Search

Transitional justice refers to a variety of measures that aim to address large-scale or systematic human rights violations in societies emerging from repression or mass violence. This chapter reviews the interdisciplinary literature on transitional justice with a particular focus on empirical studies attempting to uncover its effects on individuals affected by violence and repression, including victims, perpetrators, and communities at large. We first consider retributive and restorative justice as two distinct notions of justice that are of primary concern in the aftermath of mass atrocities, and then zoom in on the psychological implications of major transitional justice measures. These measures include criminal trials, truth commissions, material and symbolic reparations, as well as grassroot and hybrid measures. In addition, we discuss the case of impunity, or the absence of transitional justice. Our review highlights the advantages and limitations of different transitional justice measures in promoting human rights, peace, and reconciliation, and identifies directions for future research.

Mengqian Liu, Xuerong Wei, Zijun Zheng, Yicheng Li, Mengyao Li, Jiabao Lin, Lei Yang Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Lei Yang, Department of Burns, Nanfang Hospital, Southern Medical University, Jingxi Street, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1841, Email yuanyang@smu.edu.cnAbstract: Diabetes mellitus (DM) induced wound healing impairment remains a serious health problem and burden on the clinical obligation for high amputation rates. Based on the features of wound microenvironment, biomaterials loading specific drugs can benefit diabetic wound treatment. Drug delivery systems (DDSs) can carry diverse functional substances to the wound site. Nano-drug delivery systems (NDDSs), benefiting from their features related to nano size, overcome limitations of conventional DDSs application and are considered as a developing process in the wound treatment field. Recently, a number of finely designed nanocarriers efficiently loading various substances (bioactive and non-bioactive factors) have emerged to circumvent constraints faced by traditional DDSs. This review describes various recent advances of nano-drug delivery systems involved in mitigating diabetes mellitus-based non-healing wounds.Keywords: drug delivery system, nanotechnology, diabetic wound healing, nanoparticles

mRNA therapy is gaining worldwide attention as an emerging therapeutic approach. The widespread use of mRNA vaccines during the COVID-19 outbreak has demonstrated the potential of mRNA therapy. As mRNA-based drugs have expanded and their indications have broadened, more patents for mRNA innovations have emerged. The global patent landscape for mRNA therapy has not yet been analyzed, indicating a research gap in need of filling, from new technology to productization. This study uses social network analysis with the patent quality assessment to investigate the temporal trends, citation relationship, and significant litigation for 16,101 mRNA therapy patents and summarizes the hot topics and potential future directions for this industry. The information obtained in this study not only may be utilized as a tool of knowledge for researchers in a comprehensive and integrated way but can also provide inspiration for efficient production methods for mRNA drugs. This study shows that infectious diseases and cancer are currently the primary applications for mRNA drugs. Emerging patent activity and lawsuits in this field are demonstrating that delivery technology remains one of the key challenges in the field and that drug-targeting research in combination with vector technology will be one of the major directions for the industry going forward. With significant funding, new organizations have developed novel delivery technologies in an attempt to break into the patent thicket established by companies such as Arbutus. The global mRNA therapeutic landscape is undergoing a multifaceted development pattern, and the monopoly of giant companies is being challenged., I have received requests from co-authors and funding agencies to withdraw the manuscript

Autoencoder frameworks have received attention for graph embedding, particularly those utilizing generative adversarial networks (GAN). However, GAN-based frameworks do not fully utilize the original graph information and lack stable updates in the GAN component. To bridge this gap, we propose a dual-adversarial framework for graph embedding that expands mutual information (MI) in positive and negative samples for adversarial training using GAN. We further improve model performance by incorporating reinforcement learning ideas. Our framework includes two variants: a pessimistic adversarial graph autoencoder (PAGAE), and a pessimistic adversarial graph autoencoder with PO loss (PAGAEPO). Essentially, we present a pessimistic module to negative sample generator to boost original discriminator, thereby reinforcing the generator’s ability. Additionally, we designed a PO loss function on discriminator to stabilize the learning process and it will further improve the ability of model. Experimental results show that our models are competitive with state-of-the-art GAEs on benchmark datasets.

A crucial assumption underlying the most current theory of machine learning is that the training distribution is identical to the test distribution. However, this assumption may not hold in some real-world applications. In this paper, we develop a learning model based on principles of information theory by minimizing the worst-case loss at prescribed levels of uncertainty. We reformulate the empirical estimation of the risk functional and the distribution deviation constraint based on the importance sampling method. The objective of the proposed approach is to minimize the loss under maximum degradation and hence the resulting problem is a minimax problem which can be converted to an unconstrained minimum problem using the Lagrange method with the Lagrange multiplier $T$. We reveal that the minimization of the objective function under logarithmic transformation is equivalent to the minimization of the p-norm loss with $p=\frac{1}{T}$. We applied the proposed model to the face verification task on Racial Faces in the Wild datasets and showed that the proposed model performs better under large distribution deviations., Comment: 7 pages, 4 figures

Supplemental Material for Objective Communication Patterns Associated With Team Member Effectiveness in Real-World Virtual Teams by Mengyao Li, Isabel M Erickson, Ernest V Cross and John D Lee in Human Factors

Gibberellin (GA) is an important phytohormone that can participate in various developmental processes of plants. The study found that application of GA3 can induce parthenocarpy fruit and improve fruit set. However, the use of GA3 affects endogenous hormones in fruits, thereby affecting fruit quality. This study mainly investigates the effect of exogenous GA3 on endogenous hormones in sweet cherries. The anabolic pathways of each hormone were analyzed by metabolome and transcriptome to identify key metabolites and genes that affect endogenous hormones in response to exogenous GA3 application. Results showed that exogenous GA3 led to a significant increase in the content of abscisic acid (ABA) and GA and affected jasmonic acid (JA) and auxin (IAA). At the same time, the key structural genes affecting the synthesis of various hormones were preliminarily determined. Combined with transcription factor family analysis, WRKY genes were found to be more sensitive to the use of exogenous GA3, especially the genes belonging to Group III (PaWRKY16, PaWRKY21, PaWRKY38, PaWRKY52, and PaWRKY53). These transcription factors can combine with the promoters of NCED, YUCCA, and other genes to regulate the content of endogenous hormones. These findings lay the foundation for the preliminary determination of the mechanism of GA3’s effect on endogenous hormones in sweet cherry and the biological function of WRKY transcription factors.

