bluuebunny/crossref_metadata_2025 huggingface dataset:
Intercomparison of modal and sectional aerosol microphysics representations within the same 3-D global chemical transport model
Authors: Mann G. W. , Carslaw K. S. , Ridley D. A. , Spracklen D. V. , Pringle K. J. , Merikanto J. , Korhonen H. , Schwarz J. P. , Lee L. A. , Manktelow P. T. , Woodhouse M. T. , Schmidt A. , Breider T. J. , Emmerson K. M. , Reddington C. L. , Chipperfield M. P. , Pickering S. J.
Published: May 2012

Abstract. In the most advanced aerosol-climate models it is common to represent the aerosol particle size distribution in terms of several log-normal modes. This approach, motivated by computational efficiency, makes assumptions about the shape of the particle distribution that may not always capture the properties of global aerosol. Here, a global modal aerosol microphysics module (GLOMAP-mode) is evaluated and improved by comparing against a sectional version (GLOMAP-bin) and observations in the same 3-D global offline chemistry transport model. With both schemes, the model captures the main features of the global particle size distribution, with sub-micron aerosol approximately unimodal in continental regions and bi-modal in marine regions. Initial bin-mode comparisons showed that the current values for two size distribution parameter settings in the modal scheme (mode widths and inter-modal separation sizes) resulted in clear biases compared to the sectional scheme. By adjusting these parameters in the modal scheme, much better agreement is achieved against the bin scheme and observations. Annual mean surface-level mass of sulphate, sea-salt, black carbon (BC) and organic carbon (OC) are within 25% in the two schemes in nearly all regions. Surface level concentrations of condensation nuclei (CN), cloud condensation nuclei (CCN), surface area density and condensation sink also compare within 25% in most regions. However, marine CCN concentrations between 30° N and 30° S are systematically 25–60% higher in the modal model, which we attribute to differences in size-resolved particle growth or cloud-processing. Larger differences also exist in regions or seasons dominated by biomass burning and in free-troposphere and high-latitude regions. Indeed, in the free-troposphere, GLOMAP-mode BC is a factor 2–4 higher than GLOMAP-bin, likely due to differences in size-resolved scavenging. Nevertheless, in most parts of the atmosphere, we conclude that bin-mode differences are much less than model-observation differences, although some processes are missing in these runs which may pose a bigger challenge to modal schemes (e.g., boundary layer nucleation and ultra-fine sea-spray). The findings here underline the need for a spectrum of complexity in global models, with size-resolved aerosol properties predicted by modal schemes needing to be continually benchmarked and improved against freely evolving sectional schemes and observations.
Assessment of a multi-species in-situ FTIR for precise atmospheric greenhouse gas observations
Authors: Hammer S. , Griffith D. W. T. , Konrad G. , Vardag S. , Caldow C. , Levin I.
Published: May 2012

Abstract. We thoroughly evaluate the performance of a multi-species, in-situ FTIR analyser with respect to high accuracy needs for greenhouse gas monitoring networks. The in-situ FTIR analyser measures CO2, CO, CH4 and N2O mole fractions continuously, all with better reproducibility than requested by the WMO-GAW inter-laboratory compatibility (ILC) goal. Simultaneously determined δ13CO2 reaches reproducibility as good as 0.03‰. This paper focuses on the quantification of residual dependencies between the measured components and the thermodynamic properties of the sample as well as the cross-sensitivities among the sample constituents. The instrument has proven to be linear for all components in the ambient range. The temporal stability of the instrument was investigated by 10 months of continuously collected quality control measures. Based on these measures we conclude that for moderately stable laboratory conditions weekly calibrations of the instrument are sufficient to reach WMO-GAW ILC goals.
Implementation and evaluation of online gas-phase chemistry within a regional climate model (RegCM-CHEM4)
Authors: Shalaby A. , Zakey A. S. , Tawfik A. B. , Solmon F. , Giorgi F. , Stordal F. , Sillman S. , Zaveri R. A. , Steiner A. L.
Published: May 2012

Abstract. The RegCM-CHEM4 is a new online climate-chemistry model based on the International Centre for Theoretical Physics (ICTP) regional climate model (RegCM4). Tropospheric gas-phase chemistry is integrated into the climate model using the condensed version of the Carbon Bond Mechanism (CBM-Z; Zaveri and Peters, 1999) with a fast solver based on radical balances. We evaluate the model over continental Europe for two different time scales: (1) an event-based analysis of the ozone episode associated with the heat wave of August 2003 and (2) a climatological analysis of a six-year simulation (2000–2005). For the episode analysis, model simulations show good agreement with European Monitoring and Evaluation Programme (EMEP) observations of hourly ozone over different regions in Europe and capture ozone concentrations during and after the summer 2003 heat wave event. For long-term climate simulations, the model captures the seasonal cycle of ozone concentrations with some over prediction of ozone concentrations in non-heat wave summers. Overall, the ozone and ozone precursor evaluation shows the feasibility of using RegCM-CHEM4 for decadal-length simulations of chemistry-climate interactions.
The Journal of General Education and an Institutional Return to Rhetoric
Authors: Beasley James
Published: May 2012

