Subsequent Transformation Research Articles

Positive and negative effects of the COVID-19 pandemic on families of young children in rural Colombia and implications for child outcome research.

The COVID-19 pandemic has impacted the lives of children and families worldwide. The objective of this study is to examine exposures and impact of the COVID-19 pandemic on preschool-aged children and caregivers in the Atlántico region of Colombia. The COVID-19 Exposure and Family Impact Scales (CEFIS) questionnaire was administered in Fall 2021 to 63 caregivers of children in Sabanalarga, Colombia enrolled in a neurodevelopment study as healthy controls. The CEFIS assesses pandemic-related exposures/events and impact; higher scores indicate greater exposure and negative impact. Descriptive and correlation analyses among exposure and impact scores were conducted. Caregivers reported a mean (standard deviation[SD]) of 11.1 (3.2) among 25 COVID-19-related exposures/events; most common types included stay-at-home orders, school closures, disruptions to living conditions and income loss. Total number of events was correlated with higher caregiver (P < .001) and child distress (P = .002). However, the mean (SD) impact score of 2.0 (0.6) suggests a trend toward more positive impact than negative. Caregivers reported improvements to sleep, exercise and family interactions. Some caregivers (n = 21) qualitatively reported negative effects including unemployment, fear/anxiety and inability to visit family, and positive effects such as unification, family closeness and spending more time with children. This study highlights the importance of comprehensively exploring positive and negative impacts of COVID-19 and families' subsequent resilience and transformation. Using tools like the CEFIS, those seeking to mitigate negative impacts can contextualize data to better understand study outcomes and tailor services, resources and policy to families' unique needs. CEFIS data likely depend on timing, economic/public health resources and cultural values; future work should prioritize understanding the generalizability of CEFIS findings across samples.

PD04-04 MOLECULAR CORRELATES WITH PSMA EXPRESSION IN PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023PD04-04 MOLECULAR CORRELATES WITH PSMA EXPRESSION IN PROSTATE CANCER Adam Weiner, Eric Li, JJ Zhang, Elai Davicioni, Edward Schaeffer, Ashley Ross, Luca Valle, Paul Boutros, Jeremie Calais, Amar Kishan, and Robert Reiter Adam WeinerAdam Weiner More articles by this author , Eric LiEric Li More articles by this author , JJ ZhangJJ Zhang More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Ashley RossAshley Ross More articles by this author , Luca ValleLuca Valle More articles by this author , Paul BoutrosPaul Boutros More articles by this author , Jeremie CalaisJeremie Calais More articles by this author , Amar KishanAmar Kishan More articles by this author , and Robert ReiterRobert Reiter More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003228.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Not all prostate cancer (PCa) is detected by prostate-specific membrane antigen (PSMA)-based imaging or responsive to PSMA-based radiopharmaceuticals. We sought to define the molecular processes associated with PSMA expression. METHODS: Using multiple datasets (n=5 Homo sapiens; n=2 mouse xenograft models; n=1 cell line), we correlated PSMA gene expression (FOLH1) with biological processes and treatments. RESULTS: In an exploratory analysis of a prospective cohort of 7,000 tumors from radical prostatectomy, tumors with high PSMA RNA expression (one standard deviation above mean) tended to demonstrate more androgen receptor activity, high genomic risk scores (Decipher), more markers of homologous recombination deficiency, less immune content, lower predicted response to radiotherapy (“PORTOS”), and enrichment for P13K/AKT/mTOR pathways (Figure 1). In a validation cohort, adenocarcinoma tumors (n=49) expressed more PSMA than benign tissue (n=12; Wilcoxon p=0.020) and castration resistant tumors (n=27; p=0.015). An additional cohort showed adenocarcinoma (n=110) expressed more PSMA than neuroendocrine tumors (n=20; p=4.4e-6). In a mouse xenograft model (n=1) of high-grade adenocarcinoma, PSMA expression declined as the model underwent conversion to castration resistance and subsequent neuroendocrine transformation following castration. From both mouse and human data, treatment with androgen deprivation was associated with an initial increase in PSMA expression. From TCGA (n=491), tumors with high PSMA expression also tended to have a higher mutational burden and fewer tumor infiltrating lymphocytes in a subset with immunohistochemistry data (n=330). To assess the association between PSMA and P13K/AKT/mTOR, we used data from a cell line exposed to the MAPK inhibitor trametinib which upregulates P13K/AKT/mTOR pathways. VCaP cells treated with both enzalutamide and trametinib expressed two-fold more PSMA compared to those treated with the individual medications or neither. CONCLUSIONS: PCa with high PSMA expression is characterized by relevant differences in biological processes. If corroborated with PSMA-PET avidity, these results could optimize precision PCa care by informing adjunctive molecular testing or treatment paradigms for low or high PSMA expressing tumors. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e143 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adam Weiner More articles by this author Eric Li More articles by this author JJ Zhang More articles by this author Elai Davicioni More articles by this author Edward Schaeffer More articles by this author Ashley Ross More articles by this author Luca Valle More articles by this author Paul Boutros More articles by this author Jeremie Calais More articles by this author Amar Kishan More articles by this author Robert Reiter More articles by this author Expand All Advertisement PDF downloadLoading ...

