational probes, and sensors, and we summarize available systems to detect arr recruitment. Furthermore, we discuss recent findings and directions of in silico investigations in arr-GPCR complexes.

The saliva of blood-sucking leeches contains a plethora of anticoagulant substances. One of these compounds derived from Haementeria ghilianii, the 66mer three-disulfide-bonded peptide tridegin, specifically inhibits the blood coagulation factor FXIIIa. Tridegin represents a potential tool for antithrombotic and thrombolytic therapy. We recently synthesized two-disulfide-bonded tridegin variants, which retained their inhibitory potential. For further lead optimization, however, structure information is required. We thus analyzed the structure of a two-disulfide-bonded tridegin isomer by solution 2D NMR spectroscopy in a combinatory approach with subsequent MD simulations. The isomer was studied using two fragments, i.e., the disulfide-bonded N-terminal (Lys1&ndash, Cys37) and the flexible C-terminal part (Arg38&ndash, Glu66), which allowed for a simplified, label-free NMR-structure elucidation of the 66mer peptide. The structural information was subsequently used in molecular modeling and docking studies to provide insights into the structure&ndash, activity relationships. The present study will prospectively support the development of anticoagulant-therapy-relevant compounds targeting FXIIIa.

Advanced NMR methods combined with biophysical techniques have recently provided unprecedented insight into structure and dynamics of molecular chaperones and their interaction with client proteins. These studies showed that several molecular chaperones are able to dissolve aggregation-prone polypeptides in aqueous solution. Furthermore, chaperone-bound clients often feature fluid-like backbone dynamics and chaperones have a denaturing effect on clients. Interestingly, these effects that chaperones have on client proteins resemble the effects of known chaotropic substances. Following this analogy, chaotropicity could be a fruitful concept to describe, quantify and rationalize molecular chaperone function. In addition, the observations raise the possibility that at least some molecular chaperones might share functional similarities with chaotropes. We discuss these concepts and outline future research in this direction.

High amounts of glycosaminoglycans (GAG) such as hyaluronan (HA) occur in connective tissues. There is nowadays increasing evidence that a “sulfation code” exists which mediates numerous GAG functions. High molecular weight and inhomogeneity of GAG, however, aggravated detailed studies. Thus, synthetic oligosaccharides were urgently required. We will review here chemoenzymatic and analytic strategies to provide defined sulfated and anomerically modified GAG oligosaccharides of the HA type. Representative studies of protein/GAG interactions by (bio)chemical and biophysical methods are reported yielding novel insights into GAG-protein binding. Finally, the biological conclusions and in vivo applications of defined sulfated GAG oligosaccharides will be discussed.

Uncovering conserved 3D protein-ligand binding patterns at the basis of functional groups (FGs) shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions. Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature, large-scale identification and evaluation of FG-based 3D binding motifs are still lacking. Here, we developed AFTME, an alignment-free method for automatic mapping of 3D motifs to different FGs of a specific ligand through two-dimensional clustering. Applying our method to 233 nature-existing ligands, we defined 481 FG-binding motifs that are highly conserved across different ligand-binding pockets. Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs. Combinations of FG-binding motifs facilitate proteins to bind a wide spectrum of ligands with various binding affinities. Finally, we showed that these general binding patterns are also applicable to target-drug interactions, providing new insights into structure-based drug design.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this deadly virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates the host cell entry by promoting the viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2, roles of key viral factors and discuss the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics. Finally, we dive into available medications, and the current COVID-19 treatment options, which will be beneficial for the scientific community as well as for the general public.

International audience; Structural biology and functional studies are a powerful combination to elucidate fundamental knowledge about the cystic fibrosis transmembrane conductance regulator (CFTR). Here, we discuss the latest findings, including how clinically-approved drugs restore function to mutant CFTR, leading to better clinical outcomes for people with cystic fibrosis (CF). Despite the prospect of regulatory approval of a CFTR-targeting therapy for most CF mutations, strenuous efforts are still needed to fully comprehend CFTR structure-and-function for the development of better drugs to enable people with CF to live full and active lives.

The purpose of this paper is to offer a method for clustering of XML documents. Many different ways of clustering were discussed for clustering documents which can be divided to structure, content and combination of structure and content. One method that has been proposed to solve this problem is XCLS which be improved with XCLS+ later. XCLS+ is efficient algorithm for clustering XML documents and Exposure into structure based on clustering category. The conducted survey showed which XCLS+ method has problem that makes away from its optimal value too. This paper presents a method with name XCLS++ which has not related problem XCLS+ and its efficiency are diagnosed more than XCLS+

Several complementary approaches have been developed to discover modulators of protein–protein interactions (PPIs). This chapter provides a perspective on bioinformatic classifications of PPIs, which has led to a better understanding of which PPIs are more amenable to modulation. Next, workflows to target PPIs are outlined, including phenotypic screening and target-based approaches. Target-based approaches can be further categorized into structure-based design and target-based screening. The overview, benefits, and drawbacks of each workflow are discussed. Last, we illustrate two complementary computational methods to assess protein interfaces using the KIX protein.