Henry W. Sams served on the editorial boards of College English, College Composition and Communication, and the Journal of General Education. He was able to influence the kinds of articles on composition and rhetoric being published throughout this period, and he and his colleagues increased broad awareness of rhetorical study.
Looking at NAEP and the Standards through the Same Lens
Authors: Walcott Crystal , Mohr Doris , Kloosterman Peter
Published: May 2012

Math results from the National Assessment of Educational Progress (NAEP) are discussed and compared with results found in other subjects.
Palette of Problems
Authors: Rock David , Porter Mary K.
Published: May 2012

A monthly set of problems is aimed at a variety of ability levels.
CCSSM: Examining the Critical Areas in Grades 5 and 6
Authors: Polly Drew , Orrill Chandra
Published: May 2012

To support mathematics educators as they consider implications of the Common Core State Standards for Mathematics (CCSSM) for instruction and assessment, Teaching Children Mathematics is publishing a series of feature articles. In this fourth installment, authors Polly and Orrill suggest implementation strategies for grades 5 and 6. A final, cohesive article will appear in the August 2012 issue. Authored by Susan Jo Russell, the last piece concentrates on the implementation of the eight Standards of Mathematical Practice (SMP) and the constellations of Practices and Standards.
Modeling 10-ness using Tech-knowledgy
Authors: Suh Jennifer , Seshaiyer Padmanabhan
Published: May 2012

Foundational in understanding place value and our decimal number system, this concept is explored through a practiced-based activity designed to develop teachers' technology knowledge for teaching mathematics. The activity focuses on number sense using online applets and various related models and representations.
Welfare during gathering and loading of deer bred for meat in Italy
Authors: Quiliquini D , Alpigiani I
Published: May 2012

The aim of this study was to evaluate welfare status and the implementation of Regulation (EC) 1/2005 during the gathering and loading of deer(Cervus elaphus)bred for meat in Northern Italy. Four journeys overland along with related operations of 45 deer, destined for game farms, were observed over a period of four months. Planning, animal-management procedures, equipment and facilities, such as enclosures and corridors, influenced the success of the operations and affected the safety of animals and operators. Environmental factors, such as land inclination, were also extremely influential. Elements of the gathering technique led to stress and hyperventilation in a number of animals that were rounded up. Chemical restraint of deer was complicated by consequent physical manipulation and an inability to control withdrawal periods in game reserves. Where facilities were specific to deer, animals displayed no signs of distress and loading was carried out in the absence of stressful behaviour. Instances in which means of transport were nonspecific for deer were characterised by falls, escape and trauma during loading and unloading. Where operators had been trained and had extensive knowledge of deer physiology and behaviour, welfare and the safety of professionals were promoted along with an overall regard for the relevant legislation. This study demonstrates a number of the challenges associated with deer transport and related activities. The paucity of specific legislation regarding the management and transport of farmed deer and the absence of European standard procedures have created a lack of harmonisation in transport procedures, ultimately jeopardising the welfare of deer.
Captive-bolt euthanasia of cattle: determination of optimal-shot placement and evaluation of the Cash Special Euthanizer Kit® for euthanasia of cattle
Authors: Gilliam JN , Shearer JK , Woods J , Hill J , Reynolds J , Taylor JD , Bahr RJ , Crochik S , Snider TA
Published: May 2012

Humane euthanasia of cattle represents a challenge to the beef and dairy industries. Penetrating captive bolt, while traditionally considered to be only a stunning method, can be an effective single-step euthanasia method if both the cerebral cortex and brainstem are disrupted. This report describes a preliminary study investigating the likelihood of brainstem disruption for two captive-bolt shot locations. Heads were collected from 15 cattle that died or were euthanised for reason unrelated to the study and were then randomly assigned to one of two shot placement groups. Heads in the first group (n = 7) were shot at the intersection of two lines drawn from the medial canthus to the opposite horn or top of the opposite ear. Heads in the second group (n = 8) were shot at the intersection of two lines drawn for the lateral canthus to the opposite horn or top of the opposite ear. The guns were held perpendicular (as assessed visually) to the plane of the forehead. Shot placement was then assessed using computed tomography and disruption of the brainstem was determined. In the first group, the captive bolt failed to disrupt the brainstem in any of the heads. In the second group, the bolt disrupted the brainstem in 6 of 8 heads. The results suggest that selecting a higher shot location leads more readily to disruption of the brainstem which reduces the risk of regaining sensibility and should therefore improve animal welfare when cattle are euthanised with a penetrating captive bolt.
Aversion to the inhalation of nitrogen and carbon dioxide mixtures compared to high concentrations of carbon dioxide for stunning rabbits
Authors: Llonch P , Rodríguez P , Velarde A , de Lima V Abreu , Dalmau A
Published: May 2012

