Protocol For Construction Research Articles

Enantioselective Synthesis of Axially Chiral Silacyclohexylidene Oxime Ethers by Chiral Phosphoric Acid Catalysis

The first asymmetric condensation of prochiral silacyclohexanones with hydroxylamines is developed by chiral phosphoric acid catalysis, which provided a facile and straightforward protocol for the enantioselective construction of valuable axially chiral silacyclohexylidene oxime ethers that are otherwise inaccessible. Notably, this constitutes a rare example for accessing silacycles featuring an axial chirality.

Base-Mediated Annulation of ortho-Iminophenols and ortho-Vinylphenols with MBH Carbonates of Isatins: Straightforward Access to Dihydrobenzofuran and Benzofuran Derivatives.

We have developed a convenient synthetic protocol for efficient construction of significant dihydrobenzofuran and benzofuran scaffolds by Lewis base-mediated annulation reaction ortho-iminophenols and ortho-vinylphenols with MBH carbonates of isatins under mild and metal-free conditions. The selective generation of different kinds of dihydrobenzofuran and benzofuran derivatives was successfully achieved by employing different substituted isatin-derived MBH carbonates with ortho-N-tosyliminophenols and ortho-vinylphenols. The features included broad substrate scopes, excellent functional group compatibility, high molecular diversity, and atomic economy.

Facile synthesis of vinyl sulfoxides via external oxidant-free oxidative condensation of phenylglycinols with DMSO

Oxidative activation of CO, CN and CC bonds has recently emerged as a powerful method for the synthesis of valuable organic compounds. However, these strategies have often required the metal catalysts and strong external oxidants. Herein, we report a new protocol for the convenient construction of vinyl sulfoxides from phenylglycinols and DMSO under basic conditions. Notably, DMSO was used not only as a methyl sulfoxide (−SOMe) reagent, but also as an oxidizing agent. The present system features mild metal- and external oxidant-free conditions, broad scope, and excellent functionality tolerance.

Enzyme-Catalyzed Regioselective Synthesis of 4-Hetero-Functionalized 1,5-Disubstituted 1,2,3-Triazoles.

Enzyme-catalyzed novel protocols for the regioselective construction of fully substituted 1,2,3-triazoles by employing 2-azido-1,3,5-triazine (ADT) as a 1,3-dipole for the cycloaddition reaction with the activated alkene in an aqueous medium have been developed. Various 4-heterosubstituted-1,2,3-triazoles were readily assembled in good to excellent yields with high regioselectivity. This reaction also features wide substrate scope, strong functional group tolerance, gram-scale synthesis, and an environmentally friendly process.

Quantum Chemistry Dataset with Ground- and Excited-state Properties of 450 Kilo Molecules

Due to rapid advancements in deep learning techniques, the demand for large-volume high-quality datasets grows significantly in chemical research. We developed a quantum-chemistry database that includes 443,106 small organic molecules with sizes up to 10 heavy atoms including C, N, O, and F. Ground-state geometry optimizations and frequency calculations of all compounds were performed at the B3LYP/6-31G* level with the BJD3 dispersion correction, while the excited-state single-point calculations were conducted at the ωB97X-D/6-31G* level. Totally twenty-seven molecular properties, such as geometric, thermodynamic, electronic and energetic properties, were gathered from these calculations. Meanwhile, we also established a comprehensive protocol for the construction of a high-volume quantum-chemistry dataset. Our QCDGE (Quantum Chemistry Dataset with Ground- and Excited-State Properties) dataset contains a substantial volume of data, exhibits high chemical diversity, and most importantly includes excited-state information. This dataset, along with its construction protocol, is expected to have a significant impact on the broad applications of machine learning studies across different fields of chemistry, especially in the area of excited-state research.

Design, synthesis and anticancer activity of β-carboline based pseudo-natural products by inhibiting AKT/mTOR signaling pathway

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the leading cause of cancer deaths. Much progress has been made to treat NSCLC, however, only limited patients can benefit from current treatments. Thus, more efforts are needed to pursue novel molecular modalities for NSCLC treatment. It was demonstrated that pseudo-natural products (PNP) are a critical source for antitumor drug discovery. Herein, we describe a CH activation protocol for the expedient construction of a focused library utilizing the PNP rational design strategy. This protocol features a rhodium-catalyzed CH activation/ [4+2] annulation reaction between N-OAc-indole-2-carboxamide and alkynyl quinols, enabling facile access to diverse quinol substituted β-carboline derivatives (31 examples). The anticancer activities were assessed in vitro against NSCLC cell line A549, yielding a potent antiproliferative β-carboline derivative (8r) with an IC50 value of 0.8 ± 0.1 µM. Further investigation revealed that this compound could decrease the expression of Caspase 3, and increase the expression of autophagic protein Cyclin B1, thus markedly inducing autophagy and apoptosis. Mechanistic study suggested that 8r could be a potent anti-NSCLC agent through the AKT/mTOR signaling pathway in A549 cells. Moreover, the anticancer activities were also assessed against three other cancer cell lines, and 8r exhibits a broader inhibitory effect on cell proliferation in all cancer cell lines tested. These results indicated that carboline-based PNPs show great potential to induce cell autophagy and apoptosis, which serve as good leads for further drug discovery.