Mechanical Properties of Solderable Polymer Composites with Low- and High-Melting-Point Solder Mixed Filler

A solderable polymer composite (SPC) with a low-melting-point solder (LMPS)/high-melting-point solder (HMPS) mixed filler was formulated to solve the bonding property and reliability problems in an SPC system with an LMPS filler. In addition, the possibility of enhancing the mechanical bonding properties of SPC with LMPS/HMPS mixed fillers was investigated. Three types of SPCs (mixing ratios for LMPS and HMPS: 100:0, 50:50, and 0:100) were prepared, and two types of mechanical property investigations (i.e., ball shear and microhardness tests) were performed to measure the mechanical bonding properties of SPCs according to the LMPS/HMPS mixing ratios. The SPC with an LMPS/HMPS mixed filler exhibited enhanced mechanical bonding properties compared with the Sn-58Bi solder paste and SPC with LMPS or HMPS only due to the change in composition and subsequent microstructure transformation of the solder joint after adding HMPS.

Organization of the training process for athletes with high qualifications in sports sambo

In the system of training athletes of any sports qualification, physical training occupies an important place. Which during the sports calendar is qualified by a large volume, high intensity and mental tension of training and competition loads. These factors often put the athlete in extreme conditions, requiring the mobilization of all his spiritual and physical forces. Therefore, at this time there is a need to improve the system of sports training and a clear distribution of the load among transitional, preparatory and competitive periods of training. Purpose: formation of physical load in the sports improvement group during the first training camp for the World Championship.&#x0D; Determine the peculiarities of building the training process during the preparatory period. Methodology. Research methods: theoretical analysis of scientific and methodical literature, analysis of own professional coaching experience. Pedagogical observation of the process of training and preparation in sambo wrestling took place at the educational and training meeting. The training program was discussed with the athletes, as well as the analysis and generalization of their own experience and the experience of other coaches, which made it possible to formulate the main recommendations for the formation of the athlete's functional readiness for competition. Scientific novelty. Aimed at the development and improvement of the training process in sports sambo, which can be used to plan sports training in sambo for the highest qualifying competitions, which determines the possibility of achieving maximum results; will make it possible to form a training load, both at the stage of initial training and later in sports activities; formation of sports readiness by means of general and special physical training according to the level of technical and tactical skills and psychological state. Conclusions. The practice of training high-class athletes in many sports shows the expediency of planning in-depth specialization 2-3 years before the beginning of the stage of maximum realization of their capabilities. This creates objective prerequisites for the most effective sports training with subsequent transformation of opportunities into high results. Therefore, the question of determining the optimal age limits that correspond to the period of high sports achievements in sambo is very relevant.