Stunning by inhalation of nitrogen (N2) and carbon dioxide (CO2) mixtures reduces aversion compared to high concentrations of CO2in pigs and poultry. The objective of the study was to assess the aversion to 90% of CO2(90C) and an alternative gas mixture of 80% N2and 20% CO2(80N20C) in commercial rabbits(Oryctolagus cuniculus). Sixty animals, divided into two groups, were used. During the first day, the rabbits of both groups were lowered in pairs into the pit with atmospheric air and their behaviour was recorded as control. During the second day, one group was exposed, again in pairs, to 90C and the other to 80N20C for 1 min. Exploratory behaviour and general activity were assessed 2 min before the exposure, during the exposure and for 2 min subsequently. During the exposure, signs of respiratory distress, loss of balance, muscle twitching and recovery of balance were also assessed. In the control sessions (atmospheric air), animals did not show respiratory distress or muscle twitching and were less active while the crate was descending than when gas treatments were applied. The percentage of animals with respiratory distress was higher in 90C (97%) than 80N20C (40%). Muscle twitching occurred earlier in 80N20C (97%; 23.9 s) than in 90C (17%; 37.4 s). A second phase of muscle twitching occurred only in 90C at 93.0 s. Mean latency of lost of balance and recovery were lower in 80N20C (24.2 and 98.6 s, respectively) than in 90C (28.2 and 110.2 s, respectively). It is concluded that rabbits showed less signs of respiratory distress to inhalation of 80N20C than 90C but more signs of aversion than when they were exposed to atmospheric air.
Equivalency between EU and non-EU countries regarding animal welfare at slaughter
Authors: Cassidy T
Published: May 2012

Much development work has already been done by the industry and the competent authorities in countries exporting meat to the EU, and these countries are well on their way to satisfying the requirements of Regulation (EC) No 1099/2009. The major problem for animal welfare was that the electrical parameters used for water-bath stunning of poultry were not set at levels which ensured that birds were effectively stunned. In addition, there are meat quality issues when higher currents are used. Other areas to be further developed include clarification and formalisation of the tasks of the Animal Welfare Officer; certifying competence of the relevant staff; adapting and improving or completing the existing standard operating procedures. Several countries need to make changes to their transport/delivery practices or to the arrangements for accommodating animals, so that they respect the requirement to feed and bed animals if not slaughtered within 12 hours of their arrival at the slaughterhouse.
Cost Optimisation in Freight Distribution with Cross-Docking: N-Echelon Location Routing Problem
Authors: Gonzalez-Feliu Jesus
Published: May 2012

Freight transportation constitutes one of the main activities that influence the economy and society, as it assures a vital link between suppliers and customers and represents a major source of employment. Multi-echelon distribution is one of the most common strategies adopted by the transportation companies in an aim of cost reduction. Although vehicle routing problems are very common in operational research, they are essentially related to single-echelon cases. This paper presents the main concepts of multi-echelon distribution with cross-docks and a unified notation for the N-echelon location routing problem. A literature review is also presented, in order to list the main problems and methods that can be helpful for scientists and transportation practitioners.
Container Boom in the Port of Koper
Authors: Twrdy Elen , Trupac Igor , Kolenc Jurij
Published: May 2012

For the Port of Koper the Central and Eastern European market is very important. The Port of Koper is especially interesting for goods flows relating to the exchange of goods on the East – West route (and vice versa) and bound for the EU, in particular to the catchment area of the North Adriatic ports.The year 2009 was a difficult year for business, especially due to the uncertain international economic situation. In the first nine months of 2010, 16% more goods were handled in the Port of Koper than in the same period in 2009. The container transport especially exploded in tons (45% increase) as well as in container units (40% increase). Within this period they handled 355,000 TEUs (new record) in the container terminal (214,000 TEUs in the same period on the seventh pier in Trieste).The growth of container transport in the Port of Koper as well as the beginning of construction on the new container terminal have made the reconstruction and extension of the current container terminal an absolute priority. The extension is in line with the estimated growth of traffic as well as with the exploitation of present and future terminal capacities.This paper aims to present and analyse: (I) supply chains of the flow of containerised goods through the Port of Koper to/from the countries of Central and Eastern Europe; (II) the changes which enable this boom, current state and strategies to handle even more containers in the future; (iii) market potential, current and future investments in new capacities.
Searching Materials Space for Hydride Superconductors at Ambient Pressure
Authors: Cerqueira Tiago F. T. , Fang Yue‐Wen , Errea Ion , Sanna Antonio , Marques Miguel A. L.
Published: June 2024

