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Janus Kinase 3 (JAK3) is important for the signaling transduction of cytokines in immune cells and is identified as potential target for treatment of rheumatoid arthritis (RA). Recently, we designed and synthesized two JAK3 inhibitors J1b and J1f, which featured with high selectivity but mild bioactivity. Therefore, in present study the structure was optimized to increase the potency. As shown in the results, most of the compounds synthesized showed stronger inhibitory activities against JAK3 in contrast to the lead compounds, among which 9a was the most promising candidate because it had the most potent effect in ameliorating carrageenan-induced inflammation of mice and exhibited low acute in vivo toxicity (MTD > 2 g/kg). Further analysis revealed that 9a was highly selective to JAK3 (IC50 = 0.29 nM) with only minimal effect on other JAK members (>3300-fold) and those kinases bearing a thiol in a position analogous to that of Cys909 in JAK3 (>150-fold). Meanwhile, the selectivity of JAK3 was also confirmed by PBMC stimulation assay, in which 9a irreversibly bound to JAK3 and robustly inhibited the signaling transduction with mild suppression on other JAKs. Moreover, it was showed that 9a could remarkably inhibited the proliferation of lymphocytes in response to concanavalin A and significantly mitigate disease severity in collagen induced arthritis. Therefore, present data indicate that compound 9a is a selective JAK3 inhibitor and could be a promising candidate for clinical treatment of RA.
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Artritis Reumatoide , Janus Quinasa 3 , Inhibidores de Proteínas Quinasas , Pirimidinas , Janus Quinasa 3/antagonistas & inhibidores , Janus Quinasa 3/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Animales , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Humanos , Relación Estructura-Actividad , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Estructura Molecular , Relación Dosis-Respuesta a Droga , Pirroles/química , Pirroles/farmacología , Pirroles/síntesis química , Carragenina , Masculino , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/inducido químicamente , Antirreumáticos/farmacología , Antirreumáticos/química , Antirreumáticos/síntesis química , Simulación del Acoplamiento MolecularRESUMEN
Nitric oxide (NO), the smallest signaling molecule known, can be excessively produced by overexpressed inducible nitric oxide synthase (iNOS), and eventually leads to multiple inflammatory related diseases. Thus, reducing the overexpression of NO represents as very potential anti-inflammatory strategy. In current study, a series of compounds were designed and synthesized based on the hybridization of 7H-pyrrolo[2,3-d]pyrimidine and cinnamamide fragments in order to develop novel NO production inhibitors. Among them, compound S2h displayed a vigorous inhibitory activity on NO production with an IC50 value of 3.21 ± 0.67 µM, which was much lower than that of the positive control Nω-nitro-L-arginine (L-NNA, IC50 = 28.36 ± 3.13 µM). Due to its obeying Lipinski's and Veber's rules that guarantee compounds with good oral bioavailability, S2h effectively suppressed the paw swelling in carrageenan-induced mice. Additionally, compound S2h formed clear interactions with iNOS protein according to the docking analysis. Therefore, compounds S2h is a promising lead compound for further development of potent iNOS inhibitors or anti-inflammatory agents.