Edge Modes and Symmetry-Protected Topological States in Open Quantum Systems

Topological order offers possibilities for processing quantum information that can be immune to imperfections. However, the question of its stability out of equilibrium is relevant for experiments, where coupling to an environment is unavoidable. In this work, we demonstrate the robustness of certain aspects of Z2×Z2 symmetry-protected topological (SPT) order against a wide class of dissipation channels in the Lindblad and quantum trajectory formalisms of an open quantum system. This is illustrated using the one-dimensional ZXZ cluster Hamiltonian along with Pauli-string jump operators. We show that certain choices of dissipation retaining strong symmetries support a steady-state manifold consisting of two nonlocal qubits and for Hamiltonian perturbations preserving the global symmetry, states in this manifold remain metastable. In contrast, this metastability is destroyed upon breaking the above-mentioned symmetry. While the localized qubits of the cluster Hamiltonian are not conserved by the Lindbladian evolution, they do correspond to weak symmetries and thus retain a memory of their initial state at all times in the quantum trajectories. We utilize this feature to construct protocols to retrieve the quantum information either by monitoring jumps or error mitigation. Our work thus proposes a novel framework to study the dynamics of dissipative SPT phases and opens up the possibility of engineering entangled states relevant to quantum information processing. Published by the American Physical Society 2024

Amidation of β‐Keto Sulfonyl Fluorides via C−C Bond Cleavage

AbstractA simple protocol for amide bond construction using β‐keto sulfonyl fluorides (BKSFs) as the acyl surrogates has been achieved. The reaction of BKSFs with a range of amines could be performed in presence of N‐bromosuccinimide (NBS), affording various amides with diverse functionalities. Preliminary mechanistic studies revealed that the dibromo‐substituted sulfonyl fluorides could be the key intermediate in this amidation process.

Validation of cheap axial passive sampler and procedure suitable for atmospheric NO2 community-based monitoring

Nitrogen dioxide (NO2) is an air pollutant highly impacting on human health, and its measurement is crucial for air quality assessment. Use of passive samplers for long-term large-scale monitoring is a reasonably reliable and economic alternative to more sophisticated and expensive equipment employed in active air sampling by environmental control authorities. In recent years the Citizen Science approach, based on low-cost devices, is spreading more and more in environmental control. Passive samplers available on the market (like the consolidated “Palmes” tubes) are often used in community-based monitoring campaigns. We describe validation of a new cheap axial diffusion tube for NO2 monitoring, used in combination with a new user-friendly App for smartphone that represents an innovation to speed up recording of geo-localization and exposition period data. Affordability and availability of materials, simple construction protocol and easy App procedure, allow possible self-production by school students and non-expert users, making the proposed tube a potential tool to realize extended Citizen Science monitoring campaigns. Accuracy within 25% and precision within 20%, evidenced in validation, show comparability of the tube performance with Palmes-type tubes and agreement with the official monitoring station results. Two small-scale trial monitoring campaigns, involving high school students, were performed to test the efficacy of the proposed “tube-App” system in combining educational impact and community value of air quality monitoring.

A New Method of Constructing Methyleneindene and Quinoline Frameworks from Methylenecyclopropanes.

In this paper, we have established an operationally convenient protocol for the rapid construction of polysubstituted methyleneindene and quinoline derivatives under mild conditions. This new synthetic method is achieved through the conversion of acetyl-substituted methylenecyclopropanes with TsOH ⋅ H2O and ortho-amino-substituted methylenecyclopropanes with aromatic aldehyde and TsOH ⋅ H2O, respectively. A variety of transformations of the obtained products was demonstrated. The plausible reaction mechanisms were also proposed.

Comparative Vision of Nonlinear Thermo-Optical Features and Third-Order Susceptibility of Mechanically Flexible Metallosupramolecular Self-Repairing Networks with Isomeric Organic Acids.