A machine‐learning‐assisted approach is employed to search for superconducting hydrides under ambient pressure within an extensive dataset comprising over 150 000 compounds. The investigation yields ≈50 systems with transition temperatures surpassing 20 K, and some even reaching above 70 K. These compounds have very different crystal structures, with different dimensionality, chemical composition, stoichiometry, and arrangement of the hydrogens. Interestingly, most of these systems display slight thermodynamic instability, implying that their synthesis will re quire conditions beyond ambient equilibrium. Moreover, a consistent chemical composition is found in the majority of these systems, which combines alkali or alkali‐earth elements with noble metals. This observation suggests a promising avenue for future experimental investigations into high‐temperature superconductivity within hydrides at ambient pressure.
Lyotropic Liquid Crystalline Phase Nanostructure and Cholesterol Enhance Lipid Nanoparticle Mediated mRNA Transfection in Macrophages
Authors: Iscaro Joshua , Yu Haitao , Martinez Natalia , Subramaniam Santhni , Joyce Paul , Wang Hao , Dyett Brendan P. , White Jacinta , Prestidge Clive A. , Drummond Calum J. , Bozinovski Steven , Zhai Jiali
Published: June 2024

Macrophages are unique immune cells attracting growing attention as a potential candidate for cell‐based therapy for infectious diseases and cancer. Strategies that can reprogramme or gene‐edit macrophages hold potential across a spectrum of acute and chronic conditions. Herein, lipid nanoparticles (LNPs) are developed containing the ionizable lipid SM‐102, helper lipid monoolein which is known for self‐assembly in aqueous solutions into the inverse cubic lyotropic liquid crystalline mesophase, and cholesterol as an mRNA nanocarrier. The immortalized alveolar macrophage cell line (MH‐S cells) is utilized to investigate how cholesterol concentration impacts on mRNA delivery which is further validated using primary mouse alveolar macrophages isolated from the bronchoalveolar compartment and human monocyte derived macrophages. By using high‐throughput synchrotron small angle X‐ray scattering (SAXS), an acidification‐induced non‐ordered to ordered internal nanostructure transition of the formulated LNPs is observed, following the transition sequence of inverse micellar to hexagonal to cubic mesophase in the pH range from 7 to 4. Cholesterol is identified as another crucial component for superior mRNA transfection in macrophages, contributing to nanostructure transition and protein corona variation. Successful ex vivo mRNA transfection is also achieved in primary macrophages, highlighting the prospectivity of reprogramming macrophages as a cell therapy for lung diseases.
Ultrastrong and Thermo‐Remoldable Lignin‐Based Polyurethane Foam Insulation with Active‐Passive Fire Resistance
Authors: Sun Lichao , Guo Yujia , Ou Rongxian , Xu Jingwen , Gao Fei , Meng Qingzhi , Chen Sili , Guo Chuigen , Fan Qi , Wang Qingwen
Published: June 2024

Foam thermal insulators are indispensable for prevailing energy‐saving engineering, however their widespread use brings intractability such as unsustainability, “white pollution”, and fire hazards. The emergence of bio‐based foams is highly appreciated, but the fabrication approaches are economically unattractive and/or the product properties are inferior, making their large‐scale implementation unviable. Herein, a versatile, thermally remoldable phosphate‐containing polyurethane composite foam (LPU‐G) is constructed from natural lignin and expanded graphite flakes via an atmospheric pressure and scalable one‐pot strategy. The optimal LPU‐G exhibits exceptional mechanical strength, capable of supporting over 6000 times its weight without significant deformation. Moreover, the LPU‐G demonstrates the desired multifunctionality in handling extreme circumstances, including humidity‐tolerant thermal insulation, superb water vapor barrier, and withstanding ≈1200 °C flame without ignition. Based on the “expansion‐conductivity” micro‐mechanism, LPU‐G is the first foam material to be constructed as a sensitive fire alarm system with an ultra‐long alarm time (>1800 s). Surprisingly, LPU‐G can be rapidly upcycled into recyclable bulk composites for a second life through simple thermo‐molding processes rooted in the multi‐dynamic behavior of the phosphate, carbamate, and hydrogen bonds. The easy‐to‐scale LPU‐G represents a new generation of thermal insulators that address concerns regarding unsustainability, high cost, fire risk, and inferior mechanical properties.
Room Temperature Single Photon Detection at 1550 nm Using van der Waals Heterojunction
Authors: Abraham Nithin , Watanabe Kenji , Taniguchi Takashi , Majumdar Kausik
Published: June 2024