The Ruskin Speech and Great Debate in English education, 1976–1979: A study of motivation

AbstractJames Callaghan's speech at Ruskin College, Oxford in October 1976 is widely considered a pivotal moment in modern English educational policy. Whilst it is not our intention to challenge this fundamental point, the paper will critically interrogate some long‐held assumptions about the motivation that led Callaghan to deliver his speech at Ruskin College. Specifically, the paper will argue that the Ruskin Speech, which spawned a subsequent great debate on education, was motivated by a desire to protect and support comprehensive education, rather than generate more fundamental and radical educational reform away from those principles. Where successive governments have referred back to the ideals espoused by the speech as justification for subsequent educational transformation away from comprehensive ideals, this has only served to imbue the Ruskin Speech and Great Debate with motivations that were not shared at the time by Callaghan and his Labour government.

Selective Control and Characteristics of Water Oxidation and Dioxygen Reduction in Environmental Photo(electro)catalytic Systems.

ConspectusEmploying semiconductor materials is a popular engineering method to harvest solar energy, which is widely investigated for photocatalysis (PC) and photoelectrocatalysis (PEC) that convert solar light to chemical energy. In particular, environmental photo(electro)catalysis has been extensively studied as a sustainable method for water treatment, air purification, and resource recovery. Environmental PC/PEC processes working in ambient conditions are initiated mainly through hole transfer to water (water oxidation) and electron transfer to dioxygen (O2 reduction) and the subsequent photoredox transformation of water and dioxygen serves as a base of various PC/PEC systems. Through the redox transformations, different products can be generated depending on the number of transferred electrons and holes. The single electron/hole transfer generates radical species and reactive oxygen species (ROS) which initiate the degradation/transformation of various pollutants in water and air, while the multicharge transfer can generate energy-rich chemicals (e.g., H2, H2O2). Therefore, understanding the characteristics of the photoredox reactions of water and dioxygen on the semiconductor surface is critically important in controlling the selectivity and efficiency of photoconversion processes.In this Account, we describe various environmental PC/PEC conversions with a particular focus on how the phototransformation of dioxygen and water is related to the overall processes occurring on diverse semiconductor materials. The activation of water or dioxygen can be controlled by modifying the properties of semiconductors, changing the kind of counterpart half-reaction and the experimental conditions. If water can be used as a ubiquitous reductant under solar irradiation, many kinds of reductive transformations can be carried out under ambient environmental conditions. For example, various toxic oxyanions (or metal ions) can be reductively transformed to harmless or less harmful species or useful chemicals/fuels can be synthesized under ambient conditions if water can provide electrons and protons via solar water oxidation. On the other hand, dioxygen can turn into reactive oxygen species (ROS) as a versatile oxidant or to a chemical like H2O2. There should be many more possibilities of utilizing the photoconversion of water and dioxygen for environmentally significant purposes, which are yet to be further developed and demonstrated. In this Account, we highlight the recent strategies and the novel functional materials for effective activation of water and dioxygen in environmental PC/PEC systems. Design of environmentally functional PC/PEC systems should be based on better understanding of water and dioxygen activation.

Cosmography, Knowledge in Transit: A Conspectus

From a modern perspective, it could be argued that cosmography was a protoscience, or ancestral to geography. To systemize it according to its modern legacy, however, dilutes its early modern diversity. Cosmography has a place in both the history of science and in historical geography, without being confined to either discipline. The article explores how cosmography circulated across disciplines, national borders, and social classes. It materialized not only in books, but in a variety of forms, including maps, instruments, letters, and lectures. Knowledge evolved as new discoveries were made about the earth and the heavens, but ideas gain traction only with difficulty when they breach conceptual boundaries. The first parts of the article will address sites, modes, and materials of knowledge exchange. In the final part, I will focus on caution, resistance, and censorship in the transmission and subsequent transformation of knowledge, with particular reference to the Copernican revolution.

