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DNA double-strand breaks (DSBs), classified as the most harmful type of DNA damage based on the complexity of repair, lead to apoptosis or tumorigenesis. In aging, DNA damage increases and DNA repair decreases. This is exacerbated in disease, as post-mortem tissue from patients diagnosed with mild cognitive impairment (MCI) or Alzheimer's disease (AD) show increased DSBs. A novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity leads to increases in DSBs and upregulation of IEGs, while increasing DSBs and inhibiting DSB repair impairs long-term memory and alters IEG expression. Consistent with this pattern, mice carrying dominant AD mutations have increased baseline DSBs, and impaired DSB repair is observed. These data suggest an adaptive role for DSBs in the central nervous system and dysregulation of DSBs and/or repair might drive age-related cognitive decline (ACD), MCI, and AD. In this review, we discuss the adaptive role of DSBs in hippocampus-dependent learning, memory, and IEG expression. We summarize IEGs, the history of DSBs, and DSBs in synaptic plasticity, aging, and AD. DSBs likely have adaptive functions in the brain, and even subtle alterations in their formation and repair could alter IEGs, learning, and memory.
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Enfermedad de Alzheimer , Roturas del ADN de Doble Cadena , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , ADN/metabolismo , Reparación del ADN , Hipocampo/metabolismo , Ratones , Neuronas/metabolismoRESUMEN
Mitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy that minimizes brown fat activity unless obligate will have been favored during natural selection to safeguard metabolic thriftiness. Accordingly, UCP1 is constitutively inhibited and is inherently not leaky without activation. It follows that increasing brown adipocyte number or UCP1 abundance genetically or pharmacologically does not lead to an automatic increase in thermogenesis or subsequent metabolic consequences in the absence of a plausible route of concomitant activation. Despite its apparent obviousness, this tenet is frequently ignored. Consequently, incorrect conclusions are often drawn from increased BAT or brite/beige depot mass, e.g., predicting or causally linking beneficial metabolic effects. Here, we highlight the inherently inactive nature of UCP1, with a particular emphasis on the molecular brakes and releases of UCP1 activation under physiological conditions. These controls of UCP1 activity represent potential targets of therapeutic interventions to unlock constraints and efficiently harness the energy-expending potential of brown fat to prevent and treat obesity and associated metabolic disorders.
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Tejido Adiposo Pardo/metabolismo , Proteína Desacopladora 1/metabolismo , Tejido Adiposo Beige/metabolismo , Animales , Metabolismo Energético , Humanos , Lipólisis , TermogénesisRESUMEN
The United States Environmental Protection Agency (US EPA) is currently refining its approach for risk assessments conducted under the amended Toxic Substances Control Act (TSCA), largely based on recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM). We identified several issues with the current TSCA risk assessment approach that were not addressed by NASEM in its recommendations. Here, we demonstrate these issues with a case study of the 'Risk Evaluation for Asbestos, Part 1: Chrysotile Asbestos,' which US EPA released in December 2020. In this evaluation, US EPA found that occupational and some consumer uses of automotive brakes and clutches that contain asbestos result in unreasonable risks. These risks were calculated from estimated exposures during brake work and an inhalation unit risk (IUR) developed for chrysotile asbestos. We found that US EPA overestimated risk as a result of unrealistic inputs to both the exposure and toxicity components of the risk equation, and because the Agency did not fully consider relevant epidemiology and toxicity evidence in its systematic review. Our evaluation demonstrates areas in which the TSCA risk assessment approach could be improved to result in risk evaluations that are supported by the available scientific evidence.