Two self-healing-type supramolecular Ni(II)-metallogels are achieved. The choice of proper low-molecular-weight organic gelators such as trans-butenedioic acid (i.e., trans-BDA) and cis-butenedioic acid (i.e., cis-BDA) and triethylamine in N,N'-dimethylformamide solvent facilitates the metallogelation process. Through rheological investigations the mechanical robustness and viscoelastic properties of synthesized metallogels are explored. An in-depth exploration of thixotropic behavior also supports their self-healing features. Notably, distinct variations in morphologies of metallogels are also ascertained through field emission scanning electron microscopy studies. Furthermore, the existence of versatile noncovalent supramolecular interactions operating throughout the metallogel network is clearly revealed via Fourier transform infrared spectroscopy. Electrospray ionization-mass studies also explore the construction protocol of individual Ni(II)-metallogels. The Z-scan measurements with a 532 nm continuous wave laser were employed to unveil the nonlinear thermo-optical response of two synthesized self-healing metallogels, i.e., trans-BDA-TEA@Ni(II) and cis-BDA-TEA@Ni(II). Crucial parameters like the nonlinear refractive index, nonlinear absorption coefficient, thermo-optical coefficient, and third-order susceptibility of these metallogels are obtained. Metallogels show negative signs for the nonlinear refractive index and the nonlinear absorption coefficient. The real parts of the third-order susceptibility for these metallogels are much greater than the imaginary parts (i.e., χR(3) > χI(3)), making such metallogels very promising for all optical-switching applications.

Sampling Strategies for Experimentally Mapping Molecular Fitness Landscapes Using High-Throughput Methods.

Empirical studies of genotype-phenotype-fitness maps of proteins are fundamental to understanding the evolutionary process, in elucidating the space of possible genotypes accessible through mutations in a landscape of phenotypes and fitness effects. Yet, comprehensively mapping molecular fitness landscapes remains challenging since all possible combinations of amino acid substitutions for even a few protein sites are encoded by an enormous genotype space. High-throughput mapping of genotype space can be achieved using large-scale screening experiments known as multiplexed assays of variant effect (MAVEs). However, to accommodate such multi-mutational studies, the size of MAVEs has grown to the point where a priori determination of sampling requirements is needed. To address this problem, we propose calculations and simulation methods to approximate minimum sampling requirements for multi-mutational MAVEs, which we combine with a new library construction protocol to experimentally validate our approximation approaches. Analysis of our simulated data reveals how sampling trajectories differ between simulations of nucleotide versus amino acid variants and among mutagenesis schemes. For this, we show quantitatively that marginal gains in sampling efficiency demand increasingly greater sampling effort when sampling for nucleotide sequences over their encoded amino acid equivalents. We present a new library construction protocol that efficiently maximizes sequence variation, and demonstrate using ultradeep sequencing that the library encodes virtually all possible combinations of mutations within the experimental design. Insights learned from our analyses together with the methodological advances reported herein are immediately applicable toward pooled experimental screens of arbitrary design, enabling further assay upscaling and expanded testing of genotype space.

Enhancing privacy and security in smart healthcare: A blockchain-powered decentralized data dissemination scheme

Dissemination of health data in smart healthcare allows a patient’s health information to be accessible across healthcare communities for the improvement of patients’ care services. In our work, data collected from a patient’s automated health device is distributed to the communities through the blockchain network. Blockchain technology paves the way for the health sector to run in a decentralized system. To achieve a secure decentralized data dissemination, the transmitted health data must be reliable, that is, data is assured originated from a legitimate device without unlawful alteration. However, verification of such reliability may jeopardize a patient’s privacy. In healthcare, privacy is of the utmost importance to protect sensitive health data. At the same time, should misbehavior arise, malicious entities should be held accountable. We satisfy these conflicting requirements of reliability, privacy and accountability with our proposed secure decentralized data dissemination scheme for smart healthcare that integrates a certificate-based signcryption with a proxy re-encryption (Sign-Proxy) scheme and an Improved Delegated Proof-of-Stake (DPoS) consensus protocol for the system construction. The Sign-Proxy provides users a desirable level of security while delivering lightweight computation for limited computing capabilities of automated health devices. In parallel, the Improved DPoS facilitates the streamlined and secure adoption of a consortium blockchain framework. The security and performance analysis indicate that the proposed scheme is resilience against adversarial attacks, achieves overall efficiency, and feasible for real-world deployment.