The relationship between economic and political factors and the development of the manufacturing industry

With the development of global economy, people can often see many foreign products, which can not be separated from the development of national politics, economy, and there is an excellent general environment. The development of the manufacturing industry is crucial to the economic and political development of a country, through the analysis of the economic, political and Covid-19 perspectives on the development of the manufacturing industry. Many manufacturing industries are facing the possibility of bankruptcy under the influence of Covid-19. Firstly, this paper investigates that economic development and political measures have different degrees of impact on the manufacturing industry through extensive data analysis. Secondly, By analyse the impact of the global spread of coronavirus on the manufacturing industry, such as the decline in the quality of raw materials leading to a lack of market demand and the increased risk of plant closures. Businesses, oversupply. In the face of the Covid-19, regionalization and digitalization trends, a three-step countermeasure is proposed to help the manufacturing industry recover from a macro perspective and to better assist the subsequent transformation and upgrading of the manufacturing industry.

Hollow Carbon Nanopillar Arrays Encapsulated with Pd-Cu Alloy Nanoparticles for the Oxygen Evolution Reaction.

Delicate design and bottom-up synthesis of hollow nanostructures for oxygen evolution electrocatalysts is a promising way to accelerate the reaction kinetics of overall water splitting. Herein, an efficient and versatile strategy for the controllable preparation of Pd-Cu alloy nanoparticles encapsulated in carbon nanopillar arrays (PD-Cu@HPCN) is developed. Core-shell structured MOF@imidazolium-based ionic polymers (ImIPs) have been prepared and adopted as a template, along with the decomposition of the inner Cu-MOFs when an anion exchange occurs between sodium tetrachloropalladate in solution and bromides in the external ImIP shell. Pd nanoparticles will be highly dispersed in the resulting Pd-Cu@HO-ImIP array, and subsequent topotactic transformation generates Pd-Cu@HNPC. No hazardous reagents or tedious steps are used to remove the inner Cu-MOF templates in contrast to the traditional top-down methods. Remarkably, the Pd-Cu@HPCN catalyst possesses outstanding oxygen evolution reaction (OER) activity, including small overpotential with 10 mA cm-2 at an overpotential of 188 mV, a large double layer capacitance (73.8 mF cm-2), and high stability (20 h). This simple, green, and efficient synthesis methodology represents a new way to design metal alloys for OER electrocatalysts or other electrocatalytic devices.

Effects of sunlight on the fate of graphene oxide and reduced graphene oxide nanomaterials in the natural surface water

Graphene nanomaterials have been commercialized for use in the electronic and biomedical industries, increasing their dissemination into surface waters and subsequent transformation in natural aquatic environment. While the photodegradation of graphene oxide nanomaterials has been investigated in the past, previous research did not consider actual natural aquatic environment and also focused on primarily graphene oxide nanomaterials. In this study, photodegradation of graphene nanomaterials with varying oxidation levels, including graphene oxide (GO) and partially reduced graphene oxide (rGO-2 h) are evaluated in Columbia River Water and compared with each other. Our results indicate that both direct and indirect photolysis of graphene-based nanomaterials will occur simultaneously in natural surface water. However, environmentally relevant concentrations of photosensitizers in surface water are not capable of producing sufficient ·OH to initiate degradation of GO via indirect photolysis. For all conditions tested, GO showed more rapid photodegradation compared to rGO. Overall, direct and indirect photodegradation of graphene oxide nanomaterials in natural surface water is minimal and slow indicating that phototransformation of graphene-based nanomaterials will be insignificant in natural surface water.

BUILDING PREDICTIVE ELECTRICITY CONSUMPTION MODELS FOR TRADITIONAL AND SMART GRID POWER SUPPLY SCHEMES FOR IRON ORE MINES

The paper studies the peculiarities of building predictive models of electricity consumption according to the traditional and considered schemes built on the concept of Smart Grid, as well as the rapidity of changes in the mode of electricity consumption, chaotic – avalanche-like and forms a corresponding series of problematic issues. Need to be solved today: first of all – systematization of electricity consumption volumes at the iron ore mine. This problem is relevant not only in terms of reducing the irregularity in the amount of electricity consumed by the iron ore mine, but also will increase the efficiency of energy consumption, which in turn will increase the volume of products (iron ore raw materials). Predictability of electricity consumption models is carried out by isolating these relationships between these variables by statistical – mathematical method of multiple correlation, as the predicted model of electricity consumption is influenced by a large number of factors. The basis for the construction of predictive consumption models for traditional power supply schemes and their subsequent transformation are “smart technologies” of power industry development. The introduction of “smart technologies” including Smart Grid will allow to stabilize and predict the schedules for the volume of consumed electricity of iron ore mine, in contrast to the traditional schemes of its power supply. The purpose of this work is to investigate the issues of construction of mathematical predictive models of electricity consumption developed for traditional and built according to the concept of Smart Grid power supply schemes and contributing to increase the volume of production (iron ore raw materials) and reduce the cost of their production to compete in quality and price. with foreign producers of raw materials of Ukrainian iron ore mines