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Amianto , Exposición Profesional , Asbestos Serpentinas/análisis , Medición de Riesgo , Estados UnidosRESUMEN
BACKGROUND: Respirable crystalline silica causes lung carcinomas and many thousand future cancer cases are expected in e.g. Europe. Critical questions are how silica causes genotoxicity in the respiratory epithelium and if new cases can be avoided by lowered permissible exposure levels. In this study we investigate early DNA damaging effects of low doses of silica particles in respiratory epithelial cells in vitro and in vivo in an effort to understand low-dose carcinogenic effects of silica particles. RESULTS: We find DNA damage accumulation already after 5-10 min exposure to low doses (5 µg/cm2) of silica particles (Min-U-Sil 5) in vitro. DNA damage was documented as increased levels of γH2AX, pCHK2, by Comet assay, AIM2 induction, and by increased DNA repair (non-homologous end joining) signaling. The DNA damage response (DDR) was not related to increased ROS levels, but to a NLRP3-dependent mitochondrial depolarization. Particles in contact with the plasma membrane elicited a Ser198 phosphorylation of NLRP3, co-localization of NLRP3 to mitochondria and depolarization. FCCP, a mitochondrial uncoupler, as well as overexpressed NLRP3 mimicked the silica-induced depolarization and the DNA damage response. A single inhalation of 25 µg silica particles gave a similar rapid DDR in mouse lung. Biomarkers (CC10 and GPRC5A) indicated an involvement of respiratory epithelial cells. CONCLUSIONS: Our findings demonstrate a novel mode of action (MOA) for silica-induced DNA damage and mutagenic double strand breaks in airway epithelial cells. This MOA seems independent of particle uptake and of an involvement of macrophages. Our study might help defining models for estimating exposure levels without DNA damaging effects.
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Daño del ADN , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Material Particulado/toxicidad , Dióxido de Silicio/toxicidad , Animales , Línea Celular , Ensayo Cometa , Células Epiteliales , Inflamasomas , Pulmón , Macrófagos , Ratones , Mutágenos , Receptores Acoplados a Proteínas G , Mucosa RespiratoriaRESUMEN
Pd-catalysed Stille and Suzuki cross-couplings were used to prepare 9-(3-indenyl)-, 6, and 9-(2-indenyl)-anthracene, 7; addition of benzyne led to the 9-Indenyl-triptycenes, 8 and 9. In 6, [4 + 2] addition also occurred to the indenyl substituent. Reaction of 6 through 9 with Cr(CO)6 or Re2(CO)10 gave their M(CO)3 derivatives, where the Cr or Re was complexed to a six- or five-membered ring, respectively. In the 9-(2-indenyl)triptycene complexes, slowed rotation of the paddlewheel on the NMR time-scale was apparent in the η5-Re(CO)3 case and, when the η6-Cr(CO)3 was deprotonated, the resulting haptotropic shift of the metal tripod onto the five-membered ring also blocked paddlewheel rotation, thus functioning as an organometallic molecular brake. Suzuki coupling of ferrocenylboronic acid to mono- or dibromoanthracene yielded the ferrocenyl anthracenes en route to the corresponding triptycenes in which stepwise hindered rotations of the ferrocenyl groups behaved like molecular dials. CuCl2-mediated coupling of methyl- and phenyl-indenes yielded their rac and meso 2,2'-biindenyls; surprisingly, however, the apparently sterically crowded rac 2,2'-Bis(9-triptycyl)biindenyl functioned as a freely rotating set of molecular gears. The predicted high rotation barrier in 9-phenylanthracene was experimentally validated via the Pd-catalysed syntheses of di(3-fluorophenyl)anthracene and 9-(1-naphthyl)-10-phenylanthracene.
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Antracenos/química , Acoplamiento Oxidativo , Paladio/química , Antracenos/síntesis química , Técnicas de Química Sintética , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/químicaRESUMEN
Hybrid micromotors capable of both chemically powered propulsion and fuel-free light-driven actuation and offering built-in optical brakes for chemical propulsion are described. The new hybrid micromotors are designed by combining photocatalytic TiO2 and catalytic Pt surfaces into a Janus microparticle. The chemical reactions on the different surfaces of the Janus particle hybrid micromotor can be tailored by using chemical or light stimuli that generate counteracting propulsion forces on the catalytic Pt and photocatalytic TiO2 sides. Such modulation of the surface chemistry on a single micromotor leads to switchable propulsion modes and reversal of the direction of motion that reflect the tuning of the local ion concentration and hence the dominant propulsion force. An intermediate Au layer (under the Pt surface) plays an important role in determining the propulsion mechanism and operation of the hybrid motor. The built-in optical braking system allows "on-the-fly" control of the chemical propulsion through a photocatalytic reaction on the TiO2 side to counterbalance the chemical propulsion force generated on the Pt side. The adaptive dual operation of these chemical/light hybrid micromotors, associated with such control of the surface chemistry, holds considerable promise for designing smart nanomachines that autonomously reconfigure their propulsion mode for various on-demand operations.
