Structural Assignment Research Articles

Total Synthesis of Kibdelomycin.

A modular total synthesis of kibdelomycin is disclosed that should enable structure–activity relationship (SAR) studies of this interesting class of antibiotics. The route uses simple building blocks and addresses lingering questions about its structural assignment and relationship to amycolamicin, a recently described natural product reported to have a similar structure. Initial antibacterial assays reveal that both C‐22 epimers (the N‐glycosidic linkage) of the natural product have similar activity while structurally truncated analogs lose activity.

A Stochastic Optimization Approach to the Long-Term Care Structure Assignment Problem for Elderly People

The growing number of elderly people (EP) has become one of the most important problems in recent years. This part of the population is often dependent and does not tolerate environmental changes well, so long-term care (LTC) structure assignments should be well prepared. This article proposes a stochastic optimization approach to solve the LTC structure assignment problem for a population of EP while taking into account health state changes and uncertain future demand. The objective of this approach is to make the best assignment decision among several structures or to wait for a better solution if no suitable structure is available. The model is validated and calibrated on the basis of stakeholder objectives and territorial special features through simulation. We propose a numerical analysis based on both quantitative and qualitative analyses to compare our model with simple assignment policies. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —The increase in the elderly and dependent population and the lack of a long-term structure to address this aging population make it difficult to assign EP to the appropriate LTC. This decision often determines the quality of the end of life. Several parameters must be taken into account to choose the best solution: the health situation, geographic location, and financial resources. If the elderly person stays too long in a situation not suited to his/her condition, then his/her risk of a decline in health is significant. The dilemma is whether to choose: 1) to wait to have the structure most adapted to the health of the state or 2) to assign the elderly person to the most suitable structure available. We propose a stochastic optimization approach to help stakeholders assign EP to an LTC structure in a given territory. The model uses projections of the health state of the population over a time horizon to make decisions and considers elderly care requirements and characteristics, such as geographic compatibility and financial resources. The model performs better than a greedy algorithm (based on the first-in-first-out approach) and an optimization model without time projections.

Microgrewiapine C: Asymmetric Synthesis, Spectroscopic Data, and Configuration Assignment.

The first asymmetric synthesis of microgrewiapine C, a piperidine alkaloid isolated from Microcos paniculata, is reported. This synthesis prompted correction of the 1H and 13C NMR data for the natural sample of the alkaloid, which was achieved by reanalysis of the original spectra. The corrected data for the natural product were found to be identical to those of the synthetic sample prepared herein, thus confirming the structural and relative configurational assignment of microgrewiapine C. Although comparison of specific rotation values indicates that the (1R,2S,3S,6S) absolute configuration should be assigned to the alkaloid, consideration of potential common biosynthetic origins of microgrewiapine C and congeners suggests that further phytochemical investigations are warranted.

THROUGHOING FLUID-CONDUCTING STRUCTURES: MORPHOGENETIC CLASSIFICATION AND CHARACTERIZATION OF TYPES

Throughgoing fluid-conducting structures are the main elements of the plumbing system of the sedimentary cover and play an important role in fluid migration, evolution of sedimentary basins and lithogenesis, formation of fluidogenic deposits (including hydrocarbons and metals), use of geothermal energy sources, risk assessment for geological depositories of radioactive wastes, CO2 and other materials. They are widespread and characterized by a variety of morphology and origins, but are poorly systematized by these attributes, which complicates identification and interpretation of these structures. In this article, based on the analysis and generalization of literature sources and data from own field studies, morphogenetic classification of throughgoing fluid-conducting structures is developed and the characteristics of the defined types are given. At the first level, such structures are divided into four groups according to the nature of the dominant formation processes: tectonic, fluidodynamic, karstic (dissolution) and karstic-gravitational. At the second and third levels, groups and types of the structures are distinguished by structural-morphological and material features, taking into account the peculiarities of mechanisms and conditions of formation. The mechanisms of formation of structures of some types are clarified. It is shown that karstification, particularly hypogenic, is the leading process of formation of the most permeable structures and, accordingly, of the most contrasting hydrogeological anomalies and their geological consequences. Structures of relatively small vertical dimensions and stratigraphic coverage (bed-crossing, suite-crossing) can be elementary and of unambiguous origins, although they frequently show signs of superimposed changes that significantly affect their fluid-exchange function. The proposed classification is applicable mainly to small and elementary structures, while large (cross-formational, cross-sedimentary cover) are usually of complex origin, potentially involving the combined or sequential action of tectonic or hydraulic rupture, fluidization, metasomatism, dissolution / karstification and collapsing. This polygenetic nature is due to the material and mechanical heterogeneity of sections of host strata and changes in the properties of fluids during their upward migration, as well as over time. However, the assignment of structures to certain genetic categories can be carried out by the nature of the dominant formation processes.