Series of first-order phase shifts correct lattice reduction of fractional K-space indices

Lattice reduction of K-space acquisition at fractional indices refers to reducing the indices to the smallest nearby integer, thereby generating a Cartesian grid, allowing subsequent inverse Fourier Transformation. For band-limited signals, we show that the error in lattice reduction is equivalent to first order phase shifts, which in the infinite limit approaches W∞=φ(cotφ-i), where φ is a first-order phase shift vector. In general, the inverse corrections can be specified from the binary representation of the fractional part of the K-space indices. For non-uniform sparsity, we show how to incorporate the inverse corrections into compressed sensing reconstructions.

Simultaneous CO2 adsorption and conversion over Ni-Pd supported CeO2 nanoparticles during catalytic n-C7 asphaltene gasification

Shallow heavy oil reservoirs are suitable for the geo-sequestration of CO2 based on its adsorption and conversion during thermal-enhanced oil recovery processes. This study aims to evaluate multifunctional nanomaterials for CO2 adsorption and its subsequent transformation into valuable sub-products during the catalytic decomposition of asphaltenes in a steam gasification atmosphere. Three ceria nanoparticles with cubic (C-CeO2), orthorhombic (O-CeO2), and spherical (S-CeO2) shapes were tested in four stages including i) CO2 adsorption at 30, 50, 100, and 200 °C between 0.084 and 3.0 MPa, ii) dynamic in-situ CO2 adsorption in the presence of steam between 170 and 230 °C at 3.0 MPa, iii) dynamic in-situ CO2 adsorption in the presence of steam with adsorbed asphaltenes between 170 and 230 °C at 3.0 MPa and iv) CO2 conversion at the same conditions. The best nanoparticle morphology was doped with 1 wt% of Ni and Pd (C-CeNiPd) and was tested in the same experiments. Among the most important results, CO2 adsorption increased in the order S-CeO2 < O-CeO2 < C-CeO2 < C-CeNiPd, regardless of the temperature. When steam was injected, CO2 adsorption is reduced in all the systems. At 200 °C adsorption decreased by 3.0 %, 2.7 %, 2.5 %, and 2.0 % in processes assisted by S-CeO2, O-CeO2, C-CeO2, and C-CeNiPd, respectively. Nanoparticles with adsorbed asphaltenes presented a high tendency for CO2 adsorption as well. The nanoparticle with the best morphology (C-CeO2) adsorbed about 24.3 % (3.92 mmol) of CO2 at 200 °C, and the yield increased after doping with Ni and Pd, obtaining CO2 adsorption of 34 %. Finally, for CO2 conversion, a mixture of gases composed of CO, CH4, H2, and light hydrocarbons (LHC) is obtained. The hydrogen production content follows a trend that agrees well with each material's adsorptive capacity and catalytic activity. The maximum %vol of H2 produced at 200 °C during asphaltene gasification was 31 %, 29 %, 24 %, and 23 % for C-CeNiPd, C-CeO2, O-CeO2, and S-CeO2, respectively.

Tunable Ordered Nanostructured Phases by Co-assembly of Amphiphilic Polyoxometalates and Pluronic Block Copolymers.