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BACKGROUND: Kelsh et al. [2007]: Occup Med (Lond) 57:581-589 published a paper reanalyzing one of the few data sources publicly available on mesothelioma amongst brake workers, the Australian Mesothelioma Surveillance Registry (AMSR). This reanalysis was commissioned by lawyers representing the automobile manufacturing companies and did not align with an independent analysis published by Leigh and Driscoll [2003]: Occup Environ Health 9:206-217. METHODS: We sought to reevaluate the AMSR data ourselves to understand how the company-sponsored research categorized the data. RESULTS: In our re-analysis of the 78 brake-related folios in the AMSR, we determined that 57 were employed brake mechanics, 35 were employed brake mechanics with no other asbestos exposure besides brake work or repair, and 41 of these cases had no other asbestos exposure besides brake work or repair. Our classifications differed significantly from Kelsh et al. CONCLUSIONS: We discuss how Kelsh et al. methodically reduced the relevant cases by following overly stringent criteria for inclusion. Am. J. Ind. Med. 60:152-162, 2017. © 2017 Wiley Periodicals, Inc.
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Amianto/toxicidad , Carcinógenos/toxicidad , Industrias , Mesotelioma/etiología , Enfermedades Profesionales/etiología , Apoyo a la Investigación como Asunto , Australia/epidemiología , Automóviles , Humanos , Mesotelioma/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Sistema de Registros , Proyectos de InvestigaciónRESUMEN
There have been claims over the years that asbestos-containing product manufacturers did not sufficiently warn end users early enough regarding the potential health hazards associated with their products (1930s-1990s). To address this issue, we compared the content of the warnings associated with asbestos-containing friction products (brakes, clutches, and gaskets) manufactured by the US automotive industries to what was expected by regulatory agencies during the time period in which an understanding of asbestos health hazards was being developed. We ended our evaluation around 1990, since asbestos-containing manufacturer supplied automotive products were functionally removed from commerce by 1985 in the United States. We assessed the warnings issued in users' manuals, technical service bulletins, product packaging materials, and labels placed on products themselves. Based on our evaluation, regulatory agencies had no guidelines regarding specific warning language for finished friction products, particularly when a product contained encapsulated asbestos fibers (i.e., modified by a bonding agent). Even today, federal regulations do not require labeling on encapsulated products when, based on professional judgment or sampling, user exposure is not expected to exceed the OSHA PEL. We concluded that, despite limited regulatory guidance, the US automotive industry provided adequate warnings with regards to its friction products.
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Contaminantes Ocupacionales del Aire , Amianto , Automóviles , Seguridad de Productos para el Consumidor/legislación & jurisprudencia , Regulación Gubernamental/historia , Exposición Profesional/prevención & control , Gobierno Federal/historia , Fricción , Comunicación en Salud/historia , Comunicación en Salud/métodos , Historia del Siglo XX , Humanos , Materiales Manufacturados , Estados UnidosRESUMEN
Braking systems are extremely important in any vehicle. They convert the kinetic energy of motion into thermal energy that is dissipated into the atmosphere. Different vehicle groups have different nominal and maximum speeds and masses, so the amount of thermal energy that needs to be absorbed by the friction pads and then dissipated can vary significantly. Conventional friction materials are composite materials capable of withstanding high temperatures (in the order of 500-600 °C) and high mechanical loads resulting from braking intensity and vehicle weight. In small vehicles traveling at low speeds, where both the amount of thermal energy and its density are limited, the use of slightly weaker friction materials with better ecological properties can be considered. This work proposes a prototype composite friction material using flax fibers as reinforcement instead of the commonly used aramid. A number of samples were prepared and subjected to laboratory tests. The samples were prepared using components of plant origin, specifically flax fibers. This component acted as reinforcement in the composite friction material, replacing aramid commonly used for this purpose. The main tribological characteristics were determined, such as the values of the coefficients of friction and the coefficients of abrasive wear rate. For this purpose, an authorial method using ball-cratering contact was used. The results were analyzed using statistical methods. It was found that the composite material using flax fibers does not differ significantly in its tribological properties from conventional solutions; so, it can be assumed that it can be used in the vehicle's braking system.