Learning by Competition of Self-Interested Reinforcement Learning Agents

An artificial neural network can be trained by uniformly broadcasting a reward signal to units that implement a REINFORCE learning rule. Though this presents a biologically plausible alternative to backpropagation in training a network, the high variance associated with it renders it impractical to train deep networks. The high variance arises from the inefficient structural credit assignment since a single reward signal is used to evaluate the collective action of all units. To facilitate structural credit assignment, we propose replacing the reward signal to hidden units with the change in the L2 norm of the unit's outgoing weight. As such, each hidden unit in the network is trying to maximize the norm of its outgoing weight instead of the global reward, and thus we call this learning method Weight Maximization. We prove that Weight Maximization is approximately following the gradient of rewards in expectation. In contrast to backpropagation, Weight Maximization can be used to train both continuous-valued and discrete-valued units. Moreover, Weight Maximization solves several major issues of backpropagation relating to biological plausibility. Our experiments show that a network trained with Weight Maximization can learn significantly faster than REINFORCE and slightly slower than backpropagation. Weight Maximization illustrates an example of cooperative behavior automatically arising from a population of self-interested agents in a competitive game without any central coordination.

Automated Protein Secondary Structure Assignment from Cα Positions Using Neural Networks.

The assignment of secondary structure elements in protein conformations is necessary to interpret a protein model that has been established by computational methods. The process essentially involves labeling the amino acid residues with H (Helix), E (Strand), or C (Coil, also known as Loop). When particular atoms are absent from an input protein structure, the procedure becomes more complicated, especially when only the alpha carbon locations are known. Various techniques have been tested and applied to this problem during the last forty years. The application of machine learning techniques is the most recent trend. This contribution presents the HECA classifier, which uses neural networks to assign protein secondary structure types. The technique exclusively employs C coordinates. The Keras (TensorFlow) library was used to implement and train the neural network model. The BioShell toolkit was used to calculate the neural network input features from raw coordinates. The study’s findings show that neural network-based methods may be successfully used to take on structure assignment challenges when only C trace is available. Thanks to the careful selection of input features, our approach’s accuracy (above 97%) exceeded that of the existing methods.

Facile synthesis of hydrazono bis-4-oxothiazolidines

Herein, we reported on a new series of hydrazono bis-4-oxothiazolidines during the reaction of (hydrazinecarbonothioyl)hydrazinecarbothioamides with dimethyl acetylenedicarboxylate in ethanol as a solvent. The products were obtained in good yields. The structure assignment of obtained products was confirmed by NMR, mass and IR spectroscopy in addition to elemental analyses. The structure of the products was also confirmed by a single-crystal X-ray structure analysis. The possible mechanism for the reaction was also discussed.

Development and characterization of microsatellite markers, genetic diversity and population structure analysis in Sapota (Manilkara zapota (L.) P. Royen)

Manilkara zapota (L.) P. Royen, a widely adapted and popular tree meant for its appetizing fruits in tropics with no genomic resources like microsatellite markers. In order to develop genomic markers primarily for Sapota, the study sequenced partial genomic DNA using next generation sequencing technology on Illumina HiSeq 2500 platform. 3.3 Gb data assembled into 6,396,224 contigs were analysed. From these contigs, 3591 simple sequence repeats were identified. Among these different types of repeats, mononucleotide repeats (59.1%) were predominant followed by dinucleotide (28.6%) and trinucleotide repeats (8.2%). Primers were designed for 1285 microsatellite regions from which randomly selected 30 primers were standardized and employed for amplification in 53 genotypes of Sapota. Six hundred and ninty-two alleles were observed from 30 loci with a polymorphic information content that ranged from 0.85 to 0.96 with a mean of 0.9118. The Probability of Identity ranged from 0.002 to 0.043 with a mean of 0.012. The genetic diversity assessed by neighbour-joining and STRUCTURE assignment tests showed an admixed population with three groups. Analysis of molecular variance revealed a significant F st value of 0.69659 indicating high genetic differentiation among the 53 genotypes. Thus, the developed microsatellites will be advantageous in assessing genetic diversity, developing linkage map, and also molecular characterization of genotypes.