The assembly of polyoxometalate (POM) metal-oxygen clusters into ordered nanostructures is attracting a growing interest for catalytic and sensing applications. However, assembly of ordered nanostructured POMs from solution can be impaired by aggregation, and the structural diversity is poorly understood. Here, we present a time-resolved small-angle X-ray scattering (SAXS) study of the co-assembly in aqueous solutions of amphiphilic organo-functionalized Wells-Dawson-type POMs with a Pluronic block copolymer over a wide concentration range in levitating droplets. SAXS analysis revealed the formation and subsequent transformation with increasing concentration of large vesicles, a lamellar phase, a mixture of two cubic phases that evolved into one dominating cubic phase, and eventually a hexagonal phase formed at concentrations above 110 mM. The structural versatility of co-assembled amphiphilic POMs and Pluronic block copolymers was supported by dissipative particle dynamics simulations and cryo-TEM.

Generalized Method of Mathematical Prototyping of Energy Processes for Digital Twins Development

The use of digital twins in smart power systems at the stages of the life cycle is promising. The dynamics of such systems (smart energy renewable sources, smart energy hydrogen systems, etc.), are determined mainly by the physical and chemical processes occurring inside the systems. The basis for developing digital twins is reliable mathematical models of the systems. In the present paper, the authors present a method of energy processes mathematical prototyping—an overall approach to modeling processes of various physical and chemical natures based on modern non-equilibrium thermodynamics, mechanics, and electrodynamics. Controlled parameters are connected with measured ones by developing a theoretically correct system of process dynamics equations with accuracy up to the experimentally studied properties of substances and processes. Subsequent transformation into particular mathematical models of a specific class of systems makes this approach widely applicable. The properties of substances and processes are given in the form of functional dependencies on the state of the system up to experimentally determined constant coefficients. The authors consider algorithms for identifying the constant coefficients of the functions of substances and processes properties, which complement the proposed unified approach of designing models of various physical and chemical nature systems.

Mechanistic Features of Asymmetric Vinylidene ortho-Quinone Methide Construction and Subsequent Transformations

Vinylidene ortho-quinone methide (VQM), an elusive dearomatized intermediate, is widely used in asymmetric catalysis. Due to its transient nature, the current understanding of VQM was largely acquired based on computational studies and trapping experiments. Herein, the enantioselective construction of stable VQM intermediates by an organocatalyzed bromination was achieved. Kinetic studies, control experiments, and nonlinear effects were realized to obtain insights into the two sequential mechanistic events in VQM-involved reactions. The results elucidated that the stereocontrol was enforced by one catalyst molecule in the generation of the axially chiral VQM, but the subsequent transformation was independent of the catalyst. The efficiency of the VQM as axially chiral synthetic reagents was demonstrated by its reactions with carboxylic acids, cyclo-1,3-diones, and nitrone. In all cases, the VQM reacted smoothly to provide the axially chiral esters and ethers via an axial-to-axial chirality transfer, as well as the chiral α-bromo ketones through an axial-to-central chirality conversion. The properties of the isolated VQM exhibited its high potential in organic chemistry.

Kinetics of Carbon Enrichment in Austenite during Partitioning Stage Studied via In-Situ Synchrotron XRD

The present study reveals the microstructural evolution and corresponding mechanisms occurring during different stages of quenching and partitioning (Q&P) conducted on 0.6C-1.5Si steel using in-situ High Energy X-Ray Diffraction (HEXRD) and high-resolution dilatometry methods. The results support that the symmetry of ferrite is not cubic when first formed since it is fully supersaturated with carbon at the early stages of partitioning. Moreover, by increasing partitioning temperature, the dominant carbon source for austenite enrichment changes from ongoing bainitic ferrite transformation during the partitioning stage to initial martensite formed in the quenching stage. At low partitioning temperatures, a bimodal distribution of low- and high-carbon austenite, 0.6 and 1.9 wt.% carbon, is detected. At higher temperatures, a better distribution of carbon occurs, approaching full homogenization. An initial martensite content of around 11.5 wt.% after partitioning at 280 °C via bainitic ferrite transformation results in higher carbon enrichment of austenite and increased retained austenite amount by approximately 4% in comparison with partitioning at 500 °C. In comparison with austempering heat treatment with no prior martensite, the presence of initial martensite in the Q&P microstructure accelerates the subsequent low-temperature bainitic transformation.