Single‐photon detectors (SPDs) are crucial in applications ranging from space, biological imaging to quantum communication and information processing. The SPDs that operate at room temperature are of particular interest to broader application space as the energy overhead introduced by cryogenic cooling can be avoided. Although silicon‐based single photon avalanche diodes (SPADs) are well‐matured and operate at room temperature, the bandgap limitation restricts their operation at telecommunication wavelength (1550 nm) and beyond. InGaAs‐based SPADs, on the other hand, are sensitive to 1550 nm photons but suffer from relatively lower efficiency, high dark count rate, afterpulsing probability, and pose hazards to the environment from the fabrication process. In this work, the properties of nanomaterials that can be leveraged to address these challenges are demonstrated and a room‐temperature single‐photon detector capable of operating at 1550 nm is realized. This is achieved by coupling a low bandgap (≈ 350 meV) absorber (black phosphorus) to a sensitive van der Waals probe that is capable of detecting discrete electron fluctuation. The device is optimized for operation at 1550 nm and demonstrates an overall quantum efficiency of 21.4% (estimated as 42.8% for polarized light), and a minimum dark count of ≈ 720 Hz at room temperature.
Regulation of d‐Orbital Electron in Fe‐N4 by High‐Entropy Atomic Clusters for Highly Active and Durable Oxygen Reduction Reaction
Authors: Yang Gege , Cai Hairui , Zhang Nan , Wang Bin , Liang Chao , Zhang Shengli , Yang Zhimao , Yang Shengchun
Published: June 2024

Simultaneously improving activity and stability is a crucial yet challenge in the development of metallic single‐atom‐based catalysts. In current work, a novel approach is introduced to address this issue by combining post‐adsorption and secondary pyrolysis techniques to create a synergistic catalytic system, in which the single atoms (SAs) Fe sites played in the NC matrix (Fe─NC) are coupled with high‐entropy atomic clusters (HEACs). Theoretical calculations reveal that the incorporation of HEACs lead to a rehybridization of the 3d orbital configuration of Fe‐N4, which helps to balance the adsorption/desorption energy of oxygenated intermediates. In situ spectroscopy further reveals that the rate‐limiting step of OH* desorption on HEAC/Fe─NC in oxygen reduction reaction (ORR) is more facile compared to atomic Fe─NC, implying a higher ORR activity. Moreover, the synergistic effect of diffusion activation barriers and configuration entropy contributes to the structural stability of HEAC/Fe─NC, resulting in remarkable durability. Consequently, this unique catalyst exhibits half‐wave potentials of 0.927 and 0.828 V in an aqueous solution of KOH (0.1 m) and HClO4 (0.1 m), respectively, along with excellent durability. The findings propose a novel strategy for modulating the electronic structure of metallic SAs catalysts and enhancing their stability through strong interactions between SAs and HEACs.
Bioinspired Nano‐Photosensitizer‐Activated Caspase‐3/GSDME Pathway Induces Pyroptosis in Lung Cancer Cells
Authors: Gao Min , Sun Qiuting , Zhang Huiru , Liu Mengyu , Peng Rui , Qin Weiji , Wang Qian , Yang Tianhao , Zhou Man , He Xiaoyan , Sun Gengyun
Published: June 2024

Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase‐3 to lyse gasdermin E (GSDME), and this process can be used as an effective therapeutic strategy. Thus, a selective and powerful inducer of activated caspase‐3 plays a vital role in pyroptosis‐based cancer therapy. Herein, a human cell membrane vesicle‐based nanoplatform (HCNP) is designed for photodynamic therapy (PDT). HCNP is modified with vesicular stomatitis virus G‐protein (VSVG) to anchor nano‐photosensitizers on the tumor cell membrane. Photosensitizers are bonded to HCNP by clicking chemical reaction as pyroptosis inducers. The results show that HCNP effectively disrupts the mitochondrial function of cells by generating reactive oxygen species (ROS) upon laser irradiation; concomitantly, GSDME is cleaved by activated caspase‐3 and promotes pyroptosis of lung cancer cells. Here an effective intervention strategy is proposed to induce pyroptosis based on light‐activated PDT.
Efficient Orbitronic Terahertz Emission Based on CoPt Alloy
Authors: Liu Yongshan , Xu Yong , Fert Albert , Jaffrès Henri‐Yves , Nie Tianxiao , Eimer Sylvain , Zhang Xiaoqiang , Zhao Weisheng
Published: June 2024

