Gaussian Differential Privacy on Riemannian Manifolds

We develop an advanced approach for extending Gaussian Differential Privacy (GDP) to general Riemannian manifolds. The concept of GDP stands out as a prominent privacy definition that strongly warrants extension to manifold settings, due to its central limit properties. By harnessing the power of the renowned Bishop-Gromov theorem in geometric analysis, we propose a Riemannian Gaussian distribution that integrates the Riemannian distance, allowing us to achieve GDP in Riemannian manifolds with bounded Ricci curvature. To the best of our knowledge, this work marks the first instance of extending the GDP framework to accommodate general Riemannian manifolds, encompassing curved spaces, and circumventing the reliance on tangent space summaries. We provide a simple algorithm to evaluate the privacy budget $\mu$ on any one-dimensional manifold and introduce a versatile Markov Chain Monte Carlo (MCMC)-based algorithm to calculate $\mu$ on any Riemannian manifold with constant curvature. Through simulations on one of the most prevalent manifolds in statistics, the unit sphere $S^d$, we demonstrate the superior utility of our Riemannian Gaussian mechanism in comparison to the previously proposed Riemannian Laplace mechanism for implementing GDP

Implantable and Biodegradable Macroporous Iron Oxide Frameworks for Efficient Regeneration and Repair of Infracted Heart

The construction, characterization and surgical application of a multilayered iron oxide-based macroporous composite framework were reported in this study. The framework consisted of a highly porous iron oxide core, a gelatin-based hydrogel intermediary layer and a matrigel outer cover, which conferred a multitude of desirable properties including excellent biocompatibility, improved mechanical strength and controlled biodegradability. The large pore sizes and high extent of pore interconnectivity of the framework stimulated robust neovascularization and resulted in substantially better cell viability and proliferation as a result of improved transport efficiency for oxygen and nutrients. In addition, rat models with myocardial infraction showed sustained heart tissue regeneration over the infract region and significant improvement of cardiac functions following the surgical implantation of the framework. These results demonstrated that the current framework might hold great potential for cardiac repair in patients with myocardial infraction

Farmland Transitions in China: An Advocacy Coalition Approach

In recent decades, global social and economic development has resulted in substantial land-use transitions. This was first observed with respect to losses of forested land, attracting worldwide concern. Forest transitions have an important impact on global ecology, whilst farmland transitions are key in terms of global food security. However, research into farmland transitions is lacking, particularly with respect to mechanistic analysis. Using data on China’s farmland areas between 1950 and 2017, we investigated the transitional characteristics, and triggers, of farmland change through linear regression analysis. Furthermore, based on the Advocacy Coalition Framework, we reveal the internal mechanism of these transitions. Our main findings are as follows: (1) between 1950 and 2017, China’s farmland area exhibited significant growth, and there were two transitions, namely in 1984 and 2004; (2) macroscopic economic and social changes determine the overall evolution of the farmland area; (3) there were two advocacy coalitions in the farmland transition policy subsystem—the farmland supplement and farmland consumption coalitions; (4) under the influence of macroscopic economic and social development, external events play a catalytic role in the transitions, and relatively stable parameters have an indirect but lasting effect in terms of transition outcomes

Effects of the Discharge Parameters on the Efficiency and Stability of Ambient Metastable-Induced Desorption Ionization

Ionization efficiency is an important factor for ion sources in mass spectrometry and ion mobility spectrometry. Using helium as the discharge gas, acetone as the sample, and high-field asymmetric ion mobility spectrometry (FAIMS) as the ion detection method, this work investigates in detail the effects of discharge parameters on the efficiency of ambient metastable-induced desorption ionization (AMDI) at atmospheric pressure. The results indicate that the discharge power and gas flow rate are both significantly correlated with the ionization efficiency. Specifically, an increase in the applied discharge power leads to a rapid increase in the ionization efficiency, which gradually reaches equilibrium due to ion saturation. Moreover, when the discharge voltage is fixed at 2.1 kV, a maximum efficiency can be achieved at the flow rate of 9.0 m/s. This study provides a foundation for the design and application of AMDI for on-line detection with mass spectrometry and ion mobility spectrometry

Productive reorientation of a bound oxime reactivator revealed in room temperature X-ray structures of native and VX-inhibited human acetylcholinesterase