Electrochemical Oxidative Cross-Coupling Reactions of Ketene Dithioacetals and Dichalcogenides to Construct C−Se/C−S Bonds

A green protocol for construction of C−Se bonds from ketene dithioacetals and diselenides through direct electrochemical oxidative cross-coupling has been developed. This reaction was carried out in an undivided cell system with NaBF4 as the electrolyte and CH3CN as the solvent through galvanostatic electrolysis. A series of substituted ketene dithioacetals and diselenides were tolerant and the desired tetrasubstituted alkenyl selenides were obtained in moderate to excellent yields. In addition, construction of C−S bond from ketene dithioacetals and disulfides through electrochemical method in the presence of KI was also successfully realized. It exhibited high efficiency and broad functional group tolerance.

Circuit complexity of quantum access models for encoding classical data

How to efficiently encode classical data is a fundamental task in quantum computing. While many existing works treat classical data encoding as a black box in oracle-based quantum algorithms, their explicit constructions are crucial for the efficiency of practical algorithm implementations. Here, we unveil the mystery of the classical data encoding black box and study the Clifford + T complexity in constructing several typical quantum access models. For general matrices (even including sparse ones), we prove that sparse-access input models and block-encoding both require nearly linear circuit complexities relative to the matrix dimension. We also give construction protocols achieving near-optimal gate complexities. On the other hand, the construction becomes efficient with respect to the data qubit when the matrix is a linear combination of polynomial terms of efficiently implementable unitaries. As a typical example, we propose improved block-encoding when these unitaries are Pauli strings. Our protocols are built upon improved quantum state preparation and a select oracle for Pauli strings, which hold independent values. Our access model constructions provide considerable flexibility, allowing for tunable ancillary qubit numbers and offering corresponding space-time trade-offs.

Abstract 7010: A pan-tissue investigation of epigenetic aging in association with genetic risk for cancer among European descendants

Abstract Epigenetic age (EA) is recognized as a valuable biomarker of aging. The discrepancy between epigenetic and chronological age (CA), termed epigenetic age acceleration (EAA), has been associated with increased mortality from various age-related diseases, including cancer. However, previous studies primarily focused on the EA in blood cells, resulting in a notable gap in understanding the EA in cancer-relevant tissues and its relationship to cancer development. To examine if genetic risks for seven distinct cancers are associated with EAA in cancer-relevant tissues and blood cells, we utilized Illumina EPIC-array-based DNA methylation data and whole genome sequencing (WGS)-derived genotype data of 659 normal tissue and 42 whole blood samples from 315 European-ancestry subjects in the Genotype-Tissue Expression (GTEx) project. EA was estimated across 30 female breast, 167 colon, 41 kidney, 163 lung, 118 ovary, 96 prostate, 44 testis, and 42 whole blood samples via seven established epigenetic clocks: HorvathAge, GrimAge, GrimAge2, HannumAge, PhenoAge, Zhang-BLUP-Age, and Zhang-EN-Age. EAA was calculated as the residual of EA regressed on CA. For each participant, a polygenic risk score (PRS) was computed to assess the genetic risk for each cancer, using validated cancer-specific PRSs for European populations from the Polygenic Score Catalogue. Linear regression analysis was performed to evaluate the association between cancer PRS and EAA, adjusting for body mass index, sex (where applicable), cigarette smoking, and WGS platform and library construction protocol. All EA estimates of cancer-relevant tissues and blood cells exhibited significant correlations with CA (maximum P=2.44 × 10−3). Among them, GrimAge, known for its strong predictive capacity for mortality, had the most pronounced correlation with CA, with Spearman coefficients ranging from 0.80 in blood cells to 0.98 in breast tissues. A higher prostate cancer PRS was significantly associated with increased EAA in normal prostate tissues measured by PhenoAge (β=2.49; P=0.01), Zhang-BLUP-Age (β=1.71; P=0.02), HannumAge (β=1.36; P=0.04), and GrimAge (β=0.73; P=0.04). In addition, a higher PRS for renal cell carcinoma showed a significant association with increased GrimAge acceleration in normal kidney tissues (β=0.82; P=0.02). Moreover, breast and lung cancer PRSs were significantly associated with increased EAA in blood cells. Specifically, breast cancer PRS was associated with Zhang-BLUP-Age acceleration (β=0.99; P=0.04), while lung cancer PRS showed associations with HannumAge (β=1.78; P=0.01) and Zhang-EN-Age acceleration (β=0.94; P=0.02). Our results suggest a potential connection between genetic susceptibility to certain cancers and accelerated aging in relevant tissues and/or blood cells before cancer onset. Future large-scale studies are needed to substantiate and expand upon our findings. Citation Format: Yaxin Chen, Yawen Qi, Gang Wang, Yufang Xie, Yaohua Yang, Weimin Li. A pan-tissue investigation of epigenetic aging in association with genetic risk for cancer among European descendants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7010.