Orbitronic devices operate by manipulating orbitally polarized currents. Recent studies have shown that these orbital currents can be excited by femtosecond laser pulses in a ferromagnet such as Ni and converted into ultrafast charge currents via orbital‐to‐charge conversion. However, the terahertz emission from orbitronic terahertz emitters based on Ni is still much weaker than that of the typical spintronic terahertz emitter. Here, this work reports a more efficient light‐induced generation of orbital current from a CoPt alloy, and the terahertz emission from CoPt/Cu/MgO is comparable to that of benchmark spintronic terahertz emitters. By varying the composition of the CoPt alloy, the thickness of Cu, and the capping layer, this work confirms that THz emission primarily originates from the orbital accumulation generated within CoPt, propagating through Cu, followed by subsequent orbital‐to‐charge conversion due to the inverse orbital Rashba‐Edelstein effect at the Cu/MgO interface. This study provides strong evidence for the efficient orbital current generation in CoPt alloy, paving the way for efficient orbital terahertz emitters.
Enhanced Excitonic Nature of MAPbBr3 Nanocrystals in Nanoporous GaN
Authors: Bai Xinyu , Fairclough Simon M. , Dai Linjie , Sarkar Maruf , Griffin Peter H. , Gundimeda Abhiram , Sun Yuqi , Greenham Neil C. , Dar M. Ibrahim , Oliver Rachel A. , Friend Richard H.
Published: June 2024

Blue gallium nitride (GaN) light‐emitting diodes (LEDs), combined with red/green fluorescent converters, have broad potential for display applications. Metal halide perovskites now show excellent luminescence properties and may be suitable as light converters. Here a simple solution‐processed method is reported to prepare a methylammonium lead bromide (MAPbBr3) nanoporous GaN composite. Fast (within 2 ps) energy transfer is demonstrated from photoexcited nanoporous GaN to encapsulate MAPbBr3 nanocrystals, as observed by transient absorption spectroscopy. The spatial confinement of the perovskite within the nanoporous GaN is shown to increase the perovskite radiative recombination rate. These results offer guidelines for developing high‐performance perovskite/nanoporous GaN optoelectronics.
Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma
Authors: Peng Xin , Huang Xin , Zhang Shaolu , Zhang Naixin , Huang Shengfan , Wang Yingying , Zhong Zhenxing , Zhu Shan , Gao Haiwang , Yu Zixiang , Yan Xiaotong , Tao Zhennan , Dai Yuxiang , Zhang Zhe , Chen Xi , Wang Feng , Claret Francois X. , Elkabets Moshe , Ji Ning , Zhong Yuxu , Kong Dexin
Published: June 2024

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.
Lipid Nanoparticle‐Mediated Delivery of CRISPR‐Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism
Authors: Bai Yu , Nan Yanyang , Wu Tao , Zhu An , Xie Xinlei , Sun Yun , Deng Yong , Dou Zihan , Hu Xiaozhi , Zhou Rongrui , Xu Shuwen , Zhang Yuanzhen , Fan Jiajun , Ju Dianwen
Published: June 2024

Non‐alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon‐specific CRISPR‐Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism‐related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.
An examination of trends in U.S. orange and grapefruit juice consumption
Authors: Stewart Hayden , Dong Diansheng , Byrne Anne T.
Published: June 2024

The average U.S. consumer has been drinking less orange and less grapefruit juice over time. Per capita consumption is down more than 50% since the mid‐2000s. In this study, we propose and estimate a count data model. The number of times an adult consumes 100% orange or 100% grapefruit juice over a 2‐day period is modeled as a function of income, product prices, and some characteristics of the consumer such as level of education, being on a diet, and taking nutrient supplements that proxy for health concerns and nutrition knowledge. Data used in the study were collected between January 2005 and March 2020 on over 30,000 adult consumers. Tests for overdispersion favor a negative binomial model instead of the more restrictive Poison regression model. Estimation results confirm that rising juice product prices and concern over product healthfulness have been contributing to long run trends in orange and grapefruit juice consumption. Prices for these citrus juices have increased in recent years due in part to the citrus greening disease and hazardous weather in Florida. Trends in orange and grapefruit juice consumption can impact consumer diet quality, fruit growers, and agribusiness firms responsible for transforming raw fruit into juice and juice products. [EconLit Citations: D12, Q13].
European Union–Mercosur Accord's effects on Brazilian milk powder
Authors: Mendes Krisley
Published: June 2024

Milk is one of the few agricultural products in which Brazil is not competitive. The domestic market is served by domestic production and imports from Argentina and Uruguay. The Mercosur–European Union Biregional Association Agreement provides for the elimination of tariffs and the harmonization of nontariff measures between the parties. Because the EU is one of the most competitive regions in the world market for powdered milk, this study analyzes the effects of the agreement on the links in this production chain in the Brazilian market. A constant, nested, multisectoral, and vertically integrated elasticity of substitution model is structured incorporating uncertainty in the estimates of Armington elasticities through Monte Carlo simulations, as in Hallren and Opanasets. The model allows projecting the price effect (Armington) and the preference effect in the market shares of Brazil, Mercosur, and the EU on the domestic market. The results, in the most ambitious scenario of the agreement and in the most conservative estimate, show that Brazil would lose 71.7 percentage points in the domestic market. This means reducing Brazilian production by 475 thousand tons of powdered milk. The national agricultural link in this scenario would lose 15% of the current dairy demand. This loss benefits the EU, which would participate in the domestic market with a market share of 58.75%. Mercosur would add 13.41 percentage points to its current share of the Brazilian market [EconLit Citations: F13, F14].
Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease
Authors: Li Qin , Su Shu , Feng Yuxue , Jia Meng , Zhan Jiehong , Liao Zixuan , Li Jiayu , Li Xiaofeng ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: June 2024

INTRODUCTION

Long‐term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown.