Phenyl Sulfones: A Route to a Diverse Family of Trisubstituted Cyclohexenes from Three Independent Nucleophilic Additions.

A novel process is described for the synthesis of di- and trisubstituted cyclohexenes from an arene. These compounds are prepared from three independent nucleophilic addition reactions to a phenyl sulfone (PhSO2R; R = Me, Ph, and NC4H8) dihapto-coordinated to the tungsten complex {WTp(NO)(PMe3)}(Tp = trispyrazolylborate). Such a coordination renders the dearomatized aryl ring susceptible to protonation at a carbon ortho to the sulfone group. The resulting arenium species readily reacts with the first nucleophile to form a dihapto-coordinated sulfonylated diene complex. This complex can again be protonated, and the subsequent nucleophilic addition forms a trisubstituted cyclohexene species bearing a sulfonyl group at an allylic position. Loss of the sulfinate anion forms a π-allyl species, to which a third nucleophile can be added. The trisubstituted cyclohexene can then be oxidatively decomplexed, either before or after substitution of the sulfonyl group. Nucleophiles employed include masked enolates, cyanide, amines, amides, and hydride, with all three additions occurring to the same face of the ring, anti to the metal. Of the 12 novel functionalized cyclohexenes prepared as examples of this methodology, nine compounds meet five independent criteria for evaluating drug likeliness. Structural assignments are supported with nine crystal structures, density functional theory studies, and full 2D NMR analysis.

Efficient Channel Estimation for Wideband Millimeter Wave Massive MIMO Systems With Beam Squint

Massive multiple-input-multiple-output (MIMO) and millimeter wave have been adopted as the enabling technologies for the 5G and beyond 5G (B5G) systems. A challenging problem introduced by the use of large antenna size and wide bandwidth is beam squint, i.e., spatial-wideband effect. Beam squint can significantly degrade the channel estimation performance for conventional channel estimators. Research effort on channel estimation under beam squint conditions has been very limited. For the few available work that attempts to address this problem, they require either all subcarriers or multiple symbols used as pilot for channel estimation, so large overhead becomes inevitable. Therefore, in this paper, we propose an efficient channel estimation method that only requires a small number of subcarriers. The channel estimation problem is formulated as a nonlinear least squares optimization problem. Initial parameter estimation is critical, which will affect the efficiency and convergence of the proposed algorithm. Using a densely-spaced antenna structure and consecutive subcarriers assignment approach, we can effectively avoid the aliasing effect and reduce the ambiguity during the initialization phase. A subcarrier assignment criterion is proposed to achieve the optimal performance. Closed-form expressions of the Cramér-Rao lower bound (CRLB) and the achievable rate are derived to evaluate the performance. Both simulation results and theoretical analysis show that even with a small number of subcarriers, the estimation error closely approaches the CRLB, and its effect is negligible compared with the noise when evaluating the signal-to-noise ratio with a simple linear detector. Furthermore, the number of pilot subcarriers has little impact on the achievable rate.

True-atomic-resolution insights into the structure and functional role of linear chains and low-barrier hydrogen bonds in proteins.

Hydrogen bonds are fundamental to the structure and function of biological macromolecules and have been explored in detail. The chains of hydrogen bonds (CHBs) and low-barrier hydrogen bonds (LBHBs) were proposed to play essential roles in enzyme catalysis and proton transport. However, high-resolution structural data from CHBs and LBHBs is limited. The challenge is that their 'visualization' requires ultrahigh-resolution structures of the ground and functionally important intermediate states to identify proton translocation events and perform their structural assignment. Our true-atomic-resolution structures of the light-driven proton pump bacteriorhodopsin, a model in studies of proton transport, show that CHBs and LBHBs not only serve as proton pathways, but also are indispensable for long-range communications, signaling and proton storage in proteins. The complete picture of CHBs and LBHBs discloses their multifunctional roles in providing protein functions and presents a consistent picture of proton transport and storage resolving long-standing debates and controversies.