Recent Advances in Preparing Transparent Phosphor Ceramics for High-Index Color Rendering and High-Power Lighting.

In recent years, high-power white light-emitting diode (wLED)/laser diode (wLD) lighting sources based on transparent phosphor ceramic (TPC) materials have attracted increasing application interest in automotive headlights, projection displays, and space navigation lighting due to their superior brightness, lighting distance, compactness, lifespan, and environmental resistance compared with the widely used phosphor-converted wLEDs. However, preparing TPC-converted wLEDs/wLDs with high color rendering index (CRI) remains a huge challenge, which limits their widespread application. In this review, we summarize the recently adopted strategies for constructing TPCs to develop high-power wLEDs/wLDs with high CRI values (>75). The construction protocols were categorized into four groups: host regulation, red-emitter doping, host regulation/red-emitter doping combination, and composite structure design. A comprehensive discussion was conducted on the design principles, photoluminescent properties, and device performances for each strategy. The challenges and future trends of high-power and high-CRI wLEDs/wLDs based on TPCs are also discussed toward the end of this review.

ANNProof: Building a verifiable and efficient outsourced approximate nearest neighbor search system on blockchain

Data-as-a-service is increasingly prevalent, with outsourced K-approximate nearest neighbors search (K-ANNS) gaining popularity in applications like similar image retrieval and anti-money laundering. However, malicious search service providers and dataset providers in current outsourced query systems cause incorrect user query results. To address this, we propose ANNProof, a novel framework supporting verifiable outsourced K-ANNS on the blockchain. ANNProof utilizes two innovative authenticated data structures (ADS), the Merkle HNSW node tree, and the Merkle vector identifier tree, for efficient K-ANNS query verification. Additionally, we employ the Merkle sharding tree as an ADS optimization technique, reducing the overhead of delivering verifiable queries. We implement the ADS construction protocol based on blockchain smart contracts to ensure tamper-evident datasets and enhance execution efficiency via a contract state consistency checking scheme. Extensive evaluations show that ANNProof reduces VO generation time, result verification time, and VO size by 160, 120, and 28×, respectively, compared to the state-of-the-art systems. Moreover, ADS construction using ANNProof takes at most 2% of the index construction time, resulting in a negligible overhead for implementing verifiable queries. Meanwhile, the sharding optimization accelerates ADS updates by 53×.

NSP-SCD: A corpus construction protocol for child-directed print in understudied languages

Child-directed print corpora enable systematic psycholinguistic investigations, but this research infrastructure is not available in many understudied languages. Moreover, researchers of understudied languages are dependent on manual tagging because precise automatized parsers are not yet available. One plausible way forward is to limit the intensive work to a small-sized corpus. However, with little systematic enquiry about approaches to corpus construction, it is unclear how robust a small corpus can be made. The current study examines the potential of a non-sequential sampling protocol for small corpus development (NSP-SCD) through a cross-corpora and within-corpus analysis. A corpus comprising 17,584 words was developed by applying the protocol to a larger corpus of 150,595 words from children’s books for 3-to-10-year-olds. While the larger corpus will by definition have more instances of unique words and unique orthographic units, still, the selectively sampled small corpus approximated the larger corpus for lexical and orthographic diversity and was equivalent for orthographic representation and word length. Psycholinguistic complexity increased by book level and varied by parts of speech. Finally, in a robustness check of lexical diversity, the non-sequentially sampled small corpus was more efficient compared to a same-sized corpus constructed by simply using all sentences from a few books (402 books vs. seven books). If a small corpus must be used then non-sequential sampling from books stratified by book level makes the corpus statistics better approximate what is found in larger corpora. Overall, the protocol shows promise as a tool to advance the science of child language acquisition in understudied languages.

Failure investigation of a propped cantilever truss bridge

Propped cantilever truss is not a common bridge construction technique. The performance of such bridges under operational and extreme loading is not reported in the literature either. In this paper, failure mechanisms in a propped cantilever truss bridge are reported using field investigation. The field observations are supplemented by numerical analysis to identify the causes of failure. A a systematic account of damage mechanisms in bridge components is also reported. The failure of the Lamgadi Bridge over the Seti River in Nepal is used as a case study example. The loading and construction protocols are detailed, and numerical analysis results are juxtaposed with the field observations to explain the failure mechanisms. Field observations and numerical results show that lack in adequate design is the most likely cause of the bridge collapse. Numerical results also indicate that the roller support at the propped end, unlike the hinged pot bearing used in the as constructed bridge would have been a safer choice. The failure could have been easily prevented with proper numerical simulation of the bridge response during the design phase.