DNA methylation changes from primary cultures through senescence-bypass in Syrian hamster fetal cells initially exposed to benzo[a]pyrene

Current chemical testing strategies are limited in their ability to detect non-genotoxic carcinogens (NGTxC). Epigenetic anomalies develop during carcinogenesis regardless of whether the molecular initiating event is associated with genotoxic (GTxC) or NGTxC events; therefore, epigenetic markers may be harnessed to develop new approach methodologies that improve the detection of both types of carcinogens. This study used Syrian hamster fetal cells to establish the chronology of carcinogen-induced DNA methylation changes from primary cells until senescence-bypass as an essential carcinogenic step. Cells exposed to solvent control for 7 days were compared to naïve primary cultures, to cells exposed for 7 days to benzo[a]pyrene, and to cells at the subsequent transformation stages: normal colonies, morphologically transformed colonies, senescence, senescence-bypass, and sustained proliferation in vitro. DNA methylation changes identified by reduced representation bisulphite sequencing were minimal at day-7. Profound DNA methylation changes arose during cellular senescence and some of these early differentially methylated regions (DMRs) were preserved through the final sustained proliferation stage. A set of these DMRs (e.g., Pou4f1, Aifm3, B3galnt2, Bhlhe22, Gja8, Klf17, and L1l) were validated by pyrosequencing and their reproducibility was confirmed across multiple clones obtained from a different laboratory. These DNA methylation changes could serve as biomarkers to enhance objectivity and mechanistic understanding of cell transformation and could be used to predict senescence-bypass and chemical carcinogenicity.

Nickel(0)‐Catalyzed Hydrocyanation of Terminal Allenes: A Regio‐ and Enantioselective Approach to Branched Allylic Nitriles

AbstractA highly branched regioselective nickel(0)‐catalyzed hydrocyanation of mono‐ and 1,1‐disubstituted allenes as well as an asymmetric hydrocyanation of 1,1‐disubstituted allenes are reported herein, giving access to branched tertiary and quaternary β,γ‐allylic nitriles. For the regioselective hydrocyanation of terminal allenes, a nickel(0)/Biphephos catalytic system applicable to a substrate scope containing functional groups such as ester, THP‐group, primary aliphatic iodide, and a free carboxylic acid, provides yields up to 96%. By applying a catalytic system of Ni(0)/TADDOL‐based bisphosphite catalyst to 1,1‐disubstituted allenes, branched quaternary allylic nitriles are obtained in yields up to 99% and enantioselectivities up to 86%. Both protocols take advantage of a manageable HCN source and evidence good atom economy. In addition, the reaction's synthesis utility is highlighted by gram‐scale reactions with subsequent assorted transformation of the nitrile group as well as alkylation of the tertiary nitriles in α‐position.magnified image

Shape-Dependent CO2 Hydrogenation to Methanol over Cu2O Nanocubes Supported on ZnO.

The hydrogenation of CO2 to methanol over Cu/ZnO-based catalysts is highly sensitive to the surface composition and catalyst structure. Thus, its optimization requires a deep understanding of the influence of the pre-catalyst structure on its evolution under realistic reaction conditions, including the formation and stabilization of the most active sites. Here, the role of the pre-catalyst shape (cubic vs spherical) in the activity and selectivity of ZnO-supported Cu nanoparticles was investigated during methanol synthesis. A combination of ex situ, in situ, and operando microscopy, spectroscopy, and diffraction methods revealed drastic changes in the morphology and composition of the shaped pre-catalysts under reaction conditions. In particular, the rounding of the cubes and partial loss of the (100) facets were observed, although such motifs remained in smaller domains. Nonetheless, the initial pre-catalyst structure was found to strongly affect its subsequent transformation in the course of the CO2 hydrogenation reaction and activity/selectivity trends. In particular, the cubic Cu particles displayed an increased activity for methanol production, although at the cost of a slightly reduced selectivity when compared to similarly sized spherical particles. These findings were rationalized with the help of density functional theory calculations.