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Background: Atherosclerotic coronary heart disease (CHD) stands as a paramount cardiovascular concern and the primary cause of mortality. To underscore the significance of our study, it is crucial to highlight the existing gaps in current diagnostic methods and prognostic assessments of CHD. By addressing these gaps, our research aims to contribute valuable insights and advancements in the understanding and management of this prevalent cardiovascular condition. Objective: The primary objective of this study is to investigate the correlation between carotid ultrasound, the Atherogenic Index of Plasma (AIP), and the severity of CHD. Methods: We enrolled 59 patients diagnosed with coronary heart disease and categorized them into two groups (multi-vessel and single-vessel disease groups) based on disease severity. The study employed carotid ultrasound, which measures Intima-Media Thickness (IMT) and carotid artery stenosis, among other indicators. Additionally, we calculated the AIP. This approach allowed us to thoroughly analyze the correlation between these key indicators and the severity of coronary heart disease lesions. Results: The study included 59 patients, 38 with single-vessel disease and 21 with multi-vessel disease. In the multivessel disease group, we observed significantly elevated levels of AIP, IMT, and carotid stenosis compared to the single-vessel disease group. Specifically, AIP, IMT, and carotid stenosis levels were higher in the multi-vessel group. Furthermore, our analysis revealed a positive correlation between AIP and IMT (r = 0.038, P = .003), while no significant correlation was found between AIP and carotid stenosis. Additionally, there was a moderate correlation between IMT and carotid stenosis. Conclusion: The combined assessment of AIP and carotid ultrasonography emerges as a promising approach for evaluating the severity of CHD. Notably, the multi-vessel disease group exhibited higher AIP levels compared to the single-vessel disease group, along with increased IMT and carotid artery stenosis. Our findings highlight a positive correlation between AIP and IMT, as well as between IMT and the degree of carotid stenosis. These associations underscore the potential of AIP, in conjunction with carotid ultrasonography parameters, as valuable indicators for gauging CHD severity. The clinical implications of these findings warrant further exploration, particularly in their potential integration into existing diagnostic or prognostic models for CHD. This integrated approach may offer enhanced precision in distinguishing between single-vessel and multi-vessel disease, contributing to more informed clinical decision-making.
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Selective inhibition of Janus kinase 3 (JAK3) is a promising strategy for the treatment of autoimmune diseases. Based on the discovery of a hydrophobic pocket unutilized between the lead compound RB1 and the JAK3 protein, a series of covalent JAK3 inhibitors were prepared by introducing various aromatic fragments to RB1. Among them, J1b (JAK3 IC50 = 7.2 nM, other JAKs IC50 > 1000 nM) stood out because of its low toxicity (MTD > 2 g/kg) and superior anti-inflammatory activity in Institute of Cancer Research mice. Moreover, the acceptable bioavailability (F% = 31.69%) ensured that J1b displayed excellent immune regulation in collagen-induced arthritis mice, whose joints in the high-dose group were almost recovered to a normal state. Given its clear kinase selectivity (Bmx IC50 = 539.9 nM, other Cys909 kinases IC50 > 1000 nM), J1b was nominated as a highly selective JAK3 covalent inhibitor, which could be used to safely treat arthritis and other autoimmune diseases.
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Artritis Experimental , Artritis Reumatoide , Diseño de Fármacos , Janus Quinasa 3 , Inhibidores de Proteínas Quinasas , Animales , Janus Quinasa 3/antagonistas & inhibidores , Janus Quinasa 3/metabolismo , Ratones , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/inducido químicamente , Artritis Experimental/enzimología , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Ratones Endogámicos DBA , Humanos , Relación Dosis-Respuesta a Droga , Estructura Molecular , Masculino , Simulación del Acoplamiento MolecularRESUMEN
During animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, ßγ-CAT (a complex of non-lens ßγ-crystallin and trefoil factor) is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid (FA) uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and FAs, called nutrisomes, were released in the presence of ßγ-CAT. These specific nutrient vesicles were readily taken up by starved myoblast cells to support their survival. The results uncovered that pore-forming protein ßγ-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.
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Células Endoteliales , Factores Trefoil , Albúminas/metabolismo , Animales , Células Endoteliales/metabolismo , Ayuno , Nutrientes , Péptidos/metabolismo , Piel/metabolismo , Factores Trefoil/metabolismoRESUMEN
An electro-triggered cascade cyclization strategy was disclosed with concomitant phosphinylation and N-heterocycle construction. It provides a novel and environmentally friendly approach to access phosphinyl-substituted N-heterocycles with no external metal catalyst, oxidant, or heating. Mechanistic studies have revealed that anodic oxidation of H-phosphorus compounds occurs first to generate the key P-centered radical directly and cathodic reduction leads to the concurrent release of molecular hydrogen or methane. This protocol features simple operation, broad substrate scope, clean and mild conditions, and atom and step economy to form heterocycle-containing organophosphorus scaffolds.