SPI "sandwich": Combined SUMO-Peptide-Intein expression system and isolation procedure for improved stability and yield of peptides.

Recombinant peptide production in Escherichia coli is often accomplished through cloning and expression of a fusion protein. The fusion protein partner generally has two requirements: (a) it contains an affinity tag to assist with purification and (b) it can be cleaved off to leave only the desired peptide sequence behind. Common soluble fusion partners include small ubiquitin-like modifier protein (SUMO), maltose-binding protein (MBP), glutathione S-transferase (GST), or intein proteins. However, heterologously expressed peptides can suffer from proteolytic degradation or instability. This degradation can pose a major issue for applications requiring a large amount of purified peptide, such as NMR structural assignments or biochemical assays. Improving peptide yield by testing various expression and isolation conditions requires a significant amount of effort and may not lead to improved results. Here, we cloned and expressed four different peptides as SUMO fusion proteins. These peptides (lactococcin A, leucocin A, faerocin MK, neopetrosiamide A) were truncated during expression and isolation as SUMO fusions, resulting in low yields of purified peptide. To prevent this degradation and improve yield, we designed a new expression system to create a "sandwiched" fusion protein of the form: His6 -SUMO-peptide-intein (SPI). These sandwiched peptides were more stable and protected against degradation, resulting in improved yields (up to 17-fold) under a set of standard expression and isolation procedures. This SPI expression system uses only two commercially available vectors and standard protein purification techniques, and therefore may offer an economical and facile route to improve yields for peptides that undergo degradation.

Unidirectional Double- and Triple-Hydrogen Rearrangement Reactions Probed by Infrared Ion Spectroscopy.

Unidirectional double-hydrogen (2H) and triple-hydrogen (3H) rearrangement reactions occur upon electron-ionization-induced fragmentation of trans-2-(4-N,N-dimethylaminobenzyl)-1-indanol (1), trans-2-(4-methoxybenzyl)-1-indanol (2), 4-(4-N,N-dimethylaminophenyl)-2-butanol (3), and related compounds, as reported some 35 years ago (Kuck, D.; Filges, U. Org. Mass Spectrom. 1988, 23, 643-653). These unusual intramolecular redox processes were found to dominate the mass spectra of long-lived, metastable ions. The present report provides independent evidence for the structures of the product ions formed by the 2H and 3H rearrangement in an ion trap instrument. The radical cations 1•+ and 3•+ as well as ionized 1-(4-N,N-dimethylaminophenyl)-5-(4-methoxyphenyl)-3-pentanol, 5•+, were generated by electrospray ionization from anhydrous acetonitrile solutions. The 2H and 3H fragment ions were obtained by collision-induced dissociation and characterized by IR ion spectroscopy and density functional theory calculations. Comparison of the experimental and calculated infrared ion spectra enabled the identification of the 2H rearrangement product ion, C9H14N+ (m/z 136), as an N,N-dimethyl-para-toluidinium ion bearing the extra proton ortho to the amino group, a tautomer which was calculated to be 31 kJ/mol less stable than the corresponding N-protonated form. The 3H rearrangement product ion, C8H13N•+ (m/z 123), formerly assumed to be a distonic ammonium ion bearing a cyclohexadienyl radical, was now identified as a conventional radical cation, ionized N,N-dimethyl-2,3-dihydro-para-toluidine. Thus, the 3H rearrangement represents an intramolecular transfer hydrogenation between a secondary alcohol and an ionized aromatic ring. Based on these structural assignments, more detailed mechanisms for the unidirectional 2H and 3H rearrangement reactions are proposed.