METHODS

Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed‐effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity‐related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function.

RESULTS

BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition.

DISCUSSION

Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population.

Highlights

Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL).

The association between different components of BPV and brain structural changes may vary.

BPV was associated with pNfL levels independent of average blood pressure.

pNfL mediated the effects of BPV on comorbidity‐related brain structural changes and cognitive performance.
Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression‐like behaviors in 5xFAD mice
Authors: Gong Yanju , Li Mingfeng , Liu Min , Wu Xinghan , Li Yanhong , Qin Chuan , Zhang Ling
Published: June 2024

Background

Apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for late‐onset Alzheimer's disease, and it can aggravate depressive symptoms in non‐AD patients. However, the impact of ApoE4 on AD‐associated depression‐like behaviors and its underlying pathogenic mechanisms remain unclear.

Methods

This study developed a 5xFAD mouse model overexpressing human ApoE4 (E4FAD). Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice. Changes in peripheral and central lipid metabolism, as well as the levels of serotonin (5‐HT) and γ‐aminobutyric acid (GABA) neurotransmitters in the prefrontal cortex, were examined. In addition, the protein levels of 24‐dehydrocholesterol reductase/glycogen synthase kinase‐3 beta/mammalian target of rapamycin (DHCR24/GSK3β/mTOR) and postsynaptic density protein 95/calmodulin‐dependent protein kinase II/brain‐derived neurotrophic factor (PSD95/CaMK‐II/BDNF) were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice.

Results

Compared with 5xFAD mice, E4FAD mice exhibited more severe depression‐like behaviors and cognitive impairments. These mice also exhibited increased amyloid‐beta deposition in the hippocampus, increased astrocyte numbers, and decreased expression of depression‐related neurotransmitters 5‐HT and GABA in the prefrontal cortex. Furthermore, lipid metabolism disorders were observed in E4FAD, manifesting as elevated low‐density lipoprotein cholesterol and reduced high‐density lipoprotein cholesterol in peripheral blood, decreased cholesterol level in the prefrontal cortex, and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis. Abnormal expression of proteins related to the DHCR24/GSK3β/mTOR and PSD95/CaMK‐II/BDNF pathways was also observed.

Conclusion

This study found that ApoE4 overexpression exacerbates depression‐like behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice. The mechanism may involve the induction of central and peripheral lipid metabolism disorders. Therefore, modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression. This study also provided a better animal model for studying AD comorbid with depression.
Divergent Synthesis of Enantioenriched Silicon‐Stereogenic Benzyl‐, Vinyl‐ and Borylsilanes via Asymmetric Aryl to Alkyl 1,5‐Palladium Migration
Authors: Shi Yufeng , Qin Ying , Li Zhong‐Qiu , Xu Yize , Chen Shuhan , Zhang Jinyu , Li Yu‐An , Wu Yaxin , Meng Fei , Zhong Yu‐Wu , Zhao Dongbing
Published: June 2024

Functionalization of Si‐bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon‐stereogenic architectures by functionalization of Si‐bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5‐palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5‐palladium migration reaction. The key to the success is the discovery and fine‐tuning of the different substituents of α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL)‐based phosphoramidites, which ensure the enantioselectivity and desired reactivity.
Photocatalytic Cracking of non‐Biodegradable Plastics to Chemicals and Fuels
Authors: Su Kaiyi , Gao Tengshijie , Tung Chen‐Ho , Wu Li‐Zhu
Published: June 2024

Plastic pollution is worsening the living conditions on Earth, primarily due to the toxicity and stability of non‐biodegradable plastics (NBPs). Photocatalytic cracking of NBPs is emerging as a promising way to cleave inert C−C bonds and abstract the carbon atoms from these wastes into valuable chemicals and fuels. However, controlling these processes is a huge challenge, ascribed to the complicated reactions of various NBPs. Herein, we summarize recent advances in the CO2 and carbon‐radical‐mediated photocatalytic cracking of NBPs, with an emphasis on the pivotal intermediates. The CO2‐mediated cracking proceeded with indiscriminate C−H/C−C bond cleavage of NBPs and tandem photoreduction of CO2, while carbon‐radical‐mediated cracking was realized by the prior activation of C−H bonds for selective C−C bond cleavage of NBPs. Catalytic generation and conversion of different intermediates greatly depend on the kinds of active species and the structure of photocatalysts under irradiation. Meanwhile, the fate of a specific intermediate is compared with small molecule activation to reveal the key problems in the cracking of NBPs. Finally, the challenges and potential directions are discussed to improve the overall efficiency in the photocatalytic cracking of NBPs.
Molecular Engineering of Metal–Organic Frameworks for Boosting Photocatalytic Hydrogen Peroxide Production
Authors: Tang Yu‐Ying , Luo Xiao , Xia Ri‐Qin , Luo Jie , Peng Su‐Kao , Liu Zhen‐Na , Gao Qiang , Xie Mo , Wei Rong‐Jia , Ning Guo‐Hong , Li Dan
Published: June 2024

The development of novel metal–organic frameworks (MOFs) as efficient photocatalysts for hydrogen peroxide production from water and oxygen is particularly interesting, yet remains a challenge. Herein, we have prepared four cyclic trinuclear units (CTUs) based MOFs, exhibiting good light absorption ability and suitable band gaps for photosynthesis of H2O2. However, Cu‐CTU‐based MOFs are not able to photocatalyzed the formation of H2O2, while the alteration of metal nodes from Cu‐CTU to Ag‐CTU dramatically enhances the photocatalytic performance for H2O2 production and the production rates can reach as high as 17476 μmol g−1 h−1 with an apparent quantum yield of 4.72 %, at 420 nm, which is much higher than most reported MOFs. The photocatalytic mechanism is comprehensively studied by combining the isotope labeling experiments and DFT calculation. This study provides new insights into the preparation of MOF photocatalysts with high activity for H2O2 production through molecular engineering.
A Fragment‐Based Competitive 19F LB‐NMR Platform For Hotspot‐Directed Ligand Profiling
Authors: McCarthy William J. , Thomas Sherine E. , Olaleye Tayo , Boland Jennifer A. , Floto R. Andres , Williams Glyn , Blundell Tom L. , Coyne Anthony G. , Abell Chris
Published: June 2024

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites. Herein, we describe a fragment‐based competitive 19F Ligand Based NMR (LB‐NMR) screening platform that enables routine, quantitative ligand profiling focused at ligand‐binding hotspots. As a proof of concept, the method was applied to 4′‐phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium abscessus (Mabs). X‐ray crystallographic characterisation of the hits from a 960‐member fragment screen identified three ligand‐binding hotspots across the PPAT active site. From the fragment hits a collection of 19F reporter candidates were designed and synthesised. By rigorous prioritisation and use of optimisation workflows, a single 19F reporter molecule was generated for each hotspot. Profiling the binding of a set of structurally characterised ligands by competitive 19F LB‐NMR with this suite of 19F reporters recapitulated the binding affinity and site ID assignments made by ITC and X‐ray crystallography. This quantitative mapping of ligand binding events at hotspot level resolution establishes the utility of the fragment‐based competitive 19F LB‐NMR screening platform for hotspot‐directed ligand profiling
Analysis of HZSM‐5 molecular sieve particles attrition behavior under fluidized conditions
Authors: Huang Zhiwei , Gao Feng , Miao Yang
Published: June 2024

The attrition behavior of HZSM‐5 zeolite catalyst particles at room temperature was investigated in a laboratory‐scale fluidized bed. The effects of three fluidization conditions on particle attrition were investigated, and a new attrition model was proposed. The results demonstrate that the attrition rate is inversely proportional to the initial particle size and proportional to the apparent gas velocity. After increasing to 80 μm and .3 m/s respectively, they are no longer the main factor affecting attrition. The effect of bed pressure on attrition rate is nonlinear, and the lowest attrition rate is obtained when the diameter‐height ratio is 1:1. Unsteady attrition stage can be divided into initial stage and deceleration stage. Surface delamination dominates particle attrition throughout the whole process, and bulk fracture is the dominant mechanism only in the deceleration stage. Based on the Gwyn equation, a new attrition model in the form of cubic polynomial is established with the ratio of total attrition rate to unstable attrition rate P as a parameter. The model has high accuracy and repeatability and is suitable for various fluidization conditions. It can effectively describe the attrition process and change rule of particles and reasonably predict the fluidization attrition rate of particles.
Anticancer perspectives of monocarbonyl analogs of curcumin: A decade (2014–2024) review
Authors: Nagargoje Amol A. , Deshmukh Tejshri R. , Shaikh Mubarak H. , Khedkar Vijay M. , Shingate Bapurao B.
Published: June 2024

Monocarbonyl analogs of curcumin (MACs) represent structurally modified versions of curcumin. The existing literature indicates that MACs exhibit enhanced anticancer properties compared with curcumin. Numerous research articles in recent years have emphasized the significance of MACs as effective anticancer agents. This review focuses on the latest advances in the anticancer potential of MACs, from 2014 to 2024, including discussions on their mechanism of action, structure–activity relationship (SAR), and in silico molecular docking studies.