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Peroxisome proliferator-activated receptor γ (PPARγ) gene mutations in humans and mice lead to whole-body insulin resistance and partial lipodystrophy. It is unclear whether preserved fat depots in partial lipodystrophy are beneficial for whole-body metabolic homeostasis. We analyzed the insulin response and expression of metabolic genes in the preserved fat depots of PpargC/- mice, a familial partial lipodystrophy type 3 (FPLD3) mouse model resulting from a 75% decrease in Pparg transcripts. Perigonadal fat of PpargC/- mice in the basal state showed dramatic decreases in adipose tissue mass and insulin sensitivity, whereas inguinal fat showed compensatory increases. Preservation of inguinal fat metabolic ability and flexibility was reflected by the normal expression of metabolic genes in the basal or fasting/refeeding states. The high nutrient load further increased insulin sensitivity in inguinal fat, but the expression of metabolic genes became dysregulated. Inguinal fat removal resulted in further impairment of whole-body insulin sensitivity in PpargC/- mice. Conversely, the compensatory increase in insulin sensitivity of the inguinal fat in PpargC/- mice diminished as activation of PPARγ by its agonists restored insulin sensitivity and metabolic ability of perigonadal fat. Together, we demonstrated that inguinal fat of PpargC/- mice plays a compensatory role in combating perigonadal fat abnormalities.
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Resistencia a la Insulina , Lipodistrofia Parcial Familiar , PPAR gamma , Animales , Humanos , Ratones , Insulina/metabolismo , Insulina/farmacología , Resistencia a la Insulina/genética , Lipodistrofia Parcial Familiar/genética , Mutación , PPAR gamma/genética , PPAR gamma/metabolismoRESUMEN
Bacterial pore-forming toxin aerolysin-like proteins are widely distributed in animals and plants. Emerging evidence supports their roles in host innate immunity, but their direct actions in adaptive immunity remain elusive. In this study, we found that ßγ-CAT, an aerolysin-like protein and trefoil factor complex identified in the frog Bombina maxima, modulated several steps of endocytic pathways during dendritic cell antigen presentation. The protein augmented the antigen uptake of dendritic cells and actively neutralized the acidification of cellular endocytic organelles to favor antigen presentation. In addition, the release of functional exosome-like extracellular vesicles was largely enhanced in the presence of ßγ-CAT. The cellular action of ßγ-CAT increased the number of major histocompatibility complex (MHC) I-ovalbumin and MHC II molecules on dendritic cell surfaces and the released exosome-like extracellular vesicles. An enhanced antigen presentation capacity of dendritic cell for priming of naive T cells was detected in the presence of ßγ-CAT. Collectively, these effects led to strong cytotoxic T lymphocyte responses and antigen-specific antibody responses. Our findings provide evidence that a vertebrate-secreted pore-forming protein can augment antigen presentation by directly modulating cellular endocytic and exocytic pathways, leading to robust activation of adaptive immunity.
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Presentación de Antígeno/efectos de los fármacos , Células Dendríticas , Endosomas , Proteínas Citotóxicas Formadoras de Poros/farmacología , Linfocitos T , Inmunidad Adaptativa , Animales , Anuros/metabolismo , Células Cultivadas , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Endosomas/efectos de los fármacos , Endosomas/inmunología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Obesity-related cardiovascular risk, end points, and mortality are strongly related to arterial stiffening. Current therapeutic approaches for arterial stiffening are not focused on direct targeting within the vessel. Perivascular adipose tissue (PVAT) surrounding the artery has been shown to modulate vascular function and inflammation. Peroxisome proliferator-activated receptor γ (PPARγ) activation significantly decreases arterial stiffness and inflammation in diabetic patients with coronary artery disease. Thus, we hypothesized that PPARγ activation alters the PVAT microenvironment, thereby creating a favorable environment for the attenuation of arterial stiffening in obesity. METHODS: Obese ob/ob mice were used to investigate the effect of PPARγ activation on the attenuation of arterial stiffening. Various cell types, including macrophages, fibroblasts, adipocytes, and vascular smooth muscle cells, were used to test the inhibitory effect of pioglitazone, a PPARγ agonist, on the expression of elastolytic enzymes. RESULTS: PPARγ activation by pioglitazone effectively attenuated arterial stiffening in ob/ob mice. This beneficial effect was not associated with the repartitioning of fat from or changes in the browning of the PVAT depot but was strongly related to improvement of the PVAT microenvironment, as evidenced by reduction in the expression of pro-inflammatory and pro-oxidative factors. Pioglitazone treatment attenuated obesity-induced elastin fiber fragmentation and elastolytic activity and ameliorated the obesity-induced upregulation of cathepsin S and metalloproteinase 12, predominantly in the PVAT. In vitro, pioglitazone downregulated Ctss and Mmp12 in macrophages, fibroblasts, and adipocytes-cell types residing within the adventitia and PVAT. Ultimately, several PPARγ binding sites were found in Ctss and Mmp12 in Raw 264.7 and 3T3-L1 cells, suggesting a direct regulatory mechanism by which PPARγ activation repressed the expression of Ctss and Mmp-12 in macrophages and fibroblasts. CONCLUSIONS: PPARγ activation attenuated obesity-induced arterial stiffening and reduced the inflammatory and oxidative status of PVAT. The improvement of the PVAT microenvironment further contributed to the amelioration of elastin fiber fragmentation, elastolytic activity, and upregulated expression of Ctss and Mmp12. Our data highlight the PVAT microenvironment as an important target against arterial stiffening in obesity and provide a novel strategy for the potential clinical use of PPARγ agonists as a therapeutic against arterial stiffness through modulation of PVAT function.
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Tejido Adiposo/fisiopatología , Hipoglucemiantes/farmacología , Obesidad/fisiopatología , PPAR gamma/agonistas , Pioglitazona/farmacología , Rigidez Vascular/fisiología , Células 3T3 , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células RAW 264.7RESUMEN
The reconstruction of the size, position, optical properties, and structure of the object in scattering media was realized with a chaotic fiber laser. The light from the chaotic fiber laser was split into two parts. One part was used as the detection signal to detect the object, and the other was used as the reference signal; then, the two signals were cross correlated. The attenuation of light in scattering media was attributed to scattering and absorption. The theoretical model of the peak value of cross correlation of the chaotic signals as projection data were established by the attenuation law, and the filtered back-projection algorithms were used to realize the image reconstruction. The mean squared error, the normalized mean squared error, the peak signal-to-noise ratio, and the structural similarity index of the reconstructed image were analyzed. The results show that the high resolution of the reconstructed image benefits from the high signal-to-noise ratio with the chaotic fiber laser based on a delta-like cross-correlation function.
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Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore-forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear. ßγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (ß-subunit) complex (ßγ-CAT) is a complex of a bacterial pore-forming toxin aerolysin-like protein and trefoil factor identified in the frog Bombina maxima. In this study, we established mouse cutaneous wound models to explore the effects of ßγ-CAT on skin wound healing. ßγ-CAT accelerated the healing of full-thickness wounds by improving re-epithelialization. This complex relieved dermal edema and promoted scarless healing. ßγ-CAT treatment resulted in a rapid release of IL-1ß, which initiated an acute inflammation response in the early stage of healing. Meanwhile, the expression levels of TGF-ß1, VEGF, and bFGF and the recruitment of M2 macrophages around the wound significantly increased after ßγ-CAT treatment. ßγ-CAT protected skin wounds against methicillin-resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound. Overall, our results suggest that ßγ-CAT can promote tissue repair and protect skin wounds against antibiotic-resistant bacterial infection by triggering the acute inflammatory response. This is the first example that aerolysin-like pore-forming proteins widely existing in plants and animals may act in wound healing and tissue repair.-Gao, Z.-H., Deng, C.-J., Xie, Y.-Y., Guo, X.-L., Wang, Q.-Q., Liu, L.-Z., Lee, W.-H., Li, S.-A., Zhang, Y. Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.
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Proteínas Citotóxicas Formadoras de Poros/metabolismo , Toxinas Biológicas/metabolismo , Cicatrización de Heridas , Animales , Anuros , Línea Celular , Colágeno/metabolismo , Cristalinas/metabolismo , Células Epiteliales/citología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibroblastos/citología , Humanos , Interleucina-1beta/metabolismo , Macrófagos/citología , Masculino , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Ratones , Neutrófilos/citología , Conejos , Piel/lesiones , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Factor de Crecimiento Transformador beta1/metabolismo , Factores Trefoil/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Wi-Fi network has an open nature so that it needs to face greater security risks compared to wired network. The MAC address represents the unique identifier of the device, and is easily obtained by an attacker. Therefore MAC address randomization is proposed to protect the privacy of devices in a Wi-Fi network. However, implicit identifiers are used by attackers to identify user's device, which can cause the leakage of user's privacy. We propose device identification based on 802.11ac probe request frames. Here, a detailed analysis on the effectiveness of 802.11ac fields is given and a novel device identification method based on deep learning whose average f1-score exceeds 99% is presented. With a purpose of preventing attackers from obtaining relevant information by the device identification method above, we design a novel defense mechanism based on stream cipher. In that case, the original content of probe request frame is hidden by encrypting probe request frames and construction of probe request is reserved to avoid the finding of attackers. This defense mechanism can effectively reduce the performance of the proposed device identification method whose average f1-score is below 30%. In general, our research on attack and defense mechanism can preserve device privacy better.
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OBJECTIVE: To study the effect of 280â nm-LED ultraviolet irradiation on the proliferation of acute promyelocytic leukemia (APL) HL-60 cells under hypoxic conditions and related mechanism. METHODS: HL-60 cells in the logarithmic growth phase were selected and divided into control, hypoxia, ultraviolet and hypoxia+ultraviolet groups. The cells in the hypoxia group were treated with cobalt chloride (with a final concentration of 150â µmol/L), those in the ultraviolet group were irradiated by 280â nm-LED ultraviolet with an energy intensity of 30â J/m2, and those in the hypoxia+ultraviolet group were treated with cobalt chloride and then irradiated by 280â nm-LED ultraviolet. After 48 hours of treatment, the cells were placed under an invert microscope to observe cell morphology. CCK-8 assay was used to measure the inhibition rate of cell proliferation. Annexin V-FITC/PI double staining flow cytometry was used to evaluate cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression of Bcl-2. Each experiment above was repeated three times independently. RESULTS: Compared with the control group, the experimental groups showed shrinkage, decreased brightness, and disordered arrangement of cells, and the number of cells decreased over the time of culture. There were significant differences in the inhibition rate of cell proliferation and cell apoptosis rate among the groups (P<0.01), and the hypoxia+ultraviolet group showed the strongest inhibition of cell proliferation and induction of cell apoptosis, followed by the ultraviolet group and the hypoxia group. Compared with the control group, the other three groups had a gradual reduction in the mRNA expression of Bcl-2, and the hypoxia+ultraviolet group had a significantly greater reduction than the hypoxia and ultraviolet groups (P<0.01). CONCLUSIONS: Both hypoxia and ultraviolet irradiation can inhibit the proliferation of HL-60 cells and induce cell apoptosis, and ultraviolet irradiation has a better effect on proliferation inhibition and cell apoptosis under hypoxic conditions than under normoxic conditions, possibly by downregulating the mRNA expression of Bcl-2.
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Leucemia Promielocítica Aguda , Apoptosis , Hipoxia de la Célula , Proliferación Celular , HumanosRESUMEN
This paper investigates the methods to detect and classify marmoset vocalizations automatically using a large data set of marmoset vocalizations and deep learning techniques. For vocalization detection, neural networks-based methods, including deep neural network (DNN) and recurrent neural network with long short-term memory units, are designed and compared against a conventional rule-based detection method. For vocalization classification, three different classification algorithms are compared, including a support vector machine (SVM), DNN, and long short-term memory recurrent neural networks (LSTM-RNNs). A 1500-min audio data set containing recordings from four pairs of marmoset twins and manual annotations is employed for experiments. Two test sets are built according to whether the test samples are produced by the marmosets in the training set (test set I) or not (test set II). Experimental results show that the LSTM-RNN-based detection method outperformed others and achieved 0.92% and 1.67% frame error rate on these two test sets. Furthermore, the deep learning models obtained higher classification accuracy than the SVM model, which was 95.60% and 91.67% on the two test sets, respectively.
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Algoritmos , Aprendizaje Profundo , Memoria a Largo Plazo/fisiología , Redes Neurales de la Computación , Animales , Callithrix/fisiología , Máquina de Vectores de SoporteRESUMEN
The emerging connected, low-cost, and easy-to-use air quality monitoring systems have enabled a paradigm shift in the field of air pollution monitoring. These systems are increasingly being used by local government and non-profit organizations to inform the public, and to support decision making related to air quality. However, data integrity and system security are rarely considered during the design and deployment of such monitoring systems, and such ignorance leaves tremendous room for undesired and damaging cyber intrusions. The collected measurement data, if polluted, could misinform the public and mislead policy makers. In this paper, we demonstrate such issues by using a.com, a popular low-cost air quality monitoring system that provides an affordable and continuous air quality monitoring capability to broad communities. To protect the air quality monitoring network under this investigation, we denote the company of interest as a.com. Through a series of probing, we are able to identify multiple security vulnerabilities in the system, including unencrypted message communication, incompetent authentication mechanisms, and lack of data integrity verification. By exploiting these vulnerabilities, we have the ability of "impersonating" any victim sensor in the a.com system and polluting its data using fabricated data. To the best of our knowledge, this is the first security analysis of low-cost and connected air quality monitoring systems. Our results highlight the urgent need in improving the security and data integrity design in these systems.
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The Internet of Things (IoT) has gained popularity in recent years. Today's IoT applications are now increasingly deployed in cloud platforms to perform Big Data analytics. In cloud data center networks (DCN), TCP incast usually happens when multiple senders simultaneously communicate with a single receiver. However, when TCP incast happens, DCN may suffer from both throughput collapse for TCP burst flows and temporary starvation for TCP background flows. In this paper, we propose a software defined network (SDN)-based TCP congestion control mechanism, referred to as SDTCP, to leverage the features, e.g., centralized control methods and the global view of the network, in order to solve the TCP incast problems. When we detect network congestion on an OpenFlow switch, our controller can select the background flows and reduce their bandwidth by adjusting the advertised window of TCP ACK packets of the corresponding background flows so as to reserve more bandwidth for burst flows. SDTCP is transparent to the end systems and can accurately decelerate the rate of background flows by leveraging the global view of the network gained via SDN. The experiments demonstrate that our SDTCP can provide high tolerance for burst flows and achieve better flow completion time for short flows. Therefore, SDTCP is an effective and scalable solution for the TCP incast problem.
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The development of the Internet of Things (IoT) has accelerated research in indoor navigation systems, a majority of which rely on adequate wireless signals and sources. Nonetheless, deploying such a system requires periodic site-survey, which is time consuming and labor intensive. To address this issue, in this paper we present Canoe, an indoor navigation system that considers shopping mall scenarios. In our system, we do not assume any prior knowledge, such as floor-plan or the shop locations, access point placement or power settings, historical RSS measurements or fingerprints, etc. Instead, Canoe requires only that the shop owners collect and publish RSS values at the entrances of their shops and can direct a consumer to any of these shops by comparing the observed RSS values. The locations of the consumers and the shops are estimated using maximum likelihood estimation. In doing this, the direction of the target shop relative to the current orientation of the consumer can be precisely computed, such that the direction that a consumer should move can be determined. We have conducted extensive simulations using a real-world dataset. Our experiments in a real shopping mall demonstrate that if 50% of the shops publish their RSS values, Canoe can precisely navigate a consumer within 30 s, with an error rate below 9%.
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This study aimed to explore the relationship between air pollutants, particularly acidic particles, and metallic material corrosion. An atmospheric corrosion test was carried out in spring-summer 2012 at a polluted urban site, i.e., Tung Chung in western Hong Kong. Nine types of metallic materials, namely iron, Q235 steel, 20# steel, 16Mn steel, copper, bronze, brass, aluminum, and aluminum alloy, were selected as specimens for corrosion tests. Ten sets of the nine materials were all exposed to ambient air, and then each set was collected individually after exposure to ambient air for consecutive 6, 13, 20, 27, 35, 42, 49, 56, 63, and 70 days, respectively. After the removal of the corrosion products on the surface of the exposed specimens, the corrosion rate of each material was determined. The surface structure of materials was observed using scanning electron microscopy (SEM) before and after the corrosion tests. Environmental factors including temperature, relative humidity, concentrations of gaseous pollutants, i.e., sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and particulate-phase pollutants, i.e., PM2.5 (FSP) and PM10 (RSP), were monitored. Correlation analysis between environmental factors and corrosion rate of materials indicated that iron and carbon steel were damaged by both gaseous pollutants (SO2 and NO2) and particles. Copper and copper alloys were mainly corroded by gaseous pollutants (SO2 and O3), while corrosion of aluminum and aluminum alloy was mainly attributed to NO2 and particles.
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Contaminantes Atmosféricos/análisis , Atmósfera/química , Monitoreo del Ambiente , Metales/análisis , Contaminación del Aire/análisis , Contaminación del Aire/estadística & datos numéricos , Monóxido de Carbono/análisis , Corrosión , Hong Kong , Dióxido de Nitrógeno/análisis , Ozono/análisis , Estaciones del Año , Acero , Dióxido de Azufre/análisisRESUMEN
The purpose of this study is to investigate the preparation of hydroxycamptothecine (HCPT)-loaded cubic crystal liquid embolic precursor solution, and evaluate its in vitro embolic efficiency. Phytantriol was used as cubic crystal liquid embolic material, and the optimal formulation was selected according to ternary phase diagram. Polarized light microscopy, differential scanning calorimetry, and small angle X-ray scattering (SAXS) were used to characterize the cubic crystal structure. High performance liquid chromatography and X-ray diffraction analysis were used to investigate the lactone ring of HCPT. In vitro dissolution was preliminary evaluated, and the simulation embolic model was constructed to evaluate the embolic efficiency of precursor solution. Meanwhile, the gelation time and adhesion force were investigated. The results showed that HCPT-loaded precursor solution for embolization had been successfully prepared with low viscosity which was injectable. The precursor solution could transform into Pn3m structure liquid crystal phase gel rapidly when contracting with excess water. The formed HPCT gel remained its lactone form as the same in precursor solution, and expressed the good ability to block the saline flow, and HCPT could keep sustained releasing drug over 30 days. The prepared drug-loaded embolic precursor solution showed a promising potential for vascular embolization and application in clinical treatment of tumor.