The Relationship Of Provision Of Structured Assignments And Feedback On The Students Of Indonesian Learning Outcomes In Class X SMA 15 Maluku Tengah

This study aims to determine whether there is a relationship between giving structured assignments and feedback on student learning outcomes in class X-4 SMA Negeri 15 Maluku Tengah on Indonesian language skills. This research is quantitative descriptive. The population of this study were students of class X-4 SMA Negeri 15 Maluku Tengah, amounting to 33 people. The results showed that the relationship between giving structured assignments and feedback on Indonesian language learning outcomes for X-4 graders of SMA Negeri 15 Maluku Tengah was satisfactory. This is evidenced by the number of respondents' answers to the questionnaire with a presentation of 70%-89%. The application of structured tasks with feedback can improve student learning outcomes. This has been proven by researchers in class X-4 students at SMA Negeri 15 Maluku Tengah. The results obtained based on the df value of 31 which was converted to rtable at a significance level of 5% obtained a price of 0.355, while at a 1% significance level a price of 0.456 was obtained. Test criteria: if rcount rtable then Ha is accepted and Ho is rejected, otherwise if rcount rtable then Ha is rejected and Ho is accepted. It turns out that rxy which is 0.74 is bigger than rtable. Because rxy is greater than rtable, then Ha is accepted and Ho is rejected. Based on the interpretation that is matched with the results of the calculation of the correlation index number "r" product moment with a large rxy (0.74) whose magnitude lies between 0.70 - 0.90. This means that the relationship between giving structured assignments and feedback on Indonesian language learning outcomes for class X SMA Negeri 15 Maluku Tengah students has a strong correlation, with a contribution of 54.76%. This shows that there is a relationship between giving structured assignments and feedback that has a positive effect on student learning outcomes.

Diversity‐Oriented Synthesis of 2‐Iminothiazolidines: Pushing the Boundaries of the Domino Nucleophilic Displacement/Intramolecular anti‐Michael Addition Process

AbstractMethods for the synthesis of a variety of functionalized 2‐iminothiazolidines and related heterocycles through a base‐mediated domino nucleophilic displacement/intramolecular anti‐Michael addition process involving electron‐deficient allylic bromides and 1,3‐ambident nucleophiles derived from thiourea were developed. These transformations proceed under mild and simple conditions and different functional groups are well tolerated. The scope and limitations of this protocol are dependent on the structure of the allylic bromide and 1,3‐ambident nucleophile involved. The synthetic versatility of 2‐iminothiazolidines was further demonstrated through a series of chemoselective modifications, giving rise to a wide range of thiazolidine frameworks of structural complexity. In particular, the reductive cyclization of 2‐nitrobenzyl‐substituted 2‐iminothiazolidines furnished novel spiroquinolones in good to fair yields. The structural assignment of key products was unequivocally achieved by X‐ray diffraction analysis and two‐dimensional NMR techniques.

Conformational Properties of New Thiosemicarbazone and Thiocarbohydrazone Derivatives and Their Possible Targets.

The structure assignment and conformational analysis of thiosemicarbazone KKI15 and thiocarbohydrazone KKI18 were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations using Functional Density Theory (DFT). After the structure identification of the compounds, various conformations of the two compounds were calculated using DFT. The two molecules showed the most energy-favorable values when their two double bonds adopted the E configuration. These configurations were compatible with the spatial correlations observed in the 2D-NOESY spectrum. In addition, due to the various isomers that occurred, the energy of the transition states from one isomer to another was calculated. Finally, molecular binding experiments were performed to detect potential targets for KKI15 and KKI18 derived from SwissAdme. In silico molecular binding experiments showed favorable binding energy values for all four enzymes studied. The strongest binding energy was observed in the enzyme butyrylcholinesterase. ADMET calculations using the preADMET and pKCSm software showed that the two molecules appear as possible drug leads.

Bayesian Inference Applied to NMR-Based Configurational Assignments by Floating Chirality Distance Geometry Calculations.

Using NMR data, the assignment of the correct 3D configuration and conformation to unknown natural products is of pivotal importance in pharmaceutical and medicinal chemistry. In this report, we quantify the quality and probability of structural elucidations using Bayesian inference in combination with floating chirality distance geometry simulations. Here, we will discuss the configurational analysis of three complex natural products including isopinocampheol (1), plakilactone H (2), and iodocallophycoic acid A (3) using NMR restraints of various types and in different combinations (residual dipolar couplings (RDCs) and NOE-derived distances). Our results quantitatively demonstrate how reliably molecular geometries can be inferred from experimental NMR data, unequivocally unveiling remaining assignment ambiguities. The methodology presented here can dramatically reduce the risk of incorrect structural assignments based on the overinterpretation of incomplete data in chemistry.

PENGARUH PEMBELAJARAN MANDIRI BERBASIS LITERASI DIGITAL DAN KEGIATAN TERSTRUKTUR TERHADAP KEMAMPUAN KEMANDIRIAN MAHASISWA DI IAIN CURUP

The aim of this research is to find out the influence of independent learning models based on digital literacy and structured assignments on the independence abilities of students of the Islamic Education Study Program (PAI) Institut Agama Islam Negeri (IAIN) Curup. This research used a non-experimental research design. The sampling technique used is total sampling by taking the entire population to be used as research respondents. The samples in this study were students of the PAI Study Program, IAIN Curup class 5C and 5D in the 5th Semester who took the subject of Islamic Education Philosophy for the Academic Year 2021- 2022. Based on statistical analysis of this study, it was used to determine the relationship between independent learning models based on digital literacy and students' independence ability, showing tcount of 8,530 which was greater than ttable of 2,056, then to determine the relationship between structured assignments and independence ability, tcount of 35,467 was greater than ttable of 2.056, the results of the analysis also show that the Fcount is 571.6 greater than Ftable 3.34, so it can be concluded that there is the influence of independent learning models based on digital literacy, either partially or simultaneously, on the independence ability of students of the Islamic Education Study Program (PAI) Institut Agama Islam Negeri (IAIN) Curup

Isolation and detailed 1H and 13C NMR structural assignment for three trachylobanes from Psiadia punctulata (Asteraceae) grown in Africa

• New NMR data for three trachylobanes, are presented for the first time in Literature. • The presented data completely clarified the 1H and 13C NMR data assignments for these trachylobanes. • A new methodology, recently published, was applied to clarify all multiplicities, measuring all J values for all substances. • A stereochemistry clarification including W-coupling measuring is provided for each studied compound. The first isolation of a trachylobane from an African specimen of Psiadia punctulata (Asteraceae) is presented in this paper. A complete 1 H and 13 C NMR spectral analysis of this compound and two other trachylobane diterpenes, previously isolated from the same plant, are also provided. The use of NMR techniques such as g COSY, g HSQC, g HMBC and 2D- J -resolved, in combination with a software-assisted methodology, led to a complete and unequivocal assignment of 1 H and 13 C signals. This was achieved together with the measurement of all homonuclear hydrogen coupling constants. The presented detail level of the assignment data has never been published before for trachylobanes. Furthermore, with all determined NMR experimental data from the spectra and to obtain a reliability assessment, signals were simulated in the FOMSC3 and NMR_MultSim software.

Diterpenoids and p-methoxycinnamic acid diol esters from Kaempferia saraburiensis Picheans. (Zingiberaceae): Structural assignment of saraburol and their biological activities

Five undescribed compounds, including three diterpenoids namely, saraburol, saraburanes A and B, and two p-methoxycinnamic acid monoterpene diol esters, named E/Z-saraburinic esters, together with ten known oxygenated isopimarane diterpenoids, were isolated from the whole plant of Kaempferia saraburiensis Picheans. Among these compounds, saraburol possesses an unusual 6/9/6 tricyclic ring system bearing a 1,3-dioxonane-4-one scaffold, which is rarely found in natural products. The structure of isolated compounds was elucidated by spectroscopic methods, including HRESIMS, FTIR, 1D and 2D-NMR, and by comparison with published data, and their absolute configurations were determined by comparison of experimental with calculated ECD spectra and hydrolysis reaction. Using gauge-independent atomic orbital (GIAO) NMR shift calculations coupled with DP4+ probability analyses, biogenetic considerations, and optical rotation allowed for the complete characterization of saraburol. A plausible biosynthetic pathway for saraburol and saraburane A was proposed. The cytotoxicity result indicated that E-saraburinic ester exhibited the most potent activity with an IC50 value of 12.0 μM against MOLT-3 cells with a selectivity index of 12.5. Saraburane B exhibited the most potent activity against Gram-positive bacteria strain Staphylococcus epidermidis with MIC (MBC) value of 25 (50) μg/mL.