Celery is well liked for it medicinal functions and nutritive value. However, fresh celery is not resistant to storage, severely limiting its supply time and marketing region. In this study, the effects of pretreatment and freezing storage on the nutritional quality of two kinds of celery (Chinese celery cultivar ‘Lvlin Huangxinqin’ and Western celery cultivar ‘Jinnan Shiqin’) after postharvest were investigated. Under all treatment combinations, 120 s blanching at 60 °C and 75 s blanching at 75 °C were the most effective pretreatments for ‘Lvlin Huangxinqin’ and ‘Jinnan Shiqin’, respectively. These two pretreatments combinations effectively delayed the decline of chlorophyll and fiber content, and maintained the level of carotenoids, soluble protein, total sugars, DPPH radical scavenging, total phenols, and vitamin C during freezing storage. These findings suggest that blanching and quick-freezing treatments are beneficial to maintain the nutritional quality of two kinds of celery, which have important reference significance for the postharvest processing of celery.

This project aims to understand different forms of political resistance in the social movement in Chile.

In this project, we collect 3 waves of cross-sectional survey data on how value and belief systems influence (non-)compliance with containment measures as the 2019-2020 coronavirus (COVID-19) pandemic unfolds in 21 countries. Specifically, this survey research investigates how values and belief systems change in response to the pandemic, and how these changes relate to compliance with scientifically-recommended containment measures.

This project explores the impact of commemorating historical collective victimhood on conflict beliefs and attitudes toward contemporary conflicts.

This project explores the impact of commemorating historical collective victimhood on conflict beliefs and attitudes toward contemporary conflicts.

Terahertz (THz) chirality pursues customizable manipulation from narrowband to broadband. While conventional THz chirality is restricted by non-negligible linewidth and unable to handle narrowband well. Recently, the concept "quasi bound states in continuum" (quasi-BIC) is introduced to optics resonance system whose the quality factor can be extremely high with the ultra-low radiative loss, thus providing a conceptual feasibility for wave control with ultra-narrow linewidth. Herein, we construct quasi-BIC in a planar all-silicon THz metasurface with in-plane C2 and mirror symmetries breaking. Such system not only exposes the symmetry-protected BIC, but also exposes the parameter-tuned BIC assigned to single resonance type. An extremely narrow linewidth (below 0.06 GHz) with high quality factor (104 level) is obtained at quasi-BIC frequency, which achieves the ultra-narrowband THz chirality.

[eng] TE devices have countless potential application, but their high manufacturing and material costs hamper their cost-effectiveness and limit their widespread implementation. To overcome these drawbacks, TE devices must be manufactured employing high throughput technologies and using materials based on low cost and abundant elements. This thesis focuses on the development of scalable and low consumption methods for the production of TE nanomaterials with optimized performance. In these directions, the general goals of this thesis is to develop cost-effective TE devices with improved TE conversion efficiency and low production cost. The main research objectives are: a) Exploring earth abundant, low-cost and less toxic materials with high TE performance; b) Developing a simple, scalable and cost-effective methodologies to produce TE materials and modules; c) Optimize the power factor (PF) and figure of merit (ZT) through optimized either via doping or defect engineering. d) Reduce the lattice thermal conductivity (κL) through the introduction of phonon scattering sources such as point defects, dislocations and interfaces. The thesis is divided into 5 chapters. Chapter 1 introduces the research status and development prospects of TE materials. Chapter 2 reports p-type polycrystalline SnSe materials with marked crystallographic texture were produced from blends of SnSe NCs and Te NRs through hot-pressing them at a temperature above the Te melting point. The presence of Te promoted the material crystallization in the form of a laminar structure with the a-axis along the pressure direction. SnSe nanomaterials consolidated in the presence of Te showed higher electrical conductivities and lower Seebeck coefficients and thermal conductivities than pure SnSe. The TE figures of merit up to ZT ̴̴ 1.4 at 790 K were measured from the SnSe nanomaterial consolidated in the presence of Te and measured along the pressing direction. Chapter 3 presents a synthetic protocol for large scale production of covellite CuS nanoparticles at ambient temperature and atmosphere, and using water as a solvent. The crystal phase and stoichiometry of the particles are afterward tuned through an annealing process at a moderate temperature under inert or reducing atmosphere. By optimizing the charge carrier concentration through the annealing time, Cu2-xS with record figures of merit in the middle temperature range, up to 1.41 at 710 K, is obtained. We finally demonstrate that this strategy, based on a low-cost and scalable solution synthesis process, is also suitable for the production of high performance Cu2-xS layers using high throughput and cost-effective printing technologies The Chapter 4 report a large scale method to synthesize N-type Bi2Se3 nanosheets. And further doped with Sn which present notable TE performance. Incorporating Sn in Bi2Se3 increases the Seebeck coefficient and thus improves the power factor to 0.65 mWm-1K-2. The low thermal conductivity, down to 0.91 Wm-1K-1, of Bi1.93Sn0.07Se3 results in ZT values well above higher than those of pure Bi2Se3. The Chapter 5 report that semiconductor-metal composites are produced by just blending nanoparticles of a sulfide semiconductor obtained in aqueous solution and at room temperature, with a metallic Cu powder. During the annealing process, the presence of metallic copper activates a partial reduction of the PbS, resulting in the formation of PbS-Pb-CuxS composites, the introduction of metallic copper in the initial blend results in a significant improvement of the TE performance of PbS, reaching a dimensionless TE figure of merit ZT = 1.1 at 750 K, which represents about a 400% increase over bare PbS. Besides, an average ZTave = 0.72 in the temperature range 320-773 K is demonstrated. Finally, the main conclusions of this thesis and some perspectives for future work are presented., [spa] Esta tesis consta de cinco capítulos. El primer capítulo presenta principalmente los conceptos básicos de termoelectricidad (TE) y el estado actual de desarrollo y los desafíos en el campo de la TE. Los capítulos 2 a 5 presentan principalmente la parte experimental. En el marco general de la optimización de materiales TE a través de la ingeniería bottom-up, el trabajo presentado en esta tesis tiene como objetivo resolver los principales desafíos en este campo: 1) Producción de nanomateriales de textura cristalográfica. 2) Ajuste la fase cristalina controlando la atmósfera del tratamiento térmico para optimizar la conductividad eléctrica y la conductividad térmica. 3) Aumentar la concentración de portadores de nanomateriales TE mediante el dopado de partículas metálicas. 4) Incrementar el coeficiente de Seebeck de los nanomateriales aumentando la banda prohibida con el dopaje. En el capítulo dos, se produjeron materiales de SnSe policristalinos de tipo p con una textura cristalográfica marcada a partir de mezclas de nanocristales de SnSe (NCs) y nanorods de Te (NRs) mediante prensado en caliente a una temperatura por encima del punto de fusión del Te. La presencia de Te promovió la cristalización del material en forma de estructura laminar con el eje a a lo largo de la dirección de la presión. Los nanomateriales de SnSe consolidados en presencia de Te mostraron conductividades eléctricas más altas y coeficientes de Seebeck y conductividades térmicas más bajas que el SnSe puro. En el capítulo tres, presento un protocolo sintético para la producción potencial a gran escala de nanopartículas de covellite CuS a temperatura ambiente y atmósfera. La atmósfera, la temperatura y el tiempo del tratamiento térmico permiten ajustar la densidad de las vacantes de cobre y, por lo tanto, ajustar la concentración del portador de carga y las propiedades de transporte del material. En el capítulo cuatro, presento los nanomateriales Bi2Se3 con propiedades TE mejoradas al doparse con Sn. En el capítulo cinco, presento una ruta versátil, escalable, a temperatura ambiente y libre de tensioactivos para la síntesis de nanopartículas de PbS en solución acuosa, y además caracterizo las propiedades termoeléctricas del PbS tipo n obtenido y demuestro que la incorporación de Cu puede mejorar el rendimiento del material.

Additional file 11: Table S10. Primers of ripening-related genes used to detect the expression level in overexpressed fruits.

Distributed sparse learning for high dimensional parameters has attached vast attentions due to its wide application in prediction and classification in diverse fields of machine learning. Existing distributed sparse regression usually takes an average way to ensemble the local results produced by distributed machines, which enjoys low communication cost but is statistical inefficient. To address this problem, we proposed a new Weighted AVerage Estimate (WAVE) for high-dimensional regressions. The WAVE is a solution to a weighted least-square loss with an adaptive $L_1$ penalty, in which the $L_1$ penalty controls the sparsity and the weight promotes the statistical efficiency. It can not only achieve a balance between the statistical and communication efficiency, but also reach a faster rate than the average estimate with a very low communication cost, requiring the local machines delivering two vectors to the master merely. The consistency of parameter estimation and model selection is also provided, which guarantees the safety of using WAVE in the distributed system. The consistency also provides a way to make hypothisis testing on the parameter. Moreover, WAVE is robust to the heterogeneous distributed samples with varied mean and covariance across machines, which has been verified by the asymptotic normality under such conditions. Other competitors, however, do not own this property. The effectiveness of WAVE is further illustrated by extensive numerical studies and real data analyses.

Land use change could affect the carbon sink of terrestrial ecosystems, implying that future carbon storage could be estimated by simulating land use patterns, which is of great significance for the ecological environment. Therefore, the patterns of future land use and carbon storage under the combination scenarios of different Shared Socioeconomic Pathway (SSP) and Representative Concentration Pathway (RCP) of the Yangtze River Delta were simulated by introducing weight matrices into the Markov model and combining the PLUS and InVEST models. The results revealed that the woodland expands greatly during 2020–2060 under the SSP1-RCP2.6 scenario, and the carbon storage of 2060 is at a high level with an estimated value of 5069.31 × 106 t and an average annual increase of 19.13 × 106 t, indicating that the SSP1-RCP2.6 scenario contributes to the improvement of carbon storage. However, the area of built-up land is increasing under the SSP5-RCP8.5 scenario, and the estimated value of carbon storage is 3836.55 × 106 t, with an average annual decrease of 11.69 × 106 t, indicating that the SSP5-RCP8.5 scenario negatively affects carbon sink. Besides, the SSP2-RCP4.5 scenario causes almost no effect on land use change and carbon storage. The above results can help policymakers manage land use patterns and choose the best development scenario.

Multidrug-resistant Gram-negative bacteria represent a major medical challenge worldwide. New antibiotics are desperately required with ‘old’ polymyxins often being the only available therapeutic option. Here, we systematically investigated the structure–activity relationship (SAR) of polymyxins using a quantitative lipidomics-informed outer membrane (OM) model of Acinetobacter baumannii and a series of chemically synthesized polymyxin analogs. By integrating chemical biology and all-atom molecular dynamics simulations, we deciphered how each residue of the polymyxin molecule modulated its conformational folding and specific interactions with the bacterial OM. Importantly, a novel designed polymyxin analog FADDI-287 with predicted stronger OM penetration showed improved in vitro antibacterial activity. Collectively, our study provides a novel chemical biology and computational strategy to expedite the discovery of new-generation polymyxins against life-threatening Gram-negative ‘superbugs’. published

The title compound, 6-(3-chloropropoxy)-4-(2-fluorophenylamino)-7-methoxyquinazoline, was synthesized by selective nucleophilic attack at C-1 of 1-bromo-3-chloropropane by the potassium salt of 4-(2-fluorophenylamino)-7-methoxyquinazolin-6-ol, which was prepared from 7-methoxy-4-oxo-3,4-dihydroquinazolin-6-yl acetate in three steps. The compound crystallized as an ethyl acetate complex (C20H21ClFN3O3, Mr = 405.85), and X-ray crystallography showed that the crystal belongs to the orthorhombic system, space group Pbca with a = 12.7407(4) Å, b = 14.0058(5) Å, c = 21.7726(7) Å, α = 90°, β = 90° and γ = 90°. The whole molecule is stacked into a three-dimensional structure via weak N–H…N hydrogen bonding between molecules. The compound acts as an effective inhibitor on the proliferation of a lung cancer cell line.

A novel hydrosoluble near-infrared fluorescence off–on probe has been developed for detecting carboxylesterase activity. The probe was designed by introducing (4-acetoxybenzyl)oxy as a quenching and recognizing moiety to the decomposed product of IR-783, which exhibits excellent near-infrared fluorescence features and good water solubility. The responding mechanism of novel probe 1 to carboxylesterase was investigated. It would lead to the cleavage of the carboxylic ester bond by carboxylesterase catalyze the spontaneous hydrolysis of the probe, resulting in the release of a near-infrared fluorophore. This behaviour leads to the development of a simple and sensitive fluorescent method for assaying carboxylesterase activity, with a detection limit of 3.4 × 10−3 U mL−1. Moreover, the probe displays excellent selectivity toward carboxylesterase over other substances. Notably, the imaging experimental results showed that the probe 1 is cell membrane permeable, and its applicability has been demonstrated for monitoring carboxylesterase activity in HeLa cells.

The cost-effective conversion of low-grade heat into electricity using thermoelectric devices requires developing alternative materials and material processing technologies able to reduce the currently high device manufacturing costs. In this direction, thermoelectric materials that do not rely on rare or toxic elements such as tellurium or lead need to be produced using high-throughput technologies not involving high temperatures and long processes. BiSe is an obvious possible Te-free alternative to BiTe for ambient temperature thermoelectric applications, but its performance is still low for practical applications, and additional efforts toward finding proper dopants are required. Here, we report a scalable method to produce BiSe nanosheets at low synthesis temperatures. We studied the influence of different dopants on the thermoelectric properties of this material. Among the elements tested, we demonstrated that Sn doping resulted in the best performance. Sn incorporation resulted in a significant improvement to the BiSe Seebeck coefficient and a reduction in the thermal conductivity in the direction of the hot-press axis, resulting in an overall 60% improvement in the thermoelectric figure of merit of BiSe.

The demand for clean and sustainable energy has set the stage for the development of affordable and efficient electrocatalysts for hydrogen generation. MoS2, a typical transition metal dichalcogenides (TMDs), is a promising electrocatalyst for hydrogen evolution reaction (HER) owing to its tunable atomic structure. However, several key challenges, including low electrical conductivity and the limited active sites of hydrogen bonding. remain in MoS2 based electrocatalysts, which hinders its potential applications in water splitting. In this work, in order to improve the catalytic activity of MoS2, several innovative strategies have been utilized to synergistically increase active sites, reduce resistance, and lower the energy barrier of hydrogen absorption. In detail, 4 effective approaches have been designed to fabricate optimized MoS2 nanosheets for highly efficient hydrogen production, including nanoparticle decoration, phase transformation, element substitution, and single atom intercalation. The MoS2 nanosheets show excellent catalytic performance with high current density, low onset potential, reduced Tafel slope, and good catalytical stability. The underline mechanism of enhanced hydrogen production is systematically investigated, and the remarkable HER performances can be attributed to the synergistic effects of the modified MoS2. It is found that through rational control of morphology and electronic structure, the adsorption and desorption process of H atoms on MoS2 could be balanced, and the Gibbs free energy of hydrogen binding is moderate with a value relatively close to the Pt electrodes. Besides, more active sites arise from phase transformation or unsaturated single metal atoms, which also promotes the HER process dramatically. Finally, nanoparticle decoration and element substitution increase the electrical conductivity, and specific doping element leads to optimized energy level and reduced work function, facilitating the electron transfer. The controlled design strategy may also be applied to develop other TMDs based electrocatalysts with high HER activity and opens up a new direction to engineer electrochemical properties of functional materials.

The increasingly collaborative decision-making process between humans and agents demands a comprehensive, continuous, and unobtrusive measure of trust in agents. The gold standard format for measuring trust, a Likert-style survey, suffers from major limitations in dynamic human-agent interactions. We proposed a new approach to evaluate trust in a nondirective and relational conversation. The term nondirective refers to abstract word selections in open-ended prompts, which can probe respondents to freely describe their attitudes. The term relational refers to interactive conversations where respondents can clarify their responses in followup questions. We propose a systematic process for generating nondirective trust-based prompts by using text analysis from previously validated trust scales. This nondirective and relational approach provides a complementary trust measurement, which can unobtrusively elicit rich and dynamic information on situational trust throughout a human-agent interaction.

We remember the past in order not to repeat it - but does remembrance of war in fact shape support for military or diplomatic approaches to international conflict? In 7 samples from 5 countries (collected online, total N = 2493), we examined support for military and diplomatic approaches to conflict during war commemorations (e.g., Veterans Day). During war commemorations in the U.S. support for diplomacy increased, while support for military approaches did not change. We found similar results in the U.K. and Australia on Remembrance Day, but not in Germany, or France, nor in Australia on Anzac Day. Further, support for diplomacy was predicted by concern about loss of ingroup lives during war, independently of concern about harm to outgroup civilians. These studies expand our understanding of how collective memories of war may be leveraged to promote diplomatic approaches to contemporary geopolitical conflict.

Rocks in deep coal mines are usually in varying degrees of damage state before they are destabilized by impact loads such as rock bursts. For the problem of the mechanical properties and energy evolution of damaged rocks under impact loads, the authors use static loads with different cyclic load thresholds to act on sandstone specimens to make them in distinct degrees of damage. Then, the rock mechanics system (MTS-816) and the Split Hopkinson pressure bar (SHPB) are employed to perform uniaxial compression and impact dynamics tests on sandstones with different degrees of damage. The results show that, from the perspective of mechanical properties, the uniaxial compressive strength and dynamic compressive strength of the damaged sandstone gradually decrease with the increase of the upper limit of the cycle threshold and both obey the growth law of the quadratic function, and the dynamic strength increase factor (DIF) also decreases with the increase of the cyclic load threshold. In terms of energy, with the increment of the cyclic load threshold, the number of cracks in the damaged sandstone is large and the scale is enormous. Due to the effect of cracks, when the incident energy is a fixed value, the transmission energy decreases with the increase of the damage degree and the change law of the reflection energy is the opposite. The systematic study of the dynamic mechanical properties and energy evolution law of the damaged sandstone provides some reference for the prevention and mechanism research of rock bursts.

CYP gene is a member of the cytochrome P450 superfamily, which plays an important role in plant growth, signals transduction and defense responsive. The BjuCYP1 gene of Brassica juncea was cloned, and then bioinformatics of this gene was analyzed. The results showed that the gene contained a 516 bp complete open reading frame and encoded a protein of 171 amino acids, with a molecular weight of 18.09 kD and a theoretical isoelectric point (pI) of 8.66. Homologous sequence alignment revealed that BjuCYP1 was closely related to CYP proteins of turnip and radish, which all belonged to Cruciferous. Subcellular localization predicted that the protein was located in the cytoplasm. This study provides useful information to explore the molecular function of BjuCYP1 in B. juncea.

Presentation19381

Multi-aryl substituted olefins and 1,3-dienes are important structural motifs in material molecules, and the stereochemistry of these structures exerts significant influence on the material properties. At present, the lack of effective methods to control the geometry of the double bonds has been a hurdle for the discovery of advanced material. We report herein the development of a 1,4-palladium migration/Suzuki coupling sequence for the efficient synthesis of these interesting molecules. A precise reactivity balance of the used organoboronates played a vital role in this process. The practicality of this method was demonstrated by the excellent capability and flexibility in stereochemical control, broad substrate scope, excellent functional group tolerance, as well as versatile conversion with obtained products and easy scalability. Furthermore, the power of this method is also highlighted by the aggregation-induced emission (AIE) feature studies of some obtained products, especially the easy accessibility of several geometric isomer pairs with a marked difference on photolumnescent quantum yield values.

Red-skinned pear is a promising commercial fruit due to its attractive appearance and nutritious value. Anthocyanin is the determinant of the red coloration of the pear peel. However, differences in anthocyanin accumulation exist among red pear cultivars with different genetic backgrounds. In this study, we analyzed the anthocyanin content and gene expression patterns in the fruits and different tissues of the red pear ‘Red Zaosu’ at different developmental stages and found a difference in anthocyanin accumulation between ‘Red Zaosu’ pear and its green mutant. The data showed that the expression profiles of transcripts that encoded critical anthocyanin biosynthetic genes were basically consistent with a tendency to a decreased anthocyanin content during fruit development, indicating that a synergistic effect of these genes was responsible for anthocyanin biosynthesis and regulation. Tissue-specific expression analysis of anthocyanin biosynthetic genes showed that they could be expressed in all tissues but at different levels. PbF3H, PbDFR, and PbANS were mainly expressed during the early flowering period, which explained the reduced levels of anthocyanin content in petals. Additionally, the content of anthocyanins and the expression levels of PbDFR, PbANS, and PbMYB10 significantly decreased in the green mutant of ‘Red Zaosu’, suggesting that PbDFR, PbANS, and PbMYB10 probably play a decisive role in determining the skin coloration of ‘Red Zaosu’ and its green mutant.

A comprehensive search in literature and published US Food and Drug Administration reviews was conducted to assess whether physiologically based pharmacokinetic (PBPK) modeling could be prospectively used to predict clinical food effect on oral drug absorption. Among the 48 resulted food effect predictions, ∼50% were predicted within 1.25-fold of observed, and 75% within 2-fold. Dissolution rate and precipitation time were commonly optimized parameters when PBPK modeling was not able to capture the food effect. The current work presents a knowledgebase for documenting PBPK experience to predict food effect.

International audience

International audience

The discovery of topological phases has recently led to a paradigm shift in condensed matter physics, and facilitated breakthroughs in engineered photonics and acoustic metamaterials. Topological insulators (TIs) enable the generation of electronic, photonic, and acoustic modes exhibiting wave propagation that is resilient to disorder, irrespective of manufacturing precision or unpredictable defects induced by the operational environment, known as topological protection. While originally limited to a dimensionality of the protected states that is one dimension lower than the host TI material, the recent discovery of higher-order topological insulators (HOTIs) provides the potential to overcome this dimensionality limitations by offering topological protection over an extended range of dimensionalities. Here we demonstrate 2D photonic HOTI (PHOTI) with topological states two dimensions lower than the one of the host system. We consider a photonic metacrystal of distorted Kagome lattice geometry that exhibits topological bulk polarization, leading to the emergence of 1D topological edge states and of higher order 0D states confined to the corners of the structure. Interestingly, in addition to corner states due to the nearest neighbour interactions and protected by generalized chiral symmetry 1, we discover and take advantage of a new class of topological corner states sustained by long-range interactions, available in wave-based systems, such as in photonics. Our findings demonstrate that photonic HOTIs possess richer physics compared to their condensed matter counterparts, offering opportunities for engineering novel designer electromagnetic states with unique topological robustness., 13 pages, 4 figures

International audience

In the past years classical wave-systems have constituted an excellent platform for emulating complex quantum phenomena. This approach has been especially fruitful in demonstrating topological phenomena in photonics and acoustics: from chiral edge states of Chern insulators and helical edge states of topological insulators to higher-dimensional topological states of quasiperiodic systems and systems with synthetic dimensions. Recently, a new class of topological states localized in more than one dimension of a D-dimensional system, referred to as higher-order topological (HOT) states, has been reported, offering an even more versatile platform to confine and control classical radiation and mechanical motion. However, because experimental research of HOT states has so far been limited to two-dimensional (2D) systems, third and higher-order states have evaded experimental observation. Studying higher-dimensional classical systems therefore opens an opportunity to emulate higher-order topological insulators and explore HOT states beyond second order. In this letter, we design and experimentally study a 3D acoustic metamaterial supporting third-order (0D) topological corner states, along with second-order (1D) edge states within the same topological bandgap, thus establishing a full hierarchy of HOT states in three dimensions, co-existing robustly within the same topological bandgap. The metamaterial is implemented over a versatile additive manufacturing platform, which enables rapid prototyping of metaatoms and metamolecules, which can be snapped together to form 3D metamaterials with complex geometries. The assembled 3D topological metamaterial represents the acoustic analogue of a pyrochlore lattice made of interconnected molecules, and is shown to exhibit topological bulk polarization, leading to the emergence of topological HOT states localized in all three or in two dimensions., 12 pages, 3 figures

Topological photonic systems represent a new class of optical materials supporting boundary modes with unique properties, not found in conventional photonics. While the early research on topological photonics has focused on edge and surface modes in 2D and 3D systems, respectively, recently higher-order topological insulators (HOTIs) supporting lower-dimensional boundary states have been introduced. In this work we design and experimentally realize a photonic kagome metasurface exhibiting a Wannier-type higher-order topological phase. We demonstrate and visualize the emergence of a topological transition and opening of a Dirac cone by directly exciting the bulk modes of the HOTI metasurface via solid-state immersion spectroscopy. The open nature of the metasurface is then utilized to directly image topological boundary states. We show that, while the domain walls host 1D edge states, their bending induces 0D higher-order topological modes confined to the corners. The demonstrated metasurface hosting topological boundary modes of different dimensionality paves the way to a new generation of universal and resilient optical devices which can controllably scatter, trap and guide optical fields in a robust way., Comment: 14 pages, 5 figures

The properties of topological systems are inherently tied to their dimensionality. Higher-dimensional physical systems exhibit topological properties not shared by their lower dimensional counterparts and, in general, offer richer physics. One example is a d-dimensional quantized multipole topological insulator, which supports multipoles of order up to 2^d and a hierarchy of gapped boundary modes with topological 0-D corner modes at the top. While multipole topological insulators have been successfully realized in electromagnetic and mechanical 2D systems with quadrupole polarization, and a 3D octupole topological insulator was recently demonstrated in acoustics, going beyond the three physical dimensions of space is an intriguing and challenging task. In this work, we apply dimensional reduction to map a 4D higher-order topological insulator (HOTI) onto an equivalent aperiodic 1D array sharing the same spectrum, and emulate in this system the properties of a hexadecapole topological insulator. We observe the 1D counterpart of zero-energy states localized at 4D HOTI corners - the hallmark of multipole topological phase. Interestingly, the dimensional reduction guarantees that one of the 4D corner states remains localized to the edge of the 1D array, while all other localize in the bulk and retain their zero-energy eigenvalues. This discovery opens new directions in multi-dimensional topological physics arising in lower-dimensional aperiodic systems, and it unveils highly unusual resonances protected by topological properties inherited from higher dimensions., Comment: 13 pages, 4 figures

International audience

Reusing domestic sewage for crop irrigation is a promising practice, particularly in developing countries, since it is a substitute for chemical fertilizer and reduces water contamination. More attention was paid to the effect of sewage irrigation on crop yield and soil nutrients, but little attention was paid to greenhouse gas (GHG) emission from straw-returning paddy fields. In this study, a soil column monitoring experiment was conducted to assess the effects of untreated domestic sewage (dominated with ammonia) and treated domestic sewage (dominated with nitrate) irrigation on methane (CH4), nitrous oxide (N2O) emission, and related soil microorganisms in straw-returning paddy fields. Results showed that straw-returning dramatically promoted CH4 emission but had little effect on N2O emission. Both untreated and treated domestic sewage irrigation decreased CH4 emission of straw-returning paddy whether nitrogen fertilizer applied or not. The mitigating effect of treated sewage irrigation on CH4 emission was greater than untreated sewage irrigation. CH4 emission had a significant correlation with the abundance of soil methanogens and methanogens/methanotrophs. N2O emission increased with untreated or treated domestic sewage irrigation, although the total N input, including the N carried by sewage water, was the same for all treatments. No significant correlation between N2O and denitrification functional genes was found in this study. Treated domestic sewage irrigation reduced the global warming potential (GWP) by 66.7%, but untreated domestic sewage had no evident influence on the GWP. Results indicated that treated domestic sewage irrigation could significantly inhibit CH4 emission and the GWP by decreasing the ratio of methanogens to methanotrophs, and is promising in mitigating GWP from straw-returned paddy fields.

Bioprocesses of mammalian cell culture have become essential for the production of therapeutic recombinant proteins, such as monoclonal antibodies (mAb). However, the physiological state of the cells and the quality of the mAb produced, in particular their glycosylation, may vary during the process, and may lead to the alteration of the safety and efficacy of the final product. Consequently, the Process Analytical Technology (PAT) initiative has encouraged the development of online monitoring techniques, with the aim to better control the process and ensure the quality of the final product. In this context, this thesis proposes innovative approaches for online monitoring of CHO (Chinese Hamster Ovary) cells bioreactor cultures, by using three types of in situ spectroscopic measurements (dielectric, Raman, near infrared (NIR)). The first chapter presents a novel approach to predict in real-time one of the major cell physiological state parameters, the specific growth rate (µ). Based on online permittivity measured by in situ dielectric spectroscopy, the cell concentration was estimated and µ was calculated in real-time, making possible to detect the critical moment when µ begins to decrease significantly. Compared to an offline approach, this online approach allowed to maintain the cells in a stable physiological state, ensuring the glycosylation of the mAb produced in feed-harvest cultures. The second chapter shows the use of in situ NIR and Raman spectroscopies combined with chemometric methods. For the first time, the performances of these two spectroscopies were compared in parallel in the same cultures. Online models were developed to predict in real-time the concentration of different parameters (viable cells, glucose, lactate, glutamine, ammonium ions and antibodies). The evaluation of these models by the multivariate Figures of Merit (FOM) revealed some of the advantages of Raman spectroscopy. The combination of the two spectroscopies by various data fusion strategies has also been evaluated. In the third chapter, the interest of Raman spectroscopy for the online monitoring of both the quantity and the glycosylation of the mAb was demonstrated. Models were developed for online prediction of both macroheterogeneity (glycosylation site occupancy) and microheterogeneity (glycan structures) of mAb glycosylation in batch and feed-harvest cultures. The last chapter used models previously developed for NIR and dielectric spectroscopies, to integrate into a “soft sensor” by combining with cell metabolic and mass balance equations. This “soft sensor”, implemented in a fed-batch cell culture for the automatic control of the feed rate, leads to an increased mAb productivity and better mAb glycosylation; Les bioprocédés industriels mettant en œuvre la culture de cellules animales sont devenus incontournables pour la production d’anticorps monoclonaux (AcM). Cependant, l'état physiologique des cellules et la qualité des AcM produits, en particulier leur glycosylation, sont tributaires des variations intervenant au cours du procédé. Il en découle des risques d'altération de l'efficacité et de la sûreté des AcM. C'est pourquoi, depuis quelques années, l'initiative Process Analytical Technology (PAT) encourage le développement du suivi en ligne de ces procédés, avec l'objectif de mieux les maîtriser et d'assurer la qualité finale des produits. Dans ce contexte, cette thèse propose des approches innovantes pour le suivi en ligne de procédés de culture de cellules CHO (Chinese Hamster Ovary) en bioréacteur, basées sur l'utilisation de trois types de spectroscopies in situ (diélectrique, Raman, proche infrarouge(NIR)). Le premier chapitre présente une nouvelle démarche permettant de prédire en temps réel l'état physiologique des cellules, au travers de la vitesse spécifique de croissance cellulaire (μ). A partir de la mesure en ligne de la permittivité grâce à la spectroscopie diélectrique, la µ a été calculée en temps réel, permettant de détecter le moment critique correspondant au moment où μ diminue. Comparée à une démarche hors ligne, l'utilisation de cette méthode pour le pilotage de cultures en mode recharge-récolte, permet d’assurer à la fois la quantité et la qualité de glycosylation des AcM. Le second chapitre aborde l'utilisation des spectroscopies NIR et Raman in situ combinées à des méthodes chimiométriques. Les performances de ces deux spectroscopies ont été comparées en parallèle. Des modèles en ligne ont été développés pour prédire la concentration de différents paramètres (cellules viables, glucose, lactate, glutamine, ions ammonium, anticorps). L'évaluation de ces modèles par facteurs de mérite (FOM), a révélé certains avantages de la spectroscopie Raman. La combinaison de ces deux spectroscopies par diverses stratégies de fusion de données a été également évaluée. Dans le troisième chapitre, l'intérêt de la spectroscopie Raman a été démontré pour le suivi en ligne, non seulement, de la concentration, mais aussi, de la glycosylation des AcM. Des modèles ont été développés pour la prédiction en ligne, à la fois, de la macro-hétérogénéité (sites de glycosylation), et de la micro-hétérogénéité (structures glycanniques) de la glycosylation des AcM dans le cas de cultures en mode discontinu et recharge-récolte. Le dernier chapitre a utilisé les spectroscopies NIR et diélectrique, en les intégrant à un « capteur logiciel » combinant des équations de bilans de matière. Ce « capteur logiciel », mis en œuvre au cours d'une culture en mode semi-continu pour le contrôle automatique du débit d'alimentation, a conduit à une augmentation de la productivité du procédé ainsi qu'à une meilleure glycosylation des AcM produits

Bioprocesses of mammalian cell culture have become essential for the production of therapeutic recombinant proteins, such as monoclonal antibodies (mAb). However, the physiological state of the cells and the quality of the mAb produced, in particular their glycosylation, may vary during the process, and may lead to the alteration of the safety and efficacy of the final product. Consequently, the Process Analytical Technology (PAT) initiative has encouraged the development of online monitoring techniques, with the aim to better control the process and ensure the quality of the final product. In this context, this thesis proposes innovative approaches for online monitoring of CHO (Chinese Hamster Ovary) cells bioreactor cultures, by using three types of in situ spectroscopic measurements (dielectric, Raman, near infrared (NIR)). The first chapter presents a novel approach to predict in real-time one of the major cell physiological state parameters, the specific growth rate (µ). Based on online permittivity measured by in situ dielectric spectroscopy, the cell concentration was estimated and µ was calculated in real-time, making possible to detect the critical moment when µ begins to decrease significantly. Compared to an offline approach, this online approach allowed to maintain the cells in a stable physiological state, ensuring the glycosylation of the mAb produced in feed-harvest cultures. The second chapter shows the use of in situ NIR and Raman spectroscopies combined with chemometric methods. For the first time, the performances of these two spectroscopies were compared in parallel in the same cultures. Online models were developed to predict in real-time the concentration of different parameters (viable cells, glucose, lactate, glutamine, ammonium ions and antibodies). The evaluation of these models by the multivariate Figures of Merit (FOM) revealed some of the advantages of Raman spectroscopy. The combination of the two spectroscopies by various data fusion strategies has also been evaluated. In the third chapter, the interest of Raman spectroscopy for the online monitoring of both the quantity and the glycosylation of the mAb was demonstrated. Models were developed for online prediction of both macroheterogeneity (glycosylation site occupancy) and microheterogeneity (glycan structures) of mAb glycosylation in batch and feed-harvest cultures. The last chapter used models previously developed for NIR and dielectric spectroscopies, to integrate into a “soft sensor” by combining with cell metabolic and mass balance equations. This “soft sensor”, implemented in a fed-batch cell culture for the automatic control of the feed rate, leads to an increased mAb productivity and better mAb glycosylation, Les bioprocédés industriels mettant en œuvre la culture de cellules animales sont devenus incontournables pour la production d’anticorps monoclonaux (AcM). Cependant, l'état physiologique des cellules et la qualité des AcM produits, en particulier leur glycosylation, sont tributaires des variations intervenant au cours du procédé. Il en découle des risques d'altération de l'efficacité et de la sûreté des AcM. C'est pourquoi, depuis quelques années, l'initiative Process Analytical Technology (PAT) encourage le développement du suivi en ligne de ces procédés, avec l'objectif de mieux les maîtriser et d'assurer la qualité finale des produits. Dans ce contexte, cette thèse propose des approches innovantes pour le suivi en ligne de procédés de culture de cellules CHO (Chinese Hamster Ovary) en bioréacteur, basées sur l'utilisation de trois types de spectroscopies in situ (diélectrique, Raman, proche infrarouge(NIR)). Le premier chapitre présente une nouvelle démarche permettant de prédire en temps réel l'état physiologique des cellules, au travers de la vitesse spécifique de croissance cellulaire (μ). A partir de la mesure en ligne de la permittivité grâce à la spectroscopie diélectrique, la µ a été calculée en temps réel, permettant de détecter le moment critique correspondant au moment où μ diminue. Comparée à une démarche hors ligne, l'utilisation de cette méthode pour le pilotage de cultures en mode recharge-récolte, permet d’assurer à la fois la quantité et la qualité de glycosylation des AcM. Le second chapitre aborde l'utilisation des spectroscopies NIR et Raman in situ combinées à des méthodes chimiométriques. Les performances de ces deux spectroscopies ont été comparées en parallèle. Des modèles en ligne ont été développés pour prédire la concentration de différents paramètres (cellules viables, glucose, lactate, glutamine, ions ammonium, anticorps). L'évaluation de ces modèles par facteurs de mérite (FOM), a révélé certains avantages de la spectroscopie Raman. La combinaison de ces deux spectroscopies par diverses stratégies de fusion de données a été également évaluée. Dans le troisième chapitre, l'intérêt de la spectroscopie Raman a été démontré pour le suivi en ligne, non seulement, de la concentration, mais aussi, de la glycosylation des AcM. Des modèles ont été développés pour la prédiction en ligne, à la fois, de la macro-hétérogénéité (sites de glycosylation), et de la micro-hétérogénéité (structures glycanniques) de la glycosylation des AcM dans le cas de cultures en mode discontinu et recharge-récolte. Le dernier chapitre a utilisé les spectroscopies NIR et diélectrique, en les intégrant à un « capteur logiciel » combinant des équations de bilans de matière. Ce « capteur logiciel », mis en œuvre au cours d'une culture en mode semi-continu pour le contrôle automatique du débit d'alimentation, a conduit à une augmentation de la productivité du procédé ainsi qu'à une meilleure glycosylation des AcM produits