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Protocols for the isolation of peripheral blood mononuclear cells (PBMCs) from whole blood vary greatly between laboratories, especially in published studies of SARS-CoV-2-specific T cell responses following infection and vaccination. Research on the effects of different wash media types or centrifugation speeds and brake usage during the PBMC isolation process on downstream T cell activation and functionality is limited. Blood samples from 26 COVID-19-vaccinated participants were processed with different PBMC isolation methods using either PBS or RPMI as the wash media with high centrifugation speed and brakes or RPMI as the wash media with low speed and brakes (RPMI+ method). SARS-CoV-2 spike-specific T cells were quantified and characterized via a flow cytometry-based activation induced markers (AIM) assay and an interferon-γ (IFNγ) FluoroSpot assay and responses were compared between processing methods. Samples washed with RPMI showed higher AIM+ CD4 T cell responses than those washed with PBS and showed a shift away from naïve and towards an effector memory phenotype. The activation marker OX40 showed higher SARS-CoV-2 spike-induced upregulation on RPMI-washed CD4 T cells, while differences in CD137 upregulation were minimal between processing methods. The magnitude of the AIM+ CD8 T cell response was similar between processing methods but showed higher stimulation indices. Background frequencies of CD69+ CD8 T cells were increased in PBS-washed samples and were associated with higher baseline numbers of IFNγ-producing cells in the FluoroSpot assay. Slower braking in the RPMI+ method did not improve detection of SARS-CoV-2-specific T cells and caused longer processing times. Thus, the use of RPMI media with full centrifugation brakes during the wash steps of PBMC isolation was found to be most effective and efficient. Further studies are needed to elucidate the pathways involved in RPMI-mediated preservation of downstream T cell activity.
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COVID-19 , SARS-CoV-2 , Humanos , Leucocitos Mononucleares , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivosRESUMEN
Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells-hMSC) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSC from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in hMSC, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 h after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA-repair system after X-ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of hMSC from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.
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Adaptation to changes in energy availability is pivotal for the survival of animals. Adipose tissue, the body's largest reservoir of energy and a major source of metabolic fuel, exerts a buffering function for fluctuations in nutrient availability. This functional plasticity ranges from energy storage in the form of triglycerides during periods of excess energy intake to energy mobilization via lipolysis in the form of free fatty acids for other organs during states of energy demands. The subtle balance between energy storage and mobilization is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance, type 2 diabetes and cancer cachexia. As a result, adipocyte lipolysis is tightly regulated by complex regulatory mechanisms involving lipases and hormonal and biochemical signals that have opposing effects. In thermogenic brown and brite adipocytes, lipolysis stimulation is the canonical way for the activation of non-shivering thermogenesis. Lipolysis proceeds in an orderly and delicately regulated manner, with stimulation through cell-surface receptors via neurotransmitters, hormones, and autocrine/paracrine factors that activate various intracellular signal transduction pathways and increase kinase activity. The subsequent phosphorylation of perilipins, lipases, and cofactors initiates the translocation of key lipases from the cytoplasm to lipid droplets and enables protein-protein interactions to assemble the lipolytic machinery on the scaffolding perilipins at the surface of lipid droplets. Although activation of lipolysis has been well studied, the feedback fine-tuning is less well appreciated. This review focuses on the molecular brakes of lipolysis and discusses some of the divergent fine-tuning strategies in the negative feedback regulation of lipolysis, including delicate negative feedback loops, intermediary lipid metabolites-mediated allosteric regulation and dynamic protein-protein interactions. As aberrant adipocyte lipolysis is involved in various metabolic diseases and releasing the brakes on lipolysis in thermogenic adipocytes may activate thermogenesis, targeting adipocyte lipolysis is thus of therapeutic interest.