Exposure to organophosphorus compounds (OPs) may be fatal if untreated, and a clear and present danger posed by nerve agent OPs has become palpable in recent years. OPs inactivate acetylcholinesterase (AChE) by covalently modifying its catalytic serine. Inhibited AChE cannot hydrolyze the neurotransmitter acetylcholine leading to its build-up at the cholinergic synapses and creating an acute cholinergic crisis. Current antidotes, including oxime reactivators that attack the OP-AChE conjugate to free the active enzyme, are inefficient. Better reactivators are sought, but their design is hampered by a conformationally rigid portrait of AChE extracted exclusively from 100K X-ray crystallography and scarcity of structural knowledge on human AChE (hAChE). Here, we present room temperature X-ray structures of native and VX-phosphonylated hAChE with an imidazole-based oxime reactivator, RS-170B. We discovered that inhibition with VX triggers substantial conformational changes in bound RS-170B from a "nonproductive" pose (the reactive aldoxime group points away from the VX-bound serine) in the reactivator-only complex to a "semi-productive" orientation in the VX-modified complex. This observation, supported by concurrent molecular simulations, suggested that the narrow active-site gorge of hAChE may be significantly more dynamic than previously thought, allowing RS-170B to reorient inside the gorge. Furthermore, we found that small molecules can bind in the choline-binding site hindering approach to the phosphorous of VX-bound serine. Our results provide structural and mechanistic perspectives on the reactivation of OP-inhibited hAChE and demonstrate that structural studies at physiologically relevant temperatures can deliver previously overlooked insights applicable for designing next-generation antidotes

In Silico Exploration for Novel Type-I Inhibitors of Tie-2/TEK: The Performance of Different Selection Strategy in Selecting Virtual Screening Candidates

Orientador: Prof. Dr. Rodrigo Vasconcelos MachadoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Humanas, Programa de Pós-Graduação em Letras. Defesa : Curitiba, 14/02/2020Inclui referências: p. 120-130Área de concentração: Estudos literáriosResumo: Os chamados paratextos editoriais teorizados por Gérard Genette surgem como uma espécie de vestíbulo para o texto e representam escolhas do autor ou do editor da obra, carregando sempre uma intenção que justifica sua existência. Nessa perspectiva, este estudo buscou apresentar como prefácios - autorais e alógrafos, presentes no conjunto de obras da escritora mineira Conceição Evaristo podem indicar caminhos editoriais seguidos pela autora, bem como a construção de sua imagem ao longo de diferentes edições, inclusive as de uma mesma obra publicadas em períodos distintos. Ao mesmo tempo, esta pesquisa buscou verificar como esses mesmos paratextos são utilizados para colocar em evidência junto ao leitor questões centrais da obra da escritora - o sujeito-mulher-negra, a violência contra corpos negros e o expediente da memória e ancestralidade. Fazem parte dessa análise os textos introdutórios de Ponciá Vicêncio, Becos da Memória, Insubmissas Lágrimas de Mulheres, Olhos d'água e Histórias de Leves Enganos e Parecenças. Os resultados apontam para uma nova utilidade para o prefácio, considerando Evaristo como uma voz social da coletividade e detentora de um fazer literário ancorado no que ela mesma definiu como escrevivência. Palavras-chave: Conceição Evaristo. Literatura Negra. História do Livro. Paratextos editoriais. Prefácios.Abstract: The paratexts theorized by Gérard Genette appear as a sort of vestibule for the text and represent the author's or publisher's choices, always carrying an intention that justifies its existence. From this perspective, this study aims to present as prefaces - own and allographs, in the works of writer Conceição Evaristo can indicate editorial paths followed by the writer, as well as the construction of her image along different editions, including the same one published in different years. At the same time, this research aims to verify how these same paratexts highlight the central issues of the writer's work - the black woman, the violence against blacks and the expedient of memory and ancestry. It is part of this analysis the prefaces of Poncia Vicêncio, Becos da Memória, Insubmissas Lágrimas de Mulheres, Olhos d'água, e Histórias de Leves Enganos e Parecenças. The results point to a different use for the preface, considering Evaristo as a social voice of the collectivity and holder of a self-anchored writing, as she defined as escrevivência. Palavras-chave: Conceição Evaristo. Black Literature. Book History. Paratexts. Prefaces

Genetic control of thermomorphogenesis in tomato inflorescences

Abstract Understanding how plants alter their development and architecture in response to ambient temperature is crucial for breeding resilient crops. Here, we identify the quantitative trait locus qMULTIPLE INFLORESCENCE BRANCH 2 (qMIB2), which modulates inflorescence branching in response to high ambient temperature in tomato (Solanum lycopersicum). The non-functional mib2 allele may have been selected in large-fruited varieties to ensure larger and more uniform fruits under varying temperatures. MIB2 gene encodes a homolog of the Arabidopsis thaliana transcription factor SPATULA; its expression is induced in meristems at high temperature. MIB2 directly binds to the promoter of its downstream gene CONSTANS-Like1 (SlCOL1) by recognizing the conserved G-box motif to activate SlCOL1 expression in reproductive meristems. Overexpressing SlCOL1 rescue the reduced inflorescence branching of mib2, suggesting how the MIB2–SlCOL1 module helps tomato inflorescences adapt to high temperature. Our findings reveal the molecular mechanism underlying inflorescence thermomorphogenesis and provide a target for breeding climate-resilient crops

Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic Regions in Late-Onset Severe Preeclampsia: A Pilot Study

<div><p>Preeclampsia (PE) is a leading cause of perinatal morbidity and mortality. However, as a common form of PE, the etiology of late-onset PE is elusive. We analyzed 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in the placentas of late-onset severe PE patients (n = 4) and normal controls (n = 4) using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep sequencing ([h]MeDIP-seq), and the results were verified by (h)MeDIP-qPCR. The most significant differentially methylated regions (DMRs) were verified by MassARRAY EppiTYPER in an enlarged sample size (n = 20). Bioinformatics analysis identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of 5hmC that were associated with 61 genes, thus showing significant differences between the PE patients and the controls (>2-fold, <i>p</i><0.05). Further, only one gene, <i>PTPRN2</i>, had both 5mC and 5hmC changes in patients. The ErbB signaling pathway was enriched in those 403 genes that had significantly different5mC level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic roles in the regulation of the disease, but work independently. We reveal the genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset PE placentas for the first time, and the identified ErbB signaling pathway and the gene <i>PTPRN2</i> may be relevant to the epigenetic pathogenesis of late-onset PE.</p></div

Rational design, synthesis, and evaluation of uncharged, “smart” bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase

Organophosphate (OP) intoxications from nerve agent and OP pesticide exposures are managed with pyridinium aldoxime-based therapies whose success rates are currently limited. The pyridinium cation hampers uptake of OPs into the central nervous system (CNS). Furthermore, it frequently binds to aromatic residues of OP-inhibited acetylcholinesterase (AChE) in orientations that are nonproductive for AChE reactivation, and the structural diversity of OPs impedes efficient reactivation. Improvements of OP antidotes need to include much better access of AChE reactivators to the CNS and optimized orientation of the antidotes' nucleophile within the AChE active-center gorge. On the basis of X-ray structures of a CNS-penetrating reactivator, monoxime RS194B, reversibly bound to native and venomous agent X (VX)-inhibited human AChE, here we created seven uncharged acetamido bis-oximes as candidate antidotes. Both oxime groups in these bis-oximes were attached to the same central, saturated heterocyclic core. Diverse protonation of the heterocyclic amines and oxime groups of the bis-oximes resulted in equilibration among up to 16 distinct ionization forms, including uncharged forms capable of diffusing into the CNS and multiple zwitterionic forms optimal for reactivation reactions. Conformationally diverse zwitterions that could act as structural antidote variants significantly improved in vitro reactivation of diverse OP-human AChE conjugates. Oxime group reorientation of one of the bis-oximes, forcing it to point into the active center for reactivation, was confirmed by X-ray structural analysis. Our findings provide detailed structure-activity properties of several CNS-directed, uncharged aliphatic bis-oximes holding promise for use as protonation-dependent, conformationally adaptive, "smart" accelerated antidotes against OP toxicity

Comparative Transcriptomic Analysis Reveals the Negative Response Mechanism of Peanut Root Morphology and Nitrate Assimilation to Nitrogen Deficiency

Root architecture plays a fundamental role in crop yield, which is sensitive to nitrogen fertilizer. Although it is well studied that nitrogen fertilizer significantly promotes peanut (Arachis hypogaea L.) growth and yield, less information was available on how its root development responds to nitrogen deficiency. In this study, the growth and development of roots were inhibited, as indicated by the significantly decreased root dry weight and length and the lateral root number, especially under 10 days of nitrogen deficiency treatment. The activities and the expression of the genes related to nitrogen assimilation enzymes including nitrate reductase, glutamine synthetase, glutamate dehydrogenase, and glutamine oxoglutarate aminotransferase and the genes encoding the nitrate transporters were significantly decreased under 10 days of nitrogen deficiency treatment, which may lead to a decrease in nitrate content, as indicated by the significantly decreased nitrogen balance index. Transcriptome sequencing revealed a total of 293 (119 up- and 174 downregulated) and 2271 (1165 up- and 1106 downregulated) differentially expressed genes (DEGs) identified after five and ten days of nitrogen deficiency treatments, respectively. Bioinformatic analysis showed that these DEGs were mainly involved in nitrate transportation and assimilation, phytohormone signal transduction, and the lignin biosynthesis pathway. Furthermore, a putative schematic diagram of nitrogen deficiency inhibiting root growth was established, which gives us a better understanding of nitrogen metabolism in peanut roots and a theoretical basis for improving nitrogen use efficiency