International audience; Mapping the nanomechanical properties of amyloids can provide valuable insights into structure and assembly mechanisms of protein aggregates that underlie the development of various human diseases. Although it is well-known that amyloids exhibit an intrinsic stiffness comparable to that of silk (1-10 GPa), a detailed understanding of the directional dependence (anisotropy) of the stiffness of amyloids and how it relates to structural features in these protein aggregates is missing. Here we used steered molecular dynamics (SMD) simulations and amplitude modulation-frequency modulation (AM-FM) atomic force microscopy to measure the directional variation in stiffness of GNNQQNY amyloid crystals. We reveal that individual crystals display significant mechanical anisotropy and relate this anisotropy to subtle but mechanically important differences in interactions between interfaces that define the crystal architecture. Our results provide detailed insights into the structure-mechanics relationship of amyloid that may help in designing amyloid-based nanomaterials with tailored mechanical properties.

A facile way to synthesize a series of SAPO-34 zeolites was developed by using the mixed templates of morpholine and TEAOH with changing the temperature. Among these samples, SAPO-34-210 exhibited with the longest lifetime and the highest selectivity to light olefin for methanol to olefin (MTO) reaction. The characterizations suggested that SAPO-34-210 has unique Si distribution due to much more amount of TEAOH introduced into structure, which resulted in the excellent catalytic performance.

Proteases play a vital role in the removal of proteins, which become damaged due to temperature or oxidative stress. Important to this process in the cyanobacterium Synechocystis sp. PCC6803 is the family of Deg/HtrA proteases; HhoA (sll1679), HhoB (sll1427) and HtrA (slr1204). While previous studies have elucidated the structures of Deg/HtrA proteases from Escherichia coli and from the chloroplast of the higher plant Arabidopsis thaliana, no structural data have been available for any Deg/HtrA protease from cyanobacteria, the evolutionary ancestor of the chloroplast. To gain a deeper insight into the molecular mechanisms and regulation of these proteins we have solved the structure of the Synechocystis HhoA protease in complex with a co-purified peptide by X-ray crystallography. HhoA assembles into stable trimers, mediated by its protease domain and further into a cage-like hexamer by a novel interaction between the PDZ domains of opposing trimers. Each PDZ domain contains two loops for PDZ-PDZ formation: interaction clamp one and two (IC1, IC2). IC1 interacts with IC2 on the opposing PDZ domain and vice versa. Our structure shows a peptide bound to a conserved groove on the PDZ domain and the properties of this pocket suggest that it binds substrate proteins as well as the neo C-termini of cleaved substrates. In agreement with previous studies showing the proteolytic activity of HhoA to be activated by Ca

Spiroketals are key structural motifs found in diverse natural products with compelling biological activities. However, stereocontrolled synthetic access to spiroketals, independent of their inherent thermodynamic preferences, is a classical challenge in organic synthesis that has limited in-depth biological exploration of this intriguing class. Herein, we review our laboratory's efforts to advance the glycal epoxide approach to the stereocontrolled synthesis of spiroketals via kinetically controlled spirocyclization reactions. This work has provided new synthetic methodologies with applications in both diversity- and target-oriented synthesis, fundamental insights into structure and reactivity, and efficient access to spiroketal libraries and natural products for biological evaluation.

The probable E-Group assemblage was a primary focus of our investigation at the lowland Maya center of Ceibal. Tunnel excavation into Structure A-20 (the western structure of this complex) demonstrated that the Ceibal residents built the earliest version (Structure Ajaw) by carving natural marl around 950b.c.The earliest version of the eastern platform (Structure Xa'an) was also made at the same time out of the natural marl layer. Through a series of renovations, the western structure grew into a pyramidal shape, and later versions of the eastern platform were moved further to the east. In addition, excavations revealed numerous caches, many with greenstone axes, along the center line of the E-Group assemblage. These results show that a formal ceremonial complex was established at the beginning of occupation at Ceibal, and its construction and public events held there played an important role in the creation of a new community.

Anaerobic bacteria represent an underexplored source of bioactive natural products with unusual structural features. Here we report the isolation and structure elucidation of an antimycobacterial natural product, clostroindolin, produced by Clostridium beijerinckii. Furthermore, we provide first insights into structure activity relationships, which might guide the development of novel antibiotics against mycobacteria.

RNA interference (RNAi) is a major antiviral defense mechanism in nematodes. In Caenorhabditis elegans (C. elegans), Dicer-related helicase 1 (DRH-1) acts to enhance the production of primary virus-derived small interfering RNA (siRNA) in antiviral RNAi pathway. However, Dicer-related helicase 3 (DRH-3), is involved in the biogenesis of secondary siRNA in both endogenous and exogenous RNAi pathways. DRH-1 and DRH-3 are orthologs to RIG-I like receptors (RLRs), based on their structural and sequential conservation of the helicase domain (HEL) and the C-terminal RNA binding domain (CTD). The structure and function of worm-specific N-terminal domains (NTDs) of DRH-1 and DRH-3 are currently unknown. This thesis describes biochemical, biophysical and structural studies of DRH-1 and DRH-3 (DRHs) to provide new insights into the RNAi mechanism at the molecular level. We first established the methods for expressing and purifying the full-length and various domains of DRHs. The purified recombinant proteins were then fully characterized to understand their functions in RNA recognition. For DRH-3, we applied X-ray crystallography and solved the crystal structure of DRH-3 NTD, as well as two crystal structures of DRH-3 CTD in complex with 5′-triphosphate (5′-ppp) RNAs. The NTD of DRH-3 adopts a novel fold of tandem CARDs that is different from the CARDs of RIG-I. This suggests DRH-3 may recruit an unknown protein partner in the endogenous RNAi pathway. Crystal structures and RNA binding assay confirmed that CTD preferentially recognizes RNAs with 5′-ppp, which is the typical feature of secondary siRNA transcript. Furthermore, the full-length DRH-3 displays unique structural dynamics and RNA differentiation patterns that are different from RIG-I and MDA5, as revealed by the hydrogen/deuterium exchange coupled to mass spectrometry experiment (HDX-MS). For DRH-1, we provided the first evidence that the Hel-CTD of DRH-1 has a dsRNA-dependent ATPase function. Moreover, we demonstrated that DRH-1 preferred short dsRNAs, especially those with 5'-ppp and 3' overhang for its ATPase hydrolysis activity and the protein stability. Collectively, our findings reveal unique molecular features of DRHs in RNAi and provide new perspectives for advancing our understanding of small RNA processing and antiviral defense mechanism in worms. Doctor of Philosophy

The mechanisms that employ symmetrical configurations can be found in the steering mechanisms, double open refrigerator, roof boxes, and double open windows, among others. They are useful for some special applications with kinematic symmetry. There have been studies about the linkage synthesis, especially in the research of planar closed chains, from as early as 1960s. However, no study has focused on the symmetry of planar linkages. Thus, the purpose of this paper is to present a methodology to synthesize the configurations of planar linkages. The systematic methodology can be divided into structure synthesis, configuration synthesis and results produced from three major processes. Finally, four suitable results of up to six-bar linkages can be obtained, for example. The four results include one four-bar linkage and three six-bar linkages.

Human serum albumin (HSA) as the most abundant protein in human blood plasma, serves many physiological functions. The dysregulation of HSA in serum or in urine is associated with various diseases, such as cirrhosis of liver, multiple myeloma, and cardiovascular disease. Therefore, to quantify HSA in body fluids with high selectivity and sensitivity is of great significance for disease diagnosis and preventive medicine. We herein developed a series of amide-functionalized flavonoids probes, 1–3, for recognition of human serum albumin. All flavonoids could be easily prepared by a Claisen-Schmidt condensation and Algar-Flynn-Oyamada reaction, and showed positive solvatochromism on their dual emissions. The chemical structure of flavonoids played an important role on their HSA-sensing abilities. Among three probes, the compound 1 showed the highest sensitivity, the remarkable selectivity, and the quantitive response for HSA in aqueous solution. Together with its high tolerance of environmental pH, anti-interference properties, and time-insensitivity, thus it provides a promising sensing method for HSA.

The aim of the paper is focused on the analysis of the mechanical properties of the concrete specimens with plasticizer at three point bending test by the signal analysis of the acoustic emission signal. The evaluations were compared the measurement and the results obtained with theoretical presumptions. The Joint Time Frequency Analysis applied on measurement data and its evaluation is described. It is well known that the Acoustic Emission Method is a very sensitive method to determine active cracks into structure. However, evaluation of acoustic emission signals is very difficult. A non-traditional method was used to signal analysis of burst acoustic emission signals recorded during three point bending test.

GaN epitaxial films grown on Si (111) substrates were observed using a 200 kV high-resolution (HR) transmission electron microscope. Both perfect and dissociated 60° basal dislocations were found in HR images. By utilizing the image deconvolution method, the HR images were transformed into structure maps with an improved resolution, and then the atomic configurations of perfect and partial dislocations were determined. Afterwards, the possible dissociation schemes for the dissociated dislocations were derived.

Non Destructive Testing is a powerful tool for determination of properties, durability and lifetime of concrete structures. Acoustic Emission Method is an unusual technique which describes only active defects or changes into structure arising as a consequence dangerous tension into structure. The method is appropriate to be used in homogenous structures as metal structures when cracks are highly active (generates sound). Its application in civil engineering is not so much used because building structures are inhomogeneous. This article shows possible application of Acoustic Emission Method for monitoring of concrete structure changes during its lifetime. The main aim of the article is to show the application of Acoustic Emission Method during the early age to 28 days after mixing. It is believed that early age of concrete structure is very important for its quality. Common concrete cube specimens have been tested after the production by Acoustic Emission Method with using waveguides. The results of acoustic emission method will be compared to classical parameters of fresh concrete e.g. the value water-cement ratio, air void content measured by different methods (pressure methods, AVA) and similar. In the results will be compared four mixtures when two mixtures were aerated and two mixtures were without aeration.

Highlights • Coronavirus nucleocapsid proteins are appealing drug targets against coronavirus-induced diseases. • A variety of compounds targeting the coronavirus nucleocapsid protein have been developed. • Many of these compounds show potential antiviral activity., The advent of severe acute respiratory syndrome (SARS) in the 21st century and the recent outbreak of Middle-East respiratory syndrome (MERS) highlight the importance of coronaviruses (CoVs) as human pathogens, emphasizing the need for development of novel antiviral strategies to combat acute respiratory infections caused by CoVs. Recent studies suggest that nucleocapsid (N) proteins from coronaviruses and other viruses can be useful antiviral drug targets against viral infections. This review aims to provide readers with a concise survey of the structural features of coronavirus N proteins and how these features provide insights into structure-based development of therapeutics against coronaviruses. We will also present our latest results on MERS-CoV N protein and its potential as an antiviral drug target., Teaser Nucleocapsid proteins are essential for coronavirus viability and constitute potential targets for the development of therapeutics against recent coronavirus outbreaks such as SARS and MERS.

Tetraphenylethylene-based microporous organic polymers with tunable porosities can be synthesized from several acetyl-modified tetraphenylethylenes with mannitol or pentaerythritol. The employment of building blocks with different chemical structures accompanied by a linkage geometry engineering approach have led to the formation of eight polymers (PTPOP-1–4 and MTPOP-1–4) presenting different Brunauer–Emmett–Teller specific surface areas and total pore volumes. In addition, different carbon dioxide adsorption capabilities of the resulting polymers are studied, and their CO2/CH4 selectivities are assessed. These results help shed light on designing porous organic polymers with controllable porosities and gas adsorption properties.

Although there have been many advancements in scientific research and development, the cause of epilepsy still remains an open challenge. In spite of high throughput research in the field of anti-epileptic drugs, efficacy void is still prevalent before the researchers. Researchers have persistently been exploring all the possibilities to curb undesirable side effects of the anti-epileptic drugs or looking for a more substantial approach to diminish or cure epilepsy. The drug development has shown a hope to medicinal chemists and researchers to carry further research by going through a substantial literature survey. This review article attempts to describe the recent developments in the anti-epileptic agents, pertaining to different molecular scaffolds considering their structure-activity relationship, docking studies and their mechanism of actions.

This chapter explains the administrative structure of Sri Lanka, the proliferation of administrative institutions since the 1970s, and the power and relationships between the present administrative institutions at various levels of the bureaucracy. It examines the management and performance of the public sector, the recent reforms introduced by the government, their impact, and emerging issues in the sector. The chapter is based on a document review and a survey of literature on public administration, public sector reforms, New Public Management (NPM) and post-NPM ideas. The chapter fills a gap in the existing literature on public administration and management in Sri Lanka and identifies flaws in its NPM reforms, how they have been put into practice, and prospects for future reforms.

Article is devoted to issue of integration of vertical gardening into structure of high-rise building in the conditions of the constrained town-planning situation. On the basis of the analysis of the existing experience of design and building of "biopositive" high-rise building ecological, town-planning, social and constructive advantages of the organization of gardens on roofs and vertical gardens are considered [1]. As the main mechanism of increase in investment appeal of high-rise building the principle of a humanization due to gardening of high-rise building taking into account requirements of ecology, energy efficiency of buildings and improvement of quality of construction with minimization of expenses and maximizing comfort moves forward. The National Standards of Green construction designed to adapt the international requirements of architecture and construction of the energy efficient, eco-friendly and comfortable building or a complex to local conditions are considered [2,3].

The negative global impact of the AIDS pandemic is well known. In this perspective article, the utility of magic angle spinning (MAS) NMR spectroscopy to answer pressing questions related to the structure and dynamics of HIV-1 protein assemblies is examined. In the recent years, MAS NMR has undergone major technological developments enabling studies of large viral assemblies. We discuss some of these evolving methods and technologies and provide a perspective on the current state of MAS NMR as applied to the investigations into structure and dynamics of HIV-1 assemblies of CA capsid protein and of Gag maturation intermediates.