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OBJECTIVE: Antilock braking systems (ABS) prevent wheels from locking during hard braking and have been shown to reduce motorcyclists' crash risk. ABS has proliferated in the United States fleet, and the objective of the current study was to update the effectiveness estimate for ABS with additional years of data and a broader variety of motorcycle types. METHODS: Motorcycle drivers involved in fatal crashes per 10,000 registered vehicle years during 2003-19 were examined for 65 motorcycle models offering ABS as an optional feature. Fatal crash rates for motorcycles with ABS were compared with rates for the same models without it. RESULTS: ABS was associated with a statistically significant 22% reduction in motorcycle driver fatal crash involvements per 10,000 registered vehicle years. CONCLUSION: This finding adds to the growing literature demonstrating the safety benefits of motorcycle ABS.
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Accidentes de Tránsito , Motocicletas , Accidentes de Tránsito/prevención & control , Humanos , Equipos de Seguridad , Estados Unidos/epidemiologíaRESUMEN
Aldehyde dehydrogenases (ALDHs) are a family of detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. In humans, the ALDH family comprises 19 isoenzymes active in the majority of mammalian tissues. Each ALDH isoform has a specific differential expression pattern and most of them have individual functional roles in cancer. ALDHs are overexpressed in subpopulations of cancer cells with stem-like features, where they are involved in several processes including cellular proliferation, differentiation, detoxification and survival, participating in lipids and amino acid metabolism and retinoic acid synthesis. In particular, ALDH enzymes protect cancer cells by metabolizing toxic aldehydes in less reactive and more soluble carboxylic acids. High metabolic activity as well as conventional anticancer therapies contribute to aldehyde accumulation, leading to DNA double strand breaks (DSB) through the generation of reactive oxygen species (ROS) and lipid peroxidation. ALDH overexpression is crucial not only for the survival of cancer stem cells but can also affect immune cells of the tumour microenvironment (TME). The reduction of ROS amount and the increase in retinoic acid signaling impairs immunogenic cell death (ICD) inducing the activation and stability of immunosuppressive regulatory T cells (Tregs). Dissecting the role of ALDH specific isoforms in the TME can open new scenarios in the cancer treatment. In this review, we summarize the current knowledge about the role of ALDH isoforms in solid tumors, in particular in association with therapy-resistance.
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Between 9 March and 18 May 2020, strict lockdown measures were adopted in Italy for containing the COVID-19 pandemic: in Rome, despite vehicular traffic on average was more than halved, it was not observed a evident decrease of the airborne particulate matter (PM) concentrations, as assessed by air quality data. In this study, daily PM10 filters were collected from selected automated stations operated in Rome by the regional network of air quality monitoring: their magnetic properties - including magnetic susceptibility, hysteresis parameters and FORC (first order reversal curves) diagrams - were compared during and after the lockdown, for outlining the impact of the COVID-19 measures on airborne particulate matter. In urban traffic sites, the PM10 concentrations did not significantly change after the end of the lockdown, when vehicular traffic promptly returned to its usual levels; conversely, the average volume and mass magnetic susceptibilities approximately doubled, and the linear correlation between volume magnetic susceptibility and PM10 concentration became significant, pointing out the link between PM10 concentrations and the increasing levels of traffic-related magnetic emissions. Magnetite-like minerals, attributed to non-exhaust brakes emissions, dominated the magnetic fraction of PM10 near urban traffic sites, with natural magnetic components emerging in background sites and during exogenous dusts atmospheric events. Magnetic susceptibility constituted a fast and sensitive proxy of vehicular particulate emissions: the magnetic properties can play a relevant role in the source apportionment of PM10, especially when unsignificant variations in its concentration levels may mask important changes in the traffic-related magnetic fraction. As a further hint, increasing attention should be drawn to the reduction of brake wear emissions, that are overcoming by far fuel exhausts as the main particulate pollutant in traffic contexts.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Control de Enfermedades Transmisibles , Monitoreo del Ambiente , Humanos , Italia , Fenómenos Magnéticos , Pandemias , Material Particulado/análisis , Ciudad de Roma , SARS-CoV-2 , Emisiones de Vehículos/análisisRESUMEN
Braking systems have a direct impact on the safety of road users. That is why it is crucial that the performance of brakes be dependable and faultless. Unfortunately, the operating conditions of brakes during their operating time are affected by many variables, which results in changes in their tribological properties. This article presents an attempt to develop a methodology for studying how the operating time affects the value of the coefficient of friction and the abrasive wear factor. The Taguchi method of process optimization was used to plan the experiment, which was based on tests using the ball-cratering method. The results clearly show that the degree of wear affects the properties of the friction material used in the production process of brakes.
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Automobile friction brakes generate, in addition to coarse particles generated by mechanical processes, highly variable amount of nanoparticles from high temperature processes. The effects of braking conditions - speed, deceleration rate, brake rotor temperatures - on nanoparticle production were investigated here, aiming to provide practical guidance for reducing emissions through driving style and traffic management. Typical brake pads and a rotor from a common passenger car were subjected, on a brake dynamometer, to three runs of the WLTP brake cycle developed for brake wear particle measurements. Additionally, four sets of common brake pads were subjected to those parts of standardized brake performance tests believed to be reasonably realistic for common driving. Particle size distributions (5.6-560 nm electric mobility diameter, without removal of volatiles) show a dominant peak at 10 nm commensurate to the severity of braking and a non-linear increase of the total particle number at higher braking powers and higher total energy dissipated. The average emissions for three runs of the WLTP brake cycle were 3.3 × 1010 particles/km, while the harshest deceleration, 175-100 km/h at 5.28 m·s-2, has produced 8.4 to 38 × 1013 particles, corresponding to 2.5-11.5 thousands of km of WLTP-like driving. While previous studies have correlated higher PN production with higher average brake rotor temperature, a more complex relationship between nanoparticle emissions and a combination of initial rotor temperature, total energy dissipated and braking power has been observed here. From a driver behavior and regulatory perspective, it appears limiting harsh braking and braking from high speeds, possibly through improved driving practices, road design and traffic management, may potentially reduce brake wear nanoparticles. From the measurement perspective, it appears that "off-cycle" braking, even if relatively infrequent, may be associated with exponentially higher emissions and non-negligible share of the total emissions, and therefore should not be neglected.
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Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.
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Amianto/efectos adversos , Neoplasias Pulmonares/inducido químicamente , Mesotelioma/inducido químicamente , Exposición Profesional , Humanos , Masculino , Persona de Mediana Edad , Vehículos a MotorRESUMEN
Three azobenzene derivatives (2 R, 2 OR, and 2 NR) that differed in their terminal substituent (alkyl, alkyloxy, and dialkylamino, respectively) have been synthesized and investigated as molecular brakes, in which the rigid H-shaped pentiptycene group functioned as a rotor and the dinitrophenyl group as a "brake pad". The E and Zâ isomers of these compounds corresponded to the "brake-off" and "brake-on" states, respectively. The rotation rate of the rotor was evaluated by VTâ NMR spectroscopy for the brake-on state and by DFT calculations for the brake-off state. The difference between the rotation rates for the rotor in the two states was as large as eight orders of magnitude at ambient temperature. Photochemical switching of the azobenzene moieties afforded efficiencies of 55-67%. A combination of photochemical EâZ and thermal ZâE isomerization promoted the switching efficiency up to 78%. The terminal substituent affected both the photochemical and thermal switching efficiencies. Solvent polarity also played an important role in the lifetimes of the Zâ isomers. These azobenzene systems displayed similar braking powers but superior switching efficiencies to the stilbene analogue (1O R; ca. 60% vs 20%).
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This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed.